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Sample records for impaired vascular reactivity

  1. Impaired vascular reactivity in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Tetzner, Fabian; Scholze, Alexandra; Wittstock, Antje

    2008-01-01

    Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics.......Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics....

  2. Vascular Cognitive Impairment.

    Science.gov (United States)

    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.

  3. Insulin resistance impairs endothelial function but not adrenergic reactivity or vascular structure in fructose-fed rats.

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    Romanko, Olga P; Ali, M Irfan; Mintz, James D; Stepp, David W

    2009-07-01

    Obesity and diabetes are major risk factors for the development of vascular disease in the lower limbs. Previous studies have demonstrated reduced nitric oxide (NO)-mediated vasodilation, increased adrenergic constriction, and inward, atrophic remodeling in the limb circulation of obese Zucker rats, but the component of the "metabolic syndrome" driving these changes is unclear. Because insulin resistance precedes the state of frank diabetes, the current study hypothesized that insulin resistance independent of obesity induced by fructose feeding would impair microvascular function in the skeletal muscle circulation in lean Zucker rats (LZR). A 66% fructose diet impaired glucose tolerance and induced moderate insulin resistance with no changes in whole-body hemodynamics of anesthetized rats (FF-LZR), compared to control LZR. NO-mediated vasodilation of isolated gracilis arteries, assessed in vitro with acetylcholine and sodium nitroprusside, was reduced approximately 20% in FF-LZR vs. LZR. NO-independent cGMP-mediated vasodilation was unimpaired. Pretreatment of isolated vessels with the superoxide scavenger, tempol, improved responses to both vasodilators. Reactivity to adrenergic stimulation was unaltered in FF-LZR vs. LZR, although constriction to endothelin was increased. Structural and passive mechanical characteristics of isolated gracilis arteries were similar in both LZR and FF-LZR. Taken together, these findings indicate that moderate insulin resistance is sufficient to impair endothelial function in an oxidant-dependent manner in the rat hindlimb circulation. Other aspects of skeletal muscle vascular function documented in obese models, specifically adrenergic tone and inward remodeling, must reflect either severe insulin resistance or other aspects of obesity. The factors accounting for nonendothelial vasculopathies remain unknown.

  4. Assessment of impaired vascular reactivity in a rat model of diabetic nephropathy: effect of nitric oxide synthesis inhibition on intrarenal diffusion and oxygenation measured by magnetic resonance imaging.

    Science.gov (United States)

    Hueper, Katja; Hartung, Dagmar; Gutberlet, Marcel; Gueler, Faikah; Sann, Holger; Husen, Bettina; Wacker, Frank; Reiche, Dania

    2013-11-15

    Diabetes is associated with impaired vascular reactivity and the development of diabetic nephropathy. In a rat model of streptozotocin-induced diabetic nephropathy, the effects of systemic nitric oxide (NO) synthesis inhibition on intrarenal diffusion and oxygenation were determined by noninvasive magnetic resonance diffusion tensor imaging and blood O2 level-dependent (BOLD) imaging, respectively. Eight weeks after the induction of diabetes, 21 rats [n = 7 rats each in the untreated control group, diabetes mellitus (DM) group, and DM with uninephrectomy (DM UNX) group] were examined by MRI. Diffusion tensor imaging and BOLD sequences were acquired before and after NO synthesis inhibition with N-nitro-L-arginine methyl ester (L-NAME). In the same rats, mean arterial pressure and vascular conductance were determined with and without the influence of L-NAME. In control animals, NO synthesis inhibition was associated with a significant increase of mean arterial pressure of 33.8 ± 4.3 mmHg (P animals. Similarly, L-NAME challenge induced a significant reduction of renal transverse relaxation time (T2*) at MRI in control animals, indicating reduced renal oxygenation after L-NAME injection compared with baseline. DM UNX animals did not show a significant T2* reduction after NO synthesis inhibition in the renal cortex and attenuated T2* reduction in the outer medulla. MRI parameters of tissue diffusion were not affected by L-NAME in all groups. In conclusion, BOLD imaging proved valuable to noninvasively measure renal vascular reactivity upon NO synthesis inhibition in control animals and to detect impaired vascular reactivity in animals with diabetic nephropathy.

  5. N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Wittstock, Antje; Burkert, Magdalena; Zidek, Walter;

    2009-01-01

    Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity in these ......Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity...

  6. Diagnosis advances in vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Hua Zhou; Zhong Zhao

    2009-01-01

    Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.

  7. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    NARCIS (Netherlands)

    Drongelen, J. van; Koppen, A. van; Pertijs, J.C.L.M.; Gooi, J.H.; Parry, L.J.; Sweep, F.C.; Lotgering, F.K.; Smits, P.; Spaanderman, M.E.A.

    2012-01-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a re

  8. Local vascular CO2 reactivity in the infant brain assessed by functional MRI

    DEFF Research Database (Denmark)

    Toft, P.B.; Leth, H; Lou, H.C.

    1995-01-01

    hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional...

  9. Citicoline in vascular cognitive impairment and vascular dementia after stroke.

    Science.gov (United States)

    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.

  10. The concept of vascular cognitive impairment.

    Science.gov (United States)

    Bowler, J V

    2002-11-15

    Vascular dementia (VaD) is increasingly recognised to reflect an outmoded concept in that it identifies cases too late for preventive therapy to have an opportunity to prevent the development of dementia and uses a cognitive paradigm inappropriately based on Alzheimer's disease. A replacement is urgently required and a new concept, that of vascular cognitive impairment (VCI), has been proposed to meet this need. It is imperative that criteria for VCI are developed on the basis of knowledge and data rather than supposition and assumption, as was the case for VaD. This review details the state of knowledge that we have now reached concerning the fundamental points of severity and cognitive paradigm and also covers a number of other imaging-related essential points embracing atrophy, leukoaraiosis, infarct volume and infarct location. Finally, the increasingly important concept of mixed dementia (co-existent Alzheimer's disease and VCI) is discussed.

  11. Retinal Vascular Fractals and Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Yi-Ting Ong

    2014-08-01

    Full Text Available Background: Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia. Methods: This is a cross-sectional study of 300 Chinese participants (age: ≥60 years from the ongoing Epidemiology of Dementia in Singapore study who underwent detailed clinical examinations including retinal photography, brain imaging and neuropsychological testing. Retinal vascular parameters were assessed from optic disc-centered photographs using a semiautomated program. A comprehensive neuropsychological battery was administered, and cognitive function was summarized as composite and domain-specific Z-scores. Cognitive impairment no dementia (CIND and dementia were diagnosed according to standard diagnostic criteria. Results: Among 268 eligible nondemented participants, 78 subjects were categorized as CIND-mild and 69 as CIND-moderate. In multivariable adjusted models, reduced retinal arteriolar and venular fractal dimensions were associated with an increased risk of CIND-mild and CIND-moderate. Reduced fractal dimensions were associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed. Conclusion: A sparser retinal microvascular network, represented by reduced arteriolar and venular fractal dimensions, was associated with cognitive impairment, suggesting that early microvascular damage may be present in preclinical stages of dementia.

  12. Airway vascular reactivity and vascularisation in human chronic airway disease

    NARCIS (Netherlands)

    Bailey, Simon R; Boustany, Sarah; Burgess, Janette K; Hirst, Stuart J; Sharma, Hari S; Simcock, David E; Suravaram, Padmini R; Weckmann, Markus

    2009-01-01

    Altered bronchial vascular reactivity and remodelling including angiogenesis are documented features of asthma and other chronic inflammatory airway diseases. Expansion of the bronchial vasculature under these conditions involves both functional (vasodilation, hyperperfusion, increased microvascular

  13. Atherosclerotic risk factors, vascular cognitive impairment, and Alzheimer disease.

    Science.gov (United States)

    Kovacic, Jason C; Fuster, Valentin

    2012-01-01

    The involvement of vascular factors in Alzheimer dementia was first appreciated over 100 years ago. Recently, significant advances in our understanding of these brain-vascular relationships have taken place. Vascular cognitive impairment is now recognized as a distinct group of interrelated vascular-based neurological insults that can accumulate and lead to dementia. Importantly, the pathology of vascular cognitive impairment extends far beyond brain destruction wrought by major stroke. Other subtle changes may also arise that contribute to vascular cognitive impairment and dementia, including subclinical stroke, white-matter changes such as hyperintensities and lipohyalinosis, small lacunar infarcts, cerebral hypoperfusion, and compromise of the blood-brain barrier. In this review we critically examine the emerging body of evidence that relates atherosclerotic risk factors, brain functioning, and Alzheimer disease. © 2012 Mount Sinai School of Medicine.

  14. Diagnosis of vascular cognitive impairment and its main categories.

    Science.gov (United States)

    Rodríguez García, P L; Rodríguez García, D

    2015-05-01

    A review of current criteria for the diagnosis of categories related with vascular cognitive impairment, in particular the nomenclature, diagnostic criteria, and differential clinical-radiological findings. The criteria for the diagnosis of vascular cognitive impairment have evolved, but available criteria were designed basically for differentiating between vascular dementia and dementia due to Alzheimer disease, and for research purposes. Nevertheless, in clinical practice precise elements are required for: 1) Clinical diagnosis of dementia and mild cognitive impairment; 2) Clinical and neuroimaging criteria for identification of the various cerebrovascular lesions associated with cognitive dysfunction, and 3) A formulation of the aetiogenic-pathogenic relationship between cognitive impairment and cerebrovascular lesions. For this reason, a review was carried out on the diagnostic elements of vascular cognitive impairment categories, classification, and their most relevant characteristics. It highlights the characteristic for the diagnosis of multi-infarction dementia, strategic single infarct dementia, small vessel disease with dementia, mixed dementia, and vascular mild cognitive impairment. Standardisation is required, by a multidisciplinary expert team, as regards nomenclature and criteria for the diagnosis of the full spectrum associated with vascular cognitive impairment and especially for vascular dementia and its categories. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Effects of acid-base imbalance on vascular reactivity

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    A.C. Celotto

    2008-06-01

    Full Text Available Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo and those occurring within the intracellular space (pHi, although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent, prostacyclin (PGI2/cAMP-dependent and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

  16. Vascular cognitive impairments in chronic kidney disease

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    I. V. Rogova

    2015-01-01

    Full Text Available Objective: to study the specific features of development of cognitive impairments (CIs, the role of traditional cardiovascular risk factors and renal failure-induced factors in patients with Stages I–IV chronic kidney disease (CKD and to assess an association of CIs with the signs of vascular wall remodeling in them. Patients and methods. Fifty-one patients aged 53±10 years with CKD were examined. Among them, there were 20 patients with Stages I–II CKD: a glomerular filtration rate (GFR of і60 ml/min/1.73 m2, signs of renal lesion; 20 with Stages III CKD: a GFR of <60–30 ml/min/1.73 m2, and 11 with Stages VI CKD: a GFR of <30–15 ml/min/1.73 m2. Results and discussion. CIs were more common in the patients with Stages III–IV than in those with Stages I–II, as shown by the scores of the mini-mental state examination (p<0.001, the frontal assessment battery (p=0.001, and the regulatory function test (p<0.001. These tests showed that the magnitude of CIs increased with the higher stage of CKD. Stages III–IV CKD is an independent predictor of CIs in persons with predialysis-stage kidney lesion. CIs were found to be related to hyperhomocysteinemia, anemia, abdominal obesity, left ventricular hypertrophy, and patient age. The signs of atherosclerotic lesion of the common carotid arteries and the indicators of arterial stiffness were also associated with the incidence and magnitude of CIs in CKD. The detection of CIs in patients with early CKD allows one to timely initiate adequate therapy aimed particularly at improving cerebral circulation, eliminating the impact of risk factors, and slowing down the vascular remodeling. The management tactics for patients with CKD must involve the identification and correction of cardiovascular risk factors, and duplex scanning of the wall of the common carotid arteries may be used as a noninvasive method to assess the risk of the development and progression of CIs in predialysis CKD. 

  17. Diabetes and microvascular disease in Vascular Cognitive Impairment

    NARCIS (Netherlands)

    Brundel, M.

    2014-01-01

    The contribution of cerebrovascular disease in the development of cognitive dysfunction and dementia is increasingly recognized. Cerebrovascular damage is heterogeneous, ranging from a clinical stroke to more insidious brain changes. The term vascular cognitive impairment (VCI) has been introduced,

  18. Cognitive function following stroke and vascular cognitive impairment

    NARCIS (Netherlands)

    de Haan, Edward H.; Nys, Gudrun M.; Van Zandvoort, Martine J.

    2006-01-01

    Purpose of review This review of the cognitive status following stroke and vascular cognitive impairment starts by questioning the concept of vascular dementia and related concepts. Our position is that in many cases these labels promote a superficial conceptualization of an inherently complex and h

  19. Lesion-symptom mapping in vascular cognitive impairment

    NARCIS (Netherlands)

    Biesbroek, J.M.

    2016-01-01

    Cerebral vascular disease (CVD) is an important cause of cognitive decline and dementia, either alone or in combination with neurodegenerative diseases, such as Alzheimer's Disease (AD). The contribution of CVD to cognitive decline and dementia is referred to as Vascular Cognitive Impairment (VCI).

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

    Science.gov (United States)

    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.

  1. Vascular cognitive impairment: Current concepts and Indian perspective

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    Alladi Suvarna

    2010-10-01

    Full Text Available Cognitive impairment due to cerebrovascular disease is termed "Vascular Cognitive Impairment" (VCI and forms a spectrum that includes Vascular Dementia (VaD and milder forms of cognitive impairment referred to as Vascular Mild Cognitive Impairment (VaMCI. VCI represents a complex neurological disorder that occurs as a result of interaction between vascular risk factors such as hypertension, diabetes, obesity, dyslipidemia, and brain parenchymal changes such as macro and micro infarcts, haemorrhages, white matter changes, and brain atrophy occurring in an ageing brain. Mixed degenerative and vascular pathologies are increasingly being recognised and an interaction between the AD pathology, vascular risk factors, and strokes is now proposed. The high cardiovascular disease burden in India, increasing stroke incidence, and ageing population have contributed to large numbers of patients with VCI in India. Inadequate resources coupled with low awareness make it a problem that needs urgent attention, it is important identify patients at early stages of cognitive impairment, to treat appropriately and prevent progression to frank dementia.

  2. C-reactive Protein Predicts Postoperative Delirium Following Vascular Surgery

    NARCIS (Netherlands)

    Pol, Robert A.; van Leeuwen, Barbara L.; Izaks, Gerbrand J.; Reijnen, Michel M. P. J.; Visser, Linda; Tielliu, Ignace F. J.; Zeebregts, Clark J.

    2014-01-01

    Background: The etiology of postoperative delirium (POD) following vascular surgery is generally unknown. The incidence, however, can be as high as 35%. A possible neuroinflammatory basis for delirium is likely and C-reactive protein (CRP) as a marker for inflammation can possibly play a predictive

  3. Vascular cognitive impairment in Pemphigus vulgaris: a case report

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    José Ibiapina Siqueira- Neto

    Full Text Available ABSTRACT Pemphigus vulgaris is a systemic auto-immune medical condition that mainly manifests with changes in skin and vasculopathy. This is a case report of a 69-year-old male with confirmed histopathologic diagnosis of Pemphigus vulgaris presenting ulterior Cognitive Impairment, mostly in executive function. The patient was treated using steroids, immunomodulatory therapy, fluoxetine and galantamine. Neuropsychological testing and magnetic resonance (MRI were performed. This is the first report of correlational cognitive impairment with Pemphigus vulgaris in the literature. Physicians should be aware of vascular causes for cognitive impairment in patients presenting auto-immune conditions.

  4. Reactive Oxygen Species in Vascular Formation and Development

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    Yijiang Zhou

    2013-01-01

    Full Text Available Reactive oxygen species (ROS are derived from the metabolism of oxygen and are traditionally viewed as toxic byproducts that cause damage to biomolecules. It is now becoming widely acknowledged that ROS are key modulators in a variety of biological processes and pathological states. ROS mediate key signaling transduction pathways by reversible oxidation of certain signaling components and are involved in the signaling of growth factors, G-protein-coupled receptors, Notch, and Wnt and its downstream cascades including MAPK, JAK-STAT, NF-κB, and PI3K/AKT. Vascular formation and development is one of the most important events during embryogenesis and is vital for postnasal tissue repair. In this paper, we will discuss how ROS regulate different steps in vascular development, including smooth muscle cell differentiation, angiogenesis, endothelial progenitor cells recruitment, and vascular cell migration.

  5. Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity

    DEFF Research Database (Denmark)

    Abbott, Geoffrey W; Jepps, Thomas A

    2016-01-01

    Voltage-gated potassium (Kv) channels formed by Kv7 (KCNQ) α-subunits are recognized as crucial for vascular smooth muscle function, in addition to their established roles in the heart (Kv7.1) and the brain (Kv7.2-5). In vivo, Kv7 α-subunits are often regulated by KCNE subfamily ancillary (β...... transcripts, with no striking sex-specific differences. However, Kv7.4 protein expression in females was twice that in males, and was reduced in both sexes by Kcne4 deletion. Our findings confirm a crucial role for KCNE4 in regulation of Kv7 channel activity to modulate vascular tone, and provide the first...... known molecular mechanism for sex-specificity of this modulation that has important implications for vascular reactivity and may underlie sex-specific susceptibility to cardiovascular diseases....

  6. Reactive oxygen species and vascular biology: implications in human hypertension.

    Science.gov (United States)

    Touyz, Rhian M; Briones, Ana M

    2011-01-01

    Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

  7. Reactivity of the isolated perfused rat tail vascular bed

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    A.S. França

    1997-07-01

    Full Text Available Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg and heparinized (500 U. The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 µM EDTA at 36oC and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE (0.5, 1, 2 and 5 µg, bolus injection was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min. The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 µg/ml. There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity

  8. Neuropsychiatric symptoms in Vascular Cognitive Impairment: A systematic review

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    Chan Tiel

    Full Text Available Neuropsychiatric symptoms or Behavioral and Psychological Symptoms of Dementia (BPSD are common and invariably appear at some point during the course of the disease, mediated both by cerebrovascular disease and neurodegenerative processes. Few studies have compared the profiles of BPSD in Vascular Cognitive Impairment (VCI of different subtypes (subcortical or cortical and clinical stages (Vascular Cognitive Impairment No Dementia [VaCIND] and Vascular Dementia [VaD].Objective:To review the BPSD associated with different subtypes and stages of VCI using the Neuropsychiatric Inventory (NPI.Methods:Medline, Scielo and Lilacs databases were searched for the period January 2000 to December 2014, with the key words: "BPSD AND Vascular Dementia, "NPI AND Vascular Dementia" and "NPI AND VCI. Qualitative analysis was performed on studies evaluating BPSD in VCI, using the Neuropsychiatric Inventory (NPI.Results:A total of 82 studies were retrieved of which 13 were eligible and thus included. Among the articles selected, 4 compared BPSD in Subcortical Vascular Dementia (SVaD versus Cortical-Subcortical Vascular Dementia (CSVaD, 3 involved comparisons between SVaD and VaCIND, 1 study analyzed differences between CSVaD and VaCIND, while 5 studies assessed BPSD in CSVaD. Subcortical and Cortical-Subcortical VaD were associated predominantly with Apathy and Depression. VaCIND may present fewer behavioral symptoms than VaD.Conclusion:The profile of BPSD differs for different stages of VCI. Determining the most prevalent BPSD in VCI subtypes might be helpful for improving early diagnosis and management of these symptoms.

  9. Nitric oxide and reactive oxygen species in limb vascular function

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva

    2014-01-01

    Abstract Nitric oxide (NO) is known to be one of the most important regulatory compounds within the cardiovascular system where it is central for functions such as regulation of blood pressure, blood flow and vascular growth. The bioavailability of NO is determined by a balance between, on one hand......, the extent of enzymatic and non-enzymatic formation of NO and on the other hand, removal of NO, which in part is dependent on the reaction of NO with reactive oxygen species (ROS). The presence of ROS is dependent on the extent of ROS formation via mitochondria and/or enzymes such as NAD(P)H oxidase...

  10. Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia.

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    Saggu, Raman; Schumacher, Toni; Gerich, Florian; Rakers, Cordula; Tai, Khalid; Delekate, Andrea; Petzold, Gabor C

    2016-08-04

    Vascular cognitive impairment is the second most common form of dementia. The pathogenic pathways leading to vascular cognitive impairment remain unclear but clinical and experimental data have shown that chronic reactive astrogliosis occurs within white matter lesions, indicating that a sustained pro-inflammatory environment affecting the white matter may contribute towards disease progression. To model vascular cognitive impairment, we induced prolonged mild cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia within white matter tracts, demyelination and axonal degeneration, consecutive spatial memory deficits, and loss of white matter integrity, as measured by ultra high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis was accompanied by activation of the pro-inflammatory transcription factor nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant negative inhibitor of NF-kB under the control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter (GFAP-IkBα-dn), we found that transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and axonal loss, maintained white matter structural integrity, and preserved memory function. Collectively, our results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.

  11. Toxic effects of mercury, lead and gadolinium on vascular reactivity

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    D.V. Vassallo

    2011-09-01

    Full Text Available Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

  12. Toxic effects of mercury, lead and gadolinium on vascular reactivity

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    D.V. Vassallo

    2011-09-01

    Full Text Available Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

  13. Toxic effects of mercury, lead and gadolinium on vascular reactivity.

    Science.gov (United States)

    Vassallo, D V; Simões, M R; Furieri, L B; Fioresi, M; Fiorim, J; Almeida, E A S; Angeli, J K; Wiggers, G A; Peçanha, F M; Salaices, M

    2011-09-01

    Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

  14. Genistein Attenuates Vascular Endothelial Impairment in Ovariectomized Hyperhomocysteinemic Rats

    Directory of Open Access Journals (Sweden)

    Panpan Zhen

    2012-01-01

    Full Text Available Hyperhomocysteinemia (HHcy is a well-known independent risk factor for vascular diseases in the general population. This study was to explore the effect of genistein (GST, a natural bioactive compound derived from legumes, on HHcy-induced vascular endothelial impairment in ovariectomized rats in vivo. Thirty-two adult female Wistar rats were assigned randomly into four groups (n=8: (a Con: control; (b Met: 2.5% methionine diet; (c OVX + Met: ovariectomy + 2.5% methionine diet; (d OVX + Met + GST: ovariectomy + 2.5% methionine diet + supplementation with genistein. After 12 wk of different treatment, the rats' blood, toracic aortas and liver samples were collected for analysis. Results showed that high-methionine diet induced both elevation of plasma Hcy and endothelial dysfunction, and ovariectomy deteriorated these injuries. Significant improvement of both functional and morphological changes of vascular endothelium was observed in OVX + Met + GST group; meanwhile the plasma Hcy levels decreased remarkably. There were significant elevations of plasma ET-1 and liver MDA levels in ovariectomized HHcy rats, and supplementation with genistein could attenuate these changes. These results implied that genistein could lower the elevated Hcy levels, and prevent the development of endothelial impairment in ovariectomized HHcy rats. This finding may shed a novel light on the anti-atherogenic activities of genistein in HHcy patients.

  15. Quantitative analysis of brain metabolites in patients,with non-dementia vascular cognitive impairment and mild cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    刘艳艳

    2013-01-01

    Objective To investigate metabolite changes in the brain of patients with non-dementia vascular cognitive impairment(VCIND) and mild cognitive impairment(MCI) using magnetic resonance spectroscopy(MRS)

  16. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications.

  17. Vitamin D induces increased systolic arterial pressure via vascular reactivity and mechanical properties.

    Directory of Open Access Journals (Sweden)

    Priscila Portugal Dos Santos

    Full Text Available The aim of this study was to evaluate whether supplementation of high doses of cholecalciferol for two months in normotensive rats results in increased systolic arterial pressure and which are the mechanisms involved. Specifically, this study assesses the potential effect on cardiac output as well as the changes in aortic structure and functional properties.Male Wistar rats were divided into three groups: 1 Control group (C, n = 20, with no supplementation of vitamin D, 2 VD3 (n = 19, supplemented with 3,000 IU vitamin D/kg of chow; 3 VD10 (n = 21, supplemented with 10,000 IU vitamin D/kg of chow. After two months, echocardiographic analyses, measurements of systolic arterial pressure (SAP, vascular reactivity, reactive oxygen species (ROS generation, mechanical properties, histological analysis and metalloproteinase-2 and -9 activity were performed.SAP was higher in VD3 and VD10 than in C rats (p = 0.001. Echocardiographic variables were not different among groups. Responses to phenylephrine in endothelium-denuded aortas was higher in VD3 compared to the C group (p = 0.041. Vascular relaxation induced by acetylcholine (p = 0.023 and sodium nitroprusside (p = 0.005 was impaired in both supplemented groups compared to the C group and apocynin treatment reversed impaired vasodilation. Collagen volume fraction (<0.001 and MMP-2 activity (p = 0.025 was higher in VD10 group compared to the VD3 group. Elastin volume fraction was lower in VD10 than in C and yield point was lower in VD3 than in C.Our findings support the view that vitamin D supplementation increases arterial pressure in normotensive rats and this is associated with structural and functional vascular changes, modulated by NADPH oxidase, nitric oxide, and extracellular matrix components.

  18. Cognitive impairment after cerebrovascular stroke: Relationship to vascular risk factors

    Directory of Open Access Journals (Sweden)

    Eman M Khedr

    2009-02-01

    Full Text Available Eman M Khedr1, Sherifa A Hamed1, Hala K El-Shereef2, Ola A Shawky1, Khalid A Mohamed1, Effat M Awad3, Mohamed A Ahmed2, Ghaydaa A Shehata1, Mahmoud A Eltahtawy41Department of Neurology and Psychiatry, 2Department of Internal Medicine, 3Department of Physiology, 4Department of Clinical Pathology, Assiut University, Faculty of Medicine, Assiut, EgyptBackground: Cognitive decline after cerebrovascular stroke has adverse outcome consequences. Since some vascular causes can be prevented and treated, the identification of stroke-related cognitive impairment is a challenge. Patients with cognitive impairment and vascular diseases exhibit higher homocysteine (Hcy concentrations. Whether Hcy is an independent risk factor for cognitive impairment after stoke is still in question. The objectives of this study were to determine: 1 the relative frequency of first-ever post-stroke dementia (PSD (three months after onset in a consecutive sample of our population, 2 the risk factors associated with PSD, and 3 the relationship between Hcy levels and PSD.Methods: Eighty-one inpatients with first-ever stroke were prospectively evaluated with a neuropsychological battery and event-related evoked potentials (P300 at onset and then after three months. A wide range of demographic, clinical, radiological and laboratory variables were examined. PSD was diagnosed if the clinical presentation fulfilled DSM-IV criteria of vascular dementia, the patient scored ≤21 on Mini Mental State Examination (MMSE and ≤67 points on Cognitive Abilities Screening Instruments (CASI.Results: PSD was diagnosed in 21%. PSD was significantly associated with increasing age, low levels of education, large sized and lacunar infarctions, severity of stroke, prolonged P300 latency, smoking, hypertension, and elevated Hcy levels. High Hcy levels increased the odds ratio of PSD after adjustment of significantly relevant variables including age, smoking, size of infarction, and carotid stenosis

  19. Vascular function and mild renal impairment in stable coronary artery disease

    NARCIS (Netherlands)

    van der Harst, P; Smilde, TDJ; Buikema, H; Voors, AA; Navis, G; van Veldhuisen, DJ; van Gilst, WH

    2006-01-01

    Objective - In patients with coronary artery disease, the concomitant presence of renal function impairment is associated with decreased survival. We aimed to assess whether in coronary artery diseased patients renal function impairment is associated with systemic vascular function, functional param

  20. Melamine Impairs Renal and Vascular Function in Rats.

    Science.gov (United States)

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-06-21

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.

  1. Remote ischemic conditioning: A treatment for vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    David C Hess

    2015-01-01

    Full Text Available There is a strong link between hypoperfusion and white matter (WM damage in patients with leukoaraiosis and vascular cognitive impairment (VCI. Other than management of vascular risk factors, there is no treatment for WM damage and VCI that delays progression of the disease process to dementia. Observational studies suggest that exercise may prevent or slow down the progression of Alzheimer′s disease (AD and VCI. However, getting patients to exercise is challenging, especially with advancing age and disability. Remote ischemic conditioning, an "exercise equivalent," allows exercise to be given with a "device" at home for long periods of time. Since remote ischemic conditioning (RIC increases cerebral blood flow (CBF in preclinical studies and in humans, RIC may be an ideal therapy to treat VCI and WM disease and perhaps even sporadic AD. By using magnetic resonance imaging (MRI imaging of WM progression, a sample size in the range of about 100 subjects per group could determine if RIC has activity in WM disease and VCI.

  2. Cerebrovascular mental stress reactivity is impaired in hypertension

    Directory of Open Access Journals (Sweden)

    Naqvi Tasneem Z

    2009-07-01

    Full Text Available Abstract Background Brachial artery reactivity in response to shear stress is altered in subjects with hypertension. Since endothelial dysfunction is generalized, we hypothesized that carotid artery (CA reactivity would also be altered in hypertension. Purpose To compare (CA endothelium-dependent vasodilation in response to mental stress in normal and hypertensive subjects. Methods We evaluated CA reactivity to mental stress in 10 young healthy human volunteers (aged 23 ± 4 years, 20 older healthy volunteers (aged 49 ± 11 years and in 28 patients with essential hypertension (aged 51 ± 13 years. In 10 healthy volunteers and 12 hypertensive subjects, middle cerebral artery (MCA PW transcranial Doppler was performed before and 3 minutes after mental stress. Results Mental stress by Stroop color word conflict, math or anger recall tests caused CA vasodilation in young healthy subjects (0.61 ± 0.06 to 0.65 ± 0.07 cm, p Conclusion Mental stress produces CA vasodilation and is accompanied by an increase in CA and MCA blood flow in healthy subjects. This mental stress induced CA vasodilation and flow reserve is attenuated in subjects with hypertension and may reflect cerebral vascular endothelial dysfunction. Assessment of mental stress induced CA reactivity by ultrasound is a novel method for assessing the impact of hypertension on cerebrovascular endothelial function and blood flow reserve.

  3. Subcortical Vascular Cognitive Impairment, No Dementia : EEG Global Power Independently Predicts Vascular Impairment and Brain Symmetry Index Reflects Severity of Cognitive Decline

    NARCIS (Netherlands)

    Sheorajpanday, Rishi V. A.; Marien, Peter; Nagels, Guy; Weeren, Arie J. T. M.; Saerens, Jos; van Putten, Michel J. A. M.; De Deyn, Peter P.

    2014-01-01

    Background and Purpose:Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG p

  4. Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

    Directory of Open Access Journals (Sweden)

    Ekatherina Stoyanova

    Full Text Available AIMS: The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments. METHODS AND RESULTS: Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO. While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall. CONCLUSIONS: A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression.

  5. Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Eros Antonio de, E-mail: erosaa@cardiol.br; Ozaki, Michiko Regina [Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2014-07-15

    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. 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. Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16{sup th} 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%. 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. Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

  6. Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Eros Antonio de Almeida

    2014-07-01

    Full Text Available 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.

  7. Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation

    Directory of Open Access Journals (Sweden)

    Nemmar A

    2014-06-01

    , thiobarbituric acid reactive substances, catalase, and glutathione S-transferase, were not affected by SiNPs. The in vitro exposure of human umbilical vein endothelial cells to SiNPs showed a reduced cellular viability, and more potency was seen with 50 nm SiNPs. Both sizes of SiNPs caused a decrease in endothelium-dependent relaxation of isolated small mesenteric arteries. We conclude that amorphous SiNPs cause systemic inflammation and coagulation events, and alter vascular reactivity. Overall, the effects observed with 50 nm SiNPs were more pronounced than those with 500 nm SiNPs. These findings provide new insight into the deleterious effect of amorphous SiNPs on vascular homeostasis. Keywords: amorphous silica nanoparticles, thrombosis, toxicity, systemic inflammation

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

    Science.gov (United States)

    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.

  9. Quantitative EEG Markers in Mild Cognitive Impairment: Degenerative versus Vascular Brain Impairment

    Directory of Open Access Journals (Sweden)

    D. V. Moretti

    2012-01-01

    Full Text Available We evaluated the relationship between brain rhythmicity and both the cerebrovascular damage (CVD and amygdalohippocampal complex (AHC atrophy, as revealed by scalp electroencephalography (EEG in a cohort of subjects with mild cognitive impairment (MCI. All MCI subjects underwent EEG recording and magnetic resonance imaging. EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands. In the spectral band power the severity of CVD was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. On the other side, the group with moderate hippocampal atrophy showed the highest increase of alpha2 and alpha3 power. Moreover, when the amygdalar and hippocampal volumes are separately considered, within amygdalohippocampal complex (AHC, the increase of theta/gamma ratio is best associated with amygdalar atrophy whereas alpha3/alpha2 ratio is best associated with hippocampal atrophy. CVD and AHC damages are associated with specific EEG markers. So far, these EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI.

  10. Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Touyz R.M.

    2004-01-01

    Full Text Available Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Dylan Burger

    2016-01-01

    Full Text Available 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.

  14. Reactive Oxygen Species in Vascular Formation and Development

    OpenAIRE

    2013-01-01

    Reactive oxygen species (ROS) are derived from the metabolism of oxygen and are traditionally viewed as toxic byproducts that cause damage to biomolecules. It is now becoming widely acknowledged that ROS are key modulators in a variety of biological processes and pathological states. ROS mediate key signaling transduction pathways by reversible oxidation of certain signaling components and are involved in the signaling of growth factors, G-protein-coupled receptors, Notch, and Wnt and its dow...

  15. Vascular Cognitive Impairment: risk factors and brain MRI correlates

    NARCIS (Netherlands)

    Reijmer, Y.D.

    2012-01-01

    Vascular disease plays an important role in the development of dementia, also in patients diagnosed with Alzheimer’s disease. Risk factors such as hypertension, obesity, and type 2 diabetes, are associated with a two-fold increased risk of cognitive dysfunction and dementia. The development of cogni

  16. Isometric Exercise Training for Managing Vascular Risk Factors in Mild Cognitive Impairment and Alzheimer’s Disease

    Science.gov (United States)

    Hess, Nicole C. L.; Smart, Neil A.

    2017-01-01

    Alzheimer’s disease (AD) is the most common form of dementia diagnosed amongst the elderly. Mild cognitive impairment (MCI) is a condition often indicative of the earliest symptomatology of AD with 10%–15% of MCI patients reportedly progressing to a diagnosis of AD. Individuals with a history of vascular risk factors (VRF’s) are considered high risk candidates for developing cognitive impairment in later life. Evidence suggests that vascular injury resulting from untreated VRF’s promotes progression from MCI to AD and exacerbates the severity of dementia in AD, and neuroimaging studies have found that the neurodegenerative processes associated with AD are heavily driven by VRF’s that promote cerebral hypoperfusion. Subsequently, common links between vascular disorders such as hypertension and neurodegenerative disorders such as AD include compromised vasculature, cerebral hypoperfusion and chronic low grade inflammation (a hallmark of both hypertension and AD). Exercise has been demonstrated to be an effective intervention for blood pressure management, chronic low grade inflammation and improvements in cognition. Data from recent analyses suggests that isometric exercise training (IET) may improve vascular integrity and elicit blood pressure reductions in hypertensives greater than those seen with dynamic aerobic and resistance exercise. IET may also play an effective role in the management of VRF’s at the MCI stage of AD and may prove to be a significant strategy in the prevention, attenuation or delay of progression to AD. A plausible hypothesis is that the reactive hyperemia stimulated by IET initiates a cascade of vascular, neurotrophic and neuro-endocrine events that lead to improvements in cognitive function. PMID:28316570

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

    Science.gov (United States)

    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.

  18. Genetically elevated C-reactive protein and ischemic vascular disease

    DEFF Research Database (Denmark)

    Zacho, J.; Tybjaerg-Hansen, A.; Jensen, J.S.

    2008-01-01

    Background: Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association. Methods: We studied 10,276 persons from a general population cohort, including 1786 in whom...... ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients...... with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms. Results: The risk of ischemic heart...

  19. Physical Activity Prevents Progression for Cognitive Impairment and Vascular Dementia

    DEFF Research Database (Denmark)

    Verdelho, Ana; Madureira, Sofia; Ferro, José M

    2012-01-01

    BACKGROUND AND PURPOSE: We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. METHODS: The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates...... the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria....... Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. RESULTS: Six hundred thirty-nine subjects were included (74.1±5 years old, 55% women, 9.6±3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia...

  20. Influential factors of vascular cognitive impairment due to small vessel disease and its correlation with serum high-sensitivity C-reactive protein%小血管病性认知功能障碍的影响因素及其与血浆超敏C反应蛋白水平的相关性

    Institute of Scientific and Technical Information of China (English)

    安晓雷; 李传玲; 郭靖; 李晓宾

    2014-01-01

    目的:研究小血管病性认知功能障碍( VCI-SVD )的影响因素及其与血浆超敏C反应蛋白( hs-CRP)水平的相关性。方法给256例SVD患者进行蒙特利尔认知评估( MoCA)量表评分,以及临床资料收集和血糖化血红蛋白、血脂、hs-CRP水平检测。分为VCI-SVD组( MoCA量表评分≤26分)和无VCI-SVD组( MoCA量表评分>26分),对结果进行比较分析。结果 VCI-SVD组患者135例,无VCI-SVD组患者121例。 VCl-SVD组的血浆hs-CRP水平显著高于无VCI-SVD组( P<0.01),血糖化血红蛋白水平、收缩压,有房颤、吸烟、饮酒的比率显著高于无VCI-SVD组,受教育年限显著低于无VCI-SVD组(P<0.05~0.01)。多因素Logistic回归分析显示,在校正了年龄、收缩压、教育年限、房颤、吸烟、饮酒因素后,糖化血红蛋白、高hs-CRP血症是VCI-SVD的独立危险因素(OR=1.447,95%CI:1.25~5.54,OR=1.587,95%CI:1.87~5.67,均P<0.05)。相关分析显示,血浆hs-CRP水平与MoCA量表总分及视空间与执行能力、语言、延迟回忆各亚项评分呈负相关(r=-0.621~-0.430,均P<0.05);与命名、抽象力、定向力和注意力亚项评分无相关性。结论糖尿病、高血压、房颤和吸烟、饮酒、受教育年限低及高hs-CRP血症是VCI-SVD的影响因素;而糖尿病、高hs-CRP血症是VCI-SVD的独立危险因素。%Objective To investigate the influential factors of vascular cognitive impairment due to small vessel disease(VCI-SVD) and its correlation with serum high-sensitivity C-reactive protein ( hs-CRP).Methods Totally 256 patients with cerebral SVD were scored by Montreal Cognitive Assessment ( MoCA ) table and the level of glycosylated hemoglobin ,blood lipid and hs-CRP were measured respectively .They were divided into VCI-SVD group (MoCA≤26) and no VCI-SVD group(MoCA>26) , and the results were compared and analyzed

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

    Science.gov (United States)

    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.

  2. White Matter Damage in the Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment, No Dementia

    Science.gov (United States)

    Liu, Qing; Zhu, Zude; Teipel, Stefan J.; Yang, Jianwei; Xing, Yi; Tang, Yi; Jia, Jianping

    2017-01-01

    Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders. PMID:28289381

  3. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

    Directory of Open Access Journals (Sweden)

    Haroldo A Toque

    Full Text Available BACKGROUND: Elevated arginase (Arg activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO synthase (NOS and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC from Akita mice. METHODS AND RESULTS: Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177 (in aorta and CC and nNOS expression (in CC were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks. CONCLUSIONS: Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

  4. Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise

    Directory of Open Access Journals (Sweden)

    Ulf G. Bronas

    2017-01-01

    Full Text Available Chronic kidney disease (CKD is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

  5. Mechanisms of oxidative stress and vascular dysfunction

    Science.gov (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J

    2003-01-01

    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  6. Nitric oxide-mediated changes in vascular reactivity in pregnancy in spontaneously hypertensive rats.

    OpenAIRE

    Chu, Z. M.; Beilin, L J

    1993-01-01

    1. To examine the mechanisms which may account for pregnancy-induced vasodilatation in spontaneously hypertensive rats (SHR), we have investigated the changes in vascular reactivity and the effects of endothelial nitric oxide (NO) inhibition in the in situ blood-perfused, mesenteric resistance vessels of 18-20 day pregnant SHR. The effects of NG-nitro-L-arginine (L-NOARG) were compared in pregnant and nonpregnant SHR and gestation matched normotensive Wistar-Kyoto (WKY) rats. 2. Intra-arteria...

  7. Vascular Contributions to Cognitive Impairment and Treatments with Traditional Chinese Medicine

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    Xinhua Zhou

    2016-01-01

    Full Text Available The prevalence of cognitive impairment and dementia caused by cerebrovascular disease is likely to increase with the global aging population. Vascular contributions to cognitive impairment and dementia (VCID is a wide spectrum term used to include a diverse heterogeneous group of cognitive syndromes with vascular factors regardless of the cause of pathogenesis. VCID ranges from mild cognitive impairment to full-blown dementia with vascular dementia (VaD as the most severe stage. It is further complexed by the coexistence of other forms of dementia such as Alzheimer’s disease (AD. Recent researches in the functions of the neurovascular unit (NVU suggest that dysfunction of the NVU might be the cause of primary vascular events in the brain that leads to further neurodegeneration. In this review, we have briefly summarized various forms of VCID. There is currently no standard therapy for VCID or dementia. Given the fact that Traditional Chinese Medicine (TCM has gained popularity worldwide, we also reviewed recent scientific and clinical findings on various antidementia TCM for the treatment of VCID, including Salvia miltiorrhiza, Huperzia serrata, Ligusticum chuanxiong, Ginkgo biloba, Panax ginseng, and also TCM formula Sailuotong capsule (SLT and Fufangdanshen tablets (FFDS.

  8. Perceived racism and vascular reactivity in black college women: moderating effects of seeking social support.

    Science.gov (United States)

    Clark, Rodney

    2006-01-01

    This quasi-experimental study explored the association of perceived racism and seeking social support to vascular reactivity in a college sample of 110 Black women. Perceived racism and seeking social support were assessed via self-report, and vascular reactivity was measured before and during a standardized speaking task. Hierarchical regression analyses indicated that perceived racism was positively related to changes in systolic blood pressure. These analyses also indicated that seeking social support moderated the relationship between perceived racism and systolic blood pressure changes. This interaction effect persisted after controlling for several potential confounders. Follow-up regression analyses showed that perceived racism was positively associated with reactivity among participants who were low in seeking social support. A significant relationship was not observed between perceived racism and systolic blood pressure changes among participants who were high in seeking social support. Perceived racism and seeking social support were not significantly associated with changes in diastolic blood pressure. These findings highlight the importance of examining psychosocial factors that may mitigate the hypothesized relationship between perceived racism and reactivity.

  9. Pathology and pathogenesis of vascular cognitive impairment – A critical update

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    Kurt A. Jellinger

    2013-04-01

    Full Text Available Vascular cognitive impairment describes a continuum of cognitive diorders ranging from mild cognitive impairment to dementia, in which vascular brain injury involving regions important for memory, cognition and behaviour plays an important role. Classification, prevalence, and pathophysiology are a matter of current research. Clinical diagnostic criteria show moderate sensitivity (ca 50% and variable specificity (range 64-98%. In Western clinical series, VaD is suggested in 8-10% of cognitively impaired elderly subjects. Its prevalence in autopsy series varies from 0.03 to 58%. In contrast to Alzheimer disease (AD and mixed dementia showing significant age-related increase, the prevalence of VaD significantly decreases after age 80 years. Cognitive decline is commonly associated with widespread small ischemic vascular lesions involving subcortical brain areas. The lesions affect neuronal networks involved in cognition, memory, and behavior.Cerebrovascular lesions (CVLs often coexist wth Alzheimer-type lesions and other pathologies. The lesion pattern of "pure" VaD differs from that in mixed dementia (AD + CVLs, which suggests different pathogenesis of both phenotypes. Minor CVLs appear not essential for cognitive impairment in full-blown AD, while both mild AD-type pathology and small vessel disease may interact synergistically in promoting and progressing dementia. However, both AD-related and vascular brain pathologies have been reported.Despite recent suggestions for staging and grading CVLs in specific brain areas, no validated neuropathological criteria are currently available for VaD and mixed dementia. Further clinico-pathological studies and harmonization of neuropathological procedures are needed to validate the diagostic criteria for VaD and mixed dementia in order to clarify the impact of CVLs and other coexistent pathologies on cognitive impairment as a basis for further successful therapeutic options.

  10. Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer’s disease

    Science.gov (United States)

    Kimbrough, Ian F.; Robel, Stefanie

    2015-01-01

    Reduced cerebral blood flow impairs cognitive function and ultimately causes irreparable damage to brain tissue. The gliovascular unit, composed of neural and vascular cells, assures sufficient blood supply to active brain regions. Astrocytes, vascular smooth muscle cells, and pericytes are important players within the gliovascular unit modulating vessel diameters. While the importance of the gliovascular unit and the signals involved in regulating local blood flow to match neuronal activity is now well recognized, surprisingly little is known about this interface in disease. Alzheimer’s disease is associated with reduced cerebral blood flow. Here, we studied how the gliovascular unit is affected in a mouse model of Alzheimer’s disease, using a combination of ex vivo and in vivo imaging approaches. We specifically labelled vascular amyloid in living mice using the dye methoxy-XO4. We elicited vessel responses ex vivo using either pharmacological stimuli or cell-specific calcium uncaging in vascular smooth muscle cells or astrocytes. Multi-photon in vivo imaging through a cranial window allowed us to complement our ex vivo data in the presence of blood flow after label-free optical activation of vascular smooth muscle cells in the intact brain. We found that vascular amyloid deposits separated astrocyte end-feet from the endothelial vessel wall. High-resolution 3D images demonstrated that vascular amyloid developed in ring-like structures around the vessel circumference, essentially forming a rigid cast. Where vascular amyloid was present, stimulation of astrocytes or vascular smooth muscle cells via ex vivo Ca2+ uncaging or in vivo optical activation produced only poor vascular responses. Strikingly, vessel segments that were unaffected by vascular amyloid responded to the same extent as vessels from age-matched control animals. We conclude that while astrocytes can still release vasoactive substances, vascular amyloid deposits render blood vessels rigid and

  11. Impaired abstract thinking may discriminate between normal aging and vascular mild cognitive impairment O pensamento abstrato comprometido pode diferenciar o envelhecimento normal do comprometimento cognitivo leve vascular

    Directory of Open Access Journals (Sweden)

    Felipe Kenji Sudo

    2010-04-01

    Full Text Available OBJECTIVE: Cerebrovascular disease (CVD is associated with cognitive deficits. This cross-sectional study examines differences among healthy elderly controls and patients with vascular mild cognitive impairment (VaMCI and vascular dementia (VaD in performances on CAMCOG subscales. METHOD: Elderly individuals (n=61 were divided into 3 groups, according to cognitive and neuroimaging status: 16 controls, 20 VaMCI and 25 VaD. VaMCI and VaD individuals scored over 4 points on the Hachinski Ischemic Scale. RESULTS: Significant differences in total CAMCOG scores were observed across the three groups (pOBJETIVO: A doença cerebrovascular (DCV associa-se a déficits cognitivos. Este estudo transversal objetiva examinar diferenças entre controles saudáveis idosos e pacientes com comprometimento cognitivo leve vascular (CCLV e demência vascular (DV nas subescalas do CAMCOG. MÉTODO: Indivíduos idosos (n=61 foram divididos em 3 grupos, de acordo com o perfil cognitivo e com a neuroimagem: 16 controles, 20 CCLV e 25 DV. Pacientes com CCLV e DV pontuaram acima de 4 pontos no Escore Isquêmico de Hachinski. RESULTADOS: Diferenças significativas foram observadas entre os três grupos no resultado final do CAMCOG. Pacientes com DV obtiveram escores inferiores àqueles dos indivíduos com CCLV em quase todas as subescalas. Todas as subescalas mostraram diferenças entre DV e controles. O desempenho no item pensamento abstrato mostrou diferenças entre CCLV e controles. CONCLUSÃO: O CAMCOG diferenciou controles de pacientes com CCLV e DV. A avaliação do pensamento abstrato pode ser útil para discriminar CCLV de controles.

  12. Vascular Pericyte Impairment and Connexin43 Gap Junction Deficit Contribute to Vasomotor Decline in Diabetic Retinopathy.

    Science.gov (United States)

    Ivanova, Elena; Kovacs-Oller, Tamas; Sagdullaev, Botir T

    2017-08-09

    Adequate blood flow is essential to brain function, and its disruption is an early indicator in diseases, such as stroke and diabetes. However, the mechanisms contributing to this impairment remain unclear. To address this gap, in the diabetic and nondiabetic male mouse retina, we combined an unbiased longitudinal assessment of vasomotor activity along a genetically defined vascular network with pharmacological and immunohistochemical analyses of pericytes, the capillary vasomotor elements. In nondiabetic retina, focal stimulation of a pericyte produced a robust vasomotor response, which propagated along the blood vessel with increasing stimulus. In contrast, the magnitude, dynamic range, a measure of fine vascular diameter control, and propagation of vasomotor response were diminished in diabetic retinas from streptozotocin-treated mice. These functional changes were linked to several mechanisms. We found that density of pericytes and their sensitivity to stimulation were reduced in diabetes. The impaired response propagation from the stimulation site was associated with lower expression of connexin43, a major known gap junction unit in vascular cells. Indeed, selective block of gap junctions significantly reduced propagation but not initiation of vasomotor response in the nondiabetic retina. Our data establish the mechanisms for fine local regulation of capillary diameter by pericytes and a role for gap junctions in vascular network interactions. We show how disruption of this balance contributes to impaired vasomotor control in diabetes.SIGNIFICANCE STATEMENT Identification of mechanisms governing capillary blood flow in the CNS and how they are altered in disease provides novel insight into early states of neurological dysfunction. Here, we present physiological and anatomical evidence that both intact pericyte function as well as gap junction-mediated signaling across the vascular network are essential for proper capillary diameter control and vasomotor

  13. Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes

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    Seok Man Son

    2012-06-01

    Full Text Available Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in subjects with diabetes. Disorders of the physiological signaling functions of reactive oxygen species (superoxide and hydrogen peroxide and reactive nitrogen species (nitric oxide and peroxynitrite are important features of diabetes. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the vascular complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great benefit to these subjects. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigation of therapeutic interventions to prevent or delay the progression of diabetic vascular complications is needed.

  14. Treating vascular mild cognitive impairment by acupuncture: a systematic review of randomized controlled trials

    Institute of Scientific and Technical Information of China (English)

    周丽

    2014-01-01

    Objective To systematically evaluate the effect and safety of acupuncture in the treatment of vascular mild cognitive impairment(VMCI).Methods Recruited were China National Knowledge Infrastructure Database(CNKI)(1979—2012),Chinese Science and Technology Periodical Database(VIP)(1989—2012),Chinese Biomedical Database(CBM),Wanfang degree and conference papers database(1985—2012),PubMed Database(1966—2012),and The Cochrane Library(Issue 1,2012).The search date ended in

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

    Science.gov (United States)

    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.

  16. Oral P. gingivalis infection alters the vascular reactivity in healthy and spontaneously atherosclerotic mice

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    Stefanon Ivanita

    2011-05-01

    Full Text Available Abstract Background Considering that recent studies have demonstrated endothelial dysfunction in subjects with periodontitis and that there is no information about vascular function in coexistence of periodontitis and atherosclerosis, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on vascular reactivity in healthy and hypercholesterolemic apolipoprotein E-deficient (ApoE mice. In vitro preparations of mesenteric arteriolar bed were used to determine the vascular responses to acetylcholine, sodium nitroprusside and phenylephrine (PE. Results Alveolar bone resorption, an evidence of periodontitis, was assessed and confirmed in all infected mice. Acetylcholine- and sodium nitroprusside-induced vasorelaxations were similar among all groups. Non-infected ApoE mice were hyperreactive to PE when compared to non-infected healthy mice. P gingivalis infection significantly enhanced the vasoconstriction to PE in both healthy and spontaneous atherosclerotic mice, when compared to their respective controls. Conclusions This study demonstrates that oral P gingivalis affects the alpha-adrenoceptor-mediated vascular responsiveness in both healthy and spontaneous atherosclerotic mice, reinforcing the association between periodontitis and cardiovascular diseases.

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

    Science.gov (United States)

    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.

  18. Evidence-based medical research on diagnostic criteria and screening technique of vascular mild cognitive impairment

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    Xia-wei LIU

    2015-07-01

    Full Text Available Background Vascular mild cognitive impairment (VaMCI is the prodromal syndrome of vascular dementia (VaD and key target for drug treatment. There is controversy over the diagnostic criteria and screening tools of VaMCI, which affects its clinical diagnosis. This paper aims to explore the clinical features, diagnostic criteria and screening technique of VaMCI.  Methods Taking "vascular mild cognitive impairment OR vascular cognitive impairment no dementia" as retrieval terms, search in PubMed database from January 1997 to March 2015 and screen relevant literatures concerning VaMCI. According to Guidance for the Preparation of Neurological Management Guidelines revised by European Federation of Neurological Societies (EFNS in 2004, evidence grading was performed on literatures. Results A total of 32 literatures in English were selected according to inclusion and exclusion criteria, including 3 guidelines and consensus and 29 clinical studies. Seven literatures (2 on Level Ⅰ, 5 on Level Ⅱ studied on neuropsychological features in VaMCI patients and found reduced processing speed and executive function impairment were main features. Two literatures reported the diagnostic criteria of VaMCI, including VaMCI criteria published by American Heart Association (AHA/American Stroke Association (ASA in 2011 and "Diagnostic Criteria for Vascular Cognitive Disorders" published by International Society for Vascular Behavioral and Cognitive Disorders (VASCOG in 2014. Fifteen literatures (4 on LevelⅠ, 11 on Level Ⅱ described the diagnostic criteria of VaMCI used in clinical research, from which 6 operational diagnostic items were extracted. Fourteen literatures (4 on Level Ⅰ, 10 on Level Ⅱ described neuropsychological assessment tools for VaMCI screening, and found the 5-minute protocol recommended by National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN was being good consistency with other neuropsychological

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

    Energy Technology Data Exchange (ETDEWEB)

    Franco, O.S.; Paulitsch, F.S.; Pereira, A.P.C.; Teixeira, A.O. [Universidade Federal do Rio Grande, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Martins, C.N. [Universidade Federal do Rio Grande, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Fisiologia Animal Comparada, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Silva, A.M.V. [Universidade Federal de Santa Maria, Departamento de Fisioterapia e Reabilitação, Santa Maria, RS, Brasil, Departamento de Fisioterapia e Reabilitação, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil); Plentz, R.D.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Ciências da Reabilitação, Programa de Pós-Graduação em Ciências da Saúde, Porto Alegre, RS, Brasil, Programa de Pós-Graduação em Ciências da Saúde, Programa de Pós-Graduação em Ciências da Reabilitação, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Irigoyen, M.C. [Faculdade de Medicina, Universidade de São Paulo, Instituto do Coração, Unidade de Hipertensão, São Paulo, SP, Brasil, Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Signori, L.U. [Universidade Federal do Rio Grande, Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Universidade Federal do Rio Grande, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Fisiologia Animal Comparada, Rio Grande, RS, Brasil, Programa de Pós-Graduação em Fisiologia Animal Comparada, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS (Brazil); Universidade Federal de Santa Maria, Departamento de Fisioterapia e Reabilitação, Santa Maria, RS, Brasil, Departamento de Fisioterapia e Reabilitação, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2014-04-04

    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.

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

    Directory of Open Access Journals (Sweden)

    O.S. Franco

    2014-05-01

    Full Text Available 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.

  1. Differential vascular reactivity responses acutely following ingestion of a nitrate rich red spinach extract.

    Science.gov (United States)

    Haun, Cody T; Kephart, Wesley C; Holland, Angelia M; Mobley, Christopher B; McCloskey, Anna E; Shake, Joshua J; Pascoe, David D; Roberts, Michael D; Martin, Jeffrey S

    2016-12-01

    Inorganic nitrate ingestion has been posited to affect arterial blood pressure and vascular function. We sought to determine the acute effect of a red spinach extract (RSE) high in inorganic nitrate on vascular reactivity 1-h after ingestion in peripheral conduit and resistance arteries. Fifteen (n = 15; males 8, females 7) apparently healthy subjects (aged 23.1 ± 3.3 years; BMI 27.2 ± 3.7 kg/m(2)) participated in this crossover design, double-blinded study. Subjects reported to the lab ≥2-h post-prandial and consumed RSE (1000 mg dose; ~90 mg nitrate) or placebo (PBO). Venipuncture was performed on three occasions: baseline, 30-min post-ingestion and between 65 to 75-min post-ingestion. Baseline vascular measurements [i.e., calf venous occlusion plethysmography, brachial artery flow-mediated dilation (FMD)], 30-min of continuous blood pressure (BP) and heart rate (HR) analysis, and follow-up vascular measurements beginning at 40-min post-ingestion were also performed. Humoral nitrate following RSE ingestion was significantly higher at 30- (+54 %; P = 0.039) and 65 to 75-min post-ingestion compared to baseline (+255 %, P RSE ingestion, whereas it decreased (-14.0 %; P = 0.008) following PBO ingestion. No significant differential FMD responses were detected (P > 0.05), though RH was decreased following the baseline measure in both conditions. RSE significantly increased plasma nitrate 30-min post-ingestion, but acute microvascular (i.e., resistance vasculature) reactivity increases were isolated to the lower limb and no appreciable change in brachial artery FMD was observed.

  2. Mesoglycan improves vascular reactivity and insulin sensitivity in patients with metabolic syndrome.

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    Valvano, Antonio; Bosso, Giorgio; Apuzzi, Valentina; Riccone, Filippo; Saccà, Luigi; Oliviero, Ugo

    2015-12-01

    The aim of this study was to evaluate the acute and chronic effects of mesoglycan on the endothelial function and arterial elastic properties in patients with metabolic syndrome (MetS). MetS is defined by a clustering of vascular risk factors that demand both pharmacologic and non-pharmacologic interventions, including body weight reductions and physical activity. The correction of endothelial dysfunction and arterial wall distensibility associated with MetS have lately received increasing interest. Thirty consecutive ambulatory patients affected by MetS were 2:1 randomized in a double-blind fashion to receive mesoglycan or placebo, respectively. In the first phase of the study, we evaluated the acute effects of a single i.m. administration of mesoglycan (60 mg) or placebo on vascular reactivity, as assessed by brachial flow-mediated dilation (FMD). Then, patients were chronically treated with mesoglycan per os (50 mg twice a day) or placebo for 90 days. At the end of this period, vascular reactivity and the arterial wall elastic properties were evaluated. In the mesoglycan group, FMD increased above baseline after acute administration, with a maximum increment of 52% after 2 h. FMD was also significantly greater than baseline after 90 days of chronic treatment. In the placebo group, FMD was unaffected by both acute and chronic mesoglycan administration. Moreover, after 90 days of mesoglycan treatment, a marked improvement in arterial distensibility and compliance was detected and arterial stiffness reduced significantly. This small, preliminary study shows that mesoglycan exerts relevant effects on vascular physiology, both in an acute setting as well as after prolonged, three-month treatment, in patients affected by metabolic syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Chronic lead exposure decreases the vascular reactivity of rat aortas: the role of hydrogen peroxide.

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    Karolini Zuqui Nunes

    Full Text Available We investigated whether exposure to small concentrations of lead alters blood pressure and vascular reactivity. Male Wistar rats were sorted randomly into the following two groups: control (Ct and treatment with 100 ppm of lead (Pb, which was added to drinking water, for 30 days. Systolic blood pressure (BP was measured weekly. Following treatment, aortic ring vascular reactivity was assessed. Tissue samples were properly stored for further biochemical investigation. The lead concentration in the blood reached approximately 8 μg/dL. Treatment increased blood pressure and decreased the contractile responses of the aortic rings to phenylephrine (1 nM-100 mM. Following N-nitro-L arginine methyl ester (L-NAME administration, contractile responses increased in both groups but did not differ significantly between them. Lead effects on Rmax were decreased compared to control subjects following superoxide dismutase (SOD administration. Catalase, diethyldithiocarbamic acid (DETCA, and apocynin increased the vasoconstrictor response induced by phenylephrine in the aortas of lead-treated rats but did not increase the vasoconstrictor response in the aortas of untreated rats. Tetraethylammonium (TEA potentiated the vasoconstrictor response induced by phenylephrine in aortic segments in both groups, but these effects were greater in lead-treated rats. The co-incubation of TEA and catalase abolished the vasodilatory effect noted in the lead group. The present study is the first to demonstrate that blood lead concentrations well below the values established by international legislation increased blood pressure and decreased phenylephrine-induced vascular reactivity. The latter effect was associated with oxidative stress, specifically oxidative stress induced via increases in hydrogen peroxide levels and the subsequent effects of hydrogen peroxide on potassium channels.

  4. Hypercapnic evaluation of vascular reactivity in healthy aging and acute stroke via functional MRI

    OpenAIRE

    Raut, Ryan V.; Nair, Veena A.; Sattin, Justin A.; Vivek Prabhakaran

    2016-01-01

    Functional MRI (fMRI) is well-established for the study of brain function in healthy populations, although its clinical application has proven more challenging. Specifically, cerebrovascular reactivity (CVR), which allows the assessment of the vascular response that serves as the basis for fMRI, has been shown to be reduced in healthy aging as well as in a range of diseases, including chronic stroke. However, the timing of when this occurs relative to the stroke event is unclear. We used a br...

  5. Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents

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    Natália Portela

    Full Text Available Abstract Background: A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. Objective: To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. Methods: The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years and 14 without (FH-; 27 ± 5 years a family history of hypertension. Blood pressure, heart rate (DIXTAL®, forearm blood flow (Hokanson®, and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®. Results: At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96, heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18, forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16, and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21, respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86, heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86, and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25, respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03. Conclusion: Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

  6. Vascular Cognitive Impairment through the Looking Glass of Transcranial Magnetic Stimulation

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    Giuseppe Lanza

    2017-01-01

    Full Text Available In the last years, there has been a significant growth in the literature exploiting transcranial magnetic stimulation (TMS with the aim at gaining further insights into the electrophysiological and neurochemical basis underlying vascular cognitive impairment (VCI. Overall, TMS points at enhanced brain cortical excitability and synaptic plasticity in VCI, especially in patients with overt dementia, and neurophysiological changes seem to correlate with disease process and progress. These findings have been interpreted as part of a glutamate-mediated compensatory effect in response to vascular lesions. Although a single TMS parameter owns low specificity, a panel of measures can support the VCI diagnosis, predict progression, and possibly identify early markers of “brain at risk” for future dementia, thus making VCI a potentially preventable cause of both vascular and degenerative dementia in late life. Moreover, TMS can be also exploited to select and evaluate the responders to specific drugs, as well as to become an innovative rehabilitative tool in the attempt to restore impaired neural plasticity. The present review provides a perspective of the different TMS techniques by further understanding the cortical electrophysiology and the role of distinctive neurotransmission pathways and networks involved in the pathogenesis and pathophysiology of VCI and its subtypes.

  7. Vascular Cognitive Impairment through the Looking Glass of Transcranial Magnetic Stimulation

    Science.gov (United States)

    2017-01-01

    In the last years, there has been a significant growth in the literature exploiting transcranial magnetic stimulation (TMS) with the aim at gaining further insights into the electrophysiological and neurochemical basis underlying vascular cognitive impairment (VCI). Overall, TMS points at enhanced brain cortical excitability and synaptic plasticity in VCI, especially in patients with overt dementia, and neurophysiological changes seem to correlate with disease process and progress. These findings have been interpreted as part of a glutamate-mediated compensatory effect in response to vascular lesions. Although a single TMS parameter owns low specificity, a panel of measures can support the VCI diagnosis, predict progression, and possibly identify early markers of “brain at risk” for future dementia, thus making VCI a potentially preventable cause of both vascular and degenerative dementia in late life. Moreover, TMS can be also exploited to select and evaluate the responders to specific drugs, as well as to become an innovative rehabilitative tool in the attempt to restore impaired neural plasticity. The present review provides a perspective of the different TMS techniques by further understanding the cortical electrophysiology and the role of distinctive neurotransmission pathways and networks involved in the pathogenesis and pathophysiology of VCI and its subtypes. PMID:28348458

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

    Science.gov (United States)

    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.

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

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    Wender Nascimento Rouver

    Full Text Available 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.

  10. Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.

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    Bataillard, A; Blanc-Brunat, N; Vivier, G; Medeiros, I; Zhang, B L; Touraine, J L; Sassard, J

    1996-02-01

    The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.

  11. Fatty acid-induced changes in vascular reactivity in healthy adult rats.

    Science.gov (United States)

    Christon, Raymond; Marette, André; Badeau, Mylène; Bourgoin, Frédéric; Mélançon, Sébastien; Bachelard, Hélène

    2005-12-01

    Dietary fatty acids (FAs) are known to modulate endothelial dysfunction, which is the first stage of atherosclerosis. However, their exact role in this initial phase is still unclear. The effects of isolated or combined (by 2) purified FAs from the main FA families were studied on the vascular response of isolated thoracic aorta in healthy rats to get a better understanding of the mechanisms of action of dietary FAs in regulating vascular endothelial function. Cumulative contraction curves to phenylephrine and relaxation curves to carbachol and then to sodium nitroprusside were obtained in the absence or presence of the FAs studied allowing endothelium-dependent and endothelium-independent ability of the smooth muscle to relax to be assessed in each experimental group. The endothelium-dependent vasodilator response to carbachol was lowered by eicosapentaenoic acid, whereas it was not altered either by docosahexaenoic acid alone or by combined eicosapentaenoic acid-docosahexaenoic acid, oleic acid, or stearic acid, and it was increased by linoleic acid (LA). A decreased phenylephrine-induced contraction was observed after incubation with arachidonic acid and with stearic acid. On the other hand, the endothelium-dependent relaxation was reduced by the addition of combined LA-arachidonic acid and LA-oleic acid. In conclusion, these data point out the differential effects of different types of FAs and of FAs alone vs combined on vascular reactivity. The complex nature of these effects could be partially linked to metabolic specificities of endothelial cells and to interactions between some FAs.

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

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    Morteza Naghavi

    2016-01-01

    Full Text Available 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.

  13. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species.

    Science.gov (United States)

    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

  14. Vascular Parkinsonism and cognitive impairment: literature review, Brazilian studies and case vignettes

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    Thiago Cardoso Vale

    Full Text Available ABSTRACT Vascular Parkinsonism (VP is a form of secondary Parkinsonism resulting from cerebrovascular disease. Estimates of the frequency of VP vary greatly worldwide; 3% to 6% of all cases of Parkinsonism are found to have a vascular etiology. In a Brazilian community-based study on Parkinsonism, 15.1% of all cases were classified as VP, the third most common form, with a prevalence of 1.1% in an elderly cohort. Another Brazilian survey found a prevalence of 2.3% of VP in the elderly. VP is usually the result of conventional vascular risk factors, particularly hypertension, leading to strategic infarcts of subcortical gray matter nuclei, diffuse white matter ischaemic lesions and less commonly, large vessel infarcts. Patients with VP tend to be older and present with gait difficulties, symmetrical predominant lower-body involvement, poor levodopa responsiveness, postural instability, falls, cognitive impairment and dementia, corticospinal findings, urinary incontinence and pseudobulbar palsy. This article intends to provide physicians with an insight on the practical issues of VP, a disease potentially confounded with vascular dementia, idiopathic Parkinson's disease, dementia with Lewy bodies and other secondary causes of Parkinsonism.

  15. White matter hyperintensities, executive function and global cognitive performance in vascular mild cognitive impairment

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    Felipe Kenji Sudo

    2013-07-01

    Full Text Available Vascular mild cognitive impairment (VaMCI represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. Methods Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15 were compared to normal controls (NC, n=11 and correlated with Fazekas scale. Results VaMCI performed significantly worse than NC in Trail-Making Test (TMT B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors, difference TMT B-A and CAMCOG total score. Conclusion Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.

  16. The profile of behavioral and psychological symptoms in vascular cognitive impairment with and without dementia

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    Meena Gupta

    2013-01-01

    Full Text Available Objective: The objective of this study was to compare the occurrence and severity of behavioral and psychological symptoms of dementia (BPSD between vascular dementia (VaD and vascular cognitive impairment-no dementia (VCI-ND. Materials and Methods: Consecutive patients presenting with cognitive impairment at least 3 months after an ischemic stroke and with a Hachinski Ischemic Score ≥4 were included. VaD was diagnosed as per National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherche et l′Enseignement en Neurosciences criteria for probable VaD and VCI-ND on the lines of the Canadian study of health and aging. The severity of cognitive impairment and the behavioral/psychological symptoms were studied by means of the clinical dementia rating scale and the neuropsychiatric inventory (NPI respectively. Results: All patients with VaD and 89% of those with VCI-ND had at least one BPSD. The mean no. of symptoms per patient and the total NPI scores were higher in VaD than in VCI-ND. Apathy and night-time behavior disturbances were significantly more common and severe in VaD. Conclusions: BPSD are very common both in VCI-ND and in VaD. The profile of BPSD is similar in both groups, albeit more severe in VaD. The net burden of BPSD is higher in VaD as compared to VCI-ND.

  17. Lessons from a Mouse Model Characterizing Features of Vascular Cognitive Impairment with White Matter Changes

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    Masafumi Ihara

    2011-01-01

    Full Text Available With the demographic shift in age in advanced countries inexorably set to progress in the 21st century, dementia will become one of the most important health problems worldwide. Vascular cognitive impairment is the second most common type of dementia after Alzheimer's disease and is frequently responsible for the cognitive decline of the elderly. It is characterized by cerebrovascular white matter changes; thus, in order to investigate the underlying mechanisms involved in white matter changes, a mouse model of chronic cerebral hypoperfusion has been developed, which involves the narrowing of the bilateral common carotid arteries with newly designed microcoils. The purpose of this paper is to provide a comprehensive summary of the achievements made with the model that shows good reproducibility of the white matter changes characterized by blood-brain barrier disruption, glial activation, oxidative stress, and oligodendrocyte loss following chronic cerebral hypoperfusion. Detailed characterization of this model may help to decipher the substrates associated with impaired memory and move toward a more integrated therapy of vascular cognitive impairment.

  18. Disinhibited reactive attachment disorder symptoms impair social judgements from faces.

    Science.gov (United States)

    Miellet, Sebastien; Caldara, Roberto; Gillberg, Christopher; Raju, Monika; Minnis, Helen

    2014-03-30

    Typically developing adults and children can rapidly reach consensus regarding the trustworthiness of unfamiliar faces. Maltreated children can have problems with trusting others, yet those with the disinhibited form of reactive attachment disorder (dRAD) can be indiscriminately friendly. Whether children with dRAD symptoms appraise and conform to typical judgements about trustworthiness of faces is still unknown. We recorded eye movements of 10 maltreated dRAD children and 10 age and gender matched typically developing control children while they made social judgements from faces. Children were presented with a series of pairs of faces previously judged by adults to have high or low attractiveness or trustworthiness ratings. Typically developing children reached a consensus regarding which faces were the most trustworthy and attractive. There was less agreement among the children with dRAD symptoms. Judgments from the typically developing children showed a strong correlation between the attractiveness and trustworthiness tasks. This was not the case for the dRAD group, who showed less agreement and no significant correlation between trustworthiness and attractiveness judgments. Finally, both groups of children sampled the eye region to perform social judgments. Our data offer a unique insight in children with dRAD symptoms, providing novel and important knowledge for their rehabilitation.

  19. The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

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    Nilton Hideto Takiuti

    1999-09-01

    Full Text Available CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams and age (90 to 116 days. INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats; pregnant control rats (8 rats; virgin rats treated with L-NAME (10 rats; virgin control rats (12 rats. The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME, in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

  20. Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

    Science.gov (United States)

    Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

    2006-02-01

    Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all

  1. Effects of cerebrolysin on moderate cognitive impairments in cerebral vascular insufficiency (a clinical-electrophysiological study).

    Science.gov (United States)

    Damulin, I V; Koberskaya, N N; Mkhitaryan, E A

    2008-07-01

    The efficacy of treatment with cerebrolysin was studied in 40 patients with cerebral vascular insufficiency. Cerebrolysin (20 daily i.v. infusions of 10 ml in 200 ml of physiological saline) was found to be an effective means of treating this group of patients. Courses of cerebrolysin treatment decreased the severity of memory and attention impairments, improving the overall cognitive status of the patients. Clinical observations and neuropsychological testing were supported by electrophysiological results, in terms of the P300 cognitive evoked potential. The effects of treatment at the doses used here were delayed and were seen three months after completion of treatment.

  2. Prospective and retrospective memory in Alzheimer's disease and vascular dementia: similar patterns of impairment.

    Science.gov (United States)

    Livner, Asa; Laukka, Erika J; Karlsson, Sari; Bäckman, Lars

    2009-08-15

    Prospective memory (ProM) involves remembering to perform actions after a delay, such as buying groceries on the way home from work. Retrospective memory (RetM) involves remembering events from the past. It is known that the memory impairment in Alzheimer's disease (AD) generalizes across (a) these two types of memory, and (b) encoding, storage, and retrieval within RetM. Corresponding knowledge regarding these issues is sparse in vascular dementia (VaD). The aim of this study was, therefore, to compare the two dementia etiologies regarding patterns of impairment in ProM and RetM tasks. From a population-based study, 21 persons with VaD, 79 with AD, and 352 controls were included. Both dementia groups were impaired on all ProM and RetM variables, but did not differ from one another on any measure. The results are discussed relative to a network view of episodic memory, in which alterations at different sites may result in similar functional impairments.

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

    Science.gov (United States)

    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. The impact of vascular comorbidities on qualitative error analysis of executive impairment in Alzheimer's disease.

    Science.gov (United States)

    Lamar, Melissa; Libon, David J; Ashley, Angela V; Lah, James J; Levey, Allan I; Goldstein, Felicia C

    2010-01-01

    Recent evidence suggests that patients with Alzheimer's disease (AD) and vascular comorbidities (VC) perform worse across measures of verbal reasoning and abstraction when compared to patients with AD alone. We performed a qualitative error analysis of Wechsler Adult Intelligence Scale-III Similarities zero-point responses in 45 AD patients with varying numbers of VC, including diabetes, hypertension, and hypercholesterolemia. Errors were scored in set if the answer was vaguely related to how the word pair was alike (e.g., dog-lion: "they can be trained") and out of set if the response was unrelated ("a lion can eat a dog"). AD patients with 2-3 VC did not differ on Similarities total score or qualitative errors from AD patients with 0-1 VC. When analyzing the group as a whole, we found that increasing numbers of VC were significantly associated with increasing out of set errors and decreasing in set errors in AD. Of the vascular diseases investigated, it was only the severity of diastolic blood pressure that significantly correlated with out of set responses. Understanding the contribution of VC to patterns of impairment in AD may provide support for directed patient and caregiver education concerning the presentation of a more severe pattern of cognitive impairment in affected individuals.

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

    Science.gov (United States)

    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.

  6. Inflammation and vascular disease:the role of C-reactive protein

    Institute of Scientific and Technical Information of China (English)

    Matthew J. Sorrentino; Loan Pham; Thach Nguyen

    2004-01-01

    Inflammation is an important component of active atherosclerotic disease. C-reactive protein (CRP)is a non-specific inflammatory marker that is increased in inflammatory conditions. Newer more sensitive assays (high sensitivity CRP) can detect the low levels of inflammation associated with vascular disease. CRP levels can give further risk assessment to individuals beyond predictions from traditional risk factors. This measurement is most useful in helping to discriminate risk in intermediate risk patients such as metabolic syndrome patients. Exercise and weight loss have been shown to significantly lower CRP levels. Lipid lowering therapies, especially with the statin class of medications, also lower CRP levels. A reduction in inflammation may be an important component of plaque stabilization and contribute to cardiovascular risk reduction.

  7. Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study.

    Science.gov (United States)

    Cotroneo, Antonino Maria; Castagna, Alberto; Putignano, Salvatore; Lacava, Roberto; Fantò, Fausto; Monteleone, Francesco; Rocca, Filomena; Malara, Alba; Gareri, Pietro

    2013-01-01

    The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67-90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study. MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically

  8. The association between vascular factors and subjective memory impairment in older people: The HUNT Study, Norway

    Directory of Open Access Journals (Sweden)

    Ellen Melbye Langballe

    2012-11-01

    Full Text Available Objectives: Subjective memory impairment (SMI is often considered an early sign of dementia. This study investigates the relationship between SMI and dementia-related vascular factors in older people.Method: This study was based on data from 12,255 individuals, 65 years and older, participating in the Nord-Trøndelag health study, third survey 2006-08 (HUNT3. SMI, vascular diseases, exercise, smoking, and alcohol consumption were self-reported. Blood pressure, cholesterol and body mass index (BMI were clinically measured. SMI were predicted using linear regression analysis.Results: Stroke and heart disease were associated with SMI. High exercise intensity was associated with less SMI. Respondents with high systolic blood pressure (SBP reported less SMI than those with moderate SBP. In men, low SBP was associated with significantly more SMI compared to those with moderate SBP. In women, moderate alcohol consumption compared to low alcohol consumption was associated with significantly more SMI.Conclusion: SMI was positively associated with stroke and heart disease in this study. For the other investigated vascular factors, we did not find strong relationships with SMI. However, for preventive and treatment purposes, it is noteworthy that high exercise intensity and high systolic blood pressure was associated with less SMI in both genders.

  9. Impaired cardiac response to exercise in post-menopausal women: relationship with peripheral vascular function.

    Science.gov (United States)

    Yoshioka, J; Node, K; Hasegawa, S; Paul, A K; Mu, X; Maruyama, K; Nakatani, D; Kitakaze, M; Hori, M; Nishimura, T

    2003-04-01

    Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged 50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; PPost-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause.

  10. Mild cognitive impairment: vascular risk factors in community elderly in four cities of Hebei Province, China.

    Directory of Open Access Journals (Sweden)

    Yumei Wang

    Full Text Available Evidence has demonstrated that vascular risk factors (VRFs contribute to mild cognitive impairment (MCI in the elderly population. Because of the race and different diagnosis standard, there is still no definitive conclusions.To estimate the VRFs and potential protective factors for MCI in elderly population living in the community in North China.A total of 3136 participants entered the study. They were screened for hypertension, coronary heart disease (CHD, and cerebrovascular disease (CVD. Cognitive function was assessed with Mini-Mental State Examination (MMSE and the Montreal Cognitive Assessment (MoCA. The diagnosis of MCI was made according to Petersen's criteria. We investigated the relationship between vascular risk factors, potential protective factors and MCI.A total of 2511 (80% participant belonged to normal group and 625 (20% participants showed MCI. Multiple logistic regression analysis demonstrated that stroke and diabetes, but not hypertension or CHD was associated with MCI. Besides, exercise habit could lower the risk of MCI.Vascular Risk Factors, including stroke and diabetes, rather than hypertension and CHD are independent risk factors of MCI. Involvement in physical activities seems to reduce the risk of MCI.

  11. Increased renal vascular reactivity to ANG II after unilateral nephrectomy in the rat involves 20-HETE.

    Science.gov (United States)

    Joly, E; Seqqat, R; Flamion, B; Caron, N; Michel, A; Imig, J D; Kramp, R

    2006-10-01

    This study examined the role of intrarenal ANG II in the renal vascular reactivity changes occurring in the remaining kidney undergoing adaptation following contralateral nephrectomy. Renal blood flow responses to intrarenal injections of ANG II (0.25 to 5 ng) were measured in anesthetized euvolemic male Wistar rats 1, 4, 12, and 24 wk after uninephrectomy (UNX) or sham procedure (SHAM). At week 4, renal vasoconstriction induced by 2 ng ANG II was greater in UNX (69 +/- 5%) than in SHAM rats (50 +/- 3%; P < 0.01). This response was inhibited, by 50 and 66%, and by 20 and 25%, in SHAM and UNX rats, after combined injections of ANG II and losartan, or PD-123319 (P < 0.05), respectively. Characteristics of ANG II receptor binding in isolated preglomerular resistance vessels were similar in the two groups. After prostanoid inhibition with indomethacin, renal vasoconstriction was enhanced by 42 +/- 8% (P < 0.05), only in SHAM rats, whereas after 20-HETE inhibition with HET0016, it was reduced by 53 +/- 16% (P < 0.05), only in UNX rats. These differences vanished after concomitant prostanoid and 20-HETE inhibition in the two groups. After UNX, renal cortical protein expression of cytochrome P-450 2c23 isoform (CYP2c23) and cyclooxygenase-1 (COX-1) was unaltered, but it was decreased for CYP4a and increased for COX-2. In conclusion, renal vascular reactivity to ANG II was significantly increased in the postuninephrectomy adapted kidney, independently of protein expression, but presumably involving interactions between 20-HETE and COX in the renal microvasculature and changes in the paracrine activity of ANG II and 20-HETE.

  12. Apraxia for differentiating Alzheimer’s disease from subcortical vascular dementia and mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Ozkan S

    2013-07-01

    Full Text Available Serhat Ozkan,1 Demet Ozbabalik Adapinar,1 Nese Tuncer Elmaci,2 Didem Arslantas31Department of Neurology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey; 2Department of Neurology, Marmara University Medical Faculty, Istanbul, Turkey; 3Department of Public Health, Eskisehir Osmangazi University Medical Faculty, Eskisehir, TurkeyAbstract: Although ideomotor limb apraxia is considered to be a typical sign of cortical pathologies such as Alzheimer’s disease (AD, it has been also reported in subcortical neurodegenerative diseases and vascular lesions. We aimed to investigate the difference between AD, subcortical vascular dementia (SVaD and mild cognitive impairment (MCI patients by means of ideomotor limb apraxia frequency and severity. Ninety-six AD, 72 SVaD, and 84 MCI patients were assessed with the mini-mental status examination (MMSE, clinical dementia rating (CDR and the apraxia screening test of TULIA (AST. Apraxia was significantly more frequent in the AD patients (32.3% than in both of the SVaD (16.7% and MCI (4.8% patients. The frequency of apraxia was also significantly higher in SVaD patients than in MCI patients. AD patients had significantly lower apraxia scores than both SVaD and MCI patients. In addition, a significant difference was found between SVaD and MCI patients in terms of apraxia scores. These results suggest that the widespread belief of the association between apraxia and cortical dementias is not exactly correct. The significant difference between both of the dementia groups and the MCI patients suggests that the absence of apraxia can be an indicator for MCI diagnosis.Keywords: apraxia, Alzheimer’s disease, subcortical vascular dementia, mild cognitive impairment

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Binswanger's disease: Biomarkers in the inflammatory form of vascular cognitive impairment and dementia.

    Science.gov (United States)

    Rosenberg, Gary A

    2017-09-13

    Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the impact of vascular disease on Alzheimer's disease. VCID is a heterogeneous group of diseases for which there are no proven treatments. Biomarkers can be used to select more homogeneous populations. Small vessel disease is the most prevalent form of VCID and is the optimal form for treatment trials because there is a progressive course with characteristic pathological changes. Subcortical ischemic vascular disease of the Binswanger type (SIVD-BD) has a characteristic set of features that can be used both to identify patients and to follow treatment. SIVD-BD patients have clinical, neuropsychological, CSF and imaging features that can be used as biomarkers. No one feature is diagnostic but a multimodal approach defines the SIVD-BD spectrum disorder. The most important features are large white matter lesions with axonal damage, blood-brain barrier disruption as shown by MRI and CSF, and neuropsychological evidence of executive dysfunction. We have used these features to create a Binswanger Disease Scale and a probability of SIVD-BD, using a machine-learning algorithms. The patients discussed in this review are derived from published studies. Biomarkers aid in early diagnosis before the disease process have progressed too far for treatment, but also can indicate response to treatment. Refining the use of biomarkers will allow dementia treatment to enter the era of precision medicine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

    Science.gov (United States)

    Portela, Natália; Amaral, Josária Ferraz; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; Martinez, Daniel Godoy; Laterza, Mateus Camaroti

    2017-07-10

    A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®). At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03). Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. O histórico familiar para hipertensão arterial está relacionado a anormalidades vasculares e autonômicas, bem como disfunções no comportamento neuro-hemodinâmico durante o exerc

  17. Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study

    Directory of Open Access Journals (Sweden)

    Cotroneo AM

    2013-02-01

    Full Text Available Antonino Maria Cotroneo,1 Alberto Castagna,2 Salvatore Putignano,3 Roberto Lacava,2 Fausto Fantò,4 Francesco Monteleone,5 Filomena Rocca,2 Alba Malara,6 Pietro Gareri21ASL 2 Turin, Piedmont, 2Elderly Health Care, Ambulatory Center for Dementia, ASP Catanzaro, Calabria, 3ASL Napoli 1, Campania, 4University Hospital Orbassano, Turin, Piedmont, 5Regina Margherita Hospital, Rome, 6Nursing Home S Domenico Lamezia Terme, ASP Catanzaro, Calabria, ItalyBackground: The studio di intervento nel decadimento vascolare lieve (IDEALE study was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment.Methods: The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67–90 years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL and Instrumental Activities of Daily Living (IADL scales, mood was assessed by the Geriatric Depression Scale (GDS, and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0, after 3 months (T1, and after 9 months (T2, ie, 6 months after T1. The main outcomes were an improvement in MMSE, ADL, and IADL

  18. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Ju Huo; Ying Zhao; Yu Tian

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories.Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model.The fitting curves for each factor were obtained using Matlab software.Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors.Our results demonstrated that vascular cognitive impairment involves multiple factors.These factors include excitatory amino acid toxicity and nitric oxide toxicity.These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  19. Arterial blood pressure is inversely associated with vascular sympathetic reactivity (isometric handgrip exercise) in Gujarati Indian adolescents.

    Science.gov (United States)

    Shaikh, Wasim A; Patel, Minal; Shah, Hasmukh D; Nimbalkar, Archana S; Patel, Nilesh; Singh, S K

    2014-01-01

    Studies conducted earlier have found that vascular sympathetic reactivity to isometric handgrip exercise is either low or high in adolescents with higher blood pressure (Hypertensives) as compared to adolescents with relatively lower blood pressure (Normotensive). The current study was conducted to determine the correlation of vascular sympathetic reactivity to isometric handgrip exercise with blood pressure in Gujarati Indian adolescents so as to understand the pathogenesis and/consequences of Hypertension in this population. A cross-sectional study was conducted on 651 Gujarati Indian adolescents (285 girls, 366 boys) of age group 13-19 years. Blood pressure was measured by oscillometry and vascular sympathetic reactivity (Percentage rise in Diastolic Blood Pressure, %RDBP) was assessed using isometric handgrip test. Pearson's correlation coefficient was determined to study the correlation between %RDBP and blood pressure. In both girls and boys, %RDBP showed significant negative correlation with resting SBP, DBP and MAP. The study thus indicates that an inverse association exist between arterial blood pressure and vascular sympathetic reactivity to isometric handgrip exercise in Gujarati Indian adolescents.

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

    DEFF Research Database (Denmark)

    Skyhøj 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. T...

  1. Peripheral vascular insufficiency impairs functional capacity in patients with heart failure

    Directory of Open Access Journals (Sweden)

    Renato Murayama

    2014-04-01

    Full Text Available INTRODUCTION: Heart failure (HF is a complex syndrome in which effort limitation is associated with deterioration of peripheral musculature. Improving survival rates among these patients have led to the appearance of cases in which other pathologies are associated with HF, such as peripheral vascular insufficiency (PVI. The combination of these two pathologies is common, with significant repercussions for affected patients. OBJECTIVE: To compare functional limitations and quality of life between patients with HF in isolation or HF + PVI. METHOD: Twelve patients with HF+PVI were paired to 12 patients with HF in isolation. All had ejection fraction 0.05. CONCLUSIONS: The study participants who had mixed disease exhibited a greater degree of functional impairment than the group with HF, without reporting worsened quality of life.

  2. The heterogeneity of vascular cognitive impairments and the issues of therapy

    Directory of Open Access Journals (Sweden)

    Elena Anatolyevna Katunina

    2015-01-01

    Full Text Available Vascular cognitive impairments (CIs are heterogeneous in the mechanism of their occurrence and may develop in different extent of brain damage, in different locations, and the number of foci. Their etiological factors are various. The mechanism for the development of CIs may be associated with impairments of both per se the structures responsible for cognitive functions (frontal cortex, subcortical-cortical interactions, and hippocampus and deafferentation of the cortex and limbic structures due to periventricular white matter lesion or local lesion of the basal ganglia and thalamus. The pattern of CIs depends on the predominant involvement of cortical or subcortical regions or their combinations. The progression of CIs is also variable. In chronic cerebral circulatory insufficiency, CIs develop gradually over several years. Poststroke CIs manifest themselves acutely or subacutely. 6-27% of patients are diagnosed with dementia 3 months after acute cerebrovascular accident. The risk of subsequent dementia is 7% within the first year and 48% after 25 years.The paper reviews the most important trials of citicoline used in CIs. The drug has a multicomponent activity spectrum that permits its use in CIs of varying genesis. By taking into account its good tolerability and safety, the drug may be recommended for a wide circle of patients, including for elderly patients with comorbidity.

  3. Inhibition of rac1 reduces PDGF-induced reactive oxygen species and proliferation in vascular smooth muscle cells.

    OpenAIRE

    2001-01-01

    In vascular smooth muscle cells, reactive oxygen species (ROS) were known to mediate platelet-derived growth factor (PDGF)-induced cell proliferation and NADH/NADPH oxidase is the major source of ROS. NADH/NADPH oxidase is controlled by rac1 in non-phagocytic cells. In this study, we examined whether the inhibition of rac1 by adenoviral-mediated gene transfer of a dominant negative rac1 gene product (Ad.N17rac1) could reduce the proliferation of rat aortic vascular smooth muscle cells (RASMC)...

  4. Vascular Reactivity Concerning Orthosiphon stamineus Benth-Mediated Antihypertensive in Aortic Rings of Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Nurul Maizan Manshor

    2013-01-01

    Full Text Available Orthosiphon stamineus Benth has been traditionally used to treat hypertension. The study aimed to investigate the vascular reactivity of water extract (WOS and water : methanolic (1 : 1 extract (WMOS of Orthosiphon stamineus Benth and AT1 receptors blocker in the mechanisms of antihypertensive mediated by α1-adrenergic receptor and EDNO and PGI2 releases in the SHR aortic rings. SHR (230–280 g were divided into four groups: control, WOS, WMOS, and losartan. After being fed orally for 14 days, the aorta was harvested and subjected to PE (10−9 to 10−5 M and ACh (10−9 to 10−5 M with and without L-NAME (100 µM and indomethacin (10 µM, respectively. WOS, WMOS, and losartan significantly reduced the contractile responses to PE intact suggesting the importance of endothelium in vasorelaxation. Losartan significantly enhanced the ACh-induced vasorelaxation. L-NAME significantly inhibited the ACh-induced relaxation in all groups. Indomethacin enhanced ACh-induced vasorelaxation in WMOS. Collectively, Orthosiphon stamineus leaves extract reduced vasoconstriction responses by the alteration of α1-adrenergic and AT1 receptors activities. The involvement of EDNO releases was clearly observed in this plant. In WOS, PGI2 releases might not participate in the ACh-induced vasorelaxation. However, in WMOS, enhancement of vasorelaxation possibly due to continuous release of PGI2.

  5. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

    Science.gov (United States)

    Jokura, Hiroko; Watanabe, Isamu; Umeda, Mika; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans.

  6. Pyramidal and extrapyramidal scale (PEPS): a new scale for the assessment of motor impairment in vascular cognitive impairment associated with small vessel disease.

    Science.gov (United States)

    Kim, Sook Hui; Seo, Sang Won; Go, Seok Min; Chin, Juhee; Lee, Byung Hwa; Lee, Jae-Hong; Han, Seol-Heui; Na, Duk L

    2011-04-01

    Vascular cognitive impairment associated with small vessel disease (sVCI) may manifest as both cognitive and motor dysfunctions. However, few instruments exist for systematically assessing motor symptoms in sVCI, even though many neuropsychological tests exist to evaluate cognitive function. We developed a new scale for assessing motor impairments and evaluated the reliability and validity of the scale in patients with sVCI. A new motor scale, called the PEPS (Pyramidal and Extra Pyramidal Scale for sVCI), consisted of 34 items (for 60 total points) with 5 subdomains: corticospinal, corticobulbar, extrapyramidal signs, gait abnormalities, and gait severity. The PEPS was compared between 75 patients with sVCI and 73 control patients who had dementia or mild cognitive impairment (MCI) without ischemia. The PEPS had good interrater and test-retest reliability, and it was moderately to highly correlated with the UPDRS, NIHSS, MMSE, CDR, and ADL scales. An optimal cut-off score of PEPS to discriminate dementia or MCI patients with ischemia from those without ischemia was 6.5 with a sensitivity of 88% and a specificity of 100%. The PEPS is a reliable and valid scale that can be used to assess and monitor motor impairment in patients with vascular cognitive impairment due to small vessel disease. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  8. Hypercapnic evaluation of vascular reactivity in healthy aging and acute stroke via functional MRI

    Directory of Open Access Journals (Sweden)

    Ryan V. Raut

    2016-01-01

    Full Text Available Functional MRI (fMRI is well-established for the study of brain function in healthy populations, although its clinical application has proven more challenging. Specifically, cerebrovascular reactivity (CVR, which allows the assessment of the vascular response that serves as the basis for fMRI, has been shown to be reduced in healthy aging as well as in a range of diseases, including chronic stroke. However, the timing of when this occurs relative to the stroke event is unclear. We used a breath-hold fMRI task to evaluate CVR across gray matter in a group of acute stroke patients (<10 days from stroke; N = 22 to address this question. These estimates were compared with those from both age-matched (N = 22 and younger (N = 22 healthy controls. As expected, young controls had the greatest mean CVR, as indicated by magnitude and extent of fMRI activation; however, stroke patients did not differ from age-matched controls. Moreover, the ipsilesional and contralesional hemispheres of stroke patients did not differ with respect to any of these measures. These findings suggest that fMRI remains a valid tool within the first few days of a stroke, particularly for group fMRI studies in which findings are compared with healthy subjects of similar age. However, given the relatively high variability in CVR observed in our stroke sample, caution is warranted when interpreting fMRI data from individual patients or a small cohort. We conclude that a breath-hold task can be a useful addition to functional imaging protocols for stroke patients.

  9. Validation of NINDS-VCI Neuropsychology Protocols for Vascular Cognitive Impairment in Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsiu-Fen Lin

    Full Text Available To validate the three time-difference neuropsychological protocols developed by the National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS and the Canadian Stroke Network for assessment of vascular cognitive impairment (VCI in Mandarin-speaking subjects and to investigate the clinical application of the shortest form.Patients aged 50 years or older who had a stroke were invited to participate in the study. Clinical diagnosis of VCI was made. The NINDS-VCI Neuropsychology Protocols, 60-, 30-, and two 5-minute protocols, were administered. The criteria validities of the cognitive protocols against the diagnoses of stroke and VCI were determined via Receiver Operating Characteristic (ROC analysis. The optimal cut-off point for the 5-minute protocols total score was estimated for clinical use in screening.Eighty-three patients and 53 controls were recruited during the study period. Patients with stroke performed more poorly than the control group in the three neuropsychological protocols. Forty-two patients with stroke were diagnosed with VCI. VCI was used as the standard to estimate the criteria validities. The area under the ROC curve was 0.78, 0.80, 0.75, and 0.73 for the 60-, 30-, 5-mintue protocol-A and 5-minute protocol-B, respectively.These modified neuropsychological protocols can be used as valid instruments when performing comprehensive cognitive assessment or for screening of VCI in Taiwan.

  10. Diesel Exhaust Particles Induce Impairment of Vascular and Cardiac Homeostasis in Mice: Ameliorative Effect of Emodin

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2015-07-01

    Full Text Available Background/Aim: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6-methylanthraquinone, which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. Methods: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg or saline (control. Emodin (4 mg/kg was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Results: Emodin significantly prevented the increase of leukocyte (n=8, Pin vivo prothrombotic effect of DEP in pial arterioles (n=6, Pin vitro in whole blood (n=4-5, PConclusion: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution.

  11. Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment

    Science.gov (United States)

    Boehm-Sturm, Philipp; Füchtemeier, Martina; Foddis, Marco; Mueller, Susanne; Trueman, Rebecca C.; Zille, Marietta; Rinnenthal, Jan Leo; Kypraios, Theodore; Shaw, Laurence; Dirnagl, Ulrich

    2017-01-01

    Background and Purpose— Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice. Methods— We used magnetic resonance imaging to characterize brain degeneration in mice hypoperfused by refining the surgical procedure to use the smallest reported diameter microcoils (160 μm). Results— Acute cerebral blood flow decreases were observed in the hypoperfused group that recovered over 1 month and coincided with arterial remodeling. Increasing hypoperfusion resulted in a reduction in spatial learning abilities in the water maze that has not been previously reported. We were unable to observe severe white matter damage with histology, but a novel approach to analyze diffusion tensor imaging data, graph theory, revealed substantial reorganization of the hypoperfused brain network. A logistic regression model from the data revealed that 3 network parameters were particularly efficient at predicting group membership (global and local efficiency and degrees), and clustering coefficient was correlated with performance in the water maze. Conclusions— Overall, these findings suggest that, despite the autoregulatory abilities of the mouse brain to compensate for a sudden decrease in blood flow, there is evidence of change in the brain networks that can be used as neuroimaging biomarkers to predict outcome. PMID:28070001

  12. Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment.

    Science.gov (United States)

    Boehm-Sturm, Philipp; Füchtemeier, Martina; Foddis, Marco; Mueller, Susanne; Trueman, Rebecca C; Zille, Marietta; Rinnenthal, Jan Leo; Kypraios, Theodore; Shaw, Laurence; Dirnagl, Ulrich; Farr, Tracy D

    2017-02-01

    Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice. We used magnetic resonance imaging to characterize brain degeneration in mice hypoperfused by refining the surgical procedure to use the smallest reported diameter microcoils (160 μm). Acute cerebral blood flow decreases were observed in the hypoperfused group that recovered over 1 month and coincided with arterial remodeling. Increasing hypoperfusion resulted in a reduction in spatial learning abilities in the water maze that has not been previously reported. We were unable to observe severe white matter damage with histology, but a novel approach to analyze diffusion tensor imaging data, graph theory, revealed substantial reorganization of the hypoperfused brain network. A logistic regression model from the data revealed that 3 network parameters were particularly efficient at predicting group membership (global and local efficiency and degrees), and clustering coefficient was correlated with performance in the water maze. Overall, these findings suggest that, despite the autoregulatory abilities of the mouse brain to compensate for a sudden decrease in blood flow, there is evidence of change in the brain networks that can be used as neuroimaging biomarkers to predict outcome. © 2017 The Authors.

  13. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment.

    Science.gov (United States)

    Alvarez-Sabín, Jose; Ortega, Gemma; Jacas, Carlos; Santamarina, Estevo; Maisterra, Olga; Ribo, Marc; Molina, Carlos; Quintana, Manuel; Román, Gustavo C

    2013-01-01

    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. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment after stroke. We assessed the safety of long-term administration and its possible efficacy of citicoline in preventing poststroke cognitive decline in patients with first-ever ischemic stroke. Open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a qualifying stroke and randomized by age, gender, education and stroke type into parallel arms of citicoline (1 g/day) for 12 months vs. no citicoline (control group). Medical management was similar otherwise. All patients underwent neuropsychological evaluation at 1 month, 6 months and 1 year after stroke. Tests results were combined to give indexes of 6 neurocognitive domains: attention and executive function, memory, language, spatial perception, motor speed and temporal orientation. Using adjusted logistic regression models we determined the association between citicoline treatment and cognitive decline for each neurocognitive domain at 6 and 12 months. We recruited 347 subjects (mean age 67.2 years, 186 male (56.6%), mean education 5.7 years); 172 (49.6%) received citicoline for 12 months (no significant differences from controls n = 175). Demographic data, risk factors, initial stroke severity (NIHSS), clinical and etiological classification were similar in both groups. Only 37 subjects (10.7%) discontinued treatment (10.5% citicoline vs. 10.9% control) at 6 months; 30 (8.6%) due to death (16 (9.3%) citicoline vs. 14 (8.0%) control, p = 0.740), 7 lost to follow-up or incorrect treatment, and 4 (2.3%) had adverse events from citicoline without discontinuation. 199 patients underwent neuropsychological evaluation at 1 year. Cognitive functions improved 6 and 12 months after

  14. Study of diffusion tensor imaging in subcortical ischemic vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    Hui-ying GUO

    2014-04-01

    Full Text Available Objective Using diffusion tensor imaging (DTI to explore the microstructure changes of white matter in subcortical ischemic vascular cognitive impairment (SIVCI and its correlation with cognitive function.  Methods Forty-nine patients with subcortical ischemic cerebrovascular diseases were collected. By using Clinical Dementia Rating Scale (CDR, they were classified into 10 cases of vascular dementia (VaD group, 20 cases of vascular cognitive impairment-no dementia (VCIND group and 19 cases of normal cognitive function (control group. Conventional MRI and DTI were performed in all cases. Based on the DTI data, voxel-based analysis was used to assess the whole brain region. Correlation analysis was applied to illustrate the relationship between DTI parameters and cognitive scale in VaD patients.  Results Compared with the control group, fractional anisotropy (FA values of patients in VaD group decreased in medial prefrontal cortex, anterior cingulate cortex, corpus callosum stem, bilateral parietal lobes, right temporal lobe and bilateral orbitofrontal lobes (P = 0.000, for all, and FA values of patients in VCIND group decreased in right inferior frontal gyrus, right hippocampus and bilateral precuneus (P = 0.000, for all. Compared with VCIND group, FA values of patients in VaD group decreased in medial prefrontal cortex, anterior cingulate, corpus callosum, bilateral parietal lobes and right temporal lobe (P = 0.000, for all. Compared with the control group, mean diffusivity (MD values in VaD group increased in medial prefrontal cortex, corpus callosum, bilateral parietal lobes, bilateral temporal lobes and anterior cingulate (P = 0.000, for all, while in VCIND group increased in bilateral precuneus and right hippocampus (P = 0.000, for all. Compared with VCIND group, MD values in VaD group increased in right medial prefrontal cortex, anterior cingulate cortex, corpus callosum stem, bilateral parietal lobes and bilateral temporal lobes (P = 0

  15. Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients

    DEFF Research Database (Denmark)

    Sørensen, V R; Mathiesen, E R; Clausen, P

    2005-01-01

    in Type 1 diabetic patients may disturb vascular function, possibly mediated through smooth muscle cell dysfunction as well as endothelial dysfunction. We suggest that prolonged and repeated episodes of hyperglycaemia could possibly lead to permanent vascular dysfunction and thereby development...

  16. Antibodies to the α1-adrenergic receptor cause vascular impairments in rat brain as demonstrated by magnetic resonance angiography.

    Directory of Open Access Journals (Sweden)

    Peter Karczewski

    Full Text Available BACKGROUND: Circulating agonistic autoantibodies acting at G protein-coupled receptors have been associated with numerous sever pathologies in humans. Antibodies directed predominantly against the α(1-adrenergig receptor were detected in patients suffering from widespread diseases such as hypertension and type 2 diabetes. Their deleterious action has been demonstrated for peripheral organs. We postulate that antibodies to the α(1-adrenergig receptor are relevant pathomolecules in diseases of the central nervous system associated with vascular impairments. METHODOLOGY/PRINCIPAL FINDINGS: Using a rat model we studied the long-term action of antibodies against the α(1-adrenergig receptor either induced by immunization with a receptor peptide or applied by intravenous injection. The vasculature in the rat brains was investigated by time-of-flight magnetic resonance angiography using a 9.4 Tesla small animal MR imaging system. Visual examination of maximum-intensity-projections (MIPs of brain angiographs revealed the development of vascular defects in antibody- exposed animals between three and eight months of treatment. Relative vascular areas were derived from representative MIP image sections by grayscale analysis and used to form an index of vascular circulation. Animals exposed to the action of α(1-adrenergig receptor antibodies showed significantly reduced vascular areas (p<0.05. Calculated index values indicated attenuated blood flow in both antibody-treated cohorts compared to their respective controls reaching with (relative units ± standard error, n = 10 0.839 ± 0.026 versus 0.919 ± 0.026 statistical significance (p<0.05 for peptide-immunized rats. CONCLUSION/SIGNIFICANCE: We present evidence that antibodies to the α(1-adrenergig receptor cause cerebrovascular impairments in the rat. Our findings suggest the pathological significance of these antibodies in pathologies of the human central nervous system linked to impairments of

  17. Cognitive rehabilitation reduces cognitive impairment and normalizes hippocampal CA1 architecture in a rat model of vascular dementia

    OpenAIRE

    Langdon, Kristopher D.; Granter-Button, Shirley; Carolyn W Harley; Moody-Corbett, Frances; Peeling, James; Corbett, Dale

    2013-01-01

    Dementia is a major cause of morbidity in the western society. Pharmacological therapies to delay the progression of cognitive impairments are modestly successful. Consequently, new therapies are urgently required to improve cognitive deficits associated with dementia. We evaluated the effects of physical and cognitive activity on learning and memory in a rat model of vascular dementia (VasD). Male Sprague-Dawley rats (6 months old) were exposed to either regular chow or a diet rich in satura...

  18. Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation.

    Science.gov (United States)

    Davel, Ana Paula C; Kawamoto, Elisa Mitiko; Scavone, Cristoforo; Vassallo, Dalton V; Rossoni, Luciana V

    2006-07-01

    1. The aim of this study was to assess the effects of treatment with isoproterenol (ISO, 0.3 mg kg-1 day-1, s.c.) for 7 days on the vascular reactivity of rat-isolated aortic rings. Additionally, potential mechanisms underlying the changes that involved the endothelial modulation of contractility were investigated. 2. Treatment with ISO induced cardiac hypertrophy without changes in haemodynamic parameters. Aortic rings from ISO-treated rats showed an increase in the contraction response to phenylephrine (PHE) and serotonin, but did not change relaxations produced by acetylcholine or isoproterenol. Removal of the endothelium increased the responses to PHE in both groups. However, this procedure was less effective in ISO-treated as compared with control rats. Endothelial cell removal abolished the increase in the response to PHE in ISO-treated rats. The presence of Nomega-nitro-L-arginine methyl ester shifted the concentration-response curve to PHE to the left in both groups of rats. However, this effect was more pronounced in the ISO group. In addition, aminoguanidine (50 microM) potentiated the actions of PHE only in the ISO group. ISO treatment increased nitric oxide synthase (NOS) activity and neuronal NOS and endothelial NOS protein expression in the aorta. 3. Neither losartan (10 microM) nor indomethacin (10 microM) abolished the effects of ISO on the actions of PHE. Superoxide dismutase (SOD, 150 U ml-1) and L-arginine (5 mM), but neither catalase (300 U ml-1) nor apocynin (100 microM), blocked the effect of ISO treatment. In addition, we observed an increase in superoxide anion levels as measured by ethidium bromide fluorescence and of copper and zinc superoxide dismutase protein expression in ISO-treated rats. 4. In conclusion, our data suggest that ISO treatment alters the endothelial cell-mediated modulation of the contraction to PHE in rat aorta. The increased maximal response of PHE seems to be due to an increase in superoxide anion generation, which

  19. Impaired SIRT1 promotes the migration of vascular smooth muscle cell-derived foam cells.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Xu; Pi, Yan; Long, Chun-Yan; Sun, Meng-Jiao; Chen, Xue; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-07-01

    The formation of fat-laden foam cells, contributing to the fatty streaks of the plaques of atheroma, is the critical early process in atherosclerosis. The previous study demonstrated that vascular smooth muscle cells (VSMCs) contain a much larger burden of the excess cholesterol in comparison with monocyte-derived macrophages in human coronary atherosclerosis, as the main origin of foam cells. It is noteworthy that VSMC-derived foam cells are deposited in subintima but not media, where VSMCs normally deposit in. Therefore, migration from media to intima is an indispensable step for a VSMC to accrue neutral lipids and form foam cell. Whether this migration occurs paralleled with or prior to the formation of foam cell is still unclear. Herein, the present study was designed to test the VSMC migratory capability in the process of foam cell formation induced by oxidized low-density lipoprotein (oxLDL). In conclusion, we provide evidence that oxLDL induces the VSMC-derived foam cells formation with increased migration ability and MMP-9 expression, which were partly attributed to the impaired SIRT1 and enhanced nuclear factor-kappa B (NF-κB) activity. As activation of transient receptor potential vanilloid type 1 (TRPV1) has been reported to have anti-atherosclerotic effects, we investigated its role in oxLDL-treated VSMC migration. It is found that activating TRPV1 by capsaicin inhibits VSMC foam cell formation and the accompanied migration through rescuing the SIRT1 and suppressing NF-κB signaling. The present study provides evidence that SIRT1 may be a promising intervention target of atherosclerosis, and raises the prospect of TRPV1 in prevention and treatment of atherosclerosis.

  20. Efficacy Of Rivastigmine And Donepezil On Cognitive Impairment Of Vascular Dementia - Some Preliminary Observations

    Directory of Open Access Journals (Sweden)

    Jha S

    2004-01-01

    Full Text Available Background: Vascular Dementia (VaD is common, global, disabling and a rather neglected, age related dementia. It is important to identify and treat it since cognitive impairment produces dysfunction in occupational and social life. Moreso, due to increase in geriatric population, incidence and prevalence of VaD is also increasing. Aim: We share our observations on efficacy of Rivastigmine and Donepezil (drugs advocated for improving cognition in dementia in patients of VaD. Material and Method: This was a non-randomized study based on clinical evaluation. We selected 53 patients suffering from VaD (as per clinical and radiological criteria. Their age range was 55-78 years (mean 65.3 + 6.2 yrs. Clinical, biochemical and radiological (Cranial CT and MRI evaluation was done to establish etiology. Cognition was measured using modified Mini Mental State Examination (MMSE which was repeated 2 times, at interval of 3 months. We observed the role of Rivastigmine in 14 and Donepezil in 19 patients of VaD. The change in MMSE score was compared with 20 control patients of VaD. The associated risk factors like hypertension, diabetes, hyperlipidemia etc. were managed. Acetyl Salicylic Acid (ASA in dose of 150mg/day was given as an antiplatelet agent to all 53 patients in this study. Results: At end of study, no statistically significant improvement was observed in MMSE score in any of the 53 patients. Improvement in MMSE score (though statistically insignificant was observed with Rivastigmine in 11 and with Donepezil in 14 patients. Progressive decline in MMSE score was observed in 14 (70% control patients of VaD who did not receive rivastigmine or donepezil. Conclusion - Rivastigmine and Donepezil are beneficial in halting deterioration of dementia in patients suffering from VaD.

  1. Adjunct Nitrous Oxide Normalizes Vascular Reactivity Changes after Hemorrhagic Shock in Mice under Isoflurane Anesthesia

    NARCIS (Netherlands)

    Samarska, Iryna V.; van Meurs, Matijs; Buikema, Hendrik; Houwertjes, Martin C.; Wulfert, Francis M.; Molema, Grietje; Epema, Anne H.; Henning, Robert H.

    2009-01-01

    Background: Hemorrhagic shock is associated with changes in vascular responsiveness that may lead to organ dysfunction and, ultimately, multiple organ dysfunction syndrome. Volatile anesthetics interfere with vasoresponsiveness, which may contribute to organ hypoperfusion. in this study, the authors

  2. Psychosocial stress after reactivation of drug-related memory impairs later recall in abstinent heroin addicts.

    Science.gov (United States)

    Zhao, Li-Yan; Zhang, Xiao-Li; Shi, Jie; Epstein, David H; Lu, Lin

    2009-04-01

    Stress and stress hormone are known to play important roles in modulating different stages of memory including reconsolidation. In a previous study, we found that treatment with stress or corticosterone after a single memory reactivation disrupted reconsolidation of a drug-related memory in rats. Here we presumed that stress after memory reactivation can effectively inhibit drug-related memory by disrupting its reconsolidation in abstinent heroin addicts. In the present study, 21 abstinent heroin addicts learned a word list (containing ten neutral, ten heroin-related negative, and ten heroin-related positive words) on day 1; retrieval of a word list (learned 24 h earlier) was made on day 2; and immediately after retrieval, they were exposed to either a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control condition in a crossover manner. On day 3, free recall of the word list and other psychological and physical responses were assessed. The stressor induced a significant increase in salivary free cortisol and a decrease in mood. Memory recall was significantly impaired after the stress condition. Follow-up analysis revealed that heroin-related negative and positive words (i.e., heroin-related words) were affected, whereas no effect was observed for neutral words. No changes were detected for cued recall, working memory, or attention. Stress after drug-related memory retrieval significantly decreased its subsequent recall, likely through impaired drug-related memory reconsolidation process. Reconsolidation blockade may thus provide a potential therapeutic strategy for the prevention of relapse in drug addiction.

  3. Cognitive Impairments in Occupational Burnout - Error Processing and Its Indices of Reactive and Proactive Control.

    Science.gov (United States)

    Golonka, Krystyna; Mojsa-Kaja, Justyna; Gawlowska, Magda; Popiel, Katarzyna

    2017-01-01

    The presented study refers to cognitive aspects of burnout as the effects of long-term work-related stress. The purpose of the study was to investigate electrophysiological correlates of burnout to explain the mechanisms of the core burnout symptoms: exhaustion and depersonalization/cynicism. The analyzed error-related electrophysiological markers shed light on impaired cognitive mechanisms and the specific changes in information-processing in burnout. In the EEG study design (N = 80), two components of error-related potential (ERP), error-related negativity (ERN), and error positivity (Pe), were analyzed. In the non-clinical burnout group (N = 40), a significant increase in ERN amplitude and a decrease in Pe amplitude were observed compared to controls (N = 40). Enhanced error detection, indexed by increased ERN amplitude, and diminished response monitoring, indexed by decreased Pe amplitude, reveal emerging cognitive problems in the non-clinical burnout group. Cognitive impairments in burnout subjects relate to both reactive and unconscious (ERN) and proactive and conscious (Pe) aspects of error processing. The results indicate a stronger 'reactive control mode' that can deplete resources for proactive control and the ability to actively maintain goals. The analysis refers to error processing and specific task demands, thus should not be extended to cognitive processes in general. The characteristics of ERP patterns in burnout resemble psychophysiological indexes of anxiety (increased ERN) and depressive symptoms (decreased Pe), showing to some extent an overlapping effect of burnout and related symptoms and disorders. The results support the scarce existing data on the psychobiological nature of burnout, while extending and specifying its cognitive characteristics.

  4. Cognitive Impairments in Occupational Burnout – Error Processing and Its Indices of Reactive and Proactive Control

    Science.gov (United States)

    Golonka, Krystyna; Mojsa-Kaja, Justyna; Gawlowska, Magda; Popiel, Katarzyna

    2017-01-01

    The presented study refers to cognitive aspects of burnout as the effects of long-term work-related stress. The purpose of the study was to investigate electrophysiological correlates of burnout to explain the mechanisms of the core burnout symptoms: exhaustion and depersonalization/cynicism. The analyzed error-related electrophysiological markers shed light on impaired cognitive mechanisms and the specific changes in information-processing in burnout. In the EEG study design (N = 80), two components of error-related potential (ERP), error-related negativity (ERN), and error positivity (Pe), were analyzed. In the non-clinical burnout group (N = 40), a significant increase in ERN amplitude and a decrease in Pe amplitude were observed compared to controls (N = 40). Enhanced error detection, indexed by increased ERN amplitude, and diminished response monitoring, indexed by decreased Pe amplitude, reveal emerging cognitive problems in the non-clinical burnout group. Cognitive impairments in burnout subjects relate to both reactive and unconscious (ERN) and proactive and conscious (Pe) aspects of error processing. The results indicate a stronger ‘reactive control mode’ that can deplete resources for proactive control and the ability to actively maintain goals. The analysis refers to error processing and specific task demands, thus should not be extended to cognitive processes in general. The characteristics of ERP patterns in burnout resemble psychophysiological indexes of anxiety (increased ERN) and depressive symptoms (decreased Pe), showing to some extent an overlapping effect of burnout and related symptoms and disorders. The results support the scarce existing data on the psychobiological nature of burnout, while extending and specifying its cognitive characteristics. PMID:28507528

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Impairment of the serotonergic neurons underlying reinforcement elicits extinction of the repeatedly reactivated context memory

    Science.gov (United States)

    Balaban, Pavel M.; Vinarskaya, Alia Kh.; Zuzina, Alena B.; Ierusalimsky, Victor N.; Malyshev, Aleksey Yu.

    2016-01-01

    We analyzed changes in the activity of individually identifiable neurons involved in the networks underlying feeding and withdrawal behaviors in snails before, during, and after aversive learning in vitro. Responses to food in the “reinforcing” serotonergic neurons involved in withdrawal changed significantly after training, implying that these serotonergic cells participate in the reactivation of memory and are involved in the reconsolidation process. In behavioral experiments it was shown that impairment of the functioning of the serotonergic system with the selective neurotoxin 5,7-DiHT did not change the memory, when tested once, but resulted in a complete extinction of the contextual memory after repeated reactivation of memory. Conversely, the cued memory to a specific type of food was significantly reduced but still present. Thus, we conclude that it is only for the context memory, that participation of the “reinforcing” serotonergic neurons in memory retrieval may be the gate condition for the choice between extinction/reconsolidation. PMID:27841309

  8. Impaired vascular endothelial function in patients with restless legs syndrome: a new aspect of the vascular pathophysiology.

    Science.gov (United States)

    Koh, Seung Yon; Kim, Min Seung; Lee, Sun Min; Hong, Ji Man; Yoon, Jung Han

    2015-12-15

    Restless legs syndrome (RLS) is a common sleep disorder in which patients feel unpleasant leg sensations and the urge to move their legs during rest, particularly at night. Leg movement improves these symptoms. Although several studies have demonstrated an association between cardiovascular disease and RLS, the mechanisms underlying this relationship remain unclear. Recent studies have shown changes in the peripheral microvasculature, including altered blood flow and capillary tortuosity, and peripheral hypoxia. Vascular endothelial dysfunction can be assessed noninvasively with ultrasound measurements of brachial artery flow-mediated dilatation (FMD). Therefore, this study investigated FMD in RLS patients to determine the involvement of microvascular alterations in this disorder. The study enrolled 25 drug-naïve RLS patients and 25 sex- and age-matched controls and compared the FMD values of the two groups. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group. FMD was significantly lower in the RLS patients (6.6 ± 1.2%) compared to the controls (8.4 ± 1.8%; p<0.05) and the RLS patients showed a weak, negative correlation between RLS severity and FMD (r=-0.419, p=0.04). Multivariate linear regression analysis revealed that RLS (B=-1.87, 95% confidence interval [CI] -2.72 to -1.02; p<0.001) and age (B=-0.06; 95% CI -0.12 to -0.02; p<0.001) were significantly and inversely correlated with FMD. This study demonstrated that RLS patients have poorer vascular endothelial function than normal healthy subjects and provides further evidence supporting the involvement of peripheral systems in the generation of RLS. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity.

    Science.gov (United States)

    Liu, Peiying; Hebrank, Andrew C; Rodrigue, Karen M; Kennedy, Kristen M; Section, Jarren; Park, Denise C; Lu, Hanzhang

    2013-09-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right sides of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions.

  10. Vascular cognitive impairment in diabetes mellitus: are prevention and treatment effective?

    Science.gov (United States)

    Zavoreo, Iris; Madžar, Zrinko; Demarin, Vida; Kes, Vanja Bašić

    2014-09-01

    Vascular dementia is caused by progressive atherosclerosis leading to multiple small strokes and subsequent brain damage. Approximately 10%-20% of all cases of dementia are attributed to vascular dementia. The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls. It is a growing public health concern because of the lack of effective curative treatment options and rising global prevalence. Duration of diabetes mellitus of 10 years or longer, onset of diabetes before age 65, treatment with insulin and oral antidiabetic medications, and presence of diabetes complications have an impact on the incidence of vascular dementia. On the other hand, patients who suffered stroke either had or are later diagnosed with diabetes (16%-24%). Treatment of vascular dementia in diabetes patients rests on a two-pronged approach: modification of the underlying disease and prevention and treatment of dementia symptoms.

  11. Subfailure overstretch injury leads to reversible functional impairment and purinergic P2X7 receptor activation in intact vascular tissue

    Directory of Open Access Journals (Sweden)

    Weifeng Luo

    2016-09-01

    Full Text Available Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities.

  12. 血管性认知障碍研究进展%Research Progress in Vascular Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    乾栋梁; 张艳芳; 王力群; 雒扬

    2013-01-01

    Vascular cognitive impairment (VCI ) is a definition comprising subjects affected by any degree of cognitive impairment from cerebrovascular disease, ranging from mild cognitive impairment( MCI ) to vascular dementia( VaD ). Here is to make a review on the advances in VCI in the following areas: VCI definition, subtypes, prevalence, risk factors, assessment methods, diagnostic criteria, prevention, and symptomatic treatment,to intensify the consciousness of VCI to give earlier diagnosis,prevention and treatment of VCI,so as to delay the process from MCI to VaD.%血管性认知障碍(VCI)指由脑血管病以及脑血管危险因素导致的认知障碍,它包括了从轻微认知损害(MCI)到血管性痴呆(VaD).现从VCI的定义、分类、流行病学资料、危险因素、评估手段、诊断标准、预防和治疗措施等方面对VCI及其研究进展进行概述,以加强对VCI的认识,做到早诊断、早预防、早治疗,延缓MCI向VaD进展.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Thiago Bruder-Nascimento

    2015-06-01

    Full Text Available 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.

  15. Effects of Exercise Intervention on Vascular Risk Factors in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial

    OpenAIRE

    Kazuki Uemura; Takehiko Doi; Hiroyuki Shimada; Hyuma Makizako; Daisuke Yoshida; Kota Tsutsumimoto; Yuya Anan; Takao Suzuki

    2012-01-01

    Aims The purpose of this study is to clarify the effects of exercise intervention on vascular risk factors in older adults with mild cognitive impairment (MCI). Methods Community-dwelling older adults who met the definition of MCI using the Petersen criteria (n = 100; mean age = 75.3 years) were randomly allocated to the exercise (n = 50) or education control group (n = 50). Participants in the exercise group exercised under the supervision of physiotherapists for 90 min/day, 2 days/week, 80 ...

  16. 血管性认知损害的氧化应激机制%Oxidative stress mechanisms in vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    贾砚秋; 吕佩源

    2013-01-01

    血管性认知损害是指脑血管病变引起的学习、记忆功能受损.近年来的研究显示,氧化应激在血管性认知损害中起着重要作用.文章就血管性认知损害的氧化应激机制及其防治进行了综述.%Vascular cognitive impairment refers to the learning and memory impairments caused by cerebrovascular lesions.Studies in recent years have shown that oxidative stress plays an important role in vascular cognitive impairment.This article reviews the mechanisms and the prevention and treatment of oxidative stress in vascular cognitive impairment.

  17. Impaired neural reward processing in children and adolescents with reactive attachment disorder: A pilot study.

    Science.gov (United States)

    Mizuno, Kei; Takiguchi, Shinichiro; Yamazaki, Mika; Asano, Mizuki; Kato, Shiho; Kuriyama, Kikuko; Watanabe, Yasuyoshi; Sadato, Norihiro; Tomoda, Akemi

    2015-10-01

    Reactive attachment disorder (RAD) is characterized by markedly disturbed and developmentally inappropriate social relatedness due to parental maltreatment. RAD patients often display a high number of comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, and certain RAD symptoms are difficult to discriminate from ADHD. One of the core characteristics of ADHD is a decrease in neural reward processing due to dopamine dysfunction. The aim of the present study was to determine whether the brain activity involved in reward processing in RAD patients is impaired in comparison with ADHD patients and typically developed controls. Five RAD patients, 17 typically developed (TD) controls and 17 ADHD patients aged 10-16 years performed tasks with high and low monetary reward while undergoing functional magnetic resonance imaging. ADHD patients were tested before and after 3 months treatment with osmotic release oral system-methylphenidate. Before treatment, ADHD patients showed that striatal and thalamus activities only in the tasks with low monetary reward were lower than TD controls. RAD patients showed decrease in activity of the caudate, putamen and thalamus during both the high and low monetary reward conditions in comparison with all the other groups. In RAD patients, the activity of the putamen was associated with the severity of posttraumatic stress and overt dissociation. Reward sensitivity was markedly decreased in children and adolescents with RAD, as evidenced by a diminished neural response during reward perception. This suggests that dopaminergic dysfunction exists in these patients, and may inform future dopaminergic treatment strategies for RAD.

  18. Daily stressors and emotional reactivity in individuals with mild cognitive impairment and cognitively healthy controls.

    Science.gov (United States)

    Rickenbach, Elizabeth Hahn; Condeelis, Kristen L; Haley, William E

    2015-06-01

    Daily experiences of stress are common and have been associated with worse affect among older adults. People with mild cognitive impairment (PWMCI) have measurable memory deficits in between normal cognition and dementia and have been identified as having greater psychological distress than cognitively healthy older adults (CHOAs). Little is known about whether daily stressors contribute to distress among PWMCI. We hypothesized that compared with CHOAs, PWMCI would have higher daily negative affect and lower daily positive affect, report greater numbers and severity of daily stressors, and experience greater emotional reactivity to daily stressors. Fifteen clinically diagnosed PWMCI and 25 CHOAs completed daily reports of stressors, stressor severity, and positive and negative affect over an 8-day period. PWMCI reported higher daily negative affect, lower daily positive affect, and higher numbers and greater severity of memory stressors but did not differ from CHOAs in numbers or severity of general stressors. Cognitive status was a moderator of the daily stress-affect relationship. Days with greater numbers and severity of general daily stressors were associated with higher negative affect only for PWMCI. The numbers and severity of memory stressors were not associated with negative affect. In addition, more severe general daily stressors and memory stressors were associated with lower positive affect for all participants. Results suggest that PWMCI are less resilient in the face of daily stress than are CHOAs in terms of negative affect, perhaps because of declines in reserve capacity. The study presents a promising approach to understanding stress and coping in predementia states of cognition.

  19. Impaired imitation of gestures in mild dementia: comparison of dementia with Lewy bodies, Alzheimer's disease and vascular dementia.

    Science.gov (United States)

    Nagahama, Yasuhiro; Okina, Tomoko; Suzuki, Norio

    2015-11-01

    To examine whether imitation of gestures provided useful information to diagnose early dementia in elderly patients. Imitation of finger and hand gestures was evaluated in patients with mild dementia; 74 patients had dementia with Lewy bodies (DLB), 100 with Alzheimer's disease (AD) and 52 with subcortical vascular dementia (SVaD). Significantly, more patients with DLB (32.4%) compared with patients with AD (5%) or SVaD (11.5%) had an impaired ability to imitate finger gestures bilaterally. Also, significantly, more patients with DLB (36.5%) compared with patients with AD (5%) or SVaD (15.4%) had lower mean scores of both hands. In contrast, impairment of the imitation of bimanual gestures was comparable among the three patient groups (DLB 50%, AD 42%, SVaD 42.3%). Our study revealed that imitation of bimanual gestures was impaired non-specifically in about half of the patients with mild dementia, whereas imitation of finger gestures was significantly more impaired in patients with early DLB than in those with AD or SVaD. Although the sensitivity was not high, the imitation tasks may provide additional information for diagnosis of mild dementia, especially for DLB. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity

    Science.gov (United States)

    McIlwrick, Silja; Pohl, Tobias; Chen, Alon; Touma, Chadi

    2017-01-01

    Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body’s main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS. PMID:28261058

  1. A new diagnostic algorithm for vascular cognitive impairment: the proposed criteria and evaluation of its reliability and validity

    Institute of Scientific and Technical Information of China (English)

    ZHAO Qian-lu; ZHOU Yong; WANG Yi-long; DONG Ke-hui; WANG Yong-jun

    2010-01-01

    Background Vascular cognitive impairment (VCI) is considered to be the most common pattern of cognitive impairment. We aimed to devise a diagnostic algorithm for VCI, and evaluate the reliability and validity of our proposed criteria.Methods We based our new algorithm on previous literature, a Delphi consensus method, and preliminary testing. First, successive 100 patients with cerebrovascular disease (CVD) in hospital underwent a structured medical examination. Twenty-five case vignettes fulfilled the proposed criteria of diagnosis for probable or possible VCI were divided into three subtype categories: vascular cognitive impairment, no dementia (VCIND), vascular dementia (VaD) or mixed VCI/Alzheimer's disease (AD). Inter-raters reliability was assessed using a Fleiss kappa analysis. Convergent validity was also evaluated by correlation coefficients (r) between the proposed key points for each subtype and the currently accepted criteria. Forty-five patients with probable VCI were examined to determine the accuracy of identification for each subtype.Results The proposed criteria showed clinical diagnostic validity for VCI, and were able to define probable, possible and definite VCI, three VCI subtypes, and vascular causes. There was good consensus between experts (Cronbach's α=0.96 for both rounds). Significant moderate to good items-total correlations were found for two questionnaires (50-r range, 0.40-0.97 and 0.41-0.99, respectively). Significant slight and moderate inter-raters reliability were obtained for VCI (k=0.13) and three VCI subtypes (k=0.45). Furthermore, good convergent validity was observed in a comparison of significant correlations between criteria: good (4-r range, 0.75-0.92) to perfect (3-r=1.00) validity for the VCIND subtype, and moderate to good validity for the VaD subtype (1-r=0.46; 5-r range, 0.76-0.92) and for the mixed VCI/AD subtype (r=0.92 and 1.00; 4-r range, 0.47-0.70). Importantly, the area under receiver operating characteristic

  2. Effects of Exercise Intervention on Vascular Risk Factors in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Kazuki Uemura

    2012-10-01

    Full Text Available Aims: The purpose of this study is to clarify the effects of exercise intervention on vascular risk factors in older adults with mild cognitive impairment (MCI. Methods: Community-dwelling older adults who met the definition of MCI using the Petersen criteria (n = 100; mean age = 75.3 years were randomly allocated to the exercise (n = 50 or education control group (n = 50. Participants in the exercise group exercised under the supervision of physiotherapists for 90 min/day, 2 days/week, 80 times for 12 months. Anthropometric profiles, blood markers, blood pressure, and physical fitness (the 6-min walking test were measured. Total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, and TC/HDL-C risk ratio measurements were taken from blood samples. Results: The exercise group showed significantly reduced TC and TC/HDL-C risk ratio after training compared with baseline levels (p Conclusion: Exercise intervention was associated with positive changes in important vascular risk factors related to cognitive decline and vascular disease in older adults with MCI.

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

    Energy Technology Data Exchange (ETDEWEB)

    Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

    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

  4. Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

    Science.gov (United States)

    Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

    2012-01-01

    Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening

  5. C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression

    Directory of Open Access Journals (Sweden)

    Luque Ana

    2008-09-01

    Full Text Available Abstract Background Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC a direct role on modulation of angiogenesis has not been established. Results Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC and human coronary artery EC (HCAEC. CRP, at concentrations corresponding to moderate/high risk (1–5 μg/ml, induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM. CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2, a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR, platelet-derived growth factor (PDGF-BB, notch family transcription factors (Notch1 and Notch3, cysteine-rich angiogenic inducer 61 (CYR61/CCN1 and inhibitor of DNA binding/differentiation-1 (ID1. Conclusion This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.

  6. Effects of ginsenosides on vascular reactivity in rat cerebral and renal arteries

    Institute of Scientific and Technical Information of China (English)

    WONG Wing-tak; LEUNG Fung-ping; YUNG Lai-hang; TIAN Xiao-yu; WONG Ricky Ngok Shun; HUANG Yu

    2008-01-01

    Objective To investigate possible mechanisms underlying the antioxidant property (1) and the in vitro vasodilator effects (2) of the two ginsenosides, Rb1 and Rg1, in isolated rat renal and cerebral arteries. Methods Arterial rings were mounted in a multi-channel myograph for recording of isometric tension. To examine the antioxidant activity, some rings were exposed to a free radical-generating reaction (hypoxan-thine and xanthine oxidase) with and without pre-treatment with ginsenosides. The calcium antagonistic effects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions, a condition that promoted Ca2+ influx in vascular smooth muscle cells. Results Ginsenosides protected endothelial function (endothelial nitric oxide-dependent relaxation) against oxidative stress; (2) ginsenoside Rb1 reduced the high K+ -induced contractions of both renal and cerebral arteries while ginsenoside Rgl relaxed the rat cerebral artery but not the renal artery. Conclusions Ginsenosides are vaso-protective via (1) the antioxidant activity which protects endothelial cell function and (2) the inhibition of Ca2+ influx through voltage-sensitive Ca2+ channels in vascular smooth muscle. The vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.

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

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, M C [Departamento de BioingenierIa, Facultad de Ciencias Exactas y TecnologIa, Universidad Nacional de Tucuman e INSIBIO, CONICET, Tucuman (Argentina); Bonaudo, M; Conde, A [Carrera de Ingenieria de Biomedica, Facultad de Ciencias Exactas y TecnologIa, Universidad Nacional de Tucuman (Argentina); Palavecino, L [Carrera de Ingenieria de Biomedica, Facultad de Ciencias Exactas y TecnologIa, Universidad Nacional de Tucuman (Argentina)

    2007-11-15

    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.

  8. Consumption of a Western-style diet during pregnancy impairs offspring islet vascularization in a Japanese macaque model.

    Science.gov (United States)

    Pound, Lynley D; Comstock, Sarah M; Grove, Kevin L

    2014-07-01

    Children exposed to a maternal Western-style diet in utero have an increased risk of developing type 2 diabetes. Understanding the mechanisms and an investigation of possible interventions are critical to reversing this phenomenon. We examined the impact of maternal Western-style diet consumption on the development of islet vascularization and innervation, both of which are critical to normal islet function, in fetal and juvenile offspring. Furthermore, we assessed whether improved dietary intake or resveratrol supplementation could ameliorate the harmful consequences of Western-style diet consumption during pregnancy. Adult female Japanese macaques were maintained on a control or Western-style diet for 4-7 yr. One cohort of dams was switched back onto a control diet, whereas another cohort received resveratrol supplementation throughout gestation. Pregnancies were terminated in the early third trimester by C-section, or offspring were born naturally and sent to necropsy at 1 yr of age. Western-style diet consumption resulted in impaired fetal islet capillary density and sympathetic islet innervation. Furthermore, this reduction in vascularization persisted in the juvenile offspring. This effect is independent of changes in the expression of key angiogenic markers. Diet reversal normalized islet vascularization to control offspring levels, whereas resveratrol supplementation caused a significant increase in capillary density above controls. These data provide a novel mechanism by which maternal Western-style diet consumption leads to increased susceptibility to type 2 diabetes in the offspring. Importantly, an improved maternal diet may mitigate these harmful effects. However, until the long-term consequences of increased vascularization can be determined, resveratrol use during pregnancy is not advised. Copyright © 2014 the American Physiological Society.

  9. NADH/NADPH Oxidase and Vascular Function.

    Science.gov (United States)

    Griendling, K K; Ushio-Fukai, M

    1997-11-01

    The vascular NADH/NADPH oxidase has been shown to be the major source of superoxide in the vessel wall. Recent work has provided insight into its structure and activity in vascular cells. This enzyme is involved in both vascular smooth muscle hypertrophy and in some forms of impaired endothelium-dependent relaxation. Because oxidative stress in general participates in the pathogenesis of hypertension and atherosclerosis, the enzymes that produce reactive oxygen species may be important determinants of the course of vascular disease. (Trends Cardiovasc Med 1997;7:301-307). © 1997, Elsevier Science Inc.

  10. The Role of Brain-Reactive Autoantibodies in Brain Pathology and Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Simone Mader

    2017-09-01

    Full Text Available Antibodies to different brain proteins have been recently found to be associated with an increasing number of different autoimmune diseases. They need to penetrate the blood–brain barrier (BBB in order to bind antigens within the central nervous system (CNS. They can target either neuronal or non-neuronal antigen and result in damage either by themselves or in synergy with other inflammatory mediators. Antibodies can lead to acute brain pathology, which may be reversible; alternatively, they may trigger irreversible damage that persists even though the antibodies are no longer present. In this review, we will describe two different autoimmune conditions and the role of their antibodies in causing brain pathology. In systemic lupus erythematosus (SLE, patients can have double stranded DNA antibodies that cross react with the neuronal N-methyl-d-aspartate receptor (NMDAR, which have been recently linked to neurocognitive dysfunction. In neuromyelitis optica (NMO, antibodies to astrocytic aquaporin-4 (AQP4 are diagnostic of disease. There is emerging evidence that pathogenic T cells also play an important role for the disease pathogenesis in NMO since they infiltrate in the CNS. In order to enable appropriate and less invasive treatment for antibody-mediated diseases, we need to understand the mechanisms of antibody-mediated pathology, the acute and chronic effects of antibody exposure, if the antibodies are produced intrathecally or systemically, their target antigen, and what triggers their production. Emerging data also show that in utero exposure to some brain-reactive antibodies, such as those found in SLE, can cause neurodevelopmental impairment since they can penetrate the embryonic BBB. If the antibody exposure occurs at a critical time of development, this can result in irreversible damage of the offspring that persists throughout adulthood.

  11. Smoke Extract Impairs Adenosine Wound Healing. Implications of Smoke-Generated Reactive Oxygen Species

    Science.gov (United States)

    Zimmerman, Matthew C.; Zhang, Hui; Castellanos, Glenda; O’Malley, Jennifer K.; Alvarez-Ramirez, Horacio; Kharbanda, Kusum; Sisson, Joseph H.; Wyatt, Todd A.

    2013-01-01

    Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mechanism by which adenosine-mediated wound healing occurs after cigarette smoke exposure has not been investigated. The present study investigates whether cigarette smoke exposure alters adenosine-mediated reparative properties via its ability to induce a shift in the oxidant/antioxidant balance. Using an in vitro wounding model, bronchial epithelial cells were exposed to 5% cigarette smoke extract, were wounded, and were then stimulated with either 10 μM adenosine or the specific A2A receptor agonist, 5′-(N-cyclopropyl)–carboxamido–adenosine (CPCA; 10 μM), and assessed for wound closure. In a subset of experiments, bronchial epithelial cells were infected with adenovirus vectors encoding human superoxide dismutase and/or catalase or control vector. In the presence of 5% smoke extract, significant delay was evident in both adenosine-mediated and CPCA-mediated wound closure. However, cells pretreated with N-acetylcysteine (NAC), a nonspecific antioxidant, reversed smoke extract–mediated inhibition. We found that cells overexpressing mitochondrial catalase repealed the smoke extract inhibition of CPCA-stimulated wound closure, whereas superoxide dismutase overexpression exerted no effect. Kinase experiments revealed that smoke extract significantly reduced the A2A-mediated activation of cyclic adenosine monophosphate–dependent protein kinase. However, pretreatment with NAC reversed this effect. In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species–dependent mechanism, thereby providing a better understanding of adenosine signaling that may direct the development of

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

    Science.gov (United States)

    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. Endothelium-dependent Effect of Sesame Seed Feeding on Vascular Reactivity of Streptozotocin-diabetic Rats: Underlying Mechanisms.

    Science.gov (United States)

    Roghani, Mehrdad; Jalali-Nadoushan, Mohammad Reza; Baluchnejadmojarad, Tourandokht; Vaez Mahdavi, Mohammad-Reza; Naderi, Gholamali; Roghani Dehkordi, Farshad; Joghataei, Mohammad Taghi

    2013-01-01

    Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of sesame (Sesamum indicum L) seed feeding was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received sesame seed-mixed food at weight ratios of 3% and 6% for 7 weeks, one week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in sesame-treated diabetic rats (at a ratio of 6%) relative to untreated diabetics and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was also significantly higher in sesame-treated diabetic rats (at a ratio of 6%) as compared to diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME) significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity and sesame treatment significantly reversed the increased MDA content and restored activity of SOD. We thus conclude that chronic treatment of diabetic rats with sesame seed could in a dose-manner prevent some abnormal changes in vascular reactivity through nitric oxide and via attenuation of oxidative stress in aortic tissue and endothelium integrity is necessary for this beneficial effect.

  14. The effects of educational background on Montreal Cognitive Assessment screening for vascular cognitive impairment, no dementia, caused by ischemic stroke.

    Science.gov (United States)

    Wu, Yuanbo; Wang, Muqiu; Ren, Mingshan; Xu, Wenhua

    2013-10-01

    It is possible that a patient's educational background has an effect on their Montreal Cognitive Assessment (MoCA) score, which is used to evaluate patients for vascular cognitive impairment, no dementia (VCIND) after ischemic stroke. Cognitive impairment was evaluated in patients with no cognitive impairment (NCI) or VCIND using the MoCA. The receiver operating characteristic curve and maximal Youden index were used to determine the optimal cut-off values to distinguish between NCI and VCIND. The sensitivity and specificity of MoCA were calculated for patients with primary, secondary and tertiary educational levels. Patients with NCI (n=111) and VCIND (n=95) were tested. In patients with a primary education, a significant difference was found between the two groups in each of the MoCA factors, except for naming. Likewise, a significant difference was found in all factors, except for naming, attention and calculation, for patients with a secondary education. For the patients with a tertiary education, a significant difference was found only in visuospatial/executive abilities, abstraction and memory (peducated groups was 97.06%, 56.10% and 40%, respectively, with the specificity being 47.22%, 87.80% and 100%, respectively. We suggest that the MoCA score needs to be amended according to the patient's educational levels in order to improve the effectiveness of the screening. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    de Matthaeis A

    2014-05-01

    Full Text Available Angela de Matthaeis,1 Antonio Greco,2,* Mariangela Pia Dagostino,2 Giulia Paroni,2 Andrea Fontana,3 Manlio Vinciguerra,1,4,5 Gianluigi Mazzoccoli,1,* Davide Seripa,2 Gianluigi Vendemiale61Division of Internal Medicine and Chronobiology Unit, 2Geriatrics Unit and Gerontology, Geriatrics Research Laboratory, Department of Medical Sciences, 3Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, 4Euro-Mediterranean Institute of Sciences and Technology, Palermo, Italy; 5University College London, Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, London, UK; 6Geriatrics Unit, University of Foggia, Foggia, Italy*These authors contributed equally to this workAbstract: 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  18. Therapeutic effect of citicoline in vascular cognitive impairment%胞磷胆碱在血管性认知损害中的治疗作用

    Institute of Scientific and Technical Information of China (English)

    安福麗; 毛宇湘; 劉勝春

    2014-01-01

    Vascular cognitive impairment refers to all cognitive impairment syndromes associated with vascular diseases,including severe cognitive impairment from mild cognitive impairment to vascular dementia.Citicoline is a necessary intermediate of the phosphatidylcholine biosynthesis,an important component of the neuronal membranes.Experimental studies have shown that citicoline has neuroprotective and neurorepair effects in cerebral ischemia.Clinical studies have shown that citicoline may improve cognitive function in patients with vascular cognitive impairment.%血管性认知损害是指所有与血管性疾病有关的认知损害综合征,包括从轻度认知损害到血管性痴呆在内的重度认知损害.胞磷胆碱是神经元细胞膜的重要组成成分磷脂酰胆碱生物合成的必需中间体.实验研究显示,胞磷胆碱在脑缺血中具有神经保护和神经修复作用.临床研究显示,胞磷胆碱有可能改善血管性认知损害患者的认知功能.

  19. Beneficial Effects of Calcitriol on Hypertension, Glucose Intolerance, Impairment of Endothelium-Dependent Vascular Relaxation, and Visceral Adiposity in Fructose-Fed Hypertensive Rats

    Science.gov (United States)

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J. F.; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  20. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Chu-Lin Chou

    Full Text Available Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group. Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L. These results suggest a protective role of calcitriol treatment on endothelial

  1. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    Science.gov (United States)

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  2. Genetic and hormonal regulation of tryptophan kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging.

    Science.gov (United States)

    Oxenkrug, Gregory F

    2007-12-01

    Impairment of cognition that is caused by (or associated with) vascular factors has been termed vascular cognitive impairment (VCI). The hallmark of VCI is an impairment of brain executive, or planning, functions caused by inflammatory changes of brain microvessels. VCI is characterized by impairment of the executive function and is distinct from Alzheimer's-type and multi-infarct dementias, although VCI might overlap with Alzheimer's disease. This review focuses on the possible contribution of the kynurenine pathway of tryptophan (Try) catabolism to the inflammatory changes in brain microvessels. One mechanism of brain microvessel inflammation is activation of the inducible nitric oxide synthase (iNOS) by the proinflammatory cytokine interferon gamma (IFN-gamma). The effect of IFN-gamma on iNOS might be mediated by kynurenine derivatives of tryptophan because (1) IFN-gamma stimulates the rate-determining enzyme of the Try-kynurenine pathway, indoleamine-2,3-dioxygenase (IDO) and (2) some kynurenines (e.g., quinolinic and picolinic acids) can stimulate iNOS. IFN-gamma production is controlled by (IFN-gamma) + 874(T/A) genotypes, suggesting the association of a high promoter T allele with the high rate of IFN-gamma production and, consequently, with activated IDO and enhanced production of kynurenines. Although IDO is strictly an IFN-gamma-induced gene product, tumor necrosis factor alpha (TNF-alpha) can synergistically increase the transcriptional activation of the IDO gene in response to IFN-gamma. The combination of high promoter T of (IFN-gamma) + 874(T/A) with high promoter A of (TNF-alpha) -308(G/A) might "superinduce" IDO and cause (or contribute to) inflammation of brain microvessels detected as white matter hyperintensities and leading to VCI development. Hormonal induction of tryptophan dioxygenase and the ability of hormones to potentiate IFN-gamma-induced activation of IDO might contribute to the development of inflammatory changes in major depressive

  3. 血管性认知障碍的研究进展%RESEARCH OF PROGRESS OF VASCULAR COGNITIVE IMPAIRMENT

    Institute of Scientific and Technical Information of China (English)

    卢晓航; 陈丹娜

    2011-01-01

    本文对血管性认知障碍(VCI)的概念、分类、流行病学、危险因素,诊断,检测工具,预防和治疗的研究进展进行综述.以加强对血管性认知障碍的认识,务求做到早诊断、早预防,早治疗,阻断或延迟VCI向VD发展.%The paper summarized the conception, classification, epidemiology, nsk factors, diagnoses, measure tools, prevention and treatment of vascular cognitive impairment (VCI). The people ' s consciousness of VCI must be intensified to give earlier diagn08is. prevention and treatment of VCI, then to break down and delay the process of VCI to VD.

  4. Angiotensin II impairs endothelial progenitor cell number and function in vitro and in vivo: implications for vascular regeneration.

    Science.gov (United States)

    Endtmann, Cathleen; Ebrahimian, Talin; Czech, Thomas; Arfa, Omar; Laufs, Ulrich; Fritz, Mathias; Wassmann, Kerstin; Werner, Nikos; Petoumenos, Vasileios; Nickenig, Georg; Wassmann, Sven

    2011-09-01

    Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E-deficient mice compared with transplantation of apolipoprotein E-deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT(1)-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT(1)-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1-dependent proapoptotic pathways impairs EPCs in

  5. Surface modification by plasma etching impairs early vascularization and tissue incorporation of porous polyethylene (Medpor(®) ) implants.

    Science.gov (United States)

    Laschke, Matthias W; Augustin, Victor A; Sahin, Fadime; Anschütz, Dieter; Metzger, Wolfgang; Scheuer, Claudia; Bischoff, Markus; Aktas, Cenk; Menger, Michael D

    2016-11-01

    Porous polyethylene (Medpor®) is commonly used in craniofacial reconstructive surgery. Rapid vascularization and tissue incorporation are crucial for the prevention of migration, extrusion, and infection of the biomaterial. Therefore, we analyzed whether surface modification by plasma etching may improve the early tissue response to Medpor®. Medpor® samples were treated in a plasma chamber at low (20 W; LE-PE) and high energy levels (40 W; HE-PE). The samples and non-treated controls were implanted into mouse dorsal skinfold chambers to analyze angiogenesis, inflammation, and granulation tissue formation over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. Scanning electron microscopy (SEM) analyses revealed that elevating energy levels of plasma etching progressively increase the oxygen surface content and surface roughness of Medpor®. This did not affect the leukocytic response to the implants. However, LE-PE and HE-PE samples exhibited an impaired vascularization. This was associated with a reduced formation of a collagen-rich granulation tissue at the implantation site. Additional in vitro experiments showed a reduced cell attachment on plasma-etched Medpor®. Thus, plasma etching may not be recommended to improve the clinical outcome of reconstructive interventions using Medpor®. However, it may be beneficial for temporarily implanted polyethylene-based biomedical devices for which tissue incorporation is undesirable. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1738-1748, 2016. © 2015 Wiley Periodicals, Inc.

  6. Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease

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    Cheng-Jui Lin

    2016-12-01

    Full Text Available Background/Aims: Indoxyl sulfate (IS is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD. We explored the effect of IS on human early endothelial progenitor cells (EPCs and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD, pulse wave velocity (PWV, ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS and free IS (F-IS were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR, hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

  7. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    Science.gov (United States)

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  8. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia.

    Science.gov (United States)

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C

    2015-03-01

    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P epithelium. Hyperoxia reduced alveolarization in WT mice (P lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors.

  9. Self-perceived stress reactivity is an indicator of psychosocial impairment at the workplace

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    Nater Urs M

    2010-05-01

    Full Text Available Abstract Background Work related stress is associated with a range of debilitating health outcomes. However, no unanimously accepted assessment tool exists for the early identification of individuals suffering from chronic job stress. The psychological concept of self-perceived stress reactivity refers to the individual disposition of a person to answer stressors with immediate as well as long lasting stress reactions, and it could be a valid indicator of current as well as prospective adverse health outcomes. The aim of this study was to determine the extent to which perceived stress reactivity correlates with various parameters of psychosocial health, cardiovascular risk factors, and parameters of chronic stress and job stress in a sample of middle-aged industrial employees in a so-called "sandwich-position". Methods In this cross-sectional study, a total of 174 industrial employees were assessed for psychosocial and biological stress parameters. Differences between groups with high and low stress reactivity were analysed. Logistic regression models were applied to identify which parameters allow to predict perceived high versus low stress reactivity. Results In our sample various parameters of psychosocial stress like chronic stress and effort-reward imbalance were significantly increased in comparison to the normal population. Compared to employees with perceived low stress reactivity, those with perceived high stress reactivity showed poorer results in health-related complaints, depression, anxiety, sports behaviour, chronic stress, and effort-reward imbalance. The educational status of employees with perceived low stress reactivity is higher. Education, cardiovascular complaints, chronic stress, and effort-reward imbalance were moderate predictors for perceived stress reactivity. However, no relationship was found between stress reactivity and cardiovascular risk factors in our sample. Conclusions Job stress is a major burden in a relevant

  10. Self-perceived stress reactivity is an indicator of psychosocial impairment at the workplace

    Science.gov (United States)

    2010-01-01

    Background Work related stress is associated with a range of debilitating health outcomes. However, no unanimously accepted assessment tool exists for the early identification of individuals suffering from chronic job stress. The psychological concept of self-perceived stress reactivity refers to the individual disposition of a person to answer stressors with immediate as well as long lasting stress reactions, and it could be a valid indicator of current as well as prospective adverse health outcomes. The aim of this study was to determine the extent to which perceived stress reactivity correlates with various parameters of psychosocial health, cardiovascular risk factors, and parameters of chronic stress and job stress in a sample of middle-aged industrial employees in a so-called "sandwich-position". Methods In this cross-sectional study, a total of 174 industrial employees were assessed for psychosocial and biological stress parameters. Differences between groups with high and low stress reactivity were analysed. Logistic regression models were applied to identify which parameters allow to predict perceived high versus low stress reactivity. Results In our sample various parameters of psychosocial stress like chronic stress and effort-reward imbalance were significantly increased in comparison to the normal population. Compared to employees with perceived low stress reactivity, those with perceived high stress reactivity showed poorer results in health-related complaints, depression, anxiety, sports behaviour, chronic stress, and effort-reward imbalance. The educational status of employees with perceived low stress reactivity is higher. Education, cardiovascular complaints, chronic stress, and effort-reward imbalance were moderate predictors for perceived stress reactivity. However, no relationship was found between stress reactivity and cardiovascular risk factors in our sample. Conclusions Job stress is a major burden in a relevant subgroup of industrial

  11. Strategic Role of Frontal White Matter Tracts in Vascular Cognitive Impairment: A Voxel-Based Lesion-Symptom Mapping Study in CADASIL

    Science.gov (United States)

    Duering, Marco; Zieren, Nikola; Herve, Dominique; Jouvent, Eric; Reyes, Sonia; Peters, Nils; Pachai, Chahin; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

    2011-01-01

    Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and…

  12. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Science.gov (United States)

    López-Gil, Xavier; Amat-Roldan, Iván; Tudela, Raúl; Castañé, Anna; Prats-Galino, Alberto; Planas, Anna M.; Farr, Tracy D.; Soria, Guadalupe

    2014-01-01

    The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent. PMID:25100993

  13. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Directory of Open Access Journals (Sweden)

    Xavier eLópez-Gil

    2014-07-01

    Full Text Available The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

  14. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    Science.gov (United States)

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.

  15. Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO2 5% inhalation in preeclamptic women.

    Science.gov (United States)

    Sariri, Elaheh; Vahdat, Mansoureh; Behbahani, Afsaneh Shariati; Rohani, Mohammad; Kashanian, Maryam

    2013-07-01

    To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2 5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia. A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2 5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded. Baseline PI and RI were lower in the preeclamptic group (p < 0.05). Inhalation of CO2 5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006 ± 0.229 versus 0.503 ± 0.209, p = 0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583 ± 0.193 versus 0.383 ± 0.173, p = 0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve = 0.973, p = 0.0001). CVR in response to CO2 5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.

  16. Beta adrenergic overstimulation impaired vascular contractility via actin-cytoskeleton disorganization in rabbit cerebral artery.

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    Hyoung Kyu Kim

    Full Text Available BACKGROUND AND PURPOSE: Beta adrenergic overstimulation may increase the vascular damage and stroke. However, the underlying mechanisms of beta adrenergic overstimulation in cerebrovascular dysfunctions are not well known. We investigated the possible cerebrovascular dysfunction response to isoproterenol induced beta-adrenergic overstimulation (ISO in rabbit cerebral arteries (CAs. METHODS: ISO was induced in six weeks aged male New Zealand white rabbit (0.8-1.0 kg by 7-days isoproterenol injection (300 μg/kg/day. We investigated the alteration of protein expression in ISO treated CAs using 2DE proteomics and western blot analysis. Systemic properties of 2DE proteomics result were analyzed using bioinformatics software. ROS generation and following DNA damage were assessed to evaluate deteriorative effect of ISO on CAs. Intracellular Ca(2+ level change and vascular contractile response to vasoactive drug, angiotensin II (Ang II, were assessed to evaluate functional alteration of ISO treated CAs. Ang II-induced ROS generation was assessed to evaluated involvement of ROS generation in CA contractility. RESULTS: Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1 in ISO-CAs. As a cause of dysregulation of actin-cytoskeleton organization, we found decreased level of RhoA and ROCK1, which are major regulators of actin-cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca(2+ efflux and constriction response to angiotensin II and high K(+ in ISO-CAs. ISO also increased basal ROS generation and induced oxidative damage in CA; however, it decreased the Ang II-induced ROS generation rate. These results indicate that ISO disrupted actin cytoskeleton proteome network

  17. Adrenomedullin Is Associated With Surgical Trauma and Impaired Renal Function in Vascular Surgery Patients.

    Science.gov (United States)

    Gillmann, Hans-Jörg; Meinders, Antje; Larmann, Jan; Sahlmann, Bianca; Schrimpf, Claudia; Aper, Thomas; Lichtinghagen, Ralf; Teebken, Omke E; Theilmeier, Gregor

    2017-01-01

    Patients undergoing vascular surgery are prone to perioperative organ injury because of both higher prevalence of cardiovascular risk factors and the extent of surgery. Early detection of organ failure is essential to facilitate appropriate medical care. Midregional pro-adrenomedullin (MR-proADM) has been investigated in acute medical care settings to guide clinical decision-making regarding patient pathways and to identify patients prone to imminent cardiovascular or inflammatory complications. In this study, we evaluated the impact of perioperative MR-proADM levels as an early marker of perioperative cardiovascular and inflammatory stress reactions and kidney injury. The study was conducted as a monocentric, prospective, noninterventional trial at Hannover Medical School, Germany. A total of 454 consecutive patients who underwent open vascular surgery were followed from the day prior to until 30 days after surgery. The composite primary end point was defined as the occurrence of major adverse cardiac events (MACEs), acute kidney injury (AKI), or systemic inflammatory response syndrome (SIRS). Measurements were correlated with both medical history and postoperative MACE, AKI, or SIRS using univariate and multivariate regression analysis. One hundred thirty-nine (31%) of the patients reached the primary end point within the study interval. Midregional pro-adrenomedullin change was associated with the combined primary end point and with the intensity of surgical trauma. Midregional pro-adrenomedullin change was increased in patients reaching the secondary end points, SIRS (optimal cutoff: 0.2 nmol/L) and AKI (optimal cutoff: 0.7 nmol/L), but not in patients with MACEs. Increased levels of MR-proADM within the perioperative setting (1) were linked to the invasiveness of surgery and (2) identified patients with ongoing loss of renal function. Increased MR-proADM levels may therefore identify a subgroup of patients prone to excessive cardiovascular stress but did not

  18. The role of decidual NK cells in pregnancies with impaired vascular remodelling.

    Science.gov (United States)

    Cartwright, Judith E; James-Allan, Laura; Buckley, Rebecca J; Wallace, Alison E

    2017-02-01

    The pathologies of the dangerous pregnancy complications pre-eclampsia (PE) and fetal growth restriction (FGR) are established in the first trimester of human pregnancy yet we know little of how this happens. Finely tuned interactions between maternal and placental cells are essential for pregnancy to progress without complications; however, the precise nature of this cross-talk and how it can go wrong are crucial questions that remain to be answered. This review summarises recent studies examining the role played by natural killer cells in regulating normal placentation and remodelling. Their involvement when it is impaired in PE/FGR pregnancies will additionally be discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Dynamin-related protein inhibitor downregulates reactive oxygen species levels to indirectly suppress high glucose-induced hyperproliferation of vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Maimaitijiang, Alimujiang; Zhuang, Xinyu; Jiang, Xiaofei; Li, Yong, E-mail: 11211220031@fudan.edu.cn

    2016-03-18

    Hyperproliferation of vascular smooth muscle cells is a pathogenic mechanism common in diabetic vascular complications and is a putatively important therapeutic target. This study investigated multiple levels of biology, including cellular and organellar changes, as well as perturbations in protein synthesis and morphology. Quantitative and qualitative analysis was utilized to assess the effect of mitochondrial dynamic changes and reactive oxygen species(ROS) levels on high-glucose-induced hyperproliferation of vascular smooth muscle cells. The data demonstrated that the mitochondrial fission inhibitor Mdivi-1 and downregulation of ROS levels both effectively inhibited the high-glucose-induced hyperproliferation of vascular smooth muscle cells. Downregulation of ROS levels played a more direct role and ROS levels were also regulated by mitochondrial dynamics. Increased ROS levels induced excessive mitochondrial fission through dynamin-related protein (Drp 1), while Mdivi-1 suppressed the sensitivity of Drp1 to ROS levels, thus inhibiting excessive mitochondrial fission under high-glucose conditions. This study is the first to propose that mitochondrial dynamic changes and ROS levels interact with each other and regulate high-glucose-induced hyperproliferation of vascular smooth muscle cells. This finding provides novel ideas in understanding the pathogenesis of diabetic vascular remodeling and intervention. - Highlights: • Mdivi-1 inhibits VSMC proliferation by lowering ROS level in high-glucose condition. • ROS may be able to induce mitochondrial fission through Drp1 regulation. • Mdivi-1 can suppress the sensitivity of Drp1 to ROS.

  20. Promotion of the mind through exercise (PROMoTE: a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    Davis Jennifer C

    2010-02-01

    Full Text Available Abstract Background Sub-cortical vascular ischaemia is the second most common etiology contributing to cognitive impairment in older adults, and is frequently under-diagnosed and under-treated. Although evidence is mounting that exercise has benefits for cognitive function among seniors, very few randomized controlled trials of exercise have been conducted in populations at high-risk for progression to dementia. Aerobic-based exercise training may be of specific benefit in delaying the progression of cognitive decline among seniors with vascular cognitive impairment by reducing key vascular risk factors associated with metabolic syndrome. Thus, we aim to carry out a proof-of-concept single-blinded randomized controlled trial primarily designed to provide preliminary evidence of efficacy aerobic-based exercise training program on cognitive and everyday function among older adults with mild sub-cortical ischaemic vascular cognitive impairment. Methods/Design A proof-of-concept single-blinded randomized trial comparing a six-month, thrice-weekly, aerobic-based exercise training group with usual care on cognitive and everyday function. Seventy older adults who meet the diagnostic criteria for sub-cortical ischaemic vascular cognitive impairment as outlined by Erkinjuntti and colleagues will be recruited from a memory clinic of a metropolitan hospital. The aerobic-based exercise training will last for 6 months. Participants will be followed for an additional six months after the cessation of exercise training. Discussion This research will be an important first step in quantifying the effect of an exercise intervention on cognitive and daily function among seniors with sub-cortical ischaemic vascular cognitive impairment, a recognized risk state for progression to dementia. Exercise has the potential to be an effective, inexpensive, and accessible intervention strategy with minimal adverse effects. Reducing the rate of cognitive decline among seniors

  1. ESKIMO1 disruption in Arabidopsis alters vascular tissue and impairs water transport.

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    Valérie Lefebvre

    Full Text Available Water economy in agricultural practices is an issue that is being addressed through studies aimed at understanding both plant water-use efficiency (WUE, i.e. biomass produced per water consumed, and responses to water shortage. In the model species Arabidopsis thaliana, the ESKIMO1 (ESK1 gene has been described as involved in freezing, cold and salt tolerance as well as in water economy: esk1 mutants have very low evapo-transpiration rates and high water-use efficiency. In order to establish ESK1 function, detailed characterization of esk1 mutants has been carried out. The stress hormone ABA (abscisic acid was present at high levels in esk1 compared to wild type, nevertheless, the weak water loss of esk1 was independent of stomata closure through ABA biosynthesis, as combining mutant in this pathway with esk1 led to additive phenotypes. Measurement of root hydraulic conductivity suggests that the esk1 vegetative apparatus suffers water deficit due to a defect in water transport. ESK1 promoter-driven reporter gene expression was observed in xylem and fibers, the vascular tissue responsible for the transport of water and mineral nutrients from the soil to the shoots, via the roots. Moreover, in cross sections of hypocotyls, roots and stems, esk1 xylem vessels were collapsed. Finally, using Fourier-Transform Infrared (FTIR spectroscopy, severe chemical modifications of xylem cell wall composition were highlighted in the esk1 mutants. Taken together our findings show that ESK1 is necessary for the production of functional xylem vessels, through its implication in the laying down of secondary cell wall components.

  2. A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort.

    Science.gov (United States)

    Skrobot, Olivia Anna; McKnight, Amy Jayne; Passmore, Peter Anthony; Seripa, Davide; Mecocci, Patrizia; Panza, Francesco; Kalaria, Rajesh; Wilcock, Gordon; Munafò, Marcus; Erkinjuntti, Timo; Karhunen, Pekka; Pessi, Tanja; Martiskainen, Mika; Love, Seth; Kehoe, Patrick Gavin

    2016-06-15

    Vascular cognitive impairment (VCI), including its severe form, vascular dementia (VaD), is the second most common form of dementia. The genetic etiology of sporadic VCI remains largely unknown. We previously conducted a systematic review and meta-analysis of all published genetic association studies of sporadic VCI prior to 6 July 2012, which demonstrated that APOE (ɛ4, ɛ2) and MTHFR (rs1801133) variants were associated with susceptibility for VCI. De novo genotyping was conducted in a new independent relatively large collaborative European cohort of VaD (nmax = 549) and elderly non-demented samples (nmax = 552). Where available, genotype data derived from Illumina's 610-quad array for 1210 GERAD1 control samples were also included in analyses of genes examined. Associations were tested using the Cochran-Armitage trend test: MTHFR rs1801133 (OR = 1.36, 95% CI 1.16-1.58, p = <0.0001), APOE rs7412 (OR = 0.62, 95% CI 0.42-0.90, p = 0.01), and APOE rs429358 (OR = 1.59, 95% CI 1.17-2.16, p = 0.003). Association was also observed with APOE epsilon alleles; ɛ4 (OR = 1.85, 95% CI 1.35-2.52, p = <0.0001) and ɛ2 (OR = 0.67, 95% CI 0.46-0.98, p = 0.03). Logistic regression and Bonferroni correction in a subgroup of the cohort adjusted for gender, age, and population maintained the association of APOE rs429358 and ɛ4 allele.

  3. Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

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    Yaping Zhang

    2010-01-01

    Full Text Available Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm and adverse proliferation (remodeling of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

  4. Determinants of developing diabetes mellitus and vascular complications in patients with impaired fasting glucose

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    Faranak Sharifi

    2013-01-01

    Full Text Available Aims: To detect the risk factors of diabetes mellitus (DM and cardiovascular complications in subjects with impaired fasting glucose (IFG. Materials and Methods: One hundred and twenty three subjects with proved IFG in Zanjan Healthy Heart Study (2002-2003 were recalled and participated in this study (2009-2010. Demographic and laboratoryinformation of the participants were collected.Ischemic heart disease (IHD was assessed by the exercise tolerance test (ETT. All the subjects with abnormal ETT or documented past history of IHD confirmed by angiographic evaluation. Ophthalmic complications including cataract, glaucoma, and diabetic retinopathy were estimated by an ophthalmologist. Results: Incidence of DM was 19.5%. All the diabetic and pre-diabetic patients had at least one of the other components of metabolic syndrome. Obesity (P: 0.04, OR: 1.8, 95%CI: 1.2-9 and low physical activity (P < 0.001, OR: 9.6, 95%CI: 3.4-32 were the only independent prognostic risk factors for progression to DM in patients with IFG. Total incidence of IHD was 14.6% and had a strong correlation with sex (P: 0.01, OR: 1.8, 95%CI: 1.2-1.5, age (P < 0.001, OR: 23, 95%CI: 2.1-67 and cigarette smoking (P < 0.001, OR: 36.5, 95%CI: 3.9-337. Non-proliferative diabetic retinopathy was shown in 2 (1.6% subjects who were all women. Conclusion: Obesity and low physical activity are the main factors of developing DM and its macrovascular complications in subjects with IFG.

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

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    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.

  6. Double dissociation: circadian off-peak times increase emotional reactivity; aging impairs emotion regulation via reappraisal.

    Science.gov (United States)

    Tucker, Adrienne M; Feuerstein, Rebecca; Mende-Siedlecki, Peter; Ochsner, Kevin N; Stern, Yaakov

    2012-10-01

    This study explored how the effectiveness of specific emotion regulation strategies might be influenced by aging and by time of day, given that in older age the circadian peak in cognitive performance is earlier in the day. We compared the benefit gained by 40 older (60-78 years; 20 women) and 40 younger (18-30 years; 20 women) adults during either on-peak or off-peak circadian times on 2 specific types of cognitive emotion regulation strategies: distraction and reappraisal. Participants rated their negative emotional responses to negative and neutral images under 3 conditions: a baseline nonregulation condition, a distraction condition involving a working memory task, and a reappraisal condition that involved reinterpreting the situation displayed using specific preselected strategies. First, as hypothesized, there was a crossover interaction such that participants in each age group reported more negative reactivity at their off-peak time of day. Second, a double dissociation was observed as circadian rhythms affected only negative reactivity-with reactivity highest at off-peak times-and aging diminished reappraisal but not distraction ability or reactivity. These findings add to growing evidence that understanding the effects of aging on emotion and emotion regulation depends on taking both time of day and type of regulatory strategy into account.

  7. Effect of Western medicine therapy assisted byGinkgo biloba tablet on vascular cognitive impairment of none dementia

    Institute of Scientific and Technical Information of China (English)

    Shi-Jin Zhang; Zhan-You Xue

    2012-01-01

    Objective:To discuss the clinical effects ofWestern medicine therapy assisted byGinkgo biloba tablet(GBT) on patients with vascular cognitive impairment of none dementia(VCIND).Methods:A total of80 patients withVCIND were divided into two groups randomly:Conventional treatment group(control group) and combined treatment group.Conventional treatment group was given conventional treatment with anti-platelet aggregation.In this group,75 mg aspirin was given three times a day for3 months.While in combined treatment group,19.2 mgGBT was given three times a day for3 months together with conventional treatment(anti-platelet aggregation drugs). Montreal cognitive assessment(MoCA) and transcranialDoppler(TCD) were used to observe changes of cognitive ability and cerebral blood flow inVCIND patients before and after treatment in both groups.Then the clinical data were analyzed so as to compare the efficacy in two groups. Results:After3 month-treatment in combined treatment group, the scores of executive ability, attention, abstract, delayed memory, orientation in theMoCA were significantly increased compared with those before treatment and those in control group after treatment.Besides, blood flow velocity of anterior cerebral artery increased significantly than that before treatment and that in control group after treatment.Conclusions:GBT tablet can improve the therapeutic efficacy as well improve cognitive ability and cerebral blood flow supply of patients withVCIND.

  8. Cognitive rehabilitation reduces cognitive impairment and normalizes hippocampal CA1 architecture in a rat model of vascular dementia.

    Science.gov (United States)

    Langdon, Kristopher D; Granter-Button, Shirley; Harley, Carolyn W; Moody-Corbett, Frances; Peeling, James; Corbett, Dale

    2013-06-01

    Dementia is a major cause of morbidity in the western society. Pharmacological therapies to delay the progression of cognitive impairments are modestly successful. Consequently, new therapies are urgently required to improve cognitive deficits associated with dementia. We evaluated the effects of physical and cognitive activity on learning and memory in a rat model of vascular dementia (VasD). Male Sprague-Dawley rats (6 months old) were exposed to either regular chow or a diet rich in saturated fats and sucrose and chronic bilateral common carotid artery occlusion or sham surgery. First, this model of VasD was validated using a 2 × 2 experimental design (surgery × diet) and standard cognitive outcomes. Next, using identical surgical procedures, we exposed animals to a paradigm of cognitive rehabilitation or a sedentary condition. At 16 weeks post surgery, VasD animals demonstrated significant learning and memory deficits in the Morris water maze, independent of diet. Rehabilitation significantly attenuated these cognitive deficits at this time point as well as at 24 weeks. Further, rehabilitation normalized hippocampal CA1 soma size (area and volume) to that of control animals, independent of cell number. Importantly, these findings demonstrate beneficial neuroplasticity in early middle-aged rats that promoted cognitive recovery, an area rarely explored in preclinical studies.

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

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    Priscila R De Batista

    Full Text Available 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(PH 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.

  10. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome Relação entre as adipocinas, inflamação e reatividade vascular em controles magros e pacientes obesos com síndrome metabólica

    Directory of Open Access Journals (Sweden)

    Luciana Bahia

    2006-10-01

    Full Text Available PURPOSE: Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS: Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF and vascular resistance (VR responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach and independent (sodium nitroprusside-SNP vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP, plasminogen activator inhibitor 1 (PAI-1, fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS: PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION: Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.A Síndrome Metabólica é um importante fator de risco para doenças cardiovasculares. As adipocinas interferem com a ação da insulina e com a função endotelial. OBJETIVO: Investigar a rela

  11. Tritium excretion after intravenous administration of tritium labelled adrenaline and noradrenaline and digital vascular reactivity to adrenaline and noradrenaline in normotensive and labile hypertensive subjects.

    Science.gov (United States)

    De Guia, D; Mendlowitz, M; Vlachakis, N D; Gitlow, S E; Nissenbaum, M

    1980-01-01

    1. The 24-h urinary excretion of tritium after tritiated adrenaline administration and digital vascular reactivity to exogenously administered adrenaline and noradrenaline were measured in ten normotensive and in twenty-eight labile essential hypertensive subjects. Tritiated noradrenaline excretion and apparent noradrenaline secretion rate were also measured in ten and eleven of these subjects, respectively. 2. Despite overlapping, the mean 24-h tritium excretion after 3H-adrenaline administration as well as reactivity to adrenaline were significantly greater in the hypertensive than in the normotensive subjects, whether or not they had increased responsiveness to noradrenaline. Significant correlation, however, was observed between tritium excretion of adrenaline and reactivity to adrenaline in both labile hypertensive and normotensive subjects. These measurements were also both significantly correlated with percentage variability in systolic and diastolic blood pressure in the labile hypertensive subjects. 3. No significant correlation was observed between adrenaline as against noradrenaline measurements, whether physiological or biochemical, in either hypertensive or normotensive subjects.

  12. Efeitos agudos dos estrogênios associados a progestogênios sobre a trigliceridemia e reatividade vascular pós-prandial Acute effects of the use of estrogens in association with progestogens on postprandial triglyceridemia and vascular reactivity

    Directory of Open Access Journals (Sweden)

    Silvio C.M. Santos

    2004-11-01

    Full Text Available OBJETIVO: Avaliar se a terapia de reposição hormonal com estrogênios e progestogênios, em mulheres hipertensas na pós-menopausa, modifica a trigliceridemia e a reatividade vascular pós-prandial. MÉTODOS: Estudo controlado, duplo cego, cruzado contra placebo em 15 mulheres na pós-menopausa (idade de 50 a 70, média = 61,6 ± 6 anos, sorteadas para 2 semanas de placebo ou ingestão oral de 0,625 mg de estrogênios conjugados eqüinos e 2,5 mg de medroxiprogesterona e alimentadas com refeição rica em gorduras (897 calorias; 50,1% de gorduras. Foi medida a reatividade vascular (RV - % de variação dos diâmetros do vaso entre o jejum e 2h após a alimentação, usando-se método ultra-sonográfico automatizado. Foram também determinados o perfil lipídico e a glicose, em jejum e 2h após a alimentação rica em gorduras. RESULTADOS: Com o placebo, a reatividade vascular (RV diminuiu de 3,20 ± 17% em jejum para -2,1 ± 30%, 2h após a alimentação (p = 0,041, e com terapia de reposição hormonal, a reatividade vascular diminuiu de 6,14 ± 27% em jejum para -0,05±18%, 2h após a alimentação (p=NS. A trigliceridemia pós-prandial aumentou, 35 ± 25% com o placebo, e 12 ± 10% com a terapia de reposição hormonal (P OBJECTIVE: To assess whether hormone replacement therapy with estrogens in association with progestogens in postmenopausal hypertensive women alters postprandial triglyceridemia and vascular reactivity. METHODS: A double-blind, placebo-controlled, crossover study was carried out with 15 postmenopausal women (age range: 50 to 70 years, mean = 61.6 ± 6 years randomly assigned to 2 weeks of placebo or oral ingestion of 0.625 mg of equine conjugated estrogens and 2.5 mg of medroxyprogesterone, fed a high-fat diet (897 calories; 50.1% fat. Vascular reactivity (VR - % of vessel diameter variation in the fasting period and 2 hours after meals was measured by using the automated ultrasound method. Lipid profile and glycemia

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

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    Zhang, Y.P.; Niu, C.Y.; Zhao, Z.G.; Zhang, L.M.; Si, Y.H. [Institute of Microcirculation, Hebei North University, Hebei (China)

    2013-08-10

    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 Ca{sup 2+} 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 Ca{sup 2+} at various concentrations. Maximum contractility (E{sub max}) in the shock group increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) and Ca{sup 2+} (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 Ca{sup 2+} at various concentrations in the shock+drainage group (from 0.744±0.187 to 0.570±0.143 g/mg in E{sub max} for NE and from 0.729±0.037 to 0.645±0.056 g/mg in E{sub max} for Ca{sup 2+}, 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. Validation of Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), a Performance- Based Measurement of Instrumental Activities of Daily Living for Patients with Vascular Cognitive Impairment

    Science.gov (United States)

    Chen, Hui-Mei; Lin, Hsiu-Fen; Huang, Mei-Feng; Chang, Chun-Wei; Yeh, Yi-Chun; Lo, Yi-Ching; Yen, Cheng-Fang; Chen, Cheng-Sheng

    2016-01-01

    Objective Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants’ reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), for vascular cognitive impairment (VCI) by examining its psychometric properties and diagnostic accuracy. Methods Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD), 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE), Lawton-IADL and Barthel Index (BI), were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined. Results Cronbach’s alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = –0.587, p IADL (r = –0.663) than with physical domain of Lawton IADL (r = –0.541). The area under the relative operating characteristic curve was 0.888 (95% CI = 0.812–0.965) to differentiate VaD from other groups. The optimal cut-off point of the TPIADL for detecting VaD was 6/7, which gives a sensitivity of 73.3% and a specificity of 84.5%. Conclusion The TPIADL is a brief and sensitive tool for the detection of IADL impairment in patients with VaD. PMID:27851810

  15. Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment--A Resting-State Functional Magnetic Resonance Imaging Study.

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    Weina Ding

    Full Text Available Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC analysis and voxel-mirrored homotopic connectivity (VMHC techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI.

  16. Research Progress of Correlation between Vascular Reactivity and Ionic Channel%血管反应性与离子通道的关系研究进展

    Institute of Scientific and Technical Information of China (English)

    谢环英

    2013-01-01

    Vascular hyporeactivity is often met in clinical,and continuous low blood pressure,and poor response to vasoactive medicine often puzzled clinicians. A number of clinical and animal experiments on its relevant mechanism have been done,and it's thought that the change of ion channels of vascular smooth muscle is one of the mechanisms affecting vascular reactivity. In recent years, with the mature of patch clamp technique,it's confirmed that contract obstacle of vascular smooth muscle cells is related to the change of the ion channels of the smooth muscle cells from a lot of cytological research.%血管反应性降低是临床经常遇到的情况,持续低血压、对血管活性药物反应性差常常困扰着临床医师.临床及动物实验就血管反应性机制进行了大量的研究,认为血管平滑肌细胞离子通道的变化是影响血管反应性的机制之一.近年来,随着膜片钳技术的成熟,从细胞学方面进行的大量研究进一步证实,血管平滑肌收缩障碍与平滑肌细胞上的离子通道变化有关.

  17. 小脑在血管性认知功能障碍中的作用%Role of Cerebellum on Vascular Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    尹顺雄; 闵连秋

    2013-01-01

    The cerebellum is not only associated with the motor, but also the cognitive functions of the non-motor. Vascular cognitive impairment is one of the most important branches among the cognitive function disorder. It has close relations with the risk factors of cerebrovascular disease and old ages. The damage of the nerve cell and nerve ifber bundle caused by cerebral ischemia is the main pathogenesis of vascular cognitive impairment. The strategic positions associated with vascular cognitive impairment include the frontal lobe (especially the prefrontal cortex), anterior cingulate gyrus, hippocampal gyrus, hypothalamus, basal ganglia, parietal lobe (especially the gyrus angular of dominant hemisphere), and temporal cortex, most of which are associated with the cerebellum through the ifbers. This article reviews the recent studies about the modular organization and function of the cerebellum, and its relationships with vascular cognitive impairment, to investigate the role of each anatomic site of the cerebellum on vascular cognitive impairment.%小脑不仅与运动有关,而且也参与非运动的认知功能。血管性认知功能障碍是认知功能疾病中的一个重要分支,其主要与脑血管病危险因素及高龄有关。脑组织缺血导致的神经细胞及神经纤维束损害是血管性认知功能损害的主要发病机制,其关键部位在额叶(尤其是前额区)、前扣带回、海马回、下丘脑、基底节、顶叶(特别是优势半球角回)和颞叶等,这些部位多数与小脑存在纤维联系。本文综述了近年来对小脑各部分组件式结构和功能,及其与血管性认知功能损害关系等方面的研究,探讨小脑在血管性认知功能损害中的作用。

  18. NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes.

    Science.gov (United States)

    Ebrahimian, Téni G; Heymes, Christophe; You, Dong; Blanc-Brude, Olivier; Mees, Barend; Waeckel, Ludovic; Duriez, Micheline; Vilar, José; Brandes, Ralph P; Levy, Bernard I; Shah, Ajay M; Silvestre, Jean-Sébastien

    2006-08-01

    We hypothesized that diabetes-induced oxidative stress may affect postischemic neovascularization. The response to unilateral femoral artery ligation was studied in wild-type or gp91(phox)-deficient control or type 1 diabetic mice or in animals treated with the anti-oxidant N-acetyl-l-cysteine (NAC) or with in vivo electrotransfer of a plasmid encoding dominant-negative Rac1 (50 microg) for 21 days. Postischemic neovascularization was reduced in diabetic mice in association with down-regulated vascular endothelial growth factor-A protein levels. In diabetic animals vascular endothelial growth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species (ROS) by NAC administration or the inhibition of ROS generation by gp91(phox) deficiency or by administration of dominant-negative Rac1. Finally, diabetes reduced the ability of adherent bone marrow-derived mononuclear cells (BM-MNCs) to differentiate into endothelial progenitor cells. Treatment with NAC (3 mmol/L), apocynin (200 micromol/L), or the p38MAPK inhibitor LY333351 (10 micromol/L) up-regulated the number of endothelial progenitor cell colonies derived from diabetic BM-MNCs by 1.5-, 1.6-, and 1.5-fold, respectively (P < 0.05). In the ischemic hindlimb model, injection of diabetic BM-MNCs isolated from NAC-treated or gp91(phox)-deficient diabetic mice increased neovascularization by approximately 1.5-fold greater than untreated diabetic BM-MNCs (P < 0.05). Thus, inhibition of NADPH oxidase-derived ROS overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice.

  19. A naturally-occurring histone acetyltransferase inhibitor derived from Garcinia indica impairs newly acquired and reactivated fear memories.

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    Stephanie A Maddox

    Full Text Available The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD. Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica, to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.

  20. Antioxidants and vascular health.

    Science.gov (United States)

    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.

  1. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery

    DEFF Research Database (Denmark)

    Storkebaum, Erik; Ruiz de Almodovar, Carmen; Meens, Merlijn;

    2010-01-01

    BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( ...

  2. Restoring placental growth factor-soluble fms-like tyrosine kinase-1 balance reverses vascular hyper-reactivity and hypertension in pregnancy.

    Science.gov (United States)

    Zhu, Minglin; Ren, Zongli; Possomato-Vieira, José S; Khalil, Raouf A

    2016-09-01

    Preeclampsia (PE) is a pregnancy-related hypertensive disorder (HTN-Preg) with unclear mechanism. An imbalance between antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic placental growth factor (PlGF) has been observed in PE, but the vascular targets and signaling pathways involved are unclear. We assessed the extent of sFlt-1/PlGF imbalance and vascular dysfunction in a rat model of HTN-Preg produced by reduction of uteroplacental perfusion pressure (RUPP), and tested whether inducing a comparable sFlt-1/PlGF imbalance by infusing sFlt-1 (10 μg·kg(-1)·day(-1)) in day 14 pregnant (Preg) rats cause similar increases in blood pressure (BP) and vascular reactivity. Using these guiding measurements, we then tested whether restoring sFlt-1/PlGF balance by infusing PIGF (20 μg·kg(-1)·day(-1)) in RUPP rats would improve BP and vascular function. On gestational day 19, BP was in Preg+sFlt-1 and RUPP > Preg, and in RUPP+PlGF Preg, and in RUPP+PlGF RUPP, and was blocked by N(ω)-nitro-l-arginine methyl ester (l-NAME) or ODQ treatment or endothelium removal. Western blots revealed that aortic total endothelial NOS (eNOS) and activated phosphorylated-eNOS were in Preg+sFlt-1 and RUPP RUPP. ACh-induced vascular nitrate/nitrite production was in Preg+sFlt-1 and RUPP RUPP. Vascular relaxation to the exogenous NO donor sodium nitroprusside was not different among groups. Thus, a tilt in the angiogenic balance toward anti-angiogenic sFlt-1 is associated with decreased vascular relaxation and increased vasoconstriction and BP. Restoring the angiogenic/antiangiogenic balance using PlGF enhances endothelial NO-cGMP vascular relaxation and decreases vasoconstriction and BP in HTN-Preg rats and could offer a new approach in the management of PE.

  3. HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

    Science.gov (United States)

    Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

    2015-01-01

    Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

  4. Reactive carbonyl compounds impair wound healing by vimentin collapse and loss of the primary cilium.

    Science.gov (United States)

    Rodríguez-Ribera, Lara; Slattery, Craig; Mc Morrow, Tara; Marcos, Ricard; Pastor, Susana

    2017-10-01

    In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound-healing ability where the normal epithelial tissue is substituted for scar tissue caused by accumulation of extracellular matrix proteins (ECM). During the wound-healing process, epithelial cells may undergo epithelial-mesenchymal transition (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re-epithelialize the wound site. It has been reported that chronic inflammation and uremic milieu are involved in wound-healing and enhanced kidney damage in chronic kidney disease (CKD) patients. In this study we evaluated reactive carbonyl compounds (RCC) effects on renal wound healing. The compounds resulting from carbonyl stress evaluated in this study were glyoxal (GO), methylglyoxal (MGO), malondialdehyde (MDA) and 4-hydroxy-hexenal (HHE). Wound repair ability was evaluated by the wound healing assay using HK-2 cells. EMT was evaluated by morphological, protein and transcriptional changes using microscopy, western blot, zymography and RT-qPCR. Changes in the vimentin network and primary cilia were assessed by immunofluorescence. Our data demonstrated that MDA and GO delay wound closure mediated by vimentin disruption, which caused collagen I mRNA decrease, and deciliation. In contrast, HHE treatment (and MGO to a minor degree) induced morphological changes and increased mesenchymal marker expression and gelatinase activity in HK-2 cells. In this study, we have demonstrated for the first time that exposure to RCC differentially affects wound healing in proximal tubular epithelia. A better comprehension of effects of uremic toxins on wound healing and fibrosis and migration is necessary to seek mechanisms to slow down renal fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.

    Science.gov (United States)

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P R

    2016-05-18

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P mobilization by G-CSF or AMD3100 was either increased or unaffected (P mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.

  6. Expansion duroplasty improves intraspinal pressure, spinal cord perfusion pressure, and vascular pressure reactivity index in patients with traumatic spinal cord injury: injured spinal cord pressure evaluation study.

    Science.gov (United States)

    Phang, Isaac; Werndle, Melissa C; Saadoun, Samira; Varsos, Georgios; Czosnyka, Marek; Zoumprouli, Argyro; Papadopoulos, Marios C

    2015-06-15

    We recently showed that, after traumatic spinal cord injury (TSCI), laminectomy does not improve intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of spinal cord decompression (increase in intradural space, cerebrospinal fluid around the injured cord) and spinal cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebrospinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves spinal cord radiological and physiological parameters more effectively than laminectomy alone.

  7. Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia-Induced Neovascularization: The Role of Dipeptidyl Peptidase-4/Glucagon-Like Peptide-1-Adiponectin Axis.

    Science.gov (United States)

    Piao, Limei; Zhao, Guangxian; Zhu, Enbo; Inoue, Aiko; Shibata, Rei; Lei, Yanna; Hu, Lina; Yu, Chenglin; Yang, Guang; Wu, Hongxian; Xu, Wenhu; Okumura, Kenji; Ouchi, Noriyuki; Murohara, Toyoaki; Kuzuya, Masafumi; Cheng, Xian Wu

    2017-09-28

    Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon-like peptide-1 (GLP-1) metabolism, we investigated the role of DPP4/GLP-1 axis in vascular senescence and ischemia-induced neovascularization in mice under chronic stress, with a special focus on adiponectin -mediated peroxisome proliferator activated receptor-γ/its co-activator 1α (PGC-1α) activation. Seven-week-old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood-flow ratio throughout the follow-up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle DPP4 and decreased levels of GLP-1 and adiponectin in plasma and phospho-AMP-activated protein kinase α (p-AMPKα), vascular endothelial growth factor, peroxisome proliferator activated receptor-γ, PGC-1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial CD31(+)/c-Kit(+) progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting. DPP4 inhibition and GLP-1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion. These results indicate that the DPP4/GLP-1-adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults

    Science.gov (United States)

    Gallaway, Patrick J.; Miyake, Hiroji; Buchowski, Maciej S.; Shimada, Mieko; Yoshitake, Yutaka; Kim, Angela S.; Hongu, Nobuko

    2017-01-01

    A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research. PMID:28230730

  9. Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults

    Directory of Open Access Journals (Sweden)

    Patrick J. Gallaway

    2017-02-01

    Full Text Available A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research.

  10. Impaired Arterial Elasticity Identified by Pulse Waveform Analysis as a Marker for Vascular Wall Damage in Humans With Aging and Hypertension

    Institute of Scientific and Technical Information of China (English)

    Wang Yan; Tao Jun; Tu Chang; Yang Zhen; Xu Mingguo; Wang Jiemei; Jin Yafei; Ma Hong

    2005-01-01

    Objectives Cardiovascular risk factors lead to pathogenesis of atherosclerosis and its clinical events by impairing vascular wall. Endothelial dysfunction is the earliest marker for vascular wall injuries. Development of new method to detect early vascular wall damage has an important clinical implication for the prevention and treatment of cardiovascular diseases. Therefore, the present study was performed to evaluate effect of aging and hypertension, two independent risk factors for cardiovascular diseases, on arterial elasticity by using pulse waveform analysis and investigate whether the changes in arterial elasticity can be used as a risk marker for vascular structural and functional abnormalities. Methods Using modified Windkessel model of the circulation and pulse waveform analysis,C 1 large artery and C2 small artery elasticity indices of 204 Chinese normal healthy subjects ( age 15-80years) and 46 Chinese essential hypertensive patients (age 35-70 years) were measured. Age- and hypertension-related arterial elasticity changes were examined. Results C1 large artery and C2 small artery elasticity indices were reduced with advancing age in healthy subjects. C1 large artery and C2 small artery elasticity indices were negatively correlated with age (r=-0.628, P<0.001; r=-0.595, P<0.001). C1 large artery and C2 small artery elasticity indices in patients with essential hypertension compared with the agematched healthy subjects were (9.31±3.85 ml/mm Hg x 10 versus 15.13±4.14 ml/mmHg x 10, P<0.001) and (3.57± 1.62 ml/mm Hg x 100 versus 7.89±2.91 ml/mmHg ×100 P <0.001), respectively, and were significantly lower than the corresponding healthy subjects. There were negative association between C1large artery and C2 small artery elasticity indices and systolic blood pressure (r=-0.37, P<0.05; r=-0.39,P<0.05) and pulse pressure (r=-0.39, P<0.05; r=0.43,P<0.05) in patients with essential hypertension.Conclusions Advancing age and essential

  11. Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.

    Directory of Open Access Journals (Sweden)

    Zhu Jin

    Full Text Available Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191 to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day and hyroxysafflor yellow A (HSYA (10 mg/kg/day. The result show that systolic blood pressure (SBP and heart rate (HR of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lima, V.V. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil); Lobato, N.S.; Filgueira, F.P. [Curso de Medicina, Setor de Fisiologia Humana, Universidade Federal de Goiás, Jataí, GO (Brazil); Webb, R.C. [Department of Physiology, Georgia Regents University, Augusta, GA (United States); Tostes, R.C. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Giachini, F.R. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil)

    2014-08-15

    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{sup 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.

  13. Value of determining the cerebrospinal fluid protein markers of amyloidosis and neurodegeneration in the diagnosis of vascular and neurodegenerative cognitive impairments

    Directory of Open Access Journals (Sweden)

    Vladimir Yuryevich Lobzin

    2013-01-01

    Full Text Available The article presents data on different forms of moderate cognitive impairments (MCI and the specific features of their transformation to dementia. Cerebrospinal fluid (CSF was investigated in 60 patients with the amnestic and neurodynamic types of MCI, in 15 patients with vascular dementia (VD, 50 patients with Alzheimer’s disease (AD, and 23 patients with mixed vascular and neurodegenerative dementia (MVND. The specific features of β-amyloid and τ-protein concentrations were established in the preclinical stages of dementia, which reflects the main components of the pathogenesis of neurodegeneration. In the amnestic form of MCI and AD, there was drastically decreased Aβ-42 and increased τ-protein levels in SCF. As cognitive impairments progressed, there was a rise in the concentration of τ-protein; its level correlated with the severity of dementia. In MND, the level of Aβ-42 was significantly reduced while the concentration of τ-protein was much increased; moreover, to a greater extent than in AD and VD. Cerebrovascular damage and neurodegeneration were related to each other and mutually worsened clinical and pathogenic effects.

  14. The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline.

    Science.gov (United States)

    Corriveau, Roderick A; Bosetti, Francesca; Emr, Marian; Gladman, Jordan T; Koenig, James I; Moy, Claudia S; Pahigiannis, Katherine; Waddy, Salina P; Koroshetz, Walter

    2016-03-01

    The World Health Organization reports that 47.5 million people are affected by dementia worldwide. With aging populations and 7.7 million new cases each year, the burden of illness due to dementia approaches crisis proportions. Despite significant advances in our understanding of the biology of Alzheimer's disease (AD), the leading dementia diagnosis, the actual causes of dementia in affected individuals are unknown except for rare fully penetrant genetic forms. Evidence from epidemiology and pathology studies indicates that damage to the vascular system is associated with an increased risk of many types of dementia. Both Alzheimer's pathology and cerebrovascular disease increase with age. How AD affects small blood vessel function and how vascular dysfunction contributes to the molecular pathology of Alzheimer's are areas of intense research. The science of vascular contributions to cognitive impairment and dementia (VCID) integrates diverse aspects of biology and incorporates the roles of multiple cell types that support the function of neural tissue. Because of the proven ability to prevent and treat cardiovascular disease and hypertension with population benefits for heart and stroke outcomes, it is proposed that understanding and targeting the biological mechanisms of VCID can have a similarly positive impact on public health.

  15. 轻度认知障碍与非痴呆型血管性认知功能障碍%Mild cognitive impairment and vascular cognitive impairment no dementia

    Institute of Scientific and Technical Information of China (English)

    沈娜娜; 陈卫; 赵仁亮

    2010-01-01

    轻度认知障碍与非痴呆型血管性认知障碍是近年来针对阿尔茨海默病与血管性痴呆提出的早期阶段,两者在概念、诊断标准、流行病学、病理学、神经心理学、生物学标志物等方面既有不同,又有很多交叉和联系.文章就近年来的研究进展和面临的问题进行了综述.%The mild cognitive impairment and vascular cognitive impairment no dementia are the early stages for Alzheimer's disease and vascular dementia proposed in recent years.They both not only have some differences,but also have many crosses and contacts in concepts,diagnostic criteria,epidemiology,pathology,neuropsychology,and biological markers,etc.This article reviews the recent progresses and problems facing in recent years.

  16. Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.

    Science.gov (United States)

    Mandell, Erica; Powers, Kyle N; Harral, Julie W; Seedorf, Gregory J; Hunter, Kendall S; Abman, Steven H; Dodson, R Blair

    2015-12-15

    High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.

  17. The impact of vascular comorbidities on qualitative error analysis of executive impairment in Alzheimer’s disease

    OpenAIRE

    Lamar, Melissa; Libon, David. J.; Ashley, Angela V.; Lah, James J; Levey, Allan I.; Goldstein, Felicia C.

    2009-01-01

    Recent evidence suggests that patients with Alzheimer’s disease (AD) and vascular comorbidities (VC) perform worse across measures of verbal reasoning and abstraction when compared to patients with AD alone. We performed a qualitative error analysis of WAIS-III Similarities zero-point responses in 45 AD patients with varying numbers of VC including diabetes, hypertension and hypercholesterolemia. Errors were scored in set if the answer was vaguely related to the word pair (e.g., doglion: ‘the...

  18. Consumption of a Western-style diet during pregnancy impairs offspring islet vascularization in a Japanese macaque model

    OpenAIRE

    Pound, Lynley D.; Comstock, Sarah M.; Grove, Kevin L.

    2014-01-01

    Children exposed to a maternal Western-style diet in utero have an increased risk of developing type 2 diabetes. Understanding the mechanisms and an investigation of possible interventions are critical to reversing this phenomenon. We examined the impact of maternal Western-style diet consumption on the development of islet vascularization and innervation, both of which are critical to normal islet function, in fetal and juvenile offspring. Furthermore, we assessed whether improved dietary in...

  19. Sevoflurane effects on cyclic adenosine monophosphate response element binding protein, phosphorylated cyclic adenosine monophosphate response element binding protein, and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat model

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Ling Dan; Xianlin Zhu

    2009-01-01

    BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia.OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA.METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours.MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze.RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P<0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P<0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham

  20. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

    Science.gov (United States)

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

  1. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood-brain barrier function in mice.

    Science.gov (United States)

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood-brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [(3)H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [(3)H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development.

  2. Cerebral microbleeds in patients with mild cognitive impairment and small vessel disease: The Vascular Mild Cognitive Impairment (VMCI)-Tuscany study.

    Science.gov (United States)

    Valenti, Raffaella; Del Bene, Alessandra; Poggesi, Anna; Ginestroni, Andrea; Salvadori, Emilia; Pracucci, Giovanni; Ciolli, Laura; Marini, Sandro; Nannucci, Serena; Pasi, Marco; Pescini, Francesca; Diciotti, Stefano; Orlandi, Giovanni; Cosottini, Mirco; Chiti, Alberto; Mascalchi, Mario; Bonuccelli, Ubaldo; Inzitari, Domenico; Pantoni, Leonardo

    2016-09-15

    Cerebral microbleeds (CMBs) are a neuroimaging expression of small vessel disease (SVD). We investigated in a cohort of SVD patients with mild cognitive impairment (MCI): 1) the reliability of the Microbleed Anatomical Rating Scale (MARS); 2) the burden and location of CMBs and their association with cognitive performances, independent of other clinical and neuroimaging features. Patients underwent clinical, neuropsychological (4 cognitive domains), and MRI assessments. CMBs were assessed by three raters. Out of the 152 patients (57.2% males; mean age±SD: 75.5±6.7years) with gradient-echo (GRE) sequences, 41 (27%) had at least one CMB. Inter-rater agreement for number and location of CMBs ranged from good to very good [multi-rater Fleiss kappa (95%CI): 0.70-0.95]. Lacunar infarcts and some clinical variables (e.g., hypertension and physical activity) were associated with CMBs in specific regions. Total number of CMBs and of those in deep and lobar regions were associated with attention/executive and fluency domains. MARS is a reliable instrument to assess CMBs in SVD patients with MCI. Nearly one third of these patients had at least one CMB. Total CMBs burden was associated with attention/executive functions and fluency domains impairment, lacunar infarcts, and with some potentially modifiable risk factors. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Angiogenesis impairment in diabetes: role of methylglyoxal-induced receptor for advanced glycation endproducts, autophagy and vascular endothelial growth factor receptor 2.

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    Hongtao Liu

    Full Text Available Diabetes impairs physiological angiogenesis by molecular mechanisms that are not fully understood. Methylglyoxal (MGO, a metabolite of glycolysis, is increased in patients with diabetes. This study defined the role of MGO in angiogenesis impairment and tested the mechanism in diabetic animals. Endothelial cells and mouse aortas were subjected to Western blot analysis of vascular endothelial growth factor receptor 2 (VEGFR2 protein levels and angiogenesis evaluation by endothelial cell tube formation/migration and aortic ring assays. Incubation with MGO reduced VEGFR2 protein, but not mRNA, levels in a time and dose dependent manner. Genetic knockdown of the receptor for advanced glycation endproducts (RAGE attenuated the reduction of VEGFR2. Overexpression of Glyoxalase 1, the enzyme that detoxifies MGO, reduced the MGO-protein adducts and prevented VEGFR2 reduction. The VEGFR2 reduction was associated with impaired angiogenesis. Suppression of autophagy either by inhibitors or siRNA, but not of the proteasome and caspase, normalized both the VEGFR2 protein levels and angiogenesis. Conversely, induction of autophagy either by rapamycin or overexpression of LC3 and Beclin-1 reduced VEGFR2 and angiogenesis. MGO increased endothelial LC3B and Beclin-1, markers of autophagy, which were accompanied by an increase of both autophagic flux (LC3 punctae and co-immunoprecipitation of VEGFR2 with LC3. Pharmacological or genetic suppression of peroxynitrite (ONOO(- generation not only blocked the autophagy but also reversed the reduction of VEGFR2 and angiogenesis. Like MGO-treated aortas from normglycemic C57BL/6J mice, aortas from diabetic db/db and Akita mice presented reductions of angiogenesis or VEGFR2. Administration of either autophagy inhibitor ex vivo or superoxide scavenger in vivo abolished the reductions. Taken together, MGO reduces endothelial angiogenesis through RAGE-mediated, ONOO(-dependent and autophagy-induced VEGFR2 degradation, which

  4. Sodium chlorite increases production of reactive oxygen species that impair the antioxidant system and cause morphological changes in human erythrocytes.

    Science.gov (United States)

    Ali, Shaikh Nisar; Mahmood, Riaz

    2017-04-01

    Sodium chlorite (NaClO2 ) is used in the production of chlorine dioxide for bleaching and stripping of textiles, pulp, and paper. It is also used as disinfectant in municipal water treatment and as a component in therapeutic rinses and gels. The effect of NaClO2 on human erythrocytes has been studied under in vitro conditions. Incubation of 5% suspension of erythrocytes with NaClO2 (0.1-2.0 mM) at 37°C for 30 min resulted in marked cell lysis (1.2-3.8 fold) and increased their osmotic fragility. Several parameters were assayed in cell lysates prepared from NaClO2 -treated and -untreated (control) erythrocytes. Compared to controls, exposure to NaClO2 caused significant increase in protein oxidation (1.1-8.07 fold), lipid peroxidation (1.08-4.95 fold) with decrease in total sulfhydryl (-5 to -61%), and glutathione levels (-7 to -86%). Methemoglobin content was tremendously increased, by 5-52 fold when compared to control, while methemoglobin reductase activity decreased (-17 to -93%) upon NaClO2 treatment. NaClO2 enhanced the generation of reactive oxygen species by 3-21 fold and lowered the metal reducing and free radical quenching ability of erythrocytes. It also caused an increase in nitric oxide levels (2.7-15.4 fold) showing generation of nitrosative stress too. The activities of major antioxidant and membrane bound enzymes were significantly altered. Gross morphological changes, from discocytes to echinocytes, were seen in NaClO2 -treated erythrocytes under electron microscope. These results show that NaClO2 induces oxidative stress in human erythrocytes, damages the membrane, and impairs the cellular antioxidant defence system. This oxidative damage can shorten the life span of erythrocytes in blood resulting in red cell senescence. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1343-1353, 2017. © 2016 Wiley Periodicals, Inc.

  5. Interaction between maternal and offspring diet to impair vascular function and oxidative balance in high fat fed male mice.

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    Christopher Torrens

    Full Text Available AIMS: To determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring. METHODS: Female C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat or standard chow (C, 21% kcal fat pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF which were studied at 15 or 30 weeks of age. RESULTS: There were significant effects of maternal diet on offspring body weight (p<0.004, systolic blood pressure (p = 0.026 and endothelium-dependent relaxation to ACh (p = 0.004 and NO production (p = 0.005 measured in the femoral artery. With control for maternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (p<0.0001 and reduce endothelium-dependent relaxation (p = 0.022 and ACh-mediated NO production (p = 0.007. There was also a significant impact of age (p<0.005. Redox balance was perturbed, with altered regulation of vascular enzymes involved in ROS/NO signalling. CONCLUSIONS: Maternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult life.

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

    Science.gov (United States)

    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

  7. 血管性认知损害动物模型研究进展%Advances in animal models of vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    王志强; 王慶松

    2014-01-01

    With the thorough research on cognitive impairment in old age,vascular cognitive inpairment (VCI) has become a hot research field of neuroscience in recent years.Yet,the VCI-related pathogenic mechanism currently remains unknown.Therefore,the reliable and stable animal models are needed to reveal the pathogenesis and pathophysiologic changes of VCI in order to provide a theoretical basis for early warning,diagnosis and treatment of VCI.The commonly used animal models now have their own advantages and disadvantages,the results have greater differences.This article reviews the commonly used VCI animal models,related cognitive behavior changes,and change characteristics of histopathology in recent years,and the reasonable animal models of VCI according to different research objectives are investigated preliminarily.%随着对老年期认知损害研究的深入,血管性认知损害(vascular cognitive impairment,VCI)已成为近年来神经科学研究领域的热点.然而,VCI相关的致病机制目前仍不明确,需要可靠和稳定的动物模型来揭示VCI的发病机制和病理生理学变化,为VCI的预警和诊治提供理论依据.目前常用的动物模型各有其优势和不足,所得结果差异较大.文章就近年来常用的VCI动物模型及相关认知行为学改变和病理组织学变化特点进行了综述,并针对不同研究目的的合理VCI动物模型进行了初步探讨.

  8. Protective Effects of Tao-Hong-Si-Wu Decoction on Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Lan Han

    2015-01-01

    Full Text Available Tao-Hong-Si-Wu decoction (TSD as a traditional chinese medicine (TCM has been developed to treat thrombotic diseases for hundreds of years, and vascular dementia (VD is a cognitive dysfunction syndrome caused by cerebral embolism. In this study, the protective effect of TSD on memory impairment and brain damage in rat model of VD induced by middle cerebral artery occlusion (MCAO was investigated. The study showed that rats in MCAO treatment with TSD for 14 days significantly improved behavioral function, increased densities of neuron, and induced angiogenesis in the brain compared with model rats. TSD also adjusted the neurotransmitter levels, reduced the content of endothelin-1 (ET-1, and induced the activities of vascular endothelial growth factor (VEGF in hippocampus. Moreover, the immunohistochemical staining and western blotting results also revealed that TSD decreased apoptosis via upregulated B-cell lymphoma-2 (Bcl-2/Bcl-2 associated X protein (Bax ratio. These results demonstrated TSD possesses neuroprotective and antidementia properties by preventing the loss of neural cells, adjusting brain neurotransmitter, promoting cerebral blood circulation, and decreasing apoptosis. These results suggested that TSD might be developed as an effective drug for the prevention of VD.

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

    Science.gov (United States)

    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.

  10. Chronic supplementation of paeonol combined with danshensu for the improvement of vascular reactivity in the cerebral basilar artery of diabetic rats.

    Science.gov (United States)

    Hu, Jing; Li, Ya-Ling; Li, Zi-Lin; Li, Hua; Zhou, Xuan-Xuan; Qiu, Peng-Cheng; Yang, Qian; Wang, Si-Wang

    2012-11-08

    One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl(2)-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic

  11. Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Peng-Cheng Qiu

    2012-11-01

    Full Text Available One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge, protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae and danshensu (DSS, should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS

  12. C-reactive protein, advanced glycation end products and their receptor in type 2 diabetic, elderly patients with mild cognitive impairment

    OpenAIRE

    2015-01-01

    Objective: The aim of the study was to evaluate serum levels of AGEs (advanced glycation end products), RAGE (receptor for advanced glycation end products) and CRP (C-reactive protein) in elderly patients with T2DM with and without mild cognitive impairment (MCI) and to determine the predictors (including AGEs, RAGE and CRP levels) of having MCI in elderly patients with type 2 diabetes.Methods: 276 diabetics elders were screened for MCI (using the Montreal Cognitive Assessment: MoCA score). D...

  13. Cerebrovascular reactivity by using arterial spin-labeling magnetic resonance imaging in subcortical ischemic vascular disease%皮质下缺血性血管病脑血管反应性磁共振研究

    Institute of Scientific and Technical Information of China (English)

    舒敏; 章军建; 高永哲; 张洪; 吴光耀

    2014-01-01

    目的:通过观察皮质下缺血性血管病(SIVD)患者不同脑区局部脑血管反应性(CVR)的变化及认知功能的损害,探讨 SIVD 局部 CVR 的改变在认知功能损害中的作用。方法:采用动脉自旋标记(ASL)磁共振灌注技术定量测定 SIVD 患者与对照组吸入5% CO2前后额叶、颞叶、顶叶、枕叶皮质和白质局部血流量(rCBF),CVR 采用前后2次各兴趣区 rCBF 的增加率表示。结果:(1) SIVD 组额叶皮质及白质、颞叶白质、枕叶白质的 CVR 比对照组显著降低(P <0.05)。(2) SIVD 组有认知功能损害患者和无认知功能损害患者相比额叶皮质、额叶白质 CVR 下降明显(P <0.01)。结论:SIVD 患者存在广泛的脑血管自动调节功能受损,并且额叶皮质、白质的 CVR 下降与认知功能损害有关。%Objective To assess regional cerebrovascular reactivity (CVR) and cognition impairment of subcortical ischemic vascular disease (SIVD). To show whether CVR affects cognitive impairment of SIVD patients. Methods Arterial spin-labeling (ASL) by MR image was applied in measuring regional cerebral blood flow (rCBF) of frontal lobe, temporal lobe, parietal lobe, occipital lobes after 5% CO2 inhalation, and the CVR was demonstrated by increase rate of rCBF in all the subject areas. Results (1)The patients with SIVD had reduced CVR in cortex of frontal lobes, white matter of frontal lobes, temporal lobes and occipital lobes(P < 0.05). (2) CVR in the SIVD patients with cognitive impairment decreased in frontal cortex and white matter when compared with the patients without cognitive impairment(P < 0.01). Conclusion These results showed that CVR decreased significantly in cortical gray matter and white matter in elderly patients with SIVD. Also the reduction of CVR in the frontal cortex and white matter was associated with cognitive impairment.

  14. Safrole oxide induced human umbilical vein vascular endothelial cell differentiation into neuron-like cells by depressing the reactive oxygen species level at the low concentration.

    Science.gov (United States)

    Su, Le; Zhao, Jing; Zhao, Bao Xiang; Miao, Jun Ying; Yin, De Ling; Zhang, Shang Li

    2006-02-01

    Previously, we found that 5-25 microg/ml safrole oxide could inhibit apoptosis and dramatically make a morphological change in human umbilical vein vascular endothelial cells (HUVECs). But the possible mechanism by which safrole oxide function is unknown. To answer this question, in this study, we first investigated the effects of it on the activity of nitric oxide synthetase (NOS), the expressions of Fas and integrin beta4, which play important roles in HUVEC growth and apoptosis, respectively. The results showed that, at the low concentration (10 microg/ml), safrole oxide had no effects on NOS activity and the expressions of Fas and integrin beta4. Then, we investigated whether HUVECs underwent differentiation. We examined the expressions of neuron-specific enolase (NSE) and neurofilament-L (NF-L). Furthermore, we analyzed the changes of intracellular reactive oxygen species (ROS). After 10 h of treatment with 10 microg/ml safrole oxide, some HUVECs became neuron-like cells in morphology, and intensively displayed positive NSE and NF-L. Simultaneously, ROS levels dramatically decreased during HUVECs differentiation towards neuron-like cells. At the low concentration, safrole oxide induced HUVECs differentiation into neuron-like cells. Furthermore, our data suggested that safrole oxide might perform this function by depressing intracellular ROS levels instead of by affecting cell growth or apoptosis signal pathways.

  15. Associations of C-Reactive Protein to Indices of Vascular Health and the Influence of Serum 25(OHD Status in Healthy Adults

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    Ambika P. Ashraf

    2012-01-01

    Full Text Available Elevated serum high-sensitivity C-reactive protein (hs-CRP and low serum 25-hydroxyvitamin D [25(OHD] are associated with increased cardiovascular disease (CVD risk. Ethnic differences in serum hs-CRP and 25(OHD concentrations and CVD are known. Objectives: to investigate the ethnic differences in hs-CRP concentrations, to assess the influence of 25(OHD on these ethnic differences and to examine the influence of 25(OHD on association between hs-CRP and cardiovascular health indices. Subjects: 62 healthy adults [26 African Americans (AA, 26 European Americans (EA, and 10 Hispanic Americans (HA], ages 18–55 years. Serum hs-CRP and 25(OHD as well as pulse wave velocity (PWV, augmentation index (AIx, and flow-mediated dilatation (FMD were measured. hs-CRP was inversely associated with 25(OHD (r=−0.25, P=0.049, and hs-CRP was positively associated with PWV (r=0.29, P=0.04. The association of hs-CRP with PWV attenuated after adjustment for 25(OHD (P=0.15. hs-CRP was higher in AA compared to EA (P=0.05; this differences was reduced by 32% after adjusting for serum 25(OHD. Conclusion: eventhough the inverse association between serum 25(OHD and CRP does not infer causality, lower serum 25(OHD may increase risk for inflammation and endothelial dysfunction. The lower 25(OHD in AA may predispose to greater inflammation and associated vascular dysfunction.

  16. Data on the effects of losartan on protein expression, vascular reactivity and antioxidant capacity in the aorta of ethanol-treated rats

    Directory of Open Access Journals (Sweden)

    Carla S. Ceron

    2017-04-01

    Full Text Available We describe the effects of losartan, a selective AT1 receptor antagonist on the alterations induced by treatment with ethanol in the rat aorta. The data shown here are related to the article entitled “Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress” (P. Passaglia, C.S. Ceron, A.S. Mecawi, J. Antunes-Rodrigues, E.B. Coelho, C.R. Tirapelli, 2015 [1]. Here we include new data on the protective effect of losartan against ethanol-induced oxidative stress. Male Wistar rats treated for 2 weeks with ethanol (20%, vol./vol. exhibited increased aortic production of reactive oxygen species (ROS and losartan (10 mg/kg/day; p.o. gavage prevented this response. Ethanol did not alter the expression of eNOS in the rat aorta. Losartan prevented ethanol-induced increase in the aortic expression of nNOS. Neither ethanol nor losartan affected superoxide dismutase (SOD or catalase (CAT activities in the rat aorta. Treatment with ethanol increased the contraction induced by phenylephrine in both endothelium-intact and endothelium-denuded aortas and these responses were prevented by losartan. Conversely, neither ethanol nor losartan affected the endothelium-dependent relaxation induced by acetylcholine.

  17. MicroRNA-497 impairs the growth of chemoresistant neuroblastoma cells by targeting cell cycle, survival and vascular permeability genes

    Science.gov (United States)

    Soriano, Aroa; París-Coderch, Laia; Jubierre, Luz; Martínez, Alba; Zhou, Xiangyu; Piskareva, Olga; Bray, Isabella; Vidal, Isaac; Almazán-Moga, Ana; Molist, Carla; Roma, Josep; Bayascas, José R.; Casanovas, Oriol; Stallings, Raymond L.; de Toledo, José Sánchez; Gallego, Soledad; Segura, Miguel F.

    2016-01-01

    Despite multimodal therapies, a high percentage of high-risk neuroblastoma (NB) become refractory to current treatments, most of which interfere with cell cycle and DNA synthesis or function, activating the DNA damage response (DDR). In cancer, this process is frequently altered by deregulated expression or function of several genes which contribute to multidrug resistance (MDR). MicroRNAs are outstanding candidates for therapy since a single microRNA can modulate the expression of multiple genes of the same or different pathways, thus hindering the development of resistance mechanisms by the tumor. We found several genes implicated in the MDR to be overexpressed in high-risk NB which could be targeted by microRNAs simultaneously. Our functional screening identified several of those microRNAs that reduced proliferation of chemoresistant NB cell lines, the best of which was miR-497. Low expression of miR-497 correlated with poor patient outcome. The overexpression of miR-497 reduced the proliferation of multiple chemoresistant NB cell lines and induced apoptosis in MYCN-amplified cell lines. Moreover, the conditional expression of miR-497 in NB xenografts reduced tumor growth and inhibited vascular permeabilization. MiR-497 targets multiple genes related to the DDR, cell cycle, survival and angiogenesis, which renders this molecule a promising candidate for NB therapy. PMID:26824183

  18. Activated Rho kinase mediates diabetes-induced elevation of vascular arginase activation and contributes to impaired corpora cavernosa relaxation: possible involvement of p38 MAPK activation.

    Science.gov (United States)

    Toque, Haroldo A; Nunes, Kenia P; Yao, Lin; Liao, James K; Webb, R Clinton; Caldwell, Ruth B; Caldwell, R William

    2013-06-01

    Activated RhoA/Rho kinase (ROCK) has been implicated in diabetes-induced erectile dysfunction. Earlier studies have demonstrated involvement of ROCK pathway in the activation of arginase in endothelial cells. However, signaling pathways activated by ROCK in the penis remain unclear. We tested whether ROCK and p38 MAPK are involved in the elevation of arginase activity and subsequent impairment of corpora cavernosal (CC) relaxation in diabetes. Eight weeks after streptozotocin-induced diabetes, vascular functional studies, arginase activity assay, and protein expression of RhoA, ROCK, phospho-p38 MAPK, p38 MAPK, phospho-MYPT-1(Thr850), MYPT-1 and arginase levels were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT + D), partial ROCK 2(+/-) knockout (KO), and ROCK 2(+/-) KO + D mice. The expression of RhoA, ROCK 1 and 2, phosphorylation of MYPT-1(Thr850) and p38 MAPK, arginase activity/expression, endothelial- and nitrergic-dependent relaxation of CC was assayed. Diabetes significantly reduced maximum relaxation (Emax ) to both endothelium-dependent acetylcholine (WT + D: Emax; 61 ± 4% vs. WT: Emax; 75 ± 2%) and nitrergic nerve stimulation. These effects were associated with increased expression of active RhoA, ROCK 2, phospho-MYPT-1(Thr850), phospho-p38 MAPK, arginase II, and activity of corporal arginase (1.6-fold) in WT diabetic CC. However, this impairment in CC of WT + D mice was absent in heterozygous ROCK 2(+/-) KO + D mice for acetylcholine (Emax : 80 ± 5%) and attenuated for nitrergic nerve-induced relaxation. CC of ROCK 2(+/-) KO + D mice showed much less ROCK activity, did not exhibit p38 MAPK activation, and had reduced arginase activity and arginase II expression. These findings indicate that ROCK 2 mediates diabetes-induced elevation of arginase activity. Additionally, pretreatment of WT diabetic CC with inhibitors of arginase (ABH) or p38 MAPK (SB203580) partially prevented impairment of ACh- and nitrergic nerve

  19. Nutrient biomarkers and vascular risk factors in subtypes of mild cognitive impairment: a cross-sectional study.

    Science.gov (United States)

    Yin, Y; Fan, Y; Lin, F; Xu, Y; Zhang, J

    2015-01-01

    To investigate the interrelationships among blood nutrient biomarkers, the Framingham Stroke Risk Profile (FSRP), and cognitive impairment features in mild cognitive impairment (MCI) subjects and to verify whether nutrient biomarkers and FSRP are risk factors for MCI. According to the criteria for MCI developed by Petersen, 81 subjects aged 50-80 years were divided into a normal control group (NC group, n = 36) and an MCI group (n = 45). Then, the MCI group was divided into an amnestic MCI (a-MCI) and a multidomain MCI (md-MCI) group. All subjects were administered a comprehensive health history to calculate their FSRP score and a thorough neuropsychological assessment of four cognitive domains. Blood samples from all subjects were collected to measure the nutrient biomarkers. FSRP score was not only associated with memory function, but also with executive function, which itself had a negative relationship with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3 polyunsaturated fatty acids (n-3PUFAs) levels, and a positive relationship with the ratio of n-6 PUFAs to n-3 PUFAs(n6/n3). Compared with the NC group, the concentrations of EPA, DHA, 25-hydroxy vitamin D (25OHD), and folate and the ratio of n3/n6 in the md-MCI group were significantly lower. In the a-MCI group, only DHA concentrations and the ratio of n3/n6 were significantly lower. After adjustment for potential confounding variables, low education level [Adjusted OR=8.71 (95%CI: 1.83-41.50), p trend = 0.007], decreased plasma 25OHD [Adjusted OR = 4.41 (95% CI: 1.08-17.94), p trend=0.04] and decreased plasma DHA [Adjusted OR = 6.69 (95% CI: 1.37-32.72), p = 0.02] were associated with a higher risk of MCI. Several nutrient biomarkers in MCI patients, especially in md-MCI patients, were lower compared with healthy controls, suggesting that lower 25OHD and DHA levels are risk factors for MCI. However, we found no evidence that FSRP is an early biomarker of MCI.

  20. Vascular endothelial growth factor up-regulates the expression of intracellular adhesion molecule-1 in retinal endothelial cells via reactive oxygen species, but not nitric oxide

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-ling; WEN Liang; CHEN Yan-jiong; ZHU Yi

    2009-01-01

    Background The vascular endothelial growth factor (VEGF) is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 (ICAM-1) is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells (ECs) is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs.Methods Bovine retinal ECs (BRECs) were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF (100 ng/ml) and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase (eNOS) were detected using Western blotting. Griess reaction was used to detect nitric oxide (NO).Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C (PKC) altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase (PI3K) or reactive oxygen species (ROS) significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased.Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.

  1. Chronic vagus nerve stimulation attenuates vascular endothelial impairments and reduces the inflammatory profile via inhibition of the NF-κB signaling pathway in ovariectomized rats.

    Science.gov (United States)

    Li, Ping; Liu, Huaipu; Sun, Peng; Wang, Xiaoyu; Wang, Chen; Wang, Ling; Wang, Tinghuai

    2016-02-01

    Vagus nerve stimulation (VNS), a method for activating cholinergic anti-inflammatory pathways, could suppress endothelial activation and minimize tissue injury during inflammation. The aim of this study was to investigate the effects of chronic VNS on endothelial impairments and the inflammatory profile in ovariectomized (OVX) rats. Sprague-Dawley rats (7-8 months old) were randomly assigned to the following four groups: sham-OVX, OVX, OVX+sham-VNS, and OVX+VNS. Throughout the experimental period, the OVX+VNS group received VNS for 3h (20.0 Hz, 1.0 mA, and 10.00 ms pulse width) at the same time every other day. After 12 weeks of VNS, blood samples and thoracic aortas were collected for further analyses. Light microscopy and electron microscopy analyses showed that chronic VNS prevented endothelial swelling, desquamation and even necrosis in the OVX rats. In addition, it obviously improved endothelial function in the OVX rats by restoring the endothelial nitric oxide synthase (e-NOS) and serum endothelin-1 level. Increased expression of cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin) in the thoracic aortas and increases in the levels of circulating cytokines (TNF-α, IL-6, MCP-1, and CINC/KC) were also observed in the OVX rats. Chronic VNS significantly restored these detrimental changes partly by increasing the ACh concentrations in vascular walls and blocking NF-κB pathway activity. The results of this in vivo study have shown that the administration of chronic VNS during, in the early stage of estrogen deficiency, protects OVX rats from endothelial impairments and the inflammatory profile. These findings indicate that activation of the vagus nerve could be a promising supplemental therapy for reducing the risks of suffering from further CVDs in postmenopausal women.

  2. The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer's disease and vascular dementia: a proton magnetic resonance spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D. [Department of Imaging, Charing Cross Hospital and Dementia Research Group, University College London, Fulham Palace Road, W6 8RF, London (United Kingdom); Rai, G.S. [Department of Care of Older People, Whittington Hospital, Highgate Hill, London (United Kingdom)

    2003-08-01

    Previous magnetic resonance spectroscopy (MRS) studies have shown increased myo-inositol (MI) and decreased N-acetyl aspartate (NAA) levels in the parieto-occipital lobes of patients with Alzheimer's disease (AD) compared to those with other dementias and normal subjects. This study aimed to establish the quantitative relationship between metabolite ratios and degree of cognitive impairment in patients with mild to moderate AD and sub-cortical ischaemic vascular dementia (SIVD). Forty-four older people with clinical dementia were recruited from a memory clinic and followed up for 2.0-3.5 years; 20 cases were finally classified as probable AD, 18 as SIVD and 6 as mixed type. Mini Mental State Examination (MMSE) and short echo time single voxel automated MRS from the mesial parieto-occipital lobes were performed at the time of initial referral. Spearman rank correlation coefficients were calculated for MMSE scores and measured metabolite ratios MI/Cr, NAA/Cr, Cho/Cr and NAA/MI. The AD group showed a significant correlation between MMSE and NAA/MI (r=0.54, P=0.014) and NAA/Cr (r=0.48, P=0.033), and a negative, non-significant association with MI/Cr (r=-0.41, P=0.072). MI/Cr was negatively correlated with NAA/Cr (r=-0.51, P=0.021). Neither Cho/Cr ratios nor age correlated with cognitive function. The SIVD group showed no correlation between any of the measured metabolite ratios and MMSE score. This study reinforces the specific association between reduced NAA and increased MI levels in the parieto-occipital region and cognitive impairment in AD. MRS may have a role in evaluating disease progression and therapeutic monitoring in AD, as new treatments become available. (orig.)

  3. Aldosterone and vascular damage.

    Science.gov (United States)

    Duprez, D; De Buyzere, M; Rietzschel, E R; Clement, D L

    2000-06-01

    Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

  4. Persistent hepatitis C virus (HCV) infection impairs HCV-specific cytotoxic T cell reactivity through Mcl-1/Bim imbalance due to CD127 down-regulation.

    Science.gov (United States)

    Larrubia, J R; Lokhande, M U; García-Garzón, S; Miquel, J; González-Praetorius, A; Parra-Cid, T; Sanz-de-Villalobos, E

    2013-02-01

    In persistent hepatitis C virus (HCV) infection, HCV-specific cytotoxic T lymphocyte (CTL) reactivity is impaired and this affects HCV control. Interleukin-7 receptor (CD127) expression on these cells could regulate CTL reactivity through Mcl-1/Bim balance modulation. Bim is a pro-apoptotic molecule blocked by the action of Mcl-1. Mcl-1/Bim expression and T cell reactivity on HCV-specific CTLs were compared according to CD127 phenotype. Peripheral blood lymphocytes (PBL) from HLA-A2(+) HCV(+) patients were obtained. HCV-specific CTLs were visualized by staining PBL with anti-CD8 and HLA-A2/peptide pentameric complexes (pentamer). Mcl-1/Bim/CD127 phenotype of HCV-specific CTLs was tested by staining detectable CD8(+)/pentamer(+) cells with anti-Mcl-1/Bim/CD127 antibodies. HCV-specific CTL proliferation ability after specific in vitro challenge was tested in the presence and absence of pancaspase inhibitor z-VAD-fmk. All stained cells were analysed by flow cytometry. CD127(low)-expressing HCV-specific CTLs associated with high HCV viraemia, while CD127(high) correlated with undetectable viral loads (P Bim was up-regulated after antigen encounter (P Bim expression on pentamer(+) cells correlated positively with CD127 expression level (P Bim up-regulation after antigen encounter are involved in CD127(low) HCV-specific CTL hyporeactivity during chronic infection, but it can be overcome by apoptosis blockade.

  5. Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle

    Science.gov (United States)

    Gouspillou, Gilles; Scheede-Bergdahl, Celena; Spendiff, Sally; Vuda, Madhusudanarao; Meehan, Brian; Mlynarski, Heather; Archer-Lahlou, Elodie; Sgarioto, Nicolas; Purves-Smith, Fennigje M.; Konokhova, Yana; Rak, Janusz; Chevalier, Stéphanie; Taivassalo, Tanja; Hepple, Russell T.; Jagoe, R. Thomas

    2015-01-01

    Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivors of childhood ALL and may also be relevant to long-term survivors of other cancers treated with similar regimes. PMID:25732599

  6. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    Science.gov (United States)

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation.

  7. Diffusion MRI studies in vascular cognitive impairment and dementia Estudos de ressonância magnética funcional (imagens tensores de difusão nos quadros de prejuízo cognitivo vasculares e demências

    Directory of Open Access Journals (Sweden)

    Fabio L Urresta

    2003-09-01

    Full Text Available Since its introduction more than two decades ago, Magnetic Resonance Imaging (MRI has not only allowed for visualization of the macrostructure of the CNS, but also has been able to study dynamic processes which constitute the substrate of currently available MRI variants. While conventional Diffusion Weighted Imaging (DWI permits a robust visualization of lesions just a few minutes after the onset of cerebral ischemia, Diffusion Tensor Imaging (DTI measures the magnitude and direction of diffusion, leading to the characterization of cerebral white matter (WM microstructural integrity. In this paper, the potential role of MRI techniques, particularly DTI, for the study of the relationship between changes in the microstructural integrity of WM and cognitive impairment in the context of cerebrovascular disease are discussed. Significant correlations between scores of behavioral measures of cognitive function and regional anisotropy values are an example of the potential efficacy of DTI for in vivo studies of brain connectivity in vascular neurodegenerative conditions.Desde a sua introdução há mais de duas décadas, as Imagens de Ressonância Magnética (MRI não somente permitiram a visualização da macroestrutura do sistema nervoso central, mas também foram capazes de estudar múltiplos processos dinâmicos, os quais são o substrato para as variantes atuais da técnica. Enquanto que as Imagens de Difusão Ponderada permitem uma robusta visualização de lesões, apenas há minutos de iniciar-se a isquemia cerebral, as Imagens de Tensores de Difusão medem a magnitude e direção da difusão, caracterizando a integridade estrutural da substância branca (WM cerebral. Neste artigo, discute-se a utilidade potencial das técnicas de MRI, particularmente DTI, para o estudo da relação entre mudanças da integridade microestrutural da WM e a deterioração cognitiva, no contexto da doença cerebrovascular. As correlações significativas entre as

  8. p66Shc regulates renal vascular tone in hypertension-induced nephropathy.

    Science.gov (United States)

    Miller, Bradley; Palygin, Oleg; Rufanova, Victoriya A; Chong, Andrew; Lazar, Jozef; Jacob, Howard J; Mattson, David; Roman, Richard J; Williams, Jan M; Cowley, Allen W; Geurts, Aron M; Staruschenko, Alexander; Imig, John D; Sorokin, Andrey

    2016-07-01

    Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy.

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

    Science.gov (United States)

    Al Ghouleh, Imad; Meijles, Daniel N; Mutchler, Stephanie; 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

    2016-09-06

    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 p47(phox), 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 p47(phox) 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 p47(phox) This interaction is pivotal for agonist-induced smooth muscle ROS, hypertrophy, and vasoconstriction and has implications for ROS-mediated physiological and pathophysiological processes.

  10. Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vascular endothelial growth factor production by taurolidine.

    Science.gov (United States)

    Rodak, Roksana; Kubota, Hisashi; Ishihara, Hideyuki; Eugster, Hans-Pietro; Könü, Dilek; Möhler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

    2005-06-01

    Taurolidine, a derivative of the amino acid taurin, was recently found to display a potent antineoplastic effect both in vitro and in vivo. The authors therefore initiated studies to assess the potential antineoplastic activity of taurolidine in human glioma cell lines and in ex vivo malignant cell cultures. They also studied the mechanisms that induce cell death and the impact of taurolidine on tumor-derived vascular endothelial growth factor (VEGF) production. Cytotoxicity and clonogenic assays were performed using crystal violet staining. In the cytotoxicity assay 100% of glioma cell lines (eight of eight) and 74% of ex vivo glioma cultures (14 of 19) demonstrated sensitivity to taurolidine, with a mean median effective concentration (EC50) of 51 +/- 28 microg/ml and 56 +/- 23 microg/ml, respectively. Colony formation was inhibited by taurolidine, with a mean EC50 of 7 +/- 3 microg/ml for the cell lines and a mean EC50 of 3.5 +/- 1.7 microg/ml for the ex vivo glioma cultures. On observing this high activity of taurolidine in both assays, the authors decided to evaluate its cell death mechanisms. Fragmentation of DNA, externalization of phosphatidylserine, activation of poly(adenosine diphosphate-ribose) polymerase, loss of the mitochondrial membrane potential followed by a release of apoptosis-inducing factor, and typical apoptotic features were found after taurolidine treatment. Cell death was preceded by the generation of reactive O2 intermediates, which was abrogated by N-acetylcysteine but not by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction. Given all these findings, taurolidine may be a promising new agent in the treatment of malignant gliomas; it displays a combination of antineoplastic and antiangiogenic activities, inducing tumor cell

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

    Science.gov (United States)

    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.

  12. Enhancement on reactive oxygen species and COX-1 mRNA levels modulate the vascular relaxation induced by sodium nitroprusside in denuded mice aorta.

    Science.gov (United States)

    Kangussu, Lucas M; Olivon, Vania C; Arifa, Raquel D do N; Araújo, Natália; Reis, Daniela; Assis, Marieta T de A; Soriani, Frederico M; de Souza, Daniele da G; Bendhack, Lusiane M; Bonaventura, Daniella

    2015-04-01

    This study aimed to investigate the modulation of nitric oxide/reactive oxygen species in sodium nitroprusside relaxation in mice aorta. Sodium nitroprusside induced relaxation in endothelium-intact (e+) and endothelium-denuded (e-) aortas with greater potency in e+ than in e-. The nitric oxide synthase inhibitor did not alter the sodium nitroprusside relaxation in both e+ and e- aortas. However, the superoxide anion scavenger abolished the difference in sodium nitroprusside potency between e+ and e-. Sodium nitroprusside reduced dihydroethidium-derived fluorescent products in both groups; however, the difference between intact and denuded mice aorta remains. The glutathione levels and basal antioxidant activity of superoxide dismutase were reduced in e- aorta when compared with e+, and these values were not altered by sodium nitroprusside. Confirming these results, the levels of lipid peroxidation in e+ were significantly lower when compared to e-, and these values were not altered by sodium nitroprusside. The sodium nitroprusside potency in the presence of a nonselective COX inhibitor or the EP/DP prostaglandin receptor antagonist in endothelium denuded was similar to that in intact mice aorta. Based on these results, we performed the COX-1 and COX-2 mRNA level studies, and in denuded mice aorta, there was an upregulation in COX-1 mRNA levels. Taken together, our findings show that in the absence of endothelium, there is an enhancement of superoxide levels, leading to GSH consumption and higher levels of lipid peroxidation, showing an intense redox status. Furthermore, in denuded mice aorta, there was an upregulation of COX-1 mRNA expression, leading to vasoconstrictor prostanoids synthesis. The interaction of vasoconstrictor prostanoids with its receptors EP/DP negatively modulates the vascular relaxation induced by SNP in denuded mice aorta. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  13. A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults.

    Science.gov (United States)

    Oka, Saori; Hirai, Jun; Yasukawa, Takashi; Nakahara, Yasuyuki; Inoue, Yoshihiro H

    2015-08-01

    The theory that accumulation of reactive oxygen species (ROS) in internal organs is a major promoter of aging has been considered negatively. However, it is still controversial whether overexpression of superoxide dismutases (SODs), which remove ROS, extends the lifespan in Drosophila adults. We examined whether ROS accumulation by depletion of Cu/Zn-SOD (SOD1) or Mn-SOD (SOD2) influenced age-related impairment of the nervous system and muscles in Drosophila. We confirmed the efficient depletion of Sod1 and Sod2 through RNAi and ROS accumulation by monitoring of ROS-inducible gene expression. Both RNAi flies displayed accelerated impairment of locomotor activity with age and shortened lifespan. Similarly, adults with nervous system-specific depletion of Sod1 or Sod2 also showed reduced lifespan. We then found an accelerated loss of dopaminergic neurons in the flies with suppressed SOD expression. A half-dose reduction of three pro-apoptotic genes resulted in a significant suppression of the neuronal loss, suggesting that apoptosis was involved in the neuronal loss caused by SOD silencing. In addition, depletion of Sod1 or Sod2 in musculature is also associated with enhancement of age-related locomotion impairment. In indirect flight muscles from SOD-depleted adults, abnormal protein aggregates containing poly-ubiquitin accumulated at an early adult stage and continued to increase as the flies aged. Most of these protein aggregates were observed between myofibril layers. Moreover, immuno-electron microscopy indicated that the aggregates were predominantly localized in damaged mitochondria. These findings suggest that muscular and neuronal ROS accumulation may have a significant effect on age-dependent impairment of the Drosophila adults.

  14. A Clinical Study of Blood Inflammatory Markers in Patients with Vascular Cognitive Impairment no Dementia%血管性认知功能障碍非痴呆型患者外周血炎性标记物的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘增玲; 李文; 李海龙; 冯萍; 赵合庆; 刘春风

    2013-01-01

    目的 探讨血管性认知功能障碍非痴呆型(VCI-ND)患者外周血炎性标记物的变化特征.方法 选择VCI-ND患者44例为VCI-ND组,另选择认知功能正常者24例为对照组,采用流式细胞仪、免疫浊度法及血液分析仪分别测定两组患者CD64指数和白介素6(IL-6)、C-反应蛋白(CRP)及白细胞计数和中性粒细胞比率.结果 与对照组比较,VCI-ND组CD64指数、IL-6、CRP及中性粒细胞比率明显增高,差异有统计学意义(P<0.05),而白细胞计数则差异无统计学意义(P>0.05);行非条件Logistic回归分析,提示IL-6水平增高是VCI-ND的危险因素.结论 炎症反应参与VCI-ND的病理过程,IL-6可能是VCI-ND早期的血清炎性标记物,IL-6水平与认知功能程度下降相关,但中性粒细胞CD64指数与认知功能障碍的关系尚不明确.%Aim To investigate the characteristics of blood inflammatory markers in patients with vascular cognitive impairment no dementia. Methods 68 subjects were classified into two groups: vascular cognitive impairment-no dementia (44 cases) and normal cognitive (24 cases). For all the subjects, the levels of the index of CD64, C-reactive protein, interleukin-6, peripheral white blood cell count and the percent of neutrophil in the peripheral blood were measured by automatic flow cytometry, immunoturbidimetry and haematology analyzer respectively. Results The index of CD64, interleukin-6, C-reactive protein and the percentage of neutrophil in vascular cognitive impairment-no dementia group were significantly higher than those in the normal cognitive group(P0.05). At multiple regression analysis, the high level of IL-6 was an independent of risk factor of vascular cognitive impairment-no dementia. Conclusion The results suggested that inflammation may play a role in the pathological process of VCI-ND. The level of IL-6 was associated with the decline of cognitive function. IL-6 may be the candidate blood inflammatory marker in VCI

  15. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis by reactive oxygen species in ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    The aim of this study was to determine whether an increase of ROS level in cellular senescence induced by IR could mediate mtDNA deletion via impairment of mitochondria biogenesis in IMR-90 human lung fibroblast cells. Our results showed that IR induced cellular senescence, intracellular ROS, and mtDNA deletion, and in particular, suppressed the expression of mitochondrial biogenesis genes (NRF-1, TFAM). Furthermore, these IR-induced events were abolished using a potent antioxidant, NAC, which suggests that ROS is a key cause of mtDNA deletion in IR-induced cellular senescence, and that the alteration of mitochondrial biogenesis may mediate these processes

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

    Science.gov (United States)

    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.

  17. Vascular Endothelium and Hypovolemic Shock.

    Science.gov (United States)

    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.

  18. Reactive Oxygen Species-Induced Impairment of Endothelium-Dependent Relaxations in Rat Aortic Rings: Protection by Methanolic Extracts of Phoebe grandis

    Directory of Open Access Journals (Sweden)

    Mohd Rais Mustafa

    2011-04-01

    Full Text Available Generation of reactive oxygen species plays a pivotal role in the development of cardiovascular diseases. The present study describes the effects of the methanolic extract of Phoebe grandis (MPG stem bark on reactive oxygen species-induced endothelial dysfunction in vitro. Endothelium-dependent (acetylcholine, ACh and -independent relaxation (sodium nitroprusside, SNP was investigated from isolated rat aorta of Sprague-Dawley (SD in the presence of the β-NADH (enzymatic superoxide inducer and MPG extract. Superoxide anion production in aortic vessels was measured by lucigen chemiluminesence. Thirty minutes incubation of the rat aorta in vitro with β-NADH increased superoxide radical production and significantly inhibited ACh-induced relaxations. Pretreatment with MPG (0.5, 5 and 50 μg/mL restored the ACh-induced relaxations (Rmax: 92.29% ± 2.93, 91.02% ± 4.54 and 88.31 ± 2.36, respectively in the presence of β-NADH. MPG was ineffective in reversing the impaired ACh-induced relaxations caused by pyrogallol, a non-enzymatic superoxide generator. Superoxide dismutase (a superoxide scavenger, however, reversed the impaired ACh relaxations induced by both β-NADH and pyrogallol. MPG also markedly inhibited the β-NADH-induced generation of the superoxide radicals. Furthermore, MPG scavenging peroxyl radicals generated by tBuOOH (10−4 M.These results indicate that MPG may improve the endothelium dependent relaxations to ACh through its scavenging activity as well as by inhibiting the NADH/NADPH oxidase induced generation of superoxide anions.

  19. Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Demarin V

    2017-02-01

    Full Text Available Vida Demarin,1,2 Vanja Bašić Kes,1 Zlatko Trkanjec,1 Mislav Budišić,1 Marija Bošnjak Pašić,3,4 Petra Črnac,5 Hrvoje Budinčević4,5 1Department of Neurology, University Hospital Center “Sestre Milosrdnice”, 2International Institute for Brain Health, 3Department of Neurology, University Hospital Center Zagreb, Zagreb, 4Department of Neurology, School of Medicine, University Josip Juraj Strossmayer, Osijek, 5Department of Neurology, Stroke and Intensive Care Unit, University Hospital “Sveti Duh”, Zagreb, Croatia Objectives: The aim of this randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of Ginkgo biloba extract in patients diagnosed with vascular cognitive impairment (VCI. Methods: A total of 90 patients (aged 67.1±8.0 years; 59 women were randomly allocated (1:1:1 to receive G. biloba 120 mg, G. biloba 60 mg, or placebo during a 6-month period. Assessment was made for efficacy indicators, including neuropsychological tests scores (Sandoz Clinical Assessment Geriatric Scale, Folstein Mini-Mental State Examination, Mattis Dementia Rating Scale, and Clinical Global Impression and transcranial Doppler ultrasound findings. Safety indicators included laboratory findings, reported adverse reactions, and clinical examination. Results: At the end of 6-month study period, G. biloba 120 and 60 mg showed a statistically significant positive effect in comparison with placebo only on the Clinical Global Impression score (2.6±0.8 vs 3.1±0.7 vs 2.8±0.7, respectively; P=0.038. The Clinical Global Impression score showed a significant deterioration from the baseline values in the placebo group (-0.3±0.5; P=0.021 as opposed to G. biloba groups. No significant differences were found in the transcranial Doppler ultrasound findings. Adverse reactions were significantly more common and serious in the placebo group (16 subjects than in either of the two G. biloba extract groups (eight and nine subjects

  20. Vascular Cures

    Science.gov (United States)

    ... 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 ...

  1. 血管性认知障碍发病机制的研究进展%Research progress of the pathogenesis of vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    李姗姗; 李斌; 张利莎; 吕文明; 雒扬; 瞿学栋

    2014-01-01

    As the world within the scope of an ageing population , the incidence of high blood pressure,diabetes,stroke and other sharp increase in the prevalence of dementia ,neurodegenerative diseases such as Parkinson′s disease also increases obviously ,vascular cognitive impairment ( VCI) has got more and more attention and becomes a research focus in the past ten years .VCI is a potentially preventable clinical syndrome,early detection,early diagnosis and early treatment can slow down the progress of the disease to a certain extent .But etiology , pathogenesis , diagnostic criteria and other issues of VCI still have larger controversy .%随着世界范围内人口老龄化的加剧,高血压、糖尿病、脑卒中等发病率的急剧增加,痴呆、帕金森病等神经退行性疾病的患病率也明显增高,血管性认知障碍( VCI )得到越来越多的关注,成为近十余年来的研究热点。 VCI是一种具有潜在可预防性的临床综合征,早发现、早诊断、早治疗可在一定程度上延缓病情的进展。但VCI的病因、发病机制、诊断标准等问题仍有较大争议。

  2. Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis.

    Science.gov (United States)

    Fu, Chen; Zhang, Nevin Lianwen; Chen, Bao-Xin; Chen, Zhou Rong; Jin, Xiang Lan; Guo, Rong-Juan; Chen, Zhi-Gang; Zhang, Yun-Ling

    2017-05-01

    To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA). A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules. Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types. A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.

  3. Structural and functional changes in subcortical vascular mild cognitive impairment: a combined voxel-based morphometry and resting-state fMRI study.

    Directory of Open Access Journals (Sweden)

    Liye Yi

    Full Text Available The present study aimed to investigate changes in structural gray matter (GM volume and functional amplitude of spontaneous low-frequency oscillations (LFO and functional connectivity density in patients with subcortical vascular mild cognitive impairment (svMCI. Structural MRI and resting-sate functional MRI data were collected from 26 svMCI patients and 28 age- and gender-matched healthy controls. Structurally, widespread GM atrophy was found in the svMCI patients that resided primarily in frontal (e.g., the superior and middle frontal gyri and medial prefrontal cortex and temporal (the superior and inferior temporal gyri brain regions as well as several subcortical brain sites (e.g., the thalamus and the caudate. Functionally, svMCI-related changes were predominantly found in the default mode network (DMN. Compared with the healthy controls, the svMCI patients exhibited decreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontal cortex, whereas increased LFO amplitudes in the posterior part of the DMN (e.g., the posterior cingulate/precuneus. As for functional connectivity density, the DMN regions (e.g., the posterior cingulate/precuneus, the medial prefrontal cortex and the middle temporal gyrus consistently exhibited decreased functional connectivity. Finally, the overall patterns of functional alterations in LFO amplitudes and functional connectivity density remained little changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GM volume changes. Together, our results indicate that svMCI patients exhibit widespread abnormalities in both structural GM volume and functional intrinsic brain activity, which have important implications in understanding the pathophysiological mechanism of svMCI.

  4. Improving cognitive impairment by Tongxinluo via inhibiting expression of beta-secretase 1/beta-amyloid peptide in experimental vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Jia Jia; Wenbin Zhu; Lihui Wang; Yun Xu

    2008-01-01

    BACKGROUND: Tongxinluo has been clinically proven to be effective in improving memory and cognitive function in patients with post-stroke vascular dementia. Is the mechanism related to the deposition of beta-amyloid peptide (Aβ) in hippocampus? OBJECTIVE: To observe the effect of Tongxinluo on cognitive impairment in a mouse model with vascular dementia and the changes of Aβ deposition andβ-secretase 1 (BACE1) expression.DESIGN: Randomized controlled study.SETTING: State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School.MATERIALS: The experiment was carried out in the State Key Laboratory of Pharmaceutical Biotechnology of Nanjing University and Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2006 to January 2007. A total of 36 healthy Kunming mice, 18 of each gender, were chosen. The study was conducted in accordance with the National Regulations of Experimental Animal Administration, and all animal experiments were approved by the Committee of Experimental Animal Administration of Nanjing University. Tongxinluo was provided by Shijiazhuang Yiling Pharmaceutical Co., Ltd.METHODS: All mice were randomly divided into 6 groups, including naive control (n=6), sham-operated control (n=6) and experimental groups treated with different doses of Tongxinluo (0.2, 0.4, and 0.6 g/kg/d; n=6 for each group) or vehicle (n=6). Five groups were subjected to bilateral common carotid arteries (2-VO) occlusion to produce a vascular dementia model(noocclusion was performed in sham-operated group). The mice in the Tongxinluo treatment groups were intragastricly administered daily with a Tongxinluo suspension (40 g/L in distilled water) at doses of 0.2, 0.4 or 0.6 g/kg/d from day 1 to day 30 post-surgery. The animals in vehicle, sham-operated and naive groups were administered an equal volume of distilled water. MAIN OUTCOME MEASURES: ①Escape latency time

  5. Reactive Oxygen Species-mediated Loss of Phenotype of Parvalbumin Interneurons Contributes to Long-term Cognitive Impairments After Repeated Neonatal Ketamine Exposures.

    Science.gov (United States)

    Zhang, Hui; Sun, Xiao-Ru; Wang, Jing; Zhang, Zhen-Zhen; Zhao, Hong-Ting; Li, Hui-Hui; Ji, Mu-Huo; Li, Kuan-Yu; Yang, Jian-Jun

    2016-11-01

    Ketamine, a common anesthetic used for pediatric patients, has been shown to induce neurotoxicity and alter adolescent behaviors in rats when administered during neonatal period. However, the mechanisms underlying this kind of neurotoxicity remain largely to be determined. Herein, we studied whether the reactive oxygen species (ROS) due to the increased NOX2 mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Sprague-Dawley male rat pups received a daily administration of ketamine intraperitoneally (75 mg/kg) from postnatal day 6 (P6) to P8 for three consecutive days. For the interventional study, pups were treated with a NADPH oxidase inhibitor, apocynin (Apo). Learning and memory abilities were tested by the open field, fear conditioning, and Morris water maze on P40, P42-44, and P50-56, respectively. For histological and biochemical assays, a separate cohort of rats was killed on P9 or P60, and the brain tissues were harvested. Our results showed the upregulation of 8-OHdG and gp91/NOX2 and downregulation of PV and glutamic acid decarboxylase 67 (GAD67) after repeated ketamine exposures, which co-occurred with the long-term cognitive impairments as evidenced by the decreased freezing time to context. However, Apo treatment attenuated these abnormalities. Our results suggest that oxidative damage, probably due to the increased NOX2, mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Moreover, the inhibition of NADPH oxidase may protect against cognitive dysfunction.

  6. Senescence Marker Protein-30 (SMP30 Deficiency Impairs Myocardium-Induced Dilation of Coronary Arterioles Associated with Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizukami

    2013-04-01

    Full Text Available Senescence marker protein-30 (SMP30 decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30’s effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium.

  7. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  8. Ultrasound -- Vascular

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate the ... are the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces ...

  9. Preliminary Evidence for Impaired Brain Activity of Neural Reward Processing in Children and Adolescents with Reactive Attachment Disorder.

    Science.gov (United States)

    Tomoda, Akemi

    2016-01-01

    Childhood maltreatment, which markedly increases risks for psychopathology, is associated with structural and functional brain differences. Especially, exposure to parental verbal abuse (PVA) or interparental violence during childhood is associated with negative outcomes such as depression, posttraumatic stress disorder (PTSD), and reduced cognitive abilities. Other forms of childhood maltreatment have been associated with brain structure or developmental alteration. Our earlier studies elucidated potential discernible effects of PVA and witnessing domestic violence during childhood on brain morphology, including gray matter volume or cortical thickness. Brain regions that process and convey the adverse sensory input of the abuse might be modified specifically by such experiences, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in the corticolimbic regions. These findings fit with preclinical studies showing that sensory cortices are highly plastic structures. Using tasks with high and low monetary rewards while subjects underwent functional MRI, we also examined whether neural activity during reward processing was altered, or not, in children and adolescents with reactive attachment disorder (RAD). Significantly reduced activity in the caudate and nucleus accumbens was observed during a high monetary reward condition in the RAD group compared to the typically developed group. The striatal neural reward activity in the RAD group was also markedly decreased. The present results suggest that dopaminergic dysfunction occurred in the striatum in children and adolescents with RAD, potentially leading to a future risk of psychiatric disorders such as dependence.

  10. Neonatal DSP-4 treatment impairs 5-HT(1B) receptor reactivity in adult rats. Behavioral and biochemical studies.

    Science.gov (United States)

    Ferdyn-Drosik, Marzena; Nowak, Przemysław; Bojanek, Kamila; Bałasz, Michał; Kasperski, Jacek; Skaba, Dariusz; Muchacki, Rafał; Kostrzewa, Richard M

    2010-01-01

    To examine the effect of a central noradrenergic lesion on the reactivity of the 5-HT(1B) receptor we compared intact male rats with rats in which noradrenergic nerve terminals were largely destroyed with the neurotoxin DSP-4 (50 mg/kg x 2, on the 1st and 3rd days of postnatal life). When rats attained 10 weeks of age, control and DSP-4 rats were divided into two subgroups receiving either saline or the serotonin (5-HT) synthesis inhibitor (p-chlorophenylalanine; p-CPA; 100 mg/kg). Employing an elevated plus maze test, we demonstrated that CP 94,253 (5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine hydrochloride) (4.0 mg/kg; 5-HT(1B) agonist) induced an anxiogenic-like action in control rats; however, it failed to elicit this effect in the DSP-4 group. Surprisingly, in p-CPA pretreated rats anxiogenic-like activity was observed both in control and DSP-4 treated rats. CP 94,253 significantly attenuated 5-HT synthesis in the medial prefrontal cortex (mPFC) of control rats, and SB 216641 (N-{3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl}-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide hydrochloride) (4.0 mg/kg; 5-HT(1B) antagonist) was able to antagonize this effect. Conversely, CP 94,253 failed to significantly inhibit the 5-HT synthesis rate in DSP-4-treated rats. In the microdialysis study CP 94,253 induced long-lasting attenuation of 5-HT release in the mPFC of control rats but had no effect in DSP-4 rats. These data lead to the proposal that presynaptic 5-HT(1B) autoreceptors underwent desensitization in DSP-4 treated rats.

  11. Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

    Science.gov (United States)

    Demarin, Vida; Bašić Kes, Vanja; Trkanjec, Zlatko; Budišić, Mislav; Bošnjak Pašić, Marija; Črnac, Petra; Budinčević, Hrvoje

    2017-01-01

    Objectives The aim of this randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of Ginkgo biloba extract in patients diagnosed with vascular cognitive impairment (VCI). Methods A total of 90 patients (aged 67.1±8.0 years; 59 women) were randomly allocated (1:1:1) to receive G. biloba 120 mg, G. biloba 60 mg, or placebo during a 6-month period. Assessment was made for efficacy indicators, including neuropsychological tests scores (Sandoz Clinical Assessment Geriatric Scale, Folstein Mini-Mental State Examination, Mattis Dementia Rating Scale, and Clinical Global Impression) and transcranial Doppler ultrasound findings. Safety indicators included laboratory findings, reported adverse reactions, and clinical examination. Results At the end of 6-month study period, G. biloba 120 and 60 mg showed a statistically significant positive effect in comparison with placebo only on the Clinical Global Impression score (2.6±0.8 vs 3.1±0.7 vs 2.8±0.7, respectively; P=0.038). The Clinical Global Impression score showed a significant deterioration from the baseline values in the placebo group (−0.3±0.5; P=0.021) as opposed to G. biloba groups. No significant differences were found in the transcranial Doppler ultrasound findings. Adverse reactions were significantly more common and serious in the placebo group (16 subjects) than in either of the two G. biloba extract groups (eight and nine subjects, respectively), whereas laboratory findings and clinical examinations revealed no differences between the groups receiving G. biloba extract and placebo. Conclusion According to our results, G. biloba seemed to slow down the cognitive deterioration in patients with VCI, but the effect was shown in only one of the four neuropsychological tests administered. However, because of this mild effect in combination with a few adverse reactions, we cannot say that it is ineffective or unsafe either. Further studies are still needed to provide

  12. Characteristics of attention executive function impairment in patients with subcortical ischemic vascular disease%皮质下缺血性血管病患者注意执行功能损害特征的研究

    Institute of Scientific and Technical Information of China (English)

    徐群; 曹雯炜; 林岩; 潘元美; 李焰生

    2012-01-01

    目的 探讨皮质下缺血性血管病(SIVD)患者注意-执行功能损害的特征.方法 收集SIVD患者95例,并按照认知功能分为无认知障碍组(NCI组)29例、血管性认知障碍非痴呆组(VCI- ND组)40例、血管性痴呆组(VaD组)26例.对所有患者进行全面神经心理测查并分析.结果 95例SIVD患者中,有VCI患者66例,占69.5%,其中VCI-ND患者40例,占VCI总数的60.6%.3组患者执行功能各项测验(DS-F除外)均以VaD组损害最严重,NCI组最轻,3组比较差异有统计学意义(P<0.01).VCI-ND组和VaD组注意-执行标准分数在各项认知域评分中最低.结论 SIVD患者认知损害的突出领域是注意-执行功能,再认和即刻记忆相对保留是其记忆损害的特点.抑郁和其他精神行为异常多见于认知障碍患者.%Objective To study the characteristics of cognitive emotion impairment in patients with subcortical ischemic vascular disease (SIVD). Methods Ninety-five S1VD patients were divided into non-cognitive impairment NCI )group(n = 29) .vascular cognitive impairment with no demen-tia(VCI-ND) group(n = 40) and vascular dementiaCVaD) group(n = 26) according to their cognitive status. All the patients underwent neuropsychological test. Results Of the 95 SIVD patients, 66(69. 5%) had NCI,40(60. 6%) had VCI-ND. The attention executive function score Z was the lowest among all scores of different cognitive domains. Conclusion The main domain of cognitive impairment in SIVD patients is the attention executive function impairment,which is characterized by recognition and immediate recall. Depression and other abnormal psychiatric behaviors are usually found in patients with cognitive impairment.

  13. KIF6 719Arg Carrier Status Association with Homocysteine and C-Reactive Protein in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease Patients

    Directory of Open Access Journals (Sweden)

    Michael Malek-Ahmadi

    2013-01-01

    Full Text Available Recent research has demonstrated associations between statin use, KIF6 719Arg carrier status, and cholesterol levels and amnestic mild cognitive impairment (aMCI and Alzheimer’s disease (AD patients. The association between 719Arg carrier status with homocysteine (tHcy and c-reactive protein (CRP levels in aMCI and AD has not been previously investigated. Data from 175 aMCI and AD patients were used for the analysis. 719Arg carriers had significantly lower levels of tHcy than noncarriers (P=0.02. No significant difference in CRP levels between 719Arg carriers and noncarriers was present (P=0.37. Logistic regression yielded no significant effect for 719Arg status on CRP [OR = 1.79 (0.85, 3.83, P=0.13] but did demonstrate a significant effect for tHcy [OR = 0.44 (0.23, 0.83, P=0.01] after adjusting for ApoE ε4 carrier status, age, gender, and statin use. This study is the first to explore the relationship between KIF6 719Arg carrier status with tHcy and CRP levels. 719Arg carriers were more likely to have normal tHcy levels after adjusting for ApoE ε4 status, age, gender, and statin use. These results suggest that the KIF6 gene might influence cardiovascular pathways associated with AD.

  14. Vascular Cures

    Science.gov (United States)

    ... is Possible EVERY DOLLAR SAVES LIVES. Donate Now Vascular Cures innovates patient-centered research, catalyzes breakthrough collaborations and empowers people in their vascular health journey. what is vascular disease PATIENTS see ...

  15. Vascular ring

    Science.gov (United States)

    ... subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... Vascular ring is rare. It accounts for less than 1% of all congenital heart problems. The condition ...

  16. 非痴呆型血管性认知障碍的神经心理学研究%Neuropsychological study on vascular cognitive impairment without dementia

    Institute of Scientific and Technical Information of China (English)

    毛高峰; 李朝武; 聂海岭; 黎逢光; 成勇; 林培珺

    2014-01-01

    Objective This paper is explored to evaluate the applicability of a new neuropsychological system for testing cognitive dysfunction in patients with vascular cognitive impairment without dementia(VCIND). Methods Sixty normal elderly persons and 60 patients with VCIND were evaluated by two kinds of neuropsychological tests:YWG neuropsychological training system and trail making test(TMT)- Chinese version. The scores of TMT and three YWG neuropsychological training system tests - unilateral cerebral function test,graph memory test and Chinese character memory test were compared between these two groups. The correlation of mean response time in three YWG neuropsychological training system tests and TMT scores had been analyzed. Results Patients in VCIND group had a longer mean response time by 27% ~158%( P ﹤ 0. 01)and a higher error rate by 27% ~63%( P ﹤0. 01). Scores of TMT in VCIND group were significantly lower than those of control group(P﹤0. 01).In VCIND group,there was no significant difference in overall means response time and error rate between males and females or between patients with cerebral infarction or cerebral hemorrhage. The mean response time of unilateral cerebral function,graph memory and Chinese character memory were all related to scores of TMT(0. 322≤r≤0. 883,P﹤0. 01). Conclusion The result from the test by YWG neuropsychological training system indicate that it can demonstrate the executive dysfunction of VCIND;hence these tests can be clinically applied.%目的探讨测试非痴呆型血管性认知障碍者认知功能的新方法及其使用价值。方法应用YWG神经心理训练系统和修订版连线测验(TMT)对非痴呆型血管性认知障碍(VCIND)组(60例)、正常对照组(60例)进行测验。对比观察两组单侧脑功能、图形记忆、汉字记忆和数字连线测验结果,以及各指标与TMT得分的相关性。结果和对照组相比,VCIND 组YWG各项目反应时延长27%~158%

  17. Reabilitação de déficits comunicativos pós-acidente vascular cerebral Rehabilitation of post-stroke communication impairments

    Directory of Open Access Journals (Sweden)

    Gigiane Gindri

    2012-01-01

    Full Text Available Os processamentos comunicativos discursivo, léxico-semântico, pragmático-inferencial e/ou prosódico podem apresentar-se deficitários após um acidente vascular cerebral. Esses prejuízos demandam métodos e programas de intervenção para uma reabilitação efetiva da comunicação. Neste contexto, o objetivo desta revisão sistemática foi identificar e descrever métodos utilizados para reabilitação neuropsicológica da comunicação de adultos acometidos por lesão cerebrovascular, mais especificamente, abordagens sistematizadas de intervenção para cada um dos processamentos comunicativos. Foram avaliados resumos publicados nos últimos dez anos na base de dados PubMed, utilizando palavras-chave relacionadas aos construtos reabilitação, acidente vascular cerebral (AVC e comunicação. Para o construto comunicação foram utilizadas, ainda, palavras específicas dos quatro processamentos comunicativos. Inicialmente, foram encontrados 914 abstracts, dos quais, após exclusão dos repetidos, 460 foram analisados. Os critérios de inclusão de abstracts para análise de seus textos completos foram ser estudo empírico, ter a participação de pelo menos um indivíduo adulto pós-AVC, tratar de reabilitação da comunicação, apresentar intervenção para pelo menos um dos quatro processamentos comunicativos, ter avaliação pré e pós-tratamento, estar escrito em inglês, francês ou português, e ter sido publicado nos últimos dez anos. Apenas quatro artigos empíricos cumpriram tais critérios, sendo conduzidos predominantemente com adultos afásicos ou com aprosódia. Assim, tais achados podem ser considerados surpreendentes e alarmantes frente à escassez de estudos sistemáticos de reabilitação de componentes comunicativos. Ressalta-se a necessidade de descrição detalhada de procedimentos de intervenção com objetivos específicos para que estudos possam ser replicados, contribuindo também para a verificação do efeito

  18. Impaired long-chain fatty acid metabolism in mitochondria causes brain vascular invasion by a non-neurotropic epidemic influenza A virus in the newborn/suckling period: implications for influenza-associated encephalopathy.

    Science.gov (United States)

    Yao, Dengfu; Kuwajima, Masamichi; Chen, Ye; Shiota, Mayumi; Okumura, Yuushi; Yamada, Hiroshi; Kido, Hiroshi

    2007-05-01

    The neuropathogenesis of influenza-associated encephalopathy in children and Reye's syndrome remains unclear. A surveillance effort conducted during 2000-2003 in South-West Japan reveals that almost all fatal and handicapped influenza-associated encephalopathy patients exhibit a disorder of mitochondrial beta-oxidation with elevated serum acylcarnitine ratios (C(16:0)+C(18:1))/C(2). Here we show invasion by a non-neurotropic epidemic influenza A H3N2 virus in cerebral capillaries with progressive brain edema after intranasal infection of mice having impaired mitochondrial beta-oxidation congenitally or posteriorly in the newborn/ suckling periods. Mice genetically lacking of carnitine transporter OCTN2, resulting in carnitine deficiency and impaired beta-oxidation, exhibited significant higher virus-genome numbers in the brain, accumulation of virus antigen exclusively in the cerebral capillaries and increased brain vascular permeability compared to in wild type mice. Mini-plasmin, which proteolytically potentiates influenza virus multiplication in vivo and destroys the blood-brain barrier, accumulated with virus antigen in the brain capillaries of OCTN2-deficient mice but only a little in wild-type mice. These results suggest that the impaired mitochondrial beta-oxidation changes the susceptibility to a non-neurotropic influenza A virus as to multiplication in the brain capillaries and to cause brain edema. These pathological findings in the brain of mice having impaired mitochondrial beta-oxidation after influenza virus infection may have implications for human influenza-associated encephalopathy.

  19. 脑小血管病与血管性认知功能障碍的关系%Relationship between Cerebral Small Vessel Disease and Vascular Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    何敏; 朱晓钢

    2015-01-01

    主要简述脑小血管病(cerebral small vessel disease,SVD)与血管性认知功能障碍(vascular cognitive impair-ment,VCI)的关系。SVD 包括腔隙性脑梗死、脑微出血、脑白质病变或脑白质疏松三种类型,三者均与 VCI 密切相关,均可导致认知功能下降。因 SVD 起病隐袭,在临床工作中常被忽略,早发现、早干预 SVD 对预防 VCI 至关重要。%ABSTRACT:This paper reviews the relationship between cerebral small vessel disease (SVD)and vas-cular cognitive impairment (VCI).SVD includes lacunar infarction,cerebral microbleeds,and white mat-ter lesions or leukoaraiosis.The three types of SVD are closely correlated with VCI and can result in cog-nitive decline.Because of the insidious onset,SVD is often neglected in the clinical work.Therefore,early detection and intervention of SVD are very important for the prevention of VCI.

  20. C-reactive protein, advanced glycation end products and their receptor in type 2 diabetic, elderly patients with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Malgorzata eGorska-Ciebiada

    2015-10-01

    Full Text Available Objective: The aim of the study was to evaluate serum levels of AGEs (advanced glycation end products, RAGE (receptor for advanced glycation end products and CRP (C-reactive protein in elderly patients with T2DM with and without mild cognitive impairment (MCI and to determine the predictors (including AGEs, RAGE and CRP levels of having MCI in elderly patients with type 2 diabetes.Methods: 276 diabetics elders were screened for MCI (using the Montreal Cognitive Assessment: MoCA score. Data of biochemical parameters and biomarkers were collected. Results: Serum AGEs, RAGE and CRP levels were significantly increased in MCI patients compared to controls. In group of patients with MCI serum RAGE level was positively correlated with AGEs level and with CRP level. RAGE, AGEs and CRP concentrations were positively correlated with HbA1c levels and negatively correlated with MoCA score. The univariate logistic regression models revealed that variables which increased the likelihood of diagnosis of MCI in elderly patients with type 2 diabetes were: higher levels of HbA1c, RAGE, AGEs, CRP, TG, lower level of HDL cholesterol, previous CVD, HA or use of HA drugs, hiperlipidaemia, retinopathy, nephropathy, increased number of co-morbidities, older age and less years of formal education. HA or use of HA drugs, previous CVD, higher level of RAGE and CRP, older age and less years of formal education are the factors increasing the likelihood of having MCI in elderly patients with type 2 diabetes in multivariable model. Conclusions: In summary, serum AGEs, RAGE and CRP are increased in the circulation of MCI elderly diabetic patients compared to controls. A larger population-based prospective study needs to be performed to further confirm the relationship between AGEs, RAGE and the cognitive decline or progress to dementia.

  1. Neurogenesis, vascular endothelial growth factor and vascular cognitive impairment%神经发生、血管内皮生长因子与血管性认知损害

    Institute of Scientific and Technical Information of China (English)

    肖伊宁; 吕佩源

    2015-01-01

    神经发生是神经前体细胞自我增殖和分化产生新神经元的动态过程。研究证实,海马神经发生可改善认知功能,并且血管内皮生长因子(vascular endothelial growth factor, VEGF)在神经发生中发挥着重要的调控作用。文章就 VEGF 促进神经发生的机制以及神经发生改善血管性认知损害的作用进行了综述。%Neurogenesis is a dynamic process of neural precursor cel self-proliferation and differentiation into new neurons. Studies have confirmed that hippocampal neurogenesis may improve cognitive function, and vascular endothelial growth factor (VEGF) plays an important regulatory role in neurogenesis. This article reviews the mechanism of VEGF promoting neurogenesis and the role of neurogenesis in improving vascular cognitive impalrment.

  2. Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage

    Science.gov (United States)

    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

  3. Skin microvascular reactivity in patients with hypothyroidism.

    Science.gov (United States)

    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 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.

  4. Vascular endothelial dysfunction and pharmacological treatment

    Institute of Scientific and Technical Information of China (English)

    Jin; Bo; Su

    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, smo-king, 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.

  5. Venular degeneration leads to vascular dysfunction in a transgenic model of Alzheimer's disease.

    Science.gov (United States)

    Lai, Aaron Y; Dorr, Adrienne; Thomason, Lynsie A M; Koletar, Margaret M; Sled, John G; Stefanovic, Bojana; McLaurin, JoAnne

    2015-04-01

    Most patients with Alzheimer's disease exhibit accumulation of amyloid-β peptide on leptomeningeal and cortical arterioles, or cerebral amyloid angiopathy, which is associated with impaired vascular reactivity and accelerated cognitive decline. Despite widespread recognition of the significance of vascular dysfunction in Alzheimer's disease aetiology and progression, much uncertainty still surrounds the mechanism underlying Alzheimer's disease vascular injury. Studies to date have focused on amyloid-β-induced damage to capillaries and plaque-associated arterioles, without examining effects across the entire vascular bed. In the present study, we investigated the structural and functional impairment of the feeding arteriolar versus draining venular vessels in a transgenic murine Alzheimer's disease model, with a particular focus on the mural cell populations that dictate these vessels' contractility. Although amyloid-β deposition was restricted to arterioles, we found that vascular impairment extended to the venules, which showed significant depletion of their mural cell coverage by the mid-stage of Alzheimer's disease pathophysiology. These structural abnormalities were accompanied by an abolishment of the normal vascular network flow response to hypercapnia: this functional impairment was so severe as to result in hypercapnia-induced flow decreases in the arterioles. Further pharmacological depletion of mural cells using SU6668, a platelet-derived growth factor receptor-β antagonist, resulted in profound structural abnormalities of the cortical microvasculature, including vessel coiling and short-range looping, increased tortuosity of the venules but not of the arterioles, increased amyloid-β deposition on the arterioles, and further alterations of the microvascular network cerebral blood flow response to hypercapnia. Together, this work shows hitherto unrecognized structural alterations in penetrating venules, demonstrates their functional significance and

  6. 尼麦角林治疗血管性认知功能障碍疗效观察%Effect of nicergoline in treatment of vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    张薇; 张临洪

    2014-01-01

    Objective To investigate the effect of nicergoline in treatment of vascular cognitive im-pairment. Methods Eighty-seven cases of vascular cognitive impairment were divided into the control group (n=44)and the treatment group (n=43)randomly. Two groups both acceptted treatment of atherosclerosis, the patients in treatment group were additionally administered with nicergoline for 1 2 weeks,then the effect was evaluated by activities of daily living sacle (ADL)、mini-mental state examination (MMSE)and wechsler memory scale (WMS)in both groups. Results After 1 2 weeks,ADL scores were significantly decreased,and MMSE and WMS scores were significantly increased compared with pre-treatment in both two groups (P<0.05 ). And the results of ADL,MMSE and WMS in the treatment group were better than those of the control group (P<0.05 ). Obvious adverse reactions were not found during the treatment. Conclusions Nicergoline shows an obvious effect on vascular cognitive impairment.%目的:探讨尼麦角林治疗血管性认知功能障碍的疗效。方法选取血管性认知功能障碍患者87例,随机分为治疗组(44例)和对照组(43例),对照组给予抗动脉粥样硬化治疗,治疗组在此基础上服用尼麦角林,疗程为12周,通过日常生活能力量表(ADL)、简易智力状态检查表(MMSE)及韦克斯勒记忆量表(WMS)进行评分,评价两组疗效。结果治疗12周后,两组患者的ADL评分均明显下降,MMSE及WMS评分均明显升高,与治疗前比较差异均有统计学意义(P均<0.05),其中治疗组ADL、MMSE及WMS评分改善情况均明显优于对照组(P<0.05),且治疗过程中未发现有明显不良反应。结论尼麦角林治疗血管性认知功能障碍有明显的疗效。

  7. Up-regulation of endothelin receptors induced by cigarette smoke--involvement of MAPK in vascular and airway hyper-reactivity

    DEFF Research Database (Denmark)

    Zhang, Yaping; Edvinsson, Lars; Xu, Cang-Bao

    2010-01-01

    and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm) and adverse proliferation......Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway...... (remodeling) of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen...

  8. Vascular Diseases

    Science.gov (United States)

    The vascular system is the body's network of blood vessels. It includes the arteries, veins and capillaries that carry ... to and from the heart. Problems of the vascular system are common and can be serious. Arteries ...

  9. Vascular Vertigo

    OpenAIRE

    Mazyar Hashemilar; Masoud Nikanfar; Dariush Savadi Oskoui

    2017-01-01

    Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vert...

  10. The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC trial in elderly hypertensives with early cognitive impairment: Role of the renin angiotensin system inhibition

    Directory of Open Access Journals (Sweden)

    Hart Meaghan

    2009-11-01

    Full Text Available Abstract Background Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC, to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments. Methods/Design The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control" for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP 20 and without clinical diagnosis of dementia or Alzheimer's disease. Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives, 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory, cerebral blood flow, and carbon dioxide cerebral vasoreactivity. Discussion The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the

  11. Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard; Lauritzen, Martin

    2009-01-01

    trauma. Here we tested the hypothesis that single episodes of CSD induced acute hypoxia, and prolonged impairment of neurovascular and neurometabolic coupling. Cortical spreading depression was induced in rat frontal cortex, whereas cortical electrical activity and local field potentials (LFPs) were...... neurovascular coupling was explained by both reduced vascular reactivity and suppressed function of cortical inhibitory interneurons. The protracted effects of CSD on basal CMRO(2) and neurovascular coupling may contribute to cellular dysfunction in patients with migraine and acutely injured cerebral cortex....

  12. Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure

    Directory of Open Access Journals (Sweden)

    Alaeddin B. Abukabda

    2017-05-01

    Full Text Available A growing body of research links engineered nanomaterial (ENM exposure to adverse cardiovascular endpoints. The purpose of this study was to evaluate the impact of ENM exposure on vascular reactivity in discrete segments so that we may determine the most sensitive levels of the vasculature where these negative cardiovascular effects are manifest. We hypothesized that acute nano-TiO2 exposure differentially affects reactivity with a more robust impairment in the microcirculation. Sprague-Dawley rats (8–10 weeks were exposed to nano-TiO2via intratracheal instillation (20, 100, or 200 µg suspended per 250 µL of vehicle 24 h prior to vascular assessments. A serial assessment across distinct compartments of the vascular tree was then conducted. Wire myography was used to evaluate macrovascular active tension generation specifically in the thoracic aorta, the femoral artery, and third-order mesenteric arterioles. Pressure myography was used to determine vascular reactivity in fourth- and fifth-order mesenteric arterioles. Vessels were treated with phenylephrine, acetylcholine (ACh, and sodium nitroprusside. Nano-TiO2 exposure decreased endothelium-dependent relaxation in the thoracic aorta and femoral arteries assessed via ACh by 53.96 ± 11.6 and 25.08 ± 6.36%, respectively. Relaxation of third-order mesenteric arterioles was impaired by 100 and 20 µg nano-TiO2 exposures with mean reductions of 50.12 ± 8.7 and 68.28 ± 8.7%. Cholinergic reactivity of fourth- and fifth-order mesenteric arterioles was negatively affected by nano-TiO2 with diminished dilations of 82.86 ± 12.6% after exposure to 200 µg nano-TiO2, 42.6 ± 12.6% after 100 µg nano-TiO2, and 49.4 ± 12.6% after 20 µg nano-TiO2. Endothelium-independent relaxation was impaired in the thoracic aorta by 34.05 ± 25% induced by exposure to 200 µg nano-TiO2 and a reduction in response of 49.31 ± 25% caused by 100 µg nano-TiO2

  13. Intracerebral hemorrhage and cognitive impairment.

    Science.gov (United States)

    Xiong, Li; Reijmer, Yael D; Charidimou, Andreas; Cordonnier, Charlotte; Viswanathan, Anand

    2016-05-01

    Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic and hemorrhagic. However the contribution of spontaneous intracerebral hemorrhage presumed due to small vessel diseases on cognitive impairment is underestimated, in contrast to the numerous studies about the role of ischemic vascular disorders on cognition. In this review we summarize recent findings from clinical studies and appropriate basic science research to better elucidate the role and possible mechanisms of intracerebral hemorrhage in cognitive impairment and dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

  14. Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2016-10-01

    Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia.

  15. Vascular compression syndromes.

    Science.gov (United States)

    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.

  16. Circulating microparticles from Crohn's disease patients cause endothelial and vascular dysfunctions.

    Directory of Open Access Journals (Sweden)

    Daniela Leonetti

    Full Text Available BACKGROUND: Microparticles (MPs are small vesicles released during cell activation or apoptosis. They are involved in coagulation, inflammation and vascular dysfunction in several diseases. We characterized circulating MPs from Crohn's Disease (CD patients and evaluated their effects on endothelial function and vascular reactivity after in vivo injection into mice. METHODS: Circulating MPs and their cellular origins were examined by flow cytometry from blood samples from healthy subjects (HS and inactive or active CD patients. MPs were intravenously injected into mice. After 24 hours, endothelial function and vascular reactivity were assessed. RESULTS: Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD. Active CD patients compared to HS displayed increased total circulating MPs, pro-coagulant MPs and those from platelets, endothelium, erythrocytes, leukocytes, activated leukocytes and activated platelets. A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index. MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice aorta and flow-induced dilation in mice small mesenteric arteries, MPs from inactive CD patients being more effective than those from active patients. CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites. CONCLUSIONS: We provide evidence that MPs from CD patients significantly alter endothelial and vascular function and therefore, may play a role in CD pathophysiology, at least by contributing to uncontrolled vascular-dependent intestinal damage.

  17. Regulation of Vascular Tone, Angiogenesis and Cellular Bioenergetics by the 3-Mercaptopyruvate Sulfurtransferase/H2S Pathway: Functional Impairment by Hyperglycemia and Restoration by DL-α-Lipoic Acid.

    Science.gov (United States)

    Coletta, Ciro; Módis, Katalin; Szczesny, Bartosz; Brunyánszki, Attila; Oláh, Gábor; Rios, Ester C S; Yanagi, Kazunori; Ahmad, Akbar; Papapetropoulos, Andreas; Szabo, Csaba

    2015-02-18

    Hydrogen sulfide (H2S), as a reducing agent and an antioxidant molecule, exerts protective effects against hyperglycemic stress in the vascular endothelium. The mitochondrial enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is an important biological source of H2S. We have recently demonstrated that 3-MST activity is inhibited by oxidative stress in vitro and speculated that this may have an adverse effect on cellular homeostasis. In the current study, given the importance of H2S as a vasorelaxant, angiogenesis stimulator and cellular bioenergetic mediator, we first determined whether the 3-MST/H2S system plays a physiological regulatory role in endothelial cells. Next, we tested whether a dysfunction of this pathway develops during the development of hyperglycemia and μmol/L to diabetes-associated vascular complications. Intraperitoneal (IP) 3-MP (1 mg/kg) raised plasma H2S levels in rats. 3-MP (10 1 mmol/L) promoted angiogenesis in vitro in bEnd3 microvascular endothelial cells and in vivo in a Matrigel assay in mice (0.3-1 mg/kg). In vitro studies with bEnd3 cell homogenates demonstrated that the 3-MP-induced increases in H2S production depended on enzymatic activity, although at higher concentrations (1-3 mmol/L) there was also evidence for an additional nonenzymatic H2S production by 3-MP. In vivo, 3-MP facilitated wound healing in rats, induced the relaxation of dermal microvessels and increased mitochondrial bioenergetic function. In vitro hyperglycemia or in vivo streptozotocin diabetes impaired angiogenesis, attenuated mitochondrial function and delayed wound healing; all of these responses were associated with an impairment of the proangiogenic and bioenergetic effects of 3-MP. The antioxidants DL-α-lipoic acid (LA) in vivo, or dihydrolipoic acid (DHLA) in vitro restored the ability of 3-MP to stimulate angiogenesis, cellular bioenergetics and wound healing in hyperglycemia and diabetes. We conclude that diabetes leads to an impairment of the 3-MST

  18. Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

    Science.gov (United States)

    Di Pardo, A; Carrizzo, A; Damato, A; Castaldo, S; Amico, E; Capocci, L; Ambrosio, M; Pompeo, F; De Sanctis, C; Spinelli, C C; Puca, A A; Remondelli, P; Maglione, V; Vecchione, C

    2017-02-17

    Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

  19. 尼麦角林与奥拉西坦联合治疗血管性认知障碍的疗效观察%Nicergoline Oxiracetam Combination Therapy with Vascular Cognitive Impairment Efifcacy

    Institute of Scientific and Technical Information of China (English)

    岳晓棠; 王军

    2014-01-01

    目的::探讨尼麦角林联合奥拉西坦治疗血管性认知障碍的临床效果。方法:选取2011年1月至2012年12月间于我院诊断为血管性认知障碍的患者112例,按其就诊顺序进行编号并随机分为对照组(56例)和观察组(56例),对照组患者进行奥拉西坦治疗,观察组患者在对照组患者治疗基础上加用尼麦角林治疗,观察两组患者各临床指标,并进行统计对比分析。结果:治疗后观察组认知障碍程度轻度比例(73.21%)、重度比例(3.57%)均明显优于对照组相应比例(57.14%)、(8.93%),以上差异均具有统计学意义(P<0.05);观察组患者治疗有效率82.14%明显高于对照组患者治疗有效率67.86%,组间差异具有统计学意义(P<0.05);观察组患者MMSE评分(25.04±2.14)、ADL评分(34.98±7.05)优于对照组(21.31±2.05)、(37.10±8.42),以上差异均具有统计学意义(P<0.05)。结论:尼麦角林联合奥拉西坦治疗血管性认知障碍安全、有效,治疗效果更好,改善患者认知功能,增强日常生活能力,值得推广。%Objective:To explore the nicergoline oxiracetam combined treatment of vascular cognitive impairment clinical results. Methods:112 cases of patients with vascular cognitive impairment in our hospital from January 2011 to December 2012, according to their treatment of sequentially numbered and randomly divided into control group (56 cases) and observation group (56 cases),the control group patients with oxiracetam treatment, patients in the observation group with Nicergoline treatment based on the control group treatment,various clinical parameters were observed, and statistically analyzed.Results:After treatment, the proportion of mild cognitive impairment level (73.21%),severe ratio (3.57%) of the observation group were significantly better than the control group (57.14%),(8.93%), the above differences were statistically significant (P<0.05);The efficiency of treatment of

  20. Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation

    Directory of Open Access Journals (Sweden)

    Ji Hye Jun

    2016-09-01

    Full Text Available Background/Aims Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL. Methods The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs treated with lithocholic acid (LCA and siRNA-CRP. Results The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. Conclusion CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

  1. Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Erickson Michelle A

    2012-06-01

    Full Text Available Abstract Background Defects in the low density lipoprotein receptor-related protein-1 (LRP-1 and p-glycoprotein (Pgp clearance of amyloid beta (Aβ from brain are thought to contribute to Alzheimer’s disease (AD. We have recently shown that induction of systemic inflammation by lipopolysaccharide (LPS results in impaired efflux of Aβ from the brain. The same treatment also impairs Pgp function. Here, our aim is to determine which physiological routes of Aβ clearance are affected following systemic inflammation, including those relying on LRP-1 and Pgp function at the blood–brain barrier. Methods CD-1 mice aged between 6 and 8 weeks were treated with 3 intraperitoneal injections of 3 mg/kg LPS at 0, 6, and 24 hours and studied at 28 hours. 125I-Aβ1-42 or 125I-alpha-2-macroglobulin injected into the lateral ventricle of the brain (intracerebroventricular (ICV or into the jugular vein (intravenous (IV was used to quantify LRP-1-dependent partitioning between the brain vasculature and parenchyma and peripheral clearance, respectively. Disappearance of ICV-injected 14 C-inulin from brain was measured to quantify bulk flow of cerebrospinal fluid (CSF. Brain microvascular protein expression of LRP-1 and Pgp was measured by immunoblotting. Endothelial cell localization of LRP-1 was measured by immunofluorescence microscopy. Oxidative modifications to LRP-1 at the brain microvasculature were measured by immunoprecipitation of LRP-1 followed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine. Results We found that LPS: caused an LRP-1-dependent redistribution of ICV-injected Aβ from brain parenchyma to brain vasculature and decreased entry into blood; impaired peripheral clearance of IV-injected Aβ; inhibited reabsorption of CSF; did not significantly alter brain microvascular protein levels of LRP-1 or Pgp, or oxidative modifications to LRP-1; and downregulated LRP-1 protein levels and caused LRP-1 mislocalization in cultured brain

  2. Chlorambucil (nitrogen mustard) induced impairment of early vascular endothelial cell migration - effects of α-linolenic acid and N-acetylcysteine.

    Science.gov (United States)

    Steinritz, Dirk; Schmidt, Annette; Simons, Thilo; Ibrahim, Marwa; Morguet, Christian; Balszuweit, Frank; Thiermann, Horst; Kehe, Kai; Bloch, Wilhelm; Bölck, Birgit

    2014-08-05

    Alkylating agents (e.g. sulfur and nitrogen mustards) cause a variety of cell and tissue damage including wound healing disorder. Migration of endothelial cells is of utmost importance for effective wound healing. In this study we investigated the effects of chlorambucil (a nitrogen mustard) on early endothelial cells (EEC) with special focus on cell migration. Chlorambucil significantly inhibited migration of EEC in Boyden chamber and wound healing experiments. Cell migration is linked to cytoskeletal organization. We therefore investigated the distribution pattern of the Golgi apparatus as a marker of cell polarity. Cells are polarized under control conditions, whereas chlorambucil caused an encircling perinuclear position of the Golgi apparatus, indicating non-polarized cells. ROS are discussed to be involved in the pathophysiology of alkylating substances and are linked to cell migration and cell polarity. Therefore we investigated the influence of ROS-scavengers (α-linolenic acid (ALA) and N-acetylcysteine (NAC)) on the impaired EEC migration. Both substances, in particular ALA, improved EEC migration. Notably ALA restored cell polarity. Remarkably, investigations of ROS and RNS biomarkers (8-isoprostane and nitrotyrosine) did not reveal a significant increase after chlorambucil exposure when assessed 24h post exposure. A distinct breakdown of mitochondrial membrane potential (measured by TMRM) that recovered under ALA treatment was observed. In conclusion our results provide compelling evidence that the alkylating agent chlorambucil dramatically impairs directed cellular migration, which is accompanied by perturbations of cell polarity and mitochondrial membrane potential. ALA treatment was able to reconstitute cell polarity and to stabilize mitochondrial potential resulting in improved cell migration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. 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.

    Science.gov (United States)

    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.

  4. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

    Directory of Open Access Journals (Sweden)

    Mostafa Wanees Ahmed El husseny

    2017-01-01

    Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

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

    Science.gov (United States)

    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.

  6. Clinical Observation on Effect of Oxiracetam Combined with Butylphthalide for Treating Vascular Cognitive Impairment in 69 Cases%奥拉西坦联合丁苯酞治疗血管性认知障碍69例

    Institute of Scientific and Technical Information of China (English)

    李春双

    2015-01-01

    Objective To investigate the clinical effect of oxiracetam combined with butylphthalide in the treatment of the patients with vascular cognitive impairment. Methods 138 cases of vascular cognitive impairment were randomly divided into the observation group and the control group according to the random number table, 69 cases in each group. The control group received the oxiracetam treat-ment, while on this basis the observation group was combined with the butylphthalide therapy. The two groups were treated for 4 weeks. The mini-mental state examination ( MMSE ) score, activities of daily life ( ADL ) score and MoCA score before and after treatment were compared between the two groups. Results The MMSE scores after treatment in the observation group were significantly higher than those in the control group, while the ADL scores were significantly lower than those in the control group, the differences were sta-tistically different ( P < 0. 05 );the orientation, delayed recall, attention and visuospatial ability and execution ability scores after treatment in the observation group were significantly higher than those in the control group with statistically significant difference ( P < 0. 05 ) . Conclusion Oxiracetam combined with butylphthalide has significant effect for treating vascular cognitive impairment and important clinical significance.%目的:探讨奥拉西坦联合丁苯酞治疗血管性认知障碍患者的临床疗效。方法将138例血管性认知障碍患者按照随机数字表法分为两组,各69例。对照组给予奥拉西坦治疗,观察组在对照组基础上联合丁苯酞治疗,疗程均为4周。分析两组患者治疗前后认知障碍分度标准(MMSE)评分、日常生活活动能力(ADL)评分及蒙特利尔认知评估(MoCA)各项目评分。结果观察组治疗后MMSE评分显著高于对照组,ADL评分显著低于对照组,定向力、延迟回忆、注意力及视空间与执行能力

  7. What Is Vascular Disease?

    Science.gov (United States)

    ... Donors Corporate Sponsors Donor Privacy Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of ... steps to prevent vascular disease here. Understanding the Vascular System Your vascular system – the highways of the ...

  8. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae.

    Directory of Open Access Journals (Sweden)

    Christine Weinl

    Full Text Available Serum Response Factor (SRF fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(-/- mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(-/- mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF in the affected eyes. However, in Elk3(-/- mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients.

  9. Comparison of Model-Based Indices of Cerebral Autoregulation and Vasomotor Reactivity Using Transcranial Doppler versus Near-Infrared Spectroscopy in Patients with Amnestic Mild Cognitive Impairment

    Science.gov (United States)

    Marmarelis, Vasilis Z.; Shin, Dae C.; Tarumi, Takashi; Zhang, Rong

    2016-01-01

    We recently introduced model-based “physiomarkers” of dynamic cerebral autoregulation and CO2 vasomotor reactivity as an aid for diagnosis of early-stage Alzheimer’s disease (AD) [1], where significant impairment of dynamic vasomotor reactivity (DVR) was observed in early-stage AD patients relative to age-matched controls. Milder impairment of DVR was shown in patients with amnestic mild cognitive impairment (MCI) using the same approach in a subsequent study [2]. The advocated approach utilizes subject-specific data-based models of cerebral hemodynamics to quantify the dynamic effects of resting-state changes in arterial blood pressure and end-tidal CO2 (the putative inputs) upon cerebral blood flow velocity (the putative output) measured at the middle cerebral artery via transcranial Doppler (TCD). The obtained input-output models are then used to compute model-based indices of DCA and DVR from model-predicted responses to an input pressure pulse or an input CO2 pulse, respectively. In this paper, we compare these model-based indices of DVR and DCA in 46 amnestic MCI patients, relative to 20 age-matched controls, using TCD measurements with their counterparts using Near-Infrared Spectroscopy (NIRS) measurements of blood oxygenation at the lateral prefrontal cortex in 43 patients and 22 age-matched controls. The goal of the study is to assess whether NIRS measurements can be used instead of TCD measurements to obtain model-based physiomarkers with comparable diagnostic utility. The results corroborate this view in terms of the ability of either output to yield model-based physiomarkers that can differentiate the group of aMCI patients from age-matched healthy controls. PMID:27911329

  10. Efficacy of nicergoline on vascular cognitive impairment without dementia%尼麦角林治疗非痴呆型血管性认知功能障碍的疗效观察

    Institute of Scientific and Technical Information of China (English)

    龙海泳; 郭爽; 李毅

    2014-01-01

    目的 观察尼麦角林对非痴呆型血管性认知功能障碍(VCIND)患者的认知及执行功能的影响. 方法 68例VCIND患者分为尼麦角林组和对照组,尼麦角林组35例,口服尼麦角林10 mg,3次/d,连续用12周;对照组33例,仅行常规治疗用药前后均行认知及执行功能评定. 结果 与对照组相比尼麦角林组用药后词语即刻回忆、数字符号转换测验、词语流畅性测验、画钟表测验以及简易智力状态测查的成绩提高(P<0.05). 结论 尼麦角林对非痴呆型血管性认知功能障碍患者的注意力,记忆力有一定改善作用,患者总体的认知功能也有一定的提高.%Objective To investigate the effect of nicergoline on cognitive ability and executive function for patients with vascular cognitive impairment without dementia (VCIND).Methods Totally 68 patients with VCIND were divided into conventional treatment group (33 cases) and nicergoline treatment group (35 cases,nicergoline 10 mg,tid added on basal conventional treatment).All of cases were continuously treated for 12 weeks.Cognitive ability and executive function before and after treatments were evaluated.Results Test scores of immediate free recall of a list of words,the numbers and symbols transformation,the word fluency,clocks and watches painting,and minimental state examination (MMSE) were significantly higher in nicergoline treatment group than in conventional treatment group (P<0.05).Conclusions Nicergoline may improve attention and memory as well as cognitive ability in patients with vascular cognitive impairment without dementia.

  11. Voxel-based analysis of diffusion tensor imaging in patients with subcortical vascular cognitive impairment: correlates with cognitive and motor deficits.

    Science.gov (United States)

    Kim, Sook Hui; Park, Jun Sung; Ahn, Hyun-Jung; Seo, Sang Won; Lee, Jong-Min; Kim, Sung Tae; Han, Seol-Heui; Na, Duk L

    2011-10-01

    Patients with small vessel disease show high-signal intensity on T2-weighted magnetic resonance (MR) images that represent ischemic cell damage. However, despite a similar degree of ischemic change, the amount and the severity of clinical presentations may vary. We investigated the clinical correlations of ischemic changes using voxel-based morphometric analyses of diffusion tensor imaging (DTI). Twenty-seven MCI and 34 dementia patients were included who all had significant small vessel disease on magnetic resonance imaging (MRI). In all patients, neuropsychological tests, a rating on the Pyramidal and Extrapyramidal scale (PEPS) for motor deficits, and 3-Tesla MRI including DTI scans were performed. Voxel-based analysis of the fractional anisotropy and mean diffusivity maps were computed. Cognitive scores correlated with the DTI abnormalities in supratentorial areas with regional specificity according to each cognitive test. Unexpectedly, cognitive deficits in most neuropsychological tests, even in some frontal tasks, were associated with disruption of posterior white matter integrities. Motor deficits correlated with both supra- and infratentorial lesions. Our findings suggest that in patients with small vessel disease who show cognitive and motor impairments, a specific distribution of fiber tract damage is more related with clinical deficits than is the severity of the total ischemia. © 2010 by the American Society of Neuroimaging.

  12. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  13. The Clinical Research of Attention Impairment in Patients with Subcortical Ischemic Vascular Cognitive Impairment%皮质下缺血性血管性认知损害患者注意功能障碍的临床研究

    Institute of Scientific and Technical Information of China (English)

    李玲; 郑健

    2012-01-01

    目的:观察皮质下缺血性血管性认知功能损害(SIVCI)患者注意亚型障碍的特征.方法:对30例非痴呆型SIVCI(SIVCIND)患者(SIVCIND组)、15例皮质下缺血性血管性痴呆(SIVD)患者(SIVD组)和15名健康志愿者(对照组)采用计算机上持续操作任务(CPT)、Stroop试验及双任务测试法测试持续注意、选择注意和分散注意功能.结果:与对照组比较,SIVD组CPT反应时延长,漏报率增加(P<0.05); SIVCIND组漏报率与对照组比较显著增加,差异有显著统计学意义(P<0.01).SIVD患者冲突及中性条件下,反应时与错误率及干扰量均增加;SIVCIND患者Stroop试验冲突条件反应时延长(P<0.01)、双任务法耗时差无明显增加(P>0.05); SIVD患者耗时差增加(P<0.01).结论:SIVCIND早期主要以持续:注意及选择注意功能损害为主,晚期则持续注意、选择注意和分散注意功能普遍受累.%Aim: To observe the characteristics of different subtype of attention impairment in patients with subcortical ischemic vascular cognitive impairment(SIVCI). Methods: The subjects included 30 patients with vascular cognitive impairment no dementia(SrVCIND), 15 patients with subcortical ischemic vascular dementia (SIVD) and 15 control cases. Their function of sustained attention, selective attention and divided were tested by continuous performance task(CPT), Stroop test and dual task test. Results: ①Reaction time of CPT had significantly prolonged and omission rate of CPT had increased in SIVD group(.P0.05) in SIVCIND group compared with the control group. Reaction time, error rate and their interfered effect had obviously increased in SIVD group compared with the control group (P<0.01). ③ SIVD group did worse in dual task than the control group (P<0.01). Conclusion: SIVCIND patients had predominance in sustained attention impairment completely and selective attention impairment partly. SIVD patients had general, obvious disorders in sustained

  14. Effect of Green Tea Catechins on Vascular Cell Proliferation and Reactive Oxygen Species%绿茶儿茶酚对活性氧和血管细胞增殖的影响研究

    Institute of Scientific and Technical Information of China (English)

    杨红; 刘贻尧

    2011-01-01

    以内皮细胞、中膜平滑肌细胞和HL-60细胞(异常细胞模型),研究了绿茶儿茶酚对3种细胞增殖的影响.用次黄嘌吟一黄嘌吟氧化酶化学发光法研究了绿茶儿茶酚清除活性氧的效果.研究结果表明,1μg/ML的绿茶儿茶酚略可促进内皮细胞增殖;1.3 μg/mL的绿茶儿茶酚对中膜平滑肌细胞增殖没有抑制作用;10 gg/mL的绿茶儿茶酚减少中膜平滑肌细胞数童.HL-60细胞数量的减少与绿茶儿茶盼浓度呈剂量效应关系.并发现绿茶儿茶酚对细胞活性氧的清除与剂1有关.%One of the most important causes of the atherosclerosis is reactive oxygen species (ROS) to inducelipide overoxidation, which leads to endothelial cells dysfunction and vascular smooth muscle cells (VSMCs)abnormal proliferation. Recent investigations demonstrated that polyphenon has prevention effect in the treatment of atherosclerosis or other vascular diseases. In this paper, endothelial cells (ECs), VSMCs and HL-60 cell (as the abnormal cell model) were used to investigate the effects of green tea catechins on the proliferation. Furthermore,the clearance ability of ROS by catechins was detected by hypoxanthine-xanthineoxidase chemiluminescence method. It was found that the green tea catechins could lightly increase ECs proliferation at the concentration of 1 μg/mL, and green tea catechins of 1 and 3 μg/mL have no obvious effect on VSMCs proliferation. However, green tea catechins of 10 μg/mL significantly inhibited VSMCs proliferation. For HL-60 cells, the cell viability was presented in a dose-dependent manner. Similarly, the ROS clearance ability was also related to the dosage of green tea catechins.

  15. 皮质下型血管性认知障碍的核磁共振视觉半定量分析%The MRI semi-volumetric analysis of subcortical vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    徐群; 曹雯炜; 周滟; 李焰生

    2013-01-01

    目的明确皮质下型血管性认知障碍( s-VCI)的影像标志物。方法92例皮质下缺血性血管病( SIVD)患者,经神经心理检查和临床访谈,分为无认知障碍(NCI)组29例、血管性轻度认知障碍(VaMCI)组39例和血管性痴呆(VaD)组24例。登记并比较不同认知组患者的人口学、血管危险因素和影像学资料。结果三组患者在皮质下白质腔隙性梗死( LI)数量、白质病变(WML)评分、内侧颞叶萎缩(MTA)(均P<0.01)和皮质萎缩(CA)(P<0.05)评分方面的差异有统计学意义。其中,VaMCI和VaD组的白质LI数目高于NCI组(分别P<0.01和P<0.05));VaD组的WML程度重于VaMCI组和NCI组(均P<0.01);VaD组的MTA评分高于NCI组( P<0.01);VaD组和VaMCI组的CA评分高于NCI组(均P<0.05)。两个认知障碍组的WML程度、MTA评分、CA评分、皮质下白质LI数目(均P<0.01)和所有LI总数高于NCI组( P<0.05)。 Logistic回归分析显示教育程度低、糖尿病、白质的LI、MTA和CA评分是s-VCI的独立危险因素。结论 s-VCI与低教育水平、糖尿病、皮质下白质损伤和皮质及内侧颞叶萎缩独立相关。%Objective To explore the neuroimaging markers of subcortical vascular cognitive impairment ( s-VCI) . Methods Based on the detailed neuropsychological tests and clinical interview , 92 subjects with subcortical ischemic vascular disease ( SIVD ) were recruited and classified into three groups according to their cognitive state, 29 patients with no cognitive impairment (NCI), 39 patients with vascular mild cognitive impairment ( VaMCI ) , and 24 patients with vascular dementia ( VaD ) . Their demographic , vascular risk factors and neuroimaging data were compared . Results The differences between the three groups in the number of subcortical white matter lacunar infarcts ( LI) as well as the scores of the white matter lesions ( WML) , medial

  16. Vascular rings.

    Science.gov (United States)

    Backer, Carl L; Mongé, Michael C; Popescu, Andrada R; Eltayeb, Osama M; Rastatter, Jeffrey C; Rigsby, Cynthia K

    2016-06-01

    The term vascular ring refers to congenital vascular anomalies of the aortic arch system that compress the esophagus and trachea, causing symptoms related to those two structures. The most common vascular rings are double aortic arch and right aortic arch with left ligamentum. Pulmonary artery sling is rare and these patients need to be carefully evaluated for frequently associated tracheal stenosis. Another cause of tracheal compression occurring only in infants is the innominate artery compression syndrome. In the current era, the diagnosis of a vascular ring is best established by CT imaging that can accurately delineate the anatomy of the vascular ring and associated tracheal pathology. For patients with a right aortic arch there recently has been an increased recognition of a structure called a Kommerell diverticulum which may require resection and transfer of the left subclavian artery to the left carotid artery. A very rare vascular ring is the circumflex aorta that is now treated with the aortic uncrossing operation. Patients with vascular rings should all have an echocardiogram because of the incidence of associated congenital heart disease. We also recommend bronchoscopy to assess for additional tracheal pathology and provide an assessment of the degree of tracheomalacia and bronchomalacia. The outcomes of surgical intervention are excellent and most patients have complete resolution of symptoms over a period of time. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Women with a history of gestational diabetes on long-term follow up have normal vascular function despite more dysglycemia, dyslipidemia and adiposity.

    Science.gov (United States)

    Ajala, Olubukola; Jensen, Louise A; Ryan, Edmond; Chik, Constance

    2015-12-01

    Previous gestational diabetes (GDM) is a risk factor for type 2 diabetes and increased metabolic risk, but the link with vascular dysfunction is not clear. This study examined vascular function in women 4-10 years after a diagnosis of GDM who had a normal oral glucose tolerance test (OGTT) in the first postpartum year. We studied 90 women with a history of GDM and 59 age-matched controls, examining differences in insulin resistance as measured by the Homeostatic Model Assessment (HOMA-IR) and glucose responses during an OGTT, adiposity, lipid profile and C-reactive protein (CRP). Using pulse wave analysis, we also measured cardiac function, vascular compliance, and systemic vascular resistance. Women with a history of GDM had higher measures of adiposity (body mass index 28.9 ± 6.5 vs. 26.6 ± 6.9 kg/m(2), P=0.04, waist-hip ratio 0.85 ± 0.06 vs. 0.79 ± 0.07, Pfunction including pulse rate, pulse pressure, mean arterial pressure, cardiac output, systemic vascular resistance, small and large artery elasticity index. After controlling for adiposity, blood pressure, lipids and CRP, glycemic status did not contribute to vascular function. Despite a higher incidence of adiposity, dyslipidemia, and impaired glycemia, women with a history of GDM who had a normal postpartum OGTT did not have impaired vascular function 4-10 years postpartum, when compared to healthy controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Changes in the vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and c-reactive protein following administration of aqueous extract of piper sarmentosum on experimental rabbits fed with cholesterol diet

    Directory of Open Access Journals (Sweden)

    Al-Mekhlafi Hesham M

    2011-01-01

    Full Text Available Abstract Background Inflammation process plays an important role in the development of atherosclerosis. Hypercholesterolemia is one of the major risk factors for atherosclerosis. The present study aimed to evaluate the effect of aqueous extract of Piper sarmentosum (P.s on inflammatory markers like vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, and C-reactive protein (CRP. Methods Forty two male New Zealand white rabbits were divided equally into seven groups; (i C- control group fed normal rabbit chow (ii CH- cholesterol diet (1%cholesterol (iii X1- 1% cholesterol with water extract of P.s (62.5 mg/kg (iv X2- 1% cholesterol with water extract of P.s (125 mg/kg (v X3- 1% cholesterol with water extract of P.s (250 mg/kg (vi X4- 1% cholesterol with water extract of P.s (500 mg/kg and (vii SMV group fed with 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg. All animals were treated for 10 weeks. Blood serum was taken for observing the inflammatory markers at the beginning and end of the experiment. Results Rabbits fed with 1% cholesterol diet (CH showed significant increase in the level of VCAM-1, ICAM-1 and CRP compared to the C group. The levels of VCAM-1, ICAM-1 and CRP in the 1% cholesterol group and supplemented with P.s (500 mg/kg were significantly reduced compared to the cholesterol group. Similar results were also reported with simvistatin group. Conclusion These results suggest that the supplementation of Piper sarmentosum extract could inhibit inflammatory markers which in turn could prevent atherosclerosis.

  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.

    Science.gov (United States)

    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. 尼麦角林与奥拉西坦联合治疗血管性认知障碍的临床观察%Clinical Observation of Nicergoline Combined with Oxiracetam in the Treatment of Vascular Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    高红安

    2014-01-01

    目的:探讨尼麦角林联合奥拉西坦在血管性认知障碍治疗中的应用价值。方法:选取2010年6月至2013年1月间于我院诊治的血管性认知障碍患者104例,根据其药物治疗方法分为对照组(43例)和观察组(61例),对照组患者接受单纯奥拉西坦治疗,观察组患者在对照组患者接受尼麦角林联合奥拉西坦治疗,观察两组患者临床治疗效果并进行对比分析。结果:观察组患者治疗后认知障碍程度轻度(73.77%)、中度(22.95%)、重度(3.28%)比例均明显优于对照组患者(55.81%)、(34.88%)、(9.30%),组间差异在统计学上有意义(P<0.05);观察组患者治疗有效率81.87%明显高于对照组67.44%,而其MMSE评分(25.46±3.01)、ADL评分(33.14±4.22)亦优于对照组(20.48±2.34)、(38.07±5.74),以上差异均具有统计学意义(P<0.05)。结论:在血管性认知障碍治疗中,尼麦角林联合奥拉西坦治疗是一种安全、有效的治疗方案,其临床疗效好、患者认知功能及日常生活能力恢复佳,值得推广。%Objective:To explore the application value of nicergoline combined with oxiracetam in treatment of vascular cognitive impairment.Methods:104 patients with vascular cognitive impairment in our hospital from June 2010 to January 2013, According to its drug treatment methods were divided into control group (43 cases) and observation group (61 cases), The control group of patients taking oxiracetam, the observation group of patients taking olathe joint, ergot Lin treatment, Compared with the two groups of patients with clinical therapeutic effect. Results:After treatment, The degree of cognitive impairment of the Observation group mild was 73.77%, moderate was 22.95%, severe was 3.28%.The degree of cognitive impairment of the control group mild was 55.81%, moderate was 34.88%, severe was 9.30%,the Observation group was better than the control group (P<0.05) Efficient of the observation group was 81

  1. VASCULAR SURGERY

    African Journals Online (AJOL)

    Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are linked to an increased risk of PE.2 .... tool for DVT in hospitalised patients, where higher scores.

  2. Vascular Dementia

    Science.gov (United States)

    ... that includes enjoyable activities well within the comfort zone of the person with vascular dementia. New situations, ... your cholesterol in check. A healthy, low-fat diet and cholesterol-lowering medications if you need them ...

  3. Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Chakkarwar, Vishal Arvind

    2011-01-01

    The study has been designed to investigate the effect of fenofibrate on nicotine-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) was administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy of thoracic aorta. The expression of mRNA for p22phox and eNOS was assessed by using reverse transcriptase-polymerase chain reaction. Serum thiobarbituric acid reactive substances concentration (TBARS) and aortic superoxide anion concentration were estimated to assess oxidative stress. Moreover, the serum lipid profile was assessed by estimating serum cholesterol, triglycerides and high density lipoprotein. The administration of nicotine induces VED by increased oxidative stress, altered lipid profile and impaired the integrity of vascular endothelium as assessed in terms of decrease in expression of mRNA for endothelial nitric oxide synthase (eNOS), impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine produced oxidative stress, assessed in terms of increase in serum TBARS and aortic superoxide anion generation and increase in expression of mRNA for p22phox. Nicotine altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. However, treatment with fenofibrate (32 mg/kg, p.o.) markedly prevented nicotine-induced VED by decreasing oxidative stress and improving integrity of vascular endothelium, normalising the altered lipid profile, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic

  4. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  5. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  6. Evidências atuais do impacto terapêutico dos inibidores da acetilcolinesterase no transtorno cognitivo leve e na demência vascular Evidencias actuales del impacto terapéutico de los inhibidores de la acetilcolinesterasa en el trastorno cognitivo débil y en la demencia vascular Current evidence of the impact of acetylcholinesterase inhibitors on mild cognitive impairment and vascular dementia

    Directory of Open Access Journals (Sweden)

    Alexandre de Mattos Gomes

    2005-08-01

    : Lilacs, MEDLINE y EBMR. RESULTADOS Y CONCLUSIONES: Los ensayos con inhibidores de la acetilcolinesterasa en el tratamiento del trastorno cognitivo débil muestran una mejora muy modesta en los síntomas y todavía son pequeños y con poco poder de evidencia. Estudio reciente muestra que la progresión del trastorno cognitivo débil para demencia de Alzheimer disminuye durante los 12 primeros meses de tratamiento, pero no tiene una respuesta sostenida. Los ensayos con demencia vascular traen resultados animadores con el uso de esas drogas.INTRODUCTION: Acetylcholinesterase inhibitors constitute an effective class of drugs for the treatment of mild and moderate Alzheimer's disease and are allowed by the responsible agencies for this purpose only. However, concrete evidence is still necessary in what concerns the impact of the use of such drugs to treat a large variety of cognitive disorders not classified as Alzheimer's disease. The aim of this study was to review the medical literature in search for updated evidence of the impact of acetylcholinesterase inhibitors on mild cognitive impairment and vascular dementia. METHODS: The literature review was carried out in the Lilacs, MEDLINE and EBMR databases. RESULTS AND CONCLUSIONS: Assays using acetylcholinesterase inhibitors for the treatment of mild cognitive impairment are still small, present little power of evidence, and show only a modest improvement of symptoms. A recent study shows reduced progression of mild cognitive impairment to Alzheimer's disease in the first 12 months of treatment, but this effect was not continuous. On the other hand, clinical trials involving patients with vascular dementia show encouraging results associated with the use of these drugs.

  7. Vascular function in health, hypertension, and diabetes

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

    2015-01-01

    to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

  8. 血管性认知损害的中医证候与认知功能的关系%Correlation between cognitive functions and syndromes of traditional Chinese medicine in vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    时晶; 魏明清; 马福云; 苗迎春; 田金洲

    2011-01-01

    目的:探讨血管性认知损害(vascular cognitive impairment,VCI)患者的认知功能与中医证候的相关性,为VCI的中医辨证治疗提供依据.方法:2006年12月~2010年3月从北京东直门医院老年病科和社区居民中招募774名患者,筛选出认知正常组251例,VCI组107例.采用海金斯基缺血量表(Hachinski ischemic scale,HIS)、汉密尔顿抑郁评定量表(Hamilton depression scale,HAMD)、简易精神状态检查(mini-mental state examination,MMSE)中文版、临床痴呆评定量表(clinical dementia rating scale,CDR)、画钟试验(clock drawing test,CDT)及日常生活能力量表(ability of daily living,ADL)评价患者认知功能、日常生活能力和痴呆的严重程度等,采用偏相关分析法分析VCI患者认知功能与中医证候的相关性.结果:VCI组中医证候与量表成绩的相关性分析显示,MMSE总分、CDT得分均与痰浊蒙窍证呈负相关(r=-0.525,r=-0.321;P=0.000,P=0.001),ADL与痰浊蒙窍证呈正相关(r=0.424,P=0.000),与肾精亏虚证呈正相关(r=0.216,P=0.028).VCI组的认知功能与中医证候的偏相关分析显示,MMSE中总定向力以及时间和空间定向力得分均与痰浊蒙窍证呈负相关(r=-0.451,r=-0.448,r=-0.392;P=0.001,P=0.000,P=0.004),单词即刻记忆和单词延迟回忆得分与痰浊蒙窍证呈负相关(r=- 0.355,r=-0.225;P=0.000,P=0.021),计算力/注意力、语言功能及执行功能得分均与痰浊蒙窍证呈负相关(r=-0.379,r=-0.448,r=-0.321;P=0.000,P=0.000,P=0.013).痰浊蒙窍证患者的MMSE中总定向力、时间定向力、空间定向力、注意力/计算力均显著低于无痰浊蒙窍证患者(P<0.01),痰浊蒙窍证患者语言功能及单词延迟回忆得分均显著低于无痰浊蒙窍证患者(P<0.05).结论:VCI的主要中医证候为肾精亏虚、痰浊蒙窍和瘀阻脑络,其中痰浊与患者定向力、记忆力、注意力/计算力、语言功能关系密切,故化痰开窍法可用于

  9. Hypothermic Effects on Vascular Contractility and Reactivity,

    Science.gov (United States)

    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

  10. Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington’s disease transgenic R6/2 (160 CAG) mice

    Science.gov (United States)

    Di Pardo, A.; Carrizzo, A.; Damato, A.; Castaldo, S.; Amico, E.; Capocci, L.; Ambrosio, M.; Pompeo, F.; De Sanctis, C.; Spinelli, C. C.; Puca, A. A.; Remondelli, P.; Maglione, V.; Vecchione, C.

    2017-01-01

    Whereas Huntington’s disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found. PMID:28211486

  11. Hypercholesterolaemia and vascular dementia.

    Science.gov (United States)

    Appleton, Jason P; Scutt, Polly; Sprigg, Nikola; Bath, Philip M

    2017-07-15

    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors-diabetes, hypercholesterolaemia, hypertension and smoking-are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here. © 2017 The Author(s).

  12. Clinical effects of the rehabilitation therapy on senile vascular dementia and cognitive impairment%康复治疗对老年血管性痴呆患者疗效及认知功能障碍的影响

    Institute of Scientific and Technical Information of China (English)

    杜红霞

    2015-01-01

    近年来,老年血管性痴呆患者的数量逐步升高,即使在相关医疗技术不断发展并且医疗条件不断改善的前提下,我国的老年血管性痴呆患者的数量仍然上升。如何有效控制这一趋势是医学界所重点讨论的话题之一。当今社会人们的生活压力较大且饮食安全问题时有发生,同时,越来越多的老年人缺少来自于家庭的关爱,因而各类疾病时有发生,特别是老年痴呆。康复治疗作为缓解和治疗老年痴呆的有效途径,一直以来被医学界所广泛应用,在治疗过程中,这种治疗方法对老年人认知功能障碍有着或多或少的影响,如何趋利避害是康复治疗应当考虑的问题。%In recent years,the number of elderly patients with vascular dementia gradually increased,even in the premise of improving medical technology development and medicalconditions, the number of senile vascular dementia patients in our country is still rising. How to effectively control the trend is one of the focus of the medical profession. In today's society,people's life pressure and food safety problems occur from time to time, at the same time, more and more elderly people from lack of family care, so all kinds of diseases have occurred,especially in senile dementia. As an effective way to alleviate the rehabilitation and treatment of senile dementia, has been widely used in medicine, in the treatment process, the treatmentmethods have more or less influence on the elderly cognitive impairment, how to draw on the advantages and avoid disadvantages is the rehabilitation treatment should consider the question.

  13. Vascular function in health, hypertension, and diabetes: effect of physical activity on skeletal muscle microcirculation.

    Science.gov (United States)

    Nyberg, M; Gliemann, L; Hellsten, Y

    2015-12-01

    Regulation of skeletal muscle blood flow is a complex process, which involves an integration of multiple mechanisms and a number of vasoactive compounds. Overall, muscle blood flow is regulated through a balance between vasoconstrictor and vasodilator signals. In a healthy cardiovascular system, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular function by enhancing vasodilator formation and reducing the levels of vasoconstrictors and ROS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The role of cholinergic pathway lesions in vascular cognitive impairment%胆碱能通路损伤在血管性认知功能障碍中的作用

    Institute of Scientific and Technical Information of China (English)

    黄纯臣; 李林昕; 韩翔; 王亮; 董强

    2010-01-01

    目的 通过比较胆碱能通路高信号评分(CHIPS)与缺血性脑卒中患者认知功能之间的关系,探索胆碱能通路损伤在血管性认知功能障碍中的作用.方法 采用MRI对住院缺血性脑卒中患者进行CHIPS评分、总体白质高信号Schelten评分,同时使用北京版蒙特利尔认知量表(MoCA)进行认知功能评估,分析影像学评分与认知评估间的相关性.结果 共纳入34例研究对象[45~82岁,平均(62.2±8.8)岁],该群体CHIPS评分与MoCA得分间标准化回归系数β=-0.382,P=0.026,而Schelten评分与MoCA得分间β=-0.357,P=0.042;在视空间与执行功能、命名、注意与抽象分项评分中,CHIPS与分项评分存在相关性;Schelten评分与命名、注意和抽象评分亦存在相关性.结论 胆碱能通路损伤在白质病变所致血管性认知功能障碍中起作用,其主要作用可能是影响视空间与执行功能.%Objective To investigate the relationship between white matter lesions (WML) within the cholinergic pathway and vascular cognitive impairment.Method Middle-aged and elderly stroke patients underwent brain MRI examination and Montreal Cognitive Assessment (MoCA).Cholinergic Pathways Hyperintensities Scale (CHIPS) scores and the overall WML burden by Schelten on fluidattenuated inversion recovery MRI images were determined and compared with MoCA scores.Spearman partial rank correlation coefficients and standardized regression coefficients were calculated.Results Thirty four patients were included ( mean age ( 62.2 ± 8.8 ) years, 45-82 years).MoCA scores negatively correlated with WML burdens by Schelten scores ( β = - 0.357, P = 0.042) and CHIPS scores ( β =-0.382,P=0.026).CHIPS scores were negatively associated with visuospatial and executive function (r = - 0.290, P = 0.048 ), naming function ( r = - 0.486, P = 0.002 ), attention ( r = - 0.311, P =0.037) and abstraction ( r = - 0.344, P = 0.023).Schelten scores were negatively associated with naming

  15. Diabetes and ageing-induced vascular inflammation.

    Science.gov (United States)

    Assar, Mariam El; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2016-04-15

    Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  16. Diabetes and ageing‐induced vascular inflammation

    Science.gov (United States)

    Assar, Mariam El; Angulo, Javier

    2015-01-01

    Abstract Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro‐inflammatory cytokines, vascular hyperactivation of nuclear factor‐кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti‐inflammatory microRNAs, and dysfunctional stress‐response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co‐exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low‐grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes‐induced vascular impairment in the elderly. PMID:26435167

  17. Disorders of "taste cognition" are associated with insular involvement in patients with Alzheimer's disease and vascular dementia: "memory of food is impaired in dementia and responsible for poor diet".

    Science.gov (United States)

    Suto, Teiko; Meguro, Kenichi; Nakatsuka, Masahiro; Kato, Yuriko; Tezuka, Kimihiro; Yamaguchi, Satoshi; Tashiro, Manabu

    2014-07-01

    In dementia patients, dietary intake problems may occur despite the absence of swallowing problems. We investigated cognitive functions on food and taste in Alzheimer's disease (AD) and vascular dementia (VaD) patients. Participants included 15 healthy controls (HC), 30 AD and 20 VaD patients. Food Cognition Test: Replicas of three popular foods in Japan with no odors were presented visually to each participant, with the instruction to respond with the name of each food. Replicas of food materials were subsequently presented to ask whether they were included in these foods. Taste Cognition Test: Replicas of 12 kinds of foods were presented to describe their expected tastes. The AD/VaD groups exhibited significantly lower scores on Food/Taste Cognition Tests compared with the HC group. These scores correlated inversely with Mini-Mental State Examination (MMSE) scores in the AD group. Decreased dietary intake was observed in 12 of the 50 patients; 8 of the 12 exhibited decreased Taste Cognition Test scores, higher than that of the normal-intake patients. There was no difference in the filter paper taste disc test between HC/AD/VaD groups. To test the hypothesis that the insula is associated with taste cognition, two MMSE-matched AD subgroups (n = 10 vs. 10) underwent positron emission tomography. Glucose metabolism in the right insula was lower in the low taste cognition subgroup. The VaD patients with insular lesions exhibited impaired Taste Cognition Test findings. It is important to consider the cognitive aspect of dietary intake when we care for dementia patients.

  18. 不同类型的血管性认知损害的执行功能障碍%Executive dysfunction in different subtypes of vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    郭起浩; 金丽琳; 傅建辉; 周燕; 赵倩华; 洪震

    2009-01-01

    目的 分析不同类型的血管性认知功能损害(VCI)患者的执行功能损害特征.方法 经头颅MRI证实为皮质下缺血性小血管病(SIVD)患者64例,其中16例单一的执行功能损害(s-VCI-ND)、26例多个认知领域损害(m-VCI-ND)和22例血管性痴呆(VaD)患者,完成一系列神经心理测验,包括总体认知水平、记忆、语言、注意/执行功能、空间结构能力等各个认知领域.其中执行功能检查包括定势转移、优势抑制、工作记忆、概念形成和流畅性5个分因子,共15种独立的分测验.结果 汉诺塔测验、示踪排序测验、同步听觉连续加法测验等在非痴呆VCI(VCI-ND)患者中的完成率低于50%,不适合VCI-ND的检测;s-VCI-ND组与健康对照组比较,分别反映4种执行功能成分的连线测验B耗时数(216.5±69.3、137.4±37.9)、Stroop色词测验卡片C耗时数(115.4±30.1、72.9±17.5)、卡片分类测验(1.9±1.4、2.7±1.2)和范畴流畅性测验(列举动物14.2±2.3、17.7±4.4)差异具有统计学意义(t=4.73、5.72、2.04、3.53,均P<0.05);VCI-ND的认知表现介于健康老人组和VaD组之间,其中m-VCI-ND有比较严重的执行功能损害和情景与语义记忆障碍,其认知缺损模式接近VaD,很可能是VaD的前期状态.结论 SIVD所致VCI的执行功能损害缺乏选择性,部分执行功能测验可以作为早期检测VCI-ND的敏感工具.%Objective To investigate the executive function features of different subtypes of vascular cognitive impairment (VCI). Methods Sixty-four subjects with subcortical ischaemic vascular disease (SIVD) presumed by medical history and neuroimaging (cranial MRI) were recruited. The clinical and neuropsychological features of the 4 groups were compared: cognitive normal control (n=25), simple executive impairment of VCI-ND (s-VCI-ND, n=16), multi-domain impairment of VCI-ND (m-VCI-ND, n=26) and vascular dementia (VaD) patients (n=22). All participants underwent neuropsychological

  19. 尼麦角林联合高压氧治疗血管性认知功能障碍疗效观察%Efficacy of nicergline combined with hyperbaric oxygen treatment on vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    陈国军; 张燕柳; 张惠莉; 于永娜; 宋帅召

    2015-01-01

    目的 探讨尼麦角林联合高压氧治疗血管性认知功能障碍(VCI)的疗效.方法 选取血管性认知功能障碍患者120例,随机分为尼麦角林治疗组40例,高压氧治疗组40例,联合治疗组40例,疗程共8周,以简易精神状态检查表(MMSE)、韦克斯勒记忆量表(WMS)和日常生活能力量表(ADL)为评价指标,评价3组患者的疗效.结果 3组患者临床资料比较差异无统计学意义(均P>0.05),具有可比性.经8周治疗干预后,联合治疗组MMSE、WMS、ADL较治疗前均有改善(P<0.01).尼麦角林治疗组上述三项指标改善明显(P<0.05),而高压氧治疗组MMSE、ADL评分较前改善(P<0.05),联合治疗组与尼麦角林治疗组和高压氧治疗组组间比较,上述指标差异有统计学意义(P<0.05).而尼麦角林组与高压氧治疗组比较,仅MMSE差异有统计学意义.3组均无明显相关不良反应出现.结论 在血管性认知功能障碍治疗中,尼麦角林联合高压氧治疗疗效显著,患者日常生活能力和认知能力提高明显,无不良反应发生,值得在临床中推广.%Objective To investigate the efficacy of nicergoline combined with hyperbaric oxygen treatment on vascular cognitive impairment.Methods 120 patients with vascular cognitive impairment were randomly divided into 3 treatment groups:nicergoline,hyperbaric oxygen,and both treatment (n=40,each) for 8 weeks.Mini mental state examination (MMSE),Wechsler memory scale (WMS) and activities of daily living scale (ADL) were used as assessing items.The efficacy of treatment in each group was evaluated.Results There were no significant differences in clinical data among the three groups(x2=0.324,t=0.265 and 0.861,P=0.764,0.784 and 0.386).After 8 weeks of intervention,scores of MMSE,WMS and ADL were significantly improved in the combined treatment groups compared with pre-treatment (all P<0.01),and the improvements were observed in nicergoline group (all P<0.05),while only MMSE and

  20. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Kaur, Tajpreet; Goel, Rajesh Kumar; Balakumar, Pitchai

    2010-04-01

    The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor gamma agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats.

  1. Oxidative Stress and MicroRNAs in Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Fabio Martelli

    2013-08-01

    Full Text Available 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.

  2. Oxidative stress and microRNAs in vascular diseases.

    Science.gov (United States)

    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.

  3. 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species.

    Science.gov (United States)

    den Hartigh, Laura J; Han, Chang Yeop; Wang, Shari; Omer, Mohamed; Chait, Alan

    2013-11-01

    Conjugated linoleic acid (CLA) is a naturally occurring dietary trans fatty acid found in food from ruminant sources. One specific CLA isomer, 10E,12Z-CLA, has been associated with health benefits, such as reduced adiposity, while simultaneously promoting deleterious effects, such as systemic inflammation, insulin resistance, and dyslipidemia. The precise mechanisms by which 10E,12Z-CLA exerts these effects remain unknown. Despite potential health consequences, CLA continues to be advertised as a natural weight loss supplement, warranting further studies on its effects on lipid metabolism. We hypothesized that 10E,12Z-CLA impairs lipid storage in adipose tissue by altering the lipid metabolism of white adipocytes. We demonstrate that 10E,12Z-CLA reduced triglyceride storage due to enhanced fatty acid oxidation and lipolysis, coupled with diminished glucose uptake and utilization in cultured adipocytes. This switch to lipid utilization was accompanied by a potent proinflammatory response, including the generation of cytokines, monocyte chemotactic factors, and mitochondrial superoxide. Disrupting fatty acid oxidation restored glucose utilization and attenuated the inflammatory response to 10E,12Z-CLA, suggesting that fatty acid oxidation is critical in promoting this phenotype. With further investigation into the biochemical pathways involved in adipocyte responses to 10E,12Z-CLA, we can discern more information about its safety and efficacy in promoting weight loss.

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

    Science.gov (United States)

    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.

  5. Vascular emergencies.

    Science.gov (United States)

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  6. Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Topal, Gökçe; Koç, Ebru; Karaca, Cetin; Altuğ, Tuncay; Ergin, Bülent; Demirci, Cihan; Melikoğlu, Gülay; Meriçli, Ali H; Kucur, Mine; Ozdemir, Osman; Uydeş Doğan, B Sönmez

    2013-03-01

    Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), total nitrite-nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (10(-5)  M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF-α and IL-6 and by preventing lipid peroxidation. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Vascular Disease Foundation

    Science.gov (United States)

    ... 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 ...

  8. What Is Vascular Disease?

    Science.gov (United States)

    ... 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 ...

  9. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Young Sang [College of Natural Sciences, Chungnam National University, Daejeon (Korea, Republic of)

    2011-09-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated {beta}-galactosidase (SA-{beta}-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H{sub 2}O{sub 2}-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H{sub 2}O{sub 2}-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-{beta}-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

  10. Hodgkin-Reed-Sternberg cells in classical Hodgkin lymphoma show alterations of genes encoding the NADPH oxidase complex and impaired reactive oxygen species synthesis capacity.

    Science.gov (United States)

    Giefing, Maciej; Winoto-Morbach, Supandi; Sosna, Justyna; Döring, Claudia; Klapper, Wolfram; Küppers, Ralf; Böttcher, Sebastian; Adam, Dieter; Siebert, Reiner; Schütze, Stefan

    2013-01-01

    The membrane bound NADPH oxidase involved in the synthesis of reactive oxygen species (ROS) is a multi-protein enzyme encoded by CYBA, CYBB, NCF1, NCF2 and NCF4 genes. Growing evidence suggests a role of ROS in the modulation of signaling pathways of non-phagocytic cells, including differentiation and proliferation of B-cell progenitors. Transcriptional downregulation of the CYBB gene has been previously reported in cell lines of the B-cell derived classical Hodgkin lymphoma (cHL). Thus, we explored functional consequences of CYBB downregulation on the NADPH complex. Using flow cytometry to detect and quantify superoxide anion synthesis in cHL cell lines we identified recurrent loss of superoxide anion production in all stimulated cHL cell lines in contrast to stimulated non-Hodgkin lymphoma cell lines. As CYBB loss proved to exert a deleterious effect on the NADPH oxidase complex in cHL cell lines, we analyzed the CYBB locus in Hodgkin and Reed-Sternberg (HRS) cells of primary cHL biopsies by in situ hybridisation and identified recurrent deletions of the gene in 8/18 cases. Immunohistochemical analysis to 14 of these cases revealed a complete lack of detectable CYBB protein expression in all HRS cells in all cases studied. Moreover, by microarray profiling of cHL cell lines we identified additional alterations of NADPH oxidase genes including CYBA copy number loss in 3/7 cell lines and a significant downregulation of the NCF1 transcription (p=0.006) compared to normal B-cell subsets. Besides, NCF1 protein was significantly downregulated (p<0.005) in cHL compared to other lymphoma cell lines. Together this findings show recurrent alterations of the NADPH oxidase encoding genes that result in functional inactivation of the enzyme and reduced production of superoxide anion in cHL.

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

    Science.gov (United States)

    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.

  12. Blood flow controls bone vascular function and osteogenesis

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  13. Protective effect of zingerone on increased vascular contractility in diabetic rat aorta.

    Science.gov (United States)

    Ghareib, Salah A; El-Bassossy, Hany M; Elberry, Ahmed A; Azhar, Ahmad; Watson, Malcolm L; Banjar, Zainy M; Alahdal, Abdulrahman M

    2016-06-05

    The aim of the present study was to investigate the effect and possible mechanism of action of zingerone, the main constituent of ginger, on vascular reactivity in isolated aorta from diabetic rats. The results show that incubation of aortae with zingerone alleviates the exaggerated vasoconstriction of diabetic aortae to phenylephrine, as well as the impaired relaxatory response to acetylcholine in a concentration-dependent manner. Furthermore, Zingerone directly relax phenylephrine-precontracted aortae. The vasorelaxatory response is significantly attenuated by the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride and the guanylate cyclase inhibitor methylene blue but no effect of either the potassium channels blocker tetraethylammonium chloride, or the cyclooxygenase inhibitor indomethacin was observed. Zingerone had no effect on advanced glycation end product formation as well. In conclusion, zingerone ameliorates enhanced vascular contraction in diabetic aortae which may be mediated by its vasodilator effect through NO- and guanylate cyclase stimulation.

  14. Executive function of patients with mild vascular cognitive impairment%轻度血管性认知功能障碍执行功能特点的研究

    Institute of Scientific and Technical Information of China (English)

    李秋俐; 王磊; 穆飞航; 解恒革

    2012-01-01

    目的 探讨轻度血管性认知功能障碍(MVCI)患者执行功能特点,为临床诊断提供依据.方法 选择患者58例,分为MVCI组21例、脑血管病无认知障碍组(CVD组)15例、对照组22例.测查各组患者记忆力、注意力、语言能力、执行功能、视觉空间功能及头颅MRI.结果 MVCI组总体认知功能、执行功能较CVD组明显下降(P<0.01).MVCI组画钟测验、画图、语言、连线A和B、Stroop字和色、阿尔茨海默病评价量表认知分表(ADAS-cog)总分和单词回忆分项的Z值低于对照组的1.5个标准差,简易智能状态检查、语言流畅性测验、数字符号转换、Stroop字和色、ADAS-cog单词辨认成绩Z值低于对照组的1~1.5标准差.而CVD组与对照组以上指标差异无统计学意义(P>0.05).结论 MVCI患者存在执行功能异常.MVCI诊断标准有较高的一致性和准确性.%Objective To provide the evidence for the diagnosis of mild vascular cognitive impairment MVCI) by studying the executive function characteristics of such patients. Methods Fifty-eight patients were divided into MVCI group(w = 21),cerebral vascular disease(CVD) group(n = 15),and normal control group(w = 22). Their memory,attention power,linguistic function,executive function,visual space function,and brain MRI were detected. Results The general cognitive function and executive function were significantly lower in MVCI group than in CVD group(P< 0. 05). The Z value of clock drawing test,picture drawing test,linguistic function,link tests A and B.Stroop color words test(CWT) , ADAS-cog and words memory test was lower in VCIND group than in control groupd. 5 standard deviation). The Z value of mini mental state examination,verbal fluency test, number symbol conversion, CWT, ADAS-cog words identification was lower in MVCI group than in control groupd - 1. 5 standard deviation) with no difference between CVD group and control group. Conclusion The executive function of MVCI patients is

  15. 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

    Directory of Open Access Journals (Sweden)

    Guo C

    2016-10-01

    Full Text Available Caixia Guo,1,2 Man Yang,2,3 Li Jing,2,3 Ji Wang,2,3 Yang Yu,2,3 Yang Li,2,3 Junchao Duan,2,3 Xianqing Zhou,2,3 Yanbo Li,2,3 Zhiwei Sun2,3 1Department of Occupational and Environmental Health, School of Public Health, 2Beijing Key Laboratory of Environmental Toxicology, 3Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, People’s Republic of China Abstract: 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

  16. Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, high-sucrose diet.

    Science.gov (United States)

    Bourgoin, Frédéric; Bachelard, Hélène; Badeau, Mylène; Mélançon, Sébastien; Pitre, Maryse; Larivière, Richard; Nadeau, André

    2008-09-01

    This study was designed to examine the effects of a high-fat, high-sucrose (HFHS) diet on vascular and metabolic actions of insulin. Male rats were randomized to receive an HFHS or regular chow diet for 4 wk. In a first series of experiments, the rats had pulsed Doppler flow probes and intravascular catheters implanted to measure blood pressure, heart rate, and regional blood flows. Insulin sensitivity and vascular responses to insulin were assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine skeletal muscle glucose transport activity and to determine in vitro vascular reactivity, endothelial nitric oxide synthase (eNOS) protein expression in muscle and vascular tissues and endothelin content, nitrotyrosine formation, and NAD(P)H oxidase protein expression in vascular tissues. The HFHS-fed rats displayed insulin resistance, hyperinsulinemia, hypertriglyceridemia, hyperlipidemia, elevated blood pressure, and impaired insulin-mediated renal and skeletal muscle vasodilator responses. A reduction in endothelium-dependent vasorelaxation, accompanied by a decreased eNOS protein expression in muscles and blood vessel endothelium, and increased vascular endothelin-1 protein content were also noted in HFHS-fed rats compared with control rats. Furthermore, the HFHS diet induced a reduced insulin-stimulated glucose transport activity in muscles and increased levels of NAD(P)H oxidase protein and nitrotyrosine formation in vascular tissues. These findings support the importance of eNOS protein in linking metabolic and vascular disease and indicate the ability of a Westernized diet to induce endothelial dysfunction and to alter metabolic and vascular homeostasis.

  17. Macrostructure of sleep in patients with vascular cognitive impairment-no dementia%非痴呆型血管性认知障碍的睡眠结构分析

    Institute of Scientific and Technical Information of China (English)

    朱穆峰; 邓丽影; 龚黎民; 刘昊; 丁勇民

    2011-01-01

    目的 探讨非痴呆型血管性认知障碍(VCI-ND)患者的睡眠结构,了解与正常人群之间睡眠结构的差异性.方法 应用加拿大Harmonie生产的32导Stellate Harmonie视频多导睡眠监测系统,对20例VCI-ND患者的睡眠进行全夜监测,并与20名正常相同年龄范围人群对照.结果 与对照组比较,VCI-ND患者组睡眠总时间减少,觉醒时间增加,第1阶段睡眠增加,第2阶段睡眠减少和第3阶段睡眠减少,快速动眼期(REM)缩短,睡眠效率下降.结论 PSG中的浅睡眠增多,慢波睡眠S3~4期及快速动眼期(REM)期减少可能是VCI-ND病人所具有的电生理学指标之一,但是否可作为VCI-ND患者的特异性诊断指标还需要大样本多中心性的随机对照研究.%Objective To investigate the sleep structure in patients with vascular cognitive impairment-no dementia (VCI-ND) and its differences from that of normal individuals. Methods The whole night sleep record of 20 patients with VCI-ND were monitored by 32-head video-taped polysomnographic system, and the results were compared with the data of 20 normal subjects. Result Compared with normal subjects, patients with VCI-ND showed significantly reduced total sleep duration, increased waking times, increased stage 1 sleep, decreased stage 2 sleep, decreased stage 3 sleep, decreased rapid eye movement stage (REM) and reduced sleep efficiency. Conclusion Increased light sleep as well as decreased slow-wave stage 3-4 sleep and decreased REM stage may be a specific electroneurophysiologic marker forVCI-ND, but large-sampled multi-centered randomized controlled trial is necessary to test the validity of these features as specific markers for screening and early diagnostic purposes.

  18. 老年缺血性脑卒中后轻度血管性认知障碍的影响因素%The factors of mild vascular cognitive impairment in elderly patients with ischemic cerebral stroke

    Institute of Scientific and Technical Information of China (English)

    王和平; 黄燕秋

    2016-01-01

    目的:分析老年缺血性脑卒中后轻度血管性认知障碍(VCI)的影响因素。方法对患者一般资料、体格检查、认知评估及影像学资料进行收集与调查,并行单因素分析与Logistic回归分析。结果老年缺血性卒中后轻度VCI的发生与患者年龄、文化程度、冠心病、糖尿病、高血压、卒中次数、发病部位及卒中面积有关;与性别、BM I、吸烟、饮酒等无明显相关。Logistic回归分析显示,文化程度为老年缺血性脑卒中后轻度VCI发生的保护因素,而年龄、冠心病、糖尿病、高血压、卒中次数、发病部位及卒中面积是危险因素。结论老年缺血性脑卒中后轻度 VCI发生的危险因素众多,临床上可进行针对性的早期干预。%Objective To analyze the factors of mild vascular cognitive impairment (VCI) in elderly patients with ischemic cerebral stroke. Methods The general information ,physical examination ,cognitive evaluation and imaging data were collected and investigated;single factor analysis and Logistic regression analysis were used. Results The occurrence of mild VCI in eld-erly patients with ischemic cerebral stroke was related with age ,educational level ,coronary heart disease ,diabetes ,hyperten-sion ,stroke frequency ,disease location and area of stroke ,and had non-obvious relation with sex ,BMI ,smoking ,alcohol con-sumption. Logistic regression analysis showed that education was a protective factor for mild VIC in elderly patients with is-chemic cerebral stroke ,and age ,coronary heart disease ,diabetes ,hypertension ,stroke frequency ,disease location and area were the risk factors. Conclusion The risk factors for mild VCI in elderly patients with ischemic cerebral stroke are many ;targeted early intervention can be applied in clinic.

  19. Effects of Naokang II on Patients with Vascular Cognitive Impairment after Cerebral Infarction%脑康Ⅱ号对脑梗死后血管性认知障碍患者的干预研究

    Institute of Scientific and Technical Information of China (English)

    王宁群; 黄小波; 魏翠柏; 陈文强; 陈玉静

    2014-01-01

    目的:观察脑康Ⅱ号对脑梗死后无痴呆型血管性认知障碍的临床疗效。方法:将100例符合入组标准的患者随机分为治疗组(中西医结合治疗组)和对照组(西医治疗组)。观察治疗前后患者认知功能、神经功能缺损程度评分、日常生活活动能力及生存质量评分。结果:治疗组NIHSS评分的改善优于对照组(P<0.05);治疗组MoCA评分的改善优于对照组,主要表现在视空间和执行功能、注意力、计算力、延迟回忆、定向力等方面(P<0.05)。治疗组与对照组在特异性生存质量量表“卒中影响量表( SIS)”中体力、日常活动能力、行动能力、社会参与等维度的改善方面具有显著差异,治疗组优于对照组(P<0.05,P<0.01)。结论:脑康Ⅱ号能够改善脑梗死后无痴呆型血管性认知障碍患者的认知功能和生存质量。%Objective:To observe the clinical effect of Naokang II on vascular cognitive impairment without dementia after cerebral infarction.Methods:100 patients that met the inclusion criteria were randomly divided into a treatment group ( treated by combination of Chinese medicine and western medicine ) and a control group ( treated by western medi-cine) .The scores of cognitive function, the neurological function defect, the activities of daily living and life quality were observed before and after treatment.Results: The improvement of NIHSS score in the treatment group was better than that in the control group (P<0.05).The improvement of MoCA score in the treatment group was also better,espe-cially in visual spatial and executive function, attention, calculation, delayed recall and directional function ( P <0.05 ) .The treatment group and the control group showed significant differences in the improvement of physical strength, ability of daily activities, action ability, social participation and other dimensions in the specific quality of life

  20. 感染性休克微循环与血管反应性的变化及监测%Changes and monitoring of microcirculation and vascular reactivity in septic shock

    Institute of Scientific and Technical Information of China (English)

    袁慧琴(综述); 刘励军(审校)

    2016-01-01

    Shock is an acute circulation failure caused by a variety of strong pathogenic factors in the body. The characteristic is that the microcirculation perfusion is insufficient, which leads to the systemic pathological process of cell metabolism and cell damage. The hemodynamic changes of various types of shock are not the same. According to the classification of hemodynamics, there are:low cardiac output and high resistance, high cardiac output and low resistance, low cardiac output and low resis⁃tance. Of three types, high cardiac output and low resistance is the most common;the most common fea⁃ture is the lack of microcirculation perfusion. According to the treatment strategy based on shock, there are:hypovolemic, cardiogenic, distribution and obstructive shock. Distribution shock is often one of the common causes of the patient's transfer to the intensive care unit(ICU)and high mortality in ICU. In the study of pathophysiological mechanism of shock, circulatory dysfunction is an important cause of tis⁃sue perfusion. The vascular paralysis of septic shock is the main cause of circulatory dysfunction. In this paper, we reviewed the changes and monitoring of microcirculation and vessel reactivity in septic shock.%休克是各种强烈的致病因子作用于机体导致的急性血液循环衰竭,其特点是微循环灌注不足导致细胞代谢障碍和细胞损伤引起的全身性病理过程。各类休克血流动力学变化不尽相同,按血流动力学分类有低排高阻型、高排低阻型及低排低阻型。其中以高排低阻型最为常见,共同特点是微循环灌注不足。按休克的基础治疗策略分为低容量性、心源性、分布性和梗阻性休克。其中分布性休克中的感染性休克常是患者转入重症医学科(ICU)的常见原因之一,也是ICU住院患者主要的死亡原因之一。在休克病理生理机制研究中,循环功能异常是影响组织灌注的重要原因,而感染性

  1. Comparison of clinical effects of several treatments for vascular cognitive impairment not dementia%不同疗法对非痴呆性血管性认知障碍疗效观察

    Institute of Scientific and Technical Information of China (English)

    韩颖; 齐惠; 崔鹏; 李来有

    2012-01-01

    Objective:To investigate the clinical effects of several treatments for vascular cognitive impairment not dementia(VCIND). Methods:Total 90 patients with VCIND were randomly divided into the cerebellar fastigial nucleus electrical stimulation(FNS)group,oxiracetam group and nimodipine group,with 30 cases in each group. On the base of all groups receiving conventional treatments, the treatment of FNS was applied in the FNS group, oxiracetam in the oxiracetam group and nimodipine in nimodipine group. The Event-Related Potentials P300(ERP-P300),Montreal cognitive assessment(MoCA)and transcranial dopplor ultrasonic monitor(TCD)of all patients were observed and compared before and after the treatment. Results: FNS group:After the treatment, the scores of MoCA showed improvement(P 0.05). Nimodipine group: After the treatment,TCD result showed the mean velocity of blood flow improved significantly (P 0.05). After the treatment,the score of MoCA in the FNS group and oxiracetam group were both higher than that in nimodipine group(P 0.05);the amplitude of P300 in the oxiracetam group was higher than that in the FNS group and nimodipine group(P 0.05). After the treatment,TCD result showed the mean velocity of blood flow of MCA in FNS group was higher than those in oxiracetam group and nimodipine group(P 0.05 ); The mean velocity of blood flow of ACA, PCA ans VA in FNS group and nimodipine group were higher than those in oxiracetam group(P 0.05). Conclusion:The FNS,oxiracetam and nimodipine are all beneficial in treatment of VCIND. Oxiracetam can effectively improve cognitive function;nimodipine can effectively improve blood supply to the brain;FNS can effectively improve cognitive function and blood supply to the brain in patients with VCIND.%目的:观察并比较不同疗法在治疗非痴呆性血管性认知障碍(vascular cognitive impairment not dementia,VCIND)患者中的临床疗效.方法:将90例VCIND患者随机分为电刺激子脑顶核(cerebellar fastigial

  2. Estudo da reatividade vascular em portadores de HIV com e sem uso de inibidor de protease Estudio de la reactividad vascular en portadores de VIH con y sin uso de inhibidor de proteasa Study of vascular reactivity in HIV patients whether or not receiving protease inhibitor

    Directory of Open Access Journals (Sweden)

    Hamilton Nenrod Pereira Teixeira

    2009-10-01

    la función endotelial por la vasodilatación endotelio dependiente e independiente en pacientes VIH positivo y en grupo control. MÉTODOS: El estudio evaluó a 27 pacientes VIH positivo y a 16 del grupo control. La evaluación de la función endotelial se llevó a cabo mediante la vasodilatación de la arteria braquial endotelio dependiente (hiperemia reactiva e independiente (nitroglicerina SL. RESULTADOS: Pacientes VIH positivo en uso de inhibidor de proteasa (IP presentaron vasodilatación endotelio independiente significativamente menor que los subgrupos VIH negativo (p = 0,020 y VIH positivo sin uso de IP (p = 0,034. La variación del diámetro de la arteria braquial durante hiperemia reactiva no presentó significancia estadística en cualquier subgrupo. El análisis de regresión lineal múltiple evidenció que apenas el IP estaba asociado al delta relativo de la reactividad braquial por el vasodilatador, en los pacientes VIH positivo, a los 60 y 90 segundos. CONCLUSIÓN: Los pacientes VIH positivo en uso de IP presentan disfunción endotelio independiente cuando comparados a pacientes VIH positivo que no están en tratamiento con IP y a un grupo control.BACKGROUND: A great number of HIV-infected patients using antiretroviral drugs develop endothelial dysfunction and atherothrombosis, which lead to a high medical and social burden. Thus, it is important to identify pathophysiological mechanisms involved with the endothelial function in these patients, so that early intervention can be made to avoid disease progression. OBJECTIVE: To evaluate endothelial function using endothelium-dependent and independent vasodilation in HIV-positive patients and in a control group. METHODS: A total of 27 HIV-positive patients and 16 controls were evaluated. Endothelium-dependent (reactive hyperemia and independent (SL nitroglycerine vasodilation of the brachial artery was used to evaluate the endothelial function. RESULTS: HIV-positive patients receiving protease inhibitors

  3. High resolution imaging of vascular function in zebrafish.

    Directory of Open Access Journals (Sweden)

    Simon C Watkins

    Full Text Available RATIONALE: The role of the endothelium in the pathogenesis of cardiovascular disease is an emerging field of study, necessitating the development of appropriate model systems and methodologies to investigate the multifaceted nature of endothelial dysfunction including disturbed barrier function and impaired vascular reactivity. OBJECTIVE: We aimed to develop and test an optimized high-speed imaging platform to obtain quantitative real-time measures of blood flow, vessel diameter and endothelial barrier function in order to assess vascular function in live vertebrate models. METHODS AND RESULTS: We used a combination of cutting-edge optical imaging techniques, including high-speed, camera-based imaging (up to 1000 frames/second, and 3D confocal methods to collect real time metrics of vascular performance and assess the dynamic response to the thromboxane A(2 (TXA(2 analogue, U-46619 (1 µM, in transgenic zebrafish larvae. Data obtained in 3 and 5 day post-fertilization larvae show that these methods are capable of imaging blood flow in a large (1 mm segment of the vessel of interest over many cardiac cycles, with sufficient speed and sensitivity such that the trajectories of individual erythrocytes can be resolved in real time. Further, we are able to map changes in the three dimensional sizes of vessels and assess barrier function by visualizing the continuity of the endothelial layer combined with measurements of extravasation of fluorescent microspheres. CONCLUSIONS: We propose that this system-based microscopic approach can be used to combine measures of physiologic function with molecular behavior in zebrafish models of human vascular disease.

  4. Visual Impairment

    Science.gov (United States)

    ... Surgery? Choosing the Right Sport for You Shyness Visual Impairment KidsHealth > For Teens > Visual Impairment Print A A ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual problem ...

  5. Vascular function, inflammation, and variations in cardiac autonomic responses to particulate matter among welders.

    Science.gov (United States)

    Fang, Shona C; Cavallari, Jennifer M; Eisen, Ellen A; Chen, Jiu-Chiuan; Mittleman, Murray A; Christiani, David C

    2009-04-01

    Patients with health conditions associated with impaired vascular function and inflammation may be more susceptible to the adverse health effects of fine particulate (particulate matter with a mass median aerodynamic diameter of personal PM(2.5) exposure information was collected over a total of 36 person-days, including either or both welding and nonwelding days. Linear mixed models were used to examine the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to the moving PM(2.5) averages in the preceding 1-4 hours. C-reactive protein levels and 3 measures of vascular function (augmentation index, mean arterial pressure, and pulse pressure) were determined at baseline. The authors observed an inverse association between the 1-hour PM(2.5) and 5-minute SDNN. Greater SDNN declines were observed among those with C-reactive protein (P(interaction) values at or above the 75th percentile and pulse pressure values below the 75th percentile (P < 0.001). Systemic inflammation and poorer vascular function appear to aggravate particle-related declines in heart rate variability among workers.

  6. 原络配穴为主治疗血管性轻度认知障碍24例%The Combination of Yuan-source Points and Collateral Points in the Treatment of Vascular Mild Cognitive Impairment:An Analysis of 24 Cases

    Institute of Scientific and Technical Information of China (English)

    赵惠; 孔波; 喻巍; 孙波

    2011-01-01

    Objective: To observe the clinical effect of combination of yuan - source points and collateral points on vascular mild cognitive impairment.Methods:The original network - based acupuncture points combined with aricept for the treatment.Let aricept alone as the control group.Observe 48 patients with vascular mild cognitive impairment clinical symptoms and MMSE, ADL and changes in homocysteine.Results:The original network with the main acupuncture points combined aricept can improve vascular mild cognitive impairment in patients with MMSE score; ADL score improved to reduce homocysteine.The total effective rate was 83.33% compared with the control group which had a significant difference ( P < 0.05 ).Conclusion: The original network with the main acupuncture points combined aricept may improve vascular mild cognitive impairment (VMCI)in terms of intelligence and rehabilitation of patients in daily life, and more effective than aricept alone in the control group.%目的:观察原络配穴针法为主治疗血管性轻度认知障碍的临床疗效.方法:以原络配穴针法为主联合安理申为治疗手段,设单纯安理申为对照组,观察48例血管性轻度认知障碍患者治疗前后临床症状和MMSE、ADL及同型半胱氨酸变化.结果:原络配穴针法为主联合安理申能够提高血管性轻度认知障碍患者MMSE评分,改善ADL评分,降低同型半胱氨酸.临床总有效率为83.33%,与对照组比较差异显著(P<0.05).结论:原络配穴针法为主联合安理申可有效改善血管性轻度认知障碍(VMCI)患者的智能水平和恢复生活自理能力,且疗效优于单纯安理申治疗.

  7. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells

    National Research Council Canada - National Science Library

    T Inoguchi; P Li; F Umeda; H Y Yu; M Kakimoto; M Imamura; T Aoki; T Etoh; T Hashimoto; M Naruse; H Sano; H Utsumi; H Nawata

    2000-01-01

    ...)H oxidase in cultured vascular cells. T Inoguchi , P Li , F Umeda , H Y Yu , M Kakimoto , M Imamura , T Aoki , T Etoh , T Hashimoto , M Naruse , H Sano , H Utsumi and H Nawata Department of Medicine and Bioregulatory Science, Graduate...

  8. 缺血性脑卒中患者认知功能障碍的影响因素研究%Influencing Factors of Vascular Cognitive Impairment Among Patients With Ischemic Stroke

    Institute of Scientific and Technical Information of China (English)

    刘晶; 张虎; 张宪忠; 林安基; 孟宪慧; 胡皓; 池学洋; 段锦秀; 卢朋; 李书珍; 张允岭; 金香兰; 郑宏; 侯小兵; 曹晓岚; 王少杰; 杨健; 赵建军; 田军彪

    2015-01-01

    Objective To explore the influencing factors of vascular cognitive impairment(VCI)among patients with ischemic stroke. Methods 3 000 cases with ischemic stroke were selected from 14 centres( Dongfang Hospital of Beijing University of Chinese Medicine,Wangjing Hosptial of CACMS,Affiliated Hospital of Changchun University of Traditional Chinese Medicine,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Traditional Chinese Medicine Hospital of Hebei Medical University,Peking University People's Hospital,Chongqing Traditional Chinese Medicine Hospital, Beijing Shunyi Hospital of Traditional Chinese Hospital,Youanmen Community Health Service Centre of Beijing Fengtai District, Puhuangyu Community Health Service Centre of Beijing Fengtai District,Fangzhuang Community Health Service Centre of Beijing Fengtai Distriet,Shandong Rizhao Hospital of Traditional Chinese Medicine,Xinglong TCM Hospital of Beijing,and Xiamen Hospital of Traditional Chinese Medicine)during December 2010 to December 2013. The demographics,past medical history, family history and living habit of cases were collected,the cognitive function was evaluated by using the diagnostic criteria for VCI and MoCA. All participants were divided into two groups by the MoCA score as follows:the VCI group(MoCA score < 26)and control group(MoCA score ≥ 26). The influencing factors of VCI among patients with ischemic stroke were analyzed by using single - factor and multi - factor Logistic regression analysis. Results 1 504 cases had cognitive impairment,while 1 496 cases were normal. According to result of single - factor Logistic regression analysis,age,education level,occupation,marital status, living status,hypertension,cerebrovascular disease,coronary heart disease,drinking coffee,physical exercises,hobbies and interests,using mobile were influencing factors of VIC( P < 0. 05). According to result of multi - factor Logistic regression analysis,age,education level

  9. Effects on Non-dementia Vascular Cognitive Impairment with the Treatment of Scalp Acupuncture and Cognitive Training%头穴丛刺及认知训练对非痴呆型血管性认知损害的影响*

    Institute of Scientific and Technical Information of China (English)

    白晶; 李宝栋; 田守森; 田雯艳; 戈杰英; 白金君

    2013-01-01

    目的:观察头穴丛刺法联合认知训练治疗非痴呆型血管性认知损害的疗效。方法:我院非痴呆型血管性认知损害患者60例,采用随机数字表法分为治疗组及对照组。两组患者均予吡拉西坦口服、常规治疗及运动疗法、作业疗法(认知疗法),治疗组另予头穴丛刺疗法;采用蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)评定两组患者认知障碍程度,应用事件相关电位评测认知功能变化。结果:治疗后两组MoCA评分、P300潜伏期均较治疗前明显改善(P<0.05),且治疗组优于对照组(P<0.05)。结论:头穴丛刺疗法联合认知训练可以改善非痴呆型血管性认知损害程度,提高患者生活质量,值得临床推广。%Objective:To observe the effects of scalp acupuncture and cognitive training treating non-dementia vascular cognitive impairment. Meth-ods:60 patients with non-dementia vascular cognitive impairment in our hospital were randomly divided into treatment group and control group with a method of random digits table. Patients of two groups were given oral piracetam, conventional therapy, cinesiatrics and occupational therapy (cogni-tive therapy), treatment group were additionally treated with scalp acupuncture;Montreal Cognitive Assessment(MoCA) and event-related potential were used to evaluate degree of cognitive impairment and changes in cognitive function of two groups. Results:MoCA scores and P300 latency of two groups after the treatment were significantly superior to those before the treatment (P<0.05), and treatment group was better than control group (P<0.05). Conclusion:Scalp acupuncture and cognitive training can improve non-dementia vascular cognitive impairment and life quality of patients, being worthy of clinical promotion.

  10. 血管源性轻度认知障碍中医核心术语在不同人群中应答情况研究%Research of the Core Terminology of Traditional Chinese Medicine on Vascular Mild Cognitive Impairment for the Response in Different Groups

    Institute of Scientific and Technical Information of China (English)

    薛斐然; 刘文娜; 张允岭; 金香兰; 牛焕敏; 张艳霞; 陈宝鑫; 傅晨; 郑硕; 南一楠

    2013-01-01

    Objective To verify and optimize the core terminology of traditional Chinese medicine on vascular mild cognitive impairment for the response in different groups. Methods By the investigation of the chief complains of the patients and the explanation of the relatives for 945 cases of cognitive impairment, the information was collected on the scene. The chi - square analysis and reliability analysis method were a-dopted to verify and optimize the core terminology of traditional Chinese medicine for vascular mild cognitive impairment. Results Twelve core terms were verified and optimized, including memory loss , misunderstanding" , "absent mind" , " poor behavior" , " disliking speech, word repetition, mis - speaking" , " illogical and poor words , sorrow and worries , disability , keeping away from crowd , disliking movement, somnolence" ,"drowsiness at daytime and restlessness at night". For the term,"suspiciousness and hesitant decision , a further discussion and clinical re - verification was required. Conclusion The twelve core terms better reflect the state of the patients with vascular mild cognitive impairment. All of these terms distinguish from the terminology of dementia and western medicine and can be used for the symptom description.%目的 就不同人群临床应答情况验证、优化血管源性轻度认知障碍中医核心术语.方法 通过对945例有认知障碍主诉或家属代诉患者的调查,现场收集信息,采用卡方分析、信度分析的方法验证、优化血管源性轻度认知障碍中医核心术语.结果 验证并优化出"转盼遗忘""多忘善误""神思不聚""持筹握算差""言语懒、重复、言善误""言辞颠倒、贫乏""忧愁思虑""庶事皆废""居暗避人""思维反应迟钝""懒动嗜卧""日间静则瞌睡、夜间躁扰不宁"12项核心术语,"多疑寡断"需进行进一步论证及临床再验证.结论 12项核心术语能较好的体现血管源性轻度认知障碍患者的状态,所有术语

  11. Clinical study on correlation between senile vascular cognitive impairment no dementia and impaired glucose regulation%糖调节受损与老年非痴呆型血管性认知功能障碍的相关性观察

    Institute of Scientific and Technical Information of China (English)

    李伟; 赵翠; 王淼; 林璨; 王璐; 王国玉; 王兆鹏; 尹成淑

    2015-01-01

    Objective To investigate the correlation between senile impaired glucose regulation( IGR) and vascular cognitive im-pairment no dementia( VCIND) . Methods Totally 187 cases of VCIND patients over 60 years old without diabetes were selected as the research object. Meantime,200 patients without diabetes or VCIND were chosen as control group. The glucose tolerance tests were performed on patients in both groups. The correlation between IGR,other risk factors and VCIND was analyzed by single and multi factor non conditional Logistic regression analysis. Results (1) The incidence of IGR in VCIND group was 29. 41%(55/187),significantly higher than 19%(38/200)in control group and the difference was statistically significant(P60岁且无糖尿病史的VCIND患者187例为研究对象,另选取200例同期无糖尿病史且无认知功能障碍的体检人群为对照组。两组患者均进行糖耐量试验,经单因素和多因素非条件的Logistic回归分析IGR及其他危险因素与VCIND的相关性。结果(1)VCIND组患者的IGR发生率为29.41%(55/187),明显高于对照组的19.00%(38/200),差异有统计学意义(P<0.05)。(2)VCIND组患者糖尿病发生率16.04%(30/187)、高胆固醇血症发生率32.09%(60/187)、低高密度脂蛋白胆固醇发生率21.39%(40/187)、高甘油三酯血症发生率36.36%(68/187),均明显高于对照组的3%(3/200)、20.50%(41/200)、13.50%(27/200)、24.50%(49/200),差异均有统计学意义(P<0.05)。(3)多因素Logistic回归分析显示,与VCIND相关的危险因素依次为:糖尿病(OR=10.542,P<0.01)、高血压病(OR=5.365,P<0.01)、高甘油三酯血症(OR=4.144,P<0.01)、高胆固醇血症(OR=2.318,P<0.01)、糖调节受损(OR=1.786,P<0.05)。结论 IGR是VCIND的独立危险因素,即在血管性痴呆的早期已具有独立的危险性。

  12. Neckties and Cerebrovascular Reactivity in Young Healthy Males: A Pilot Randomised Crossover Trial

    Directory of Open Access Journals (Sweden)

    Mark Rafferty

    2011-01-01

    Full Text Available Background. A necktie may elevate intracranial pressure through compression of venous return. We hypothesised that a tight necktie would deleteriously alter cerebrovascular reactivity. Materials and Methods. A necktie was simulated using bespoke apparatus comprising pneumatic inner-tube with aneroid pressure-gauge. Using a randomised crossover design, cerebrovascular reactivity was measured with the “pseudo-tie” worn inflated or deflated for 5 minutes (simulating tight/loose necktie resp.. Reactivity was calculated using breath hold index (BHI and paired “t” testing used for comparative analysis. Results. We enrolled 40 healthy male volunteers. There was a reduction in cerebrovascular reactivity of 0.23 units with “tight” pseudotie (BHI loose 1.44 (SD 0.48; BHI tight 1.21 (SD 0.38 P<.001. Conclusion. Impairment in cerebrovascular reactivity was found with inflated pseudo-tie. However, mean BHI is still within a range of considered normal. The situation may differ in patients with vascular risk factors, and confirmatory work is recommended.

  13. Vascular Function and Structure in Veteran Athletes after Myocardial Infarction.

    NARCIS (Netherlands)

    Maessen, M.F.H.; Eijsvogels, T.M.H.; Hijmans-Kersten, B.T.P.; Grotens, A.; Schreuder, T.H.A.; Hopman, M.T.E.; Thijssen, D.H.J.

    2017-01-01

    PURPOSE: Although athletes demonstrate lower cardiovascular risk and superior vascular function compared with sedentary peers, they are not exempted from cardiac events (i.e., myocardial infarction [MI]). The presence of an MI is associated with increased cardiovascular risk and impaired vascular

  14. 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

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

    2011-01-01

    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...

  15. 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

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

    2011-01-01

    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...

  16. Valpar系统联合计算机辅助技术治疗早期血管性认知障碍的疗效观察%Valpar technology can improve the treatment of early vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    房辉; 谢凌锋; 贾澄杰; 张秀花; 苏彬; 任志恒

    2016-01-01

    目的 观察Valpar系统联合计算机辅助技术治疗早期血管性认知障碍(VCI)的疗效.方法 选取40例符合人选标准的早期VCI患者,按照随机数字表法将其分为治疗组和对照组,每组20例.2组患者均给予常规认知康复训练和计算机辅助治疗,治疗组在此基础上采用Valpar系统进行认知功能训练.治疗前、治疗4周后及8周后,采用洛文斯顿作业疗法认知功能评定量表(LOTCA)和改良Barthel指数(MBI)对2组患者进行认知功能和ADL能力评定.结果 治疗前,2组患者LOTCA评分和MBI评分之间比较,差异无统计学意义(P>0.05).治疗组治疗4周后及8周后,LOTCA各项评分、LOTCA总分及MBI评分均较治疗前改善(P<0.05).对照组治疗4周后,定向能力[(3.50±0.89)分]、视知觉[(13.50±1.43)分]、空间知觉[(2.40土0.50)分]、视运动组织[(24.00±1.17)分]及注意力评分[(2.30土0.87)分]较治疗前明显改善(P<0.05),治疗8周后LOTCA各项评分、LOTCA总分及MBI评分均较治疗前改善(P<0.05).与对照组治疗后同时间点比较,治疗组治疗4周后及8周后LOTCA各项评分、LOTCA总分、MBI评分均较为优异(P<0.05).结论 Valpar系统联合计算机辅助技术能显著改善早期VCI患者的认知功能和ADL能力,值得临床应用、推广.%Objective To observe the therapeutic effect of the Valpar system combined with computer-aided technology in treating early vascular cognitive impairment (VCI).Methods Forty patients in the early stage of VCI were randomly divided into a treatment group and a control group,each of 20.Regular and computer-aided cognition training were applied in both groups,while training using the Valpar system was additionally used in the treatment group.Patients in both groups were assessed using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the modified Barthel Index (MBI) before,and after 4 and 8 weeks of treatment.Results Before the treatment,there were no

  17. Involvement of Rho-kinase in experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Shah, Dhvanit I; Singh, Manjeet

    2006-02-01

    The present study has been designed to investigate the effect of fasudil (Rho-kinase inhibitor) in diabetes mellitus (DM) and hyperhomocyteinemia (HHcy) induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg(-1), i.v., once only) and methionine (1.7% w/w, p.o., daily for 4 weeks) were administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum homocysteine >10 microM) respectively. VED was assessed using isolated aortic ring, electron microscopy of thoracic aorta, and serum concentration of nitrite/nitrate. Serum thiobarbituric acid reactive substances (TBARS) concentration was estimated to assess oxidative stress. Atorvastatin has been employed in the present study as standard agent to improve vascular endothelial dysfunction. Fasudil (15 mg kg(-1) and 30 mg kg(-1), p.o., daily) and atorvastatin (30 mg kg(-1), p.o., daily) treatments significantly attenuated increase in serum glucose and homocysteine but their concentrations remained markedly higher than sham control value. Fasudil and atorvastatin treatments markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine induced endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum TBARS. It may be concluded that fasudil prevented DM and HHcy-induced VED partially by decreasing serum glucose and homocysteine concentration due to inhibition of Rho-kinase. Moreover, inhibition of Rho-kinase by fasudil and consequent prevention of oxidative stress may have directly improved VED in diabetic and hyperhomocysteinemic rats. The Rho-kinase appears to be a pivotal target site involved in DM and HHcy-induced VED.

  18. 谷红注射液联合奥拉西坦治疗血管性认知障碍的疗效观察%Efficacy of combiration therapy with Kingtag and Oxiracetam for the patients with vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    陈敏; 罗欣; 张玉方; 王霆; 李苌清

    2012-01-01

    Objective To observe the efficacy and safety of the combiration therapy with Kingtag and Oxiracetam for the patients with vascular cognitive impairment(VCI).Methods According to the score of neuropsy chological test,a total of 226 patients with vascular cognitive impairment were divided in two groups: vascular cognitive impairment no dementia(VCIND,n = 115) and vascular dementia(VaD,n = 111) ,who were randomized to receive Kingtag and Oxiracetam(intervention group) ,physiological saline and OxiracetamC control group) respectively.Before and after treatment,the Montreal Cognitive Assessment(MoCA) and activities of daily living(ADL) were assessed.Results The scores of neuropsy chological test of two groups were significantly improved after treatment for 8 weeks.There was significant difference between the two groups(P<0.05).In the VCIND group,the scores in intervention group were signficantly better than those in the control group(P<0.05).The same results were presented by intervention group among VCIND group and VaD group(P<0.05).The incidence of adverse reaction in two groups were 6.25% and 4.50% respectively.No serious adverse events occured during the experment.Conclusion The combiration therapy with Kingtag and Oxiracetam has positive effect and cause less adverse reaction for patients with vascular cognitive impairment,it s worth popularizing in clinic.%目的 观察谷红注射液联合奥拉西坦治疗血管性认知功能障碍(VCI)的临床疗效及其不良反应.方法 筛选住院的血管性认功能知障碍患者226例,按神经心理学评分标准分为血管性非痴呆的认知功能损害(VCIND)层115例、血管性痴呆(VaD)层111例,每层再随机分为观察组和对照组.观察组给予谷红注射液联合奥拉西坦治疗,对照组给予生理盐水加奥拉西坦治疗.治疗前、后采用MoCA和ADL评分对患者进行神经心理学评分.结果 治疗8周后,观察组和对照组的神经心理学评分均提

  19. UP-REGULATION OF EXPRESSION OF ADHESION MOLECULE ON THE SURFACE OF HUMAN VASCULAR ENDOTHELIAL CELLS BY REACTIVE CARBONYL COMPOUNDS%活性羰基化合物对人血管内皮细胞粘附分子表达的影响

    Institute of Scientific and Technical Information of China (English)

    梁敏; 侯凡凡; 张训

    2001-01-01

    为探讨活性羰基化合物蓄积在慢性肾功能衰竭和糖尿病血管并发症发病机制中的作用,应用流式细胞仪检测3-脱氧葡糖醛酮和甲基乙二醛对人血管内皮细胞表达粘附分子的影响。结果显示,3-脱氧葡糖醛酮和甲基乙二醛均可上调人血管内皮细胞对ICAM-1和VCAM-1的表达,并呈时间和剂量依赖关系;羰基化合物清除剂(氨基胍)对上述羰基化合物产生的上调效应具有抑制作用。结果提示,活性羰基化合物可能与慢性肾衰和糖尿病血管病变的形成有关。%To elucidate the role of reactive carbonyl compounds in the pathogenesis of vascular complication in patients with chronic renal failure or diabetes. Vascular endothelial cells (VECs) were isolated from human umbilical vein and cultured with 3-deoxyglucosone (3-DG) or methylglyoxal(MGO) in vitro. Expression of ICAM-1 and VCAM-1 on the surface of VECs was detected by flow cytometer. The results showed that up-regulation of expression of ICAM-1 and VCAM-1 was observed when either 3-DG or MGO was added into the cultures, which was inhibited by a carbonyl compounds scavanger, aminoguanidine. These data suggested that accumulation of reactive carbonyl compounds in patients with chronic renal failure or diabetes might be involved in the mechanism of arteriosclerosis.

  20. Reactive Hypoglycemia

    Science.gov (United States)

    ... from low blood sugar (hypoglycemia) that occurs while fasting. Signs and symptoms of reactive hypoglycemia may include ... and very important. It's also important to include physical activity in your daily routine. Your doctor can help ...

  1. Reactive Arthritis

    Directory of Open Access Journals (Sweden)

    Eren Erken

    2013-06-01

    Full Text Available Reactive arthritis is an acute, sterile, non-suppurative and inflammatory arthropaty which has occured as a result of an infectious processes, mostly after gastrointestinal and genitourinary tract infections. Reiter syndrome is a frequent type of reactive arthritis. Both reactive arthritis and Reiter syndrome belong to the group of seronegative spondyloarthropathies, associated with HLA-B27 positivity and characterized by ongoing inflammation after an infectious episode. The classical triad of Reiter syndrome is defined as arthritis, conjuctivitis and urethritis and is seen only in one third of patients with Reiter syndrome. Recently, seronegative asymmetric arthritis and typical extraarticular involvement are thought to be adequate for the diagnosis. However, there is no established criteria for the diagnosis of reactive arthritis and the number of randomized and controlled studies about the therapy is not enough. [Archives Medical Review Journal 2013; 22(3.000: 283-299

  2. Cyclosporine A, FK506, and NIM811 ameliorate prolonged CBF reduction and impaired neurovascular coupling after cortical spreading depression

    DEFF Research Database (Denmark)

    Hansen, Henning Piilgaard; Witgen, Brent Marvin; Rasmussen, Peter

    2011-01-01

    that cyclosporine A (CsA), which blocks both mPTP and CaN, ameliorates the persistent reduction of cerebral blood flow (CBF), impaired vascular reactivity, and a persistent rise in the cerebral metabolic rate of oxygen (CMRO(2)) following CSD. In addition to CsA, we used the specific mPTP blocker NIM811......), and neurovascular and neurometabolic coupling were unaffected by all three drugs under control conditions. NIM811 augmented the rise in CBF observed during CSD. Cyclosporine A and FK506 ameliorated the persistent decrease in CBF after CSD. All three drugs prevented disruption of neurovascular coupling after CSD...

  3. Vascular development in Arabidopsis.

    Science.gov (United States)

    Ye, Zheng-Hua; Freshour, Glenn; Hahn, Michael G; Burk, David H; Zhong, Ruiqin

    2002-01-01

    Vascular tissues, xylem and phloem, form a continuous network throughout the plant body for transport of water, minerals, and food. Characterization of Arabidopsis mutants defective in various aspects of vascular formation has demonstrated that Arabidopsis is an ideal system for investigating the molecular mechanisms controlling vascular development. The processes affected in these mutants include initiation or division of procambium or vascular cambium, formation of continuous vascular cell files, differentiation of procambium or vascular cambium into vascular tissues, cell elongation, patterned secondary wall thickening, and biosynthesis of secondary walls. Identification of the genes affected by some of these mutations has revealed essential roles in vascular development for a cytokinin receptor and several factors mediating auxin transport or signaling. Mutational studies have also identified a number of Arabidopsis mutants defective in leaf venation pattern or vascular tissue organization in stems. Genetic evidence suggests that the vascular tissue organization is regulated by the same positional information that determines organ polarity.

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

    Science.gov (United States)

    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.

  5. Molecular signal transduction in vascular cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.

  6. Obesity Induces Artery-Specific Alterations: Evaluation of Vascular Function and Inflammatory and Smooth Muscle Phenotypic Markers

    Directory of Open Access Journals (Sweden)

    Antonio Garcia Soares

    2017-01-01

    Full Text Available Vascular alterations are expected to occur in obese individuals but the impact of obesity could be different depending on the artery type. We aimed to evaluate the obesity effects on the relaxing and contractile responses and inflammatory and smooth muscle (SM phenotypic markers in two vascular beds. Obesity was induced in C57Bl/6 mice by 16-week high-fat diet and vascular reactivity, mRNA expression of inflammatory and SM phenotypic markers, and collagen deposition were evaluated in small mesenteric arteries (SMA and thoracic aorta (TA. Endothelium-dependent relaxation in SMA and TA was not modified by obesity. In contrast, contraction induced by depolarization and contractile agonists was reduced in SMA, whereas only contraction induced by adrenergic agonist was reduced in TA of obese mice. Obesity increased the mRNA expression of pro- and anti-inflammatory cytokines in SMA and TA. The expression of genes necessary for maintaining contractile ability was increased by obesity, but the increase was more pronounced in TA. Collagen deposition was increased in SMA, but not in TA, of obese mice. Although the endothelial function was still preserved, the SM of the two artery types was impaired by obesity, but the impairment was higher in SMA, which could be associated with SM phenotypic changes.

  7. Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

    LENUS (Irish Health Repository)

    Walsh, Sarah K

    2012-01-31

    Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

  8. Branding of vascular surgery.

    Science.gov (United States)

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  9. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  10. Vaccine-induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    N.J. Paine; C. Ring; J.A. Bosch; M.T. Drayson; S. Aldred; J.J.C.S. Veldhuijzen van Zanten

    2014-01-01

    Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male

  11. The Nature of Episodic Memory Deficits in MCI with and without Vascular Burden

    Science.gov (United States)

    Villeneuve, Sylvia; Massoud, Fadi; Bocti, Christian; Gauthier, Serge; Belleville, Sylvie

    2011-01-01

    This study measured episodic memory deficits in individuals with mild cognitive impairment (MCI) as a function of their vascular burden. Vascular burden was determined clinically by computing the number of vascular risk factors and diseases and neuroradiologically by assessing the presence and severity of white matter lesions (WML). Strategic…

  12. Effects of catechins on vascular tone in rat thoracic aorta with endothelium.

    Science.gov (United States)

    Sanae, Fujiko; Miyaichi, Yukinori; Kizu, Haruhisa; Hayashi, Hisao

    2002-10-11

    The effects of eight catechin derivatives on vascular tone in rat thoracic aorta were examined. Catechin derivatives (10 microM) potentiated the contractile response to phenylephrine in endothelium-intact arteries. The potentiations produced by EGCg and EGC were almost absent in endothelium-denuded arteries and abolished by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis. The catechin derivatives also inhibited endothelium-dependent relaxation in response to acetylcholine. The order of catechin derivatives ranked in terms of both increasing vascular reactivity and impairing endothelium-dependent relaxation was similar; (-)-gallocatechin (GC) >or= (-)-epigallocatechin (EGC) >or= (-)-gallocatechin gallate (GCg) >or= (-)-epigallocatechin gallate (EGCg) >or= (-)-catechin (C) >or= (-)-epicatechin (EC) >or= (-)-catechin gallate (Cg) >or= (-)-epicatechin gallate (ECg). In addition, EGC inhibited the endothelium-independent relaxation evoked by both sodium nitroprusside and NOC-7, a spontanous NO releaser, but EGCg inhibited only that by NOC-7. These findings indicate that catechin derivatives produce a potentiation of the contractile response and an inhibition of the vasorelaxant response, probably through inactivation of endothelium-derived nitric oxide (NO), and that the hydroxyl on C-5 of the B ring together with the stereoscopic structure between the C-3 group and the B ring of flavanols was of importance in mediating the above effects and that the substitution of a gallate group of C-3 attenuated the effects, probably due to a decreased response to solube guanylate cyclase in vascular smooth muscle cells.

  13. Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

    Science.gov (United States)

    Manzini, S; Pinna, C; Busnelli, M; Cinquanta, P; Rigamonti, E; Ganzetti, G S; Dellera, F; Sala, A; Calabresi, L; Franceschini, G; Parolini, C; Chiesa, G

    2015-11-01

    Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. Copyright © 2015. Published by Elsevier Inc.

  14. Hearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging.

    Science.gov (United States)

    Gauthier, Claudine Joëlle; Lefort, Muriel; Mekary, Saïd; Desjardins-Crépeau, Laurence; Skimminge, Arnold; Iversen, Pernille; Madjar, Cécile; Desjardins, Michèle; Lesage, Frédéric; Garde, Ellen; Frouin, Frédérique; Bherer, Louis; Hoge, Richard D

    2015-01-01

    Human aging is accompanied by both vascular and cognitive changes. Although arteries throughout the body are known to become stiffer with age, this vessel hardening is believed to start at the level of the aorta and progress to other organs, including the brain. Progression of this vascular impairment may contribute to cognitive changes that arise with a similar time course during aging. Conversely, it has been proposed that regular exercise plays a protective role, attenuating the impact of age on vascular and metabolic physiology. Here, the impact of vascular degradation in the absence of disease was investigated within 2 groups of healthy younger and older adults. Age-related changes in executive function, elasticity of the aortic arch, cardiorespiratory fitness, and cerebrovascular reactivity were quantified, as well as the association between these parameters within the older group. In the cohort studied, older adults exhibited a decline in executive functions, measured as a slower performance in a modified Stroop task (1247.90 ± 204.50 vs. 898.20 ± 211.10 ms on the inhibition and/or switching component, respectively) than younger adults. Older participants also showed higher aortic pulse wave velocity (8.98 ± 3.56 vs. 3.95 ± 0.82 m/s, respectively) and lower VO₂ max (29.04 ± 6.92 vs. 42.32 ± 7.31 mL O2/kg/min, respectively) than younger adults. Within the older group, faster performance of the modified Stroop task was associated with preserved aortic elasticity (lower aortic pulse wave velocity; p = 0.046) and higher cardiorespiratory fitness (VO₂ max; p = 0.036). Furthermore, VO₂ max was found to be negatively associated with blood oxygenation level dependent cerebrovascular reactivity to CO₂ in frontal regions involved in the task (p = 0.038) but positively associated with cerebrovascular reactivity in periventricular watershed regions and within the postcentral gyrus. Overall, the results of this study support the hypothesis that cognitive

  15. Interferon regulatory factor-1 together with reactive oxygen species promotes the acceleration of cell cycle progression by up-regulating the cyclin E and CDK2 genes during high glucose-induced proliferation of vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Xi; Liu, Long; Chen, Chao; Chi, Ya-Li; Yang, Xiang-Qun; Xu, Yan; Li, Xiao-Tong; Guo, Shi-Lei; Xiong, Shao-Hu; Shen, Man-Ru; Sun, Yu; Zhang, Chuan-Sen; Hu, Kai-Meng

    2013-10-14

    The high glucose-induced proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of diabetic vascular diseases. In a previous study, we confirmed that Interferon regulatory factor-1 (Irf-1) is a positive regulator of the high glucose-induced proliferation of VSMCs. However, the mechanisms remain to be determined. The levels of cyclin/CDK expression in two cell models involving Irf-1 knockdown and overexpression were quantified to explore the relationship between Irf-1 and its downstream effectors under normal or high glucose conditions. Subsequently, cells were treated with high glucose/NAC, normal glucose/H₂O₂, high glucose/U0126 or normal glucose/H₂O₂/U0126 during an incubation period. Then proliferation, cyclin/CDK expression and cell cycle distribution assays were performed to determine whether ROS/Erk1/2 signaling pathway was involved in the Irf-1-induced regulation of VSMC growth under high glucose conditions. We found that Irf-1 overexpression led to down-regulation of cyclin D1/CDK4 and inhibited cell cycle progression in VSMCs under normal glucose conditions. In high glucose conditions, Irf-1 overexpression led to an up-regulation of cyclin E/CDK2 and an acceleration of cell cycle progression, whereas silencing of Irf-1 suppressed the expression of both proteins and inhibited the cell cycle during the high glucose-induced proliferation of VSMCs. Treatment of VSMCs with antioxidants prevented the Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression in high glucose conditions. In contrast, under normal glucose conditions, H₂O₂ stimulation and Irf-1 overexpression induced cell proliferation, up-regulated cyclin E/CDK2 expression and promoted cell cycle acceleration. In addition, overexpression of Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were treated with U0126, the specific Erk1/2 inhibitor

  16. Cross-sectional analysis of cognitive impairment and relative factors after acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    ZHOU Yu-ying

    2013-04-01

    Full Text Available Background Acute ischemic stroke may decline cognitive function and induce vascular dementia (VaD. In early identification of vascular cognitive impairment (VCI, active searching for relevant factors, effective and timely treatment can reduce or even prevent further decline of cognitive function. The purpose of this study is to investigate the cognitive impairment after acute ischemic stroke and its associated factors. Methods A total of 314 cases of acute ischemic stroke patients were recruited in this study. The Montreal Cognitive Assessment (MoCA was used to evaluate the degree of cognitive impairment. The American National Institutes of Health Stroke Scale (NIHSS was used to evaluate the extent of neurological deficit. The Barthel Index (BI was used to evaluate activities of daily living. Hamilton Depression Rating Scale (HAMD was used to evaluate the patients' mental or emotional state. Results Based on the examination results, post-stroke cognitive impairment (PSCI group were less educated ( P = 0.000 with lower BI score ( P = 0.008, higher HAMD score and higher NIHSS score ( P = 0.000, for all, and elevated serum high-sensitivity C-reactive protein (hs-CRP, P = 0.002 and glycosylated hemoglobin A1c (HbA1c levels (P = 0.005 than those in post-stroke no cognitive impairment (PSNCI group. In PSCI group, the concentration of serum hs-CRP and HbA1c, NIHSS and HAMD scores were negatively correlated with the MoCA rating (P < 0.05, for all; whereas, BI score was positively correlated with the MoCA rating (P < 0.05. The subjects in PSCI group had more cortical ischemic vascular disease (CIVD and left hemisphere ischemic vascular disease (LHIVD than subjects in PSNCI group ( P < 0.05. Logistic regression analysis indicated that lower education, history of diabetes, higher HAMD score, higher serum hs-CRP and HbA1c levels were independent risk factors for PSCI. Conclusion Cognitive impairment after acute ischemic stroke may be closely related to

  17. tion of vascular malformations

    African Journals Online (AJOL)

    classification of vascular anomalies outside of the central ... The current classification of CNS vascular ... tural proteins within the wall of caver- .... ing (or established) loss of function or a threat to ..... natural history of the strawberry nevus. Arch.

  18. Society for Vascular Medicine

    Science.gov (United States)

    ... 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.

  19. Collagen vascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on this ... previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many specific ...

  20. Mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Pavlović Dragan M.

    2009-01-01

    Full Text Available Mild cognitive impairment (MCI is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer's disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.

  1. Diagnosing vascular causes of renal failure.

    Science.gov (United States)

    Abuelo, J G

    1995-10-15

    The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

  2. The novel role of fenofibrate in preventing nicotine- and sodium arsenite-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Kaur, Jagdeep; Reddy, Krishna; Balakumar, Pitchai

    2010-09-01

    The present study investigated the effect of fenofibrate, an agonist of PPAR-alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning electron microscopy study in thoracic aorta revealed that administration of nicotine or sodium arsenite impaired the integrity of vascular endothelium. Further, administration of nicotine or sodium arsenite significantly decreased serum and aortic concentrations of nitrite/nitrate and subsequently reduced acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide generation. However, treatment with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a standard agent) significantly prevented nicotine- and sodium arsenite-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Conversely, co-administration of L-NAME (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated these vascular protective effects of fenofibrate. The administration of nicotine or sodium arsenite altered the lipid profile by increasing serum cholesterol and triglycerides and consequently decreasing high-density lipoprotein levels, which were significantly prevented by treatment with fenofibrate or atorvastatin. It may be concluded that fenofibrate improves the integrity and function of vascular endothelium, and the vascular protecting potential of fenofibrate in preventing the development of nicotine- and sodium arsenite-induced VED may be attributed to its

  3. The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy.

    Science.gov (United States)

    Zekry, Dina; Duyckaerts, Charles; Belmin, Joël; Geoffre, Caroline; Herrmann, François; Moulias, Robert; Hauw, Jean-Jacques

    2003-01-01

    Vascular dementia appears rarer than previously thought, but the contribution of vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected patients (mixed dementias) is now recognized as frequent. The role of strategic areas of the brain involved in the cognitive decline induced by vascular lesions and their relative contributions to the severity of the dementing process remain poorly understood. We determined the relationship between the severity of clinical dementia and the volume of different brain areas affected by infarcts in a prospective clinicopathological study in elderly patients. A volumetric study of the functional zones of Mesulam's human brain map affected by vascular lesions was made and correlations between quantified neuropathological data and the severity of dementia were performed in cases with large vascular lesions only, pure AD, and both lesions. The severity of cognitive impairment was significantly correlated with the total volume of infarcts but in a multi-variate model the volume destroyed in the limbic and heteromodal association areas, including the frontal cortex and in the white matter explained 50% of the variability in MMSE and GDS. The total volume of ischemic lesions explained only 0.1-5% of the variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study confirms that infarcts located in strategic areas have a role in the mechanism of cognitive impairment and brings a key for their quantification. It may be useful for developing neuropathological criteria in multi-infarct and mixed dementias.

  4. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt;

    2000-01-01

    was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...... patients (P analysis showed that vascular grading contributed with independent prognostic value in all patients (P

  5. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.

    Science.gov (United States)

    Garrido-Urbani, Sarah; Jemelin, Stephane; Deffert, Christine; Carnesecchi, Stéphanie; Basset, Olivier; Szyndralewiez, Cédric; Heitz, Freddy; Page, Patrick; Montet, Xavier; Michalik, Liliane; Arbiser, Jack; Rüegg, Curzio; Krause, Karl Heinz; Imhof, Beat A; Imhof, Beat

    2011-02-07

    Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.

  6. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.

    Directory of Open Access Journals (Sweden)

    Sarah Garrido-Urbani

    Full Text Available Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.

  7. Effects of acrylic resin monomers on porcine coronary artery reactivity.

    Science.gov (United States)

    Abebe, Worku; West, Daniel; Rueggeberg, Frederick A; Pashley, David; Mozaffari, Mahmood S

    2016-07-01

    The purpose of the present investigation was to assess the reactivity of porcine coronary arteries under in vitro conditions following their exposure to methyl methacrylate (MMA) and hydroxyethyl methacrylate (HEMA) monomers. Confirming previous studies using rat aortas, both MMA and HEMA induced acute/direct relaxation of coronary ring preparations, which was partly dependent on the endothelium. With prolonged tissue exposure, both monomers caused time- and concentration-dependent inhibition of receptor-mediated contraction of the vascular smooth muscle caused by prostaglandin F2∝ (PGF2∝), with HEMA causing more inhibition than MMA. Hydroxyethyl methacrylate, but not MMA, also produced impairment of non-receptor-mediated contraction of the coronary smooth muscle induced by KCl. On the other hand, neither HEMA nor MMA altered relaxation of the smooth muscle produced by the direct-acting pharmacological agent, sodium nitroprusside (SNP). While exposure to HEMA impaired endothelium-dependent vasorelaxation caused by bradykinin (BK), MMA markedly enhanced this endothelial-mediated response of the arteries. The enhanced endothelial response produced by MMA was linked to nitric oxide (NO) release. In conclusion, with prolonged tissue exposure, MMA causes less pronounced effects/adverse consequences on coronary smooth muscle function relative to the effect of HEMA, while enhancing vasorelaxation associated with release of NO from the endothelium. Accordingly, MMA-containing resin materials appear to be safer for human applications than materials containing HEMA.

  8. Reactive Systems

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand

    A reactive system comprises networks of computing components, achieving their goals through interaction among themselves and their environment. Thus even relatively small systems may exhibit unexpectedly complex behaviours. As moreover reactive systems are often used in safety critical systems......, the need for mathematically based formal methodology is increasingly important. There are many books that look at particular methodologies for such systems. This book offers a more balanced introduction for graduate students and describes the various approaches, their strengths and weaknesses, and when...... they are best used. Milner's CCS and its operational semantics are introduced, together with the notions of behavioural equivalences based on bisimulation techniques and with recursive extensions of Hennessy-Milner logic. In the second part of the book, the presented theories are extended to take timing issues...

  9. [The effects of microgravity on blood vessels and vascular endothelial cells].

    Science.gov (United States)

    Tang, Na-Ping; Li, Hua; Qiu, Yun-Liang; Zhou, Guo-Mina; Wang, Yan; Ma, Jing; Mei, Qi-Bing

    2014-10-01

    The dysfunction of vascular system is one of the main causes of orthostatic intolerance induced by microgravity. Vascular endothelial cell is a single layer on the inner wall of the blood vessel and is the important component of the blood vessel wall. Vascular endothelial cell plays a pivotal role in the regulation of vascular functions, such as serving as a permeability barrier, regulating vasoconstriction and vasodilatation. Recent studies have demonstrated that microgravity may have different effects on vascular sys- tem and vascular endothelial cells in different parts of the body, such as increasing vasoconstrictor reactivity and decreasing vasodilator reactivity of cerebral arteries, decreasing vasoconstrictor and vasodilator reactivity of carotid and abdominal aortic arteries, decreasing vasoconstrictor reactivity and increasing vasodilator reactivity of pulmonary arteries, decreasing vasoconstrictor reactivity of mesenteric arteries and veins and lower extremity arteries. In addition, microgravity can promote the growth of vascular endothelial cells in the large vessels and inhibit the growth of microvascular endothelial cells. This paper summarized the research progress in the effects of microgravity on blood vessels and vascular endothelial cells.

  10. Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults.

    Science.gov (United States)

    Pollack, Rena M; Barzilai, Nir; Anghel, Valentin; Kulkarni, Ameya S; Golden, Aaron; O'Broin, Pilib; Sinclair, David A; Bonkowski, Michael S; Coleville, Alexander J; Powell, Danielle; Kim, Sharon; Moaddel, Ruin; Stein, Daniel; Zhang, Kehao; Hawkins, Meredith; Crandall, Jill P

    2017-03-16

    Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive. In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry. Skeletal muscle samples were obtained for gene expression using RNA-Seq analysis and to assess mitochondrial morphology. There were no changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile following resveratrol treatment. Fasting reactive hyperemia index improved with resveratrol (2.02 ± 0.2 vs 1.76 ± 0.02, p = .002). RNA-Seq analysis yielded 140 differentially expressed transcripts (corrected p-value ≤ .05), predominantly associated with mitochondrial genes and noncoding RNA. Ingenuity Pathway Analysis confirmed that mitochondrial dysfunction (p = 2.77 × 10-12) and oxidative phosphorylation (p = 1.41 × 10-11) were the most significantly perturbed pathways. Mitochondrial number, but not size, was increased. Resveratrol treatment of older adults with impaired glucose regulation may have beneficial effects on vascular function, but not glucose metabolism or insulin sensitivity. Changes in gene expression suggest effects similar to those observed with caloric restriction, which has been shown to increase life and health span in animal models, although its significance for humans is uncertain. Future human studies should address the appropriate dose range and low bioavailability of resveratrol.

  11. Proinflammatory Stimulation of Toll-Like Receptor 9 with High Dose CpG ODN 1826 Impairs Endothelial Regeneration and Promotes Atherosclerosis in Mice.

    Directory of Open Access Journals (Sweden)

    Alexander O Krogmann

    Full Text Available Toll-like receptors (TLR of the innate immune system have been closely linked with the development of atherosclerotic lesions. TLR9 is activated by unmethylated CpG motifs within ssDNA, but also by CpG motifs in nucleic acids released during vascular apoptosis and necrosis. The role of TLR9 in vascular disease remains controversial and we sought to investigate the effects of a proinflammatory TLR9 stimulation in mice.TLR9-stimulation with high dose CpG ODN at concentrations between 6.25 nM to 30 nM induced a significant proinflammatory cytokine response in mice. This was associated with impaired reendothelialization upon acute denudation of the carotid and increased numbers of circulating endothelial microparticles, as a marker for amplified endothelial damage. Chronic TLR9 agonism in apolipoprotein E-deficient (ApoE-/- mice fed a cholesterol-rich diet increased aortic production of reactive oxygen species, the number of circulating endothelial microparticles, circulating sca-1/flk-1 positive cells, and most importantly augmented atherosclerotic plaque formation when compared to vehicle treated animals. Importantly, high concentrations of CpG ODN are required for these proatherogenic effects.Systemic stimulation of TLR9 with high dose CpG ODN impaired reendothelialization upon acute vascular injury and increased atherosclerotic plaque development in ApoE-/- mice. Further studies are necessary to fully decipher the contradictory finding of TLR9 agonism in vascular biology.

  12. Cutaneous vascular control in the arms of women with postmastectomy oedema.

    Science.gov (United States)

    Stanton, A W; Levick, J R; Mortimer, P S

    1996-05-01

    The control of forearm skin blood flow was examined in the swollen arms of twelve women with oedema caused by breast cancer treatment. The swollen arm was compared with the opposite unaffected (control) arm. Using laser Doppler flux (LDF) and continuous finger blood pressure (BP) measurements, vascular control was tested by applying a range of provocations previously shown to alter cutaneous vascular resistance (CVR) in healthy subjects. The tests and the accepted mechanism were: post-ischaemic hyperaemia (locally mediated vasodilatation), inspiratory gasp and cool reflex (both sympathetically mediated vasoconstriction), arm dependency (locally mediated vasoconstriction), and core heat load (sympathetically mediated vasodilatation). CVR was calculated as BP/(LDF-biological zero). Three differences between the control and swollen arms were identified. (i) The laser Doppler biological zero signal was significantly higher on the swollen side (P = 0.005, Student's paired t test). (ii) Baseline LDF was significantly lower on the swollen side (P = 0.002), and apparent CVR correspondingly higher. (iii) Cumulative reactive hyperaemia (area under the LDF curve above baseline) was significantly less on the swollen side (P = 0.03), although peak flux was not significantly different. Inspiratory gasp, cool reflex, arm dependency and core heat load produced changes of similar magnitude in both arms. It appears that sympathetic neural control and local vasoconstrictor control in arm dependency are normal in arm lymphoedema but that locally mediated vasodilator control is impaired. In addition, baseline skin blood flow may be reduced in this condition. The results provide no support for impairment of vascular tone as a contributory factor to the oedematous state.

  13. Visual Impairment

    Science.gov (United States)

    ... What Causes Visual Impairment? People rarely lose their eyesight during their teen years. When they do, it's ... inflammation in the eye. It's often found in poor rural countries that have overcrowded living conditions and ...

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

    Science.gov (United States)

    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

  15. Correlation between serum leptin, adiponectin, C -reactive protein and degree of gestational impaired glucose tolerance%血清瘦素、脂联素和C反应蛋白与妊娠期糖耐量异常程度的相关性

    Institute of Scientific and Technical Information of China (English)

    李苑艳; 李喜梅; 张常乐

    2012-01-01

    目的:探讨血清瘦素、脂联素和C反应蛋白与妊娠期糖耐量异常的相关性.方法:选取2010年2~6月90例孕妇为研究对象,将其分为妊娠期糖尿病组30例、糖耐量异常组30例和正常孕妇组30例,将3组孕妇的血清瘦素、脂联素和C反应蛋白水平及孕妇、新生儿不良情况发生率进行比较.结果:妊娠期糖尿病组与糖耐量异常组血清瘦素、C反应蛋白水平、孕妇及新生儿的不良情况发生率均高于正常组,而脂联素水平低于正常组;而妊娠期糖尿病组与糖耐量异常组在这些评估项目也存在一定的差异(P<0.05).结论:血清瘦素、脂联素和C反应蛋白水平与妊娠期糖耐量异常程度有较大的相关性,可引起孕产妇及新生儿的不良情况发生.%Objective: To explore the correlation between serum leptin, adiponectin, C - reactive protein and degree of gestational impaired glucose tolerance. Methods; Ninety pregnant women were selected from February to June in 2010, then they were divided into gestational diabetes mellitus (GDM) group, gestational impaired glucose tolerance group, and normal pregnant women group, 30 cases in each group. The serum levels of leptin, adiponectin, and C - reactive protein, adverse reactions of pregnant women and neonates in the three groups were compared. Results; The serum levels of leptin and C - reactive protein, the incidences of adverse reactions of pregnant women and neonates in GDM group and gestational impaired glucose tolerance group were higher than those in normal pregnant women group, but the serum levels of adiponectin in GDM group and geslational impaired glucose tolerance group were lower than that in normal pregnant women group; there was significant difference in the indexes above - mentioned between GDM group and gestational impaired glucose tolerance group (P < 0. 05) . Conclusion; There was high correlation between serum leptin, adiponectin, C - reactive protein levels and

  16. The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

    2010-10-01

    The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

  17. 行为认知疗法对血管性认知功能损害的缺血性脑卒中患者的影响%Influence of Behavior and Cognitive Therapy on Ischemic Strock Inpatients with Mild Vascular Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    张敏; 董津平; 赵爱焕; 孟丽娜; 王姗姗

    2011-01-01

    Objective To investigate the incidence of mild vascular cognitive impairment(VCI) in inpa-tients with ischemic stroke, and to observe the influence of behavior and cognitive therapy to cognitive state. Methods Of 422 inpatients in the Neurology Department of No. 254 Hospital of PLA from July to December 2010,167 were detected with vascular cognitive impairment no dementia(VCI-ND) using clinical dementia rating(CDR). The VCI-ND patients were divided randomly into treatment group(N = 84) and control group (N=83). The patients in both groups were treated with the routine nursing. In addition,the treatment group was treated with behavior and cognitive therapy. The improvements in cognition function were compared using Montreal cognitive assessment (MoCA) two weeks later. Results The incidence of VCI-ND was 39. 57% in ischemic stroke inpatients. The cognitive scores were significantly improved in treatment group (P<0. 05) ,but no improvement was observed in the control group(P>0. 05). Conclusion The incidence of VCI-ND is high, which strongly influences the prognosis of patients. Thus,more attention should be attached to the clinical nursing procedures. The cognitive function can be improved using multiple nursing strategy,including psychological nursing.%目的 了解缺血性脑卒中住院患者血管性认知功能损害的发生率,并探讨行为认知疗法对患者认知功能状态的影响.方法 选择2010年7-12月在解放军第254医院神经内科住院治疗的缺血性脑卒中患者共422例,经临床痴呆评定量表(clinical dementia rating,CDR)检出血管性认知功能损害非痴呆(vascular cognitive impairment no dementia,VCI-ND)患者167例,采用随机数字表法将其分为观察组(N=84)和对照组(N=83).对照组患者采用常规护理,观察组患者在常规治疗基础上加用行为、认知疗法等多项护理措施.2周后采用蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)比较两组患者认知

  18. 规范化康复程序对脑卒中血管性认知障碍患者功能结局的影响%The effect of standardized rehabilitation program on functional rehabilita-tion of stroke survivors with vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    韩华

    2016-01-01

    目的:研究规范化康复程序对脑卒中血管性认知障碍患者功能结局的影响。方法选取2013年2月-2014年2月在康复科治疗的脑卒中血管性认知障碍患者63例作为研究对象,根据随机数字表法分为对照组31例和康复治疗组32例。对照组常规治疗,康复治疗组在对照组治疗基础上采用规范化康复程序。结果治疗后2组患者 Fugl-Meyer 评分较治疗前均升高;治疗后康复治疗组 Fugl-Meyer 评分高于对照组(t =3.124,P =0.002)。治疗后,2组患者简易精神量表(MMSE)评分、蒙特利埃认知评估量表(MoCA )评分均增加;康复治疗组患者 MMSE 评分、MoCA评分均高于对照组。治疗后,2组患者 ADL 评分较治疗前均降低;康复治疗组患者 ADL 评分低于对照组(t =3.490,P =0.000)。结论规范化康复程序可显著改善脑卒中血管性认知障碍患者的认知功能,提高患者日常生活能力,增强患者运动功能,改善患者预后。%Objective To study the effect of standardized rehabilitation program on functional outcomes of stroke survivors with vascular cognitive impairment . Methods Sixty-three stroke survivors with vascular cognitive impairment treated in our hospital between February 2013 and 2014 were selected and divided into a rehabilitation group (n = 32) and a control group (n = 31) according to a random number table .Both groups were given routine drug treatment ,while the rehabilitation group was additionally provided with standardized rehabilitation program . Both groups were evaluated before and after the treatment using the Fugl-Meyer assessment scale ,Monterey cognitive assessment scale (MoCA) ,mini-mental state examination (MMSE) and activity of daily living scale (ADL) .Results After the treatment ,the Fugl-Meyer ,MMSE and MoCA scores of the two groups were significantly higher than before treatment ,and the increase of the rehabilitation group

  19. 养血清脑颗粒联合胞二磷胆碱对轻度血管性认知障碍的疗效观察%Efficacy of Yangxueqingnao granule combined with citicoline on patients with mild vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    蔡鸣凡

    2014-01-01

    Objective To observe and discuss the clinical efficacy of Yangxueqingnao granule plus citcoline on patients with mild vascular cognitive impairment.Methods A total of 104 cases with mild vascular cognitive impairment were selected as study objects and were applied with Yangxueqingnao granule and citicoline tablet for 3 months,after which MMSE,ADAS-Cog,MoCA score was introduced into neuropsychological evaluation on patients;meanwhile,patientsclinical safety was observed.Results There was no significant difference in MMSE score between post and pretreatment(P >0.05),MoCA score after treatment was significantly higher than that of pretreatment(P <0.05),and ADAS-Cog score was significantly lower than that of pretreatment(P <0.05).During MoCA evaluation,visual spatial &executive ability,memory,language,delayed memory scores of patients after treatment were significantly higher than those before treatment (P <0.05).During ADAS-Cog evaluation,word recall,word recognition,recall test instruction,oral language,word finding difficulties,language compre-hension ability scores of patients after treatment were significantly lower than those before treatment(P <0.05).Conclusion Yangxueqing-nao granule combined with citicoline tablet can significantly improve the cognitive function of patients with mild vascular cognitive impair-ment,especially works well in memory,delayed recall test,executive function,language an