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Sample records for abnormal vascular reactivity

  1. Catalase and superoxide dismutase conjugated with platelet-endothelial cell adhesion molecule antibody distinctly alleviate abnormal endothelial permeability caused by exogenous reactive oxygen species and vascular endothelial growth factor.

    PubMed

    Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-01

    Reactive oxygen species (ROS) superoxide anion (O(2)()) and hydrogen peroxide (H(2)O(2)) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H(2)O(2)-induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H(2)O(2) in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O(2)() in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of

  2. Carotid Vascular Abnormalities in Primary Hyperparathyroidism

    PubMed Central

    Walker, M. D.; Fleischer, J.; Rundek, T.; McMahon, D. J.; Homma, S.; Sacco, R.; Silverberg, S. J.

    2009-01-01

    Context: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting. Objective: This study evaluated carotid structure and function in PHPT patients compared with population-based controls. Design: This is a case-control study. Setting: The study was conducted in a university hospital metabolic bone disease unit. Participants: Forty-nine men and women with PHPT and 991 controls without PHPT were studied. Outcome Measures: We measured carotid intima-media thickness (IMT), carotid plaque presence and thickness, and carotid stiffness, strain, and distensibility. Results: IMT, carotid plaque thickness, carotid stiffness, and distensibility were abnormal in PHPT patients, and IMT was higher in patients than controls (0.959 vs. 0.907 mm, P < 0.0001). In PHPT, PTH levels, but not calcium concentration, predicted carotid stiffness (P = 0.04), strain (P = 0.06), and distensibility (P = 0.07). Patients with increased carotid stiffness had significantly higher PTH levels than did those with normal stiffness (141 ± 48 vs. 94.9 ± 44 pg/ml, P = 0.002), and odds of abnormal stiffness increased 1.91 (confidence interval = 1.09–3.35; P = 0.024) for every 10 pg/ml increase in PTH, adjusted for age, creatinine, and albumin-corrected calcium. Conclusions: Mild PHPT is associated with subclinical carotid vascular manifestations. IMT, a predictor of cardiovascular outcomes, is increased. Measures of carotid stiffness are associated with extent of PTH elevation, suggesting that those with more severe PHPT may have impaired vascular compliance and that PTH, rather than calcium, is the mediator. PMID:19755478

  3. Pleiotrophin is a driver of vascular abnormalization in glioblastoma.

    PubMed

    Zhang, Lei; Dimberg, Anna

    2016-01-01

    In a recent report by Zhang et al., pleiotrophin (PTN) was demonstrated to enhance glioma growth by promoting vascular abnormalization. PTN stimulates glioma vessels through anaplastic lymphoma kinase (Alk)-mediated perivascular deposition of vascular endothelial growth factor (VEGF). Targeting of Alk or VEGF signaling normalizes tumor vessels in PTN-expressing tumors.

  4. Pulmonary vascular development goes awry in congenital lung abnormalities.

    PubMed

    Kool, Heleen; Mous, Daphne; Tibboel, Dick; de Klein, Annelies; Rottier, Robbert J

    2014-12-01

    Pulmonary vascular diseases of the newborn comprise a wide range of pathological conditions with developmental abnormalities in the pulmonary vasculature. Clinically, pulmonary arterial hypertension (PH) is characterized by persistent increased resistance of the vasculature and abnormal vascular response. The classification of PH is primarily based on clinical parameters instead of morphology and distinguishes five groups of PH. Congenital lung anomalies, such as alveolar capillary dysplasia (ACD) and PH associated with congenital diaphragmatic hernia (CDH), but also bronchopulmonary dysplasia (BPD), are classified in group three. Clearly, tight and correct regulation of pulmonary vascular development is crucial for normal lung development. Human and animal model systems have increased our knowledge and make it possible to identify and characterize affected pathways and study pivotal genes. Understanding of the normal development of the pulmonary vasculature will give new insights in the origin of the spectrum of rare diseases, such as CDH, ACD, and BPD, which render a significant clinical problem in neonatal intensive care units around the world. In this review, we describe normal pulmonary vascular development, and focus on four diseases of the newborn in which abnormal pulmonary vascular development play a critical role in morbidity and mortality. In the future perspective, we indicate the lines of research that seem to be very promising for elucidating the molecular pathways involved in the origin of congenital pulmonary vascular disease.

  5. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension. PMID:23897679

  6. Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia.

    PubMed

    Mourani, Peter M; Abman, Steven H

    2015-12-01

    Despite advances in the care of preterm infants, these infants remain at risk bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, showing that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities. Several epidemiologic studies have delineated the incidence of PH in preterm infants and the impact on outcomes. These studies have also highlighted gaps in the understanding of PVD in BPD.

  7. Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment

    PubMed Central

    Hida, Yasuhiro; Maishi, Nako; Towfik, Alam Mohammad; Inoue, Nobuo; Shindoh, Masanobu; Hida, Kyoko

    2013-01-01

    There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, >30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment. PMID:24260373

  8. Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats

    PubMed Central

    Zhou, Rong; Ding, Xiao-li; Liu, Liang-ming

    2014-01-01

    Aim: Ryanodine receptor 2 (RyR2) is a critical component of intracellular Ca2+ signaling in vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats. Methods: SD rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries (SMA) rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca2+ release in VSMCs was assessed using Fura-2/AM. Results: The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage (30 min), but decreased in the late stage (2 h) of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 min or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine (1 mmol/L) significantly increased Ca2+ release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA. Conclusion: RyR2-mediated Ca2+ release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia. PMID:25263335

  9. Vascular and baroreceptor abnormalities in young males with a family history of hypertension.

    PubMed

    Boutcher, Yati N; Park, Young J; Boutcher, Stephen H

    2009-12-01

    Vascular and baroreceptor abnormalities in 44 young males, mean age 21 years, comprising of offspring with (FH(+); n = 22) and without (FH(-); n = 22) hypertensive parents, were investigated. Peak forearm blood flow (FBF), which was defined as the highest blood flow obtained following reactive hyperaemia, was assessed using strain gauge plethysmography following 5 min of ischemia. Cardiopulmonary baroreceptor sensitivity was assessed using lower body negative pressure for 5 min at -20 mmHg and was determined by calculating change of stroke volume and forearm vascular resistance (FVR) to lower body negative pressure. Carotid baroreceptor sensitivity was assessed using neck suction at -20, -40, -60, and -80 mmHg and was calculated by dividing RR interval by systolic blood pressure. Augmentation index, a measure of wave reflection, was assessed using applanation tonometry and was calculated as the ratio of augmented pressure and pulse pressure. Peak FBF of FH(+) was 19% lower than the FH(-) (p = 0.02). Also FH(+) had 17% higher peak FVR compared to FH(-) (p = 0.04). However, there were no significant differences between groups for cardiopulmonary, carotid baroreceptor sensitivity, and augmentation index. These results suggest that peripheral vascular dysfunction appears earlier than abnormal baroreceptor sensitivity in young males with a family history of hypertension.

  10. HIV-1, Reactive Oxygen Species and Vascular Complications

    PubMed Central

    Porter, Kristi M.; Sutliff, Roy L.

    2012-01-01

    Over 1 million people in the United States and 33 million individuals worldwide suffer from HIV/AIDS. Since its discovery, HIV/AIDS has been associated with an increased susceptibility to opportunistic infection due to immune dysfunction. Highly active antiretroviral therapies (HAART) restore immune function and, as a result, people infected with HIV-1 are living longer. This improved survival of HIV-1 patients has revealed a previously unrecognized risk of developing vascular complications, such as atherosclerosis and pulmonary hypertension. The mechanisms underlying these HIV-associated vascular disorders are poorly understood. However, HIV-induced elevations in reactive oxygen species, including superoxide and hydrogen peroxide, may contribute to vascular disease development and progression by altering cell function and redox-sensitive signaling pathways. In this review, we summarize the clinical and experimental evidence demonstrating HIV- and HIV antiretroviral therapy-induced alterations in reactive oxygen species (ROS) and how these effects likely contribute to vascular dysfunction and disease. PMID:22564529

  11. Effects of sodium selenite on vascular smooth muscle reactivity.

    PubMed

    Togna, G; Russo, P; Pierconti, F; Caprino, L

    2000-02-01

    The effects of sodium selenite (Na(2)SeO(3)) on the vascular smooth muscle reactivity of rabbit aorta were studied. In isolated rabbit aorta, Na(2)SeO(3) inhibited contractile response to phenylephrine and developed a lasting contracture in the vascular tissue. Relaxation in phenylephrine-precontracted aortic rings induced by sodium nitroprusside and 8-bromo-guanosine 3':5'-cyclic-monophosphate was also inhibited. Preliminary data obtained with ascorbic acid suggested a partial involvement of an oxidative mechanism. Excluding the possibility that Se damages actin or modifies its distribution (immunohistochemical evaluation), results indicate that Se alters vascular smooth muscle reactivity by inhibiting both its contracting and relaxing properties. Calcium-dependent mechanisms appear to be primarily involved and an interference with calcium re-uptake by sarcoplasmic reticulum as a possible site of Se vascular action could be hypothesized.

  12. Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus.

    PubMed

    Tesauro, Manfredi; Rizza, Stefano; Iantorno, Micaela; Campia, Umberto; Cardillo, Carmine; Lauro, Davide; Leo, Roberto; Turriziani, Mario; Cocciolillo, Giulio Cesare; Fusco, Angelo; Panza, Julio A; Scuteri, Angelo; Federici, Massimo; Lauro, Renato; Quon, Michael J

    2007-03-01

    Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1beta, tumor necrosis factor alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications.

  13. Fetal and postnatal ovine mesenteric vascular reactivity

    PubMed Central

    Nair, Jayasree; Gugino, Sylvia F.; Nielsen, Lori C.; Caty, Michael G.; Lakshminrusimha, Satyan

    2016-01-01

    BACKGROUND Intestinal circulation and mesenteric arterial (MA) reactivity may play a role in preparing the fetus for enteral nutrition. We hypothesized that MA vasoreactivity changes with gestation and vasodilator pathways predominate in the postnatal period. METHODS Small distal MA rings (0.5-mm diameter) were isolated from fetal (116-d, 128-d, 134-d, and 141-d gestation, term ~ 147 d) and postnatal lambs. Vasoreactivity was evaluated using vasoconstrictors (norepinephrine (NE) after pretreatment with propranolol and endothelin-1(ET-1)) and vasodilators (NO donors A23187 and s-nitrosopenicillamine (SNAP)). Protein and mRNA assays for receptors and enzymes (endothelin receptor A, alpha-adrenergic receptor 1A (ADRA1A), endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase5 (PDE5)) were performed in mesenteric arteries. RESULTS MA constriction to NE and ET-1 peaked at 134 d. Relaxation to A23187 and SNAP was maximal after birth. Basal eNOS activity was low at 134 d. ADRA1A mRNA and protein increasedsignificantlyat134danddecreasedpostnatally.sGC and PDE5 protein increased from 134 to 141 d. CONCLUSION Mesenteric vasoconstriction predominates in late-preterm gestation (134 d; the postconceptional age with the highest incidence of necrotizing enterocolitis (NEC)) followed by a conversion to vasodilatory influences near the time of full-term birth. Perturbations in this ontogenic mechanism, including preterm birth, may be a risk factor for NEC. PMID:26672733

  14. A Review of Vascular Abnormalities of the Spine

    PubMed Central

    Singh, Rahul; Lucke-Wold, Brandon; Gyure, Kymberly; Boo, Sohyun

    2017-01-01

    Patients with spinal vascular lesions present with unique symptoms and have important anatomical and physiologic changes that must be considered prior to treatment. In this mini-review, we provide an overview of normal spinal vascular anatomy and discuss several key spinal vascular lesions. We provide an overview of cavernous malformations, intradural arteriovenous malformations, perimedullary arteriovenous fistulas, and dural arteriovenous fistulas. Important considerations are addressed in terms of pathologic characterization, specific imaging findings, and treatment approaches. PMID:28191502

  15. Congenital vascular malformation associated with multiple cranial, vertebral and upper limb skeletal abnormalities.

    PubMed

    Marsden, N; Shokrollahi, K; Maw, K; Sierakowski, A; Bhat, F A; Mathur, B

    2010-07-01

    The association between congenital vascular malformations and altered bone growth, the so-called vascular bone syndrome, is well documented. Various eponymous syndromes each with their individual traits, such as Klippel-Trenaunay, Parkes-Weber and Servelle-Martorell syndrome have been described, along with variations. We report on a previously undescribed case of congenital vascular malformation associated with multiple skeletal abnormalities affecting the skull, vertebrae and right upper limb, and discuss the literature.

  16. Do subclinical vascular abnormalities precede impaired physical ability and ADL disability?

    PubMed

    den Ouden, Marjolein E M; Schuurmans, Marieke J; Mueller-Schotte, Sigrid; Bots, Michiel L; van der Schouw, YvonneT

    2014-10-01

    Cardiovascular disease is an important cause of disability in activities of daily living (ADL) through its effect on physical functioning. However, it is unclear whether subclinical vascular abnormalities and rate of change in subclinical vascular abnormalities is also associated with an impaired physical ability and with ADL disability. In a longitudinal study, 490 middle-aged and older persons were included. Physical ability was measured using the Short Physical Performance Battery and ADL disability using a questionnaire on self-reported basic and instrumental ADL. Subclinical vascular abnormalities were measured by pulse wave velocity (PWV) and carotid intima media thickness (CIMT, in men only). Longitudinal associations between baseline markers of subclinical vascular abnormalities, their rate of change, and change in physical ability or ADL disability were assessed using generalized estimation equation models. After adjustment for confounders, higher baseline PWV, change in PWV, baseline CIMT (in men) and change in CIMT (in men) were associated with a higher rate of change in physical ability (regression coefficients 0.035, 95% CI [0.018; 0.052]; 0.047, 95% CI [0.024; 0.069]; 0.214, 95% CI [0.070; 0.358] and 0.148, 95% CI [0.019; 0.277], respectively). No relations were found for change in ADL disability. In subjects with incident cardiovascular disease, higher change in PWV was associated with a higher rate of change in ADL disability (regression coefficient 0.054, 95% CI [0.001; 0.106]). The present study showed that subclinical vascular abnormalities and rate of change were associated with higher rate of change in physical ability. The association between (change in) subclinical vascular abnormalities and ADL disability tended to be stronger in persons with incident and prevalent cardiovascular disease. These data may suggest that ADL decline is more a direct effect of experienced clinically manifest vascular events rather than the effect of progression of

  17. Postprandial vascular reactivity in obese and normal weight young adults.

    PubMed

    Ayer, Julian G; Harmer, Jason A; Steinbeck, Katherine; Celermajer, David S

    2010-05-01

    As humans spend a significant amount of time in the postprandial state, we examined whether vascular reactivity (a key indicator of cardiovascular health) was different after a high-fat meal in 11 obese (median BMI 46.4, age 32.1 +/- 6.3 years, 7 men) and 11 normal weight (median BMI 22.6) age- and sex-matched controls. At baseline and 1 and 3 h postmeal, blood pressure (BP), heart rate (HR), reactive hyperemia peripheral artery tonometry (RH-PAT) index, radial augmentation index adjusted for HR (AIx75), brachial pulse wave velocity (PWV(b)), glucose, insulin, total and high-density lipoprotein (HDL) cholesterol, and triglycerides were measured. Brachial flow-mediated dilatation (FMD) and, by venous plethysmography, resting and hyperemic forearm blood flows (FBFs) were measured at baseline and 3 h. At baseline, obese subjects had higher systolic BP, HR, resting FBF, insulin and equivalent FMD, RH-PAT, hyperemic FBF, AIx75, PWV(b), glucose, total cholesterol, triglycerides, and lower HDL cholesterol. In obese and lean subjects, FMD at baseline and 3 h was not significantly different (6.2 +/- 1.7 to 5.8 +/- 4.3% for obese and 4.7 +/- 4.1 to 4.3 +/- 3.9% for normal weight, P = 0.975 for group x time). The meal did not produce significant changes in RH-PAT, hyperemic FBF, and PWV(b) in either group (P > 0.1 for the effect of time and for group x time interactions). In conclusion, the vascular responses to a high-fat meal are similar in obese and normal weight young adults. An exaggerated alteration in postprandial vascular reactivity is thus unlikely to contribute importantly to the increased cardiovascular risk of obesity.

  18. Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation

    PubMed Central

    Jones, Helen N.; Olbrych, Stephanie K.; Smith, Kathleen L.; Cnota, James F.; Habli, Mounira; Gonzales-Ramos, Osniel; Owens, Kathryn J; Hinton, Andrea C.; Polzin, William J.; Muglia, Louis J.; Hinton, Robert B.

    2015-01-01

    Introduction Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. Methods HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. Results HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 grams, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Discussion Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases. PMID:26278057

  19. Vascular Reactivity is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication.

    PubMed

    Silva, Rita de Cassia Gengo E; Wolosker, Nelson; Yugar-Toledo, Juan Carlos; Consolim-Colombo, Fernanda Marciano

    2015-08-01

    We verified whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and peripheral artery disease (PAD) severity in patients with intermittent claudication (IC). We studied 63 patients and 17 age- and sex-matched volunteers without PAD. Vascular reactivity was evaluated in the brachial artery during reactive hyperemia (flow-mediated dilation [FMD]) and after a sublingual single dose of nitroglycerin (nitroglycerin-induced vasodilation [NID]). Walking ability was verified by a 6-minute walk test. Vascular reactivity and walking ability were significantly worse in patients with IC compared with control participants. The ankle-brachial index correlated with FMD, NID, as well as total and pain-free distances. The NID and walking ability progressively decreased as PAD severity increased. Walking ability correlated with NID but not with FMD. In patients with IC, vascular reactivity is impaired and is related to the severity of PAD and to walking ability.

  20. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas.

    PubMed

    Zhang, Lei; Kundu, Soumi; Feenstra, Tjerk; Li, Xiujuan; Jin, Chuan; Laaniste, Liisi; El Hassan, Tamador Elsir Abu; Ohlin, K Elisabet; Yu, Di; Olofsson, Tommie; Olsson, Anna-Karin; Pontén, Fredrik; Magnusson, Peetra U; Nilsson, Karin Forsberg; Essand, Magnus; Smits, Anja; Dieterich, Lothar C; Dimberg, Anna

    2015-12-08

    Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with increased deposition of vascular endothelial growth factor (VEGF) in direct proximity to the vasculature. The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor. Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization.

  1. Severe diffuse hypoplasia of the aorta associated with multiple vascular abnormalities.

    PubMed

    Grebeldinger, Slobodan P; Balj, Svetlana S; Adic, Oto

    2011-06-01

    Hypoplasia of the thoracic and abdominal aorta is an extremely rare vascular pathology. The most common clinical manifestation is severe uncontrolled hypertension in adolescents and young adults. Medical treatment alone can decrease blood pressure, but often very high doses of antihypertensive drugs are needed. When hypertension is refractory to the antihypertensive medications, surgical revascularization is considered as the treatment of choice. We report the case of a severe and diffuse hypoplasia of the aorta, beginning with the aortic isthmus, to the aortic bifurcation, associated with an aberrant celiac trunk and superior mesenteric artery, and with other multiple vascular abnormalities. Unlikely, the only manifestation of this extensive vascular malformation was medicamentously controllable hypertension. To our knowledge, this severe vascular anomaly, with such a minimal clinical manifestation, has not been previously described in the English literature.

  2. Cerebral vascular reactivity on return from the International Space Station

    NASA Astrophysics Data System (ADS)

    Zuj, Kathryn; Greaves, Danielle; Shoemaker, Kevin; Blaber, Andrew; Hughson, Richard L.

    Returning from spaceflight, astronauts experience a high incidence of orthostatic intolerance and syncope. Longer duration space flight may result in greater adaptations to microgravity which could increase the post-flight incidence of syncope. CCISS (Cardiovascular and Cerebovascular Control on return from the International Space Station) is an ongoing project designed to help determine adaptations that occur during spaceflight which may contribute to orthostatic intolerance. One component of this project involves looking at cerebral vascular responses before and after long duration spaceflight. As a known vasodilator, carbon dioxide (CO2) has been frequently used to assess changes in cerebral vascular reactivity. In this experiment, end tidal PCO2 was manipulated through changes in respired air. Two breaths of a 10% CO2 gas mixture were administered at 1-min intervals resulting in an increase in end tidal PCO2 . Throughout the testing, cerebral blood flow velocity (CBFV) was determined using transcranial Doppler ultrasound. The cerebral resistance index (RI) was calculated from the Doppler wave form using the equation; RI=(CBFVsystolic-CBFVdiastolic)/CBFVsystolic. Changes in this index have been shown to reflect changes in cerebral vascular resistance. Peak responses to the CO2 stimulus were determined and compared to baseline measures taken at the beginning of the testing. Cerebral blood flow velocity increased and RI decreased with the two breaths of CO2. Preliminary data show a 36.0% increase in CBFV and a 9.0% decrease in RI pre-flight. Post flight, the response to CO2 appears to change showing a potentially blunted decrease in resistance (6.8%) and a smaller increase in CBFV (22.8%). Long term spaceflight may result in cerebrovascular changes which could decrease the vasodilatory capacity of cerebral resistance vessels. Further investigations in the CCISS project will reveal the interactive role of CO2 and arterial blood pressure on maintenance of brain

  3. Classification of urticaria and the reactive inflammatory vascular dermatoses.

    PubMed

    Jorizzo, J L

    1985-01-01

    The common feature of all the conditions discussed in this article is that they are inflammatory vascular dermatoses that may occur as reactive processes in association with other diseases. The histopathologic characteristics of the lesions range from mild, perivascular dermal infiltration with inflammatory cells and vasodilation to various degrees of vessel damage (endothelial swelling to fibrinoid necrosis). The vessel damage is reflected in varying degrees of secondary changes including extravasation of edema fluid, extravasation of erythrocytes, epidermal necrosis, separation of the dermal-epidermal junction zone, and widespread tissue necrosis. The etiology of most of these conditions is still unknown, although strong evidence indicates that type III (circulating immune-complex-mediated) pathogenesis may be responsible for necrotizing venulitis (leukocytoclastic vasculitis) and that a type I (IgE-mediated) pathogenesis may be involved in some types of urticaria. For many of the reactions described, the patients have serum sickness-like systemic signs and symptoms in addition to cutaneous lesions, and a circulating immune-complex-mediated pathogenesis has been considered. Future investigations must address the types of antigens and antibodies present in the circulating immune complexes, the detection of specific antigen in cutaneous blood vessels, the reproduction of lesions in experimental animals, and the mechanisms responsible for the spectrum of clinicopathologic lesions produced, with special attention to the possibility that vessel damage results from circulating immune complex-induced lymphocytic rather than only leukocytoclastic vasculitis.

  4. Isometric Stretch Alters Vascular Reactivity of Mouse Aortic Segments

    PubMed Central

    De Moudt, Sofie; Leloup, Arthur; Van Hove, Cor; De Meyer, Guido; Fransen, Paul

    2017-01-01

    Most vaso-reactive studies in mouse aortic segments are performed in isometric conditions and at an optimal preload, which is the preload corresponding to a maximal contraction by non-receptor or receptor-mediated stimulation. In general, this optimal preload ranges from about 1.2 to 8.0 mN/mm, which according to Laplace's law roughly correlates with transmural pressures of 10–65 mmHg. For physiologic transmural pressures around 100 mmHg, preloads of 15.0 mN/mm should be implemented. The present study aimed to compare vascular reactivity of 2 mm mouse (C57Bl6) aortic segments preloaded at optimal (8.0 mN/mm) vs. (patho) physiological (10.0–32.5 mN/mm) preload. Voltage-dependent contractions of aortic segments, induced by increasing extracellular K+, and contractions by α1-adrenergic stimulation with phenylephrine (PE) were studied at these preloads in the absence and presence of L-NAME to inhibit basal release of NO from endothelial cells (EC). In the absence of basal NO release and with higher than optimal preload, contractions evoked by depolarization or PE were attenuated, whereas in the presence of basal release of NO PE-, but not depolarization-induced contractions were preload-independent. Phasic contractions by PE, as measured in the absence of external Ca2+, were decreased at higher than optimal preload suggestive for a lower contractile SR Ca2+ content at physiological preload. Further, in the presence of external Ca2+, contractions by Ca2+ influx via voltage-dependent Ca2+ channels were preload-independent, whereas non-selective cation channel-mediated contractions were increased. The latter contractions were very sensitive to the basal release of NO, which itself seemed to be preload-independent. Relaxation by endogenous NO (acetylcholine) of aortic segments pre-contracted with PE was preload-independent, whereas relaxation by exogenous NO (diethylamine NONOate) displayed higher sensitivity at high preload. Results indicated that stretching aortic

  5. Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

    PubMed Central

    de Almeida, Eros Antonio; Ozaki, Michiko Regina

    2014-01-01

    Background Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. Objective To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Methods Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Results Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Conclusion Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits. PMID:25014056

  6. Catechin averts experimental diabetes mellitus-induced vascular endothelial structural and functional abnormalities.

    PubMed

    Bhardwaj, Pooja; Khanna, Deepa; Balakumar, Pitchai

    2014-03-01

    Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA.

  7. Abnormal proactive and reactive cognitive control during conflict processing in major depression.

    PubMed

    Vanderhasselt, Marie-Anne; De Raedt, Rudi; De Paepe, Annick; Aarts, Kristien; Otte, Georges; Van Dorpe, Jan; Pourtois, Gilles

    2014-02-01

    According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes.

  8. Abnormal vascular development in zebrafish models for fukutin and FKRP deficiency.

    PubMed

    Wood, Alasdair J; Müller, Juliane S; Jepson, Catherine D; Laval, Steve H; Lochmüller, Hanns; Bushby, Kate; Barresi, Rita; Straub, Volker

    2011-12-15

    Fukutin and fukutin-related protein (FKRP) are involved in the glycosylation of α-dystroglycan, a key receptor for basement membrane proteins. Aberrant α-dystroglycan glycosylation leads to a broad spectrum of disorders, ranging from limb girdle muscular dystrophy to Walker-Warburg syndrome. This is the first study investigating a role of fukutin and FKRP-mediated glycosylation in angiogenesis. Transgenic zebrafish expressing enhanced green fluorescent protein in blood vessels were treated with morpholino antisense oligonucleotides that blocked the expression of fukutin, FKRP and dystroglycan. All morphant fish showed muscle damage and vascular abnormalities at day 1 post-fertilization. Intersegmental vessels of somites failed to reach the dorsal longitudinal anastomosis and in more severe phenotypes retracted further or were in some cases even completely missing. In contrast, the eye vasculature was distorted in both fukutin and FKRP morphants, but not in dystroglycan morphants or control fish. The eye size was also smaller in the fukutin and FKRP morphants when compared with dystroglycan knockdown fish and controls. In general, the fukutin morphant fish had the most severe skeletal muscle and eye phenotype. Our findings suggest that fukutin and FKRP have functions that affect ocular development in zebrafish independently of dystroglycan. Despite anecdotal reports about vascular abnormalities in patients affected by dystroglycanopathies, the clinical relevance of such lesions remains unclear and should be subject to further review and investigations.

  9. The effect of bilateral adrenal demedullation on vascular reactivity and blood pressure in spontaneously hypertensive rats.

    PubMed Central

    Borkowski, K. R.; Quinn, P.

    1983-01-01

    Bilateral adrenal demedullation of juvenile spontaneously hypertensive rats attenuated, but did not prevent, the development of hypertension. Neither did it affect the subsequent vascular reactivity to phenylephrine though it significantly reduced the vascular effects of sympathetic nerve stimulation. Demedullation of adult spontaneously hypertensive rats did not alter blood pressure, but did attenuate the pressor responses to both alpha-adrenoceptor agonists and sympathetic nerve stimulation. In acutely demedullated adult rats, vascular reactivity to sympathetic nerve stimulation, but not to exogenous amines, could be restored by slow i.v. infusion of adrenaline in a dose-dependent manner. The results support a possible facilitatory role for adrenaline in sympathetic neurotransmitter release, both during the development of genetic hypertension and in vascular responses to sympathetic nerve stimulation. PMID:6640199

  10. Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions.

    PubMed

    Togna, G I; Togna, A R; Caprino, L

    2001-05-01

    To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied.

  11. Digital thermal monitoring (DTM) of vascular reactivity closely correlates with Doppler flow velocity.

    PubMed

    McQuilkin, Gary L; Panthagani, David; Metcalfe, Ralph W; Hassan, Haider; Yen, Albert A; Naghavi, Morteza; Hartley, Craig J

    2009-01-01

    The noninvasive measurement of peripheral vascular reactivity, as an indicator of vascular function, provides a valuable tool for cardiovascular screening of at-risk populations. Practical and economical considerations demand that such a test be low-cost and simple to use. To this end, it is advantageous to substitute digital thermal monitoring (DTM) for the more costly and complex Doppler system commonly used for this measurement. A signal processing model was developed to establish the basis for the relationship between finger temperature reactivity and blood flow reactivity following a transient brachial artery occlusion and reperfusion protocol (reactive hyperemia). Flow velocity signals were acquired from the radial artery of human subjects via an 8 MHz Doppler probe while simultaneous DTM signals were acquired from a distal fingertip via DTM sensors. The model transforms the DTM temperature signals into normalized flow signals via a deconvolution method which employs an exponential impulse function. The DTM normalized flow signals were compared to simultaneous, low-frequency, normalized flow signals computed from Doppler sensors. The normalized flow signals, derived from DTM and Doppler sensors, were found to yield similar reactivity responses during reperfusion. The reactivity areas derived from DTM and Doppler sensors, indicative of hyperemic volumes, were found to be within +/- 15%. In conclusion, this signal processing model provides a means to measure vascular reactivity using DTM sensors, that is equivalent to that obtained by more complex Doppler systems.

  12. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  13. Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis.

    PubMed

    Arai, Takehiro; Kasper, Jocelyn S; Skaar, Jeffrey R; Ali, Syed Hamid; Takahashi, Chiaki; DeCaprio, James A

    2003-08-19

    Cul1, a member of the cullin ubiquitin ligase family, forms a multiprotein complex known as SCF and plays an essential role in numerous cellular and biological activities. A Cul1 homologue, p185 (Cul7), has been isolated as an simian virus 40 large T antigen-binding protein. To understand the physiological role of p185, we generated mice lacking p185. p185-/- embryos are runted and die immediately after birth because of respiratory distress. Dermal and hypodermal hemorrhage is detected in mutant embryos at late gestational stage. p185-/- placentas show defects in the differentiation of the trophoblast lineage with an abnormal vascular structure. We demonstrate that p185 forms an SCF-like complex with Skp1, Rbx1, Fbw6 (Fbx29), and FAP68 (FAP48, glomulin). FAP68 has recently been identified as a gene responsible for familial glomuvenous malformation. These results suggest that p185 forms a multiprotein complex and plays an important role in vascular morphogenesis.

  14. Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis

    PubMed Central

    Arai, Takehiro; Kasper, Jocelyn S.; Skaar, Jeffrey R.; Ali, Syed Hamid; Takahashi, Chiaki; DeCaprio, James A.

    2003-01-01

    Cul1, a member of the cullin ubiquitin ligase family, forms a multiprotein complex known as SCF and plays an essential role in numerous cellular and biological activities. A Cul1 homologue, p185 (Cul7), has been isolated as an simian virus 40 large T antigen-binding protein. To understand the physiological role of p185, we generated mice lacking p185. p185–/– embryos are runted and die immediately after birth because of respiratory distress. Dermal and hypodermal hemorrhage is detected in mutant embryos at late gestational stage. p185–/– placentas show defects in the differentiation of the trophoblast lineage with an abnormal vascular structure. We demonstrate that p185 forms an SCF-like complex with Skp1, Rbx1, Fbw6 (Fbx29), and FAP68 (FAP48, glomulin). FAP68 has recently been identified as a gene responsible for familial glomuvenous malformation. These results suggest that p185 forms a multiprotein complex and plays an important role in vascular morphogenesis. PMID:12904573

  15. Vascular C-reactive protein in the pathogenesis of coronary artery disease: role of vascular inflammation and oxidative stress.

    PubMed

    Inoue, Nobutaka

    2006-12-01

    Atherosclerosis is considered to be a chronic inflammatory disease. Vascular inflammation occurs in response to injury induced by various stimuli, such as oxidative stress, shear stress, infection, and so on. This concept is supported by the recent clinical findings that C-reactive protein (CRP) is an independent risk factor for coronary heart disease. CRP, which was originally identified as a protein that could precipitate the C-polysaccharide of pneumococcal cell walls, has been widely used as a clinical marker of the state of inflammation, since its production by hepatocytes increases during the acute phase of the inflammatory response. Recent investigations have provided two new concepts for the research field of CRP, namely, its extra-hepatic production and its potent biological activities such as the induction of adhesion molecules and chemokines. Recently, we demonstrated that smooth muscle cells and macrophages in coronary arteries expressed CRP protein and mRNA, as evaluated using coronary specimens of coronary artery disease (CAD) patients obtained by atherectomy. The expression of vascular CRP was closely associated with NAD(P)H oxidase, an important enzymatic origin of reactive oxygen species (ROS) in vessel walls. Furthermore, CRP directly up-regulated NAD(P)H oxidase p22(phox) and enhanced ROS generation in cultured coronary artery smooth muscle cells. Thus, vascular CRP is likely to be a direct participant in vascular inflammation and lesion formation via its potent biological effects. Since lysophosphatidylcholine, a major atherogenic lipid of oxidized LDL, was reported to activate vascular NAD(P)H oxidase, we speculate that there is a vicious circle consisting of vascular NAD(P)H oxidase, ROS and oxidized LDL. Since phagocytic NAD(P)H oxidase is at the first line of the host defense system, it is important to selectively suppress vascular NAD(P)H oxidase in the localized inflammatory lesions in therapeutic strategies for CAD. In this review, we

  16. Visualization of tumor vascular reactivity in response to respiratory challenges by optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kim, Hoon Sup; Lee, Songhyun; Lee, Kiri; Eom, Tae Joong; Kim, Jae G.

    2016-02-01

    We previously reported the potential of using vascular reactivity during respiratory challenges as a marker to predict the response of breast tumor to chemotherapy in a rat model by using a continuous wave near-infrared spectroscopy. However, it cannot visualize how the vascular reactivity from tumor vessel can predict the tumor response to its treatment. In this study, we utilized a spectral domain optical coherence tomography (SD-OCT) system to visualize vascular reactivity of both tumor and normal vasculature during respiratory challenges in a mouse model. We adapted intensity based Doppler variance algorithm to draw angiogram from the ear of mouse (8-week-old Balb/c nu/nu). Animals were anesthetized using 1.5% isoflurane, and the body temperature was maintained by a heating pad. Inhalational gas was switched from air (10min) to 100% oxygen (10min), and a pulse oximeter was used to monitor arterial oxygen saturation and heart rate. OCT angiograms were acquired 5 min after the onset of each gas. The vasoconstriction effect of hyperoxic gas on vasculature was shown by subtracting an en-face image acquired during 100% oxygen from the image acquired during air inhalation. The quantitative change in the vessel diameter was measured from the en-face OCT images of the individual blood vessels. The percentage of blood vessel diameter reduction varied from 1% to 12% depending on arterial, capillary, or venous blood vessel. The vascular reactivity change during breast tumor progression and post chemotherapy will be monitored by OCT angiography.

  17. Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats.

    PubMed

    Abebe, Worku; Liu, Jun Yao; Wimborne, Hereward; Mozaffari, Mahmood S

    2010-01-01

    Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

  18. Use of temperature alterations to characterize vascular reactivity.

    PubMed

    Ley, Obdulia; Dhindsa, Mandeep; Sommerlad, Shawn M; Barnes, Jill N; Devan, Allison E; Naghavi, Morteza; Tanaka, Hirofumi

    2011-01-01

    Monitoring alterations in fingertip temperature during ischaemia and the subsequent hyperaemia provides a novel way of studying microvascular reactivity. The relations between parameters characterizing blood perfusion and the thermal response of fingertips were studied using experimental and theoretical approaches. During the experimental protocol, two brachial artery occlusion tests were conducted in 12 healthy volunteers, and fingertip temperature, heat flux and skin perfusion using laser Doppler flowmetry (LDF) were measured. The temperature curves provide a smooth and robust response that is able to capture occlusion and reperfusion. The temperature fall during occlusion as well as the maximum temperature recorded depended linearly on the initial temperature. The magnitude of the LDF signal was associated with local tissue temperature and followed an exponential response. Heat flux measurements demonstrated rapid changes and followed variations in blood perfusion closely. The time points at which the heat flux reached its maximum corresponded to the time at which the fingertip temperature curves showed an inflection point after cuff release. The time required for the fingertip temperature to arrive at the maximum temperature was greater than the time to peak for the heat flux signal, which was greater than the LDF signal to reach a maximum. The time lag between these signals was a function of the finger size and finger temperature at the moment reperfusion restarted. Our present results indicate that finger temperature, heat flux and perfusion display varying rates of recovery following ischaemic stimuli and that differential responses are associated with the initial finger temperature.

  19. Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

    NASA Technical Reports Server (NTRS)

    Papadaki, M.; Eskin, S. G.; Ruef, J.; Runge, M. S.; McIntire, L. V.

    1999-01-01

    Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

  20. Do iodinated nano-emulsions designed for preclinical vascular imaging alter the vascular reactivity in rat aorta?

    PubMed

    Anton, Nicolas; Atzenhoffer, Marina; Daubeuf, François; Li, Xiang; Schini-Kerth, Valérie B; Delmotte, Barbara; Vandamme, Thierry F; Chataigneau, Thierry

    2013-09-15

    This study proposes a new methodology to evaluate the putative consequences of the long-lasting circulation in the blood pool of nanoparticulate systems widely used in nanomedicine, Indeed, the blood pool contrast agent for micro-computed tomography, i.e. iodinated nano-emulsions, have recently been developed, for their great potential in medical applications such as advanced diagnosis, image-guided surgery, personalized medicine or theragnostics. Stealth nanoparticles exhibit a low recognition by the reticuloendothelial system, resulting in a prolonged circulation in the bloodstream and long-lasting contact with the endothelium. Therefore, the aim of the present study is to determine whether this prolonged interaction could induce an alteration of the vascular reactivity in rat aorta. The Iodinated nano-emulsions were intravenously injected in anesthetized rats. After 1h of contrast agent circulation in the blood pool, the thoracic aorta was removed for the study of vascular reactivity. These animals were compared with control (untreated) rats and a third group of rats receiving an injection of phosphate buffered saline (i.e. dispersing phase of the nano-emulsions). Phenylephrine-induced concentration-dependent contractions of the isolated rat thoracic aorta were not modified whatever the group. Sodium nitroprusside (a nitric oxide (NO) donor)-induced relaxations of endothelium-denuded aorta were also unaltered in response to the different administrations. In contrast, in comparison with control animals, endothelium-dependent NO-mediated relaxations to acetylcholine were significantly impaired in thoracic aorta from PBS-treated rats, but not in animals receiving the iodinated nano-emulsion. In addition, neither isoprenaline-induced nor levcromakalim-induced relaxations were modified in the aorta from the three groups of animals. These findings indicate that even with a long-lasting residence time of the iodinated nano-emulsion in the blood flow, these iodinated

  1. Comparison of two mathematical models for the study of vascular reactivity.

    PubMed

    Ley, Obdulia; Deshpande, Chinmay V

    2009-07-01

    This work is based on the premise that fingertip temperature variation during arterial occlusion and subsequent reperfusion can be used as an indirect measurement of vascular reactivity, commonly assessed by directly measuring flow and its temporal alterations in response to arterial occlusion. Temperature of the fingers depends on blood perfusion and environmental factors. The temperature change experienced during hyperemia or high blood flow after occlusion depend on the capacity of the occluded arteries to restore normal circulation or vascular reactivity. This work uses two mathematical models of heat transfer to show the relationship between blood flow and changes in fingertip temperature experienced during vascular occlusion and reperfusion. The models consider different levels of complexity and anatomical detail. One model is a lumped or zero-order model that neglects tissue composition; the second model (first-order model) considers a simplified anatomy of the finger and allows the analysis of tissue composition which cannot be addressed with the lumped system. Thermal models provide a way of estimating the influence of different factors on the dynamic temperature response recorded during the reactivity tests. The models intend to increase the interest of the clinical community in the thermal study of vascular reactivity compared to other techniques that focus on the analysis of flow. The differences of the calculated dynamic temperature during arterial occlusion and reperfusion using both models were analyzed. Such comparison indicated that the zero-order model suffices to analyze the temperature variation during the reactivity test, as long as the proper variation between initial condition and environmental parameters affecting the response is used.

  2. Diabetic retinopathy: retina-specific methods for maintenance of diabetic rodents and evaluation of vascular histopathology and molecular abnormalities

    PubMed Central

    Veenstra, Alexander; Liu, Haitao; Lee, Chieh Allen; Du, Yunpeng; Tang, Jie; Kern, Timothy S.

    2015-01-01

    Diabetic retinopathy is a major cause of visual impairment, which continues to increase in prevalence as more and more people develop diabetes. Despite the importance of vision, the retina is one of the smallest tissues in the body, and specialized techniques to study the retinopathy have been developed. This chapter will summarize several methods used to (i) induce diabetes, (ii) maintain the diabetic animals throughout the months required for the development of typical vascular histopathology, (iii) evaluate vascular histopathology of diabetic retinopathy, and (iv) quantitate abnormalities implicated in the development of the retinopathy. PMID:26331759

  3. Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na(+) and restricted dietary Na().

    PubMed

    Alshahrani, Saeed; Rapoport, Robert M; Soleimani, Manoocher

    2017-03-01

    Reduced renal Na(+) reabsorption along with restricted dietary Na(+) depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na(+) reabsorption and restricted dietary Na(+) associated with considerable hypotension and renin-angiotensin system activation: (1) the Na(+)-Cl(-)-Co-transporter (NCC) knockout (KO) with Na(+) restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na(+)-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na(+)-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na(+) reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.

  4. Severe Sprengel deformity associated with Klippel-Feil syndrome and a complex vascular abnormality that determined the corrective surgery technique.

    PubMed

    Fontecha, Cesar G; Navarro Cano, Ester; Soldado, Francisco; Barber, Ignasi

    2014-11-01

    Sprengel deformity (SD), a congenital condition characterized by elevation of the scapula, is a cause of functional and aesthetic defects that can be improved by surgical correction. Many cases of SD are associated with Klippel-Feil syndrome (KFS), in which there may be abnormalities of the supra-aortic vessels. We present the case of an 11-year-old girl with severe SD and KFS. The left vertebral artery arose from the subclavian artery in a very high cervical location, which made surgical descent of the scapula unfeasible. The patient was treated using a Mears procedure, with osteotomy of the scapula and tenotomy of the long head of the triceps. The appearance and range of motion of the shoulders improved considerably, and there were no vascular complications. A morphologic vascular assessment is essential in children with SD and concomitant KFS to avoid potentially serious iatrogenic vascular injury when performing a scapular-descending surgical technique.

  5. Altering dietary lysine: arginine ratio has little effect on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The effect of dietary protein type on cardiovascular risk factors and vascular reactivity, with specific focus on the lysine to arginine (Lys:Arg) ratio, has been studied sporadically. Objective: Determine effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reacti...

  6. Reactivation of Lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells.

    PubMed

    Zou, Jianlong; Hu, Bo; Arpag, Sezgi; Yan, Qing; Hamilton, Audra; Zeng, Yuan-Shan; Vanoye, Carlos G; Li, Jun

    2015-04-29

    Loss of function of FIG4 leads to Charcot-Marie-Tooth disease Type 4J, Yunis-Varon syndrome, or an epilepsy syndrome. FIG4 is a phosphatase with its catalytic specificity toward 5'-phosphate of phosphatidylinositol-3,5-diphosphate (PI3,5P2). However, the loss of FIG4 decreases PI3,5P2 levels likely due to FIG4's dominant effect in scaffolding a PI3,5P2 synthetic protein complex. At the cellular level, all these diseases share similar pathology with abnormal lysosomal storage and neuronal degeneration. Mice with no FIG4 expression (Fig4(-/-)) recapitulate the pathology in humans with FIG4 deficiency. Using a flow cytometry technique that rapidly quantifies lysosome sizes, we detected an impaired lysosomal fission, but normal fusion, in Fig4(-/-) cells. The fission defect was associated with a robust increase of intralysosomal Ca(2+) in Fig4(-/-) cells, including FIG4-deficient neurons. This finding was consistent with a suppressed Ca(2+) efflux of lysosomes because the endogenous ligand of lysosomal Ca(2+) channel TRPML1 is PI3,5P2 that is deficient in Fig4(-/-) cells. We reactivated the TRPML1 channels by application of TRPML1 synthetic ligand, ML-SA1. This treatment reduced the intralysosomal Ca(2+) level and rescued abnormal lysosomal storage in Fig4(-/-) culture cells and ex vivo DRGs. Furthermore, we found that the suppressed Ca(2+) efflux in Fig4(-/-) culture cells and Fig4(-/-) mouse brains profoundly downregulated the expression/activity of dynamin-1, a GTPase known to scissor organelle membranes during fission. This downregulation made dynamin-1 unavailable for lysosomal fission. Together, our study revealed a novel mechanism explaining abnormal lysosomal storage in FIG4 deficiency. Synthetic ligands of the TRPML1 may become a potential therapy against diseases with FIG4 deficiency.

  7. Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

    PubMed

    Khammy, Makhala M; Angus, James A; Wright, Christine E

    2016-02-15

    In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction.

  8. Targeted interception of signaling reactive oxygen species in the vascular endothelium

    PubMed Central

    Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2017-01-01

    Reactive oxygen species (ROS) are implicated as injurious and as signaling agents in human maladies including inflammation, hyperoxia, ischemia-reperfusion and acute lung injury. ROS produced by the endothelium play an important role in vascular pathology. They quench, for example, nitric oxide, and mediate pro-inflammatory signaling. Antioxidant interventions targeted for the vascular endothelium may help to control these mechanisms. Animal studies have demonstrated superiority of targeting ROS-quenching enzymes catalase and superoxide dismutase to endothelial cells over nontargeted formulations. A diverse arsenal of targeted antioxidant formulations devised in the last decade shows promising results for specific quenching of endothelial ROS. In addition to alleviation of toxic effects of excessive ROS, these targeted interventions suppress pro-inflammatory mechanisms, including endothelial cytokine activation and barrier disruption. These interventions may prove useful in experimental biomedicine and, perhaps, in translational medicine. PMID:22834201

  9. Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

    PubMed Central

    Franco, O.S.; Paulitsch, F.S.; Pereira, A.P.C.; Teixeira, A.O.; Martins, C.N.; Silva, A.M.V.; Plentz, R.D.M.; Irigoyen, M.C.; Signori, L.U.

    2014-01-01

    Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia. PMID:24820225

  10. Cerebral/Peripheral Vascular Reactivity and Neurocognition in Middle-Age Athletes

    PubMed Central

    Tarumi, Takashi; Gonzales, Mitzi M.; Fallow, Bennett; Nualnim, Nantinee; Lee, Jeongseok; Pyron, Martha; Tanaka, Hirofumi; Haley, Andreana P.

    2015-01-01

    Introduction Midlife vascular disease risk is associated with higher incidence of cognitive impairment in late life. Regular aerobic exercise improves vascular function, which in turn may translate into better cognitive function. The purpose of this study was to determine the associations among cardiorespiratory fitness, cerebral and peripheral vascular reactivity, and cognitive function in the sedentary and endurance-trained middle-aged adults. Methods Thirty-two endurance-trained and 27 healthy sedentary participants aged 43–65 years underwent measurements of maximal oxygen uptake (VO2max), neurocognitive assessment, cerebrovascular reactivity to CO2 (CVR), and brachial artery flow-mediated dilation (FMD). Results There were no group differences in age, sex, education level, fasting blood glucose, and blood pressure. Compared with sedentary subjects, endurance-trained athletes demonstrated better cognitive performance on memory (z-score: −0.36±1.11 vs. 0.30±0.76, P<0.01), attention-executive function (z-score: −0.21±0.53 vs. 0.18±0.72, P=0.02), and total cognitive composite scores (z-score: −0.27±0.63 vs. 0.23±0.57, P<0.01). Furthermore, brachial FMD (4.70±2.50 % vs. 7.13±3.09 %, P<0.01) and CVR (4.19±0.71 %/mmHg vs. 4.69±1.06 %/mmHg, P=0.052) were greater in endurance-trained individuals than in the sedentary subjects. Total cognitive composite scores showed a significant positive association with brachial FMD (r = 0.36, P < 0.01) and CVR (r = 0.30, P = 0.03). Finally, when brachial FMD and CVR were entered as covariates, fitness-related group differences in total cognitive composite score were significantly attenuated (all P>0.05). Conclusion Endurance-trained middle-aged adults demonstrated better cognitive performance which may, at least in part, be mediated by their enhanced vascular function, including cerebral and endothelial-dependent vascular reactivity. PMID:26083772

  11. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    PubMed

    Rouver, Wender Nascimento; Delgado, Nathalie Tristão Banhos; Menezes, Jussara Bezerra; Santos, Roger Lyrio; Moyses, Margareth Ribeiro

    2015-01-01

    The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

  12. Effect of magnesium on vascular reactivity in NOS inhibition-induced hypertension.

    PubMed

    Basralı, Filiz; Nasırcılar Ülker, Seher; Koçer, Günnur; Ülker Karadamar, Pınar; Özyurt, Dilek; Cengiz, Melike; Şentürk, Ümit Kemal

    2015-06-01

    This study investigated the effect of magnesium on the vascular reactivity of conduit and resistance arteries in a nitric oxide synthase inhibition-induced hypertension model. The aorta and third-order branches of the mesenteric artery were dissected from normotensive control and hypertensive rats, and their constriction and dilation responses in physiological saline solution containing normal (1.2 mM) or high (4.8 mM) magnesium concentrations were examined. The responses of the vessels were evaluated using potassium chloride (KCl) and phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside. The Phe-induced constriction response of the aortic rings increased, whereas the ACh-induced dilation response decreased, in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium did not alter these responses in either group. Both the KCl- and Phe-induced constriction responses of the mesenteric arteries increased, and the ACh-induced dilation response decreased in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium significantly decreased the KCl and Phe-induced constriction and increased the ACh-induced dilation response of the mesenteric arteries in the hypertensive group, while it did not alter these responses in controls. This study suggests that high magnesium improves vascular reactivity of resistance-, but not conduit-type arteries in the nitric oxide synthase inhibition-induced hypertension model.

  13. Antenatal betamethasone alters vascular reactivity in adult female ovine cerebral arteries.

    PubMed

    Eckman, Delrae M; Kerr, Brady A; Fuloria, Mamta; Simandle, Steve A; Watt, Suzanne E; Rose, James C; Figueroa, Jorge P

    2010-10-01

    Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta-exposed and control sheep, whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there seemed to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep.

  14. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry.

    PubMed

    Naghavi, Morteza; Yen, Albert A; Lin, Alex W H; Tanaka, Hirofumi; Kleis, Stanley

    2016-01-01

    Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM) as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI) was normally distributed and inversely correlated with age (r = -0.21, p < 0.0001). Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0), 70 percent as intermediate (1.0 ≤ VRI < 2.0), and 17 percent as good (VRI ≥ 2.0). Poor VRI (<1.0) was noted in 6% of <50 y, 10% of 50-70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care.

  15. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry

    PubMed Central

    Yen, Albert A.; Lin, Alex W. H.; Tanaka, Hirofumi; Kleis, Stanley

    2016-01-01

    Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM) as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI) was normally distributed and inversely correlated with age (r = −0.21, p < 0.0001). Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0), 70 percent as intermediate (1.0 ≤ VRI < 2.0), and 17 percent as good (VRI ≥ 2.0). Poor VRI (<1.0) was noted in 6% of <50 y, 10% of 50–70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care. PMID:27830091

  16. Generation of Reactive Oxygen Species Contributes to the Development of Carbon Black Cytotoxicity to Vascular Cells

    PubMed Central

    Lee, Jong Gwan; Noh, Won Jun; Kim, Hwa

    2011-01-01

    Carbon black, a particulate form of pure elemental carbon, is an industrial chemical with the high potential of occupational exposure. Although the relationship between exposure to particulate matters (PM) and cardiovascular diseases is well established, the cardiovascular risk of carbon black has not been characterized clearly. In this study, the cytotoxicity of carbon black to vascular smooth muscle and endothelial cells were examined to investigate the potential vascular toxicity of carbon black. Carbon black with distinct particle size, N330 (primary size, 28~36 nm) and N990 (250~350 nm) were treated to A-10, rat aortic smooth muscle cells and human umbilical vein endothelial cell line, ECV304, and cell viability was assessed by lactate dehydrogenase (LDH) leakage assay. Treatment of carbon black N990 resulted in the significant reduction of viability in A-10 cells at 100 μg/ml, the highest concentration tested, while N330 failed to cause cell death. Cytotoxicity to ECV304 cells was induced only by N330 at higher concentration, 200 μg/ml, suggesting that ECV304 cells were relatively resistant to carbon black. Treatment of 100 μg/ml N990 led to the elevation of reactive oxygen species (ROS) detected by dichlorodihydrofluorescein (DCF) in A-10 cells. Pretreatment of antioxidants, N-acetylcysteine (NAC) and sulforaphane restored decreased viability of N990-treated A-10 cells, and N-acetylcysteine, but not sulforaphane, attenuated N990-induced ROS generation in A-10 cells. Taken together, present study shows that carbon black is cytotoxic to vascular cells, and the generation of reactive oxygen contributes to the development of cytotoxicity. ROS scavenging antioxidant could be a potential strategy to attenuate the toxicity induced by carbon black exposure. PMID:24278567

  17. Oral supplementation with the rutin improves cardiovagal baroreflex sensitivity and vascular reactivity in hypertensive rats.

    PubMed

    Mendes-Junior, Leônidas das Graças; Monteiro, Matheus Morais de Oliveira; Carvalho, Alynne Dos Santos; de Queiroz, Thyago Moreira; Braga, Valdir de Andrade

    2013-11-01

    The hypothesis that oral supplementation with the flavonoid rutin improves baroreflex sensitivity and vascular reactivity in hypertensive (2-kidney-1-clip (2K1C)) rats was tested. Sixty-four rats were divided in 4 groups: sham + saline; sham + rutin; 2K1C + saline, and 2K1C + rutin. Six weeks after 2K1C surgery, the animals were treated with saline or rutin (40 mg·kg(-1)·day(-1)) by gavage for 7 days. Baroreflex sensitivity test using phenylephrine (8 μg·kg(-1), iv) and sodium nitroprusside (25 μg·kg(-1), iv), vascular reactivity, and thiobarbituric acid reactive substances assay were performed. Baroreflex sensitivity in hypertensive rats was impaired and compared with sham (-2.77 ± 0.15 vs. -1.53 ± 0.27 beats·min(-1)·mm Hg(-1); n = 8; p < 0.05). Oral supplementation with rutin restored baroreflex sensitivity in 2K1C rats (-2.40 ± 0.24 vs. -2.77 ± 0.15 beats·min(-1)·mm Hg(-1); n = 8; p > 0.05). Besides, hypertensive rats have greater contraction to phenylephrine (129.49% ± 4.46% vs. 99.50% ± 11.36%; n = 8; p < 0.05), which was restored by rutin (99.10% ± 1.77% vs. 99.50% ± 11.36%; n = 8; p > 0.05). Furthermore, vasorelaxation to acetylcholine was diminished in hypertensive rats (96.42% ± 2.80% vs. 119.35% ± 5.60%; n = 8; p < 0.05), which was also restored by rutin (117.55% ± 6.94% vs. 119.35% ± 5.60%; n = 8; p > 0.05). Finally, oxidative stress was greater in hypertensive rats (1.54 ± 0.12 vs. 0.53 ± 0.12 nmol MDA·mL(-1); n = 8; p < 0.05) and rutin supplementation significantly decreased oxidative stress in those animals (0.70 ± 0.13 vs. 1.54 ± 0.12 nmol MDA·mL(-1); n = 8; p < 0.05). We concluded that oral supplementation with rutin restores impaired baroreflex sensitivity and vascular reactivity in hypertensive rats by decreasing oxidative stress.

  18. Microstructural White Matter Abnormalities and Cognitive Dysfunction in Subcortical Ischemic Vascular Disease: an Atlas-Based Diffusion Tensor Analysis Study.

    PubMed

    Lin, Lin; Xue, Yunjing; Duan, Qing; Sun, Bin; Lin, Hailong; Chen, Xiaodan; Luo, Ling; Wei, Xiaofan; Zhang, Zhongping

    2015-06-01

    Recent studies in subcortical ischemic vascular disease (SIVD) suggest the involvement of white matter (WM) abnormalities underlying the pathogenesis of cognitive function impairment. Here, we performed magnetic resonance diffusion tensor imaging (DTI) on detecting WM damage and to investigate the correlations between DTI measures and cognitive dysfunction in SIVD patients. Fifty right-handed SIVD patients were recruited and divided into vascular cognitive impairment on dementia (VCIND) group and normal cognition (NC) group. Twenty-two VCIND patients and 28 NC patients underwent DTI scanning and neuropsychological assessment. Atlas-based analysis (ABA) was performed on each subject for extracting FA and MD measures from supratentorial tracts. Among VCIND, as compared to NC patients, decreased FA and increased MD were observed in all projection fibers (bilateral anterior, posterior limb, and retrolenticular part of internal capsule, anterior, superior, and posterior corona radiata and posterior thalamic radiation), association fibers (bilateral sagittal stratum, external capsule, cingulum, fornix, and stria terminalis, superior longitudinal fasciculus, superior fronto-occipital fasciculus, and uncinate fasciculus), and commissural fibers (genu, body, splenium, and bilateral tapetum of corpus callosum). Furthermore, we also found that MoCA scores correlated with DTI values in all supratentorial WM tracts. The results suggested that SIVD patients demonstrated abnormal WM connectivity in all supratentorial regions. Moreover, the severity of damage in WM tracts correlated with cognitive dysfunction.

  19. Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein.

    PubMed

    Cossette, Émilie; Cloutier, Isabelle; Tardif, Kim; DonPierre, Geneviève; Tanguay, Jean-François

    2013-01-01

    In addition of being an important inflammatory biomarker and a risk factor for cardiovascular disease, much evidence indicates that the C-reactive protein (CRP) contributes to the atherosclerosis development process. This plasmatic protein synthesized by hepatocytes in response to inflammation and tissue injury induces pro-inflammatory molecules' expression by endothelial cells (ECs). Previous studies showed that the 17β-estradiol (E2) has beneficial effects on vascular cells by reducing in vitro pro-inflammatory molecules expressions in EC. Therefore, we hypothesize that E2 blocks or reduces CRP-mediated inflammatory responses by modulating endogenous production of CRP in EC and/or activation mechanisms. Using human aortic ECs (HAECs), we first evaluated CRP production by vascular EC and second demonstrated its self-induction. Indeed, recombinant human CRP stimulation induces a fivefold increase of CRP expression. A 1-h pre-treatment of E2 at a physiologic dose (10(-9 )M) leads to an important decrease of CRP production suggesting a partial blockage of its amplification loop mechanism. Furthermore, in HAEC, E2 reduces the secretion of the most potent agonist of CRP induction, the IL-6, by 21 %. E2 pre-treatment also decreased the expression of pro-inflammatory molecules IL-8, VCAM-1, and ICAM-1 induced by CRP and involved in leukocytes recruitment. In addition, we demonstrated that E2 could restore vascular endothelial growth factor-mediated EC migration response impaired by CRP suggesting another pro-angiogenic property of this hormone. These findings suggest that E2 can interfere with CRP pro-inflammatory effects via activation signals using its rapid, non-genomic pathway that may provide a new mechanism to improve vascular repair.

  20. Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans.

    PubMed

    Gilmartin, Geoffrey S; Tamisier, Renaud; Curley, Matthew; Weiss, J Woodrow

    2008-08-01

    Recurrent and intermittent nocturnal hypoxia is characteristic of several diseases including chronic obstructive pulmonary disease, congestive heart failure, obesity-hypoventilation syndrome, and obstructive sleep apnea. The contribution of hypoxia to cardiovascular morbidity and mortality in these disease states is unclear, however. To investigate the impact of recurrent nocturnal hypoxia on hemodynamics, sympathetic activity, and vascular tone we evaluated 10 normal volunteers before and after 14 nights of nocturnal sustained hypoxia (mean oxygen saturation 84.2%, 9 h/night). Over the exposure, subjects exhibited ventilatory acclimatization to hypoxia as evidenced by an increase in resting ventilation (arterial Pco(2) 41.8 +/- 1.5 vs. 37.5 +/- 1.3 mmHg, mean +/- SD; P < 0.05) and in the isocapnic hypoxic ventilatory response (slope 0.49 +/- 0.1 vs. 1.32 +/- 0.2 l/min per 1% fall in saturation; P < 0.05). Subjects exhibited a significant increase in mean arterial pressure (86.7 +/- 6.1 vs. 90.5 +/- 7.6 mmHg; P < 0.001), muscle sympathetic nerve activity (20.8 +/- 2.8 vs. 28.2 +/- 3.3 bursts/min; P < 0.01), and forearm vascular resistance (39.6 +/- 3.5 vs. 47.5 +/- 4.8 mmHg.ml(-1).100 g tissue.min; P < 0.05). Forearm blood flow during acute isocapnic hypoxia was increased after exposure but during selective brachial intra-arterial vascular infusion of the alpha-blocker phentolamine it was unchanged after exposure. Finally, there was a decrease in reactive hyperemia to 15 min of forearm ischemia after the hypoxic exposure. Recurrent nocturnal hypoxia thus increases sympathetic activity and alters peripheral vascular tone. These changes may contribute to the increased cardiovascular and cerebrovascular risk associated with clinical diseases that are associated with chronic recurrent hypoxia.

  1. Abnormal thallium kinetics in postoperative coarctation of the aorta: evidence for diffuse hypertension-induced vascular pathology

    SciTech Connect

    Kimball, B.P.; Shurvell, B.L.; Mildenberger, R.R.; Houle, S.; McLaughlin, P.R.

    1986-03-01

    After operative correction of congenital coarctation of the aorta, patients continue to have excess cardiovascular mortality, including manifestations of ischemic heart disease. Previous morphologic studies support the concept of direct hypertensive vascular injury in these patients. To determine whether abnormalities of myocardial perfusion were present in an asymptomatic group of patients with coarctation repair, 18 men and 9 women with a mean age of 26 years (range 19 to 41) were studied between 2 and 25 years after operative correction. Stress electrocardiography and quantitative thallium imaging by a circumferential profile technique were used. These patients were compared with a normal group, statistically defined as having a less than 1% prevalence of significant obstructive coronary artery disease. The postoperative coarctation group demonstrated a reduction in global thallium redistribution in each view analyzed. As compared with findings in the control subjects, thallium washout in the anterior view (41.9 versus 48.6%, p = 0.02) and left anterior oblique projection (40.5 versus 48.2%, p = 0.007) was significantly diminished. Although the postoperative coarctation group had a lower thallium redistribution rate in the lateral view (41.4 versus 46.3%, p = 0.09) this difference did not reach statistical significance because of the intrinsic variability of this projection. Plots of the median percent thallium washout revealed independence from circumferential profile angle, indicating global abnormalities in perfusion. No correlation between clinical variables and thallium kinetics could be established, suggesting marked individual variability in the development of this vascular lesion. The observation of abnormal thallium kinetics in patients with coarctation repair may have consequences for long-term follow-up and therapy.

  2. DIVERSITY OF VASCULAR REACTIVITY AND THE TREATMENT RESPONSE IN DIABETIC, HYPERTENSIVE, HYPERLIPIDEMIC, AND HEALTHY RATS SUBJECTED TO HEMORRHAGIC SHOCK.

    PubMed

    Wu, Yue; Zhu, Yu; Chen, Xiang-Yun; Liu, Liang-Ming; Li, Tao

    2016-02-01

    The current diagnosis and treatment guidelines for severe trauma and shock are all for healthy population. Few studies focused on the pathophysiological features and treatments in metabolic diseases after severe trauma and shock. Vascular reactivity is significantly decreased after severe trauma and shock. Improving the vascular reactivity with arginine vasopressin (AVP) and phorbol-12 myristate-13-acetate (PMA) is beneficial to trauma and shock. Whether the cardiovascular function and treatment responses have the own features in hypertensive, diabetic, and hyperlipidemic patients after traumatic hemorrhagic shock is not known. Using hypertensive, diabetic, and hyperlipidemic and healthy rats, we compared the change patterns in cardiovascular function including vascular reactivity, tissue perfusion, and the hemodynamics after hemorrhagic shock and their responses to AVP, PMA, and common antishock agents including dopamine and norepinephrine. A same degree of hemorrhagic shock (40% hemorrhage or mean arterial pressure maintained at 40 mm Hg for 2 h) resulted in a more obvious decrease in vascular reactivity, hemodynamics, tissue perfusion, and mitochondrial function of liver and kidney in hypertensive, diabetic, and hyperlipidemic rats, and a more rapidly natural death than in healthy rats. The effectiveness of AVP and PMA in these diseased rats was lower than in healthy rats. The effective dosage of common antishock agents including norepinephrine, dopamine, and AVP in healthy rats was wider than that in these diseased rats. Among the antishock agents used in the current study, AVP had the best effect in improving animal survival and vascular reactivity both in healthy and in diseased rats. These findings suggest that hypertensive, diabetic, and hyperlipidemic rats have a worse vascular reactivity and organ function than the healthy rats after traumatic hemorrhagic shock, which result in the worse treatment responses and effects to vasoactive agents. Lower dose

  3. The vascular steal phenomenon is an incomplete contributor to negative cerebrovascular reactivity in patients with symptomatic intracranial stenosis.

    PubMed

    Arteaga, Daniel F; Strother, Megan K; Faraco, Carlos C; Jordan, Lori C; Ladner, Travis R; Dethrage, Lindsey M; Singer, Robert J; Mocco, J; Clemmons, Paul F; Ayad, Michael J; Donahue, Manus J

    2014-09-01

    'Vascular steal' has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients (n=40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree<50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant (P<0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.

  4. Optical tomographic imaging of vascular and metabolic reactivity in rheumatoid joints

    NASA Astrophysics Data System (ADS)

    Lasker, Joseph M.; Dwyer, Edward; Hielscher, Andreas H.

    2005-04-01

    Our group has recently established that joints affected by Rheumatoid Arthritis (RA) can be distinguished from healthy joints through measurements of the scattering coefficient. We showed that a high scattering coefficient in the center of the joint is indicative of a joint with RA. While these results were encouraging, data to date still suffers from low sensitivity and specificity. Possibly higher specificities and sensitivities can be achieved if dynamic measurements of hemodynamic and metabolic processes in the synovium are considered. Using our dual-wavelength imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed initial dynamic imaging studies involving healthy human volunteers and patients affected by RA. These case studies seem to confirm our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints.

  5. Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints.

    PubMed

    Lasker, Joseph M; Fong, Christopher J; Ginat, Daniel T; Dwyer, Edward; Hielscher, Andreas H

    2007-01-01

    Dynamic optical imaging is increasingly applied to clinically relevant areas such as brain and cancer imaging. In this approach, some external stimulus is applied and changes in relevant physiological parameters (e.g., oxy- or deoxyhemoglobin concentrations) are determined. The advantage of this approach is that the prestimulus state can be used as a reference or baseline against which the changes can be calibrated. Here we present the first application of this method to the problem of characterizing joint diseases, especially effects of rheumatoid arthritis (RA) in the proximal interphalangeal finger joints. Using a dual-wavelength tomographic imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed initial dynamic imaging case studies on a limited number of healthy volunteers and patients diagnosed with RA. Focusing on three cases studies, we illustrated our major finds. These studies support our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints.

  6. Vascular stents with submicrometer-scale surface patterning realized via titanium deep reactive ion etching

    NASA Astrophysics Data System (ADS)

    Gott, Shannon C.; Jabola, Benjamin A.; Rao, Masaru P.

    2015-08-01

    Herein, we report progress towards realization of vascular stents that will eventually provide opportunity for evaluating cellular response to rationally-designed, submicrometer-scale surface patterning in physiologically-relevant contexts, i.e. those that provide exposure to the complex multicellular milieu, flow-induced shear, and tissue-device interactions present in vivo. Specifically, using our novel titanium deep reactive ion etching technique (Ti DRIE), we discuss recent advances that have enabled: (a) fabrication of precisely-defined, grating-based surface patterns on planar Ti foils with minimum feature sizes as small as 0.15 μm (b) creation of cylindrical stents from micromachined planar Ti foils; and (c) integration of these processes to produce the first submicrometer-scale surface-patterned Ti stents that are compatible with conventional balloon catheter deployment techniques. We also discuss results from elastoplastic finite element simulations and preliminary mechanical testing of these devices to assess their mechanical performance. These efforts represent key steps towards our long-term goal of developing a new paradigm in stenting, where rationally-designed surface patterning provides a physical means for facilitating healing, and thus, improving outcomes in vascular intervention applications.

  7. Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity.

    PubMed

    Atkins, Kevin B; Seki, Yoshinori; Saha, Jharna; Eichinger, Felix; Charron, Maureen J; Brosius, Frank C

    2015-02-01

    Previous studies have shown that expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT4 rather than on some systemic effect we developed and tested smooth-muscle-specific GLUT4 transgenic mice (SMG4). When made hypertensive with angiotensin II, both wild-type and SMG4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin F2α was significantly increased in endothelium-intact aortic rings from hypertensive wild-type mice but not in aortae of SMG4 mice. Inhibition of Rho-kinase equally reduced serotonin-stimulated contractility in aortae of hypertensive wild-type and SMG4-mice. In addition, acetylcholine-stimulated relaxation was significantly decreased in aortic rings of hypertensive wild-type mice, but not in rings of SMG4 mice. Inhibition of either prostacylin receptors or cyclooxygenase-2 reduced relaxation in rings of hypertensive SMG4 mice. Inhibition of cyclooxygenase-2 had no effect on relaxation in rings of hypertensive wild-type mice. Cyclooxygenase-2 protein expression was decreased in hypertensive wild-type aortae but not in hypertensive SMG4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT4 exerts a major effect on smooth muscle contractile responses and endothelium-dependent vasorelaxation and that normal expression of GLUT4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses.

  8. Raloxifene improves vascular reactivity in pressurized septal coronary arteries of ovariectomized hamsters fed cholesterol diet.

    PubMed

    Chan, Yau-Chi; Leung, Fung Ping; Tian, Xiao Yu; Yung, Lai Ming; Lau, Chi Wai; Chen, Zhen Yu; Yao, Xiaoqiang; Laher, Ismail; Huang, Yu

    2012-02-01

    Although vascular effects of selective estrogen receptor modulators (SERMs) have been extensively examined in conduit arteries, whether SERMs could favorably modulate myogenic response in resistance arteries is unknown. The impact of raloxifene therapy and cholesterol diet on myogenic constriction during estrogen deficiency is unresolved. This study investigated changes in vascular reactivity and myogenic responses in female ovariectomized (Ovx) hamsters fed high-cholesterol diet (HCD) with and without chronic treatment of raloxifene. Functional studies were performed on hamster septal coronary arteries cannulated in a pressure myograph. Acetylcholine (ACh)-induced dilatation was reduced in arteries from cholesterol-fed Ovx hamsters, but not in those from cholesterol-fed hamsters, while pressure-induced myogenic constriction was unaffected. Chronic treatment with raloxifene restored ACh-induced dilatation in cholesterol-fed Ovx hamsters. U46619-induced constriction was increased in arteries from cholesterol-fed Ovx hamsters but not from cholesterol-fed control hamsters, which was normalized by chronic raloxifene treatment. The pressure-diameter relationship is presented as normalized diameter versus intraluminal pressure, while the effect of ACh or U46619 is expressed as percentage of tone at 80 mm Hg. Two-way analysis of variance (ANOVA) followed by Bonferroni post-tests were used for statistical evaluation among different treatment groups. P<0.05 was taken as statistically significant. The present results show that chronic treatment with raloxifene could benefit myogenically active coronary arteries by (i) restoring ACh-induced dilatation and (ii) reducing U46619-induced constriction without affecting pressure-induced myogenic responses in cholesterol-fed hamsters during estrogen deficiency. If such benefit can be observed in humans, raloxifene and other SERMs may be useful to preserve endothelial function and curtail vascular hypersensitivity in resistance

  9. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  10. Abnormal Mammary Adipose Tissue Environment of Brca1 Mutant Mice Show a Persistent Deposition of Highly Vascularized Multilocular Adipocytes.

    PubMed

    Jones, Laundette P; Buelto, Destiney; Tago, Elaine; Owusu-Boaitey, Kwadwo E

    2011-12-08

    A major challenge to breast cancer research is the identification of alterations in the architecture and composition of the breast that are associated with breast cancer progression. The aim of the present investigation was to characterize the mammary adipose phenotype from Brca1 mutant mice in the expectation that this would shed light on the role of the mammary tissue environment in the early stages of breast tumorigenesis. We observed that histological sections of mammary tissue from adult Brca1 mutant mice abnormally display small, multilocular adipocytes that are reminiscent of brown adipose tissue (BAT) as compared to wildtype mice. Using a marker for BAT, the uncoupling protein 1 (UCP1), we demonstrated that these multilocular adipose regions in Brca1 mutant mice stain positive for UCP1. Transcriptionally, UCP1 mRNA levels in the Brca1 mutant mice were elevated greater than 50-fold compared to age-matched mammary glands from wildtype mice. Indeed, BAT has characteristics that are favorable for tumor growth, including high vascularity. Therefore, we also demonstrated that the multilocular brown adipose phenotype in the mammary fat pad of Brca1 mutant mice displayed regions of increased vascularity as evidenced by a significant increase in the protein expression of CD31, a marker for angiogenesis. This Brca1 mutant mouse model should provide a physiologically relevant context to determine whether brown adipose tissue can play a role in breast cancer development.

  11. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function

    PubMed Central

    Burger, Dylan; Turner, Maddison; Munkonda, Mercedes N.; Touyz, Rhian M.

    2016-01-01

    Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs) and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS) and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2∙−) generation, and nitric oxide (NO) production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47phox, p67phox, and p22phox and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2∙− production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation. PMID:27313830

  12. Lumped parameter thermal model for the study of vascular reactivity in the fingertip.

    PubMed

    Ley, O; Deshpande, C; Prapamcham, B; Naghavi, M

    2008-06-01

    Vascular reactivity (VR) denotes changes in volumetric blood flow in response to arterial occlusion. Current techniques to study VR rely on monitoring blood flow parameters and serve to predict the risk of future cardiovascular complications. Because tissue temperature is directly impacted by blood flow, a simplified thermal model was developed to study the alterations in fingertip temperature during arterial occlusion and subsequent reperfusion (hyperemia). This work shows that fingertip temperature variation during VR test can be used as a cost-effective alternative to blood perfusion monitoring. The model developed introduces a function to approximate the temporal alterations in blood volume during VR tests. Parametric studies are performed to analyze the effects of blood perfusion alterations, as well as any environmental contribution to fingertip temperature. Experiments were performed on eight healthy volunteers to study the thermal effect of 3 min of arterial occlusion and subsequent reperfusion (hyperemia). Fingertip temperature and heat flux were measured at the occluded and control fingers, and the finger blood perfusion was determined using venous occlusion plethysmography (VOP). The model was able to phenomenologically reproduce the experimental measurements. Significant variability was observed in the starting fingertip temperature and heat flux measurements among subjects. Difficulty in achieving thermal equilibration was observed, which indicates the important effect of initial temperature and thermal trend (i.e., vasoconstriction, vasodilatation, and oscillations).

  13. Endotoxin "priming" potentiates lung vascular abnormalities in response to Escherichia coli hemolysin: an example of synergism between endo- and exotoxin

    PubMed Central

    1994-01-01

    The pore-forming hemolysin of Escherichia coli (HlyA), an important virulence factor in extraintestinal E. coli infections, causes thromboxane generation and related vasoconstriction in perfused rabbit lungs (Seeger, W., H. Walter, N. Suttorp, M. Muhly, and S. Bhakdi. 1989. J. Clin. Invest. 84:220). We investigated the influence of pulmonary vascular "priming" with endotoxin on the responsiveness of the lung to a low-dose HlyA challenge. Rabbit lungs were perfused with Krebs Henseleit buffer containing 0.1-100 ng/ml Salmonella abortus equii lipopolysaccharide (LPS) for 60-180 min. This treatment caused protracted release of tumor necrosis factor into the recirculating medium, but did not induce significant alterations of pulmonary hemodynamics and fluid balance. At a dose of 1 ng/ml, HlyA elicited only moderate thromboxane release (< 200 pg/ml) and pulmonary artery pressure increase (< or = 6 mmHg) in control lungs. Acceleration and potentiation of both the metabolic and vasoconstrictor response occurred in lungs primed with LPS. This priming effect displayed dose (threshold integral of 0.1-1 ng/ml LPS) and time dependencies (threshold integral of 60-90 min LPS incubation). Maximum thromboxane release and pulmonary artery pressure increase surpassed the responses to HlyA in nonprimed lungs by more than 15-fold. Cyclooxygenase inhibition and thromboxane-receptor antagonism blocked these effects. These data demonstrate that LPS priming synergizes with HlyA challenge to provoke vascular abnormalities that are possibly relevant to the pathogenesis of organ failure in severe local and systemic infections. PMID:7931076

  14. Vascular tone and reactivity to serotonin in the internal and external carotid vascular beds of the dog.

    PubMed

    Vidrio, H; Hong, E

    1976-04-01

    The effects of intra-arterial infusions of serotonin on internal and external carotid blood flow were determined in anesthetized dogs by electromagnetic flow measurements. Serotonin decreased flow in the internal carotid and increased it in the external carotid. Both responses were blocked by the serotonin antagonist methysergide. The alpha adrenergic antagonist zolertine, the ganglionic blocking agent chlorisondamine and the vasodilator diazoxide blocked external carotid dilator responses but did not modify constriction in the internal carotid. Blockade of external carotid responses by the three drugs was also demonstrated in experiments in which this bed was perfused at a constant rate. These results indicate that the internal and external carotid vascular beds of the dog react in opposite ways to serotonin, that both responses are mediated through the same type of serotonin receptors and that the dilator responses of the external carotid are dependent on vascular tone.

  15. Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation.

    PubMed

    Eccles, J A; Garfinkel, S N; Harrison, N A; Ward, J; Taylor, R E; Bewley, A P; Critchley, H D

    2015-10-01

    Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal.

  16. Blood pressure and vascular reactivity changes in spontaneously hypertensive rats fed fish oil.

    PubMed Central

    Yin, K.; Chu, Z. M.; Beilin, L. J.

    1991-01-01

    1. To examine possible mechanisms of antihypertensive effects of feeding fish oil rich in n-3 fatty acids, we have studied vascular reactivity of aortic rings and perfused mesenteric resistance vessels of spontaneously hypertensive rats (SHR) given such a diet. 2. In two experiments, rats were fed a semi-synthetic diet containing either 'fish oil' (10 and 20% by weight) or hydrogenated coconut oil (control) (10 and 20%) for 4 weeks. 3. Blood pressure rose significantly less in the fish oil group than in controls in both experiments. 4. Aortic rings from control rats showed endothelium-dependent relaxations to low concentrations of acetylcholine (ACh) but relaxed less at higher concentrations. In contrast, rings from the fish oil group had relaxations which increased through the range of concentrations used. Indomethacin (10 microM) also increased the relaxation responses seen in rings from control rats, suggesting that fish oil inhibits a contractile cyclo-oxygenase product. This contractile substance may be thromboxane A2 (TxA2) or its endoperoxide precursor, prostaglandin H2 (PGH2) as aortic incubates and serum levels of TxB2 (the stable product of TxA2) were greatly reduced in fish oil-fed rats, and the decrease of relaxant responses to high concentrations of ACh were also blocked by a TxA2/PGH2 receptor blocker (SQ 29548). 5. In contrast to aortic rings, perfused preconstricted mesenteric resistance vessels of control rats relaxed to ACh in a similar fashion to tissues from fish oil-fed rats. However, in this preparation, fish oil feeding enhanced relaxations to sodium nitroprusside (SNP) and contractile responses to noradrenaline were less than controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1855129

  17. Altering dietary lysine:arginine ratio has little effect on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults

    PubMed Central

    Vega-López, Sonia; Matthan, Nirupa R.; Ausman, Lynne M.; Harding, Scott V.; Rideout, Todd C.; Ai, Masumi; Otokozawa, Seiko; Freed, Alicia; Kuvin, Jeffrey T; Jones, Peter J; Schaefer, Ernst J; Lichtenstein, Alice H.

    2010-01-01

    Background Information is scarce regarding the effect of dietary protein type, with specific focus on the lysine to arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans. Objective Determine effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults. Design Randomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 y, LDL cholesterol ≥120 mg/dL). Diets had 20% energy (E) protein, 30%E fat, 50%E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL)-cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT). Results No differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (−24%, P=0.001) and triglycerides (−23%, P=0.001), and small but significant differences in fasting (−3%, P=0.003) and postprandial (−3%, P=0.018) apo AI, and fasting adiponectin concentrations (+7%, P=0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P=0.020 for both). Conclusions Diets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity. PMID:20042191

  18. Cerebral Hemodynamics and Vascular Reactivity in Mild and Severe Ischemic Rodent Middle Cerebral Artery Occlusion Stroke Models

    PubMed Central

    Sim, Jeongeun; Jo, Areum; Kang, Bok-Man; Lee, Sohee; Bang, Oh Young; Heo, Chaejeong; Jhon, Gil-Ja; Lee, Youngmi

    2016-01-01

    Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia. PMID:27358581

  19. Rho kinase acts as a downstream molecule to participate in protein kinase Cε regulation of vascular reactivity after hemorrhagic shock in rats.

    PubMed

    Li, Tao; Zhu, Yu; Zang, Jia-tao; Peng, Xiao-yong; Lan, Dan; Yang, Guang-ming; Xu, Jing; Liu, Liang-ming

    2014-09-01

    Our previous study demonstrated that Rho kinase and protein kinase C (PKC) played important parts in the regulation of vascular reactivity after shock. Using superior mesenteric arteries (SMAs) from hemorrhagic shock rats and hypoxia-treated vascular smooth muscle cells (VSMCs), relationship of PKCε regulation of vascular reactivity to Rho kinase, as well as the signal transduction after shock, was investigated. The results showed that inhibition of Rho kinase with the Rho kinase-specific inhibitor Y-27632 antagonized the PKCε-specific agonist carbachol and highly expressed PKCε-induced increase of vascular reactivity in SMAs and VSMCs, whereas inhibition of PKCε with its specific inhibitory peptide did not antagonize the Rho kinase agonist (U-46619)-induced increase of vascular reactivity in SMAs and VSMCs. Activation of PKCε or highly expressed PKCε upregulated the activity of Rho kinase and the phosphorylation of PKC-dependent phosphatase inhibitor 17 (CPI-17), zipper interacting protein kinase (ZIPK), and integrin-linked kinase (ILK), whereas activation of Rho kinase increased only CPI-17 phosphorylation. The specific neutralization antibodies of ZIPK and ILK antagonized PKCε-induced increases in the activity of Rho kinase, but CPI-17 neutralization antibody did not antagonize this effect. These results suggested that Rho kinase takes part in the regulation of PKCε on vascular reactivity after shock. Rho kinase is downstream of PKCε. Protein kinase Cε activates Rho kinase via ZIPK and ILK; CPI-17 is downstream of Rho kinase.

  20. E-Cigarette Aerosol Exposure Induces Reactive Oxygen Species, DNA Damage, and Cell Death in Vascular Endothelial Cells.

    PubMed

    Anderson, Chastain; Majeste, Andrew; Hanus, Jakub; Wang, Shusheng

    2016-12-01

    Cigarette smoking remains one of the leading causes of preventable death worldwide. Vascular cell death and dysfunction is a central or exacerbating component in the majority of cigarette smoking related pathologies. The recent development of the electronic nicotine delivery systems known as e-cigarettes provides an alternative to conventional cigarette smoking; however, the potential vascular health risks of e-cigarette use remain unclear. This study evaluates the effects of e-cigarette aerosol extract (EAE) and conventional cigarette smoke extract (CSE) on human umbilical vein endothelial cells (HUVECs). A laboratory apparatus was designed to produce extracts from e-cigarettes and conventional cigarettes according to established protocols for cigarette smoking. EAE or conventional CSE was applied to human vascular endothelial cells for 4-72 h, dependent on the assay. Treated cells were assayed for reactive oxygen species, DNA damage, cell viability, and markers of programmed cell death pathways. Additionally, the anti-oxidants α-tocopherol and n-acetyl-l-cysteine were used to attempt to rescue e-cigarette induced cell death. Our results indicate that e-cigarette aerosol is capable of inducing reactive oxygen species, causing DNA damage, and significantly reducing cell viability in a concentration dependent fashion. Immunofluorescent and flow cytometry analysis indicate that both the apoptosis and programmed necrosis pathways are triggered by e-cigarette aerosol treatment. Additionally, anti-oxidant treatment provides a partial rescue of the induced cell death, indicating that reactive oxygen species play a causal role in e-cigarette induced cytotoxicity.

  1. Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed.

    PubMed

    Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M; Murillo, M Divina; Gálvez, José A; Díaz-de-Villegas, María D; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

    2016-08-01

    Opening of intermediate-conductance calcium-activated potassium channels (KC a 3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KC a 3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KC a 3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KC a currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KC a 3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KC a 3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KC a 3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KC a 3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease.

  2. Nafamostat Mesilate Inhibits TNF-α-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production.

    PubMed

    Kang, Min-Woong; Song, Hee-Jung; Kang, Shin Kwang; Kim, Yonghwan; Jung, Saet-Byel; Jee, Sungju; Moon, Jae Young; Suh, Kwang-Sun; Lee, Sang Do; Jeon, Byeong Hwa; Kim, Cuk-Seong

    2015-05-01

    Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-α (TNF-α). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 µg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-α (3 ng/mL), and it dose dependently prevented the TNF-α-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-α-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-α-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

  3. Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

    PubMed Central

    Bruder-Nascimento, Thiago; Silva, Samuel T.; Boer, Patrícia A.; Cordellini, Sandra

    2015-01-01

    Background: Physical exercise may modify biologic stress responses. Objective: To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method: Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load), stressed (2 h-immobilization), and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10). Results: None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary). Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed). Indomethacin determined a decrease in sensitivity (EC50) in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions: Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination. PMID:26083604

  4. Cyclooxygenase pathway is involved in the vascular reactivity and inhibition of the Na+, K+-ATPase activity in the tail artery from L-NAME-treated rats.

    PubMed

    dos Santos, Leonardo; Xavier, Fabiano E; Vassallo, Dalton V; Rossoni, Luciana V

    2003-12-19

    L-NAME (LN) induces hypertension by blocking nitric oxide (NO) synthesis. It produces vascular hyperreactivity to phenylephrine (PHE) associated with a reduced vascular Na+, K+-ATPase activity. The aim of this work was to investigate whether products of the cyclooxygenase pathway are involved in alterations of vascular reactivity and Na+-pump activity in the tail artery from LN-induced hypertension rats. Four groups of rats were used: Control (CT, normotensive), LN (50 mg/kg/day, hypertensive), indomethacin (Indo-4 mg/kg/day, normotensive), and LN plus Indo (LN + Indo, partially prevented hypertension). All drugs were administered in drinking water during 7 days. In isolated rat tail vascular beds; the reactivity to PHE, acetylcholine (ACh), sodium nitroprusside (SNP), the functional activity of the Na+, K+-ATPase (K+-induced relaxation) and the modulation of PHE-induced vasoconstriction by constitutively available NO were evaluated. LN increased vascular sensitivity (pD2) and reactivity (Emax) to PHE and Indo blocked the effect of LN on Emax without changing pD2. Emax and pD2 values for ACh were reduced by LN and partially reverted by Indo. SNP-induced vasodilatation was similar in all groups. LN reduced the activity of Na+, K+-ATPase and Indo prevented LN effects. LN also abolished NO ability to modulate PHE-induced contractions. This effect was partially prevented by Indo suggesting that products from the cyclooxygenase pathway might reduce NO actions. Indo itself did not affect vascular reactivity to PHE, ACh or SNP or the Na+,K+-ATPase activity. Results suggested that products from cyclooxygenase pathway are involved in the genesis or maintenance of LN-induced hypertension, playing a role in the increased vascular reactivity, in the reduction of the endothelium-dependent relaxation and in the inhibition of the functional activity of the Na+, K+-ATPase.

  5. VASCULAR INFLAMMATION AND ABNORMAL AORTIC HISTOMORPHOMETRY IN PATIENTS FOLLOWING PULSATILE AND CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICE PLACEMENT

    PubMed Central

    Lee, Mike; Akashi, Hirokazu; Kato, Tomoko S.; Takayama, Hiroo; Wu, Christina; Xu, Katherine; Collado, Elias; Weber, Matthew P.; Kennel, Peter J.; Brunjes, Danielle L; Ji, Ruiping; Naka, Yoshifumi; George, Isaac; Mancini, Donna; Farr, Maryjane; Schulze, P. Christian

    2017-01-01

    Objective Left ventricular assist devices are increasingly used in patients with advanced heart failure as both destination therapy and bridge-to-transplantation. We aimed to analyze histomorphometric, structural and inflammatory changes following pulsatile and continuous flow left ventricular assist device placement. Method Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous flow support. Both device types showed an increased inflammatory response following left ventricular assist device placement with variable T cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusion Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous flow left ventricular assist and associated with aortic media decellularization. These findings help to explain the progressive aortic root dilation and vascular dysfunction in patients following continuous flow device placement. PMID:26899764

  6. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    SciTech Connect

    Simões, Maylla Ronacher; Aguado, Andrea; Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice; Zhenyukh, Olha; Briones, Ana María; Alonso, María Jesús; Vassallo, Dalton Valentim; Salaices, Mercedes

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  7. 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

  8. Control of vascular smooth muscle function by Src-family kinases and reactive oxygen species in health and disease.

    PubMed

    MacKay, Charles E; Knock, Greg A

    2015-09-01

    Reactive oxygen species (ROS) are now recognised as second messenger molecules that regulate cellular function by reversibly oxidising specific amino acid residues of key target proteins. Amongst these are the Src-family kinases (SrcFKs), a multi-functional group of non-receptor tyrosine kinases highly expressed in vascular smooth muscle (VSM). In this review we examine the evidence supporting a role for ROS-induced SrcFK activity in normal VSM contractile function and in vascular remodelling in cardiovascular disease. VSM contractile responses to G-protein-coupled receptor stimulation, as well as hypoxia in pulmonary artery, are shown to be dependent on both ROS and SrcFK activity. Specific phosphorylation targets are identified amongst those that alter intracellular Ca(2+) concentration, including transient receptor potential channels, voltage-gated Ca(2+) channels and various types of K(+) channels, as well as amongst those that regulate actin cytoskeleton dynamics and myosin phosphatase activity, including focal adhesion kinase, protein tyrosine kinase-2, Janus kinase, other focal adhesion-associated proteins, and Rho guanine nucleotide exchange factors. We also examine a growing weight of evidence in favour of a key role for SrcFKs in multiple pro-proliferative and anti-apoptotic signalling pathways relating to oxidative stress and vascular remodelling, with a particular focus on pulmonary hypertension, including growth-factor receptor transactivation and downstream signalling, hypoxia-inducible factors, positive feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK and NADPH oxidase dependent ROS production. We also discuss evidence for and against the potential therapeutic targeting of SrcFKs in the treatment of pulmonary hypertension.

  9. Arsenite induces endothelial cell permeability increase through a reactive oxygen species-vascular endothelial growth factor pathway.

    PubMed

    Bao, Lingzhi; Shi, Honglian

    2010-11-15

    As a potent environmental oxidative stressor, arsenic exposure has been reported to exacerbate cardiovascular diseases and increase vascular endothelial cell monolayer permeability. However, the underlying mechanism of this effect is not well understood. In this paper, we test our hypothesis that reactive oxygen species (ROS)-induced vascular endothelial growth factor (VEGF) expression may play an important role in an arsenic-caused increase of endothelial cell monolayer permeability. The mouse brain vascular endothelial cell bEnd3 monolayer was exposed to arsenite for 1, 3, and 6 days. The monolayer permeability, VEGF protein release, and ROS generation were determined. In addition, VE-cadherin and zonula occludens-1 (ZO-1), two membrane structure proteins, were immunostained to elucidate the effects of arsenite on the cell-cell junction. The roles of ROS and VEGF in arsenite-induced permeability was determined by inhibiting ROS with antioxidants and immuno-depleting VEGF with a VEGF antibody. We observed that arsenite increased bEnd3 monolayer permeability, elevated the production of cellular ROS, and increased VEGF release. VE-cadherin and ZO-1 disruptions were also found in cells treated with arsenite. Furthermore, both antioxidant (N-acetyl cysteine and tempol) and the VEGF antibody treatments significantly lowered the arsenite-induced permeability of the bEnd3 monolayer as well as VEGF expression. VE-cadherin and ZO-1 disruptions were also diminished by N-acetyl cysteine and the VEGF antibody. Our data suggest that the increase in VEGF expression caused by ROS may play an important role in the arsenite-induced increase in endothelial cell permeability.

  10. Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

    NASA Technical Reports Server (NTRS)

    Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

    2002-01-01

    We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

  11. Vascular Reactivity: Evaluation of an acute suprasystolic occlusion with impedance plethysmography

    NASA Astrophysics Data System (ADS)

    Herrera, M. C.; Bonaudo, M.; Conde, A.; Palavecino, L.

    2007-11-01

    In the clinical set, the evaluation of endothelium- dependent vasodilator response of large vessels is carried out using ultrasound equipment for vascular flow determinations and during administration of vasoactive drugs. This work proposes to use a substantially cheaper technique and a sustained cuff arterial occlusion in order to cause vasodilation. Impedance plethysmography is used to detect the arterial pulse wave over radial artery while the forearm is occluded by above the recording site. From these plethysmographic waves, three indexes and their changes -between control and maximal response post-occlusion- were calculated. 33 complete records obtained from healthy low-risk volunteers were analyzed. Between control and post-occlusion maximal response, "average percentual change of pulse wave amplitude" were (35±13)%, "stiffness index" did not show significant differences (6,38±0,98 vs 6,38±0,94 and "reflection index" was significant lower (58±15 vs 35±16)%. These results indicate that: 1- cuff occlusion maneuver was effective to cause endothelium-dependent vasodilation, 2-changes of pulse wave amplitude and reflection index could be used as markers of athero-arteriosclerotic damage in the vascular bed, even in sub-clinical conditions.

  12. Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    de Matthaeis, Angela; Greco, Antonio; Dagostino, Mariangela Pia; Paroni, Giulia; Fontana, Andrea; Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Seripa, Davide; Vendemiale, Gianluigi

    2014-01-01

    Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium. PMID:24904207

  13. Regional cerebral blood flow and cerebrovascular reactivity in Alzheimer's disease and vascular dementia assessed by arterial spinlabeling magnetic resonance imaging.

    PubMed

    Gao, Yong-Zhe; Zhang, Jun-Jian; Liu, Hui; Wu, Guang-Yao; Xiong, Li; Shu, Min

    2013-02-01

    Hemodynamic disturbance in cerebral blood flow (CBF) is common in both Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to investigate the different patterns of regional cerebral blood flow (rCBF) change and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance, separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2 inhalation. The ASL results showed that, rCBF was significantly lower in both the bilateral frontal and temporal lobes in AD group and lower in left frontal and temporal white matter in patients with VaD. CVR calculated by rCBF was impaired more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed to demonstrate significant difference in MFV and CVR between the two groups. It is concluded that the different patterns detected by ASL in resting rCBF change and cerebrovascular reactivity in response to carbogen inhalation may serve as a potential marker to distinguish AD and VaD.

  14. Vascular endothelial growth factor mediates reactive angiogenesis in the postnatal developing brain.

    PubMed

    Ment, L R; Stewart, W B; Fronc, R; Seashore, C; Mahooti, S; Scaramuzzino, D; Madri, J A

    1997-05-20

    Although chronic sublethal hypoxia has been shown to promote angiogenesis in the developing brain, the pathogenesis of this response is unknown. We hypothesized that this response may be mediated in part by vascular endothelial growth factor (VEGF). We reared newborn rats (P3) in a chamber with FIO2 of 9.5 +/- 1% (exposed, E). At P33, the animals were removed from the chamber and the brains prepared for immunohistochemistry, mRNA extraction, or horseradish peroxidase (HRP) permeability studies. We also isolated beagle brain germinal matrix endothelial cells from PND 1 beagle pups and placed them in three-dimensional (3-D) coculture with PND 1 rat forebrain astrocytes. Cultures were grown for 6 days in 11% O2 and compared to control 3-D cocultures. When compared to age-matched controls, the experimental rats had significantly increased cortical vascular density (vessels/mm2: 518 +/- 18 vs. 400 +/- 15, P = 0.025). HRP studies demonstrated significantly increased permeability in all cortical vessels examined in experimental rats compared to controls. Compared to controls, VEGF mRNA from hypoxic pups was increased 2.4 times, and immunohistochemical studies of VEGF protein confirmed this finding. Similarly, when compared to controls, hypoxic cocultures of brain microvascular endothelial cells and astrocytes demonstrated significant increase in tubelike structures representing in vitro angiogenesis. Additionally, astrocyte VEGF protein levels increased 4.4-fold in hypoxic compared to control astrocyte cultures and VEGF protein levels increased 1.7-fold in hypoxic compared to control cocultures. Finally, addition of VEGF (10 ng/ml culture medium) to BBMEC alone in 3-D culture elicited not only significant proliferation (P = 0.001) but also increased tube formation. These data demonstrate that the developing brain responds to chronic sublethal hypoxia with increases in permeability and angiogenesis and suggest that VEGF mediates this response.

  15. The Effects of Antidepressants “Fluoxetine and Imipramine” on Vascular Abnormalities and Toll Like Receptor-4 Expression in Diabetic and Non-Diabetic Rats Exposed to Chronic Stress

    PubMed Central

    Habib, Mohamed; Shaker, Safaa; El-Gayar, Nesreen; Aboul-Fotouh, Sawsan

    2015-01-01

    Several studies reveal that diabetes doubles the odds of comorbid depression with evidence of a pro-inflammatory state underlying its vascular complications. Indeed, little information is available about vascular effects of antidepressant drugs in diabetes. Method: We investigated the effect of chronic administration of fluoxetine “FLU” and imipramine “IMIP” on behavioral, metabolic and vascular abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS). Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP in a comparable manner. Diabetic and non-diabetic rats exposed to CRS exhibited abnormalities in glucose homeostasis, lipid profile and vascular function, manifested by decreased endothelium-dependent relaxation, increased systolic blood pressure and histopathological atherosclerotic changes. Vascular and metabolic dysfunctions were associated with significant increase in aortic expression of TLR-4, and pro-inflammatory cytokines (TNF-α and IL-1ß). FLU ameliorated these metabolic, vascular and inflammatory abnormalities, while IMIP induced either no change or even worsening of some parameters. Conclusion: FLU has favorable effect over IMIP on metabolic, vascular and inflammatory aberrations associated with DM and CRS in Wistar rats, clarifying the preference of FLU over IMIP in management of comorbid depression in diabetic subjects. PMID:25826421

  16. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults

    PubMed Central

    Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.

    2015-01-01

    Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects

  17. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

    PubMed

    Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Davis, Simon W; Shafto, Meredith A; Taylor, Jason R; Williams, Nitin; Cam-Can; Rowe, James B

    2015-06-01

    In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task

  18. Dose-rate dependent effects of ionizing radiation on vascular reactivity.

    PubMed

    Suvorava, T; Luksha, L; Bulanova, K Ya; Lobanok, L M

    2006-01-01

    This study was designed to investigate the dose-rate dependent effects of ionising radiation on endothelium- and NO-mediated reactivity of aorta and coronary vessels. Rats were exposed to acute ((137)Cs, 9 x 10(-4) Gy s(-1), 18 min) and chronic ((137)Cs, 2.8 x 10(-7) Gy s(-1), 41 days) radiation in 1 Gy dose. Acute irradiation transiently increased coronary flow in eNOS-activity-dependent manner on day 3 after exposure. In striking contrast, chronic irradiation caused a significant depression of coronary flow even on day 90 after irradiation and abolished the effects of NO-synthase inhibitor N-nitro-L-arginine methyl ester (10 micromol l(-1)). Furthermore, low intensity radiation strongly diminished the vasodilator properties of NO-donor sodium nitroprusside (5 micromol l(-1)). A similar pattern was observed in aortic rings. Endothelium-dependent vasodilation was increased on days 3 and 10 after acute irradiation, but strongly inhibited following chronic exposure for the entire post-radiation period. This was accompanied by a diminished vasodilator response to NO-donor on days 3, 10 and 30 of post-radiation but not on day 90. The data suggest that ionising radiation in 1 Gy induces changes of aortic and coronary vessels reactivity depending on the dose-rate and the interval after exposure.

  19. Peanut witches' broom (PnWB) phytoplasma-mediated leafy flower symptoms and abnormal vascular bundles development.

    PubMed

    Liu, Chi-Te; Huang, Hsin-Mei; Hong, Syuan-Fei; Kuo-Huang, Ling-Long; Yang, Chiao-Yin; Lin, Yen-Yu; Lin, Chan-Pin; Lin, Shih-Shun

    2015-01-01

    The peanut witches' broom (PnWB) phytoplasma causes virescence symptoms such as phyllody (leafy flower) in infected peanuts. However, the obligate nature of phytoplasma limits the study of host-pathogen interactions, and the detailed anatomy of PnWB-infected plants has yet to be reported. Here, we demonstrate that 4',6'-diamidino-2-phenylindole (DAPI) staining can be used to track PnWB infection. The DAPI-stained phytoplasma cells were observed in phloem/internal phloem tissues, and changes in vascular bundle morphology, including increasing pith rays and thinner cell walls in the xylem, were found. We also discerned the cell types comprising PnWB in infected sieve tube members. These results suggest that the presence of PnWB in phloem tissue facilitates the transmission of phytoplasma via sap-feeding insect vectors. In addition, PnWB in sieve tube members and changes in vascular bundle morphology might strongly promote the ability of phytoplasmas to assimilate nutrients. These data will help further an understanding of the obligate life cycle and host-pathogen interactions of phytoplasma.

  20. Wholemount imaging reveals abnormalities of the aqueous outflow pathway and corneal vascularity in Foxc1 and Bmp4 heterozygous mice.

    PubMed

    van der Merwe, Elizabeth L; Kidson, Susan H

    2016-05-01

    Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congenital anterior segment dysgenesis (ASD) and the development of the aqueous outflow structures throughout the limbus. The aim of this study was to advance our understanding of anterior segment abnormalities in mouse models of ASD using a 3-D imaging approach. Holistic imaging information combined with quantitative measurements were carried out on PECAM-1 stained individual components of the aqueous outflow vessels and corneal vasculature of Foxc1(+/-) on the C57BL/6Jx129 and ICR backgrounds, Bmp4(+/-) ICR mice, and wildtype mice from each background. In both wildtype and heterozygotes, singular, bifurcated and plexus forms of Schlemm's canal were noted. Of note, missing portions of the canal were seen in the heterozygous groups but not in wildtype animals. In general, we found the number of collector channels to be reduced in both heterozygotes. Lastly, we found a significant increase in the complexity of the corneal arcades and their penetration into the cornea in heterozygotes as compared with wild types. In conclusion, our 3-D imaging studies have revealed a more complex arrangement of both the aqueous vessels and corneal arcades in Foxc1(+/-) and Bmp4(+/-) heterozygotes, and further advance our understanding of how such abnormalities could impact on IOP and the aetiology of glaucoma.

  1. Markers of endothelial dysfunction and evaluation of vascular reactivity tests in Behçet disease.

    PubMed

    Ozuguz, Pinar; Karabulut, Ayse Anil; Tulmac, Murat; Kisa, Ucler; Kocak, Mukadder; Gunduz, Ozgur

    2014-11-01

    We assessed endothelial dysfunction (ED) in patients with Behcet disease (BD; n=40) and healthy controls (n=20). Serum lipid, homocysteine, asymmetric dimethylarginine (ADMA) and high-sensitivity C-reactive protein (hsCRP) levels, erythrocyte sedimentation rates (ESRs), and ultrasonographic flow-mediated dilatation (FMD) were measured. Mean hsCRP, ESR, homocysteine, and ADMA were significantly higher in the BD group (P<.001 for all). Patients with active BD had higher serum levels of hsCRP, homocysteine, and ESR compared with those in remission (P<.001, P<.001, and P=.005, respectively). Flow-mediated dilatation was significantly lower in patients with BD than in controls (P=.001). Flow-mediated dilatation correlated negatively with BD duration and serum ADMA levels (P<.001, r=-.745 and P<.001, r=-.682); a positive correlation was seen between serum ADMA levels and BD duration (P<.001, r=.552). Only stepwise multivariate regression analysis revealed BD duration to have a significant effect on FMD. Flow-mediated dilatation, in conjunction with markers of inflammation, may evaluate ED in patients with BD.

  2. [Haematuria as the presentation of a vascular abnormality of the kidney or its excretory system (author's transl)].

    PubMed

    Beurton, D; Pascal, B; Moreau, J F; Michel, J R; Cukier, J

    1980-01-01

    The authors report 18 cases of a vascular pathology of the kidney or of its excretory system presenting with heavy and recurrent haematuria. In contrast to data in the literature, their series includes a majority of capillary angiomas (8 cases), as against 6 aneurysms, 2 arteriovenous fistulae and 2 peripyelo-ureteric varices. Of the six arterial aneurysms, all recognised by arteriography, 4 underwent surgery: 2 endo-aneurysmorrhaphies with success, 1 nephrectomy for rupture of the aneurysm and 1 nephrectomy made necessary by the multiplicity of aneurysms inaccessible in situ. Both cases of arteriovenous fistula were recognised by arteriography. One was treated by polar nephrectomy (success) whilst the other underwent nephrectomy after failure of an attempt at embolisation. Of the two cases of peri-uretero-pelvic varices identified by selective phlebography under cover of an intra-renal-artery injection of angiotensin, only one was treated successfully by excision of the varicosities. The eight cases of capillary angioma were divided into two groups: one, of 4 cases where the diagnosis was made by selective renal phlebography without angiotensin and renal arteriography; and another of 4 cases not identified by these vascular investigations. In these 4 cases, after elimination of Berger's disease by a surgical renal biopsy, the authors exposed the kidney, performed a pyelocalyscopy during a period of haematuria, localised the haemorrhagic segment of the kidney and treated the lesion by partial nephrectomy in the presence of a pathologist to immediately identify the haemorrhagic lesion and examine it histologically. Amongst the 7 angiomas treated, 5 partial nephrectomies gave successful results whilst two nephrectomies were necessary: one because of a diagnostic error and the other following failure of an attempt at hyperselective arterial embolisation.

  3. Abnormalities in three-dimensional capillary architecture and imbalance between vascular endothelial growth factor-A and thrombospondin-1 in soleus muscle of ovariectomized rat.

    PubMed

    Tanaka, Masayuki; Kanazashi, Miho; Maezawa, Toshiyuki; Kondo, Hiroyo; Fujino, Hidemi

    2015-09-01

    Reduced ovarian hormone levels associated with menopause or ovariectomy (OVX) not only result in vascular dysfunction but also lead to structural abnormalities in capillaries. Therefore, the effect of OVX on the three-dimensional (3-D) architecture of capillary networks and the underlying molecular mechanisms were investigated in rat soleus muscle. Seven-week-old female Wistar rats were divided into the OVX and sham-treated (Sham) groups. The OVX group exhibited lower endurance exercise capacity compared to the sham group and resulted in decreased capillary diameter, number of anastomoses and capillary/anastomosis volume in soleus muscle, indicating 3-D structural abnormalities of capillary networks. Furthermore, OVX led to increased concentrations of thrombospondin-1 (TSP-1) protein and a decreased VEGF-A/TSP-1 ratio, an indicator of angio-adaptations, in soleus muscle compared with the Sham group. These results indicate OVX may induce 3-D capillary regression in soleus muscle through an imbalance between VEGF-A and TSP-1 expression, possibly associated with decreased exercise tolerance in ovariectomized rats.

  4. Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injury

    SciTech Connect

    Shishido, Tetsuro . E-mail: Tetsuro_Shishido@URMC.Rochester.edu; Nozaki, Naoki; Takahashi, Hiroki; Arimoto, Takanori; Niizeki, Takeshi; Koyama, Yo; Abe, Jun-ichi; Takeishi, Yasuchika; Kubota, Isao

    2006-07-14

    Background: It is now evident that inflammation after vascular injury has significant impact on the restenosis after revascularization procedures such as angioplasty, stenting, and bypass grafting. However, the mechanisms that regulate inflammation and repair after vascular injury are incompletely understood. Here, we report that vascular injury-mediated cytokine expression, reactive oxygen species (ROS) production, as well as subsequent neointimal formation requires Toll-like receptor-2 (TLR-2) mediated signaling pathway in vivo. Methods and results: Vascular injury was induced by cuff-placement around the femoral artery in non-transgenic littermates (NLC) and TLR-2 knockout (TLR-2KO) mice. After cuff-placement in NLC mice, expression of TLR-2 was significantly increased in both smooth muscle medial layer and adventitia. Interestingly, we found that inflammatory genes expression such as tumor necrosis factor-{alpha}, interleukin-1{beta} (IL-1{beta}), IL-6, and monocyte chemoattractant protein-1 were markedly decreased in TLR-2KO mice compared with NLC mice. In addition, ROS production after vascular injury was attenuated in TLR-2KO mice compared with NLC mice. Since we observed the significant role of endogenous TLR-2 activation in regulating inflammatory responses and ROS production after vascular injury, we determined whether inhibition of endogenous TLR-2 activation can inhibit neointimal proliferation after vascular injury. Neointimal hyperplasia was markedly suppressed in TLR-2KO mice compared with WT mice at both 2 and 4 weeks after vascular injury. Conclusions: These findings suggested that endogenous TLR-2 activation might play a central role in the regulation of vascular inflammation as well as subsequent neointimal formation in injured vessels.

  5. Effects of chronic swimming training and oestrogen therapy on coronary vascular reactivity and expression of antioxidant enzymes in ovariectomized rats.

    PubMed

    Claudio, Erick R G; Endlich, Patrick W; Santos, Roger L; Moysés, Margareth R; Bissoli, Nazaré S; Gouvêa, Sônia A; Silva, Josiane F; Lemos, Virginia S; Abreu, Glaucia R

    2014-01-01

    The aim of this study was to evaluate the effects of swimming training (SW) and oestrogen replacement therapy (ERT) on coronary vascular reactivity and the expression of antioxidant enzymes in ovariectomized rats. Animals were randomly assigned to one of five groups: sham (SH), ovariectomized (OVX), ovariectomized with E2 (OE2), ovariectomized with exercise (OSW), and ovariectomized with E2 plus exercise (OE2+SW). The SW protocol (5×/week, 60 min/day) and/or ERT were conducted for 8 weeks; the vasodilator response to bradykinin was analysed (Langendorff Method), and the expression of antioxidant enzymes (SOD-1 and 2, catalase) and eNOS and iNOS were evaluated by Western blotting. SW and ERT improved the vasodilator response to the highest dose of bradykinin (1000 ng). However, in the OSW group, this response was improved at 100, 300 and 1000 ng when compared to OVX (p<0,05). The SOD-1 expression was increased in all treated/trained groups compared to the OVX group (p<0,05), and catalase expression increased in the OSW group only. In the trained group, eNOS increased vs. OE2, and iNOS decreased vs. SHAM (p<0,05). SW may represent an alternative to ERT by improving coronary vasodilation, most likely by increasing antioxidant enzyme and eNOS expression and augmenting NO bioavailability.

  6. Determination of Vascular Reactivity of Middle Cerebral Arteries from Stroke and Spinal Cord Injury Animal Models Using Pressure Myography.

    PubMed

    Anwar, Mohammad A; Eid, Ali H

    2016-01-01

    Stroke and other neurovascular derangements are main causes of global death. They, along with spinal cord injuries, are responsible for being the principal cause of disability due to neurological and cognitive problems. These problems then lead to a burden on scarce financial resources and societal care facilities as well as have a profound effect on patients' families. The mechanism of action in these debilitating diseases is complex and unclear. An important component of these problems arises from derangement of blood vessels, such as blockage due to clotting/embolism, endothelial dysfunction, and overreactivity to contractile agents, as well as alteration in endothelial permeability. Moreover, the cerebro-vasculature (large vessels and arterioles) is involved in regulating blood flow by facilitating auto-regulatory processes. Moreover, the anterior (middle cerebral artery and the surrounding region) and posterior (basilar artery and its immediate locality) regions of the brain play a significant role in triggering the pathological progression of ischemic stroke particularly due to inflammatory activity and oxidative stress. Interestingly, modifiable and non-modifiable cardiovascular risk factors are responsible for driving ischemic and hemorrhagic stroke and spinal cord injury. There are different stroke animal models to examine the pathophysiology of middle cerebral and basilar arteries. In this context, arterial myography offers an opportunity to determine the etiology of vascular dysfunction in these diseases. Herein, we describe the technique of pressure myography to examine the reactivity of cerebral vessels to contractile and vasodilator agents and a prelude to stroke and spinal cord injury.

  7. Modification of the liver fatty acids by Hibiscus sabdariffa Linnaeus (Malvaceae) infusion, its possible effect on vascular reactivity in a metabolic syndrome model.

    PubMed

    Pérez-Torres, Israel; Zúñiga Muñoz, Alejandra; Beltrán-Rodríguez, Ulises; Díaz-Díaz, Eulises; Martínez-Memije, Raúl; Guarner Lans, Verónica

    2014-01-01

    We investigated the effects of Hibiscus sabdariffa Linnaeus (HSL)-fed infusion on the fatty acid (FA) profile in liver of metabolic syndrome (MS) rats and its possible effect on vascular reactivity. Body mass, intra-abdominal fat, triglycerides, insulin, blood pressure, saturated, monounsaturated FA, NEFAs, Δ(9)-, Δ(6)-desaturases and vasoconstriction were increased, while vasorelaxation, polyunsaturated FA, endothelial nitric oxide and [Formula: see text]/[Formula: see text] ratio decreased in MS versus Control, but HSL infusion modified it and increased Δ(5)-desaturase. The results suggest that the alteration in FA liver metabolism in the MS contributes to impaired vascular reactivity, but treatment with of HSL infusion can improve this condition.

  8. Increased diuresis, renal vascular reactivity, and blood pressure levels in young rats fed high sodium, moderately high fructose, or their association: a comparative evaluation.

    PubMed

    Da Silva, Rita de Cássia Vilhena A F; de Souza, Priscila; da Silva-Santos, José Eduardo

    2016-12-01

    Excessive intakes of sodium or fructose have been described as risk factors for hypertension. We hypothesized that even a moderately high fructose diet (6% fructose), either alone or in combination with high sodium (4% NaCl), may impair diuresis and renal and systemic vascular reactivity, contributing to the onset of high blood pressure in rats. Male Wistar rats were fed chow containing 4% NaCl (HS), 6% fructose (MHF), or both 4% NaCl and 6% fructose (HSMHF) for 6 weeks and had their diuresis, plasma creatinine, vascular reactivity of perfused kidneys and systemic arterial pressure evaluated. We found no differences in augmented diuresis among animals given HS, MHF, or HSMHF diets. After 6 weeks both the HS and HSMHF groups had increased weight in their left kidneys, but only the HSMHF group showed augmented plasma creatinine. The effects of phenylephrine on renal vascular perfusion pressure were similarly enhanced in kidneys from the HS, MHF, and HSMHF groups, but not on the systemic arterial pressure. Although when evaluated in anesthetized rats, only the HSMHF group presented augmented blood pressure, evaluation in conscious animals revealed that both the MHF and HSMHF diets, but not the HS alone, were able to induce tachycardia and hypertension. In conclusion, a MHF diet containing 6% fructose was enough to render the renal vascular bed hyperreactive to phenylephrine and to induce both hypertension and tachycardia. The combination of 6% fructose with 4% NaCl led to plasma accumulation of creatinine and accelerated the development of tachycardia.

  9. Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge?

    PubMed

    Jahanian, Hesamoddin; Christen, Thomas; Moseley, Michael E; Pajewski, Nicholas M; Wright, Clinton B; Tamura, Manjula K; Zaharchuk, Greg

    2016-01-01

    Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R(2 )= 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

  10. Blood flow and vascular reactivity during attacks of classic migraine--limitations of the Xe-133 intraarterial technique

    SciTech Connect

    Skyhoj Olsen, T.; Lassen, N.A.

    1989-01-01

    The present study reports cerebral blood flow (CBF) measurements in 11 patients during attacks of classic migraine (CM)--migraine with aura. In 6 and 7 patients, respectively, cerebral vascular reactivity to increased blood pressure and to hypocapnia was also investigated during the CM attacks. The Xenon-133 intraarterial injection technique was used to measure CBF. In this study, based in part on previously published data, methodological limitations, in particular caused by scattered radiation (Compton scatter), are critically analysed. Based on this analysis and the results of the CBF studies it is concluded: During CM attacks CBF appears to decrease focally in the posterior part of the brain to a level around 20 ml/100 g/min which is consistent with a mild degree of ischemia. Changes of CBF in focal low flow areas are difficult to evaluate accurately with the Xe-133 technique. In most cases true CBF may change 50% or more in the low flow areas without giving rise to significantly measurable changes of CBF. This analysis suggests that the autoregulation response cannot be evaluated in the low flow areas with the technique used while the observations are compatible with the concept that a vasoconstrictive state, unresponsive to hypocapnia, prevails in the low flow areas during CM attacks. The gradual increase in size of the low flow area seen in several cases may be interpreted in two different ways. A spreading process may actually exist. However, due to Compton scatter, a gradual decrease of CBF in a territory that does not increase in size will also appear as a gradually spreading low flow area when studied with the Xe-133 intracarotid technique.

  11. Blueberry intervention improves vascular reactivity and lowers blood pressure in high-fat-, high-cholesterol-fed rats.

    PubMed

    Rodriguez-Mateos, Ana; Ishisaka, Akari; Mawatari, Kazuaki; Vidal-Diez, Alberto; Spencer, Jeremy P E; Terao, Junji

    2013-05-28

    Growing evidence suggests that intake of flavonoid-containing foods may exert cardiovascular benefits in human subjects. We have investigated the effects of a 10-week blueberry (BB) supplementation on blood pressure (BP) and vascular reactivity in rats fed a high-fat/high-cholesterol diet, known to induce endothelial dysfunction. Rats were randomly assigned to follow a control chow diet, a chow diet supplemented with 2 % (w/w) BB, a high-fat diet (10 % lard; 0·5 % cholesterol) or the high fat plus BB for 10 weeks. Rats supplemented with BB showed significant reductions in systolic BP (SBP) of 11 and 14 %, at weeks 8 and 10, respectively, relative to rats fed the control chow diet (week 8 SBP: 107·5 (SEM 4·7) v. 122·2 (SEM 2·1) mmHg, P= 0·018; week 10 SBP: 115·0 (SEM 3·1) v. 132·7 (SEM 1·5) mmHg, P< 0·0001). Furthermore, SBP was reduced by 14 % in rats fed with the high fat plus 2 % BB diet at week 10, compared to those on the high-fat diet only (SBP: 118·2 (SEM 3·6) v. 139·5 (SEM 4·5) mmHg, P< 0·0001). Aortas harvested from BB-fed animals exhibited significantly reduced contractile responses (to L-phenylephrine) compared to those fed the control chow or high-fat diets. Furthermore, in rats fed with high fat supplemented with BB, aorta relaxation was significantly greater in response to acetylcholine compared to animals fed with the fat diet. These data suggest that BB consumption can lower BP and improve endothelial dysfunction induced by a high fat, high cholesterol containing diet.

  12. GNG11 (G-protein γ subunit 11) suppresses cell growth with induction of reactive oxygen species and abnormal nuclear morphology in human SUSM-1 cells.

    PubMed

    Takauji, Yuki; Kudo, Ikuru; En, Atsuki; Matsuo, Ryo; Hossain, Mohammad; Nakabayashi, Kazuhiko; Miki, Kensuke; Fujii, Michihiko; Ayusawa, Dai

    2017-04-05

    Enforced expression of GNG11, G-protein γ subunit 11, induces cellular senescence in normal human diploid fibroblasts. We here examined the effect of the expression of GNG11 on the growth of immortalized human cell lines, and found that it suppressed the growth of SUSM-1 cells, but not of HeLa cells. We then compared these two cell lines to understand the molecular basis for the action of GNG11. We found that expression of GNG11 induced the generation of reactive oxygen species (ROS) and abnormal nuclear morphology in SUSM-1 cells but not in HeLa cells. Increased ROS generation by GNG11 would likely be caused by the down-regulation of the antioxidant enzymes in SUSM-1 cells. We also found that SUSM-1 cells, even under normal culture conditions, showed higher levels of ROS and higher incidence of abnormal nuclear morphology than HeLa cells, and that abnormal nuclear morphology was relevant to the increased ROS generation in SUSM-1 cells. Thus, SUSM-1 and HeLa cells showed differences in the regulation of ROS and nuclear morphology, which might account for their different responses to the expression of GNG11. Then, SUSM-1 cells may provide a unique system to study the regulatory relationship between ROS generation, nuclear morphology, and G-protein signaling.

  13. Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats.

    PubMed

    Zhang, Y P; Niu, C Y; Zhao, Z G; Zhang, L M; Si, Y H

    2013-07-01

    Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40 ± 2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca²⁺ were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca²⁺ at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179 ± 0.038 to 0.440 ± 0.177 g/mg, P<0.05) and Ca²⁺ (from 0.515 ± 0.043 to 0.646 ± 0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca²⁺ at various concentrations in the shock+drainage group (from 0.744 ± 0.187 to 0.570 ± 0.143 g/mg in Emax for NE and from 0.729 ± 0.037 to 0.645 ± 0.056 g/mg in Emax for Ca²⁺, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.

  14. Abnormal reactivity of the approximately 20-Hz motor cortex rhythm in Unverricht Lundborg type progressive myoclonus epilepsy.

    PubMed

    Silén, T; Forss, N; Jensen, O; Hari, R

    2000-12-01

    The approximately 20-Hz component of the human mu rhythm originates predominantly in the primary motor cortex. We monitored with a whole-scalp neuromagnetometer the reactivity of the approximately 20-Hz rhythm as an index of the functional state of the primary motor cortex in seven patients suffering from Unverricht-Lundborg type (ULD) progressive myoclonus epilepsy (PME) and in seven healthy control subjects. In patients, the motor cortex rhythm was on average 5 Hz lower in frequency and its strength was double compared with controls. To study reactivity of the approximately 20-Hz rhythm, left and right median nerves were stimulated alternately at wrists. In controls, these stimuli elicited a small transient decrease, followed by a strong increase ("rebound") of the approximately 20-Hz level. In contrast, the patients showed no significant rebounds of the rhythm. As the approximately 20-Hz rebounds apparently reflect increased cortical inhibition, our results indicate that peripheral stimuli excite motor cortex for prolonged periods in patients with ULD.

  15. Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes.

    PubMed

    Koçak, G; Aktan, F; Canbolat, O; Ozoğul, C; Elbeğ, S; Yildizoglu-Ari, N; Karasu, C

    2000-12-01

    The present study investigated the effects of alpha-lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, oxidative stress and antioxidant status were assessed in non-diabetic controls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined by electron microscopy technique. Alpha-lipoic acid treatment effectively reversed body weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha-lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untreated diabetic rats. Alpha-lipoic acid treatment improved catalase activity in diabetic aorta. The contractile effect of phenylephrine markedly increased in diabetic rings, which was completely reversed by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre-contracted aortic rings exposed to cumulatively increased concentrations of acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium nitroprusside-induced endothelium-independent relaxations were similar in all experimental groups. Various alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha-lipoic acid treatment. The potency of alpha-lipoic acid on the reversal of hypertension by affecting vascular reactivity and morphology as well as general metabolism of diabetic rats confirms the importance of hyperglycemia-induced oxidative stress in

  16. Role of the α-adrenergic system in femoral vascular reactivity in neonatal llamas and sheep: a comparative study between highland and lowland species

    PubMed Central

    Moraga, Fernando A.; Reyes, Roberto V.; Herrera, Emilio A.; Riquelme, Raquel A.; Ebensperger, Germán; Pulgar, Víctor M.; Parer, Julian T.; Giussani, Dino A.

    2011-01-01

    Using an integrative approach at the whole animal, isolated vessels, and molecular levels, we tested the hypothesis that the llama, a species that undergoes pregnancy under the influence of the chronic hypoxia of high altitude, delivers offspring with an increased α-adrenergic peripheral vascular reactivity compared with neonates from lowland species. We studied the femoral vascular response to acute hypoxia in vivo, the reactivity of femoral vessels ex vivo, and the expression of femoral α1-adrenergic receptor subtypes using RT-PCR in vitro. The increase in femoral resistance during hypoxia was 3.6 times greater in newborn llamas than newborn sheep (P < 0.05). The sensitivity of the contractile response to noradrenaline (pD2 = 5.18 ± 0.06 vs. 4.84 ± 0.05, P < 0.05) and the maximal response (Rmax = 101.3 ± 1.4 vs. 52.4 ± 1.4% K+max, P < 0.05) and sensitivity (pD2 = 5.47 ± 0.03 vs. 4.57 ± 0.05, P < 0.05) to phenylephrine were higher in femoral vessels from newborn llamas than newborn sheep. Competitive inhibition with prazosin of noradrenaline-induced contraction followed by Schild analysis showed higher affinity in the llama than the sheep (pA2 = 10.08 ± 0.093 vs. 8.98 ± 0.263, respectively, P < 0.05), consistent with greater α1B-adrenergic receptor transcript expression observed in small femoral arteries from neonatal llama. The llama newborn demonstrates significantly greater α-adrenergic peripheral vascular reactivity compared with neonates from lowland species that could be partially explained by preferential expression of α1B-adrenergic receptor subtype. PMID:21795632

  17. Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy.

    PubMed Central

    Limb, G A; Chignell, A H; Green, W; LeRoy, F; Dumonde, D C

    1996-01-01

    AIMS: This study investigated the presence of the cytokine tumour necrosis factor alpha (TNF alpha) and the vascular adhesion glycoproteins ICAM-1, VCAM-1, E-selectin, P-selectin, and PECAM within fibrovascular membranes of eyes with proliferative diabetic retinopathy (PDR). METHODS: The presence of these molecules was determined by immunohistochemical staining using monoclonal antibodies and the APAAP technique. RESULTS: Staining for TNF alpha was observed on the retinal vascular endothelium of five of 12 specimens, on infiltrating cells within all membranes, and on the extracellular matrix of nine specimens. This staining wa abolished by absorption of the monoclonal antibody with human recombinant TNF alpha. Likewise, ICAM-1 staining was given by infiltrating cells and extracellular matrix of nine membranes and by the endothelium of three of the specimens. VCAM-1, E-selectin, and P-selectin staining was observed on the vascular endothelium of 5/12, 4/12, and 3/12 epiretinal membranes respectively. PECAM was expressed by the endothelium of 4/12 specimens, by infiltrating cells of 8/12 membranes, and also by the extracellular matrix of two of the specimens. CONCLUSION: The widespread distribution of TNF alpha and the nature of the adhesion molecules expressed by vascular endothelial cells in PDR membranes suggest that local activation of TNF alpha and enhanced expression of vascular cell adhesion molecules may play an important role in the development of the proliferative phase of diabetic retinopathy. Images PMID:8814750

  18. Increased superoxide dismutase and Na+, K+-ATPase activities in aortic strips from potassium-adapted rats: implication for altered vascular reactivity.

    PubMed

    Ozolua, Raymond I; Omogbai, Eric K I; Ebeigbe, Anthony B; Asagba, Samuel O

    2003-05-01

    The contributions of superoxide dismutase (SOD) and Na(+), K(+)-ATPase to the altered vascular reactivity in potassium-adapted rats were investigated to test the hypothesis that smooth muscle hyperpolarisation may be involved. Isometric contractions to noradrenaline (NA), 5-hydroxytryptamine (5-HT), and relaxations to acetylcholine (ACh), levcromakalim (LEV) and sodium nitroprusside (SNP), were measured in aortic rings from potassium-adapted rats. Pieces of the aortae were also excised from the animals and assayed for SOD and Na(+), K(+)-ATPase. Maximum contractile responses were significantly attenuated (P<0.05) in aortic rings from the potassium-adapted rats to NA and 5-HT, while relaxations were also significantly augmented (P<0.05) in the same rings to LEV and SNP, but not to ACh. Both SOD and Na(+), K(+)-ATPase activities were significantly higher (P<0.05) in the aortae from the potassium-adapted rats compared to controls. It is concluded that the alteration in vascular smooth muscle reactivity may be due to hyperpolarisation caused by the activities of SOD and Na(+), K(+)-ATPase.

  19. The 18-kDa Translocator Protein Inhibits Vascular Cell Adhesion Molecule-1 Expression via Inhibition of Mitochondrial Reactive Oxygen Species

    PubMed Central

    Joo, Hee Kyoung; Lee, Yu Ran; Kang, Gun; Choi, Sunga; Kim, Cuk-Seong; Ryoo, Sungwoo; Park, Jin Bong; Jeon, Byeong Hwa

    2015-01-01

    Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10–100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO (0.1–0.5 μM), a specific mitochondrial antioxidants, and cyclosporin A (1–5 μM), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam (1–50 μM), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells. PMID:26608360

  20. Cerebral vascular autoregulation and CO2 reactivity following onset of the delayed postischemic hypoperfusion state in dogs.

    PubMed

    Christopherson, T J; Milde, J H; Michenfelder, J D

    1993-03-01

    A small number of animal studies have suggested that during the delayed postischemic hypoperfusion state, CO2 reactivity of the cerebral vasculature is lost whereas autoregulation is retained. These findings, however, are inconsistent with the bulk of experimental evidence which demonstrates that CO2 reactivity is more robust and may be retained in pathologic circumstances which abolish autoregulation. These opposing viewpoints were therefore further evaluated in 18 dogs in which complete global ischemia was induced by cerebrospinal fluid (CSF) compression for periods of 12 (n = 12) and 18 (n = 6) min. Following 45 min of reperfusion and with onset of the delayed postischemic hypoperfusion state, autoregulation and CO2 reactivity were evaluated using a continuous measurement of CBF (by sagittal sinus outflow). CO2 reactivity was tested over a PaCO2 range of 20 to 60 mm Hg; autoregulation was tested over a blood pressure range of 60 to 140 mm Hg. Results demonstrated that after both 12 and 18 min of complete global ischemia, autoregulation and CO2 reactivity of the cerebral vasculature were both present, but attenuated. In the case of CO2 reactivity, the slope of the CBF response was decreased approximately 75%. In the case of autoregulation, the response in some dogs was incomplete as compared with their preischemic response.

  1. Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

    PubMed Central

    Lima, V.V.; Lobato, N.S.; Filgueira, F.P.; Webb, R.C.; Tostes, R.C.; Giachini, F.R.

    2014-01-01

    O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction. PMID:25140811

  2. Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain.

    PubMed

    Lima, V V; Lobato, N S; Filgueira, F P; Webb, R C; Tostes, R C; Giachini, F R

    2014-10-01

    O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2 ± 2 vs 7.9 ± 1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4 ± 2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3 ± 2 vs 7.5 ± 2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1 ± 2 vs 7.4 ± 2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca(2+)/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

  3. Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel β1 subunit degradation in diabetic mice.

    PubMed

    Lu, Tong; Chai, Qiang; Yu, Ling; d'Uscio, Livius V; Katusic, Zvonimir S; He, Tongrong; Lee, Hon-Chi

    2012-07-01

    Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is tightly regulated by its accessory β(1) subunit (BK-β(1)). Downregulation of BK-β(1) expression in diabetic vessels is associated with upregulation of the forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box-only protein (FBXO) expression. However, the upstream signaling regulating this process is unclear. Overproduction of reactive oxygen species (ROS) is a common finding in diabetic vasculopathy. We hypothesized that ROS signaling cascade facilitates the FOXO-3a/FBXO-mediated BK-β(1) degradation and leads to diabetic BK channel dysfunction. Using cellular biology, patch clamp, and videomicroscopy techniques, we found that reduced BK-β(1) expression in streptozotocin (STZ)-induced diabetic mouse arteries and in human coronary smooth muscle cells (SMCs) cultured with high glucose was attributable to an increase in protein kinase C (PKC)-β and NADPH oxidase expressions and accompanied by attenuation of Akt phosphorylation and augmentation of atrogin-1 expression. Treatment with ruboxistaurin (a PKCβ inhibitor) or with GW501516 (a peroxisome proliferator-activated receptor δ activator) reduced atrogin-1 expression and restored BK channel-mediated coronary vasodilation in diabetic mice. Our results suggested that oxidative stress inhibited Akt signaling and facilitated the FOXO-3a/FBXO-dependent BK-β(1) degradation in diabetic vessels. Suppression of the FOXO-3a/FBXO pathway prevented vascular BK-β(1) degradation and protected coronary function in diabetes.

  4. Imbalanced Production of Reactive Oxygen Species and Mitochondrial Antioxidant SOD2 in Fabry Disease-Specific Human Induced Pluripotent Stem Cell-Differentiated Vascular Endothelial Cells.

    PubMed

    Tseng, Wei-Lien; Chou, Shih-Jie; Chiang, Huai-Chih; Wang, Mong-Lien; Chien, Chian-Shiu; Chen, Kuan-Hsuan; Leu, Hsin-Bang; Wang, Chien-Ying; Chang, Yuh-Lih; Liu, Yung-Yang; Jong, Yuh-Jyh; Lin, Shinn-Zong; Chiou, Shih-Hwa; Lin, Shing-Jong; Yu, Wen-Chung

    2017-03-13

    Fabry disease (FD) is an X-linked inherited lysosomal storage disease caused by α-galactosidase A (GLA) deficiency. Progressive intracellular accumulation of globotriaosylceramide (Gb3) is considered to be pathogenically responsible for the phenotype variability of FD that causes cardiovascular dysfunction; however, molecular mechanisms underlying the impairment of FD-associated cardiovascular tissues remain unclear. In this study, we reprogrammed human induced pluripotent stem cells (hiPSCs) from peripheral blood cells of patients with FD (FD-iPSCs); subsequently differentiated them into vascular endothelial-like cells (FD-ECs) expressing CD31, VE-cadherin, and vWF; and investigated their ability to form vascular tube-like structures. FD-ECs recapitulated the FD pathophysiological phenotype exhibiting intracellular Gb3 accumulation under a transmission electron microscope. Moreover, compared with healthy control iPSC-derived endothelial cells (NC-ECs), reactive oxygen species (ROS) production considerably increased in FD-ECs. Microarray analysis was performed to explore the possible mechanism underlying Gb3 accumulation-induced ROS production in FD-ECs. Our results revealed that superoxide dismutase 2 (SOD2), a mitochondrial antioxidant, was significantly downregulated in FD-ECs. Compared with NC-ECs, AMPK activity was significantly enhanced in FD-ECs. Furthermore, to investigate the role of Gb3 in these effects, human umbilical vein endothelial cells (HUVECs) were treated with Gb3. After Gb3 treatment, we observed that SOD2 expression was suppressed and AMPK activity was enhanced in a dose-dependent manner. Collectively, our results indicate that excess accumulation of Gb3 suppressed SOD2 expression, increased ROS production, enhanced AMPK activation, and finally caused vascular endothelial dysfunction. Our findings suggest that dysregulated mitochondrial ROS may be a potential target for treating FD.

  5. Vascular function measured by fingertip thermal reactivity is impaired in patients with metabolic syndrome and diabetes mellitus.

    PubMed

    Ahmadi, Naser; Hajsadeghi, Fereshteh; Gul, Khawar; Leibfried, Michael; DeMoss, Daniel; Lee, Robert; Flores, Ferdinand; Nasir, Khurram; Hecht, Harvey; Naghavi, Morteza; Budoff, Matthew J

    2009-11-01

    Digital thermal monitoring (DTM) of vascular function has already been shown to correlate well with coronary artery calcium (CAC) score and coronary artery disease. To determine its utility in the metabolic syndrome (MS) and diabetes mellitus (DM), 233 asymptomatic patients with DM/MS but without coronary artery disease underwent DTM during and after 5 minutes of supra-systolic arm cuff inflation, as well as CAC. Post-cuff deflation adjusted temperature rebound (aTR) was lower in MS and DM compared with the normal group. The odds ratio of lowest vs upper 2 tertiles of aTR was 2.3 for MS and 3.5 for DM compared with the normal group, independent of age, sex, and risk factors. The area under the receiver operating characteristic curve to predict CAC > or =100 was 0.69 for metabolic status (DM/MS), 0.79 for aTR, and 0.87 for both. This study demonstrates that vascular dysfunction measured by DTM is associated with DM/MS and could potentially be used to detect asymptomatic individuals with increased subclinical atherosclerosis.

  6. Congenital Abnormalities

    MedlinePlus

    ... Listen Español Text Size Email Print Share Congenital Abnormalities Page Content Article Body About 3% to 4% ... of congenital abnormalities earlier. 5 Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic ...

  7. KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine.

    PubMed

    Goodwill, Adam G; Fu, Lijuan; Noblet, Jillian N; Casalini, Eli D; Sassoon, Daniel; Berwick, Zachary C; Kassab, Ghassan S; Tune, Johnathan D; Dick, Gregory M

    2016-03-15

    Hydrogen peroxide (H2O2) and voltage-dependent K(+) (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli.

  8. KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine

    PubMed Central

    Goodwill, Adam G.; Fu, Lijuan; Noblet, Jillian N.; Casalini, Eli D.; Berwick, Zachary C.; Kassab, Ghassan S.; Tune, Johnathan D.

    2016-01-01

    Hydrogen peroxide (H2O2) and voltage-dependent K+ (KV) channels play key roles in regulating coronary blood flow in response to metabolic, ischemic, and paracrine stimuli. The KV channels responsible have not been identified, but KV7 channels are possible candidates. Existing data regarding KV7 channel function in the coronary circulation (limited to ex vivo assessments) are mixed. Thus we examined the hypothesis that KV7 channels are present in cells of the coronary vascular wall and regulate vasodilation in swine. We performed a variety of molecular, biochemical, and functional (in vivo and ex vivo) studies. Coronary arteries expressed KCNQ genes (quantitative PCR) and KV7.4 protein (Western blot). Immunostaining demonstrated KV7.4 expression in conduit and resistance vessels, perhaps most prominently in the endothelial and adventitial layers. Flupirtine, a KV7 opener, relaxed coronary artery rings, and this was attenuated by linopirdine, a KV7 blocker. Endothelial denudation inhibited the flupirtine-induced and linopirdine-sensitive relaxation of coronary artery rings. Moreover, linopirdine diminished bradykinin-induced endothelial-dependent relaxation of coronary artery rings. There was no effect of intracoronary flupirtine or linopirdine on coronary blood flow at the resting heart rate in vivo. Linopirdine had no effect on coronary vasodilation in vivo elicited by ischemia, H2O2, or tachycardia. However, bradykinin increased coronary blood flow in vivo, and this was attenuated by linopirdine. These data indicate that KV7 channels are expressed in some coronary cell type(s) and influence endothelial function. Other physiological functions of coronary vascular KV7 channels remain unclear, but they do appear to contribute to endothelium-dependent responses to paracrine stimuli. PMID:26825518

  9. The Dietary Approaches to Stop Hypertension eating plan affects C-reactive protein, coagulation abnormalities, and hepatic function tests among type 2 diabetic patients.

    PubMed

    Azadbakht, Leila; Surkan, Pamela J; Esmaillzadeh, Ahmad; Willett, Walter C

    2011-06-01

    Few studies exist regarding the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on novel cardiovascular risk factors among type 2 diabetic patients. We evaluated the effects of the DASH eating pattern on C-reactive protein (CRP) level, coagulation abnormalities, and hepatic function tests in type 2 diabetic patients. In this randomized, crossover clinical trial, 31 type 2 diabetic patients consumed a control diet or the DASH diet for 8 wk. The DASH diet was rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, and sweets, with a total of 2400 mg/d sodium. The control diet was a standard diet for diabetic patients. There was a 4-wk washout between the 2 trial phases. The main outcome measures were CRP level, coagulation indices, and hepatic function tests. The mean percent change for plasma CRP level was -26.9 ± 3.5% after the DASH diet period and -5.1 ± 3.8% after the control diet period (P = 0.02). Decreases in both alanine aminotransferase and aspartate aminotransferase levels were greater after consuming the DASH diet compared with the control diet (-14.8 ± 3.0% vs -6.6 ± 3.4%; P = 0.001; -29.4 ± 3.7% vs -5.9 ± 1.4%; P = 0.001, respectively). The decrease in the plasma fibrinogen level during the DASH diet period (-11.4 ± 3.6%) was greater than that during the control diet (0.5 ± 3.4%) (P = 0.03). Among diabetic patients, the DASH diet can play an important role in reducing inflammation, plasma levels of fibrinogen, and liver aminotransferases. Future longer term studies are recommended.

  10. Vascular endothelial overexpression of human CYP2J2 (Tie2-CYP2J2 Tr) modulates cardiac oxylipin profiles and enhances coronary reactive hyperemia in mice

    PubMed Central

    Hanif, Ahmad; Edin, Matthew L.; Zeldin, Darryl C.; Morisseau, Christophe; Falck, John R.

    2017-01-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases. EETs and HETEs often have opposite biologic effects; EETs are vasodilatory and protect against ischemia/reperfusion injury, while ω-terminal HETEs are vasoconstrictive and cause vascular dysfunction. Other oxylipins, such as epoxyoctadecaenoic acids (EpOMEs), hydroxyoctadecadienoic acids (HODEs), and prostanoids also have varied vascular effects. Post-ischemic vasodilation in the heart, known as coronary reactive hyperemia (CRH), protects against potential damage to the heart muscle caused by ischemia. The relationship among CRH response to ischemia, in mice with altered levels of CYP2J epoxygenases has not yet been investigated. Therefore, we evaluated the effect of endothelial overexpression of the human cytochrome P450 epoxygenase CYP2J2 in mice (Tie2-CYP2J2 Tr) on oxylipin profiles and CRH. Additionally, we evaluated the effect of pharmacologic inhibition of CYP-epoxygenases and inhibition of ω-hydroxylases on CRH. We hypothesized that CRH would be enhanced in isolated mouse hearts with vascular endothelial overexpression of human CYP2J2 through modulation of oxylipin profiles. Similarly, we expected that inhibition of CYP-epoxygenases would reduce CRH, whereas inhibition of ω-hydroxylases would enhance CRH. Compared to WT mice, Tie2-CYP2J2 Tr mice had enhanced CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05). Similarly, inhibition of ω-hydroxylases increased repayment volume and repayment duration, in Tie2-CYP2J2 Tr compared to WT mice (P < 0.05). Endothelial overexpression of CYP2J2 significantly changed oxylipin profiles, including increased EETs (P < 0.05), increased EpOMEs (P < 0.05), and decreased 8-iso-PGF2α (P < 0.05). Inhibition of CYP epoxygenases with MS-PPOH attenuated CRH (P < 0.05). Ischemia caused a decrease in mid

  11. Inhibitory role of reactive oxygen species in the differentiation of multipotent vascular stem cells into vascular smooth muscle cells in rats: a novel aspect of traditional culture of rat aortic smooth muscle cells.

    PubMed

    Song, Haibo; Wang, Hui; Wu, Weiwei; Qi, Lei; Shao, Lei; Wang, Fang; Lai, Yimu; Leach, Desiree; Mathis, Bryan; Janicki, Joseph S; Wang, Xing Li; Tang, Dongqi; Cui, Taixing

    2015-10-01

    Proliferative or synthetic vascular smooth muscle cells (VSMCs) are widely accepted to be mainly derived from the dedifferentiation or phenotypic modulation of mature contractile VSMCs, i.e., a phenotype switch from a normally quiescent and contractile type into a proliferative or synthetic form. However, this theory has been challenged by recent evidence that synthetic VSMCs predominantly originate instead from media-derived multipotent vascular stem cells (MVSCs). To test these hypotheses further, we re-examine whether the conventional rat aortic SMC (RASMC) culture involves the VSMC differentiation of MVSCs or the dedifferentiation of mature VSMCs and the potential mechanism for controlling the synthetic phenotype of RASMCs. We enzymatically isolated RASMCs and cultured the cells in both a regular growth medium (RGM) and a stem cell growth medium (SCGM). Regardless of culture conditions, only a small portion of freshly isolated RASMCs attaches, survives and grows slowly during the first 7 days of primary culture, while expressing both SMC- and MVSC-specific markers. RGM-cultured cells undergo a process of synthetic SMC differentiation, whereas SCGM-cultured cells can be differentiated into not only synthetic SMCs but also other somatic cells. Notably, compared with the RGM-cultured differentiated RASMCs, the SCGM-cultured undifferentiated cells exhibit the phenotype of MVSCs and generate greater amounts of reactive oxygen species (ROS) that act as a negative regulator of differentiation into synthetic VSMCs. Knockdown of phospholipase A2, group 7 (Pla2g7) suppresses ROS formation in the MVSCs while enhancing SMC differentiation of MVSCs. These results suggest that cultured synthetic VSMCs can be derived from the SMC differentiation of MVSCs with ROS as a negative regulator.

  12. Hass avocado modulates postprandial vascular reactivity and postprandial inflammatory responses to a hamburger meal in healthy volunteers.

    PubMed

    Li, Zhaoping; Wong, Angela; Henning, Susanne M; Zhang, Yanjun; Jones, Alexis; Zerlin, Alona; Thames, Gail; Bowerman, Susan; Tseng, Chi-Hong; Heber, David

    2013-02-26

    Hass avocados are rich in monounsaturated fatty acids (oleic acid) and antioxidants (carotenoids, tocopherols, polyphenols) and are often eaten as a slice in a sandwich containing hamburger or other meats. Hamburger meat forms lipid peroxides during cooking. After ingestion, the stomach functions as a bioreactor generating additional lipid peroxides and this process can be inhibited when antioxidants are ingested together with the meat. The present pilot study was conducted to investigate the postprandial effect of the addition of 68 g of avocado to a hamburger on vasodilation and inflammation. Eleven healthy subjects on two separate occasions consumed either a 250 g hamburger patty alone (ca. 436 cal and 25 g fat) or together with 68 grams of avocado flesh (an additional 114 cal and 11 g of fat for a total of 550 cal and 36 g fat), a common culinary combination, to assess effects on vascular health. Using the standard peripheral arterial tonometry (PAT) method to calculate the PAT index, we observed significant vasoconstriction 2 hours following hamburger ingestion (2.19 ± 0.36 vs. 1.56 ± 0.21, p = 0.0007), which did not occur when the avocado flesh was ingested together with the burger (2.17 ± 0.57 vs. 2.08 ± 0.51, NS p = 0.68). Peripheral blood mononuclear cells were isolated from postprandial blood samples and the Ikappa-B alpha (IκBα) protein concentration was determined to assess effects on inflammation. At 3 hours, there was a significant preservation of IκBα (131% vs. 58%, p = 0.03) when avocado was consumed with the meat compared to meat alone, consistent with reduced activation of the NF-kappa B (NFκB) inflammatory pathway. IL-6 increased significantly at 4 hours in postprandial serum after consumption of the hamburger, but no change was observed when avocado was added. Postprandial serum triglyceride concentration increased, but did not further increase when avocado was ingested with the burger compared to burger alone despite the added fat and

  13. Reactive oxygen species and RhoA signaling in vascular smooth muscle: role in chronic hypoxia-induced pulmonary hypertension.

    PubMed

    Resta, Thomas C; Broughton, Brad R S; Jernigan, Nikki L

    2010-01-01

    Increases in myofilament Ca2+ sensitivity resulting from stimulation of RhoA and Rho kinase represent a primary mechanism of vasoconstriction and associated pulmonary hypertension resulting from chronic hypoxia (CH). This chapter summarizes recent advances in the understanding of RhoA/Rho kinase signaling mechanisms in pulmonary vascular smooth muscle (VSM) that increase the sensitivity of the contractile apparatus to Ca2+ and contribute to vasoconstriction in this setting. Such advances include the discovery of myogenic tone in small pulmonary arteries from CH rats that contributes to vasoconstriction through a mechanism inherent to the VSM, dependent on Rho kinase-induced Ca2+ sensitization but independent of L-type voltage-gated Ca2+ channels. Additional studies have revealed an important contribution of superoxide anion (O2-)-induced RhoA activation to both receptor-mediated and membrane depolarization-induced myofilament Ca2+ sensitization in hypertensive pulmonary arteries. Xanthine oxidase and NADPH oxidase isoforms are potential sources of O2- that mediate RhoA-dependent vasoconstriction and associated pulmonary hypertension.

  14. Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn.

    PubMed

    Kim, Jeong-A; Formoso, Gloria; Li, Yunhua; Potenza, Maria A; Marasciulo, Flora L; Montagnani, Monica; Quon, Michael J

    2007-05-04

    Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, mimics metabolic actions of insulin to inhibit gluconeogenesis in hepatocytes. Because signaling pathways regulating metabolic and vasodilator actions of insulin are shared in common, we hypothesized that EGCG may also have vasodilator actions to stimulate production of nitric oxide (NO) from endothelial cells. Acute intra-arterial administration of EGCG to mesenteric vascular beds isolated ex vivo from WKY rats caused dose-dependent vasorelaxation. This was inhibitable by L-NAME (NO synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), or PP2 (Src family kinase inhibitor). Treatment of bovine aortic endothelial cells (BAEC) with EGCG (50 microm) acutely stimulated production of NO (assessed with NO-specific fluorescent dye DAF-2) that was inhibitable by l-NAME, wortmannin, or PP2. Stimulation of BAEC with EGCG also resulted in dose- and time-dependent phosphorylation of eNOS that was inhibitable by wortmannin or PP2 (but not by MEK inhibitor PD98059). Specific knockdown of Fyn (but not Src) with small interfering RNA inhibited both EGCG-stimulated phosphorylation of Akt and eNOS as well as production of NO in BAEC. Treatment of BAEC with EGCG generated intracellular H(2)O(2) (assessed with H(2)O(2)-specific fluorescent dye CM-H(2)DCF-DA), whereas treatment with N-acetylcysteine inhibited EGCG-stimulated phosphorylation of Fyn, Akt, and eNOS. We conclude that EGCG has endothelial-dependent vasodilator actions mediated by intracellular signaling pathways requiring reactive oxygen species and Fyn that lead to activation of phosphatidylinositol 3-kinase, Akt, and eNOS. This mechanism may explain, in part, beneficial vascular and metabolic health effects of green tea consumption.

  15. The impact of the catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract.

    PubMed

    Miller, Rosalind J; Jackson, Kim G; Dadd, Tony; Mayes, Andrew E; Brown, A Louise; Minihane, Anne M

    2011-04-01

    The beneficial effects of green tea catechins, such as the proposed improvement in endothelial function, may be influenced by phase II metabolism during and after absorption. The methylation enzyme, catechol-O-methyltransferase (COMT), has a missense mutation rs4680 (G to A), proposed to result in a 40 % reduction in enzyme activity. In the present pilot study, twenty subjects (ten of each homozygous COMT genotype) were recruited. Green tea extract capsules (836 mg green tea catechins) were given in a fasted state, and a high-carbohydrate breakfast was given after 60 min. Blood samples and vascular function measurements were taken at regular intervals. The change in digital volume pulse stiffness index (SI) from baseline was shown to be different between genotype groups at 120 and 240 min, with a lower SI in the GG individuals (P ≤ 0·044). The change in blood pressure from baseline also differed between genotype groups, with a greater increase in systolic (P = 0·023) and diastolic (P = 0·034) blood pressure at 120 min in the GG group. The GG [corrected] group was shown to have a greater increase in insulin concentrations at 120 min (P = 0·019) and 180 min (P = 0·008) compared with baseline, despite similar glucose profiles. No genotypic differences were found in vascular reactivity measured using laser Doppler iontophoresis, total nitrite, lipids, plasma total antioxidant capacity or inflammatory markers after ingestion of the green tea extract. In conclusion, SI and insulin response to the glucose load differed between the COMT genotype groups, and this may be suggestive of a green tea extract and genotype interaction.

  16. Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model.

    PubMed

    Basralı, Filiz; Koçer, Günnur; Ülker Karadamar, Pınar; Nasırcılar Ülker, Seher; Satı, Leyla; Özen, Nur; Özyurt, Dilek; Şentürk, Ümit Kemal

    2015-01-01

    The aim of this study was to assess the effect of oral magnesium supplementation (Mg-supp) on blood pressure (BP) and possible mechanism in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension and/or Mg-supp were created by N-nitro-l-arginine methyl ester (25 mg/kg/day by drinking water) and magnesium-oxide (0.8% by diet) for 6 weeks. Systolic BP was measured weekly by tail-cuff method. The effects of hypertension and/or Mg-supp in thoracic aorta and third branch of mesenteric artery constriction and relaxation responses were evaluated. NOS-inhibition produced a gradually developing hypertension and the magnitude of the BP was significantly attenuated after five weeks of Mg-supp. The increased phenylephrine-induced contractile and decreased acetylcholine (ACh)-induced dilation responses were found in both artery segments of hypertensive groups. Mg-supp was restored ACh-relaxation response in both arterial segments and also Phe-constriction response in thoracic aorta but not in mesenteric arteries. The contributions of NO, prostaglandins and K(+) channels to the dilator response of ACh were similar in the aorta of all the groups. The contribution of the NO to the ACh-mediated relaxation response of mesenteric arteries was suppressed in hypertensive rats, whereas this was corrected by Mg-supp. The flow-mediated dilation response of mesenteric arteries in hypertensive rats failed and could not be corrected by Mg-supp. Whereas, vascular eNOS protein and magnesium levels were not changed and plasma nitrite levels were reduced in hypertensive rats. The results of this study showed that Mg-supp lowered the arterial BP in NOS-inhibition induced hypertension model by restoring the agonist-induced relaxation response of the arteries.

  17. Exercise training in doxorubicin-induced heart failure: effects on the L-arginine-NO pathway and vascular reactivity.

    PubMed

    Matsuura, Cristiane; Brunini, Tatiana M C; Carvalho, Lenize C M M; Resende, Angela C; Carvalho, Jorge J; de Castro, João Pedro Werneck; Mendes-Ribeiro, Antonio C

    2010-01-01

    Heart failure (HF) is the end-stage of cardiovascular disease and is associated with a high incidence of thrombotic events. Nitric oxide (NO) mediates vasodilation and prevents platelet activation, providing an important antithrombotic effect. The aim of this study was to investigate the effects of aerobic training on survival, platelet L-arginine-NO pathway, and vasodilator properties in doxorubicin (DOX)-induced HF. Sprague Dawley rats were randomly assigned to saline/sedentary (SAL/SED), saline/exercise (SAL/EX), DOX/sedentary (DOX/SED), and DOX/exercise (DOX/EX) groups. Four weeks after intraperitoneal DOX injection (1mg/kg(-1)/d(-1); 10 days), shortening fraction in DOX/SED and DOX/EX was significantly reduced. Treadmill exercise was performed during 6 weeks, 5 days/week(-1), 30minutes/day(-1), 50% to 60% of maximum velocity. Survival was higher in DOX/EX (67%) than DOX/SED (33%). No differences were observed in intraplatelet L-arginine transport assessed by incubation with L- [(3)H]-arginine, nor in NOS activity measured by the conversion of L- [(3)H]-arginine into L- [(3)H]-citrulline among the groups. Vasodilation response to acetylcholine was impaired in DOX/SED and DOX/EX; in nitroglycerine, it was limited to DOX/SED. Aerobic training reduced mortality in DOX-induced HF animals and restored vascular smooth muscle relaxation properties. However, it did not ameliorate intraplatelet NO bioavailability and endothelial function during the period studied.

  18. Toll-like receptor 4 upregulation by angiotensin II contributes to hypertension and vascular dysfunction through reactive oxygen species production.

    PubMed

    De Batista, Priscila R; Palacios, Roberto; Martín, Angela; Hernanz, Raquel; Médici, Cindy T; Silva, Marito A S C; Rossi, Emilly M; Aguado, Andrea; Vassallo, Dalton V; Salaices, Mercedes; Alonso, María J

    2014-01-01

    Hypertension is considered as a low-grade inflammatory disease, with adaptive immunity being an important mediator of this pathology. TLR4 may have a role in the development of several cardiovascular diseases; however, little is known about its participation in hypertension. We aimed to investigate whether TLR4 activation due to increased activity of the renin-angiotensin system (RAS) contributes to hypertension and its associated endothelial dysfunction. For this, we used aortic segments from Wistar rats treated with a non-specific IgG (1 µg/day) and SHRs treated with losartan (15 mg/kg·day), the non-specific IgG or the neutralizing antibody anti-TLR4 (1 µg/day), as well as cultured vascular smooth muscle cells (VSMC) from Wistar and SHRs. TLR4 mRNA levels were greater in the VSMC and aortas from SHRs compared with Wistar rats; losartan treatment reduced those levels in the SHRs. Treatment of the SHRs with the anti-TLR4 antibody: 1) reduced the increased blood pressure, heart rate and phenylephrine-induced contraction while it improved the impaired acetylcholine-induced relaxation; 2) increased the potentiation of phenylephrine contraction after endothelium removal; and 3) abolished the inhibitory effects of tiron, apocynin and catalase on the phenylephrine-induced response as well as its enhancing effect of acetylcholine-induced relaxation. In SHR VSMCs, angiotensin II increased TLR4 mRNA levels, and losartan reduced that increase. CLI-095, a TLR4 inhibitor, mitigated the increases in NAD(P)H oxidase activity, superoxide anion production, migration and proliferation that were induced by angiotensin II. In conclusion, TLR4 pathway activation due to increased RAS activity is involved in hypertension, and by inducing oxidative stress, this pathway contributes to the endothelial dysfunction associated with this pathology. These results suggest that TLR4 and innate immunity may play a role in hypertension and its associated end-organ damage.

  19. Pharmacological reactivity of resistance vessels in a rat PCOS model - vascular effects of parallel vitamin D₃ treatment.

    PubMed

    Sara, Levente; Nadasy, Gyorgy L; Antal, Peter; Monori-Kiss, Anna; Szekeres, Maria; Masszi, Gabriella; Monos, Emil; Varbiro, Szabolcs

    2012-12-01

    The aim of this study was to clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) on pharmacological reactivity of a resistance vessel in a rat model and the possible modulatory role of 1,25-(OH)₂-cholecalciferol (vitamin D₃). The PCOS model was induced in adolescent female Wistar rats by a 10-week DHT treatment. Norepinephrine induced contractility and acetylcholine relaxation were tested in arterioles by pressure arteriography in control as well as DHT- and DHT plus vitamin D₃-treated (DHT+D3) animals. Decreased vasoconstriction and dilatation were detected after DHT treatment. Concomitant vitamin D₃ treatment increased the contractile response and resulted in more relaxed vessels. Endothelial dilation tested with acetylcholine was lower after DHT treatment, this effect was not depend on vitamin D₃ supplementation. In conclusion, hyperandrogenic state resulted in reduced endothelium- and smooth muscle-dependent vasorelaxation and constriction with a complete loss of nitric oxide (NO)-dependent relaxation compared with controls. These alterations caused by chronic DHT treatment were partially reversed by concomitant vitamin D₃ administration.

  20. IL-17 induces reactive astrocytes and up-regulation of vascular endothelial growth factor (VEGF) through JAK/STAT signaling

    PubMed Central

    You, Tao; Bi, Yihui; li, Jun; Zhang, Mingkai; Chen, Xuezhou; Zhang, Keke; Li, Jun

    2017-01-01

    Spinal cord injury is a grave neurological disability resulting in neuron degeneration and permanent paralysis. The inflammation triggered by the injury would promote the spinal cord lesion in turn. Activated astrocytes during inflammatory response could promote glial scar formation and contribute to the progression of the spinal cord injury. Interleukin 17 (IL-17) was upregulated in inflammatory responses to contusion or compression of the spinal cord. in this study, IL-17 could induce reactive astrocytes which was indicated by a well-known hallmark glial fibrillary acidic protein (GFAP) in vitro and in vivo. Moreover, we demonstrated that the upregulation of VEGF was induced by IL-17 human astrocytoma cells. In our further investigation, IL-17 induced the expression of VEGF in spinal cord injury by activating JAK/STAT signaling pathway both in vitro and in vivo. In addition, we also found that IL-17 significantly changed tissue preservation and residual urine volumes and blood-spinal cord-barrier integrity in vivo. This newly found IL-17-JAK/STAT-VEGF axis improves our understanding of the molecular mechanism of spinal cord injury during inflammatory response and provides another potential target of spinal cord injury. PMID:28281545

  1. Multiple, delayed post-tonsillectomy bleedings in 11-year-old girl as a result of vascular abnormality and anastomosis. Case report.

    PubMed

    Pucher, Beata; Szydlowski, Jaroslaw; Smoczyk, Wieslaw; Jonczyk-Potoczna, Katarzyna; Grzegorowski, Michal; Korytowska, Aleksandra

    2016-11-01

    Tonsillectomy and adenoidectomy are the most common surgical procedures in pediatric otolaryngology. The incidence of primary hemorrhage after tonsillectomy in children ranges from 0.38 to 6%. The prevalence of secondary bleeding occurs in 0.5%-9.3% cases [1]. Authors present a case of an 11-year-old girl who experienced 6 delayed, massive post-tonsillectomy bleedings as a result of presence of vascular malformation and the activation of collateral circulation as a result of the left ECA ligature.

  2. Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells

    PubMed Central

    Zhou, X; Chen, M; Zeng, X; Yang, J; Deng, H; Yi, L; Mi, M-t

    2014-01-01

    Mitochondrial reactive oxygen species (mtROS) homeostasis plays an essential role in preventing oxidative injury in endothelial cells, an initial step in atherogenesis. Resveratrol (RSV) possesses a variety of cardioprotective activities, however, little is known regarding the effects of RSV on mtROS homeostasis in endothelial cells. Sirt3 is a mitochondrial deacetylase, which plays a key role in mitochondrial bioenergetics and is closely associated with oxidative stress. The goal of the study is to investigate whether RSV could attenuate oxidative injury in endothelial cells via mtROS homeostasis regulation through Sirt3 signaling pathway. We found that pretreatment with RSV suppressed tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in human umbilical vein endothelial cells (HUVECs) by increasing cell viability, inhibiting cell apoptosis, repressing collapse of mitochondrial membrane potential and decreasing mtROS generation. Moreover, the enzymatic activities of isocitrate dehydrogenase 2 (IDH2), glutathione peroxidase (GSH-Px) and manganese superoxide dismutase (SOD2) as well as deacetylation of SOD2 were increased by RSV pretreatment, suggesting RSV notably enhanced mtROS scavenging in t-BHP-induced endothelial cells. Meanwhile, RSV remarkably reduced mtROS generation by promoting Sirt3 enrichment within the mitochondria and subsequent upregulation of forkhead box O3A (FoxO3A)-mediated mitochondria-encoded gene expression of ATP6, CO1, Cytb, ND2 and ND5, thereby leading to increased complex I activity and ATP synthesis. Furthermore, RSV activated the expressions of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and Sirt3, as well as estrogen-related receptor-α (ERRα)-dependent Sirt3 mRNA transcription, which were abolished in the presence of AMPK inhibitor and AMPK, PGC-1α or Sirt3 siRNA transfection, indicating the effects of RSV on mt

  3. Congenital partial absence of the pericardium presenting with a rare concurrent abnormality of vascular ring diagnosed by cardiac magnetic resonance imaging

    PubMed Central

    Sani, Zahra Alizadeh; Savand-Roomi, Zahra; Vojdanparast, Mohammad; Sarafan, Shadi; Seifi, Azin; Nezafati, Pouya

    2016-01-01

    Congenital absence of the pericardium is a rare abnormality that can be diagnosed by cardiac imaging procedures. A 49-year-old male needed medical attention due to the appearance of palpitation with a systolic murmur, and a notable aortic arch deviation was seen in the chest X-ray. In the echocardiogram, a poor echo window was detected. A cardiac magnetic resonance imaging (MRI) showed a rare concomitant anomaly of partial absence of the pericardium including a rare defect of the right-sided aortic arch. Using cardiac MRI, the pericardium can be easily visualized, and thus, its absence more easily detected, aiding appropriate clinical decision-making. PMID:28217641

  4. Inner Ear Conductive Hearing Loss and Unilateral Pulsatile Tinnitus Associated with a Dural Arteriovenous Fistula: Case Based Review and Analysis of Relationship between Intracranial Vascular Abnormalities and Inner Ear Fluids

    PubMed Central

    Cassandro, Ettore; Cassandro, Claudia; Sequino, Giuliano; Scarpa, Alfonso; Petrolo, Claudio; Chiarella, Giuseppe

    2015-01-01

    While pulsatile tinnitus (PT) and dural arteriovenous fistula (DAVF) are not rarely associated, the finding of a conductive hearing loss (CHL) in this clinical picture is unusual. Starting from a case of CHL and PT, diagnosed to be due to a DAVF, we analyzed relationship between intracranial vascular abnormalities and inner ear fluids. DAVF was treated with endovascular embolization. Following this, there was a dramatic recovery of PT and of CHL, confirming their cause-effect link with DAVF. We critically evaluated the papers reporting this association. This is the first case of CHL associated with PT and DAVF. We describe the most significant experiences and theories reported in literature, with a personal analysis about the possible relationship between vascular intracranial system and labyrinthine fluids. In conclusion, we believe that this association may be a challenge for otolaryngologists. So we suggest to consider the possibility of a DAVF or other AVMs when PT is associated with CHL, without alterations of tympanic membrane and middle ear tests. PMID:26693371

  5. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I.

    PubMed

    Paneni, Francesco; Beckman, Joshua A; Creager, Mark A; Cosentino, Francesco

    2013-08-01

    Hyperglycemia and insulin resistance are key players in the development of atherosclerosis and its complications. A large body of evidence suggest that metabolic abnormalities cause overproduction of reactive oxygen species (ROS). In turn, ROS, via endothelial dysfunction and inflammation, play a major role in precipitating diabetic vascular disease. A better understanding of ROS-generating pathways may provide the basis to develop novel therapeutic strategies against vascular complications in this setting. Part I of this review will focus on the most current advances in the pathophysiological mechanisms of vascular disease: (i) emerging role of endothelium in obesity-induced insulin resistance; (ii) hyperglycemia-dependent microRNAs deregulation and impairment of vascular repair capacities; (iii) alterations of coagulation, platelet reactivity, and microparticle release; (iv) epigenetic-driven transcription of ROS-generating and proinflammatory genes. Taken together these novel insights point to the development of mechanism-based therapeutic strategies as a promising option to prevent cardiovascular complications in diabetes.

  6. Relationship of seminal reactive nitrogen and oxygen species and total antioxidant capacity with sperm DNA fragmentation in infertile couples with normal and abnormal sperm parameters.

    PubMed

    Khosravi, F; Valojerdi, M R; Amanlou, M; Karimian, L; Abolhassani, F

    2014-02-01

    The objective of this study was to investigate the association between the amount of superoxide anion, peroxynitrite as oxidative stress (OS) markers and total antioxidant capacity (TAC) with sperm DNA fragmentation in infertile men with abnormal semen parameters. Semen samples were obtained from 102 infertile couples and divided into groups with normal and abnormal semen parameters according to the World Health Organization (WHO). Peroxynitrite and superoxide anions were detected using spectrofluorometric assays combined with 2,7 dicholorofluorescein (DCF)-DA and 4-chloro-7-nitrobenzo-2-oxa -1, 3-diazole (NBD-CL). Colorimetric assay was used for evaluation of TAC, while DNA fragmentation was studied by using sperm chromatin dispersion test. Superoxide anion, peroxynitrite and DNA fragmentation were significantly higher in infertile couples with abnormal semen parameters as compared to infertile couples with normal semen (P < 0.01). TAC was significantly lower in infertile men with abnormal semen parameters (P < 0.01). There was also a significant positive correlation between OS markers with sperm DNA fragmentation (r = 0.59, P < 0.01 and r = 0.67, P < 0.01, respectively). We have found that imbalance between superoxide anion and peroxynitrite with antioxidant capacity in infertile men with abnormal sperm parameters is associated with higher sperm DNA fragmentation.

  7. Binding of EBP50 to Nox organizing subunit p47phox is pivotal to cellular reactive species generation and altered vascular phenotype

    PubMed Central

    Al Ghouleh, Imad; Meijles, Daniel N.; Zhang, Qiangmin; Sahoo, Sanghamitra; Gorelova, Anastasia; Henrich Amaral, Jefferson; Rodríguez, Andrés I.; Mamonova, Tatyana; Song, Gyun Jee; Bisello, Alessandro; Friedman, Peter A.; Cifuentes-Pagano, M. Eugenia; Pagano, Patrick J.

    2016-01-01

    Despite numerous reports implicating NADPH oxidases (Nox) in the pathogenesis of many diseases, precise regulation of this family of professional reactive oxygen species (ROS) producers remains unclear. A unique member of this family, Nox1 oxidase, functions as either a canonical or hybrid system using Nox organizing subunit 1 (NoxO1) or p47phox, respectively, the latter of which is functional in vascular smooth muscle cells (VSMC). In this manuscript, we identify critical requirement of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50; aka NHERF1) for Nox1 activation and downstream responses. Superoxide (O2•−) production induced by angiotensin II (AngII) was absent in mouse EBP50 KO VSMC vs. WT. Moreover, ex vivo incubation of aortas with AngII showed a significant increase in O2•− in WT but not EBP50 or Nox1 nulls. Similarly, lipopolysaccharide (LPS)-induced oxidative stress was attenuated in femoral arteries from EBP50 KO vs. WT. In silico analyses confirmed by confocal microscopy, immunoprecipitation, proximity ligation assay, FRET, and gain-/loss-of-function mutagenesis revealed binding of EBP50, via its PDZ domains, to a specific motif in p47phox. Functional studies revealed AngII-induced hypertrophy was absent in EBP50 KOs, and in VSMC overexpressing EBP50, Nox1 gene silencing abolished VSMC hypertrophy. Finally, ex vivo measurement of lumen diameter in mouse resistance arteries exhibited attenuated AngII-induced vasoconstriction in EBP50 KO vs. WT. Taken together, our data identify EBP50 as a previously unidentified regulator of Nox1 and support that it promotes Nox1 activity by binding p47phox. This interaction is pivotal for agonist-induced smooth muscle ROS, hypertrophy, and vasoconstriction and has implications for ROS-mediated physiological and pathophysiological processes. PMID:27540115

  8. Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

    PubMed

    Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

    2016-07-01

    Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes.

  9. Lower-limb veins are thicker and vascular reactivity is decreased in a rat PCOS model: concomitant vitamin D3 treatment partially prevents these changes.

    PubMed

    Várbíró, Szabolcs; Sára, Levente; Antal, Péter; Monori-Kiss, Anna; Tőkés, Anna-Mária; Monos, Emil; Benkő, Rita; Csibi, Noémi; Szekeres, Maria; Tarszabo, Robert; Novak, Agnes; Paragi, Péter; Nádasy, György L

    2014-09-15

    Polycystic ovary syndrome (PCOS) causes vascular damage to arteries; however, there are no data for its effect on veins. Our aim was to clarify the effects of dihydrotestosterone (DHT)-induced PCOS both on venous biomechanics and on pharmacological reactivity in a rat model and to test the possible modulatory role of vitamin D3 (vitD). PCOS was induced in female Wistar rats by DHT treatment (83 μg/day, subcutaneous pellet). After 10 wk, the venous biomechanics, norepinephrine (NE)-induced contractility, and acetylcholine-induced relaxation were tested in saphenous veins from control animals and from animals treated with DHT or DHT with vitD using pressure angiography. Additionally, the expression levels of endothelial nitric oxide synthase (eNOS) and cyclooxygenase (COX-2) were measured using immunohistochemistry. Increased diameter, wall thickness, and distensibility as well as decreased vasoconstriction were detected after the DHT treatment. Concomitant vitD treatment lowered the mechanical load on the veins, reduced distensibility, and resulted in vessels that were more relaxed. Although there was no difference in the endothelial dilation tested using acetylcholine (ACh), the blocking effect of N(G)-nitro-l-arginine methyl ester (l-NAME) was lower and was accompanied by lower COX-2 expression in the endothelium after the DHT treatment. Supplementation with vitD prevented these alterations. eNOS expression did not differ among the three groups. We conclude that the hyperandrogenic state resulted in thicker vein walls. These veins showed early remodeling and altered vasorelaxant mechanisms similar to those of varicose veins. Alterations caused by the chronic DHT treatment were prevented partially by concomitant vitD administration.

  10. Cardio-Ankle Vascular Index and C-Reactive Protein Are Useful Parameters for Identification of Ischemic Heart Disease in Acute Heart Failure Patients

    PubMed Central

    Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

    2017-01-01

    Background The most common cause of heart failure (HF) is ischemic heart disease (IHD). Evaluation of IHD with non-invasive examinations is useful for the treatment of HF, and cardio-ankle vascular index (CAVI) is a good parameter for detecting systemic arteriosclerosis. However, the relationship between IHD and CAVI in acute HF (AHF) patients is still unclear. Therefore, we investigated the effect of non-invasive examinations, including CAVI to detect IHD. Methods We studied 53 consecutive patients (average age of 66.5 ± 10.9 years old, 36 males) with AHF from January 2009 to December 2012. These patients were classified into the IHD group (n = 19) and non-IHD group (n = 34) according to the coronary artery angiography results. We evaluated the vital signs, laboratory findings and CAVI. Results According to the laboratory findings, the C-reactive protein (CRP) in IHD group was significantly higher than non-IHD group (1.5 ± 2.1 mg/dL vs. 0.4 ± 0.4 mg/dL, P = 0.002). CAVI in IHD group was significantly higher than non-IHD group (9.58 ± 1.73 vs. 7.83 ± 1.86, P < 0.001). In the receiver operating characteristic (ROC) curve for discriminating the probability of IHD, the cut-off point of the CRP plus CAVI was 9.00. At that cut-off point, the sensitivity and the specificity were 69.7% and 89.5%, respectively. The mean area under the ROC curve (AUC) defined by the CRP plus CAVI was the greatest at all parameters. Conclusion The CRP and CAVI were useful parameters for the identification of IHD in patients with AHF. PMID:28392865

  11. Alveolar abnormalities

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001093.htm Alveolar abnormalities To use the sharing features on this page, please enable JavaScript. Alveolar abnormalities are changes in the tiny air sacs in ...

  12. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... 2012:chap 71. Zaiac MN, Walker A. Nail abnormalities associated with systemic pathologies. Clin Dermatol . 2013;31: ...

  13. Vascular Cures

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  14. Assessing the effect of unilateral cerebral revascularisation on the vascular reactivity of the non-intervened hemisphere: a retrospective observational study

    PubMed Central

    Sam, Kevin; Poublanc, Julien; Sobczyk, Olivia; Han, Jay S; Battisti-Charbonney, Anne; Mandell, Daniel M; Tymianski, Michael; Crawley, Adrian P; Fisher, Joseph A; Mikulis, David J

    2015-01-01

    Objectives Unilateral haemodynamically significant large-vessel intracranial stenosis may be associated with reduced blood-oxygen-level-dependent (BOLD) cerebrovascular reactivity (CVR), an indicator of autoregulatory reserve. Reduced CVR has been associated with ipsilateral cortical thinning and loss in cognitive function. These effects have been shown to be reversible following revascularisation. Our aim was to study the effects of unilateral revascularisation on CVR in the non-intervened hemisphere in bilateral steno-occlusive or Moyamoya disease. Study Design A retrospective observational study. Setting A routine follow-up assessment of CVR after a revascularisation procedure at a research teaching hospital in Toronto (Journal wants us to generalise). Participants Thirteen patients with bilateral Moyamoya disease (age range 18 to 52 years; 3 males), seven patients with steno-occlusive disease (age range 18 to 78 years; six males) and 27 approximately age-matched normal control subjects (age range 19–71 years; 16 males) with no history or findings suggestive of any neurological or systemic disease. Intervention Participants underwent BOLD CVR MRI using computerised prospective targeting of CO2, before and after unilateral revascularisation (extracranial–intracranial bypass, carotid endarterectomy or encephaloduroarteriosynangiosis). Pre-revascularisation and post-revascularisation CVR was assessed in each major arterial vascular territory of both hemispheres. Results As expected, surgical revascularisation improved grey matter CVR in the middle cerebral artery (MCA) territory of the intervened hemisphere (0.010±0.023 to 0.143±0.010%BOLD/mm Hg, p<0.01). There was also a significant post-revascularisation improvement in grey matter CVR in the MCA territory of the non-intervened hemisphere (0.101±0.025 to 0.165±0.015%BOLD/mm Hg, p<0.01). Conclusions Not only does CVR improve in the hemisphere ipsilateral to a flow restoration procedure, but it

  15. Alkali-Metal-Mediated Magnesiations of an N-Heterocyclic Carbene: Normal, Abnormal, and "Paranormal" Reactivity in a Single Tritopic Molecule.

    PubMed

    Martínez-Martínez, Antonio J; Fuentes, M Ángeles; Hernán-Gómez, Alberto; Hevia, Eva; Kennedy, Alan R; Mulvey, Robert E; O'Hara, Charles T

    2015-11-16

    Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6-tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N-heterocyclic carbene (NHC) IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]. Remarkably, magnesiation of IPr occurs at the para-position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr(2-). Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr(-) monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali-metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC.

  16. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  17. Uterine Vascular Lesions

    PubMed Central

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  18. Leukocyte abnormalities.

    PubMed

    Gabig, T G

    1980-07-01

    Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.

  19. Vascular parkinsonism: Deconstructing a syndrome

    PubMed Central

    Vizcarra, Joaquin A.; Lang, Anthony E.; Sethi, Kapil D; Espay, Alberto J.

    2015-01-01

    Progressive ambulatory impairment and abnormal white matter signal on neuroimaging come together under the diagnostic umbrella of vascular parkinsonism. A critical appraisal of the literature, however, suggests that (1) no abnormal structural imaging pattern is specific to vascular parkinsonism; (2) there is poor correlation between brain magnetic resonance imaging hyperintensities and microangiopathic brain disease and parkinsonism from available clinicopathologic data; (3) pure parkinsonism from vascular injury (“definite” vascular parkinsonism) consistently results from ischemic or hemorrhagic strokes involving the substantia nigra and/or nigrostriatal pathway but sparing the striatum itself, the cortex, and the intervening white matter; and (4) many cases reported as vascular parkinsonism may represent pseudovascular parkinsonism (e.g., Parkinson disease or another neurodegenerative parkinsonism such as progressive supranuclear palsy with non-specific neuroimaging signal abnormalities), vascular pseudoparkinsonism (e.g., akinetic mutism due to bilateral mesial frontal strokes or apathetic depression from bilateral striatal lacunar strokes), or pseudovascular pseudoparkinsonism (e.g., higher-level gait disorders, including normal pressure hydrocephalus with transependimal exudate). These syndromic designations are preferable over vascular parkinsonism until pathology or validated biomarkers confirm the underlying nature and relevance of the leukoaraiosis. PMID:25997420

  20. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  1. Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

    PubMed Central

    Cai, Yujun; Knight, Walter E.; Guo, Shujie; Li, Jian-Dong; Knight, Peter A.

    2012-01-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  2. Radiologic atlas of pulmonary abnormalities in children

    SciTech Connect

    Singleton, E.B.; Wagner, M.L.; Dutton, R.V.

    1988-01-01

    This book is an atlas about thoracic abnormalities in infants and children. The authors include computed tomographic, digital subtraction angiographic, ultrasonographic, and a few magnetic resonance (MR) images. They recognize and discuss how changes in the medical treatment of premature infants and the management of infection and pediatric tumors have altered some of the appearances and considerations in these diseases. Oriented toward all aspects of pulmonary abnormalities, the book starts with radiographic techniques and then discusses the normal chest, the newborn, infections, tumors, and pulmonary vascular diseases. There is comprehensive treatment of mediastinal abnormalities and a discussion of airway abnormalities.

  3. Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

    PubMed

    Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

    2016-01-01

    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.

  4. Isolation of vascular smooth muscle antigen-reactive CD4(+)αβTh1 clones that induce pulmonary vasculitis in MRL/Mp-Fas(+/+) mice.

    PubMed

    Fujita, Yoshimasa; Fujii, Takao; Shimizu, Hironori; Sato, Tomomi; Nakamura, Takuji; Iwao, Haruka; Nakajima, Akio; Miki, Miyuki; Sakai, Tomoyuki; Kawanami, Takafumi; Tanaka, Masao; Masaki, Yasufumi; Fukushima, Toshihiro; Okazaki, Toshiro; Umehara, Hisanori; Mimori, Tsuneyo

    2016-05-01

    Here, we established CD4(+)αβTh1 clones specific for rat vascular smooth muscle antigen (VSMAg) that induced vasculitis lesions in the lungs of MRL/Mp-Fas(+/+) mice following adoptive transfer. Six different T cell clones, MV1b1 (Vβ1), MV1b4 (Vβ4), MV1b8.3 (Vβ8.3), MV1b61 (Vβ6), MV1b62 (Vβ6), and MV1b63 (Vβ6), were isolated from the MV1 T cell line from the regional lymph nodes of immunized MRL/Mp-Fas(+/+) mice; the three (Vβ6) clones had unique CDR3 amino acid sequences. Following stimulation with VSMAg-pulsed antigen presenting cells, MV1b61 and MV1b62 failed to secrete interferon-γ and tumor necrosis factor-α, although the other four clones secreted high levels of both cytokines. In adoptive transfer experiments, MV1b61 and MV1b62 did not induce organ involvement including pulmonary vasculitis. In contrast, MV1b1, MV1b4, MV1b8.3, and MV1b63 induced perivascular mononuclear cell infiltration in pulmonary small arteries. These clones may provide useful tools for investigating the underlying mechanisms of vasculitis syndromes and for developing therapeutic strategies.

  5. Acute Effects of Prostaglandin E1 and E2 on Vascular Reactivity and Blood Flow in situ in the Chick Chorioallantoic Membrane

    PubMed Central

    Fay, K.; Dunn, B.E.; Gruenloh, S.K.; Narayanan, J.; Jacobs, E.R.; Medhora, M.

    2013-01-01

    1. The chick chorioallantoic membrane (CAM) subserves gas exchange in the developing embryo and shell-less culture affords a unique opportunity for direct observations over time of individual blood vessels to pharmacologic interventions. We tested a number of lipids including prostaglandins PGE1&2 for vascular effects and signaling in the CAM. Application of PGE1&2 induced a decrease in the diameter of large blood vessels and a concentration-dependent, localized, reversible loss of blood flow through small vessels. The loss of flow was also mimicked by misoprostol, an agonist for 3 of 4 known PGE receptors, EP2-4, and by U46619, a thromboxane mimetic. Selective receptor antagonists for EP3 and thromboxane each partially blocked the response. This is a first report of the effects of prostaglandins on vasoreactivity in the CAM. Our model allows the unique ability to examine simultaneous responses of large and small vessels in real time and in vivo. PMID:22858445

  6. NF1 Signal Transduction and Vascular Dysfunction

    DTIC Science & Technology

    2014-05-01

    following Rheb expression, as shown in Figure 3. We have seen negligible effect on cellular proliferation in complete media. Rheb expression is not...ras signaling bypasses senescence and causes abnormal vascular morphogenesis. Cancer research 70, 3803-3812. Bajaj, A., Zheng, Q. X., Adam, A...Vincent, P., and Pumiglia, K. (2010b). Activation of Endothelial Ras Signaling Bypasses Senescence and Causes Abnormal Vascular Morphogenesis. Cancer

  7. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases.

  8. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

    PubMed Central

    2011-01-01

    Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. Methods and Results P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score ≥400, carotid intima-media thickness (CIMT) > 0.90 mm, ankle-brachial index < 0.90, and/or toe-brachial index < 0.64, respectively. Carotid artery compliance was also determined and the reactive hyperaemia index (RHI) measured by peripheral artery tonometry was used as a surrogate for endothelial function. P-NT-proBNP was associated with atherosclerosis in the unadjusted analysis, but not after adjustment for conventional risk factors. P-NT-proBNP was not associated with vascular dysfunction. The prevalence of atherosclerosis in the coronary, carotid and peripheral arteries was 35%, 10% and 21% of all patients, respectively. In total 49% had atherosclerosis in one territory and 15.6% and 1.0% in two and three territories. Low RHI was an independent predictor of coronary atherosclerosis (odds ratio [CI], 2.60 [1.15-5.88] and systolic blood pressure was the only independent determinant of CIMT (0.02 mm increase in CIMT per 10 mmHg increase in systolic blood pressure [p = 0.003]). Conclusions Half of asymptomatic patients with type 2 diabetes mellitus and microalbuminuria had significant

  9. Beta-Glucans Supplementation Associates with Reduction in P-Cresyl Sulfate Levels and Improved Endothelial Vascular Reactivity in Healthy Individuals

    PubMed Central

    De Angelis, Maria; Rocchetti, Maria Teresa; Montemurno, Eustacchio; Maranzano, Valentina; Dalfino, Giuseppe; Manno, Carlo; Zito, Annapaola; Gesualdo, Michele; Ciccone, Marco Matteo; Gobbetti, Marco; Gesualdo, Loreto

    2017-01-01

    Background Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD). Objective The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD. Methods We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro “Cuore Mio” pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment. Results The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged. Conclusions We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease. PMID:28107445

  10. Role of a novel soluble nucleotide phospho-hydrolase from sheep plasma in inhibition of platelet reactivity: hemostasis, thrombosis, and vascular biology.

    PubMed

    Birk, Alex V; Bubman, Darya; Broekman, M Johan; Robertson, Hugh D; Drosopoulos, Joan H F; Marcus, Aaron J; Szeto, Hazel H

    2002-02-01

    Ecto- and exoenzymes that metabolize extracellular adenosine diphosphate (ADP), the major promoter of platelet activation and recruitment, are of potential clinical importance because they can metabolically prevent excessive thrombus growth. An ecto-ADPase (CD39, NTPDase1) has been identified on endothelial cells. We demonstrate that ADP and adenosine triphosphate (ATP) are rapidly metabolized to adenosine monophosphate (AMP) in sheep plasma at pH 7.4. This hydrolysis is sensitive to P(1), P(5)-di-(adenosine-5') pentaphosphate (Ap(5)A), and ethylene glycol bis (beta-aminoethyl ether) - N, N, N(-), N(-) tetra-acetate (EGTA) but insensitive to tetramisole (an alkaline phosphatase inhibitor). A specific phosphodiesterase substrate, p -nitrophenol-5'-thymidine monophosphate (TMP) (p -Nph-5'-TMP), was readily hydrolyzed in sheep plasma at a rate of approximately 0.25 nmol/min/mg protein, and this hydrolysis was inhibited by ADP, ATP, and Ap(5)A. Furthermore, 200-fold purified p -Nph-5'-TMP-hydrolyzing activity also hydrolyzed ATP and ADP directly to AMP. When ADP was preincubated in plasma, its ability to induce platelet aggregation was inhibited in a time-dependent manner. This effect was abolished by Ap(5)A. The inhibitory effects on platelet aggregation correlated with hydrolysis of the ADP in plasma. These data suggest that the endogenous soluble plasma phosphohydrolase metabolizes ATP and ADP by means of cleavage of the alpha-beta-phosphodiester bond of nucleoside 5'-phosphate derivatives. This novel biochemical activity inhibits platelet reactivity through hydrolysis of extracellular nucleotides released by activated platelets during (patho)physiological processes, serving a homeostatic and antithrombotic function in vivo.

  11. Role of reactive oxygen species in the signalling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells

    PubMed Central

    López-Ongil, S; Hernández-Perera, O; Navarro-Antolín, J; Pérez de Lema, G; Rodríguez-Puyol, M; Lamas, S; Rodríguez-Puyol, D

    1998-01-01

    Cyclosporine A (CsA) increases eNOS mRNA expression in bovine cultured aortic endothelial cells (BAEC). As some effects of CsA may be mediated by reactive oxygen species (ROS), present experiments were devoted to test the hypothesis that the CsA-induced eNOS up-regulation could be dependent on an increased synthesis of ROS.CsA induced a dose-dependent increase of ROS synthesis, with the two fluorescent probes used, DHR123 (CsA 1 μM: 305±7% over control) and H2DCFDA (CsA 1 μM: 178±6% over control).Two ROS generating systems, xanthine plus xanthine oxidase (XXO) and glucose oxidase (GO), increased the expression of eNOS mRNA in BAEC, an effect which was maximal after 8 h of incubation (XXO: 168±21% of control values. GO: 208±18% of control values). The ROS-dependent increased eNOS mRNA expression was followed by an increase in eNOS activity.The effect of CsA on eNOS mRNA expression was abrogated by catalase, and superoxide dismutase (SOD). In contrast, the antioxidant PDTC augmented eNOS mRNA expression, both in basal conditions and in the presence of CsA.The potential participation of the transcription factor AP-1 was explored. Electrophoretic mobility shift assays were consistent with an increase in AP-1 DNA-binding activity in BAEC treated with CsA or glucose oxidase.The present results support a role for ROS, particularly superoxide anion and hydrogen peroxide, as mediators of the CsA-induced eNOS mRNA up-regulation. Furthermore, they situate ROS as potential regulators of gene expression in endothelial cells, both in physiological and pathophysiological situations. PMID:9647467

  12. Antioxidants and vascular health.

    PubMed

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  13. Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways.

    PubMed

    Chen, Yali; Jiang, Jinyao; Miao, Huibing; Chen, Xingjuan; Sun, Xuejun; Li, Yongjun

    2013-03-01

    Hydrogen-rich saline has been reported to prevent neointimal hyperplasia induced by carotid balloon injury. The purpose of the present study was to further investigate the molecular mechanisms underlying this phenomenon. Daily injection of a hydrogen-rich saline solution (HRSS) in rats was employed to study the effect of hydrogen on balloon injury-induced neointimal hyperplasia and the neointima/media ratio was assessed. HRSS significantly decreased the neointima area and neointima/media ratio in a dose-dependent manner. In vitro effects of hydrogen on fetal bovine serum (FBS)-induced vascular smooth muscle cell (VSMC) proliferation were also investigated. Hydrogen-rich medium (HRM) inhibited rat VSMC proliferation and migration induced by 10% FBS. FBS-induced reactive oxygen species (ROS) production and activation of intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), Akt were significantly inhibited by HRM. In addition, HRM blocked FBS-induced progression from the G0/G1 to the S-phase and increased the apoptosis rate of VSMCs. These results showed that hydrogen-rich saline was able to attenuate FBS-induced VSMC proliferation and neointimal hyperplasia by inhibiting ROS production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Thus, HRSS may have potential therapeutic relevance for the prevention of human restenosis.

  14. Role of 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of vascular function in a model of hypertension and endothelial dysfunction.

    PubMed

    Yousif, Mariam H M; Benter, Ibrahim F

    2010-01-01

    The objective of this study was to determine if acute inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis or reduced inactivation of epoxyeicosatrienoic acids (EETs) can correct L-N(G)-nitro-arginine-methyl-ester (L-NAME)-induced abnormal vascular reactivity in the perfused mesenteric bed and the carotid artery of spontaneously hypertensive rats (SHR). Administration of L-NAME in drinking water (80 mg/l) to SHR for 3 weeks resulted in abnormal vascular reactivity to norepinephrine and carbachol in the perfused mesenteric vascular bed and carotid artery, and significantly elevated mean arterial blood pressure (244 +/- 9 mm Hg) as compared to SHR controls drinking regular water (176 +/- 3 mm Hg). In the perfused mesenteric vascular bed, the impaired vascular responsiveness to norepinephrine was corrected by acute treatment with N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET0016), an inhibitor of 20-HETE formation, but not by 1-cyclohexyl-3-dodecyl urea (CDU), an inhibitor of soluble epoxide hydrolase. Treatment with either HET0016 or CDU did not improve impaired carbachol-induced vasodilation in the perfused mesenteric vascular bed. In the isolated carotid artery, treatment with HET0016 corrected the L-NAME-induced increase in norepinephrine-induced vasoconstriction, whereas only CDU treatment could improve impaired carbachol-induced vasodilation. Results of this study indicate that vascular function in a state of compromised nitric oxide formation is differentially modulated by 20-HETE and EETs, and that treatment with HET0016 or CDU may improve vascular function in a state of high blood pressure and endothelial dysfunction.

  15. Negative Association of Circulating MicroRNA-126 with High-sensitive C-reactive Protein and Vascular Cell Adhesion Molecule-1 in Patients with Coronary Artery Disease Following Percutaneous Coronary Intervention

    PubMed Central

    Wang, Jun-Nan; Yan, You-You; Guo, Zi-Yuan; Jiang, Ya-Juan; Liu, Lu-Lu; Liu, Bin

    2016-01-01

    Background: Percutaneous coronary intervention (PCI) causes endothelial damage, resulting in an inflammatory response with elevation of markers such as high-sensitive C-reactive protein (hs-CRP) and vascular cell adhesion molecule-1 (VCAM-1), which are associated with restenosis after PCI. Evidence suggests that microRNA-126 (miR-126) plays an important role in vascular inflammation, but its correlation with PCI-mediated inflammation has not been investigated. In this study, we investigated the effect of PCI on circulating miR-126 and inflammation markers such as hs-CRP and VCAM-1. Methods: We enrolled 130 patients with coronary artery disease (CAD) in the Second Hospital of Jilin University from October 2015 to December 2015. Among them, 82 patients with CAD, defined as at least one major epicardial vessel with >70% stenosis who planned to undergo PCI, were divided into acute coronary syndrome (ACS) group (46 patients) and stable angina (SA) group (36 patients). Forty-eight patients confirmed by coronary angiography without PCI were used as controls. The plasmas of all patients were collected prior to PCI and at 30 min, 24 h, and 72 h after PCI. The plasma VCAM-1 and hs-CRP were detected by enzyme-linked immunosorbent assay, and the miR-126 was evaluated by quantitative reverse transcription-polymerase chain reaction. Results: Plasma concentrations of hs-CRP and VCAM-1 in patients with either ACS (n = 46) or SA (n = 36) were significantly higher than in controls (n = 48) (P < 0.01) prior to PCI, and increased further at 24 h and 72 h after PCI, compared with prior PCI. Moreover, VCAM-1 was positively correlated with balloon time and pressure. In contrast, the plasma concentration of miR-126 was significantly lower in patients with CAD than in controls, and further decreased with time post-PCI. A negative correlation was observed between miR-126 and hs-CRP and VCAM-1 at 72 h after PCI. Conclusion: There was a negative correlation of miR-126 with the PCI

  16. Ultrasound -- Vascular

    MedlinePlus

    ... plan for their effective treatment. detect blood clots (deep venous thrombosis (DVT) in the major veins of ... What are the limitations of Vascular Ultrasound? Vessels deep in the body are harder to see than ...

  17. Vascular Dementia

    MedlinePlus

    ... attack) may increase your risk of developing dementia. Atherosclerosis. This condition occurs when deposits of cholesterol and ... in your arteries and narrow your blood vessels. Atherosclerosis can increase your risk of vascular dementia — and ...

  18. OBESITY AND VASCULAR DYSFUNCTION

    PubMed Central

    Stapleton, Phoebe A.; James, Milinda E.; Goodwill, Adam G.; Frisbee, Jefferson C.

    2008-01-01

    One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects. PMID:18571908

  19. Palmitic acid exerts pro-inflammatory effects on vascular smooth muscle cells by inducing the expression of C-reactive protein, inducible nitric oxide synthase and tumor necrosis factor-α.

    PubMed

    Wu, Di; Liu, Juntian; Pang, Xiaoming; Wang, Shuyue; Zhao, Jingjing; Zhang, Xiaolu; Feng, Liuxin

    2014-12-01

    Atherosclerosis is a chronic inflammatory disease in the vessel, and inflammatory cytokines play an important role in the inflammatory process of atherosclerosis. A high level of free fatty acids (FFAs) produced in lipid metabolism disorders are known to participate in the formation of atherosclerosis through multiple bioactivities. As the main saturated fatty acid in FFAs, palmitic acid stimulates the expression of inflammatory cytokines in macrophages. However, it is unclear whether palmitic acid exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of palmitic acid on the expression of C-reactive protein (CRP), tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in VSMCs. Rat VSMCs were cultured, and palmitic acid was used as a stimulant for CRP, TNF-α and iNOS expression. mRNA expression was assayed with reverse transcription-polymerase chain reaction, and protein expression was detected with western blot analysis and immunocytochemistry. The results showed that palmitic acid significantly stimulated mRNA and protein expression of CRP, TNF-α and iNOS in VSMCs in time- and concentration-dependent manners, and therefore, palmitic acid is able to exert a pro-inflammatory effect on VSMCs via stimulating CRP, TNF-α and iNOS expression. The findings provide a novel explanation for the direct pro-inflammatory and atherogenic effects of palmitic acid, and for the association with metabolic syndrome, such as type 2 diabetes mellitus, obesity and atherosclerosis. Therefore, the intervention with anti-inflammatory agents may effectively delay the formation and progression of atherosclerosis in patients with metabolic syndrome.

  20. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling

    PubMed Central

    Rey, Sergio; Semenza, Gregg L.

    2010-01-01

    The vascular system delivers oxygen and nutrients to every cell in the vertebrate organism. Hypoxia-inducible factor 1 (HIF-1) is a master regulator of hypoxic/ischaemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and the mobilization and homing of bone marrow-derived angiogenic cells. This review will focus on the pivotal role of HIF-1 in vascular homeostasis, the involvement of HIF-1 in vascular diseases, and recent advances in targeting HIF-1 for therapy in preclinical models. PMID:20164116

  1. Hypothermic Effects on Vascular Contractility and Reactivity,

    DTIC Science & Technology

    1986-01-01

    RESEARCH INSTITUTE OF ENVIRONMENTAL MEDICINE Natick, Massachuse sittsET DTIC .. &S;;.LECTEI .- 1 "JANUARY 1986 JUN 2 4 W6-I UNITED STATES ARMY c...DOCMENTTIONPAGEBEFORE COMPLETING FORM . REPORT NUMBER .A ACESSION No I. RECIPIENT’S CATALOG NUMBER AI 4. TITLE (and Subtitle) Aa. TYPE OF REPORT & PERIOD COVERED...Institute of Environmental WU-001 Medicine , Natick, MA 01760-5007 11. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Cold Research Division I

  2. Endothelial GRK2 regulates vascular homeostasis through the control of free radical oxygen species

    PubMed Central

    Ciccarelli, Michele; Sorriento, Daniela; Franco, Antonietta; Fusco, Anna; Giudice, Carmine Del; Annunziata, Roberto; Cipolletta, Ersilia; Monti, Maria Gaia; Dorn, Gerald W; Trimarco, Bruno; Iaccarino, Guido

    2014-01-01

    Objective The role of endothelial GRK2 was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2fl/fl). Approach and Results Aortas from Tie2-CRE/GRK2fl/fl presented functional and structural alterations as compared to control GRK2fl/fl mice. In particular, vasoconstriction was blunted to different agonists, and collagen and elastic rearrangement and macrophage infiltration were observed. In primary cultured endothelial cells deficient for GRK2, mitochondrial reactive oxygen species (ROS) was increased, leading to expression of cytokines. Chronic treatment with a ROS scavenger in mice corrected the vascular phenotype by recovering vasoconstriction, structural abnormalities and reducing macrophage infiltration. Conclusions These results demonstrate that GRK2 removal compromises vascular phenotype and integrity by increasing endothelial ROS production. PMID:23950144

  3. Characterization of vascular tree architecture using the Tokunaga taxonomy

    NASA Astrophysics Data System (ADS)

    Galarreta-Valverde, Miguel A.; Zoghbi, Jihan M.; Pereira, Fabricio; Beregi, Jean-Paul; Mekkaoui, Choukri; Jackowski, Marcel P.

    2015-03-01

    The diagnosis of cardiovascular disease is usually assisted by resonance angiography (MRA) or computed tomography angiography (CTA) imaging. The identification of abnormal vascular architecture from angiographic three-dimensional images is therefore crucial to the diagnosis of cardiovascular disease. Automated detection and quantification of vascular structure and architecture thus holds significant clinical value. In this work, we employ a Lindenmayer system to represent vascular trees from angiographic images and describe a quantitative measure based on the Tokunaga taxonomy to differentiate vascular architectures. Synthetic vessel architectures with varying bifurcation patterns were compared and results showed that this architectural measure is proportional to the level of branching. In real MRA images, this measure was able to differentiate between normal and abnormal intracerebral vasculature containing an aneurysm. Hence, this methodology not only allows for compact representation of vascular architectures but also provides a quantitative metric of bifurcation complexity, which has the potential to characterize different types of vascular abnormalities.

  4. Polycystic ovary syndrome and obesity do not affect vascular parameters related to early atherosclerosis in young women without glucose metabolism disturbances, arterial hypertension and severe abnormalities of lipid profile.

    PubMed

    Barcellos, Cristiano Roberto Grimaldi; Lage, Silvia Helena Gelás; Rocha, Michelle Patrocínio; Hayashida, Sylvia Asaka Yamashita; Baracat, Edmund Chade; Romano, Angela; Brito, Vinicius Nahime; Marcondes, José Antonio Miguel

    2013-04-01

    The aim of this study was to evaluate the influence of polycystic ovary syndrome (PCOS) and obesity on vascular parameters related to early atherosclerosis (VP-EA) [brachial flow-mediated dilation (FMD), carotid intima-media thickness (CIMT) and carotid arterial compliance (CAC)] in women with minor cardiovascular risk factors (CVRFs). Twenty-five young women with PCOS and 23 eumenorrheic women matched for body mass index (BMI) were studied. The women were subdivided according to BMI and PCOS status, and comparisons were done between PCOS and Control group, regardless of BMI, and between Obese and Lean group, regardless of the presence of PCOS. Insulin resistance was higher in PCOS-group than in control-group and in obese-group than in lean-group. The median of all VP-EA evaluated were similar between PCOS-group and Control-group [FMD: 6.6 versus 8.4% (p = NS); CIMT: 48.0 versus 47.0 mm.10-2 (p = NS); CAC: 6.2 versus 5.6N-1.m4.10-10 (p = NS)] and between obese-group and lean-group [FMD: 7.8 versus 6.6% (p = NS); CIMT: 48.0 versus 47.0 mm.10-2 (p = NS); CAC: 5.7 versus 6.3N-1.m4.10-10 (p = NS)]. These results suggest that PCOS and obesity do not affect VP-EA in women with minor CVRFs.

  5. What Is Vascular Disease?

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  6. Vascular Disease Foundation

    MedlinePlus

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  7. Vascular endothelium and platelet preparations for the prediction of xenobiotic effects on the vascular system.

    PubMed

    Togna, G; Togna, A R; Caprino, L

    1985-01-01

    Platelets and vascular cells play a fundamental role in the pathogenesis of cardiovascular diseases including thrombus formation and atherosclerotic phenomena. Preparations of platelets and aortic rings have been developed to study the potential of xenobiotics to produce evidence of vascular toxicity in vitro. The xenobiotics cadmium and mercury which exert vascular toxicity in vivo, modify platelet and endothelial-cell reactivity in these in vitro systems.

  8. [Aging and retinal vascular diseases].

    PubMed

    Takagi, Hitoshi

    2007-03-01

    Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been

  9. NADPH Oxidases in Vascular Pathology

    PubMed Central

    Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

  10. Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase (Tie2-sEH Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and ω-Hydroxylases

    PubMed Central

    Zeldin, Darryl C.; Morisseau, Christophe; Falck, John R.

    2017-01-01

    Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(ω)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas ω-terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic vasodilation known as coronary reactive hyperemia (CRH). CRH prevents the potential harm associated with transient ischemia. The beneficial effects of EETs are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). ω-terminal HETEs are formed by ω-hydroxylase family members. The relationship among endothelial over-expression of sEH (Tie2-sEH Tr), the changes in oxylipins it may produce, the pharmacologic inhibition of ω-hydroxylases, activation of PPARγ, and CRH response to a brief ischemia is not known. We hypothesized that CRH is attenuated in isolated mouse hearts with endothelial sEH over-expression through modulation of oxylipin profiles, whereas both inhibition of ω-hydroxylases and activation of PPARγ enhance CRH. Compared to WT mice, Tie2-sEH Tr mice had decreased CRH, including repayment volume, repayment duration, and repayment/debt ratio (P < 0.05), whereas inhibition of ω-hydroxylases increased these same CRH parameters in Tie2-sEH Tr mice. Inhibition of sEH with t-AUCB reversed the decreased CRH in Tie2-sEH Tr mice. Endothelial over-expression of sEH significantly changed oxylipin profiles, including decreases in DHETs, mid-chain HETEs, and prostaglandins (P < 0.05). Treatment with rosiglitazone, PPARγ-agonist, enhanced CRH (P < 0.05) in both Tie2-sEH Tr and wild type (WT) mice. These data demonstrate that endothelial over-expression of sEH (through changing the oxylipin profiles) attenuates CRH, whereas inhibition of

  11. Vascular remodeling underlies rebleeding in hemophilic arthropathy.

    PubMed

    Bhat, Vikas; Olmer, Merissa; Joshi, Shweta; Durden, Donald L; Cramer, Thomas J; Barnes, Richard Fw; Ball, Scott T; Hughes, Tudor H; Silva, Mauricio; Luck, James V; Moore, Randy E; Mosnier, Laurent O; von Drygalski, Annette

    2015-11-01

    Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

  12. Laminins and retinal vascular development.

    PubMed

    Edwards, Malia M; Lefebvre, Olivier

    2013-01-01

    The mechanisms controlling vascular development, both normal and pathological, are not yet fully understood. Many diseases, including cancer and diabetic retinopathy, involve abnormal blood vessel formation. Therefore, increasing knowledge of these mechanisms may help develop novel therapeutic targets. The identification of novel proteins or cells involved in this process would be particularly useful. The retina is an ideal model for studying vascular development because it is easy to access, particularly in rodents where this process occurs post-natally. Recent studies have suggested potential roles for laminin chains in vascular development of the retina. This review will provide an overview of these studies, demonstrating the importance of further research into the involvement of laminins in retinal blood vessel formation.

  13. Aldosterone and the vascular system.

    PubMed

    Cachofeiro, Victoria; Miana, Maria; de Las Heras, Natalia; Martín-Fernández, Beatriz; Ballesteros, Sandra; Fernández-Tresguerres, Jesús; Lahera, Vicente

    2008-04-01

    Aldosterone can act in different tissues exerting physiological and pathological effects. At the vascular level, aldosterone affects endothelial function since administration of aldosterone impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorate relaxation to acetylcholine in models of both hypertension and atherosclerosis and in patients with heart failure. A reduction in nitric oxide levels seems to be the main mechanism underlying this effect due to a reduction in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone is a pro-inflammatory factor that can participate in the vascular inflammatory process associated with different pathologies including hypertension through activation of the NFkappaB system, which mediates the vascular production of different cytokines. This mineralocorticoid also participates in the vascular remodeling observed in hypertensive rats since the administration of eplerenone improved the media-to-lumen ratio in these animals. This effect seems to be due to an increase in extracellular matrix. In summary, aldosterone through mineralocorticoid receptors can participate in the vascular damage associated with different pathologies including hypertension through its prooxidant, pro-inflammatory and profibrotic effects that triggered endothelial dysfunction, an inflammatory process and vascular remodeling.

  14. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  15. Urine - abnormal color

    MedlinePlus

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  16. Tooth - abnormal colors

    MedlinePlus

    ... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

  17. Abnormal Head Position

    MedlinePlus

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  18. Skeletal limb abnormalities

    MedlinePlus

    ... medlineplus.gov/ency/article/003170.htm Skeletal limb abnormalities To use the sharing features on this page, please enable JavaScript. Skeletal limb abnormalities refers to a variety of bone structure problems ...

  19. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... PROBLEMS Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... treat abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...

  20. Vascular dementia

    PubMed Central

    Korczyn, Amos D; Vakhapova, Veronika; Grinberg, Lea T

    2012-01-01

    The epidemic grow of dementia causes great concern for the society. It is customary to consider Alzheimer’s disease (AD) as the most common cause of dementia, followed by vascular dementia (VaD). This dichotomous view of a neurodegenerative disease as opposed to brain damage caused by extrinsic factors led to separate lines of research in these two entities. Indeed, accumulated data suggest that the two disorders have additive effects and probably interact; however it is still unknown to what degree. Furthermore, epidemiological studies have shown “vascular” risk factors to be associated with AD. Therefore, a clear distinction between AD and VaD cannot be made in most cases, and is furthermore unhelpful. In the absence of efficacious treatment for the neurodegenerative process, special attention must be given to vascular component, even in patients with presumed mixed pathology. Symptomatic treatment of VaD and AD are similar, although the former is less effective. For prevention of dementia it is important to treat aggressively all factors, even in stroke survivors who do not show evidence of cognitive decline,. In this review, we will give a clinical and pathological picture of the processes leading to VaD and discuss it interaction with AD. PMID:22575403

  1. Vascular hyperpolarization in human physiology and cardiovascular risk conditions and disease.

    PubMed

    Schinzari, F; Tesauro, M; Cardillo, C

    2017-01-01

    Hyperpolarization causing smooth muscle relaxation contributes to the maintenance of vascular homeostasis, particularly in small-calibre arteries and arterioles. It may also become a compensatory vasodilator mechanism upregulated in states with impaired nitric oxide (NO) availability. Bioassay of vascular hyperpolarization in the human circulation has been hampered by the complexity of mechanisms involved and the limited availability of investigational tools. Firm evidence, however, supports the notion that hyperpolarization participates in the regulation of resting vasodilator tone and vascular reactivity in healthy subjects. In addition, an enhanced endothelium-derived hyperpolarization contributes to both resting and agonist-stimulated vasodilation in a variety of cardiovascular risk conditions and disease. Thus, hyperpolarization mediated by epoxyeicosatrienoic acids (EETs) and H2 O2 has been observed in coronary arterioles of patients with coronary artery disease. Similarly, ouabain-sensitive and EETs-mediated hyperpolarization has been observed to compensate for NO deficiency in patients with essential hypertension. Moreover, in non-hypertensive patients with multiple cardiovascular risk factors and in hypercholesterolaemia, KCa channel-mediated vasodilation appears to be activated. A novel paradigm establishes that perivascular adipose tissue (PVAT) is an additional regulator of vascular tone/function and endothelium is not the only agent in vascular hyperpolarization. Indeed, some PVAT-derived relaxing substances, such as adiponectin and angiotensin 1-7, may exert anticontractile and vasodilator actions by the opening of KCa channels in smooth muscle cells. Conversely, PVAT-derived factors impair coronary vasodilation via differential inhibition of some K(+) channels. In view of adipose tissue abnormalities occurring in human obesity, changes in PVAT-dependent hyperpolarization may be relevant for vascular dysfunction also in this condition.

  2. Vascular risk factors, endothelial function, and carotid thickness in patients with migraine: relationship to atherosclerosis.

    PubMed

    Hamed, Sherifa A; Hamed, Enas A; Ezz Eldin, Azza M; Mahmoud, Nagia M

    2010-03-01

    Recent studies indicated that migraine is associated with specific vascular risk profile. However, the functional and structural vascular abnormalities in migraine are rarely addressed. We evaluated the vascular risk factors, endothelial function, and carotid artery (CA)-intima-media thickness (IMT), segregators of preclinical atherosclerosis, in migraineurs. This preliminary study included 63 adults with headache (migraine with aura [n=14], migraine without aura [n=24], transformed migraine [n=6], and tension headache [n=19]) and 35 matched healthy subjects. The following vascular risks were assessed: body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures (DBP), serum levels of C-reactive protein, fasting glucose, fasting insulin, total cholesterol, and triglycerides. Plasma endothelin (ET)-1, a vasoactive peptide produced by vascular smooth muscle cells and marker for endothelial injury and atherosclerosis, was measured. Endothelial-dependent vasoreactivity was assessed using brachial artery flow-mediated dilatation (FMD) in response to hyperemia. CA-IMT, structural marker of early atherosclerosis, was measured. Compared with control subjects, SBP, DBP, glucose, insulin, ET-1, and CA-IMT were elevated with migraine. FMD% was inversely correlated with SBP (P < .001), DBP (P < .01), glucose (P < .001), and insulin levels (P < .01). CA-IMT was correlated with BMI (P < .05), SBP (P < .01), total cholesterol (P < .01), triglycerides (P < .001), glucose (P < .001), insulin (P < .01), and FMD% (P < .05). In multivariate analysis, ET-1 was correlated with duration of illness, SBP, DBP, glucose, insulin, IMT, and FMD%. We conclude that endothelial injury, impaired endothelial vasoreactivity, and increased CA-IMT occur with migraine and are associated with vascular risk factors that strongly suggest that migraine could be a risk for atherosclerosis.

  3. Vascular Abnormalities Associated with Thermal and Electrical Trauma,

    DTIC Science & Technology

    1992-01-01

    catheters into central veins . Reported me- in whom repeated punctures may result in hema- chanical complication rates of central venous access toma...by Indicator-dilu- 41, Moosman, D.A.: The anatomy of infraclavicular subclavian tion technique. J, Appl. Physiol., 63:907, 1987. vein catheterization ...techniques quate debridement. used to gain central venous access. Additionally, Proper wound care after fasciotomy is important pulmonary infarcts

  4. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  5. Vascular permeability, vascular hyperpermeability and angiogenesis

    PubMed Central

    Nagy, Janice A.; Benjamin, Laura; Zeng, Huiyan; Dvorak, Ann M.

    2008-01-01

    The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both provide useful but complementary information. Vascular permeability by any measure is dramatically increased in acute and chronic inflammation, cancer, and wound healing. This hyperpermeability is mediated by acute or chronic exposure to vascular permeabilizing agents, particularly vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A). We demonstrate that three distinctly different types of vascular permeability can be distinguished, based on the different types of microvessels involved, the composition of the extravasate, and the anatomic pathways by which molecules of different size cross-vascular endothelium. These are the basal vascular permeability (BVP) of normal tissues, the acute vascular hyperpermeability (AVH) that occurs in response to a single, brief exposure to VEGF-A or other vascular permeabilizing agents, and the chronic vascular hyperpermeability (CVH) that characterizes pathological angiogenesis. Finally, we list the numerous (at least 25) gene products that different authors have found to affect vascular permeability in variously engineered mice and classify them with respect to their participation, as far as possible, in BVP, AVH and CVH. Further work will be required to elucidate the signaling pathways by which each of these molecules, and others likely to be discovered, mediate the different types of vascular permeability. PMID:18293091

  6. Morphological abnormalities among lampreys

    USGS Publications Warehouse

    Manion, Patrick J.

    1967-01-01

    The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.

  7. Rho kinase as a target for cerebral vascular disorders

    PubMed Central

    Bond, Lisa M; Sellers, James R; McKerracher, Lisa

    2015-01-01

    The development of novel pharmaceutical treatments for disorders of the cerebral vasculature is a serious unmet medical need. These vascular disorders are typified by a disruption in the delicate Rho signaling equilibrium within the blood vessel wall. In particular, Rho kinase overactivation in the smooth muscle and endothelial layers of the vessel wall results in cytoskeletal modifications that lead to reduced vascular integrity and abnormal vascular growth. Rho kinase is thus a promising target for the treatment of cerebral vascular disorders. Indeed, preclinical studies indicate that Rho kinase inhibition may reduce the formation/growth/rupture of both intracranial aneurysms and cerebral cavernous malformations. PMID:26062400

  8. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  9. Exercise and vascular function: how much is too much?

    PubMed

    Durand, Matthew J; Gutterman, David D

    2014-07-01

    Exercise is a powerful therapy for preventing the onset of and slowing the progression of cardiovascular disease. Increased shear stress during exercise improves vascular homeostasis by both decreasing reactive oxygen species and increasing nitric oxide bioavailability in the endothelium. While these observations are well accepted as they apply to individuals at risk for cardiovascular disease, less is known about how exercise, especially intense exercise, affects vascular function in healthy individuals. This review highlights examples of how vascular function can paradoxically be impaired in otherwise healthy individuals by extreme levels of exercise, with a focus on the causative role that reactive oxygen species play in this impairment.

  10. Advances in Vascular Hyporeactivity After Shock: The Mechanisms and Managements.

    PubMed

    Duan, Chenyang; Yang, Guangming; Li, Tao; Liu, Liangming

    2015-12-01

    Vascular reactivity to vasoconstrictors and vasodilators is greatly reduced after severe trauma, shock, and sepsis or multiple organ dysfunction syndrome. This reduced vascular reactivity severely interferes with the treatment of shock and other critical conditions. In particular, it interferes with the efficacy of vasoactive agents. Consequently, it is very important to elucidate the mechanisms and search for the effective treatment measures. In recent years, a lot of studies focused on the characteristics and the change rules of vascular hyporeactivity and mechanisms following shock. Also, the treatment approaches based on various mechanisms have been a hot pot these years.

  11. Coexistence of pheochromocytoma with uncommon vascular lesions

    PubMed Central

    Kota, Sunil Kumar; Kota, Siva Krishna; Meher, Lalit Kumar; Jammula, Sruti; Panda, Sandip; Modi, Kirtikumar D.

    2012-01-01

    Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14%) had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis. PMID:23226643

  12. Plant Vascular Biology 2013: vascular trafficking.

    PubMed

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä

    2014-04-01

    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland (http://www.pvb2013.org). The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  13. Vascular involvement in systemic sclerosis (scleroderma)

    PubMed Central

    Pattanaik, Debendra; Brown, Monica; Postlethwaite, Arnold E

    2011-01-01

    Systemic sclerosis (SSc) is an acquired multiorgan connective tissue disease with variable mortality and morbidity dictated by clinical subset type. The etiology of the basic disease and pathogenesis of the systemic autoimmunity, fibrosis, and fibroproliferative vasculopathy are unknown and debated. In this review, the spectrum of vascular abnormalities and the options currently available to treat the vascular manifestations of SSc are discussed. Also discussed is how the hallmark pathologies (ie, how autoimmunity, vasculopathy, and fibrosis of the disease) might be effected and interconnected with modulatory input from lysophospholipids, sphingosine 1-phosphate, and lysophosphatidic acid. PMID:22096374

  14. Mechanotransduction in Embryonic Vascular Development

    PubMed Central

    Roman, Beth L.; Pekkan, Kerem

    2015-01-01

    A plethora of biochemical signals provides spatial and temporal cues that carefully orchestrate the complex process of vertebrate embryonic development. The embryonic vasculature develops not only in the context of these biochemical cues, but also in the context of the biomechanical forces imparted by blood flow. In the mature vasculature, different blood flow regimes induce distinct genetic programs, and significant progress has been made toward understanding how these forces are perceived by endothelial cells and transduced into biochemical signals. However, it cannot be assumed that paradigms that govern the mature vasculature are pertinent to the developing embryonic vasculature. The embryonic vasculature can respond to the mechanical forces of blood flow, and these responses are critical in vascular remodeling, certain aspects of sprouting angiogenesis, and maintenance of arterial-venous identity. Here, we review data regarding mechanistic aspects of endothelial cell mechanotransduction, with a focus on the response to shear stress, and elaborate upon the multifarious effects of shear stress on the embryonic vasculature. In addition, we discuss emerging predictive vascular growth models and highlight the prospect of combining signaling pathway information with computational modeling. We assert that correlation of precise measurements of hemodynamic parameters with effects on endothelial cell gene expression and cell behavior is required for fully understanding how blood flow-induced loading governs normal vascular development and shapes congenital cardiovascular abnormalities. PMID:22744845

  15. Importance of insulin resistance to vascular repair and regeneration.

    PubMed

    Cubbon, Richard M; Mercer, Ben N; Sengupta, Anshuman; Kearney, Mark T

    2013-07-01

    Metabolic insulin resistance is apparent across a spectrum of clinical disorders, including obesity and diabetes, and is characterized by an adverse clustering of cardiovascular risk factors related to abnormal cellular responses to insulin. These disorders are becoming increasingly prevalent and represent a major global public health concern because of their association with significant increases in atherosclerosis-related mortality. Endogenous repair mechanisms are thought to retard the development of vascular disease, and a growing evidence base supports the adverse impact of the insulin-resistant phenotype upon indices of vascular repair. Beyond the impact of systemic metabolic changes, emerging data from murine studies also provide support for abnormal insulin signaling at the level of vascular cells in retarding vascular repair. Interrelated pathophysiological factors, including reduced nitric oxide bioavailability, oxidative stress, altered growth factor activity, and abnormal intracellular signaling, are likely to act in conjunction to impede vascular repair while also driving vascular damage. Understanding of these processes is shaping novel therapeutic paradigms that aim to promote vascular repair and regeneration, either by recruiting endogenous mechanisms or by the administration of cell-based therapies.

  16. Renal vascular lesions in systemic lupus erythematosus.

    PubMed

    Katz, S M; Korn, S; Umlas, S L; DeHoratius, R J

    1990-01-01

    In the past, necrotizing vasculitis has been considered to be one of the dominant intrarenal vascular abnormalities in systemic lupus erythematosus (SLE). To test the validity of this statement, 70 consecutive renal biopsies from patients with SLE were reviewed. Light microscopy (LM) and immunofluorescence (IF) studies documented abnormalities, including thrombosis and nephrosclerosis, in 30 patients (43 percent), but no cellular infiltration of the vessel walls or other evidence of acute necrotizing vasculitis was seen. It is concluded that while intrarenal vasculopathy with thrombosis and nephrosclerosis is a common finding in SLE, our data and recently published studies suggest that acute necrotizing vasculitis occurs rarely, if at all, in SLE nephritis.

  17. Society for Vascular Medicine

    MedlinePlus

    ... Certification with this new online course from the Society for Vascular Medicine. Learn more. Looking for a ... jobs are listed right now. Copyright © 2016 The Society for Vascular Medicine. All Rights Reserved.

  18. Primary vascular access.

    PubMed

    Gibbons, C P

    2006-05-01

    Primary vascular access is usually achievable by a distal autogenous arterio-venous fistula (AVF). This article describes the approach to vascular access planning, the usual surgical options and the factors affecting patency.

  19. Society for Vascular Medicine

    MedlinePlus

    ... Journal Scientific Sessions Website FAQ Copyright © 2017 The Society for Vascular Medicine. All Rights Reserved. Phone: +1- ... page Videos Training Programs Journal Access the Journal Society Communications Patient Information Pages Vascular Medicine Journal CME ...

  20. Pathogenesis of diabetic cerebral vascular disease complication

    PubMed Central

    Xu, Ren-Shi

    2015-01-01

    Diabetes mellitus is one of the most potent independent risk factors for the development of diabetic cerebral vascular disease (CVD). Many evidences suggested that hyperglycemia caused excess free fatty acids, the loss of endothelium-derived nitric oxide, insulin resistance, the prothrombotic state, endothelial dysfunction, the abnormal release of endothelial vasoactivators, vascular smooth muscle dysfunction, oxidative stress, and the downregulation of miRs participated in vessel generation and recovery as well as the balance of endotheliocytes. In turn, these abnormalities, mainly via phosphatidylinositol 3 kinase, mitogen-activated protein kinase, polyol, hexosamine, protein kinase C activation, and increased generation of advanced glycosylation end products pathway, play an important role in inducing diabetic CVD complication. A deeper comprehension of pathogenesis producing diabetic CVD could offer base for developing new therapeutic ways preventing diabetic CVD complications, therefore, in the paper we mainly reviewed present information about the possible pathogenesis of diabetic CVD complication. PMID:25685278

  1. Vascular Endothelium and Hypovolemic Shock.

    PubMed

    Gulati, Anil

    2016-01-01

    Endothelium is a site of metabolic activity and has a major reservoir of multipotent stem cells. It plays a vital role in the vascular physiological, pathophysiological and reparative processes. Endothelial functions are significantly altered following hypovolemic shock due to ischemia of the endothelial cells and by reperfusion due to resuscitation with fluids. Activation of endothelial cells leads to release of vasoactive substances (nitric oxide, endothelin, platelet activating factor, prostacyclin, mitochondrial N-formyl peptide), mediators of inflammation (tumor necrosis factor α, interleukins, interferons) and thrombosis. Endothelial cell apoptosis is induced following hypovolemic shock due to deprivation of oxygen required by endothelial cell mitochondria; this lack of oxygen initiates an increase in mitochondrial reactive oxygen species (ROS) and release of apoptogenic proteins. The glycocalyx structure of endothelium is compromised which causes an impairment of the protective endothelial barrier resulting in increased permeability and leakage of fluids in to the tissue causing edema. Growth factors such as angiopoetins and vascular endothelial growth factors also contribute towards pathophysiology of hypovolemic shock. Endothelium is extremely active with numerous functions, understanding these functions will provide novel targets to design therapeutic agents for the acute management of hypovolemic shock. Hypovolemic shock also occurs in conditions such as dengue shock syndrome and Ebola hemorrhagic fever, defining the role of endothelium in the pathophysiology of these conditions will provide greater insight regarding the functions of endothelial cells in vascular regulation.

  2. PHACE Syndrome: Persistent Fetal Vascular Anomalies

    PubMed Central

    Prochazka, V.; Hrbac, T.; Chmelova, J.; Skoloudik, D.; Prochazka, M.

    2005-01-01

    Summary PHACE(S) syndrome is an acronym for neurocutaneous disease encompassing the expression of (P) posterior cranial fossa malformations, (H) facial haemangiomas, (A) arterial anomalies, (C) aortic coarctaion and other cardiac defects, (E) eye abnormalities and (S) for sternal malformation or stenotic arterial diseases. We report on a case of PHACE syndrome complete expression with persistent fetal vascular anomalies unusually in a 55-year-old women with large bilateral facial and neck haemangioma and posterior fossa circulation insufficiency. PMID:20584448

  3. Maternal homocystinuria and Moebius syndrome? Vascular aetiology.

    PubMed

    Gupta, N; Anthony, M Y

    2011-02-14

    A case of Moebius syndrome is reported in an infant of a mother known to have pyridoxine-unresponsive homocystinuria. The authors suggest that Moebius syndrome could result from early vascular insufficiency or disruption occurring early in development related to maternal homocystinuria. Moebius syndrome consists of congenital complete or partial facial nerve palsy with or without paralysis of other cranial nerves and often in association with other malformations of the limbs and orofacial structures, but usually without gross structural brain abnormalities.

  4. [The relativity of abnormity].

    PubMed

    Nilson, Annika

    2006-01-01

    In the late 19th century and in the beginning of the 20th century, mental diseases and abnormal behavior was considered to be a great danger to culture and society. "Degeneration" was the buzzword of the time, used and misused by artists and scientists alike. At the same time, some scientists saw abnormity as the key to unlock the mysteries of the ordinary mind. Naturalistic curiosity left Pandoras box open when religion declined in Darwins wake. Two swedish scientists, the physician Bror Gadelius (1862-1938) and his friend the philosopher Axel Herrlin (1870-1937), inspired by the French psychologist Theodule Ribots (1839-1916) "psychology without a soul", denied all fixed demarcation lines between abnormity and normality. All humans are natures creatures ruled by physiological laws, not ruled by God or convention. Even ordinary morality was considered to be an utterly backward explanation and guideline for complex human behavior. Different forms of therapy, not various kinds of penalties for wicked and disturbing behavior, are the now the solution for lots of people, "normal" as well as "abnormal". Psychiatry is expanding.

  5. Abnormalities of gonadal differentiation.

    PubMed

    Berkovitz, G D; Seeherunvong, T

    1998-04-01

    Gonadal differentiation involves a complex interplay of developmental pathways. The sex determining region Y (SRY) gene plays a key role in testis determination, but its interaction with other genes is less well understood. Abnormalities of gonadal differentiation result in a range of clinical problems. 46,XY complete gonadal dysgenesis is defined by an absence of testis determination. Subjects have female external genitalia and come to clinical attention because of delayed puberty. Individuals with 46,XY partial gonadal dysgenesis usually present in the newborn period for the valuation of ambiguous genitalia. Gonadal histology always shows an abnormality of seminiferous tubule formation. A diagnosis of 46,XY true hermaphroditism is made if the gonads contain well-formed testicular and ovarian elements. Despite the pivotal role of the SRY gene in testis development, mutations of SRY are unusual in subjects with a 46,XY karyotype and abnormal gonadal development. 46,XX maleness is defined by testis determination in an individual with a 46,XX karyotype. Most affected individuals have a phenotype similar to that of Klinefelter syndrome. In contrast, subjects with 46,XX true hermaphroditism usually present with ambiguous genitalia. The majority of subjects with 46,XX maleness have Y sequences including SRY in genomic DNA. However, only rare subjects with 46,XX true hermaphroditism have translocated sequences encoding SRY. Mosaicism and chimaerism involving the Y chromosome can also be associated with abnormal gonadal development. However, the vast majority of subjects with 45,X/46,XY mosaicism have normal testes and normal male external genitalia.

  6. Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study

    PubMed Central

    Rathod, Krishnaraj S; Jones, Daniel A; Van-Eijl, T J A; Tsang, Hilda; Warren, Helen; Hamshere, Stephen M; Kapil, Vikas; Jain, Ajay K; Deaner, Andrew; Poulter, Neil; Caulfield, Mark J; Mathur, Anthony; Ahluwalia, Amrita

    2016-01-01

    Introduction The mainstay treatment for reducing the symptoms of angina and long-term risk of heart attacks in patients with heart disease is stent implantation in the diseased coronary artery. While this procedure has revolutionised treatment, the incidence of secondary events remains a concern. These repeat events are thought to be due, in part, to continued enhanced platelet reactivity, endothelial dysfunction and ultimately restenosis of the stented artery. In this study, we will investigate whether a once a day inorganic nitrate administration might favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis. Methods and design NITRATE-OCT is a double-blind, randomised, single-centre, placebo-controlled phase II trial that will enrol 246 patients with stable angina due to have elective percutaneous coronary intervention procedure with stent implantation. Patients will be randomised to receive 6 months of a once a day dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo) starting up to 1 week before their procedure. The primary outcome is reduction of in-stent late loss assessed by quantitative coronary angiography and optical coherence tomography at 6 months. The study is powered to detect a 0.22±0.55 mm reduction in late loss in the treatment group compared with the placebo group. Secondary end points include change from baseline assessment of endothelial function measured using flow-mediated dilation at 6 months, target vessel revascularisation (TVR), restenosis rate (diameter>50%) and in-segment late loss at 6 months, markers of inflammation and platelet reactivity and major adverse cardiac events (ie, myocardial infarction, death, cerebrovascular accident, TVR) at 12 and 24 months. Ethics and dissemination The study was approved by the Local Ethics Committee (15/LO/0555). Trial results will be published according to the CONSORT statement and will be presented at

  7. Regulatory Circuits Controlling Vascular Cell Calcification

    PubMed Central

    Sallam, Tamer; Cheng, Henry; Demer, Linda L.; Tintut, Yin

    2013-01-01

    Vascular calcification is a common feature of chronic kidney disease, cardiovascular disease, and aging. Such abnormal calcium deposition occurs in medial and/or intimal layers of blood vessels as well as in cardiac valves. Once considered a passive and inconsequential finding, the presence of calcium deposits in the vasculature is widely accepted as a predictor of increased morbidity and mortality. Recognition of the importance of vascular calcification in health is driving research into mechanisms that govern its development, progression, and regression. Diverse, but highly interconnected factors, have been implicated, including disturbances in lipid metabolism, oxidative stress, inflammatory cytokines, and mineral and hormonal balances, which can lead to formation of osteoblast-like cells in the artery wall. A tight balance of procalcific and anticalcific regulators dictates the extent of disease. In this review, we focus on the main regulatory circuits modulating vascular cell calcification. PMID:23269436

  8. Effects of vascularization on cancer nanochemotherapy outcomes

    NASA Astrophysics Data System (ADS)

    Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

    2016-08-01

    Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

  9. Vascular restoration therapy and bioresorbable vascular scaffold

    PubMed Central

    Wang, Yunbing; Zhang, Xingdong

    2014-01-01

    This article describes the evolution of minimally invasive intervention technologies for vascular restoration therapy from early-stage balloon angioplasty in 1970s, metallic bare metal stent and metallic drug-eluting stent technologies in 1990s and 2000s, to bioresorbable vascular scaffold (BVS) technology in large-scale development in recent years. The history, the current stage, the challenges and the future of BVS development are discussed in detail as the best available approach for vascular restoration therapy. The criteria of materials selection, design and processing principles of BVS, and the corresponding clinical trial results are also summarized in this article. PMID:26816624

  10. Multifocal vascular lesions.

    PubMed

    Levin, Laura E; Lauren, Christine T

    2016-09-01

    Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations.

  11. Initiation of vascular development.

    PubMed

    Ohashi-Ito, Kyoko; Fukuda, Hiroo

    2014-06-01

    The initiation of vascular development occurs during embryogenesis and the development of lateral organs, such as lateral roots and leaves. Understanding the mechanism underlying the initiation of vascular development has been an important goal of plant biologists. Auxin flow is a crucial factor involved in the initiation of vascular development. In addition, recent studies have identified key factors that regulate the establishment of vascular initial cells in embryos and roots. In this review, we summarize the recent findings in this field and discuss the initiation of vascular development.

  12. Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia.

    PubMed

    Shah, Dania A; Khalil, Raouf A

    2015-06-15

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca(2+), protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

  13. Bioactive Factors in Uteroplacental and Systemic Circulation Link Placental Ischemia to Generalized Vascular Dysfunction in Hypertensive Pregnancy and Preeclampsia

    PubMed Central

    Shah, Dania A.; Khalil, Raouf A.

    2015-01-01

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca2+, protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia. PMID:25916268

  14. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome.

    PubMed

    Ullrich, N J; Silvera, V M; Campbell, S E; Gordon, L B

    2012-09-01

    HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the scope of structural bone and soft-tissue craniofacial abnormalities in HGPS through CT or MR imaging. Using The Progeria Research Foundation Medical and Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age, were comprehensively reviewed. Eight newly identified abnormalities involving the calvaria, skull base, and soft tissues of the face and orbits were present with prevalences between 43% and 100%. These included J-shaped sellas, a mottled appearance and increased vascular markings of the calvaria, abnormally configured mandibular condyles, hypoplastic articular eminences, small zygomatic arches, prominent parotid glands, and optic nerve kinking. This expanded craniofacial characterization helps link disease features and improves our ability to evaluate how underlying genetic and cellular abnormalities culminate in a disease phenotype.

  15. Heritable bovine fetal abnormalities.

    PubMed

    Whitlock, B K; Kaiser, L; Maxwell, H S

    2008-08-01

    The etiologies for congenital bovine fetal anomalies can be divided into heritable, toxic, nutritional, and infectious categories. Although uncommon in most herds, inherited congenital anomalies are probably present in all breeds of cattle and propagated as a result of specific trait selection that inadvertently results in propagation of the defect. In some herds, the occurrence of inherited anomalies has become frequent, and economically important. Anomalous traits can affect animals in a range of ways, some being lethal or requiring euthanasia on humane grounds, others altering structure, function, or performance of affected animals. Veterinary practitioners should be aware of the potential for inherited defects, and be prepared to investigate and report animals exhibiting abnormal characteristics. This review will discuss the morphologic characteristics, mode of inheritance, breeding lines affected, and the availability of genetic testing for selected heritable bovine fetal abnormalities.

  16. Liver abnormalities in pregnancy.

    PubMed

    Than, Nwe Ni; Neuberger, James

    2013-08-01

    Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication.

  17. Chemerin Regulates Crosstalk Between Adipocytes and Vascular Cells Through Nox.

    PubMed

    Neves, Karla Bianca; Nguyen Dinh Cat, Aurelie; Lopes, Rheure Alves Moreira; Rios, Francisco Jose; Anagnostopoulou, Aikaterini; Lobato, Nubia Souza; de Oliveira, Ana Maria; Tostes, Rita C; Montezano, Augusto C; Touyz, Rhian M

    2015-09-01

    Adipocytes produce adipokines, including chemerin, a chemoattractant that mediates effects through its ChemR23 receptor. Chemerin has been linked to endothelial dysfunction and vascular injury in pathological conditions, such as obesity, diabetes mellitus, and hypertension. Molecular mechanisms underlying this are elusive. Here we assessed whether chemerin through redox-sensitive signaling influences molecular processes associated with vascular growth, apoptosis, and inflammation. Human microvascular endothelial cells and vascular smooth muscle cells were stimulated with chemerin (50 ng/mL). Chemerin increased generation of reactive oxygen species and phosphorylation of mitogen-activated protein kinases, effects that were inhibited by ML171, GKT137831 (Nox inhibitors), and N-acetylcysteine (reactive oxygen species scavenger). Chemerin increased mRNA expression of proinflammatory mediators in vascular cells and increased monocyte-to-endothelial cell attachment. In human vascular smooth muscle cells, chemerin induced phosphorylation of mitogen-activated protein kinases and stimulated proliferation (increased proliferating cell nuclear antigen expression [proliferation marker] and BrdU incorporation [proliferation assay]). Chemerin decreased phosphatidylinositol 3-kinase/protein kinase B activation and increased TUNEL-positive human vascular smooth muscle cells. In human microvascular endothelial cells, chemerin reduced endothelial nitric oxide synthase activity and nitric oxide production. Adipocyte-conditioned medium from obese/diabetic mice (db/db), which have elevated chemerin levels, increased reactive oxygen species generation in vascular smooth muscle cells, whereas adipocyte-conditioned medium from control mice had no effect. Chemerin actions were blocked by CCX 832, a ChemR23 inhibitor. Our data demonstrate that chemerin, through Nox activation and redox-sensitive mitogen-activated protein kinases signaling, exerts proapoptotic, proinflammatory, and

  18. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed.

  19. Anatomical Abnormalities in Autism?

    PubMed

    Haar, Shlomi; Berman, Sigal; Behrmann, Marlene; Dinstein, Ilan

    2016-04-01

    Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old.

  20. Vascular effects of maternal alcohol consumption

    PubMed Central

    Magness, Ronald R.

    2012-01-01

    Maternal alcohol consumption during pregnancy is a significant field of scientific exploration primarily because of its negative effects on the developing fetus, which is specifically defined as fetal alcohol spectrum disorders. Though the effects on the mother are less explored compared with those on the fetus, alcohol produces multiple effects on the maternal vascular system. Alcohol has major effects on systemic hemodynamic variables, endocrine axes, and paracrine factors regulating vascular resistance, as well as vascular reactivity. Alcohol is also reported to have significant effects on the reproductive vasculature including alterations in blood flow, vessel remodeling, and angiogenesis. Data presented in this review will illustrate the importance of the maternal vasculature in the pathogenesis of fetal alcohol spectrum disorders and that more studies are warranted in this field. PMID:22730388

  1. Reactive sintering and reactive hot

    NASA Astrophysics Data System (ADS)

    Murray, J. C.; German, R. M.

    1992-09-01

    NbAl3 has been synthesized from elemental powders by reactive sintering (RS) and reactive hot isostatic pressing (RHIP). Both processes involve a self-propagating exothermic reaction between the constituent powders to form an intermetallic compound. The RHIP approach uses simultaneous external pressurization to make a higher density product. This study focused on developing a method to use reactive synthesis to form high-density NbAl3 compacts. High RS and RHIP densities were possible with the appropriate raw materials and processing parameters. These include powder purity, particle sizes, degassing, heating rate, furnace temperature, and compaction pressures. Near full density was attained with RHIP, and up to 95 pct density was attained with RS.

  2. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  3. [Molecular abnormalities in lymphomas].

    PubMed

    Delsol, G

    2010-11-01

    Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities

  4. Structural Abnormalities of the Inner Macula in Incontinentia Pigmenti

    PubMed Central

    Basilius, Jacob; Young, Marielle P.; Michaelis, Timothy C.; Hobbs, Ronald; Jenkins, Glen; Hartnett, M. Elizabeth

    2016-01-01

    Importance This report presents evidence from spectral domain optical coherence tomography (sdOCT) and fluorescein angiography (FA) of inner foveal structural abnormalities associated with vision loss in Incontinentia pigmenti (IP). Observations Two children had reduced visual behavior in association with abnormalities of the inner foveal layers on sdOCT. FA showed filling defects in retinal and choroidal circulations and irregularities of the foveal avascular zones (FAZ). The foveal/parafoveal ratios were greater than 0.57 in 6 eyes of 3 patients who had extraretinal NV and/or peripheral avascular retina on FA and were treated with laser. Of these, 3 eyes of 2 patients had irregularities in FAZ and poor vision. Conclusions and Relevance Besides traction retinal detachment, visual loss in IP can occur with abnormalities of the inner fovea structure seen on sdOCT, consistent with prior descriptions of foveal hypoplasia. The evolution of abnormalities in the neural and vascular retina suggests a vascular cause of the foveal structural changes. More study is needed to determine any potential benefit of the foveal/parafoveal ratio in children with IP. Even with marked foveal structural abnormalities, vision can be preserved in some patients with IP with vigilant surveillance in the early years of life. PMID:26043102

  5. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  6. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  7. Haemostasis in ischaemic stroke and vascular dementia.

    PubMed

    Stott, D J; Spilg, E; Campbell, A M; Rumley, A; Mansoor, M A; Lowe, G D

    2001-12-01

    Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.

  8. Vascular Remodeling in Pulmonary Hypertension

    PubMed Central

    Shimoda, Larissa A; Laurie, Steven S.

    2013-01-01

    Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

  9. Exercises to Improve Gait Abnormalities

    MedlinePlus

    ... Home About iChip Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  10. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  11. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  12. Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

    PubMed Central

    Guo, Caixia; Yang, Man; Jing, Li; Wang, Ji; Yu, Yang; Li, Yang; Duan, Junchao; Zhou, Xianqing; Li, Yanbo; Sun, Zhiwei

    2016-01-01

    Environmental exposure to silica nanoparticles (SiNPs) is inevitable due to their widespread application in industrial, commercial, and biomedical fields. In recent years, most investigators focus on the evaluation of cardiovascular effects of SiNPs in vivo and in vitro. Endothelial injury and dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases. This study aimed to explore interaction of SiNPs with endothelial cells, and extensively investigate the exact effects of reactive oxygen species (ROS) on the signaling molecules and cytotoxicity involved in SiNPs-induced endothelial injury. Significant induction of cytotoxicity as well as oxidative stress, apoptosis, and autophagy was observed in human umbilical vein endothelial cells following the SiNPs exposure (P<0.05). The oxidative stress was induced by ROS generation, leading to redox imbalance and lipid peroxidation. SiNPs induced mitochondrial dysfunction, characterized by membrane potential collapse, and elevated Bax and declined bcl-2 expression, ultimately leading to apoptosis, and also increased number of autophagosomes and autophagy marker proteins, such as LC3 and p62. Phosphorylated ERK, PI3K, Akt, and mTOR were significantly decreased, but phosphorylated JNK and p38 MAPK were increased in SiNPs-exposed endothelial cells. In contrast, all of these stimulation phenomena were effectively inhibited by N-acetylcysteine. The N-acetylcysteine supplement attenuated SiNPs-induced endothelial toxicity through inhibition of apoptosis and autophagy via MAPK/Bcl-2 and PI3K/Akt/mTOR signaling, as well as suppression of intracellular ROS property via activating antioxidant enzyme and Nrf2 signaling. In summary, the results demonstrated that SiNPs triggered autophagy and apoptosis via ROS-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling in endothelial cells, and subsequently disturbed the endothelial homeostasis and impaired endothelium. Our findings may provide

  13. [Microscopic anatomy of abnormal structure in root tuber of Pueraria lobata].

    PubMed

    Duan, Hai-yan; Cheng, Ming-en; Peng, Hua-sheng; Zhang, He-ting; Zhao, Yu-jiao

    2015-11-01

    Puerariae Lobatae Radix, also known as Gegen, is a root derived from Pueraria lobata. Based on field investigation and the developmental anatomy of root tuber, we have elucidated the relationship between the growth of root tuber and the anomalous structure. The results of analysis showed that the root system of P. lobata was developed from seed and adventitious root and there existed root tuber, adventitious root and conductive root according to morphology and function. The root tuber was developed from adventitious root, its secondary structure conformed to the secondary structure of dicotyledon's root. With the development of root, the secondary phloem of root tuber appeared abnormal vascular tissue, which was distributed like ring in the outside of secondary vascular tissue. The root tuber might have 4-6 concentric circular permutation abnormal vascular tissuelobate, and was formed by the internal development of abnormal vascular tissue. The xylem and phloem of abnormal vascular tissue were the main body of the root tuber. The results reveal the abnormal anatomical structure development of P. lobata, also provides the theoretical basis for reasonable harvest medicinal parts and promoting sustainable utilization of resources of P. lobata.

  14. Vascular and metabolic reserve in Alzheimer's disease.

    PubMed

    Nagata, K; Kondoh, Y; Atchison, R; Sato, M; Satoh, Y; Watahiki, Y; Hirata, Y; Yokoyama, E

    2000-01-01

    Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

  15. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Blood pressure (BP) is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM) and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN). In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i), which forms a complex with calmodulin, activates myosin light chain (MLC) kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC). PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK), a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs) in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in concert with

  16. Epilepsy and chromosomal abnormalities

    PubMed Central

    2010-01-01

    Background Many chromosomal abnormalities are associated with Central Nervous System (CNS) malformations and other neurological alterations, among which seizures and epilepsy. Some of these show a peculiar epileptic and EEG pattern. We describe some epileptic syndromes frequently reported in chromosomal disorders. Methods Detailed clinical assessment, electrophysiological studies, survey of the literature. Results In some of these congenital syndromes the clinical presentation and EEG anomalies seems to be quite typical, in others the manifestations appear aspecific and no strictly linked with the chromosomal imbalance. The onset of seizures is often during the neonatal period of the infancy. Conclusions A better characterization of the electro clinical patterns associated with specific chromosomal aberrations could give us a valuable key in the identification of epilepsy susceptibility of some chromosomal loci, using the new advances in molecular cytogenetics techniques - such as fluorescent in situ hybridization (FISH), subtelomeric analysis and CGH (comparative genomic hybridization) microarray. However further studies are needed to understand the mechanism of epilepsy associated with chromosomal abnormalities. PMID:20438626

  17. Increased vascular density and vitreo-retinal membranes accompany vascularization of the pigment epithelium in the dystrophic rat retina.

    PubMed

    Caldwell, R B; Roque, R S; Solomon, S W

    1989-09-01

    Observations of vascularization of the retinal pigment epithelium (RPE) and formation of vitreo-retinal membranes (VRMs) in Royal College of Surgeons (RCS) rats with inherited retinal dystrophy suggest that vascular proliferation occurs in this model. To test this hypothesis, we studied the progression of vascular changes in RCS and age-matched control rats using quantitative light microscope morphometry and electron microscopy. At 2 weeks, prior to photoreceptor degeneration, the dystrophic retina is comparable with the control. By 2 months, extensive degeneration of photoreceptor cells results in significant thinning of the dystrophic retina as compared with the control. Signs of vascular degeneration are evident at the electron microscope level--"ghost" vessels consisting of acellular basal lamina surrounded by amorphous electron-dense material; degenerating endothelial cells and pericytes; and abnormal deposits of extracellular matrix (ECM) material around blood vessels. Vascular degeneration is accompanied by glial changes in the form of necrotic perivascular glial processes and abnormal ECM deposits among the altered Muller cell processes. At 2-4 months in the dystrophic retina, numbers of vessel profiles in dystrophic retinas are decreased as compared with controls. However, vascular degeneration is overshadowed by the formation of numerous capillary tufts within the RPE layer, which together with retinal thinning results in increased vessel density. Between 4-12 months, the retinal thickness diminishes further, vascularization of the RPE increases, vitreo-retinal membranes are formed, and vascular density increases. In summary, following an initial period of vascular degeneration, vascularization of the RPE is accompanied by an increase in retinal vessel density and by the formation of vitreo-retinal membranes.

  18. Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization

    PubMed Central

    Seshan, Surya V.; Kappel, Barry J.; Chattopadhyay, Debjit; May, Chad; McDevitt, Michael R.; Nolan, Daniel; Mittal, Vivek; Benezra, Robert; Scheinberg, David A.

    2007-01-01

    Background Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. Methodology and Principal Findings Actinium-225 (225Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, 225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in 225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following 225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following 225Ac-E4G10 therapy. Conclusions The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy. PMID:17342201

  19. Adult presentation with vascular ring due to double aortic arch.

    PubMed

    Kafka, Henryk; Uebing, Anselm; Mohiaddin, Raad

    2006-11-01

    This is a case report on the use of cardiovascular magnetic resonance imaging to diagnose vascular ring due to double aortic arch in an adult presenting with an abnormal chest X-ray. The experience in this case and the literature review identify the benefits of using cardiovascular magnetic resonance imaging to clarify complex aortic arch anatomy.

  20. [Pulmonary arterial hypertension and BMP system abnormality].

    PubMed

    Otsuka, Fumio

    2008-11-01

    Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.

  1. [Vascular factors in glaucoma].

    PubMed

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation.

  2. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD.

  3. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  4. Skeletal abnormalities in homocystinuria.

    PubMed Central

    Brenton, D. P.

    1977-01-01

    The skeletal changes of thirty-four patients with the biochemical and clinical features of cystathionine synthase deficiency are described. It is emphasized that there is clinical evidence of excessive bone growth and the formation for bone which is structurally weaker than normal. The similarities and differences between this condition and Marfan's syndrome are stressed and the possible nature of the connective tissue defect leading to the skeletal changes discussed. The most characteristic skeletal changes in homocystinuria are the skeletal disproportion (pubis-heel length greater than crown-pubis length), the abnormal vertebrae, sternal deformities, genu valgum and large metaphyses and epiphyses. Images Fig. 2 Fig. 3 Fig. 4 Fig. 8 Fig. 9 Fig. 10 PMID:917963

  5. Eye movement abnormalities.

    PubMed

    Moncayo, Jorge; Bogousslavsky, Julien

    2012-01-01

    Generation and control of eye movements requires the participation of the cortex, basal ganglia, cerebellum and brainstem. The signals of this complex neural network finally converge on the ocular motoneurons of the brainstem. Infarct or hemorrhage at any level of the oculomotor system (though more frequent in the brain-stem) may give rise to a broad spectrum of eye movement abnormalities (EMAs). Consequently, neurologists and particularly stroke neurologists are routinely confronted with EMAs, some of which may be overlooked in the acute stroke setting and others that, when recognized, may have a high localizing value. The most complex EMAs are due to midbrain stroke. Horizontal gaze disorders, some of them manifesting unusual patterns, may occur in pontine stroke. Distinct varieties of nystagmus occur in cerebellar and medullary stroke. This review summarizes the most representative EMAs from the supratentorial level to the brainstem.

  6. What Is Reactive Arthritis?

    MedlinePlus

    ... Arthritis PDF Version Size: 69 KB November 2014 What is Reactive Arthritis? Fast Facts: An Easy-to- ... Information About Reactive Arthritis and Other Related Conditions What Causes Reactive Arthritis? Sometimes, reactive arthritis is set ...

  7. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  8. Why is placentation abnormal in preeclampsia?

    PubMed Central

    Fisher, Susan J.

    2015-01-01

    The causes of preeclampsia remain one of the great medical mysteries of our time. This syndrome is thought to occur in two stages with abnormal placentation leading to a maternal inflammatory response. Specific regions of the placenta have distinct pathological features. During normal pregnancy, cytotrophoblasts emigrate from the chorionic villi and invade the uterus, reaching the inner third of the myometrium. This unusual process is made even more exceptional by the fact that the placental cells are hemi-allogeneic, co-expressing maternal and paternal genomes. Within the uterine wall, cytotrophoblasts deeply invade the spiral arteries. Cytotrophoblasts migrate up these vessels and replace, in a retrograde fashion, the maternal endothelial lining. They also insert themselves amongst the smooth muscle cells that form the tunica media. As a result, the spiral arteries attain the physiological properties that are required to adequately perfuse the placenta. In comparison, invasion of the venous side of the uterine circulation is minimal, sufficient to enable venous return. In preeclampsia, cytotrophoblast invasion of the interstitial uterine compartment is frequently shallow, although not consistently so. In many locations, spiral artery invasion is incomplete. There are many fewer endovascular cytotrophoblasts and some vessels retain portions of their endothelial lining with relatively intact muscular coats while others are not modified. Work from our group showed that these defects mirror deficits in the differentiation program that enables cytotrophoblast invasion of the uterine wall. During normal pregnancy, invasion is accompanied by downregulation of epithelial-like molecules that are indicative of their ectodermal origin and upregulation of numerous receptors and ligands that are typically expressed by endothelial or vascular smooth muscle cells. For example, the expression of epithelial-cadherin, the cell-cell adhesion molecule that many ectodermal

  9. Inhibitory Effects of Hydrogen on Proliferation and Migration of Vascular Smooth Muscle Cells via Down-Regulation of Mitogen/Activated Protein Kinase and Ezrin-Radixin-Moesin Signaling Pathways.

    PubMed

    Zhang, Ya-Xing; Xu, Jing-Ting; You, Xin-Chao; Wang, Chen; Zhou, Ke-Wen; Li, Ping; Sun, Peng; Wang, Ling; Wang, Ting-Huai

    2016-02-29

    Molecular hydrogen (H₂) has recently attracted considerable attention for the prevention of oxidative stress-related vascular diseases. The purpose of this study is to evaluate the effects of hydrogen on proliferation and migration of vascular smooth muscle cells (VSMCs) stimulated by angiotensin II (Ang II) in vitro, and on vascular hypertrophy induced by abdominal aortic coarctation (AAC) in vivo. Hydrogen-rich medium (0.6~0.9 ppm) was added 30 min before 10⁻⁷ M Ang II administration, then the proliferation and migration index were determined 24 h after Ang II stimulation. Hydrogen gas (99.999%) was given by intraperitoneal injection at the dose of 1 ml/100 g/day consecutively for one week before AAC and lasted for 6 weeks in vivo. Hydrogen inhibited proliferation and migration of VSMCs with Ang II stimulation in vitro, and improved the vascular hypertrophy induced by AAC in vivo. Treatment with hydrogen reduced Ang II- or AAC-induced oxidative stress, which was reflected by diminishing the induction of reactive oxygen species (ROS) in Ang II-stimulated VSMCs, inhibiting the levels of 3-nitrotyrosine (3-NT) in vascular and serum malondialdehyde (MDA). Hydrogen treatment also blocked Ang II-induced phosphorylation of the extracellular signal-regulated kinase1/2 (ERK1/2), p38 MAPK, c-Jun NH₂-terminal kinase (JNK) and the ezrin/radixin/moesin (ERM) in vitro. Taken together, our studies indicate that hydrogen prevents AAC-induced vascular hypertrophy in vivo, and inhibits Ang II-induced proliferation and migration of VSMCs in vitro possibly by targeting ROS-dependent ERK1/2, p38 MAPK, JNK and ERM signaling. It provides the molecular basis of hydrogen on inhibiting the abnormal proliferation and migration of VSMCs and improving vascular remodeling diseases.

  10. Relationship between serum sodium level and coronary artery abnormality in Kawasaki disease

    PubMed Central

    Park, Sora; Kim, Ji Hong

    2017-01-01

    Purpose Kawasaki disease (KD) is an immune-related multisystemic vasculitis that occurs in children, especially ensuing from a coronary artery abnormality. Sodium level is known to be related to vascular injury, which could affect the progress of KD. The purpose of this study was to determine the serum sodium levels that could predict the occurrence of cardiac and coronary artery events in KD. Methods We conducted a retrospective review of medical records for 104 patients with KD from January 2015 to December 2015. Patients with serum Na levels of <135 mEq/L at the time of initial diagnosis were assigned to the hyponatremia group. Laboratory findings and echocardiographic data were analyzed for various aspects. Results Among the 104 patients with KD, 91 were included in the study, of whom 48 (52.7%) had hyponatremia. The degree of fever, white blood cell count, percentage of neutrophils, percentage of lymphocytes, total bilirubin level, brain natriuretic peptide level, erythrocyte sedimentation rate, and C-reactive protein level were higher in the patients with hyponatremia. They also demonstrated a trend of larger coronary artery diameters based on Z scores. Conclusion The severity of vascular inflammation in acute KD with hyponatremia might worsen the prognosis of coronary vasculature. Although no statistically significant correlation was found between the initial serum sodium levels and coronary arteriopathy in the patients with KD in this study, a long-term follow-up study with a larger number of enrolled patients should be designed in the future to elucidate the relationship between serum sodium level and coronary arteriopathy in patients with KD. PMID:28289432

  11. Vascular Access in Children

    SciTech Connect

    Krishnamurthy, Ganesh Keller, Marc S.

    2011-02-15

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the 'expert procedural pyramid' is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

  12. Retinal vascular tree reconstruction with anatomical realism.

    PubMed

    Lin, Kai-Shun; Tsai, Chia-Ling; Tsai, Chih-Hsiangng; Sofka, Michal; Chen, Shih-Jen; Lin, Wei-Yang

    2012-12-01

    Motivated by the goals of automatically extracting vessel segments and constructing retinal vascular trees with anatomical realism, this paper presents and analyses an algorithm that combines vessel segmentation and grouping of the extracted vessel segments. The proposed method aims to restore the topology of the vascular trees with anatomical realism for clinical studies and diagnosis of retinal vascular diseases, which manifest abnormalities in either venous and/or arterial vascular systems. Vessel segments are grouped using extended Kalman filter which takes into account continuities in curvature, width, and intensity changes at the bifurcation or crossover point. At a junction, the proposed method applies the minimum-cost matching algorithm to resolve the conflict in grouping due to error in tracing. The system was trained with 20 images from the DRIVE dataset, and tested using the remaining 20 images. The dataset contained a mixture of normal and pathological images. In addition, six pathological fluorescein angiogram sequences were also included in this study. The results were compared against the groundtruth images provided by a physician, achieving average success rates of 88.79% and 90.09%, respectively.

  13. Vascular anomalies in children.

    PubMed

    Weibel, L

    2011-11-01

    Vascular anomalies are divided in two major categories: tumours (such as infantile hemangiomas) and malformations. Hemangiomas are common benign neoplasms that undergo a proliferative phase followed by stabilization and eventual spontaneous involution, whereas vascular malformations are rare structural anomalies representing morphogenetic errors of developing blood vessels and lymphatics. It is important to properly diagnose vascular anomalies early in childhood because of their distinct differences in morbidity, prognosis and need for a multidisciplinary management. We discuss a number of characteristic clinical features as clues for early diagnosis and identification of associated syndromes.

  14. Calcium intake, vascular calcification, and vascular disease.

    PubMed

    Spence, Lisa A; Weaver, Connie M

    2013-01-01

    Recent research has reported a possible link between calcium supplementation and increased risk of cardiovascular disease and its endpoints in healthy, older adults. To evaluate the current evidence regarding the impact of calcium supplementation on cardiovascular disease risk and to address research gaps, the present review was conducted. Systematic reviews and meta-analyses were included, when available, along with original articles. The articles included in the review were obtained from PubMed using the following search terms: calcium intake, calcium supplementation, cardiovascular disease, myocardial infarction, mortality, and vascular calcification. The majority of the studies reviewed demonstrated no statistically significant adverse or beneficial effect of calcium supplementation on cardiovascular disease or its endpoints. While some studies indicate a possible increased risk, there is a lack of consensus on these findings and a need exists to further elucidate a mechanism. More experimental data are necessary to understand the impact of calcium intake, both levels and sources, on vascular calcification and vascular disease. The use of (41)C kinetic modeling in the Ossabaw swine provides an approach for assessing soft tissue calcification in an atherosclerotic and normal state to address research gaps.

  15. Collagen vascular disease

    MedlinePlus

    ... developed these disorders were previously said to have "connective tissue" or "collagen vascular" disease. We now have names ... be used. These include as undifferentiated systemic rheumatic (connective tissue) diseases or overlap syndromes. Images Dermatomyositis, heliotrope eyelids ...

  16. [Complex vascular access].

    PubMed

    Mangiarotti, G; Cesano, G; Thea, A; Hamido, D; Pacitti, A; Segoloni, G P

    1998-03-01

    Availability of a proper vascular access is a basic condition for a proper extracorporeal replacement in end-stage chronic renal failure. However, biological factors, management and other problems, may variously condition their middle-long term survival. Therefore, personal experience of over 25 years has been critically reviewed in order to obtain useful information. In particular "hard" situations necessitating complex procedures have been examined but, if possible, preserving the peripherical vascular features.

  17. Distinct vascular conduction with cortical spreading depression.

    PubMed

    Brennan, Kevin C; Beltrán-Parrazal, Luis; López-Valdés, Hector E; Theriot, Jeremy; Toga, Arthur W; Charles, Andrew C

    2007-06-01

    Cortical spreading depression (CSD) is associated with significant vasodilatation and vasoconstriction, but the relationship between the cortical parenchymal and vascular phenomena remains poorly understood. We used optical intrinsic signal (OIS) imaging and electrophysiology to simultaneously examine the vascular and parenchymal changes that occur with CSD in anesthetized mice and rats. CSD was associated with a propagated multiphasic change in optical reflectance, with correlated negative DC shift in field potential. Dilatation of cortical surface arterioles propagated with a significantly greater intrinsic velocity than the parenchymal CSD wavefront measured by OIS and electrophysiology. Dilatation traveled in a circuitous pattern along individual arterioles, indicating specific vascular conduction as opposed to concentric propagation of a parenchymal signal. Arteriolar dilatation propagated into areas beyond the spread of parenchymal OIS and electrophysiological changes of CSD. Conversely, vasomotor activity could be experimentally dissociated from the parenchymal CSD wave. Frequent repetitive CSD evoked by continuous stimulation was associated with a reduced or absent arteriolar response despite preserved parenchymal OIS and electrophysiological changes. Similarly, dimethylsulfoxide at high concentrations (10%) inhibited arteriolar reactivity despite preserved parenchymal OIS and electrophysiological changes. These results suggest a mechanism, intrinsic to the vasculature, for propagation of vasodilatation associated with CSD. Distinct vascular conduction could be important for the pathogenesis of conditions that involve CSD, including migraine, stroke, and traumatic brain injury.

  18. Vascular compression syndromes.

    PubMed

    Czihal, Michael; Banafsche, Ramin; Hoffmann, Ulrich; Koeppel, Thomas

    2015-11-01

    Dealing with vascular compression syndromes is one of the most challenging tasks in Vascular Medicine practice. This heterogeneous group of disorders is characterised by external compression of primarily healthy arteries and/or veins as well as accompanying nerval structures, carrying the risk of subsequent structural vessel wall and nerve damage. Vascular compression syndromes may severely impair health-related quality of life in affected individuals who are typically young and otherwise healthy. The diagnostic approach has not been standardised for any of the vascular compression syndromes. Moreover, some degree of positional external compression of blood vessels such as the subclavian and popliteal vessels or the celiac trunk can be found in a significant proportion of healthy individuals. This implies important difficulties in differentiating physiological from pathological findings of clinical examination and diagnostic imaging with provocative manoeuvres. The level of evidence on which treatment decisions regarding surgical decompression with or without revascularisation can be relied on is generally poor, mostly coming from retrospective single centre studies. Proper patient selection is critical in order to avoid overtreatment in patients without a clear association between vascular compression and clinical symptoms. With a focus on the thoracic outlet-syndrome, the median arcuate ligament syndrome and the popliteal entrapment syndrome, the present article gives a selective literature review on compression syndromes from an interdisciplinary vascular point of view.

  19. Resident vascular progenitor cells.

    PubMed

    Torsney, Evelyn; Xu, Qingbo

    2011-02-01

    Homeostasis of the vessel wall is essential for maintaining its function, including blood pressure and patency of the lumen. In physiological conditions, the turnover rate of vascular cells, i.e. endothelial and smooth muscle cells, is low, but markedly increased in diseased situations, e.g. vascular injury after angioplasty. It is believed that mature vascular cells have an ability to proliferate to replace lost cells normally. On the other hand, recent evidence indicates stem/progenitor cells may participate in vascular repair and the formation of neointimal lesions in severely damaged vessels. It was found that all three layers of the vessels, the intima, media and adventitia, contain resident progenitor cells, including endothelial progenitor cells, mesenchymal stromal cells, Sca-1+ and CD34+ cells. Data also demonstrated that these resident progenitor cells could differentiate into a variety of cell types in response to different culture conditions. However, collective data were obtained mostly from in vitro culture assays and phenotypic marker studies. There are many unanswered questions concerning the mechanism of cell differentiation and the functional role of these cells in vascular repair and the pathogenesis of vascular disease. In the present review, we aim to summarize the data showing the presence of the resident progenitor cells, to highlight possible signal pathways orchestrating cell differentiation toward endothelial and smooth muscle cells, and to discuss the data limitations, challenges and controversial issues related to the role of progenitors. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  20. Nanocarriers for vascular delivery of antioxidants

    PubMed Central

    Hood, Elizabeth; Simone, Eric; Wattamwar, Paritosh; Dziubla, Thomas; Muzykantov, Vladimir

    2012-01-01

    Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) detoxify harmful reactive oxygen species, but the therapeutic utility of AOEs is hindered by inadequate delivery. AOE modification by polyethylene glycol (PEG) and encapsulation in PEG-coated liposomes increases the AOE bioavailability and enhances protective effects in animal models. Pluronic-based micelles formed with AOEs show even more potent protective effects. Furthermore, polymeric nanocarriers (PNCs) based on PEG-copolymers protect encapsulated AOEs from proteolysis and improve delivery to the target cells, such as the endothelium lining the vascular lumen. Antibodies to endothelial determinants conjugated to AOEs or AOE carriers provide targeting and intracellular delivery. Targeted liposomes, protein conjugates and magnetic nanoparticles deliver AOEs to sites of vascular oxidative stress in the cardiovascular, pulmonary and nervous systems. Further advances in nanodevices for AOE delivery will provide a basis for the translation of this approach in the clinical domain. PMID:21929460

  1. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  2. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  3. Mesenteric vascular reactivity to histamine receptor agonists and antagonists. [Dogs

    SciTech Connect

    Walus, K.M.; Fondacaro, J.D.; Jacobson, E.D.

    1981-05-01

    Response patterns of intestinal blood flow, oxygen extraction and consumption, blood flow distribution, and motility were assessed during intraarterial infusions of histamine, histamine after H1 or H2 blockade, dimaprit or dimaprit after H2 blockade. Histamine produced an initial peak response of blood flow with a slow decrease thereafter. Oxygen extraction was evenly depressed throughout the infusion, and oxygen consumption increased at the beginning. All initial responses were blocked by tripelennamine. Ranitidine, a new H2 antagonist, accelerated the decay of all responses. Dimaprit produced effects identical to those of histamine after tripelennamine. Distribution of blood flow was unchanged at the beginning of histamine infusion, but subsequently showed a shift to muscularis which was blocked by tripelennamine. Histamine usually stimulated intestinal contractions and this effect was abolished by tripelennamine. Thus, H1 stimulation, besides producing an initial vasodilation, increases oxygen uptake and redistributes flow to the muscularis.

  4. The 'reactive

    NASA Astrophysics Data System (ADS)

    Battista Piccardo, Giovanni; Guarnieri, Luisa

    2010-05-01

    The Ligurian ophiolitic peridotites [South Lanzo, Erro-Tobbio, Internal Ligurides and Corsica] are characterized by the abundance of spinel(Sp) peridotites showing depleted compositions and ranging from Cpx-poor Sp lherzolites to Sp harzburgites. They were recognized in the last decades as refractory residua by MORB-forming partial melting of the asthenosphere, and were similar to abyssal peridotites. Recent structural and compositional studies promoted a better understanding of their structural and compositional features and their genetic processes. In the field these depleted peridotites replace with primary contacts pyroxenite-bearing fertile Sp lherzolites that have been recognized as sub-continental lithospheric mantle. Field relationships evidence that decametric-hectometric bodies of pristine pyroxenite-veined lithospheric Sp lherzolites are preserved as structural remnants within the km-scale masses of depleted peridotites. The depleted peridotites show coarse-grained recrystallized textures and reaction micro-structures indicating pyroxene dissolution and olivine precipitation that have been considered as records of melt/peridotite interaction during reactive diffuse porous flow of undersaturated melts. They show, moreover, contrasting bulk and mineral chemistries that cannot be produced by simple partial melting and melt extraction. In particular, their bulk compositions are depleted in SiO2 and enriched in FeO with respect to refractory residua after any kind of partial melting, as calculated by Niu (1997), indicating that they cannot be formed by simple partial melting and melt extraction processes. Moreover, TiO2 content in Sp is usually significantly higher (up to 0.8-1.0 wt%) than typical TiO2 contents of spinels (usually < 0.1-0.2 wt %) in fertile mantle peridotites and melting refractory residua, indicating that spinel attained element equilibration with a Ti-bearing basaltic melt. The depleted peridotites usually show strongly variable Cpx modal

  5. Pressurized vascular systems for self-healing materials

    PubMed Central

    Hamilton, A. R.; Sottos, N. R.; White, S. R.

    2012-01-01

    An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen. PMID:21957119

  6. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis

    PubMed Central

    Tse, Gary; Yan, Bryan P.; Chan, Yin W. F.; Tian, Xiao Yu; Huang, Yu

    2016-01-01

    Background: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS), which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis. Method: A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function, remodeling and arrhythmogenesis. Results: Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS, which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation of mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signaling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP). Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signaling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry. Conclusion: ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension, and heart failure. PMID:27536244

  7. Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension.

    PubMed

    Harris, David M; Cohn, Heather I; Pesant, Stéphanie; Zhou, Rui-Hai; Eckhart, Andrea D

    2007-11-01

    More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.

  8. Chromosomal abnormalities and mental illness.

    PubMed

    MacIntyre, D J; Blackwood, D H R; Porteous, D J; Pickard, B S; Muir, W J

    2003-03-01

    Linkage studies of mental illness have provided suggestive evidence of susceptibility loci over many broad chromosomal regions. Pinpointing causative gene mutations by conventional linkage strategies alone is problematic. The breakpoints of chromosomal abnormalities occurring in patients with mental illness may be more direct pointers to the relevant gene locus. Publications that describe patients where chromosomal abnormalities co-exist with mental illness are reviewed along with supporting evidence that this may amount to an association. Chromosomal abnormalities are considered to be of possible significance if (a) the abnormality is rare and there are independent reports of its coexistence with psychiatric illness, or (b) there is colocalisation of the abnormality with a region of suggestive linkage findings, or (c) there is an apparent cosegregation of the abnormality with psychiatric illness within the individual's family. Breakpoints have been described within many of the loci suggested by linkage studies and these findings support the hypothesis that shared susceptibility factors for schizophrenia and bipolar disorder may exist. If these abnormalities directly disrupt coding regions, then combining molecular genetic breakpoint cloning with bioinformatic sequence analysis may be a method of rapidly identifying candidate genes. Full karyotyping of individuals with psychotic illness especially where this coexists with mild learning disability, dysmorphism or a strong family history of mental disorder is encouraged.

  9. Chromosomal abnormalities in human sperm

    SciTech Connect

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

  10. Haematological abnormalities in mitochondrial disorders

    PubMed Central

    Finsterer, Josef; Frank, Marlies

    2015-01-01

    INTRODUCTION This study aimed to assess the kind of haematological abnormalities that are present in patients with mitochondrial disorders (MIDs) and the frequency of their occurrence. METHODS The blood cell counts of a cohort of patients with syndromic and non-syndromic MIDs were retrospectively reviewed. MIDs were classified as ‘definite’, ‘probable’ or ‘possible’ according to clinical presentation, instrumental findings, immunohistological findings on muscle biopsy, biochemical abnormalities of the respiratory chain and/or the results of genetic studies. Patients who had medical conditions other than MID that account for the haematological abnormalities were excluded. RESULTS A total of 46 patients (‘definite’ = 5; ‘probable’ = 9; ‘possible’ = 32) had haematological abnormalities attributable to MIDs. The most frequent haematological abnormality in patients with MIDs was anaemia. 27 patients had anaemia as their sole haematological problem. Anaemia was associated with thrombopenia (n = 4), thrombocytosis (n = 2), leucopenia (n = 2), and eosinophilia (n = 1). Anaemia was hypochromic and normocytic in 27 patients, hypochromic and microcytic in six patients, hyperchromic and macrocytic in two patients, and normochromic and microcytic in one patient. Among the 46 patients with a mitochondrial haematological abnormality, 78.3% had anaemia, 13.0% had thrombopenia, 8.7% had leucopenia and 8.7% had eosinophilia, alone or in combination with other haematological abnormalities. CONCLUSION MID should be considered if a patient’s abnormal blood cell counts (particularly those associated with anaemia, thrombopenia, leucopenia or eosinophilia) cannot be explained by established causes. Abnormal blood cell counts may be the sole manifestation of MID or a collateral feature of a multisystem problem. PMID:26243978

  11. Vascular Anomalies: From Genetics toward Models for Therapeutic Trials

    PubMed Central

    Uebelhoer, Melanie; Boon, Laurence M.; Vikkula, Miikka

    2012-01-01

    Vascular anomalies are localized abnormalities that occur during vascular development. Several causative genes have been identified not only for inherited but also for some sporadic forms, and the molecular pathways involved are becoming understood. This gives us the opportunity to generate animals carrying the causative genetic defects, which we hope model the phenotype seen in human patients. These models would enable us not only to test known antiangiogenic drugs, but also to develop novel approaches for treatment, directly targeting the mutated protein or molecules implicated in the pathophysiological signaling pathways. PMID:22908197

  12. [Vascularization of hepatoceliular carcinoma].

    PubMed

    Tumanova, U N; Shchegolev, A I

    2015-01-01

    The paper gives the data available in the literature on vascularization of hepatocellular carcinoma (HCC). Sinusoidal capillarization and unpaired arteries are shown to play an important role in the development and progression of HCC. The density of microvessels detected by immunohistochemical techniques is a morphological indicator of the degree of angiogenic processes. Higher-grade HCC is followed by changes in its vascularization and concurrent with a progressive increase in the proportion of blood entering along the hepatic artery. The morphological indicators of microvessel density are recommended to use as addi- tional criteria for determining the prognosis of the disease, designing targeted anti-angiogenic drugs, and evaluating the efficiency of performed therapy.

  13. Congenital abnormalities and selective abortion.

    PubMed

    Seller, M J

    1976-09-01

    The technique of amniocentesis, by which an abnormal fetus can be detected in utero, has brought a technological advance in medical science but attendant medical and moral problems. Dr Seller describes those congenital disabilities which can be detected in the fetus before birth, for which the "remedy" is selective abortion. She then discusses the arguments for and against selective abortion, for the issue is not simple, even in the strictly genetic sense of attempting to ensure a population free of congenital abnormality.

  14. Flaxseed oil increases aortic reactivity to phenylephrine through reactive oxygen species and the cyclooxygenase-2 pathway in rats

    PubMed Central

    2014-01-01

    Background Flaxseed oil has the highest concentration of omega-3 α-linolenic acid, which has been associated with cardiovascular benefit. However, the mechanism underlying the vascular effects induced through flaxseed oil is not well known. Thus, in the present study, we investigated the effects of flaxseed oil on vascular function in isolated rat aortic rings. Methods Wistar rats were treated daily with flaxseed oil or a control (mineral oil) intramuscular (i.m.) for fifteen days. Isolated aortic segments were used to evaluate cyclooxygenase-2 (COX-2) protein expression, superoxide anion levels and vascular reactivity experiments. Results Flaxseed oil treatment increased the vasoconstrictor response of aortic rings to phenylephrine. Endothelium removal increased the response to phenylephrine in aortic segments isolated from both groups, but the effect was smaller in the treated group. L-NAME incubation similarly increased the phenylephrine response in segments from both groups. The TXA2 synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the reactive oxygen species (ROS) scavenger apocynin, the superoxide anion scavengers tiron and the phospholipase A2 inhibitor dexamethasone partially reversed the flaxseed oil-induced increase in reactivity to phenylephrine. Conclusions These findings suggest that flaxseed oil treatment increased vascular reactivity to phenylephrine through an increase in ROS production and COX-2-derived TXA2 production. The results obtained in the present study provide new insight into the effects of flaxseed oil treatment (i.m.) on vascular function. PMID:24993607

  15. Effects of pre- and post-natal treatment with KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, on retinal vascular development and patterning in mice.

    PubMed

    Morita, Akane; Nakahara, Tsutomu; Abe, Naomichi; Kurauchi, Yuki; Mori, Asami; Sakamoto, Kenji; Nagamitsu, Tohru; Ishii, Kunio

    2014-03-01

    The impaired function of angiogenic factors, including vascular endothelial growth factor (VEGF), during pregnancy is associated with preeclampsia and intrauterine growth restriction. To determine how the attenuation of VEGF signals during retinal vascular development affects retinal vascular growth and patterns, we examined the effects of pre- and post-natal treatment of mice with KRN633, a VEGF receptor tyrosine kinase inhibitor, on retinal vascular development and structure. Delays in retinal vascular development were observed in the pups of mother mice that were treated daily with KRN633 (5 mg/kg/day) from embryonic day 13.5 until the day of delivery. A more marked delay was seen in pups treated with the inhibitor (5 mg/kg/day) on the day of birth and on the following day. Pups treated postnatally with KRN633 showed abnormal retinal vascular patterns, such as highly dense capillary networks and decreased numbers of central arteries and veins. The high-density vascular networks in KRN633-treated pups showed a greater sensitivity to VEGF signaling inhibition than the normal vascular networks in vehicle-treated pups. Compared to vehicle-treated pups, more severe hypoxia and stronger VEGF mRNA expression were observed in avascular areas in KRN633-treated pups. These results suggest that a short-term loss of VEGF function at the earliest stages of vascular development suppresses vascular growth, leading to abnormal vascular patterning, at least in part via mechanisms involving VEGF in the mouse retina.

  16. Vascular calcifications, vertebral fractures and mortality in haemodialysis patients

    PubMed Central

    Rodríguez-García, Minerva; Gómez-Alonso, Carlos; Naves-Díaz, Manuel; Diaz-Lopez, Jose Bernardino; Diaz-Corte, Carmen; Cannata-Andía, Jorge B.

    2009-01-01

    Background. Vascular calcifications and the bone fractures caused by abnormal bone fragility, also called osteoporotic fractures, are frequent complications associated with chronic kidney diseases (CKD). The aim of this study was to investigate the association between vascular calcifications, osteoporotic bone fractures and survival in haemodialysis (HD) patients. Methods. A total of 193 HD patients were followed up to 2 years. Vascular calcifications and osteoporotic vertebral fractures (quoted just as vertebral fractures in the text) were assessed by thoracic, lumbar spine, pelvic and hand X-rays and graded according to their severity. Clinical, biochemical and therapeutic data gathered during the total time spent on HD were collected. Results. The prevalence of aortic calcifications was higher in HD patients than in a random-based general population (79% versus 37.5%, P < 0.001). Total time on any renal replacement therapy (RRT) and diabetes were positively associated with a higher prevalence of vascular calcifications. In addition to these factors, time on HD was also positively associated with the severity of vascular calcifications, and higher haemoglobin levels were associated with a lower prevalence of severe vascular calcifications in large and medium calibre arteries. The prevalence of vertebral fractures in HD patients was similar to that of the general population (26.5% versus 24.1%). Age and time on HD showed a positive and statistically significant association with the prevalence of vertebral fractures. Vascular calcifications in the medium calibre arteries were associated with a higher rate of prevalent vertebral fractures. In women, severe vascular calcifications and vertebral fractures were positively associated with mortality [RR = 3.2 (1.0–10.0) and RR = 4.8 (1.7–13.4), respectively]. Conclusions. Positive associations between vascular calcifications, vertebral fractures and mortality have been found in patients on HD. PMID:18725376

  17. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    PubMed

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  18. Heart and vascular services

    MedlinePlus

    ... MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Heart and vascular services URL of this page: //medlineplus.gov/ency/article/ ...

  19. Pathogenesis of Vascular Anomalies

    PubMed Central

    Boon, Laurence M.; Ballieux, Fanny; Vikkula, Miikka

    2010-01-01

    Vascular anomalies are localized defects of vascular development. Most of them occur sporadically, i.e. there is no familial history of lesions, yet in a few cases clear inheritance is observed. These inherited forms are often characterized by multifocal lesions that are mainly small in size and increase in number with patient’s age. On the basis of these inherited forms, molecular genetic studies have unraveled a number of inherited mutations giving direct insight into the pathophysiological cause and the molecular pathways that are implicated. Genetic defects have been identified for hereditary haemorrhagic telangiectasia (HHT), inherited cutaneomucosal venous malformation (VMCM), glomuvenous malformation (GVM), capillary malformation - arteriovenous malformation (CM-AVM), cerebral cavernous malformation (CCM) and some isolated and syndromic forms of primary lymphedema. We focus on these disorders, the implicated mutated genes and the underlying pathogenic mechanisms. We also call attention to the concept of Knudson’s double-hit mechanism to explain incomplete penetrance and the large clinical variation in expressivity of inherited vascular anomalies. This variability renders the making of correct diagnosis of the rare inherited forms difficult. Yet, the identification of the pathophysiological causes and pathways involved in them has had an unprecedented impact on our thinking of their etiopathogenesis, and has opened the doors towards a more refined classification of vascular anomalies. It has also made it possible to develop animal models that can be tested for specific molecular therapies, aimed at alleviating the dysfunctions caused by the aberrant genes and proteins. PMID:21095468

  20. Nonthrombogenic polymer vascular prosthesis.

    PubMed

    Nojiri, C; Senshu, K; Okano, T

    1995-01-01

    Although many synthetic vascular grafts have been developed and evaluated experimentally or clinically, none of them have met long-term patency when applied as a small diameter vascular substitute. We have recently developed a small caliber vascular graft (3 mm i.d.) using a nonthrombogenic polymer coating. The graft consists of three layered structures: Dacron for the outer layer, polyurethane in the middle layer, and a HEMA/styrene block copolymer (HEMA-st) coating for the inner layer. HEMA-st is an amphiphilic block copolymer composed of 2-hydroxyethyl methacrylate and styrene which has demonstrated improved blood compatibility over existing biomedical polymers in both in vitro and ex vivo experiments. Ten grafts were evaluated in a dog bilateral carotid replacement model. The grafts were electively retrieved at 7, 14, 30, 92, and 372 days after implantation. All grafts were patent without detectable thrombi along the graft length including anastomotic sites. Scanning electron micrographs of retrieved graft lumen showed fairly clean surfaces covered with a homogenous protein-like layer without microthrombi or endothelial cell lining. The thickness of the surface protein layer measured by a transmission electron microscopy was what can be described as monolayer protein adsorption regardless of implantation periods of as much as 372 days. A stable monolayer adsorbed protein layer formed on HEMA-st surfaces demonstrated nonthrombogenic activities in vivo and secure long-term patency of small caliber vascular grafts with the absence of an endothelial cell lining.

  1. Amputation in vascular disease.

    PubMed Central

    Robinson, K.

    1980-01-01

    The management of vascular amputees in the Roehampton Limb Surgery Unit since its opening in 1975 is outlined and the results in 167 cases presented. Of the 35 patients over the age of 80, 57% were walking independently at the time of their discharge from the unit. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7377693

  2. The sesame lignan sesamin attenuates vascular dysfunction in streptozotocin diabetic rats: involvement of nitric oxide and oxidative stress.

    PubMed

    Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Jalali Nadoushan, Mohammad-Reza; Vaez Mahdavi, Mohammad-Reza; Kalalian-Moghaddam, Hamid; Roghani-Dehkordi, Farshad; Dariani, Sharareh; Raoufi, Safoura

    2013-01-05

    The effect of chronic administration of sesamin was studied on aortic reactivity of streptozotocin diabetic rats. Male diabetic rats received sesamin for 7 weeks after diabetes induction. Contractile responses to KCl and phenylephrine and relaxation response to acetylcholine were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to phenylephrine was significantly lower in sesamin-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine was significantly higher in sesamin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde and decreased superoxide dismutase activity and sesamin treatment significantly improved these changes. Therefore, chronic treatment of diabetic rats with sesamin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and via attenuation of oxidative stress and tissue integrity of endothelium is necessary for its beneficial effect.

  3. Vascular wall extracellular matrix proteins and vascular diseases

    PubMed Central

    Xu, Junyan; Shi, Guo-Ping

    2014-01-01

    Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension. PMID:25045854

  4. Arterial Abnormalities Leading to Tinnitus.

    PubMed

    Miller, Timothy R; Serulle, Yafell; Gandhi, Dheeraj

    2016-05-01

    Tinnitus is a common symptom that usually originates in the middle ear. Vascular causes of pulsatile tinnitus are categorized by the location of the source of the noise within the cerebral-cervical vasculature: arterial, arteriovenous, and venous. Arterial stenosis secondary to atherosclerotic disease or dissection, arterial anatomic variants at the skull base, and vascular skull base tumors are some of the more common causes of arterial and arteriovenous pulsatile tinnitus. Noninvasive imaging is indicated to evaluate for possible causes of pulsatile tinnitus, and should be followed by catheter angiography if there is a strong clinical suspicion for a dural arteriovenous fistula.

  5. Vascular endothelial dysfunction and pharmacological treatment

    PubMed Central

    Su, Jin Bo

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  6. [Diagnosticum of abnormalities of plant meiotic division].

    PubMed

    Shamina, N V

    2006-01-01

    Abnormalities of plant meiotic division leading to abnormal meiotic products are summarized schematically in the paper. Causes of formation of monads, abnormal diads, triads, pentads, polyads, etc. have been observed in meiosis with both successive and simultaneous cytokinesis.

  7. Cerebrovascular reactivity mapping without gas challenges.

    PubMed

    Liu, Peiying; Li, Yang; Pinho, Marco; Park, Denise C; Welch, Babu G; Lu, Hanzhang

    2017-02-01

    Cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or constrict, has been shown to provide valuable information in the diagnosis and treatment evaluation of patients with various cerebrovascular conditions. CVR mapping is typically performed using hypercapnic gas inhalation as a vasoactive challenge while collecting BOLD images, but the inherent need of gas inhalation and the associated apparatus setup present a practical obstacle in applying it in routine clinical use. Therefore, we aimed to develop a new method to map CVR using resting-state BOLD data without the need of gas inhalation. This approach exploits the natural variation in respiration and measures its influence on BOLD MRI signal. In this work, we first identified a surrogate of the arterial CO2 fluctuation during spontaneous breathing from the global BOLD signal. Second, we tested the feasibility and reproducibility of the proposed approach to use the above-mentioned surrogate as a regressor to estimate voxel-wise CVR. Third, we validated the "resting-state CVR map" with a conventional CVR map obtained with hypercapnic gas inhalation in healthy volunteers. Finally, we tested the utility of this new approach in detecting abnormal CVR in a group of patients with Moyamoya disease, and again validated the results using the conventional gas inhalation method. Our results showed that global BOLD signal fluctuation in the frequency range of 0.02-0.04Hz contains the most prominent contribution from natural variation in arterial CO2. The CVR map calculated using this signal as a regressor is reproducible across runs (ICC=0.91±0.06), and manifests a strong spatial correlation with results measured with a conventional hypercapnia-based method in healthy subjects (r=0.88, p<0.001). We also found that resting-state CVR was able to identify vasodilatory deficit in patients with steno-occlusive disease, the spatial pattern of which matches that obtained using the conventional gas method (r

  8. VASCULAR ACTIONS OF ESTROGENS: FUNCTIONAL IMPLICATIONS

    PubMed Central

    Miller, Virginia M.; Duckles, Sue P.

    2009-01-01

    The impact of estrogen exposure in preventing or treating cardiovascular disease is controversial. But it is clear that estrogen has important effects on vascular physiology and pathophysiology, with potential therapeutic implications. Therefore, it is the goal of this review to summarize, using an integrated approach, current knowledge of the vascular effects of estrogen, both in humans and in experimental animals. Aspects of estrogen synthesis and receptors, as well as general mechanisms of estrogenic action are reviewed with an emphasis on issues particularly relevant to the vascular system. Recent understanding of the impact of estrogen on mitochondrial function suggests that the longer lifespan of women compared to men may depend in part on the ability of estrogen to decrease production of reactive oxygen species in mitochondria. Mechanisms by which estrogen increases endothelial vasodilator function, promotes angiogenesis and modulates autonomic function are summarized. Key aspects of the relevant pathophysiology of inflammation, atherosclerosis, stroke, migraine and thrombosis are reviewed concerning current knowledge of estrogenic effects. A number of emerging concepts are addressed throughout. These include the importance of estrogenic formulation and route of administration and the impact of genetic polymorphisms, either in estrogen receptors or in enzymes responsible for estrogen metabolism, on responsiveness to hormone treatment. The importance of local metabolism of estrogenic precursors and the impact of timing for initiation of treatment and its duration are also considered. While consensus opinions are emphasized, controversial views are presented in order to stimulate future research. PMID:18579753

  9. Vascular Dysfunction in Horses with Endocrinopathic Laminitis

    PubMed Central

    Morgan, Ruth A.; Keen, John A.; Walker, Brian R.; Hadoke, Patrick W. F.

    2016-01-01

    Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing’s disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing’s syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10−9–10-5M) and 5-hydroxytryptamine (5HT; 10−9–10-5M) and the vasodilator acetylcholine (10−9–10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof. PMID:27684374

  10. Vascular Dysfunction in Horses with Endocrinopathic Laminitis.

    PubMed

    Morgan, Ruth A; Keen, John A; Walker, Brian R; Hadoke, Patrick W F

    Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10-9-10-5M) and 5-hydroxytryptamine (5HT; 10-9-10-5M) and the vasodilator acetylcholine (10-9-10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof.

  11. Soluble Endoglin Modulates Aberrant Cerebral Vascular Remodeling

    PubMed Central

    Chen, Yongmei; Hao, Qi; Kim, Helen; Su, Hua; Letarte, Michelle; Karumanchi, S. Ananth; Lawton, Michael T.; Barbaro, Nicholas M.; Yang, Guo-Yuan; Young, William L.

    2009-01-01

    Objective Brain arteriovenous malformations (AVMs) are an important cause of neurological morbidity in young adults. The pathophysiology of these lesions is poorly understood. A soluble form of endoglin (sEng) has been shown to cause endothelial dysfunction and induce preeclampsia. We tested if sEng would be elevated in brain AVM tissues relative to epilepsy brain tissues, and also investigated whether sEng overexpression via gene transfer in the mouse brain would induce vascular dysplasia and associated changes in downstream signaling pathways. Methods Expression levels of sEng in surgical specimens were determined by Western blot assay and ELISA. Vascular dysplasia, levels of MMP and oxidative stress were determined by immunohistochemistry and gelatin zymography. Results Brain AVMs (n=33) had higher mean sEng levels (245 ± 175 vs 100 ± 60, % of control, P=0.04) compared with controls (n=8), as determined by Western blot. In contrast, membrane-bound Eng was not significantly different (108 ± 79 vs 100 ± 63, % of control, P=0.95). sEng gene transduction in the mouse brain induced abnormal vascular structures. It also increased matrix metalloproteinase (MMP) activity by 490 ± 30% (MMP-9), 220 ± 30% (MMP-2), and oxidants by 260 ± 20% (4-hydroxy-2-nonenal) at 2 weeks after injection, suggesting that MMPs and oxidative radicals may mediate sEng-induced pathological vascular remodeling. Interpretation The results suggest that elevated sEng may play a role in the generation of sporadic brain AVMs. Our findings may provide new targets for therapeutic intervention for patients with brain AVMs. PMID:19670444

  12. Contribution of granulocyte colony-stimulating factor to the acute mobilization of endothelial precursor cells by vascular disrupting agents.

    PubMed

    Shaked, Yuval; Tang, Terence; Woloszynek, Jill; Daenen, Laura G; Man, Shan; Xu, Ping; Cai, Shi-Rong; Arbeit, Jeffrey M; Voest, Emile E; Chaplin, David J; Smythe, Jon; Harris, Adrian; Nathan, Paul; Judson, Ian; Rustin, Gordon; Bertolini, Francesco; Link, Daniel C; Kerbel, Robert S

    2009-10-01

    Vascular disrupting agents (VDA) cause acute shutdown of abnormal established tumor vasculature, followed by massive intratumoral hypoxia and necrosis. However, a viable rim of tumor tissue invariably remains from which tumor regrowth rapidly resumes. We have recently shown that an acute systemic mobilization and homing of bone marrow-derived circulating endothelial precursor (CEP) cells could promote tumor regrowth following treatment with either a VDA or certain chemotherapy drugs. The molecular mediators of this systemic reactive host process are unknown. Here, we show that following treatment of mice with OXi-4503, a second-generation potent prodrug derivative of combretastatin-A4 phosphate, rapid increases in circulating plasma vascular endothelial growth factor, stromal derived factor-1 (SDF-1), and granulocyte colony-stimulating factor (G-CSF) levels are detected. With the aim of determining whether G-CSF is involved in VDA-induced CEP mobilization, mutant G-CSF-R(-/-) mice were treated with OXi-4503. We found that as opposed to wild-type controls, G-CSF-R(-/-) mice failed to mobilize CEPs or show induction of SDF-1 plasma levels. Furthermore, Lewis lung carcinomas grown in such mice treated with OXi-4503 showed greater levels of necrosis compared with tumors treated in wild-type mice. Evidence for rapid elevations in circulating plasma G-CSF, vascular endothelial growth factor, and SDF-1 were also observed in patients with VDA (combretastatin-A4 phosphate)-treated cancer. These results highlight the possible effect of drug-induced G-CSF on tumor regrowth following certain cytotoxic drug therapies, in this case using a VDA, and hence G-CSF as a possible therapeutic target.

  13. Vascular imaging in the elderly.

    PubMed

    Kalva, Sanjeeva P; Mueller, Peter R

    2008-07-01

    Though a myriad of vascular conditions affect the elderly, atherosclerosis remains the most common vascular disorder, followed by venous thromboembolism and varicose veins. In this article, the authors discuss the imaging of atherosclerosis affecting various vascular territories and pay special attention to the elderly population. The authors also discuss imaging findings of segmental arterial mediolysis, giant cell arteritis, and venous thromboembolism.

  14. The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

    PubMed Central

    Guan, Yong; Wendong, Sun; Zhao, Shengtian; Liu, Tongyan; Liu, Yuqiang; Zhang, Xiulin; Yuan, Mingzhen

    2015-01-01

    ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED. PMID:26689522

  15. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    PubMed Central

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  16. Aspirin for vascular dementia

    PubMed Central

    Rands, Gianetta; Orrell, Martin

    2014-01-01

    Background Aspirin is widely prescribed for patients with a diagnosis of vascular dementia. In a survey of UK geriatricians and psychiatrists 80% of patients with clinical diagnoses of vascular dementia were prescribed aspirin. However, a number of queries remain unanswered. Is there convincing evidence that aspirin benefits patients with vascular dementia? Does aspirin affect cognition and behaviour, or improve prognosis? Does the risk of cerebral or gastric haemorrhage outweigh any benefit? Objectives To assess the randomised trial evidence for efficacy and safety of aspirin in the treatment of vascular dementia. Search methods We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 12 March 2012 using the terms: aspirin OR “acetylsalicylic acid”. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. In addition, relevant websites were searched and some journals were handsearched. Specialists in the field were approached for unpublished material and any publications found were searched for additional references. Selection criteria Randomised controlled trials investigating the effect of aspirin for vascular dementia were eligible for inclusion. Data collection and analysis Retrieved studies were analysed independently by both review authors. Methodology and results were critically appraised and outcomes scanned included cognition, behavioural change, mortality and institutionalisation. Main results No trials were eligible for inclusion in this review. Authors’ conclusions The most recent search for references to relevant research was carried out in March 2012. No trials were found for inclusion in this systematic review. Low-dose aspirin is frequently used as ‘treatment as normal’ in control groups and as a baseline treatment in pharmacological trials. There is still no good evidence that

  17. Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

    PubMed Central

    Chen, Qishan; Jin, Min; Yang, Feng; Zhu, Jianhua; Xiao, Qingzhong; Zhang, Li

    2013-01-01

    Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) and its interaction with extracellular matrix (ECM) play a critical role in the processes. Matrix metalloproteinases (MMPs), well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential. PMID:23840100

  18. Role of methylglyoxal adducts in the development of vascular complications in diabetes mellitus.

    PubMed

    Bourajjaj, M; Stehouwer, C D A; van Hinsbergh, V W M; Schalkwijk, C G

    2003-12-01

    Various theories have been proposed to explain the hyperglycaemia-induced pathogenesis of vascular complications of diabetes, including detrimental effects of AGEs (advanced glycation end products) on vascular tissues. Increased formation of the very reactive dicarbonyl compound MGO (methylglyoxal), one of the side-products of glycolysis, and MGO-derived AGEs seem to be implicated in the development of diabetic vascular complications. Although the exact role of MGO and MGO adducts in the development of vascular complications is unknown, receptor-mediated activation of vascular cells by the MGO-arginine adduct hydroimidazolone, as well as intracellular modifications of protein by MGO, seem to be involved. The aim of this mini-review is to assess to what extent MGO is related to vascular complications in diabetes.

  19. Abnormal insulin levels and vertigo.

    PubMed

    Proctor, C A

    1981-10-01

    Fifty patients with unexplained vertigo (36) or lightheadedness (14) are evaluated, all of whom had abnormal ENGs and normal audiograms. Five hour insulin glucose tolerance tests were performance on all patients, with insulin levels being obtained fasting and at one-half, one, two, and three hours. The results of this investigation were remarkable. Borderline or abnormal insulin levels were discovered in 82% of patients; 90% were found to have either an abnormal glucose tolerance test or at least borderline insulin levels. The response to treatment in these dizzy patients was also startling, with appropriate low carbohydrate diets improving the patient's symptoms in 90% of cases. It is, therefore, apparent that the earliest identification of carbohydrate imbalance with an insulin glucose tolerance test is extremely important in the work-up of the dizzy patients.

  20. Complex patterns of abnormal heartbeats

    NASA Technical Reports Server (NTRS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

    2002-01-01

    Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

  1. Brain Vascular Imaging Techniques

    PubMed Central

    Laviña, Bàrbara

    2016-01-01

    Recent major improvements in a number of imaging techniques now allow for the study of the brain in ways that could not be considered previously. Researchers today have well-developed tools to specifically examine the dynamic nature of the blood vessels in the brain during development and adulthood; as well as to observe the vascular responses in disease situations in vivo. This review offers a concise summary and brief historical reference of different imaging techniques and how these tools can be applied to study the brain vasculature and the blood-brain barrier integrity in both healthy and disease states. Moreover, it offers an overview on available transgenic animal models to study vascular biology and a description of useful online brain atlases. PMID:28042833

  2. Pelvic Vascular Malformations

    PubMed Central

    Christenson, Brian M.; Gipson, Matthew G.; Smith, Mitchell T.

    2013-01-01

    Vascular malformations (VMs) comprise a wide spectrum of lesions that are classified by content and flow characteristics. These lesions, occurring in both focal and diffuse forms, can involve any organ and tissue plane and can cause significant morbidity in both children and adults. Since treatment strategy depends on the type of malformation, correct diagnosis and classification of a vascular lesion are crucial. Slow-flow VMs (venous and lymphatic malformations) are often treated by sclerotherapy, whereas fast-flow lesions (arteriovenous malformations) are generally managed with embolization. In addition, some cases of VMs are best treated surgically. This review will present an overview of VMs in the female pelvis as well as a discussion of endovascular therapeutic techniques. PMID:24436563

  3. Vascular trauma historical notes.

    PubMed

    Rich, Norman M

    2011-03-01

    This article provides a brief historical review of treatment of vascular trauma. Although methods for ligation came into use in the second century, this knowledge was lost during the Dark Ages and did not come back until the Renaissance. Many advances in vascular surgery occurred during the Balkan Wars, World War I, and World War II, although without antibiotics and blood banking, the philosophy of life over limb still ruled. Documenting and repairing both arteries and veins became more common during the Korean and Vietnam conflicts. Increased documentation has revealed that the current conflicts have resulted in more arterial injuries than in previous wars, likely because of improved body armor, improvised explosive device attacks, tourniquet use, and improved medical evacuation time. This brief review emphasizes the great value of mentorship and the legacy of the management of arterial and venous injuries to be passed on.

  4. [Vascular endothelial Barrier Function].

    PubMed

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  5. Plant Vascular Biology 2010

    SciTech Connect

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  6. Anaesthesia for vascular emergencies.

    PubMed

    Ellard, L; Djaiani, G

    2013-01-01

    Patients presenting with vascular emergencies including acute aortic syndrome, ruptured thoracic or abdominal aortic aneurysms, thoracic aortic trauma and acute lower limb ischaemia have a high risk of peri-operative morbidity and mortality. Although anatomical suitability is not universal, endovascular surgery may improve mortality and the results of ongoing randomised controlled trials are awaited. Permissive hypotension pre-operatively should be the standard of care with the systolic blood pressure kept to 50-100 mmHg as long as consciousness is maintained. The benefit of local anaesthesia over general anaesthesia is not definitive and this decision should be tailored for a given patient and circumstance. Cerebrospinal fluid drainage for prevention of paraplegia is often impractical in the emergency setting and is not backed by strong evidence; however, it should be considered postoperatively if symptoms develop. We discuss the pertinent anaesthetic issues when a patient presents with a vascular emergency and the impact that endovascular repair has on anaesthetic management.

  7. The Adventitia: Essential Role in Pulmonary Vascular Remodeling

    PubMed Central

    Stenmark, Kurt R.; Nozik-Grayck, Eva; Gerasimovskaya, Evgenia; Anwar, Adil; Li, Min; Riddle, Suzette; Frid, Maria

    2014-01-01

    A rapidly emerging concept is that the vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. It is the most complex compartment of the vessel wall and comprises a variety of cells including fibroblasts, immunomodulatory cells, resident progenitor cells, vasa vasorum endothelial cells, and adrenergic nerves. In response to vascular stress or injury, resident adventitial cells are often the first to be activated and reprogrammed to then influence tone and structure of the vessel wall. Experimental data indicate that the adventitial fibroblast, the most abundant cellular constituent of adventitia, is a critical regulator of vascular wall function. In response to vascular stresses such as overdistension, hypoxia, or infection, the adventitial fibroblast is activated and undergoes phenotypic changes that include proliferation, differentiation, and production of extracellular matrix proteins and adhesion molecules, release of reactive oxygen species, chemokines, cytokines, growth factors, and metalloproteinases that, collectively, affect medial smooth muscle cell tone and growth directly and that stimulate recruitment and retention of circulating inflammatory and progenitor cells to the vessel wall. Resident dendritic cells also participate in “sensing” vascular stress and actively communicate with fibroblasts and progenitor cells to simulate repair processes that involve expansion of the vasa vasorum, which acts as a conduit for further delivery of inflammatory/progenitor cells. This review presents the current evidence demonstrating that the adventitia acts as a key regulator of pulmonary vascular wall function and structure from the “outside in.” PMID:23737168

  8. Ectodermal dysplasia and abnormal thumbs.

    PubMed

    Lucky, A W; Esterly, N B; Tunnessen, W W

    1980-05-01

    Two unrelated children, a girl and a boy, with alopecia, anomalous cutaneous pigmentation, abnormal thumbs, and endocrine disorders, including short stature and delayed bone age in one patient and juvenile onset diabetes mellitus in the other, are described. In one instance, the mother and the maternal grandmother had similar abnormalities, although of a less severe nature. Both children had normal nails and no unusual susceptibility to infections. We believe these two patients represent a previously undescribed syndrome of ectodermal dysplasia that may be inherited as an autosomal-dominant trait.

  9. Vascular Cambium Development

    PubMed Central

    Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

    2015-01-01

    Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

  10. Vestibular abnormalities in congenital disorders.

    PubMed

    Sando, I; Orita, Y; Miura, M; Balaban, C D

    2001-10-01

    This paper reviews the histopathologic features of vestibular abnormalities in congenital disorders affecting the inner ear, based upon a comprehensive literature survey and a review of cases in our temporal bone collection. The review proceeds in three systematic steps. First, we surveyed associated diseases with the major phenotypic features of congenital abnormalities of the inner ear (including the internal auditory canal and otic capsule). Second, the vestibular anomalies are examined specifically. Finally, the anomalies are discussed from a developmental perspective. Among vestibular anomalies, a hypoplastic endolymphatic duct and sac are observed most frequently. Anomalies of the semicircular canals are also often observed. From embryological and clinical viewpoints, many of these resemble the structural features from fetal stages and appear to be associated with vestibular dysfunction. It is expected that progress in genetic analysis and accumulation of temporal bone specimens with vestibular abnormalities in congenital diseases will provide crucial information not only for pathology of those diseases, but also for genetic factors that are responsible for the specific vestibular abnormalities.

  11. Retinal Vascular Changes are a Marker for Cerebral Vascular Diseases.

    PubMed

    Moss, Heather E

    2015-07-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk.

  12. System for reactivating catalysts

    SciTech Connect

    Ginosar, Daniel M.; Thompson, David N.; Anderson, Raymond P.

    2010-03-02

    A method of reactivating a catalyst, such as a solid catalyst or a liquid catalyst is provided. The method comprises providing a catalyst that is at least partially deactivated by fouling agents. The catalyst is contacted with a fluid reactivating agent that is at or above a critical point of the fluid reactivating agent and is of sufficient density to dissolve impurities. The fluid reactivating agent reacts with at least one fouling agent, releasing the at least one fouling agent from the catalyst. The at least one fouling agent becomes dissolved in the fluid reactivating agent and is subsequently separated or removed from the fluid reactivating agent so that the fluid reactivating agent may be reused. A system for reactivating a catalyst is also disclosed.

  13. Vascular Manifestations of von Recklinghausen's Disease

    PubMed Central

    Fye, Kenneth H.; Jacobs, Richard P.; Roe, Robert L.

    1975-01-01

    A casual relationship between von Recklinghausen's disease, or neurofibromatosis, and arteriolar abnormalities has been reported in the European literature. A patient was seen who had biopsy-proved neurofibromatosis and renovascular hypertension and retroperitoneal bleeding. An arteriographic study showed multiple small aneurysms throughout the coeliac axis, the superior mesenteric artery and in several small intrarenal vessels. Renal vein renin levels were elevated particularly in the right renal vein, supporting the diagnosis of renovascular hypertension. Both the aneurysms seen in angiographic studies and the retroperitoneal hemorrhage are probably vascular manifestations of von Recklinghausen's disease. Support for this conclusion is enhanced by the absence of clinical, laboratory or histologic data supporting the only tenable differential diagnosis, periarteritis nodosa. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:803743

  14. Digital image processing of vascular angiograms

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Beckenbach, E. S.; Blankenhorn, D. H.; Crawford, D. W.; Brooks, S. H.

    1975-01-01

    The paper discusses the estimation of the degree of atherosclerosis in the human femoral artery through the use of a digital image processing system for vascular angiograms. The film digitizer uses an electronic image dissector camera to scan the angiogram and convert the recorded optical density information into a numerical format. Another processing step involves locating the vessel edges from the digital image. The computer has been programmed to estimate vessel abnormality through a series of measurements, some derived primarily from the vessel edge information and others from optical density variations within the lumen shadow. These measurements are combined into an atherosclerosis index, which is found in a post-mortem study to correlate well with both visual and chemical estimates of atherosclerotic disease.

  15. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract

    PubMed Central

    Ramanathan, Subramaniyan; Kumar, Devendra; Khanna, Maneesh; Al Heidous, Mahmoud; Sheikh, Adnan; Virmani, Vivek; Palaniappan, Yegu

    2016-01-01

    Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management. PMID:26981222

  16. Not all symptoms disappear after vascular ring division: a pathophysiological interpretation.

    PubMed

    Zani, Augusto; Morini, Francesco; Paolantonio, Pasquale; Cozzi, Denis A

    2008-05-01

    Vascular rings are a group of cardiovascular lesions due to faulty embryological development derived from an abnormality of neural crest cells (cephalic neurocristopathy). In addition to peculiar symptoms due to compression on the trachea and/or the esophagus, patients with vascular rings might present further features of neural crest-related defects. We report on a case of a child with complete vascular ring, affected both by compressive symptoms and by autonomic disturbances and minor facial anomalies. The autonomic disturbances are clinical features of maturational dysautonomia and tend to disappear with aging, whereas major compressive symptoms are solved by surgery.

  17. [Cervical vascular penetrating trauma].

    PubMed

    Etl, S; Hafer, G; Mundinger, A

    2000-01-01

    The case of a 25 year old male with a stab wound of common carotid artery and the internal jugular vein is reported. He was admitted in severe hemorrhagic shock and immediately treated successfully by arterial reconstruction by means of a venous patch. Mild, declining neurological deficits correlated in magnetic resonance imaging with disturbances in the perfusion area of the medial cerebral artery. A survey of the literature shows that the fast repair of the carotid artery is clearly to be given preference to ligature. First can be executed successfully in exceptional emergency cases also by non-carotid surgeons, if basic vascular-surgical techniques are controlled.

  18. Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

    PubMed Central

    Mima, Akira

    2016-01-01

    Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular andmicrovascular complications. Macrovascular complications include coronary artery diseaseand cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications. PMID:26881236

  19. Skin microvascular reactivity in patients with hypothyroidism.

    PubMed

    Mihor, Ana; Gergar, Maša; Gaberšček, Simona; Lenasi, Helena

    2016-11-04

    Hypothyroidism is associated with impaired vascular function; however, little is known about its impact on microcirculation. We aimed to determine skin microvascular reactivity in hypothyroidism focusing on endothelial function and the sympathetic response. We measured skin laser Doppler (LD) flux (LDF) on the volar forearm and the finger pulp using LD flowmetry in hypothyroid patients (N = 13) and healthy controls (N = 15). Skin microvascular reactivity was assessed by a three-minute occlusion of the brachial artery, inducing postocclusive reactive hyperaemia (PRH), and by a four-minute local cooling of the hand. An electrocardiogram (ECG), digital artery blood pressure and skin temperature at the measuring sites were recorded. Baseline LDF, the digital artery blood pressure and the heart rate were comparable between patients and controls. On the other hand, patients exhibited significantly longer PRH duration, significantly higher blood pressure during cooling (unpaired t-test, p <0.05) and lower, albeit not significant, LDF in the ipsilateral finger pulp during cooling compared to controls. Unexpectedly, the results of the present study point to an increased vasodilator capacity of skin microcirculation and an apparent increase in sympathetic reactivity after local cooling in hypothyroid patients. Hypothyroidism induces subtle changes of some haemodynamic parameters in skin microcirculation implying altered endothelial function and altered sympathetic reactivity.

  20. Modeling and processing of laser Doppler reactive hyperaemia signals

    NASA Astrophysics Data System (ADS)

    Humeau, Anne; Saumet, Jean-Louis; L'Huiller, Jean-Pierre

    2003-07-01

    Laser Doppler flowmetry is a non-invasive method used in the medical domain to monitor the microvascular blood cell perfusion through tissue. Most commercial laser Doppler flowmeters use an algorithm calculating the first moment of the power spectral density to give the perfusion value. Many clinical applications measure the perfusion after a vascular provocation such as a vascular occlusion. The response obtained is then called reactive hyperaemia. Target pathologies include diabetes, hypertension and peripheral arterial occlusive diseases. In order to have a deeper knowledge on reactive hyperaemia acquired by the laser Doppler technique, the present work first proposes two models (one analytical and one numerical) of the observed phenomenon. Then, a study on the multiple scattering between photons and red blood cells occurring during reactive hyperaemia is carried out. Finally, a signal processing that improves the diagnosis of peripheral arterial occlusive diseases is presented.

  1. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  2. The association between vibration and vascular injury in rheumatic diseases: a review of the literature.

    PubMed

    Wang, Yu-Jie; Huang, Xiao-Lei; Yan, Jun-Wei; Wan, Ya-Nan; Wang, Bing-Xiang; Tao, Jin-Hui; Chen, Bing; Li, Bao-Zhu; Yang, Guo-Jun; Wang, Jing

    2015-02-01

    Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.

  3. Abnormalities of the lungs and thoracic cage in the Ehlers-Danlos syndrome.

    PubMed Central

    Ayres, J G; Pope, F M; Reidy, J F; Clark, T J

    1985-01-01

    Twenty patients with the Ehlers-Danlos syndrome, (10 type I, six type II, and four type IV) were studied to assess the frequency of respiratory abnormalities in this condition. Five patients (25%) had had at least one episode of haemoptysis, but none had any defect of coagulation. There was a high frequency of recurrent sinusitis, notably in those with the type I syndrome. Two patients had bullous lung disease, one of whom (type IV) had had three pneumothoraces and subsequent pleurodesis; he also had tracheomegaly (the Mounier-Kuhn abnormality). Minor skeletal abnormalities such as pectus excavatum were common, particularly in patients with type IV disease. Three patients had the straight back syndrome. There were no consistent spirometric or lung volume abnormalities, but eight patients (40%) had a raised gas transfer coefficient (Kco), possibly due to an increased intrapulmonary vascular volume. Two other patients had very low values of Kco that were unexplained. Images PMID:4023980

  4. Endocrine abnormalities in anorexia nervosa.

    PubMed

    Lawson, Elizabeth A; Klibanski, Anne

    2008-07-01

    Anorexia nervosa (AN) is a psychiatric disease associated with notable medical complications and increased mortality. Endocrine abnormalities, including hypogonadotropic hypogonadism, hypercortisolemia, growth hormone resistance and sick euthyroid syndrome, mediate the clinical manifestations of this disease. Alterations in anorexigenic and orexigenic appetite-regulating pathways have also been described. Decreases in fat mass result in adipokine abnormalities. Although most of the endocrine changes that occur in AN represent physiologic adaptation to starvation, some persist after recovery and might contribute to susceptibility to AN recurrence. In this Review, we summarize key endocrine alterations in AN, with a particular focus on the profound bone loss that can occur in this disease. Although AN is increasingly prevalent among boys and men, the disorder predominantly affects girls and women who are, therefore, the focus of this Review.

  5. Eye abnormalities in Fryns syndrome.

    PubMed

    Pierson, Diane M; Taboada, Eugenio; Butler, Merlin G

    2004-03-15

    Fryns syndrome is a rare, generally lethal, autosomal recessive multiple congenital anomaly (MCA) syndrome first described in 1979. Patients with the syndrome present with the classical findings of cloudy cornea, brain malformations, diaphragmatic defects, and distal limb deformities. Over 70 patients have been reported revealing a wide variety of phenotypic features. Although initially considered a major feature of Fryns syndrome, cloudy cornea has been relegated as a minor diagnostic sign and not commonly reported in patients since the original description. However, eye findings per se are not uncommon. Abnormal eye findings occasionally reported in Fryns syndrome potentially result in amblyopia and blindness, profoundly affecting neurologic outcome of those who survive the neonatal period. We reviewed 77 reported patients with Fryns syndrome and summarized the abnormal eye findings identified in 12 of the reported cases. In addition, we contribute three new patients with Fryns syndrome, one of which demonstrated unilateral microphthalmia and cloudy cornea.

  6. [Chromosome abnormalities in human cancer].

    PubMed

    Salamanca-Gómez, F

    1995-01-01

    Recent investigation on the presence of chromosome abnormalities in neoplasias has allowed outstanding advances in the knowledge of malignant transformation mechanisms and important applications in the clinical diagnosis and prognosis of leukaemias, lymphomas and solid tumors. The purpose of the present paper is to discuss the most relevant cytogenetic aberrations, some of them described at the Unidad de Investigación Médica en Genética Humana, Instituto Mexicano del Seguro Social, and to correlate these abnormalities with recent achievements in the knowledge of oncogenes, suppressor genes or antioncogenes, their chromosome localization, and their mutations in human neoplasia; as well as their perspectives in prevention and treatment of cancer that such findings permit to anticipate.

  7. Neuroendocrine abnormalities in Parkinson's disease.

    PubMed

    De Pablo-Fernández, Eduardo; Breen, David P; Bouloux, Pierre M; Barker, Roger A; Foltynie, Thomas; Warner, Thomas T

    2017-02-01

    Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research.

  8. Hypertension in Metabolic Syndrome: Vascular Pathophysiology

    PubMed Central

    Mendizábal, Yolanda; Llorens, Silvia; Nava, Eduardo

    2013-01-01

    Metabolic syndrome is a cluster of metabolic and cardiovascular symptoms: insulin resistance (IR), obesity, dyslipemia. Hypertension and vascular disorders are central to this syndrome. After a brief historical review, we discuss the role of sympathetic tone. Subsequently, we examine the link between endothelial dysfunction and IR. NO is involved in the insulin-elicited capillary vasodilatation. The insulin-signaling pathways causing NO release are different to the classical. There is a vasodilatory pathway with activation of NO synthase through Akt, and a vasoconstrictor pathway that involves the release of endothelin-1 via MAPK. IR is associated with an imbalance between both pathways in favour of the vasoconstrictor one. We also consider the link between hypertension and IR: the insulin hypothesis of hypertension. Next we discuss the importance of perivascular adipose tissue and the role of adipokines that possess vasoactive properties. Finally, animal models used in the study of vascular function of metabolic syndrome are reviewed. In particular, the Zucker fatty rat and the spontaneously hypertensive obese rat (SHROB). This one suffers macro- and microvascular malfunction due to a failure in the NO system and an abnormally high release of vasoconstrictor prostaglandins, all this alleviated with glitazones used for metabolic syndrome therapy. PMID:23573411

  9. Vascular Distribution of Nanomaterials

    PubMed Central

    Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

    2014-01-01

    Once considered primarily occupational, novel nanotechnology innovation and application has led to widespread domestic use and intentional biomedical exposures. With these exciting advances, the breadth and depth of toxicological considerations must also be expanded. The vascular system interacts with every tissue in the body, striving to homeostasis. Engineered nanomaterials (ENM) have been reported to distribute in many different organs and tissues. However, these observations have tended to use approaches requiring tissue homogenization and/or gross organ analyses. These techniques, while effective in establishing presence, preclude an exact determination of where ENM are deposited within a tissue. It is necessary to identify this exact distribution and deposition of ENM throughout the cardiovascular system, with respect to vascular hemodynamics and in vivo/ in vitro ENM modifications taken into account if nanotechnology is to achieve its full potential. Distinct levels of the vasculature will first be described as individual compartments. Then the vasculature will be considered as a whole. These unique compartments and biophysical conditions will be discussed in terms of their propensity to favor ENM deposition. Understanding levels of the vasculature will also be discussed. Ultimately, future studies must verify the mechanisms speculated on and presented herein. PMID:24777845

  10. History of vascular access.

    PubMed

    Dudrick, Stanley J

    2006-01-01

    Milestones in the history of the development of vascular access and the subsequent advances in practical clinical applications of the knowledge, techniques, technology, and experience to the beneficial management of a variety of patients are described. The original achievements are presented and briefly discussed primarily, but not exclusively, in relationship to the successful development of parenteral nutrition (PN). Beginning with the discovery of the circulation of blood, landmark events, resulting from astute observations, experimentation, and ingenious technological advances, are summarized or outlined chronologically over the past 4 centuries, with emphasis on the many recent accomplishments of basic and clinical scientists during the past 6 decades. Brief descriptions of several seminal contributions to safe and effective IV access, management, and therapy acknowledge and recognize the historical highlights that have allowed a complex and potentially hazardous therapeutic modality to evolve into a commonly applied useful adjunct to our current inpatient and outpatient armamentarium. A comprehensive list of references documents the highlights of the development of vascular access for the student of history.

  11. Vascular pattern formation in plants.

    PubMed

    Scarpella, Enrico; Helariutta, Ykä

    2010-01-01

    Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns.

  12. Congenital abnormalities of the goat.

    PubMed

    Basrur, P K

    1993-03-01

    Congenital abnormalities of genetic and environmental causes constitute a striking proportion of the afflictions seen in goats. These include a variety of malformations and metabolic diseases that could occur in all breeds but tend to exhibit predisposition in some breeds of goats. Genetic abnormalities for which the carrier state is detectable with the aid of enzymes and surface protein markers can be eliminated from goat populations, whereas common polygenic disorders including udder problems in does and gynecomastia in bucks are more difficult to eradicate because the mutant genes responsible for these traits generally do not declare themselves until inbreeding brings together a critical concentration of liability genes to create a crisis. A substantial reduction of common abnormalities in this species, such as intersexuality in dairy breeds, abortion in Angora breed, and arthritis in the Pygmy breed, will require a change in breeders' preference and selection practice. In making these changes, however, the beneficial traits will have to be balanced against the undesirable effects of the selected mutant genes (pleiotropy), which hold the key to success or failure of a breed under domestication.

  13. Meiotic abnormalities in infertile males.

    PubMed

    Egozcue, J; Sarrate, Z; Codina-Pascual, M; Egozcue, S; Oliver-Bonet, M; Blanco, J; Navarro, J; Benet, J; Vidal, F

    2005-01-01

    Meiotic anomalies, as reviewed here, are synaptic chromosome abnormalities, limited to germ cells that cannot be detected through the study of the karyotype. Although the importance of synaptic errors has been underestimated for many years, their presence is related to many cases of human male infertility. Synaptic anomalies can be studied by immunostaining of synaptonemal complexes (SCs), but in this case their frequency is probably underestimated due to the phenomenon of synaptic adjustment. They can also be studied in classic meiotic preparations, which, from a clinical point of view, is still the best approach, especially if multiplex fluorescence in situ hybridization is at hand to solve difficult cases. Sperm chromosome FISH studies also provide indirect evidence of their presence. Synaptic anomalies can affect the rate of recombination of all bivalents, produce achiasmate small univalents, partially achiasmate medium-sized or large bivalents, or affect all bivalents in the cell. The frequency is variable, interindividually and intraindividually. The baseline incidence of synaptic anomalies is 6-8%, which may be increased to 17.6% in males with a severe oligozoospermia, and to 27% in normozoospermic males with one or more previous IVF failures. The clinical consequences are the production of abnormal spermatozoa that will produce a higher number of chromosomally abnormal embryos. The indications for a meiotic study in testicular biopsy are provided.

  14. Vascular mechanisms in the pathogenesis of stroke.

    PubMed

    Sierra, Cristina; Coca, Antonio; Schiffrin, Ernesto L

    2011-06-01

    Stroke is one of the most devastating manifestations of two common diseases, atherosclerosis and hypertension. It represents the second leading cause of death and a major cause of disability worldwide. Besides age (a nonmodifiable risk factor), hypertension is the most important cardiovascular risk factor for developing both ischemic and hemorrhagic stroke, as well as small vessel disease predisposing to lacunar infarction, white matter lesions, and cerebral microbleeds. In addition, hypertension predisposes to atherosclerosis and cardiac diseases (notably atrial fibrillation), thereby promoting cerebral embolism. Inflammatory mechanisms play a central role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Endothelial dysfunction, in part resulting from excessive production of reactive oxygen species, is an important mechanism of cerebrovascular damage. This article reviews recent data on vascular mechanisms that participate in the pathogenesis of stroke.

  15. Visual pathway abnormalities in tuberculous meningitis.

    PubMed

    Maurya, Pradeep Kumar; Singh, Ajai Kumar; Sharma, Lalit; Kulshreshtha, Dinkar; Thacker, Anup Kumar

    2016-11-01

    Ophthalmological complications are common and disabling in patients with tuberculous meningitis. We aimed to study the visual pathway abnormalities in patients with tuberculous meningitis. Forty-three patients with tuberculous meningitis were subjected to visual evoked responses (VER) and neuroophthalmologic assessment. Neuroophthalmologic assessment revealed abnormalities in 22 (51.3%) patients. VER were found to be abnormal in 27 (62.8%) patients. The VER abnormalities included prolonged P100 latencies with relatively normal amplitude and significant interocular latency differences. Visual pathways abnormalities are common in patients with tuberculous meningitis and are often subclinical. Pathophysiologic explanations for electrophysiological abnormalities on VER in these patients are incompletely understood and needs further exploration.

  16. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    PubMed

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-01-10

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  17. Painful unilateral temporalis muscle enlargement: reactive masticatory muscle hypertrophy.

    PubMed

    Katsetos, Christos D; Bianchi, Michael A; Jaffery, Fizza; Koutzaki, Sirma; Zarella, Mark; Slater, Robert

    2014-06-01

    An instance of isolated unilateral temporalis muscle hypertrophy (reactive masticatory muscle hypertrophy with fiber type 1 predominance) confirmed by muscle biopsy with histochemical fiber typing and image analysis in a 62 year-old man is reported. The patient presented with bruxism and a painful swelling of the temple. Absence of asymmetry or other abnormalities of the craniofacial skeleton was confirmed by magnetic resonance imaging and cephalometric analyses. The patient achieved symptomatic improvement only after undergoing botulinum toxin injections. Muscle biopsy is key in the diagnosis of reactive masticatory muscle hypertrophy and its distinction from masticatory muscle myopathy (hypertrophic branchial myopathy) and other non-reactive causes of painful asymmetric temporalis muscle enlargement.

  18. Endothelial dysfunction - a major mediator of diabetic vascular disease.

    PubMed

    Sena, Cristina M; Pereira, Ana M; Seiça, Raquel

    2013-12-01

    The vascular endothelium is a multifunctional organ and is critically involved in modulating vascular tone and structure. Endothelial cells produce a wide range of factors that also regulate cellular adhesion, thromboresistance, smooth muscle cell proliferation, and vessel wall inflammation. Thus, endothelial function is important for the homeostasis of the body and its dysfunction is associated with several pathophysiological conditions, including atherosclerosis, hypertension and diabetes. Patients with diabetes invariably show an impairment of endothelium-dependent vasodilation. Therefore, understanding and treating endothelial dysfunction is a major focus in the prevention of vascular complications associated with all forms of diabetes mellitus. The mechanisms of endothelial dysfunction in diabetes may point to new management strategies for the prevention of cardiovascular disease in diabetes. This review will focus on the mechanisms and therapeutics that specifically target endothelial dysfunction in the context of a diabetic setting. Mechanisms including altered glucose metabolism, impaired insulin signaling, low-grade inflammatory state, and increased reactive oxygen species generation will be discussed. The importance of developing new pharmacological approaches that upregulate endothelium-derived nitric oxide synthesis and target key vascular ROS-producing enzymes will be highlighted and new strategies that might prove clinically relevant in preventing the development and/or retarding the progression of diabetes associated vascular complications.

  19. Regulation of thrombosis and vascular function by protein methionine oxidation.

    PubMed

    Gu, Sean X; Stevens, Jeff W; Lentz, Steven R

    2015-06-18

    Redox biology is fundamental to both normal cellular homeostasis and pathological states associated with excessive oxidative stress. Reactive oxygen species function not only as signaling molecules but also as redox regulators of protein function. In the vascular system, redox reactions help regulate key physiologic responses such as cell adhesion, vasoconstriction, platelet aggregation, angiogenesis, inflammatory gene expression, and apoptosis. During pathologic states, altered redox balance can cause vascular cell dysfunction and affect the equilibrium between procoagulant and anticoagulant systems, contributing to thrombotic vascular disease. This review focuses on the emerging role of a specific reversible redox reaction, protein methionine oxidation, in vascular disease and thrombosis. A growing number of cardiovascular and hemostatic proteins are recognized to undergo reversible methionine oxidation, in which methionine residues are posttranslationally oxidized to methionine sulfoxide. Protein methionine oxidation can be reversed by the action of stereospecific enzymes known as methionine sulfoxide reductases. Calcium/calmodulin-dependent protein kinase II is a prototypical methionine redox sensor that responds to changes in the intracellular redox state via reversible oxidation of tandem methionine residues in its regulatory domain. Several other proteins with oxidation-sensitive methionine residues, including apolipoprotein A-I, thrombomodulin, and von Willebrand factor, may contribute to vascular disease and thrombosis.

  20. 219 vascular fellows' perception of the future of vascular surgery.

    PubMed

    Hingorani, Anil P; Ascher, Enrico; Marks, Natalie; Shiferson, Alexander; Puggioni, Alessandra; Tran, Victor; Patel, Nirav; Jacob, Theresa

    2009-01-01

    In an attempt to identify the fellows' concerns about the future of the field of vascular surgery, we conducted a survey consisting of 22 questions at an annual national meeting in March from 2004 to 2007. In order to obtain accurate data, all surveys were kept anonymous. The fellows were asked (1) what type of practice they anticipated they would be in, (2) what the new training paradigm for fellows should be, (3) to assess their expectation of the needed manpower with respect to the demand for vascular surgeons, (4) what were major threats to the future of vascular surgery, (5) whether they had heard of and were in favor of the American Board of Vascular Surgery (ABVS), (6) who should be able to obtain vascular privileges, and (7) about their interest in an association for vascular surgical trainees. Of 273 attendees, 219 (80%) completed the survey. Males made up 87% of those surveyed, and 60% were between the ages of 31 and 35 years. Second-year fellows made up 82% of those surveyed. Those expecting to join a private, academic, or mixed practice made up 35%, 28%, and 20% of the respondents, respectively, with 71% anticipating entering a 100% vascular practice. Forty percent felt that 5 years of general surgery with 2 years of vascular surgery should be the training paradigm, while 45% suggested 3 and 3 years, respectively. A majority, 79%, felt that future demand would exceed the available manpower, while 17% suggested that manpower would meet demand. The major challenges to the future of vascular surgery were felt to be competition from cardiology (82%) or radiology (30%) and lack of an independent board (29%). Seventeen percent were not aware of the ABVS, and only 2% were against it; 71% suggested that vascular privileges be restricted to board-certified vascular surgeons. Seventy-six percent were interested in forming an association for vascular trainees to address the issues of the future job market (67%), endovascular training during fellowship (56

  1. A case of multiple abnormalities with eustachian tube obstruction by a protruded internal carotid artery.

    PubMed

    Shinnabe, Akihiro; Hara, Mariko; Matsuzawa, Shingo; Hasegawa, Masayo; Kodama, Kozue; Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

    2011-03-01

    We report a case of multiple abnormalities with eustachian tube obstruction by a protruded internal carotid artery. A 10-year-old male presented with multiple abnormalities including anomalous pinna, poor eyesight, facial palsy, moderate conductive deafness, and otitis media with effusion. Temporal bone computed tomography demonstrated obstruction of the right eustachian tube by a protruded internal carotid artery. Insertion of a tympanostomy tube did not improve his hearing, indicating a possible ossicular chain anomaly. Although tympanoplasty is necessary to improve the patients' hearing, the poor drainage function makes this difficult. Knowledge of this vascular anomaly is important when performing myringotomy or tympanoplasty.

  2. Orientin inhibits high glucose-induced vascular inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Kwak, Soyoung; Bae, Jong-Sup

    2014-12-01

    Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Orientin, a C-glycosyl flavonoid, is known to have anxiolytic and antioxidative activity. In this study, we assessed whether orientin can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, the expression of cell adhesion molecules (CAMs), the formation of reactive oxygen species (ROS), and the activation of nuclear factor kappa B (NF-κB). Remarkably, the vascular inflammatory effects of HG were attenuated by pretreatment with orientin. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that orientin may have significant benefits in the treatment of diabetic complications and atherosclerosis.

  3. Hyperoside inhibits high-glucose-induced vascular inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Kwak, Soyoung; Kwon, O-Jun; Bae, Jong-Sup

    2014-10-01

    Hyperoside, an active compound from the genera of Hypericum and Crataegus, was reported to have antioxidant, antihyperglycemic, anticancer, anti-inflammatory, and anticoagulant activities. Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether hyperoside can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB. Remarkably, all of the above-mentioned vascular inflammatory effects of HG were attenuated by pretreatment with hyperoside. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications; therefore, our results suggest that hyperoside may have significant therapeutic benefits against diabetic complications and atherosclerosis.

  4. [Oxidative stress: one of the major causes of vascular calcification in chronic kidney disease patients].

    PubMed

    Nyitrai, Mónika; Balla, György; Balla, József

    2015-11-22

    The leading cause of high mortality in dialyzed patients is cardiovascular disease. One of the main contributors of cardiovascular event is vascular calcification, which occurs even in very young patients. Multiple factors and complex mechanisms are involved in the formation of robust vascular calcification which affects a large vascular area observed in chronic kidney diseases. Patients on dialysis are exposed to enhanced oxidative stress as a result of increased pro-oxidant activity and reduced anti-oxidant systems. The oxidation of lipoprotein particles is implicated in the development of vascular damage representing oxidative threat, which leads to endothelial dysfunction. Moreover, in a pro-oxidant environment osteoblastic trans-differentiation of smooth muscle cells was shown to occur. Heme derived from oxidized hemoglobin might contribute to the formation of reactive lipid metabolites. This oxidative burden contributes to the development of atherosclerosis and vascular calcification. Heme oxygenase-1 and ferritin may serve as intracellular defense mechanisms against such an insult.

  5. Civil War vascular injuries.

    PubMed

    Blaisdell, F William

    2005-01-01

    As the result of the insistence of the Surgeon General during the United States Civil War, there was extensive documentation of injuries to major blood vessels and their resulting complications. The specific treatment of vascular injuries during the Civil War was ligation of the injured vessel or amputation. This was before there was any knowledge of the cause and prevention of infection. Overall, the results were dismal, with a mortality rate of nearly 60% for the more than 1000 soldiers treated by arterial ligation. The most important contribution of these medical reports was to define how the injuries should be diagnosed and managed. Many of the principles that developed as the result of this post-war review are as valid today as they were then. Unfortunately, it seems that many of these lessons have had to be relearned by the surgeons who have participated in each of our subsequent military conflicts.

  6. Vascular access for hemodialysis.

    PubMed

    Vanholder, R; Ringoir, S

    1994-04-01

    Indwelling central venous catheters were consecutively used as access for acute and chronic hemodialysis, emergency treatment of pulmonary fluid overload, intoxication and electrolyte disturbances, plasmapheresis, and semiacute continuous dialysis strategies, such as continuous arteriovenous hemofiltration (CAVH). Modification in catheter structure also made it possible to use this access for long-term treatment (e.g., surgically insertable catheters [Hickman], soft large-bore catheters for blind insertion). We discuss the remaining open questions in this field: Which is the insertion site of preference (i.e., subclavian, femoral, or deep jugular)? Should we prefer stiff or soft catheters? Should soft catheters be positioned surgically or is blind insertion by nonsurgeons as adequate? Is it necessary to couple catheter insertion to adjuvant techniques, such as echographic guidance, to reduce complications? Is the currently used polymer structure of the catheters acceptable? Should catheter dialysis be used with single or double vascular access?

  7. Vascularity in the reptilian spectacle.

    PubMed

    Mead, A W

    1976-07-01

    Vascularization of the spectacle or brille of the reptile was demonstrated by biomicroscopy, histology, fluorescein (in vivo), and Microfil silicone rubber (in situ) injections. This unusual vascularity provides new evidence for reassessment of the origin and development of this structure, and a useful tool with which to do so.

  8. Hybrid haemodialysis vascular access salvage.

    PubMed

    Potisek, Maja; Ključevšek, Tomaž; Leskovar, Boštjan

    2017-03-01

    A well-functioning vascular access is essential for successful haemodialysis in patients with end-stage kidney failure. Sometimes, when we have exploited all conventional ways of vascular access salvage, we have to find a unique solution to preserve it.

  9. [Banks of vascular homografts].

    PubMed

    Polvani, G L; Guarino, A; Pompilio, G; Parolari, A; Piccolo, G; Sala, A; Biglioli, P

    2001-01-01

    We define as Banking of the tissues all the procedures that include the finding, preparation, conservation and distribution of the homograft. The vascular homografts are taken and put into a solution of transportation at +4 degrees C and kept at this temperature till their arrival at the Bank. The following step is the dissection of the homograft which will have to be performed as quickly as possible at most 24 hours after the taking in conditions of maximum sterility. At the Italian Homograft Bank at Centro Cardiologico, the vascular homografts are kept at +4 degrees C for 96 hours on average with antibiotics. After a phase of sterilization at +4 degrees C the tissue is frozen according to a homogeneous and controlled thermic decrease and stored at -150 degrees C/-180 degrees C in fumes of liquid nitrogen till the moment of their employment allowing a long term conservation. The aim of all these procedures of cryopreservation is to keep the structural and functional integrity of cells and tissues. The thermic decrease of the tissues must occur so that to avoid all the damages of the cellular vitality and functionality and especially of the tissue structure in toto. In order to limitate these events some cryoprotector agents are employed because they reduce the concentration of the solutes, the cellular dehydration, the formation of micro-macro crystals. Another step to establish if the homograft is proper is the study of bacteriological and viral aspects. The viral screenings are performed on the donor's blood and the bacteriological tests are performed on the tissue and on the liquids. For each phase of the banking a series of information about the donor and about the tissues are recorded and filed both on paper and database so that to grant always a right conduct of the material.

  10. Low-set ears and pinna abnormalities

    MedlinePlus

    Low-set ears; Microtia; "Lop" ear; Pinna abnormalities; Genetic defect-pinna; Congenital defect-pinna ... most cases, a health care provider finds pinna abnormalities during the first well-baby exam. This exam ...

  11. Detrimental effects of high-fat diet loading on vascular endothelial function and therapeutic efficacy of ezetimibe and statins in patients with type 2 diabetes.

    PubMed

    Kurozumi, Akira; Okada, Yosuke; Mori, Hiroko; Kobayashi, Takuya; Masuda, Daisaku; Yamashita, Shizuya; Tanaka, Yoshiya

    2016-05-31

    Several recent reports from large clinical trials have described the role of postprandial hyperlipidemia in the onset of atherosclerosis. In this pilot study, the effects of postprandial lipid abnormalities induced by high-fat diet loading on vascular endothelial function in type 2 diabetes were investigated and the effects of ezetimibe and statins on endothelial function were compared. In 20 patients in Study 1, peripheral arterial tonometry tests were performed before and 4h after loading to measure the reactive hyperemia index (RHI). In Study 2, the same patients were randomly allocated to ezetimibe or rosuvastatin. After 1 week of treatment, loading tests were conducted in the same manner. In Study 1, the RHI decreased from 1.86 to 1.60. There were no significant correlations between changes in RHI and the area under the curve (AUC) or coefficient of variation (CV) of each metabolic marker. In Study 2, ezetimibe treatment resulted in a significant improvement in RHI. The two drugs had comparable effects on changes in AUC. There were no significant correlations between changes in RHI and changes in AUC or changes in CV. When age, sex, drug, hemoglobin A1c, and changes in each lipid were evaluated as independent variables with RHI improvement as the dependent variable, drug differences were found to exert the greatest effect on RHI improvement using a stepwise procedure. The results of this study suggest that the progression of atherosclerosis is due to abnormalities in postprandial lipid metabolism and that ezetimibe can potentially inhibit the aggravation of vascular endothelial dysfunction after high-fat diet loading.

  12. Molecular dissection of reactive astrogliosis and glial scar formation

    PubMed Central

    Sofroniew, Michael V.

    2009-01-01

    Reactive astrogliosis, whereby astrocytes undergo varying molecular and morphological changes, is a ubiquitous but poorly understood hallmark of all central nervous system pathologies. Now genetic tools are enabling the molecular dissection of the functions and mechanisms of reactive astrogliosis in vivo. Recent studies provide compelling evidence that reactive astrogliosis may exert both beneficial and detrimental effects in a context-dependent manner determined by specific molecular signaling cascades. Reactive astrocytes may have both loss of normal functions and gain of abnormal effects that can feature prominently in a variety of disease processes. This article reviews developments in the signaling mechanisms that regulate specific aspects of reactive astrogliosis and highlights the potential to identify novel therapeutic molecular targets for diverse neurological disorders. PMID:19782411

  13. Vascular surgery: the European perspective.

    PubMed

    Harris, P

    1999-09-01

    Isaac Newton, among others, observed that 'we see so far because we are standing upon the shoulders of giants'. In vascular surgery most of the giants have been European, and this is a heritage which we as Europeans can take pride in and build upon if we chose to do so. As in other areas of life, commitment is essential in order to influence the future. For vascular surgeons in Europe this means active participation in the European scientific societies for vascular surgery and in the UEMS. The main value of the EBSQ.VASC assessments to date has been to expose the uneven standards of training in vascular surgery within the European Union. Only if action follows to address these inequalities will the tactics of the European Board of Vascular Surgery be vindicated.

  14. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  15. Abnormalities of the erythrocyte membrane.

    PubMed

    Gallagher, Patrick G

    2013-12-01

    Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy.

  16. Foot abnormalities of wild birds

    USGS Publications Warehouse

    Herman, C.M.; Locke, L.N.; Clark, G.M.

    1962-01-01

    The various foot abnormalities that occur in birds, including pox, scaly-leg, bumble-foot, ergotism and freezing are reviewed. In addition, our findings at the Patuxent Wildlife Research Center include pox from dove, mockingbird, cowbird, grackle and several species of sparrows. Scaly-leg has been particularly prevalent on icterids. Bumble foot has been observed in a whistling swan and in a group of captive woodcock. Ergotism is reported from a series of captive Canada geese from North Dakota. Several drug treatments recommended by others are presented.

  17. Citicoline in vascular cognitive impairment and vascular dementia after stroke.

    PubMed

    Alvarez-Sabín, Jose; Román, Gustavo C

    2011-01-01

    Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.

  18. Phenylethynyl reactive diluents

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor)

    1995-01-01

    A composition of matter having a specified general structure is employed to terminate a nucleophilic reagent, resulting in the exclusive production of phenylethynyl terminated reactive oligomers which display unique thermal characteristics. A reactive diluent having a specified general structure is employed to decrease the melt viscosity of a phenylethynyl terminated reactive oligomer and to subsequently react with to provide a thermosetting material of enhanced density. These materials have features which make them attractive candidates for use as composite matrices and adhesives.

  19. Lower extremity abnormalities in children.

    PubMed

    Sass, Pamela; Hassan, Ghinwa

    2003-08-01

    Rotational and angular problems are two types of lower extremity abnormalities common in children. Rotational problems include intoeing and out-toeing. Intoeing is caused by one of three types of deformity: metatarsus adductus, internal tibial torsion, and increased femoral anteversion. Out-toeing is less common than intoeing, and its causes are similar but opposite to those of intoeing. These include femoral retroversion and external tibial torsion. Angular problems include bowlegs and knock-knees. An accurate diagnosis can be made with careful history and physical examination, which includes torsional profile (a four-component composite of measurements of the lower extremities). Charts of normal values and values with two standard deviations for each component of the torsional profile are available. In most cases, the abnormality improves with time. A careful physical examination, explanation of the natural history, and serial measurements are usually reassuring to the parents. Treatment is usually conservative. Special shoes, cast, or braces are rarely beneficial and have no proven efficacy. Surgery is reserved for older children with deformity from three to four standard deviations from the normal.

  20. Normal and abnormal lid function.

    PubMed

    Rucker, Janet C

    2011-01-01

    This chapter on lid function is comprised of two primary sections, the first on normal eyelid anatomy, neurological innervation, and physiology, and the second on abnormal eyelid function in disease states. The eyelids serve several important ocular functions, the primary objectives of which are protection of the anterior globe from injury and maintenance of the ocular tear film. Typical eyelid behaviors to perform these functions include blinking (voluntary, spontaneous, or reflexive), voluntary eye closure (gentle or forced), partial lid lowering during squinting, normal lid retraction during emotional states such as surprise or fear (startle reflex), and coordination of lid movements with vertical eye movements for maximal eye protection. Detailed description of the neurological innervation patterns and neurophysiology of each of these lid behaviors is provided. Abnormal lid function is divided by conditions resulting in excessive lid closure (cerebral ptosis, apraxia of lid opening, blepharospasm, oculomotor palsy, Horner's syndrome, myasthenia gravis, and mechanical) and those resulting in excessive lid opening (midbrain lid retraction, facial nerve palsy, and lid retraction due to orbital disease).

  1. Sleep and vascular disorders.

    PubMed

    Plante, Gérard E

    2006-10-01

    It is not surprising that cardiovascular diseases such as congestive heart failure and coronary insufficiency can give rise to varying degrees of sleep impairment; it is less readily appreciated that certain physiologic events occurring during sleep-as well as long-term unsatisfactory sleep-may cause or increase the risk of cardiovascular conditions such as hypertension, atherosclerosis, stroke, and cardiac arrythmias. Heart rate abnormalities during sleep in normotensive subjects predict later cardiovascular disease, and their early identification alerts the physician to undertake preventive measures. Maneuvers, such as induction of hypoxia, can elicit abnormal blood pressure responses during sleep, and such responses have been used to identify impending cardiovascular problems that could become therapeutic targets. The spontaneously hypertensive rat has been used to examine the effect of sympathetic nervous system (SNS) activity on the heart under a variety of experimental conditions, including quiet and paradoxical sleep. The results have disclosed significant differences between the responses of spontaneously hypertensive rats and normal rats to SNS stimulation. Exploration of other pathophysiologic pathways affected by exposure to light and dark, including those responsive to the cyclic production of melatonin, will improve our understanding of the effect of disruptions of the circadian cycle on cardiovascular function. There is growing evidence that melatonin can influence important processes such as fluid, nitrogen, and acid-base balance. Human subjects whose nocturnal arterial blood pressure fails to show the "normal" decrement during sleep ("nondippers") are also prone to sleep poorly, exhibit increased SNS activity during sleep, and have an increased risk of total and cardiovascular disease mortality. Chronic sleep deficit is now known to be a risk factor for obesity and may contribute to the visceral form of obesity that underlies the metabolic syndrome

  2. In Vivo Angiography Quantifies Oxygen-Induced Retinopathy Vascular Recovery

    PubMed Central

    Mezu-Ndubuisi, Olachi J.

    2016-01-01

    ABSTRACT Purpose Retinopathy of prematurity (ROP) is a potentially blinding vasoproliferative disease. There is no standardized way to quantify plus disease (tortuous and dilated retinal vessels) or characterize abnormal recovery during ROP monitoring. This study objectively studies vascular features in live mice during development using noninvasive retinal imaging. Methods Using fluorescein angiography (FA), retinal vascular features were quantified in live mice with oxygen induced retinopathy (OIR). A total of 105 wild-type mice were exposed to 77% oxygen from postnatal day 7 (P7) till P12 (OIR mice). Also, 105 age-matched pups were raised in room air (RA mice). In vivo FA was performed at early (P16 to P20), mid (P23 to P27), late (P30 to P34), and mature (P47) phases of retinal vascular development. Retinal vascular area, retinal vein width, and retinal artery tortuosity were quantified. Results Retinal artery tortuosity was higher in OIR than RA mice at early (p < 0.0001), mid (p < 0.0001), late (p < 0.0001), and mature (p < 0.0001) phases. Retinal vascular area in OIR mice increased from early to mid-phase (p < 0.0001), but remained unchanged from mid to late (p = 0.23), and from late to mature phase (p = 0.98). Retinal vein width was larger in OIR mice compared to RA mice during early phase only. Arteries in OIR mice were more tortuous from early to mid-phase (p < 0.0001), but tortuosity remained stable from mid through mature phase. RA mice had an increase in retinal vascular area from early to late phase, but maintained uniform retinal vein width and retinal artery tortuosity in all phases. Conclusions In vivo FA distinguished arterial and venous features, similar to plus disease, and revealed aberrant recovery of OIR mice (arterial tortuosity, reduced capillary density, and absent neovascular buds) that persisted into adulthood. Retinal artery tortuosity may be a reliable, objective marker of severity of ROP. Infants with abnormal retinal vascular

  3. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development

    PubMed Central

    Jung, Bongnam; Obinata, Hideru; Galvani, Sylvain; Mendelson, Karen; Ding, Bisen; Skoura, Athanasia; Kinzel, Bernd; Brinkmann, Volker; Rafii, Shahin; Evans, Todd; Hla, Timothy

    2012-01-01

    SUMMARY During angiogenesis, nascent vascular sprouts fuse to form vascular networks enabling efficient circulation. Mechanisms that stabilize the vascular plexus are not well understood. Sphingosine 1-phosphate (S1P) is a blood-borne lipid mediator implicated in the regulation of vascular and immune systems. Here we describe a mechanism by which the G protein-coupled S1P receptor-1 (S1P1) stabilizes the primary vascular network. A gradient of S1P1 expression from the mature regions of the vascular network to the growing vascular front was observed. In the absence of endothelial S1P1, adherens junctions are destabilized, barrier function is breached, and flow is perturbed resulting in abnormal vascular hypersprouting. Interestingly, S1P1 responds to S1P as well as laminar shear stress to transduce flow-mediated signaling in endothelial cells both in vitro and in vivo. These data demonstrate that blood flow and circulating S1P activate endothelial S1P1 to stabilize blood vessels in development and homeostasis. PMID:22975328

  4. Phosphoinositide 3-kinase: a new kid on the block in vascular anomalies.

    PubMed

    Castillo, Sandra D; Vanhaesebroeck, Bart; Sebire, Neil J

    2016-12-01

    Vascular anomalies are broadly divided into vascular tumours and malformations. These lesions are composed of abnormal vascular elements of various types, and mainly affect infants, children, and young adults. Vascular anomalies may be painful, may be complicated by bleeding, infection, or organ dysfunction, and can have secondary effects on other tissues. Current treatment strategies include surgical excision, pulsed laser, and sclerotherapy, which are invasive, with risks of recurrence. There are growing pharmacological options for these vascular anomalies, but, to date, no specific targeted therapies have been developed. Phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinases that are involved in signal transduction and vesicular traffic, and that modulate important cellular processes such as proliferation, growth, and migration. Recent findings have indicated that the PI3K signalling pathway is important in the pathogenesis of vascular anomalies. This provides an opportunity to use PI3K inhibitors, which are in clinical trials for cancer treatment, for such lesions. Here, we provide an update on the classification of vascular anomalies, with their major features, and discuss the role of the PI3K signalling pathway in the pathogenesis of vascular anomalies, and their clinical implications and therapeutic opportunities. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. Vascular access in oncology patients.

    PubMed

    Gallieni, Maurizio; Pittiruti, Mauro; Biffi, Roberto

    2008-01-01

    Adequate vascular access is of paramount importance in oncology patients. It is important in the initial phase of surgical treatment or chemotherapy, as well as in the chronic management of advanced cancer and in the palliative care setting. We present an overview of the available vascular access devices and of the most relevant issues regarding insertion and management of vascular access. Particular emphasis is given to the use of ultrasound guidance as the preferred technique of insertion, which has dramatically decreased insertion-related complications. Vascular access management has considerably improved after the publication of effective guidelines for the appropriate nursing of the vascular device, which has reduced the risk of late complications, such as catheter-related bloodstream infection. However, many areas of clinical practice are still lacking an evidence-based background, such as the choice of the most appropriate vascular access device in each clinical situation, as well as prevention and treatment of thrombosis. We suggest an approach to the choice of the most appropriate vascular access device for the oncology patient, based on the literature available to date.

  6. Vascular Injuries: Trends in Management

    PubMed Central

    Wani, Mohd Lateef; Ahangar, Ab Gani; Ganie, Farooq Ahmad; Wani, Shadab Nabi; Wani, Nasir-ud-din

    2012-01-01

    Abstract Vascular injury presents a great challenge to the emergency resident because these injuries require urgent intervention to prevent loss of life or limb. Sometimes serious vascular injury presents with only subtle or occult signs or symptoms. The patient may present weeks or months after initial injury with symptoms of vascular insufficiency, embolization, pseudoaneurysm, arteriovenous fistula etc. Although the majority of vascular injuries are caused by penetrating trauma from gunshot wounds, stabbing or blast injury, the possibility of vascular injury needs to be considered in patients presenting with displaced long bone fractures, crush injury, prolonged immobilization in a fixed position by tight casts or bandages and various invasive procedures. iatrogenic vascular injuries constitute about 10% of cases in most series; however the incidence is an increasing trend because more endovascular procedures such as angioplasty and cardiac catheterization are being performed routinely. Civilian trauma is more frequently seen in young males. However, it can occur at any age due to road accidents, firearms, bomb blasts and diagnostic procedures. Most of the time, civilian trauma causes less tissue damage. There is an epidemic of vascular injuries in Kashmir valley because of problems in law and order in the past two decades. This review deals with the topic in detail. PMID:24350103

  7. [The future of vascular medicine].

    PubMed

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step.

  8. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis.

    PubMed

    Toraldo, Domenico Maurizio; Peverini, Francesco; De Benedetto, Michele; De Nuccio, Francesco

    2013-02-01

    Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis and arterial thrombosis, which are associated with high cardiovascular (CV) morbidity and mortality. In studies performed in clinical populations with elevated CV event risk profiles, the occurrence of moderate to severe OSAS was very often accompanied by a worsened vascular function and increased prevalence of structural abnormalities. Recent investigations of atherosclerosis in OSAS have focused on thrombotic tendency and blood viscosity, providing new insight into mechanisms of the disease. Despite that knowledge about the mechanisms of development of CV disease in patients with OSAS is still incomplete, observations confirm a relationship between sleep-disordered breathing and the rheological properties (flow properties) of blood. While platelet dysfunction and hypercoagulability (PDMPs, PaI-1, and SF) play important roles in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS.

  9. Noninvasive Characterization of Vascular Tone by Model-Based System Identification in Healthy and Heart Failure Patients.

    PubMed

    Zheng, Ya-Li; Yan, Bryan P; Zhang, Yuan-Ting; Poon, Carmen C Y

    2015-09-01

    Current markers for heart failure (HF) diagnosis and prognosis are mainly for the evaluation of cardiac functions. Since previous studies have reported that HF patients demonstrated abnormal vascular responses to external stimuli, it is speculated that vascular tone, a measure of activation level of vascular wall, may be able to reflect these abnormalities to assist HF detection. Nevertheless, vascular tone is difficult to be objectively quantified using existing tools. In this study, a vascular tone index was estimated from noninvasive blood pressure and pulse transit time measurements using system identification technique. This method was evaluated in 35 subjects (10 healthy, 13 with HF risk factors and 12 HF patients) in a regular maximal exercise test. It was found that the vascular tone index significantly increased by 24.4 ± 26.6% (p < 0.01) during maximal exercise in the healthy subjects. Moreover, the response was gradually attenuated in the risk-factor and HF groups (15.8 ± 36.5 and 0.9 ± 17.9%, respectively). The results reveal the association between the vascular tone response to maximal exercise and HF disease or risks. To conclude, the proposed method provides a quantitative characterization of vascular tone which may be a useful indicator of the pathological changes of the arteries or the heart.

  10. Vascular Calcification: Mechanisms of Vascular Smooth Muscle Cell Calcification

    PubMed Central

    Leopold, Jane A.

    2014-01-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk. PMID:25435520

  11. The role of the vascular endothelium in arenavirus haemorrhagic fevers.

    PubMed

    Kunz, Stefan

    2009-12-01

    Viral haemorrhagic fevers (VHF) caused by arenaviruses are among the most devastating emerging human diseases. The most important pathogen among the arenaviruses is Lassa virus (LASV), the causative agent of Lassa fever that is endemic to West Africa. On the South American continent, the New World arenavirus Junin virus (JUNV), Machupo (MACV), Guanarito (GTOV), and Sabia virus (SABV) have emerged as causative agents of severe VHFs. Clinical and experimental studies on arenavirus VHF have revealed a crucial role of the endothelium in their pathogenesis. However, in contrast to other VHFs, haemorrhages are not a salient feature of Lassa fever and fatal cases do not show overt destruction of vascular tissue. The functional alteration of the vascular endothelium that precede shock and death in fatal Lassa fever may be due to more subtle direct or indirect effects of the virus on endothelial cells. Haemorrhagic disease manifestations and vascular involvement are more pronounced in the VHF caused by the South American haemorrhagic fever viruses. Recent studies on JUNV revealed perturbation of specific endothelial cell function, including expression of cell adhesion molecules, coagulation factors, and vasoactive mediators as a consequence of productive viral infection. These studies provided first possible links to some of the vascular abnormalities observed in patients, however, their relevance in vivo remains to be investigated.

  12. Aberrant Pulmonary Vascular Growth and Remodeling in Bronchopulmonary Dysplasia

    PubMed Central

    Alvira, Cristina M.

    2016-01-01

    In contrast to many other organs, a significant portion of lung development occurs after birth during alveolarization, thus rendering the lung highly susceptible to injuries that may disrupt this developmental process. Premature birth heightens this susceptibility, with many premature infants developing the chronic lung disease, bronchopulmonary dysplasia (BPD), a disease characterized by arrested alveolarization. Over the past decade, tremendous progress has been made in the elucidation of mechanisms that promote postnatal lung development, including extensive data suggesting that impaired pulmonary angiogenesis contributes to the pathogenesis of BPD. Moreover, in addition to impaired vascular growth, patients with BPD also frequently demonstrate alterations in pulmonary vascular remodeling and tone, increasing the risk for persistent hypoxemia and the development of pulmonary hypertension. In this review, an overview of normal lung development will be presented, and the pathologic features of arrested development observed in BPD will be described, with a specific emphasis on the pulmonary vascular abnormalities. Key pathways that promote normal pulmonary vascular development will be reviewed, and the experimental and clinical evidence demonstrating alterations of these essential pathways in BPD summarized. PMID:27243014

  13. Vascular mechanobiology: endothelial cell responses to fluid shear stress.

    PubMed

    Ando, Joji; Yamamoto, Kimiko

    2009-11-01

    Endothelial cells (ECs) lining blood vessel walls respond to shear stress, a fluid mechanical force generated by flowing blood, and the EC responses play an important role in the homeostasis of the circulatory system. Abnormal EC responses to shear stress impair various vascular functions and lead to vascular diseases, including hypertension, thrombosis, and atherosclerosis. Bioengineering approaches in which cultured ECs are subjected to shear stress in fluid-dynamically designed flow-loading devices have been widely used to analyze EC responses at the cellular and molecular levels. Remarkable progress has been made, and the results have shown that ECs alter their morphology, function, and gene expression in response to shear stress. Shear stress affects immature cells, as well as mature ECs, and promotes differentiation of bone-marrow-derived endothelial progenitor cells and embryonic stem cells into ECs. Much research has been done on shear stress sensing and signal transduction, and their molecular mechanisms are gradually coming to be understood. However, much remains uncertain, and many candidates have been proposed for shear stress sensors. More extensive studies of vascular mechanobiology should increase our understanding of the molecular basis of the blood-flow-mediated control of vascular functions.

  14. Narp knockout mice show normal reactivity to novelty but attenuated recovery from neophobia.

    PubMed

    Blouin, Ashley M; Lee, Jongah J; Tao, Bo; Smith, Dani R; Johnson, Alexander W; Baraban, Jay M; Reti, Irving M

    2013-11-15

    Narp knockout (KO) mice demonstrate cognitive inflexibility and addictive behavior, which are associated with abnormal reactivity to a novel stimulus. To assess reactivity to novelty, we tested Narp KO and wild-type (WT) mice on a neophobia procedure. Both Narp KO and WT mice showed a similar decrease in consumption upon initial exposure to a novel flavor, but Narp KO mice did not increase consumption with subsequent exposures to the novel flavor like the WT mice. Therefore, Narp KO mice do not have abnormal reactivity to novelty but show deficits in adapting behavior to reflect the updated value of a stimulus.

  15. Lymphatic Vessel Abnormalities Arising from Disorders of Ras Signal Transduction

    PubMed Central

    Sevick-Muraca, Eva M.; King, Philip D.

    2013-01-01

    A number of genetic diseases in man have been described in which abnormalities in the development and function of the lymphatic vascular (LV) system are prominent features. The genes that are mutated in these diseases are varied and include genes that encode lymphatic endothelial cell (LEC) growth factor receptors and their ligands and transcription factors that control LEC fate and function. In addition, an increasing number of genes have been identified that encode components of the Ras signal transduction pathway that conveys signals from cell surface receptors to regulate cell growth, proliferation and differentiation. Gene targeting studies performed in mice have confirmed that the LV system is particularly susceptible to perturbations in the Ras pathway. PMID:24183794

  16. Vascular action of polyphenols.

    PubMed

    Ghosh, Dilip; Scheepens, Arjan

    2009-03-01

    Dietary patterns are widely recognised as contributors to cardiovascular and cerebrovascular disease. Endothelial function, the elastic properties of large arteries and the magnitude and timing of wave reflections are important determinants of cardiovascular performance. Several epidemiological studies suggest that the regular consumption of foods and beverages rich in flavonoids is associated with a reduction in the risk of several pathological conditions ranging from hypertension to coronary heart disease, stroke and dementia. The impairment of endothelial function is directly related to ageing and an association between decreased cerebral perfusion and dementia has been shown to exist. Cerebral blood flow (CBF) must be maintained to ensure a constant delivery of oxygen and glucose as well as the removal of waste products. Increasing blood flow is one potential way for improving brain function and the prospect for increasing CBF with dietary polyphenols is extremely promising. The major polyphenols shown to have some of these effects in humans are primarily from cocoa, wine, grape seed, berries, tea, tomatoes (polyphenolics and nonpolyphenolics), soy and pomegranate. There has been a significant paradigm shift in polyphenol research during the last decade. This review summarises our current knowledge in this area and points the way for the development of new types of functional foods targeted to brain health through improving vascular health.

  17. Constructal vascularized structures

    NASA Astrophysics Data System (ADS)

    Cetkin, Erdal

    2015-06-01

    Smart features such as self-healing and selfcooling require bathing the entire volume with a coolant or/and healing agent. Bathing the entire volume is an example of point to area (or volume) flows. Point to area flows cover all the distributing and collecting kinds of flows, i.e. inhaling and exhaling, mining, river deltas, energy distribution, distribution of products on the landscape and so on. The flow resistances of a point to area flow can be decreased by changing the design with the guidance of the constructal law, which is the law of the design evolution in time. In this paper, how the flow resistances (heat, fluid and stress) can be decreased by using the constructal law is shown with examples. First, the validity of two assumptions is surveyed: using temperature independent Hess-Murray rule and using constant diameter ducts where the duct discharges fluid along its edge. Then, point to area types of flows are explained by illustrating the results of two examples: fluid networks and heating an area. Last, how the structures should be vascularized for cooling and mechanical strength is documented. This paper shows that flow resistances can be decreased by morphing the shape freely without any restrictions or generic algorithms.

  18. Haemolysis and abnormal haemorheology in sickle cell anaemia.

    PubMed

    Connes, Philippe; Lamarre, Yann; Waltz, Xavier; Ballas, Samir K; Lemonne, Nathalie; Etienne-Julan, Maryse; Hue, Olivier; Hardy-Dessources, Marie-Dominique; Romana, Marc

    2014-05-01

    Although pulmonary hypertension, leg ulcers, priapism, stroke and glomerulopathy in sickle cell anaemia (SCA) result from the adverse effects of chronic haemolysis on vascular function (haemolytic phenotype), osteonecrosis, acute chest syndrome and painful vaso-occlusive crises are caused by abnormal vascular cell adhesion and increased blood viscosity (viscosity-vaso-occlusion phenotype). However, this model with two sub-phenotypes does not take into account the haemorheological dimension. We tested the relationships between the biological parameters reflecting the haemolytic rate (haemolytic component) and red blood cell (RBC) rheological characteristics in 97 adults with SCA. No significant difference in the proportion of patients with low or high haemolytic component in the low and high blood viscosity groups was observed. The RBC elongation index (i.e. deformability) was negatively correlated with the haemolytic component. The RBC aggregates strength (i.e. RBC aggregates robustness) was negatively correlated with RBC elongation index. Sickle RBCs with high density had lower elongation index and higher aggregates strength. In conclusion, (i) the 'haemolytic' phenotype is characterized by decreased RBC deformability and increased RBC aggregates strength and (ii) the viscosity-vaso-occlusive phenotype is characterized by increased RBC deformability but not always by increased blood viscosity. α-thalassaemia modulates the haemorheological properties but other factors seem to be involved.

  19. [The characteristics of vascular psychoses in the residents of Chernivtsi Province].

    PubMed

    Rusina, S M

    1998-01-01

    Vascular affections of the brain remain a formidable psychiatric challenge nowadays. According to WHO reports cerebrovascular disorders constitute one of the three chief causes of mortality in the population of the economically developed countries of the world. The most important cause of vascular psychoses is considered to be atherosclerosis and hypertensive disease. Today vascular psychoses have become a most common type of abnormal mental states in young adults (greater then 30-40 years old). The studies made have yielded evidence in support of the psychoses morbidity to be dependent upon particular season of year as well as on the climatic features of the locality. Natural factors have been found out to affect the prevalence of vascular psychoses in Chernivtsi Province. The findings obtained suggest to us a substantial prevalence of atherosclerotic and hypertensive psychoses in the plains-men living under conditions of a mild climate.

  20. 3D numerical study of tumor microenvironmental flow in response to vascular-disrupting treatments.

    PubMed

    Wu, Jie; Cai, Yan; Xu, Shixiong; Longs, Quan; Ding, Zurong; Dong, Cheng

    2012-06-01

    The effects of vascular-disrupting treatments on normalization of tumor microvasculature and its microenvironmental flow were investigated, by mathematical modeling and numerical simulation of tumor vascular-disrupting and tumor haemodynamics. Four disrupting approaches were designed according to the abnormal characteristics of tumor microvasculature compared with the normal one. The results predict that the vascular-disrupting therapies could improve tumor microenvironment, eliminate drug barrier and inhibit metastasis of tumor cells to some extent. Disrupting certain types of vessels may get better effects. In this study, the flow condition on the networks with "vascular-disrupting according to flowrate" is the best comparing with the other three groups, and disrupting vessels of lower maturity could effectively enhance fluid transport across vasculature into interstitial space.

  1. Pulmonary vascular complications in portal hypertension and liver disease: a concise review.

    PubMed

    Porres-Aguilar, M; Gallegos-Orozco, J F; Garcia, H; Aguirre, J; Macias-Rodriguez, R U; Torre-Delgadillo, A

    2013-01-01

    Chronic liver disease and/or portal hypertension may be associated with one of the two pulmonary vascular complications: portopulmonary hypertension and hepatopulmonary syndrome. These pulmonary vascular disorders are notoriously underdiagnosed; however, they have a substantial negative impact on survival and require special attention in order to understand their diagnostic approach and to select the best therapeutic options. Portopulmonary hypertension results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. On the other hand, abnormal intrapulmonary vascular dilations, profound hypoxemia, and a wide alveolar-arterial gradient are the hallmarks of the hepatopulmonary syndrome, resulting in difficult-to-treat hypoxemia. The aim of this review is to summarize the latest pathophysiologic concepts, diagnostic approach, therapy, and prognosis of portopulmonary hypertension and hepatopulmonary syndrome, as well as to discuss the role of liver transplantation as a definitive therapy in selected patients with these conditions.

  2. Vascular access today

    PubMed Central

    Pantelias, Konstantinos; Grapsa, Eirini

    2012-01-01

    The number of patients with chronic kidney disease requiring renal replacement therapy has increased worldwide. The most common replacement therapy is hemodialysis (HD). Vascular access (VA) has a key role for successful treatment. Despite the advances that have taken place in the field of the HD procedure, few things have changed with regards to VA in recent years. Arteriovenous fistula (AVF), polytetrafluoroethylene graft and the cuffed double lumen silicone catheter are the most common used for VA. In the long term, a number of complications may present and more than one VA is needed during the HD life. The most common complications for all of VA types are thrombosis, bleeding and infection, the most common cause of morbidity in these patients. It has been estimated that VA dysfunction is responsible for 20% of all hospitalizations. The annual cost of placing and looking after dialysis VA in the United States exceeds 1 billion dollars per year. A good functional access is also vital in order to deliver adequate HD therapy. It seems that the native AVF that Brescia and Cimino described in 1966 still remains the first choice for VA. The native forearm AVFs have the longest survival and require the fewest interventions. For this reason, the forearm AVF is the first choice, followed by the upper-arm AVF, the arteriovenous graft and the cuffed central venous catheter is the final choice. In conclusion, VA remains the most important issue for patients on HD and despite the technical improvements, a number of problems and complications have to be resolved. PMID:24175244

  3. Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage

    PubMed Central

    Nigro, Cecilia; Leone, Alessia; Raciti, Gregory Alexander; Longo, Michele; Mirra, Paola; Formisano, Pietro; Beguinot, Francesco; Miele, Claudia

    2017-01-01

    The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs. MGO and its advanced glycated end products (AGEs) are associated with age-related diseases including diabetes, vascular dysfunction and neurodegeneration. Endothelial dysfunction is the first step in the initiation, progression and clinical outcome of vascular complications, such as retinopathy, nephropathy, impaired wound healing and macroangiopathy. Because of these considerations, studies have been centered on understanding the molecular basis of endothelial dysfunction in diabetes, unveiling a central role of MGO-Glo1 imbalance in the onset of vascular complications. This review focuses on the current understanding of MGO accumulation and Glo1 activity in diabetes, and their contribution on the impairment of endothelial function leading to diabetes-associated vascular damage. PMID:28106778

  4. The role of adiponectin in human vascular physiology.

    PubMed

    Vaiopoulos, Aristeidis G; Marinou, Kyriakoula; Christodoulides, Constantinos; Koutsilieris, Michael

    2012-03-08

    Adiponectin (ApN) is an adipose tissue-derived hormone which is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology via actions on a broad spectrum of target organs including liver, skeletal muscle, and vascular endothelium. Besides possessing insulin sensitizing and anti-inflammatory properties ApN also exerts a pivotal role in vascular protection through activation of multiple intracellular signaling cascades. Enhancement of nitric oxide generation and attenuation of reactive oxygen species production in endothelial cells along with reduced vascular smooth muscle cell proliferation and migration constitute some of ApN's vasoprotective actions. Additionally, recent data indicate that ApN has direct myocardio-protective effects. Decreased plasma ApN levels are implicated in the pathogenesis of the metabolic syndrome and atherosclerosis and may serve as a diagnostic and prognostic biomarker as well as a rational pharmaco-therapeutic target to treat these disorders. This review article summarizes recent work on the cardiovascular actions of ApN.

  5. Sympathetic vascular transduction is augmented in young normotensive blacks

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.

  6. Association between Bacterial Infection and Peripheral Vascular Disease: A Review

    PubMed Central

    Budzyński, Jacek; Wiśniewska, Joanna; Ciecierski, Marek; Kędzia, Anna

    2015-01-01

    There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti-pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints. PMID:26900306

  7. Cerebral ultrasound abnormalities in preterm infants caused by late-onset sepsis

    PubMed Central

    van den Dungen, F. A. M.; Vermeulen, R. J.; van Weissenbruch, M. M.

    2017-01-01

    Introduction This study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams. Methods The prospective study (“INFANT study”) included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities. Results Eighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found. Conclusion No differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities. PMID:28301503

  8. Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): A Case Report

    PubMed Central

    Hudson, Lauren E.; Mendoza, Pia R.; Yan, Jiong; Grossniklaus, Hans E.

    2017-01-01

    Purpose To report the clinical and histopathological findings of a reactive retinal astrocytic tumor (RRAT) that progressed to massive retinal gliosis. Observations The patient presented with an elevated, white-yellow retinal mass and extensive retinal exudation in the left eye. Progressive enlargement of the mass and proliferative vitreoretinopathy eventually led to phthisis bulbi and enucleation. Histologically, the mass showed a predominant astrocytic component with intense glial fibrillary acidic protein staining, hyperplasia, fibrous metaplasia, and osseous metaplasia of the retinal pigment epithelium. The Ki-67 proliferative index was <5%, and few scattered vascular channels were observed. Conclusions and Importance These findings show that this tumor is the result of a reactive glial process rather than of neoplastic vascular proliferation. Massive retinal gliosis probably represents the advanced stage of RRAT.

  9. Electrocardiographic abnormalities in patients with Lassa fever.

    PubMed

    Cummins, D; Bennett, D; Fisher-Hoch, S P; Farrar, B; McCormick, J B

    1989-10-01

    Electrocardiograms from 32 patients with acute Lassa fever were abnormal in over 70% of cases. The changes noted included non-specific ST-segment and T-wave abnormalities, ST-segment elevation, generalized low-voltage complexes, and changes reflecting electrolyte disturbance. None of the abnormalities correlated with clinical severity of infection, serum transaminase levels, or eventual outcome. ECG changes are common in Lassa fever, but usually unassociated with clinical manifestations of myocarditis.

  10. [Renal abnormalities in ankylosing spondylitis].

    PubMed

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease.

  11. Abnormal band of lateral meniscus.

    PubMed

    Giordano, Brian; Goldblatt, John

    2009-01-01

    This article describes a case of an "abnormal band" of the lateral meniscus, extending from the posterior horn of the true lateral meniscus to its antero-mid portion, observed during arthroscopy in a 45-year-old white man of Bosnian descent. The periphery of the aberrant lateral meniscus was freely mobile, and not connected to the underlying true lateral meniscus. Preoperative physical examination findings were consistent with medial-sided meniscal pathology only; however, evidence of an anomalous lateral meniscus was seen with magnetic resonance imaging. This anatomical pattern is rare and has been reported in the literature only once, in a report of 2 Asian patients. This article illustrates an anatomical variant of the lateral meniscus in a non-Asian patient with a clinical presentation that has not been previously described. In addition to the case report, the article presents a comprehensive review of the existing body of literature on anomalous lateral meniscus patterns. We believe that the definitions of the types of aberrant meniscus can be clarified to establish improved accuracy in reporting.

  12. Biochemical abnormalities in Pearson syndrome.

    PubMed

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders.

  13. What is vascular dementia?

    PubMed

    Kurz, A F

    2001-05-01

    Cerebrovascular disease (CVD) and dementia frequently coexist in elderly patients. The question of whether the CVD causes the dementia depends on how 'dementia' is defined. Traditional definitions specified that dementia involved a decline in intellectual ability as a core feature. However, revised definitions have since stipulated two key elements: 1) a global rather than focal neurobehavioural deficit and 2) impairment in activities of daily living (ADL). When applied to CVD, these latter concepts of dementia raise difficulty: Focal cerebrovascular lesions in the cortex generate location-specific neurobehavioural deficits that are part of the dementia syndrome, but, even in combination, do not represent a global intellectual decline. Most cerebrovascular lesions are associated with physical symptoms that make it difficult to evaluate whether cognitive impairments have an independent impact on ADL. The majority of neurobehavioural symptoms in CVD are caused by small-vessel-type subcortical lesions and are dissimilar to those seen in Alzheimer's disease. There are several pathogenetic mechanisms, however, by which large-vessel or small-vessel CVD can cause global cognitive and intellectual impairments, allowing a diagnosis of vascular dementia (VaD): An accumulation of ischaemic lesions in the cortex may produce global intellectual impairment, particularly if they affect important areas of the brain. Single small infarcts, or haemorrhages in strategic subcortical locations, may interfere with specific circuits connecting the prefrontal cortex to the basal ganglia, or with nonspecific thalamocortical projections. This may generate combinations of executive dysfunction, personality change or apathy, which are associated with hypoperfusion and hypometabolism predominantly in frontal cortical areas. Extensive white matter lesions probably affect cognitive function through a loss of axons, producing a functional disconnection of the cortex. This can manifest as

  14. Contemporary Management of Wartime Vascular Trauma

    DTIC Science & Technology

    2004-06-01

    From the Society for Vascular Surgery Contemporary management of wartime vascular trauma Charles J. Fox, MD,a,b David L. Gillespie, MD,a,b Sean D...injuries. ( J Vasc Surg 2005;41:638-44.)From the time of Hippocrates, the field of vascular surgery has been advanced by the application of lessons...diagnostic and therapeutic approach to the care of the wounded soldier with a vascular injury. From the Department of Surgery , Peripheral Vascular

  15. When is arthritis reactive?

    PubMed Central

    Hamdulay, S S; Glynne, S J; Keat, A

    2006-01-01

    Reactive arthritis is an important cause of lower limb oligoarthritis, mainly in young adults. It is one of the spondyloarthropathy family; it is distinguishable from other forms of inflammatory arthritis by virtue of the distribution of affected sites and the high prevalence of characteristic extra‐articular lesions. Many terms have been used to refer to this and related forms of arthritis leading to some confusion. Reactive arthritis is precipitated by an infection at a distant site and genetic susceptibility is marked by possession of the HLA‐B27 gene, although the mechanism remains uncertain. Diagnosis is a two stage process and requires demonstration of a temporal link with a recognised “trigger” infection. The identification and management of “sexually acquired” and “enteric” forms of reactive arthritis are considered. Putative links with HIV infection are also discussed. The clinical features, approach to investigation, diagnosis, and management of reactive arthritis are reviewed. PMID:16822921

  16. Pathological Analysis of the Ruptured Vascular Wall of Hypoperfusion-induced Abdominal Aortic Aneurysm Animal Model.

    PubMed

    Kugo, Hirona; Zaima, Nobuhiro; Tanaka, Hiroki; Hashimoto, Keisuke; Miyamoto, Chie; Sawaragi, Ayaka; Urano, Tetsumei; Unno, Naoki; Moriyama, Tatsuya

    2017-04-04

    Abdominal aortic aneurysm (AAA) is a vascular disease that results in the gradual dilation of the abdominal aorta and has a high rupture-related mortality rate. However, the mechanism of AAA rupture remains unknown. In our previous study, we established a novel AAA animal model (hypoperfusion-induced AAA rat model) with spontaneous AAA rupture. Using the hypoperfusion-induced AAA rat model, we demonstrated that the abnormal appearance of adipocytes in the vascular wall is associated with AAA rupture. However, pathological analysis of the rupture area has not been performed because it is particularly difficult to identify the rupture point. In this study, we succeeded in obtaining samples from the rupture point and performed a histological analysis of the ruptured area in the vascular wall in the hypoperfusion-induced AAA rat model. Adipocytes were observed along the AAA-ruptured area of the vascular wall. In the areas around the adipocytes, macrophage infiltration and protein levels of matrix metalloproteinases 2 and 9 were significantly increased and collagen-positive areas were significantly decreased, as compared with areas without adipocytes. The AAA diameter was correlated with the number of adipocytes in the vascular wall of the hypoperfusion-induced AAA rat model. On the other hand, serum triglyceride levels and serum total cholesterol levels were not correlated with the number of adipocytes in the vascular wall. These results suggest that local adipocyte accumulation in the vascular wall, not serum lipids, has an important role in AAA rupture.

  17. Vascular waveform analysis of flap-feeding vessels using color Doppler ultrasonography.

    PubMed

    Ogino, Akihiro; Onishi, Kiyoshi

    2014-01-01

    We performed vascular waveform analysis of flap-feeding vessels using color Doppler ultrasonography and evaluated the blood flow in the flaps prior to surgery. Vascular waveform analysis was performed in 19 patients. The analyzed parameters included the vascular diameter, flow volume, flow velocity, resistance index, pulsatility index, and acceleration time. The arterial waveform was classified into 5 types based on the partially modified blood flow waveform classification reported by Hirai et al.; in particular, D-1a, D-1b, and D-2 were considered as normal waveforms. They were 4 patients which observed abnormal vascular waveform among 19 patients (D-4 : 1, D-3 : 1, and Poor detect : 2). The case which presented D-4 waveform changed the surgical procedure, and a favorable outcome was achieved. Muscle flap of the case which presented D-3 waveform was partially necrosed. The case which detected blood flow poorly was judged to be the vascular obstruction of the internal thoracic artery. In the evaluation of blood flow in flaps using color Doppler ultrasonography, determination of not only basic blood flow information, such as the vascular distribution and diameter and flow velocity, but also the flow volume, vascular resistance, and arterial waveform is essential to elucidate the hemodynamics of the flap.

  18. Vascular hand-arm vibration syndrome--magnetic resonance angiography.

    PubMed

    Poole, C J M; Cleveland, T J

    2016-01-01

    The diagnosis of vascular hand-arm vibration syndrome (HAVS) requires consistent symptoms, photographic evidence of digital blanching and sufficient exposure to hand-transmitted vibration (HTV; A(8) > 2.5 m/s2). There is no reliable quantitative investigation for distinguishing HAVS from other causes of Raynaud's phenomenon and from normal individuals. Hypothenar and thenar hammer syndromes produce similar symptoms to HAVS but are difficult to diagnose clinically and may be confused with HAVS. Magnetic resonance angiography (MRA) is a safe and minimally invasive method of visualizing blood vessels. Three cases of vascular HAVS are described in which MRA revealed occlusions of the ulnar, radial and superficial palmar arteries. It is proposed that HTV was the cause of these occlusions, rather than blows to the hand unrelated to vibration, the assumed mechanism for the hammer syndromes. All three cases were advised not to expose their hands to HTV despite one of them being at Stockholm vascular stage 2 (early). MRA should be the investigation of choice for stage 2 vascular HAVS or vascular HAVS with unusual features or for a suspected hammer syndrome. The technique is however technically challenging and best done in specialist centres in collaboration with an occupational physician familiar with the examination of HAVS cases. Staging for HAVS should be developed to include anatomical arterial abnormalities as well as symptoms and signs of blanching. Workers with only one artery supplying a hand, or with only one palmar arch, may be at increased risk of progression and therefore should not be exposed to HTV irrespective of their Stockholm stage.

  19. Monitoring cerebrovascular pressure reactivity with rheoencephalography

    NASA Astrophysics Data System (ADS)

    Brady, K. M.; Mytar, J. O.; Kibler, K. K.; Easley, R. B.; Koehler, R. C.; Czosnyka, M.; Smielewski, P.; Zweifel, C.; Bodo, M.; Pearce, F. J.; Armonda, R. A.

    2010-04-01

    Determining optimal perfusion pressure for patients with traumatic brain injury can be accomplished by monitoring the pressure reactivity index, or PRx, which requires an intracranial pressure monitor. We hypothesized that pressure reactivity could be quantified using a rheoencephalography index, or REGx. We measured the REGx and PRx as repetitive, low-frequency linear correlation between arterial blood pressure and intracranial pressure (PRx) or arterial blood pressure and REG pulse amplitude (REGx) in a piglet model of progressive hypotension. We compared the PRx and REGx against a gold standard determination of the lower limit of autoregulation using laser-Doppler measurements of cortical red cell flux. The PRx produced an accurate metric of vascular reactivity in this cohort, with area under the receiver-operator characteristic curves of 0.91. REGx was moderately correlated to the PRx, (Spearman r = 0.63, p < 0.0001; Bland-Altman bias-0.13). The area under the receiver-operator curve for the REGx was 0.86. Disagreement occurred at extremes of hypotension.

  20. Vascular effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fyodorov, Svyatoslav N.; Kopayeva, V. G.; Andreev, J. B.; Ponomarev, Gelii V.; Stranadko, Eugeny P.; Suchin, H. M.

    1996-01-01

    Vascular effect of PDT has been studied in patients with corneal vascularized leucomas (10 patients) and in patients with corneal neovascularized transplant (3 patients). For vascularized leucomas the method of photodynamic therapy consisted of the local injection of dimegin (deiteroporphyrin derivative) into the space of the newly-formed vessels under operating microscope (opton) with the microneedle (diameter 200 microns) and corneal irradiation by the operating microscope light. For corneal neovascularized transplant the injection of photogem (hematoporphyrin derivative) intravenously were made with subsequent irradiation by light of dye laser (5 hours after the injection) with light density of 150 mW/cm2 for 15 minutes. In all the cases at the time of irradiation the aggregated blood flow was appeared, followed by blood flow stasis. In postoperative period the vessels disintegrated into separate fragments which disappeared completely after 10 - 15 days. Taking into account the data of light microscopy, the disappearance of the vessels took place as a result of the vascular endothelium lisis along the vascular walls. Neovascularized cornea and newly-formed vessels in tumor stroms have much in common. The vessel alterations study presented in this paper, may serve to specify the mechanism of photodynamic destruction of neovascularized stroma of tumor.

  1. Pediatric Interventional Radiology: Vascular Interventions.

    PubMed

    Kandasamy, Devasenathipathy; Gamanagatti, Shivanand; Gupta, Arun Kumar

    2016-07-01

    Pediatric interventional radiology (PIR) comprises a range of minimally invasive diagnostic and therapeutic procedures that are performed using image guidance. PIR has emerged as an essential adjunct to various surgical and medical conditions. Over the years, technology has undergone dramatic and continuous evolution, making this speciality grow. In this review, the authors will discuss various vascular interventional procedures undertaken in pediatric patients. It is challenging for the interventional radiologist to accomplish a successful interventional procedure. There are many vascular interventional radiology procedures which are being performed and have changed the way the diseases are managed. Some of the procedures are life saving and have become the treatment of choice in those patients. The future is indeed bright for the practice and practitioners of pediatric vascular and non-vascular interventions. As more and more of the procedures that are currently being performed in adults get gradually adapted for use in the pediatric population, it may be possible to perform safe and successful interventions in many of the pediatric vascular lesions that are otherwise being referred for surgery.

  2. Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain.

    PubMed

    Arnold, Thomas D; Niaudet, Colin; Pang, Mei-Fong; Siegenthaler, Julie; Gaengel, Konstantin; Jung, Bongnam; Ferrero, Gina M; Mukouyama, Yoh-suke; Fuxe, Jonas; Akhurst, Rosemary; Betsholtz, Christer; Sheppard, Dean; Reichardt, Louis F

    2014-12-01

    Vascular development of the central nervous system and blood-brain barrier (BBB) induction are closely linked processes. The role of factors that promote endothelial sprouting and vascular leak, such as vascular endothelial growth factor A, are well described, but the factors that suppress angiogenic sprouting and their impact on the BBB are poorly understood. Here, we show that integrin αVβ8 activates angiosuppressive TGFβ gradients in the brain, which inhibit endothelial cell sprouting. Loss of αVβ8 in the brain or downstream TGFβ1-TGFBR2-ALK5-Smad3 signaling in endothelial cells increases vascular sprouting, branching and proliferation, leading to vascular dysplasia and hemorrhage. Importantly, BBB function in Itgb8 mutants is intact during early stages of vascular dysgenesis before hemorrhage. By contrast, Pdgfb(ret/ret) mice, which exhibit severe BBB disruption and vascular leak due to pericyte deficiency, have comparatively normal vascular morphogenesis and do not exhibit brain hemorrhage. Our data therefore suggest that abnormal vascular sprouting and patterning, not BBB dysfunction, underlie developmental cerebral hemorrhage.

  3. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  4. An Abnormal Psychology Community Based Interview Assignment

    ERIC Educational Resources Information Center

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  5. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  6. Nail abnormalities in patients with vitiligo*

    PubMed Central

    Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa

    2016-01-01

    Background Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. Methods This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Results Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Conclusions Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study. PMID:27579738

  7. Reactive Power Compensator.

    DOEpatents

    El-Sharkawi, M.A.; Venkata, S.S.; Chen, M.; Andexler, G.; Huang, T.

    1992-07-28

    A system and method for determining and providing reactive power compensation for an inductive load. A reactive power compensator (50,50') monitors the voltage and current flowing through each of three distribution lines (52a, 52b, 52c), which are supplying three-phase power to one or more inductive loads. Using signals indicative of the current on each of these lines when the voltage waveform on the line crosses zero, the reactive power compensator determines a reactive power compensator capacitance that must be connected to the lines to maintain a desired VAR level, power factor, or line voltage. Alternatively, an operator can manually select a specific capacitance for connection to each line, or the capacitance can be selected based on a time schedule. The reactive power compensator produces control signals, which are coupled through optical fibers (102/106) to a switch driver (110, 110') to select specific compensation capacitors (112) for connections to each line. The switch driver develops triggering signals that are supplied to a plurality of series-connected solid state switches (350), which control charge current in one direction in respect to ground for each compensation capacitor. During each cycle, current flows from ground to charge the capacitors as the voltage on the line begins to go negative from its positive peak value. The triggering signals are applied to gate the solid state switches into a conducting state when the potential on the lines and on the capacitors reaches a negative peak value, thereby minimizing both the potential difference and across the charge current through the switches when they begin to conduct. Any harmonic distortion on the potential and current carried by the lines is filtered out from the current and potential signals used by the reactive power compensator so that it does not affect the determination of the required reactive compensation. 26 figs.

  8. Reactive power compensator

    DOEpatents

    El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.; Chen, Mingliang; Andexler, George; Huang, Tony

    1992-01-01

    A system and method for determining and providing reactive power compensation for an inductive load. A reactive power compensator (50,50') monitors the voltage and current flowing through each of three distribution lines (52a, 52b, 52c), which are supplying three-phase power to one or more inductive loads. Using signals indicative of the current on each of these lines when the voltage waveform on the line crosses zero, the reactive power compensator determines a reactive power compensator capacitance that must be connected to the lines to maintain a desired VAR level, power factor, or line voltage. Alternatively, an operator can manually select a specific capacitance for connection to each line, or the capacitance can be selected based on a time schedule. The reactive power compensator produces control signals, which are coupled through optical fibers (102/106) to a switch driver (110, 110') to select specific compensation capacitors (112) for connections to each line. The switch driver develops triggering signals that are supplied to a plurality of series-connected solid state switches (350), which control charge current in one direction in respect to ground for each compensation capacitor. During each cycle, current flows from ground to charge the capacitors as the voltage on the line begins to go negative from its positive peak value. The triggering signals are applied to gate the solid state switches into a conducting state when the potential on the lines and on the capacitors reaches a negative peak value, thereby minimizing both the potential difference and across the charge current through the switches when they begin to conduct. Any harmonic distortion on the potential and current carried by the lines is filtered out from the current and potential signals used by the reactive power compensator so that it does not affect the determination of the required reactive compensation.

  9. Pulpal vascular changes in inflammation.

    PubMed

    Takahashi, K

    1992-01-01

    Changes in pulpal vessels in experimentally induced acute and chronic pulpitis in dog tooth were investigated using corrosive resin casts and scanning electron microscopic examination. Following a cavity preparation without water spray, increased permeability of blood vessels occurred in the primary stage of acute pulpitis. This was evidenced by the extravasation of resin from the vessel. This phenomenon was found initially in the venular network as well as in the capillary network located under the dentin. The morphological change was minimal in the vascular network underneath the cavity. This is in contrast to an expanded and tortuous vascular network representing an ulceration which was found around an abscess in chronic pulpitis. Furthermore, formation of vascular loops and AVAlc close to the inflamed region may represent a protective change in the pulp against inflammation.

  10. Vascular aging and geriatric patient.

    PubMed

    Nicita-Mauro, V; Maltese, G; Nicita-Mauro, C; Basile, G

    2007-08-01

    Advancing age is associated with changes in structure and function of different segments of the vascular system and is the dominant risk factor for cardiovascular diseases. The oxidative stress represents a key event of vascular aging, mainly characterized by endothelium dysfunction and reduced arterial elasticity. Age-related changes include intimal and medial thickening, arterial calcification, increased deposition of matrix substances, thus leading to a reduced compliance and increased wall stiffness, that significantly contributes to an increase in systolic blood pressure. Frail elderly patients, because of their complex clinical presentations and needs, require a special approach: the comprehensive geriatric assessment, a multidimensional process intended to determine medical, psychosocial and functional capabilities and problems in order to develop a plan for treatment and continued care. All physicians, and geriatricians in particular, must, therefore, educate their patients to healthy lifestyle to prevent or delay vascular aging, cardiovascular diseases, and to maintain a good quality of life and increase life expectancy.

  11. Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis.

    PubMed

    Lund, Amie K; Knuckles, Travis L; Obot Akata, Chrys; Shohet, Ralph; McDonald, Jacob D; Gigliotti, Andrew; Seagrave, Jean Clare; Campen, Matthew J

    2007-02-01

    Epidemiological evidence indicates that environmental air pollutants are positively associated with the development of chronic vascular disease; however, the mechanisms involved have not been fully elucidated. In the present study we examined molecular pathways associated with chronic vascular disease in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice, including markers of vascular remodeling and oxidative stress, in response to exposure to the ubiquitous environmental pollutant, gasoline engine emissions. ApoE(-/-) mice, on a high-fat diet, were exposed by inhalation to either filtered air; 8, 40, or 60 mug/m(3) particulate matter whole exhaust; or filtered exhaust with gases matching the 60-mug/m(3) concentration, for 7 weeks. Aortas and plasma were collected and assayed for changes in histochemical markers, real-time reverse transcriptase-polymerase chain reaction, and indicators of oxidative damage. Inhalational exposure to gasoline engine emissions resulted in increased aortic mRNA expression of matrix metalloproteinase-3 (MMP-3), MMP-7, and MMP-9, tissue inhibitor of metalloproteinases-2, endothelin-1 and heme oxygenase-1 in ApoE(-/-) mice; increased aortic MMP-9 protein levels were confirmed through immunohistochemistry. Elevated reactive oxygen species were also observed in arteries from exposed animals, despite absence of plasma markers. Similar findings were also observed in the aortas of ApoE(-/-) mice exposed to particle-filtered atmosphere, implicating the gaseous components of the whole exhaust in mediating the expression of markers associated with the vasculopathy. These findings demonstrate that exposure to gasoline engine emissions results in the transcriptional upregulation of factors associated with vascular remodeling, as well as increased markers of vascular oxidative stress, which may contribute to the progression of atherosclerosis and reduced stability of vulnerable plaques.

  12. Crucial Role of Hyaluronan in Neointimal Formation after Vascular Injury

    PubMed Central

    Kashima, Yuichiro; Takahashi, Masafumi; Shiba, Yuji; Itano, Naoki; Izawa, Atsushi; Koyama, Jun; Nakayama, Jun; Taniguchi, Shun'ichiro; Kimata, Koji; Ikeda, Uichi

    2013-01-01

    Background Hyaluronan (HA) is a primary component of the extracellular matrix of cells, and it is involved in the pathogenesis of atherosclerosis. The purpose of this study was to investigate the role of HA in neointimal formation after vascular injury and determine its tissue-specific role in vascular smooth muscle cells (VSMCs) by using a cre-lox conditional transgenic (cTg) strategy. Methods and Results HA was found to be expressed in neointimal lesions in humans with atherosclerosis and after wire-mediated vascular injury in mice. Inhibition of HA synthesis using 4-methylumbelliferone markedly inhibited neointimal formation after injury. In vitro experiments revealed that low-molecular-weight HA (LMW-HA) induced VSMC activation, including migration, proliferation, and production of inflammatory cytokines, and reactive oxygen species (ROS). The migration and proliferation of VSMCs were mediated by the CD44/RhoA and CD44/ERK1/2 pathways, respectively. Because HA synthase 2 (HAS2) is predominantly expressed in injured arteries, we generated cTg mice that overexpress the murine HAS2 gene specifically in VSMCs (cHAS2/CreSM22α mice) and showed that HA overexpression markedly enhanced neointimal formation after cuff-mediated vascular injury. Further, HA-overexpressing VSMCs isolated from cHAS2/CreSM22α mice showed augmented migration, proliferation, and production of inflammatory cytokines and ROS. Conclusion VSMC-derived HA promotes neointimal formation after vascular injury, and HA may be a potential therapeutic target for cardiovascular disease. PMID:23484050

  13. Can transcutaneous recordings detect gastric electrical abnormalities?

    PubMed Central

    Familoni, B O; Bowes, K L; Kingma, Y J; Cote, K R

    1991-01-01

    The ability of transcutaneous recordings of gastric electrical activity to detect gastric electrical abnormalities was determined by simultaneous measurements of gastric electrical activity with surgically implanted serosal electrodes and cutaneous electrodes in six patients undergoing abdominal operations. Transient abnormalities in gastric electrical activity were seen in five of the six patients during the postoperative period. Recognition of normal gastric electrical activity by visual analysis was possible 67% of the time and with computer analysis 95% of the time. Ninety four per cent of abnormalities in frequency were detected by visual analysis and 93.7% by computer analysis. Abnormalities involving a loss of coupling, however, were not recognised by transcutaneous recordings. Transcutaneous recordings of gastric electrical activity assessed by computer analysis can usually recognise normal gastric electrical activity and tachygastria. Current techniques, however, are unable to detect abnormalities in electrical coupling. PMID:1864531

  14. Standardized Definitions for Hemodialysis Vascular Access

    PubMed Central

    Lee, Timmy; Mokrzycki, Michele; Moist, Louise; Maya, Ivan; Vazquez, Miguel; Lok, Charmaine

    2014-01-01

    Vascular access dysfunction is one of the leading causes of morbidity and mortality among end-stage renal disease patients 1,2. Vascular access dysfunction exists in all 3 types of available accesses: arteriovenous fistulas, arteriovenous grafts, and tunneled catheters. In order to improve clinical research and outcomes in hemodialysis access dysfunction, the development of a multidisciplinary network of collaborative investigators with various areas of expertise, and common standards for terminology and classification in all vascular access types is required. The North American Vascular Access Consortium (NAVAC) is a newly formed multidisciplinary and multicenter network of experts in the area of hemodialysis vascular access, who include nephrologists and interventional nephrologists from the United States and Canada with: (1) a primary clinical and research focus in hemodialysis vascular access dysfunction, (2) national and internationally recognized experts in vascular access, and (3) a history of productivity measured by peer-reviewed publications and funding among members of this consortium. The consortium’s mission is to improve the quality and efficiency in vascular access research, and impact the research in the area of hemodialysis vascular access by conducting observational studies and randomized controlled trials. The purpose of the consortium’s initial manuscript is to provide working and standard vascular access definitions relating to (1) epidemiology, (2) vascular access function, (3) vascular access patency, and (4) complications in vascular accesses relating to each of the vascular access types. PMID:21906166

  15. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species.

    PubMed

    Amaral, Sandra; Oliveira, Paulo J; Ramalho-Santos, João

    2008-02-01

    Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested

  16. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Vascular calcification in chronic kidney disease-mineral and bone disorder (CKD-MBD)].

    PubMed

    Omata, Momoyo; Fukagawa, Masafumi; Kakuta, Takatoshi

    2015-05-01

    Chronic kidney disease-mineral and bone disorder (CKD-MBD), is sequential pathophysiology that starts in the very early stages of CKD. Three major aspects of CKD-MBD are laboratory abnormalities, bone abnormalities and vascular calcification. In dialysis patients, the prevalence of death due to cardiovascular disease accounts for more than 40% of all-cause mortality. Therefore, arteriosclerosis with vascular calcification may be an important pathophysiological mechanism in the development of cardiovascular disease. Vascular calcification is known to be an important risk factor influencing mortality in CKD patients. A number of studies have suggested a close association between serum FGF23 concentration and the risks of mortality, cardiovascular disease vascular calcification as well as CKD progression. Renal insufficiency leads to decline in klotho level and impaired phosphate excretion. However serum phosphate levels are maintained in the normal range by up regulation of FGF23 and PTH in early CKD stage. Early treatment intervention is necessary to improve the prognosis of the CKD patient.

  17. Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

    PubMed Central

    Hanson, Daniel R; Gottesman, Irving I

    2005-01-01

    Background Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. Discussion A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune

  18. Vascular Injury in Orthopedic Trauma.

    PubMed

    Mavrogenis, Andreas F; Panagopoulos, George N; Kokkalis, Zinon T; Koulouvaris, Panayiotis; Megaloikonomos, Panayiotis D; Igoumenou, Vasilios; Mantas, George; Moulakakis, Konstantinos G; Sfyroeras, George S; Lazaris, Andreas; Soucacos, Panayotis N

    2016-07-01

    Vascular injury in orthopedic trauma is challenging. The risk to life and limb can be high, and clinical signs initially can be subtle. Recognition and management should be a critical skill for every orthopedic surgeon. There are 5 types of vascular injury: intimal injury (flaps, disruptions, or subintimal/intramural hematomas), complete wall defects with pseudoaneurysms or hemorrhage, complete transections with hemorrhage or occlusion, arteriovenous fistulas, and spasm. Intimal defects and subintimal hematomas with possible secondary occlusion are most commonly associated with blunt trauma, whereas wall defects, complete transections, and arteriovenous fistulas usually occur with penetrating trauma. Spasm can occur after either blunt or penetrating trauma to an extremity and is more common in young patients. Clinical presentation of vascular injury may not be straightforward. Physical examination can be misleading or initially unimpressive; a normal pulse examination may be present in 5% to 15% of patients with vascular injury. Detection and treatment of vascular injuries should take place within the context of the overall resuscitation of the patient according to the established principles of the Advanced Trauma Life Support (ATLS) protocols. Advances in the field, made mostly during times of war, have made limb salvage the rule rather than the exception. Teamwork, familiarity with the often subtle signs of vascular injuries, a high index of suspicion, effective communication, appropriate use of imaging modalities, sound knowledge of relevant technique, and sequence of surgical repairs are among the essential factors that will lead to a successful outcome. This article provides a comprehensive literature review on a subject that generates significant controversy and confusion among clinicians involved in the care of trauma patients. [Orthopedics. 2016; 39(4):249-259.].

  19. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  20. 123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

    PubMed Central

    Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

    2015-01-01

    Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on Da

  1. Megakaryocytes, malignancy and bone marrow vascular niches.

    PubMed

    Psaila, B; Lyden, D; Roberts, I

    2012-02-01

    Dynamic interactions between hematopoietic cells and their specialized bone marrow microenvironments, namely the vascular and osteoblastic 'niches', regulate hematopoiesis. The vascular niche is conducive for thrombopoiesis and megakaryocytes may, in turn, regulate the vascular niche, especially in supporting vascular and hematopoietic regeneration following irradiation or chemotherapy. A role for platelets in tumor growth and metastasis is well established and, more recently, the vascular niche has also been implicated as an area for preferential homing and engraftment of malignant cells. This article aims to provide an overview of the dynamic interactions between cellular and molecular components of the bone marrow vascular niche and the potential role of megakaryocytes in bone marrow malignancy.

  2. Vascular calcification in chronic kidney disease: a clinical review.

    PubMed

    Eddington, Helen; Sinha, Smeeta; Kalra, Philip A

    2009-03-01

    Vascular calcification, which is associated with arterial stiffness, is now known to be an important predictor of cardiovascular and all-cause mortality in patients with renal disease. This calcification starts developing in the early stages of chronic kidney disease (CKD) and is present in over 50% of patients at the time of dialysis commencement. Once calcification is present it continues to progress, though some medications have been shown to slow this progression. Vascular calcification and bone abnormalities are now both encompassed by the term of CKD-mineral bone disorder and are thought to be part of the same disease process in CKD. Vascular calcification and arterial stiffness have been extensively researched in the renal population and many factors are known to be associated with their presence and progression. This calcification is an important factor to be considered in the management of the renal patient but there are different methods available for its measurement. These details will be discussed further in this review along with evidence available for management of this important complication of renal disease.

  3. Risk factors and prevention of vascular complications in polycythemia vera.

    PubMed

    Barbui, T; Finazzi, G

    1997-01-01

    Risk factors for vascular complications in polycythemia vera (PV) include laboratory and clinical findings. Among laboratory values, the hematocrit has been clearly associated with thrombosis, particularly in the cerebral circulation. Platelet count is a possible but not yet clearly established predictor of vascular complications. Platelet function tests are of little help in prognostic evaluation because most attempts to correlate these abnormalities with clinical events have been disappointing. Clinical predictors of thrombosis include increasing age and a previous history of vascular events. Identifying risk factors for thrombosis is important to initiate therapy. Phlebotomy is associated with an increased incidence of thrombosis in the first 3 to 5 years, whereas chemotherapy may induce a higher risk of secondary malignancies after 7 to 10 years of follow-up. New cytoreductive drugs virtually devoid of mutagenic risk include interferon-alpha and anagrelide, but their role in reducing thrombotic complications remains to be demonstrated. Antithrombotic drugs, such as aspirin, are frequently used in PV, despite doubts regarding safety and efficacy. Two recent studies from the Gruppo Italiano Studio Policitemia Vera (GISP) assessed the rate of major thrombosis as well as the tolerability of low-dose aspirin in PV patients. These investigations created a favorable scenario for launching a European collaborative clinical trial (ECLAP study) aimed at testing the efficacy of low-dose aspirin in preventing thrombosis and prolonging survival in patients with PV.

  4. IR imaging of blood circulation of patients with vascular disease

    NASA Astrophysics Data System (ADS)

    Wang, Hsin; Wade, Dwight R., Jr.; Kam, Jack

    2004-04-01

    We conducted a preliminary IR imaging study of blood circulation in patients with peripheral vascular diseases. Abnormal blood flow is common in older adults, especially those with elevated blood lipids, diabetes, hypertension, and a history of smoking. All of these conditions have a high prevalence in our population, often with more than one condition in the same individual. The differences in blood flow is revealed by temperature differences in areas of the extremities as well as other regions of the body. However, what is needed is an imaging technique that is relatively inexpensive and can reveal the blood flow in real time. The IR imaging can show detailed venous system and small tempearture changes associated with blood flow. Six patients with vascular diseases were tested in a clinic set up. Their legs and feet were imaged. We observed large temperature differences (cooling of more than 10° C) at the foot, especially toes. More valuable information were obtained from the temperature distribution maps. IR thermography is potentially a very valuable tool for medical application, especially for vascular diseases.

  5. Vascular and Autonomic Dysregulation in Primary Open-Angle Glaucoma

    PubMed Central

    Pasquale, Louis R.

    2015-01-01

    Purpose of the review To discuss whether vascular dysfunction and autonomic dysfunction are related to primary open-angle glaucoma stratified by the intraocular pressure (IOP) level (the high tension glaucoma and normal tension glaucoma subtypes). Recent findings Patients with POAG across the spectrum of IOP exhibit a variety of ocular and non-ocular vascular abnormalities. Interestingly common genetic variation in NOS3 and the CAV1/CAV2 genomic regions, which code for proteins involved in setting vascular tone, are associated with POAG. These markers seem to stratify with POAG subtypes by sex or pattern of initial visual field loss. Overall it is clear that there is also cardiovascular autonomic dysfunction in HTG and NTG but it is unclear if this dysfunction is more common in NTG compared to HTG. Summary Overall POAG is likely a heterogeneous disease but stratifying cases by IOP level associated with initial optic nerve damage may be less useful than using other endophenotype approaches. Embracing the evidence suggesting systemic endothelial and autonomic dysfunction are operative in POAG will help move beyond an IOP-centric view of the disease and facilitate “tearing down the wall” that divides treating physicians and a better understanding of POAG pathogenesis. PMID:26720776

  6. Phenylethynyl terminated reactive oligomer

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor)

    1995-01-01

    A composition of matter having the general structure: ##STR1## (wherein X is F, Cl, or NO.sub.2, and Y is CO, SO.sub.2 or C(CF.sub.3).sub.2) is employed to terminate a nucleophilic reagent, resulting in the exclusive production of phenylethynyl terminated reactive oligomers which display unique thermal characteristics. A reactive diluent having the general structure: ##STR2## (wherein R is any aliphatic or aromatic moiety) is employed to decrease the melt viscosity of a phenylethynyl terminated reactive oligomer and to subsequently react therewith to provide a thermosetting material of enhanced density. These materials have features which make them attractive candidates for use as composite matrices and adhesives.

  7. Interactive chemical reactivity exploration.

    PubMed

    Haag, Moritz P; Vaucher, Alain C; Bosson, Maël; Redon, Stéphane; Reiher, Markus

    2014-10-20

    Elucidating chemical reactivity in complex molecular assemblies of a few hundred atoms is, despite the remarkable progress in quantum chemistry, still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chemical reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mechanical response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which technical difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the samson programming environment.

  8. Thioredoxin in vascular biology: role in hypertension.

    PubMed

    Ebrahimian, Talin; Touyz, Rhian M

    2008-06-01

    The thioredoxin (TRX) system consists of TRX, TRX reductase, and NAD(P)H, and is able to reduce reactive oxygen species (ROS) through interactions with the redox-active center of TRX, which in turn can be reduced by TRX reductase in the presence of NAD(P)H. Among the TRX superfamily is peroxiredoxin (PRX), a family of non-heme peroxidases that catalyzes the reduction of hydroperoxides into water and alcohol. The TRX system is active in the vessel wall and functions either as an important endogenous antioxidant or interacts directly with signaling molecules to influence cell growth, apoptosis, and inflammation. Recent evidence implicates TRX in cardiovascular disease associated with oxidative stress, such as cardiac failure, arrhythmia, ischemia reperfusion injury, and hypertension. Thioredoxin activity is influenced by many mechanisms, including transcription, protein-protein interaction, and post-translational modification. Regulation of TRX in hypertensive models seems to be related to oxidative stress and is tissue- and cell-specific. Depending on the models of hypertension, TRX system could be upregulated or downregulated. The present review focuses on the role of TRX in vascular biology, describing its redox activities and biological properties in the media and endothelium of the vessel wall. In addition, the pathopysiological role of TRX in hypertension and other cardiovascular diseases is addressed.

  9. CT pulmonary angiography of adult pulmonary vascular diseases: Technical considerations and interpretive pitfalls.

    PubMed

    Taslakian, Bedros; Latson, Larry A; Truong, Mylene T; Aaltonen, Eric; Shiau, Maria C; Girvin, Francis; Alpert, Jeffrey B; Wickstrom, Maj; Ko, Jane P

    2016-11-01

    Computed tomography pulmonary angiography (CTPA) has become the primary imaging modality for evaluating the pulmonary arteries. Although pulmonary embolism is the primary indication for CTPA, various pulmonary vascular abnormalities can be detected in adults. Knowledge of these disease entities and understanding technical pitfalls that can occur when performing CTPA are essential to enable accurate diagnosis and allow timely management. This review will cover a spectrum of acquired abnormalities including pulmonary embolism due to thrombus and foreign bodies, primary and metastatic tumor involving the pulmonary arteries, pulmonary hypertension, as well as pulmonary artery aneurysms and stenoses. Additionally, methods to overcome technical pitfalls and interventional treatment options will be addressed.

  10. Onychomycosis in patients with chronic leg ulcer and toenail abnormalities.

    PubMed

    Cabete, Joana; Galhardas, Célia; Apetato, Margarida; Lestre, Sara

    2015-01-01

    Nails have a limited number of reactive patterns to disease. Accordingly, toenail changes of different etiologies may mimic onychomycosis. OBJECTIVE To determine the prevalence of toenail onychomycosis among patients with leg ulcer and toenail abnormalities attending a dermatology clinic. METHODS A cross-sectional study was conducted through the analysis of clinical records and results of mycological examination. RESULTS A total of 81 patients were included, with a median age of 76.0 years. Most ulcers were of venous etiology, followed by those of mixed and arterial pathogenesis. The mycological evaluation confirmed the diagnosis of onychomycosis in 27.2% of the patients. The etiologic agent was a dermatophyte in 59.1% of isolates in nail samples, while Trichophyton interdigitale was the most frequent fungal species (40.9%). CONCLUSIONS Most toenail abnormalities in patients with chronic leg ulcer were not onychomycosis. This study highlights the importance of systematic mycological examination in these patients, in order to avoid overtreatment with systemic antifungals, unnecessary costs and side effects.

  11. Spondylodiscitis after Cervical Nucleoplasty without Any Abnormal Laboratory Findings

    PubMed Central

    Lee, Seung Jun; Choi, Eun Joo

    2013-01-01

    Infective spondylodiscitis is a rare complication that can occur after interventional spinal procedures, of which symptoms are usually back pain and fever. Early diagnosis of infective spondylodiscitis is critical to start antibiotics and to improve prognosis. Laboratory examinations including complet blood cell count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are conventional tools for the early detection of infectious spondylitis. However, we experienced infective spondylodiscitis after cervical nucleoplasty which did not display any laboratory abnormalities, but was diagnosed through an MRI. A patient with cervical disc herniation received nucleoplasty at C5/6 and C6/7. One month later, the patient complained of aggravated pain. There were neither signs of chill nor fever, and the laboratory results appeared normal. However, the MRI findings were compatible with infectious spondylodiscitis at the nucleoplasty site. In conclusion, infectious spondylodiscitis can develop after cervical nucleoplasty without any laboratory abnormalities. Therefore, an MRI should be taken when there is a clinical suspicion for infection in order to not miss complications after interventional procedures, even if the laboratory findings are normal. PMID:23614083

  12. The relationships of vascular plants.

    PubMed Central

    Kenrick, P

    2000-01-01

    Recent phylogenetic research indicates that vascular plants evolved from bryophyte-like ancestors and that this involved extensive modifications to the life cycle. These conclusions are supported by a range of systematic data, including gene sequences, as well as evidence from comparative morphology and the fossil record. Within vascular plants, there is compelling evidence for two major clades, which have been termed lycophytes (clubmosses) and euphyllophytes (seed plants, ferns, horsetails). The implications of recent phylogenetic work are discussed with reference to life cycle evolution and the interpretation of stratigraphic inconsistencies in the early fossil record of land plants. Life cycles are shown to have passed through an isomorphic phase in the early stages of vascular plant evolution. Thus, the gametophyte generation of all living vascular plants is the product of massive morphological reduction. Phylogenetic research corroborates earlier suggestions of a major representational bias in the early fossil record. Mega-fossils document a sequence of appearance of groups that is at odds with that predicted by cladogram topology. It is argued here that the pattern of appearance and diversification of plant megafossils owes more to changing geological conditions than to rapid biological diversification. PMID:10905613

  13. Platelets can enhance vascular permeability.

    PubMed

    Cloutier, Nathalie; Paré, Alexandre; Farndale, Richard W; Schumacher, H Ralph; Nigrovic, Peter A; Lacroix, Steve; Boilard, Eric

    2012-08-09

    Platelets survey blood vessels, searching for endothelial damage and preventing loss of vascular integrity. However, there are circumstances where vascular permeability increases, suggesting that platelets sometimes fail to fulfill their expected function. Human inflammatory arthritis is associated with tissue edema attributed to enhanced permeability of the synovial microvasculature. Murine studies have suggested that such vascular leak facilitates entry of autoantibodies and may thereby promote joint inflammation. Whereas platelets typically help to promote microvascular integrity, we examined the role of platelets in synovial vascular permeability in murine experimental arthritis. Using an in vivo model of autoimmune arthritis, we confirmed the presence of endothelial gaps in inflamed synovium. Surprisingly, permeability in the inflamed joints was abrogated if the platelets were absent. This effect was mediated by platelet serotonin accumulated via the serotonin transporter and could be antagonized using serotonin-specific reuptake inhibitor antidepressants. As opposed to the conventional role of platelets to microvascular leakage, this demonstration that platelets are capable of amplifying and maintaining permeability adds to the rapidly growing list of unexpected functions for platelets.

  14. Peripheral vascular imaging and intervention

    SciTech Connect

    Kim, D. ); Orron, D.E. )

    1990-01-01

    This reference addresses the entire clinical approach to the vascular system from the diagnosis of pathology to surgery or interventional radiological management. All diagnostic imaging modalities currently available are included with specific information on how to interpret various results. It features discussions of the latest therapeutic techniques, including laser angioplasty, intravascular stents, and transluminal embolization.

  15. [Vascular access guidelines for hemodialysis].

    PubMed

    Rodríguez Hernández, J A; González Parra, E; Julián Gutiérrez, J M; Segarra Medrano, A; Almirante, B; Martínez, M T; Arrieta, J; Fernández Rivera, C; Galera, A; Gallego Beuter, J; Górriz, J L; Herrero, J A; López Menchero, R; Ochando, A; Pérez Bañasco, V; Polo, J R; Pueyo, J; Ruiz, Camps I; Segura Iglesias, R

    2005-01-01

    Quality of vascular access (VA) has a remarkable influence in hemodialysis patients outcomes. Dysfunction of VA represents a capital cause of morbi-mortality of these patients as well an increase in economical. Spanish Society of Neprhology, aware of the problem, has decided to carry out a revision of the issue with the aim of providing help in comprehensión and treatment related with VA problems, and achieving an homogenization of practices in three mayor aspects: to increase arteriovenous fistula utilization as first vascular access, to increment vascular access monitoring practice and rationalise central catheters use. We present a consensus document elaborated by a multidisciplinar group composed by nephrologists, vascular surgeons, interventional radiologysts, infectious diseases specialists and nephrological nurses. Along six chapters that cover patient education, creation of VA, care, monitoring, complications and central catheters, we present the state of the art and propose guidelines for the best practice, according different evidence based degrees, with the intention to provide help at the professionals in order to make aproppiate decissions. Several quality standars are also included.

  16. Sleep Physiology, Abnormal States, and Therapeutic Interventions

    PubMed Central

    Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

    2012-01-01

    Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

  17. Congenital abnormalities of the ovine paramesonephric ducts.

    PubMed

    Smith, K C; Long, S E; Parkinson, T J

    1995-01-01

    A 15 month survey of ovine reproductive tracts was undertaken in slaughterhouses in southwest England. A total of 33506 tracts were examined; 23536 from lambs and 9970 from adults. In total, 3.4% of tracts were pregnant and 3.3% exhibited abnormalities. Twenty cases of uterus unicornis, six of uterus didelphys and 11 of segmental aplasia were encountered, such that partial aplasia of the paramesonephric ducts accounted for 3.3% of all abnormalities. Although developmental abnormalities of the ovine female genital system are relatively uncommon, a substantial proportion of these can be accounted for by development defects of the paramesonephric ducts.

  18. [Radionuclide studies of congenital kidney abnormalities].

    PubMed

    Vlakhov, N

    1984-06-01

    Using the potentialities of isotope nephrograms as a screening test a total of 4746 patients suspected of renal abnormalities were examined. The author established pathological deviations in 561 cases (11.8%). During further verification using scintigraphy unsuspected congenital renal abnormalities (aplasia, hypoplasia, dystopia, double kidney, horseshoe kidney, solitary cyst and polycystic renal disease) were found in 46 patients (8.2%). The diagnosis was confirmed at subsequent venous x-ray urography. A conclusion has been made as to the role of comprehensive nephrographic-scintigraphic examination in the diagnosis of congenital renal abnormalities.

  19. Numerically abnormal chromosome constitutions in humans

    SciTech Connect

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  20. Vascular lesions in lupus nephritis.

    PubMed

    Grishman, E; Venkataseshan, V S

    1988-05-01

    Three groups of kidney specimens from patients with systemic lupus erythematosus (SLE) were examined for histologic evidence of vascular lesions in small arteries and arterioles. Group 1 consisted of 24 autopsy kidneys from patients who died before the advent of steroid therapy, and Group 2, of 26 more recent autopsy specimens from patients treated with steroids and/or immunosuppressive drugs. Group 3 comprised 276 renal biopsies. Group 1 showed characteristic subendothelial eosinophilic deposits in small arteries and arterioles of 8 cases; Group 2 showed similar lesions in 5 specimens, while 3 others revealed evidence of resorption of deposits. Deposits were characterized by clumping and were delimited toward the media by a thick basement membrane. Only one case showed necrotizing arteritis resembling polyarteritis nodosa. Group 3 presented vascular deposits in 19 cases and thrombotic microangiopathy in 2. Electron microscopic appearance of some of the deposits is described. Immunofluorescence microscopy showed a mixture of IgG, IgA, and IgM in 7 cases, a finding that was not seen in a group of non-lupus patients with various vascular lesions. Vascular deposits are generally rare in systemic lupus erythematosus, although in autopsies widely scattered involvement of arteries and arterioles was seen in nearly 1/3 of the cases. The deposits were more common in male patients. The evolution of the lesions could be followed through various stages to eventual sclerosis, particularly in patients treated with steroids or immunosuppressants. Some deposits appeared to resolve after treatment. Patients with vascular deposits had more severe glomerular disease and a more serious clinical course. Thrombotic microangiopathy appears to be a secondary phenomenon whose pathogenesis is unknown.

  1. Prognostic value of an abnormal ankle-brachial index in patients receiving drug-eluting stents.

    PubMed

    Ribera, Aida; Ferreira-González, Ignacio; Marsal, Josep Ramón; Cascant, Purificación; Permanyer-Miralda, Gaietà; Abdul-Jawad, Omar; Iñigo-Garcia, Luis Antonio; Guarinos-Oltra, Jordi; Cequier, Angel; Goicolea-Güemez, Leire; García-Del-Blanco, Bruno; Martí, Gerard; García-Dorado, David

    2011-11-01

    Advanced atherosclerotic disease increases the risk of stent thrombosis after drug-eluting stent (DES) implantation. We aimed to determine if an abnormal ankle-brachial index (ABI) value as a surrogate of atherosclerotic disease and vascular inflammation provides information on 1-year risk of cardiovascular events after DES implantation. A prospective cohort of 1,437 consecutive patients undergoing DES implantation from January through April 2008 in 26 Spanish hospitals was examined. ABI was calculated by Doppler in a standardized manner. Patients were followed to 12 months after the percutaneous coronary intervention to determine total and cardiovascular mortality, stroke, nonfatal acute coronary syndrome (ACS), and new revascularizations. Association of an abnormal ABI value (i.e., ≤ 0.9 or ≥ 1.4) with outcomes was assessed by conventional logistic regression and by propensity-score analysis. Patients with abnormal ABI values (n = 582, 40.5%) in general had higher global cardiovascular risk, the reason for DES implantation was more often ACS, and had a higher rate of complications during admission (heart failure or stroke or major hemorrhage 11.3% vs 5.3%, p <0.001). An abnormal ABI value was independently associated with 1-year total mortality (odds ratio 2.23, 95% confidence interval 1.13 to 4.4) and cardiovascular mortality (odds ratio 2.06, 95% confidence interval 1.04 to 4.22). No independent association was found between an abnormal ABI value and 1-year nonfatal ACS, stroke, and new revascularizations. In conclusion, although an abnormal ABI value was associated with fatal outcomes in patients receiving DESs, no association was found with nonfatal ACS and new revascularizations. A clear relation between abnormal ABI and surrogates of DES thrombosis could not be established.

  2. Strategies for vascular disease prevention: the role of lipids and related markers including apolipoproteins, low-density lipoproteins (LDL)-particle size, high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA₂) and lipoprotein(a) (Lp(a)).

    PubMed

    Dallmeier, Dhayana; Koenig, Wolfgang

    2014-06-01

    Considerable progress has been achieved in the treatment of dyslipidemias. However, half of cardiovascular events occur in individuals with average or low cholesterol levels and there is still a considerable residual risk with 70% of patients having an event despite statin treatment. In the era of personalized medicine there is increased interest in the incorporation of individual biomarkers in risk score algorithms in order to improve cardiovascular risk stratification followed by the prompt initiation of preventive measures. Since the 2001 third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment on High Blood Cholesterol in Adults (ATP III) several studies have evaluated the prognostic value of lipid related biomarkers such as non-HDL-cholesterol, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, lipoprotein(a), lipoprotein-associated phospholipase A2, and C-reactive protein. This article tries to summarize the most recent results in this area.

  3. Vascular injury in the United kingdom.

    PubMed

    Stannard, Adam; Brohi, Karim; Tai, Nigel

    2011-03-01

    Surgeons working within the United Kingdom's National Health Service have an established history of clinical innovation, research, and development in the field of vascular surgery but lack a unified trauma system to deliver optimal care for patients with vascular injury. The low incidence of vascular trauma, combined with lack of regional trauma systems, works against optimal delivery of care to the polytrauma patient. Providing care, robust data capture, and opportunities for training and education in vascular injury lag behind other elective domains of vascular practice. The challenge is to define ideal care pathways, referral networks, and standards of practice and to integrate the care of such patients. In 2010, a trauma system for London was introduced; it has provided vascular surgeons with a unique opportunity to study and advance the care of patients with vascular injury. This article discusses developing trauma network issues, particularly the organization and evolution of vascular trauma services in the United Kingdom.

  4. Vascular Alterations Underlie Developmental Problems Manifested in Cloned Cattle before or after Birth

    PubMed Central

    Favaron, Phelipe Oliveira; dos Santos, Caio Rodrigues; Alberto, Miryan Lanca; Meirelles, Flavio Vieira; Miglino, Maria Angelica

    2015-01-01

    Although assisted reproductive techniques are commonly applied in humans and animals, they are frequently associated with major developmental deficits and reduced viability. To explore abnormalities associated with cloning or nuclear transfer (NT) as the most invasive of these methods, we used a bovine model to characterize abnormalities. Detailed necropsy examinations were done on 13 calves that died soon after birth; in addition, we included data from embryos and fetuses (produced by NT) that terminated prematurely. Bovine clones that survived until the neonatal period differed quantitatively and qualitatively from in-vivo-derived cattle. Although alterations affected a variety of organs (e.g. heart, lung and liver), there was a clear association with abberant vascular developmental during the early intrauterine phase. Therefore, we concluded that vascular problems were key alterations induced by cloning (presumably via epigenetic modifications). PMID:25584533

  5. Vascular alterations underlie developmental problems manifested in cloned cattle before or after birth.

    PubMed

    Maiorka, Paulo Cesar; Favaron, Phelipe Oliveira; Mess, Andrea Maria; dos Santos, Caio Rodrigues; Alberto, Miryan Lanca; Meirelles, Flavio Vieira; Miglino, Maria Angelica

    2015-01-01

    Although assisted reproductive techniques are commonly applied in humans and animals, they are frequently associated with major developmental deficits and reduced viability. To explore abnormalities associated with cloning or nuclear transfer (NT) as the most invasive of these methods, we used a bovine model to characterize abnormalities. Detailed necropsy examinations were done on 13 calves that died soon after birth; in addition, we included data from embryos and fetuses (produced by NT) that terminated prematurely. Bovine clones that survived until the neonatal period differed quantitatively and qualitatively from in-vivo-derived cattle. Although alterations affected a variety of organs (e.g. heart, lung and liver), there was a clear association with abberant vascular developmental during the early intrauterine phase. Therefore, we concluded that vascular problems were key alterations induced by cloning (presumably via epigenetic modifications).

  6. Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins.

    PubMed

    Galambos, Csaba; Sims-Lucas, Sunder; Ali, Noorjahan; Gien, Jason; Dishop, Megan K; Abman, Steven H

    2015-01-01

    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal neonatal lung disease characterised by severe pulmonary hypertension, abnormal vasculature and intractable hypoxaemia. Mechanisms linking abnormal lung vasculature with severe hypoxaemia in ACD/MPV are unknown. We investigated whether bronchopulmonary anastomoses form right-to-left shunt pathways in ACD/MVP. We studied 2 infants who died of ACD/MPV postmortem with direct injections of coloured ink into the pulmonary artery, bronchial artery and pulmonary veins. Extensive histological evaluations included serial sectioning, immunostaining and 3-dimensional reconstruction demonstrated striking intrapulmonary vascular pathways linking the systemic and pulmonary circulations that bypass the alveolar capillary bed. These data support the role of prominent right-to-left intrapulmonary vascular shunt pathways in the pathophysiology of ACD/MPV.

  7. [Therapeutic indications for percutaneous laser in patients with vascular malformations and tumors].

    PubMed

    Labau, D; Cadic, P; Ouroussoff, G; Ligeron, C; Laroche, J-P; Guillot, B; Dereure, O; Quéré, I; Galanaud, J-P

    2014-12-01

    Lasers are increasingly used to treat vascular abnormalities. Indeed, this technique is non-invasive and allows a specific treatment. The aim of this review is to present some biophysical principles of the lasers, to describe the different sorts of lasers available for treatment in vascular medicine indications. Three principal lasers exist in vascular medicine: the pulsed-dye laser, for the treatment of superficial pink lesions, the NdYAG-KTP laser for purple and bigger lesions, and the NdYAG long pulse laser for even deeper and bigger vascular lesions. In vascular malformations, port wine stains can also be treated by pulsed-dye laser, KTP or NdYAG when they are old and thick. Telangiectasias are good indications for the three sorts of lasers, depending on their depth, color and size. Microcystic lymphatic malformations can be improved by laser treatment. Arterio-venous malformations constitute a contraindication of laser treatment. In vascular tumors, involuted infantile hemangiomas constitute an excellent indication of pulsed-dye laser treatment. Controlled studies are necessary to evaluate and to compare the efficacy of each laser, in order to determine their optimal indications and optimal parameters for each machine.

  8. Endothelial C-type natriuretic peptide maintains vascular homeostasis.

    PubMed

    Moyes, Amie J; Khambata, Rayomand S; Villar, Inmaculada; Bubb, Kristen J; Baliga, Reshma S; Lumsden, Natalie G; Xiao, Fang; Gane, Paul J; Rebstock, Anne-Sophie; Worthington, Roberta J; Simone, Michela I; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F; Djordjevic, Snezana; Caulfield, Mark J; MacAllister, Raymond J; Selwood, David L; Ahluwalia, Amrita; Hobbs, Adrian J

    2014-09-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor-C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders.

  9. Oxidative stress and microRNAs in vascular diseases.

    PubMed

    Magenta, Alessandra; Greco, Simona; Gaetano, Carlo; Martelli, Fabio

    2013-08-22

    Oxidative stress has been demonstrated to play a causal role in different vascular diseases, such as hypertension, diabetic vasculopathy, hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen species (ROS) production is known to impair endothelial and vascular smooth muscle cell functions, contributing to the development of cardiovascular diseases. MicroRNAs (miRNAs) are non-coding RNA molecules that modulate the stability and/or the translational efficiency of target messenger RNAs. They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance. In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity. In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity. In this review, we will discuss miRNAs modulated by ROS or involved in ROS production, and implicated in vascular diseases in which redox imbalance has a pathogenetic role.

  10. Endothelial C-type natriuretic peptide maintains vascular homeostasis

    PubMed Central

    Moyes, Amie J.; Khambata, Rayomand S.; Villar, Inmaculada; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne-Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F.; Djordjevic, Snezana; Caulfield, Mark J.; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

    2014-01-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders. PMID:25105365

  11. Chemical Reactivity Test (CRT)

    SciTech Connect

    Zaka, F.

    2016-12-13

    The Chemical Reactivity Test (CRT) is used to determine the thermal stability of High Explosives (HEs) and chemical compatibility between (HEs) and alien materials. The CRT is one of the small-scale safety tests performed on HE at the High Explosives Applications Facility (HEAF).

  12. Reactive power compensating system

    DOEpatents

    Williams, Timothy J.; El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.

    1987-01-01

    The reactive power of an induction machine is compensated by providing fixed capacitors on each phase line for the minimum compensation required, sensing the current on one line at the time its voltage crosses zero to determine the actual compensation required for each phase, and selecting switched capacitors on each line to provide the balance of the compensation required.

  13. Reactive Sensor Networks (RSN)

    DTIC Science & Technology

    2003-10-01

    Networks,” Distributed Autonomous Robotic Systems DARS 2000, pp. 471-472, Springer Verlag, Tokyo. R. R. Brooks. “Stigmergy an intelligence metric...Paper, March 2003. • R. Brooks, et al. “Reactive Sensor Networks: Mobile Code Support for Autonomous Sensor Networks,” Distributed Autonomous Robotic Systems DARS

  14. Reactive transport modeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This special section in the Vadose Zone Journal focusing on reactive transport modeling was developed from a special symposium jointly sponsored by the Soil Physics and Soil Chemistry Divisions of the Soil Science Society of America at the 2010 annual meetings held in Long Beach, CA. It contains eig...

  15. Reactive Power Compensating System.

    DOEpatents

    Williams, Timothy J.; El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.

    1985-01-04

    The circuit was designed for the specific application of wind-driven induction generators. It has great potential for application in any situation where a varying reactive power load is present, such as with induction motors or generators, or for transmission network compensation.

  16. Modeling Atmospheric Reactive Nitrogen

    EPA Science Inventory

    Nitrogen is an essential building block of all proteins and thus an essential nutrient for all life. Reactive nitrogen, which is naturally produced via enzymatic reactions, forest fires and lightning, is continually recycled and cascades through air, water, and soil media. Human ...

  17. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension.

    PubMed

    Kossmann, Sabine; Lagrange, Jeremy; Jäckel, Sven; Jurk, Kerstin; Ehlken, Moritz; Schönfelder, Tanja; Weihert, Yvonne; Knorr, Maike; Brandt, Moritz; Xia, Ning; Li, Huige; Daiber, Andreas; Oelze, Matthias; Reinhardt, Christoph; Lackner, Karl; Gruber, Andras; Monia, Brett; Karbach, Susanne H; Walter, Ulrich; Ruggeri, Zaverio M; Renné, Thomas; Ruf, Wolfram; Münzel, Thomas; Wenzel, Philip

    2017-02-01

    Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 expression and integrin αMβ2- and platelet-dependent leukocyte adhesion to arterial vessels. The resulting vascular inflammation and dysfunction was mediated by activation of thrombin-driven factor XI (FXI) feedback, independent of factor XII. The FXI receptor glycoprotein Ibα on platelets was required for this thrombin feedback activation in angiotensin II-infused mice. Inhibition of FXI synthesis with an antisense oligonucleotide was sufficient to prevent thrombin propagation on platelets, vascular leukocyte infiltration, angiotensin II-induced endothelial dysfunction, and arterial hypertension in mice and rats. Antisense oligonucleotide against FXI also reduced the increased blood pressure and attenuated vascular and kidney dysfunction in rats with established arterial hypertension. Further, platelet-localized thrombin generation was amplified in an FXI-dependent manner in patients with uncontrolled arterial hypertension, suggesting that platelet-localized thrombin generation may serve as an inflammatory marker of high blood pressure. Our results outline a coagulation-inflammation circuit that promotes vascular dysfunction, and highlight the possible utility of FXI-targeted anticoagulants in treating hypertension, beyond their application as antithrombotic agents in

  18. Prostacyclin and pathogenesis of hemodynamic abnormalities of diabetic ketoacidosis in rats.

    PubMed

    Quyyumi, A A; Iaffaldano, R; Guerrero, J L; Ryan, C A; Powell, W J; Axelrod, L

    1989-12-01

    The pathogenesis of the hemodynamic abnormalities of diabetic ketoacidosis (DKA) is not well understood. Previous studies suggest that prostacyclin (PGI2) production by adipose tissue is increased in DKA. We investigated the role of PGI2 in the pathogenesis of the reduced vascular resistance in DKA. Rats with streptozocin-induced DKA were anesthetized with pentobarbital sodium, and flow was measured with an electromagnetic probe on the infradiaphragmatic aorta. The plasma level of 6-keto-PGF1 alpha (stable derivative of PGI2) was higher (mean +/- SE 0.91 +/- 0.05 ng/ml) and vascular resistance lower (4.9 +/- 0.2 mmHg.ml-1.min-1.100 g-1 [resistance units, RU]) in 67 rats with DKA than in 21 normal rats (0.34 +/- 0.03 ng/ml, P less than .01, and 9.0 +/- 0.7 RU, P less than .01, respectively). Inhibition of cyclooxygenase activity with either indomethacin or meclofenamic acid reduced the plasma 6-keto-PGF1 alpha level but failed to raise vascular resistance. Infusions of PGI2 in rats with DKA demonstrated that the vasculature was responsive to PGI2. Inhibition of cyclooxygenase activity not only reduced PGI2 production but also suppressed renin release. When the effects of the renin-angiotensin system were excluded by bilateral nephrectomy, indomethacin caused a significant increase (P less than .05) in vascular resistance. Thus, the failure of cyclooxygenase inhibitors to raise vascular resistance in DKA was a result of concurrent suppression of vasodilator (PGI2) and vasoconstrictor (renin-angiotensin system) mechanisms that are activated in DKA. Insulin administration increased vascular resistance (P less than .01) and decreased the level of plasma 6-keto-PGF1 alpha (P less than .01). Combined administration of PGI2 and insulin did not alter vascular resistance, suggesting that the increase in vascular resistance with insulin was predominantly due to the reduction of circulating PGI2. Thus, vascular resistance is decreased in DKA primarily as a result of the

  19. Report to Congress on abnormal occurrences

    SciTech Connect

    Not Available

    1991-03-01

    Section 208 of the Energy Reorganization Act of 1974 identified an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from October 1 through December 31, 1990. The report discusses five abnormal occurrences, none of which involved a nuclear power plant. Two involved significant overexposures to the hands of two radiographers, two involved medical therapy misadministrations, and one involved a medical diagnostic misadministration. No abnormal occurrences were reported by the Agreement States. The report also contains information that updates a previously reported abnormal occurrence. 8 refs.

  20. MRI Helps Assess Fetal Brain Abnormalities

    MedlinePlus

    ... decisions about their pregnancy," said lead author Paul Griffiths. He's a professor of radiology at the University ... the fetus may have a suspected brain abnormality," Griffiths said in a journal news release. In this ...

  1. Abnormal Position and Presentation of the Fetus

    MedlinePlus

    ... Interest (Quiz) Breast Cancer (Video) Overview of the Female Reproductive System (News) Study: Plenty of IV Fluids May Make Childbirth Safer, Easier (News) Zejula Approved for Certain Female Cancers Additional Content Medical News Abnormal Position and ...

  2. Abnormalities of lung function in hay fever.

    PubMed Central

    Morgan, E J; Hall, D R

    1976-01-01

    Twenty subjects with symptoms of hay fever were studied to see whether abnormalities could be detected in the function of small airways. The investigations included dynamic compliance at varying respiratory frequencies, closing capacity, residual volume, transfer factor, and maximal expiratory flow-volume curves. The tests were repeated in the winter when symptoms had resolved. Frequency dependence of compliance was found in eight subjects with symptoms (40%), closing capacities being abnormal in only two instances. Conventional pulmonary function tests, including expiratory flow rates at mid vital capacity, were within the predicted range of all subjects. When tests were repeated in the winter, frequency dependence of compliance was no longer present in subjects whose symptoms had resolved. The study suggests that reversible small airway abnormalities are present in a significant proportion of subjects with symptoms of hay fever and that such abnormalities are best detected by the measurement of dynamic compliance at varying respiratory frequencies. PMID:769243

  3. Arsenic, reactive oxygen, and endothelial dysfunction.

    PubMed

    Ellinsworth, David C

    2015-06-01

    Human exposure to drinking water contaminated with arsenic is a serious global health concern and predisposes to cardiovascular disease states, such as hypertension, atherosclerosis, and microvascular disease. The most sensitive target of arsenic toxicity in the vasculature is the endothelium, and incubation of these cells with low concentrations of arsenite, a naturally occurring and highly toxic inorganic form of arsenic, rapidly induces reactive oxygen species (ROS) formation via activation of a specific NADPH oxidase (Nox2). Arsenite also induces ROS accumulation in vascular smooth muscle cells, but this is relatively delayed because, depending on the vessel from which they originate, these cells often lack Nox2 and/or its essential regulatory cytosolic subunits. The net effect of such activity is attenuation of endothelium-dependent conduit artery dilation via superoxide anion-mediated scavenging of nitric oxide (NO) and inhibition and downregulation of endothelia