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Sample records for systemic microvascular dysfunction

  1. Cardiovascular deconditioning: From autonomic nervous system to microvascular dysfunctions.

    Science.gov (United States)

    Coupé, M; Fortrat, J O; Larina, I; Gauquelin-Koch, G; Gharib, C; Custaud, M A

    2009-10-01

    Weightlessness induces an acute syndrome called the cardiovascular deconditioning, associating orthostatic intolerance with syncope, increase in resting heart rate and decrease in physical capability. Orthostatic intolerance occurs after short term and long term head down bed rest and after long term space flight. Both head down bed rest and space flight induce a significant decrease of the spontaneous baroreflex sensitivity. However, spontaneous baroreflex sensitivity only characterizes the cardiac baroreflex loop. To go further with the analysis of cardiovascular deconditioning we were interested in the microcirculation. As the endothelium plays a crucial role in the regulation of vascular homeostasis and local blood flow, we hypothesized that endothelial dysfunction is associated with bed rest induced changes. We investigated endothelial properties before and after 56 days of bed rest in 8 women of control group and in 8 women who regularly performed physical exercise as countermeasure. Our study shows that prolonged bed rest causes impairment of endothelium-dependent functions at the microcirculation level, along with an increase in circulating endothelial cells. Endothelium should be a target for countermeasures during periods of prolonged bed rest or exposure to weightlessness.

  2. Treatment of Angina and Microvascular Coronary Dysfunction

    Science.gov (United States)

    Samim, Arang; Nugent, Lynn; Mehta, Puja K.; Shufelt, Chrisandra; Merz, C. Noel Bairey

    2014-01-01

    Opinion statement Microvascular coronary dysfunction (MCD) is an increasingly recognized cause of cardiac ischemia and angina, more commonly diagnosed in women. Patients with MCD present with the triad of persistent chest pain, ischemic changes on stress testing, and no obstructive coronary artery disease (CAD) on cardiac catheterization. Data from National Heart, Lung and Blood Institute (NHLBI)-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study has shown that the diagnosis of MCD is not benign, with a 2.5% annual risk of adverse cardiac events including myocardial infarction, stroke, congestive heart failure, or death. The gold standard diagnostic test for MCD is an invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test the endothelial dependent and independent, microvascular and macrovascular coronary function. The CRT allows for diagnostic and treatment options as well as further risk stratifying patients for future cardiovascular events. Treatment of angina and MCD should be aimed at ischemia disease management to reduce risk of adverse cardiac events, ameliorating symptoms to improve quality of life, and to decrease the morbidity from unnecessary and repeated cardiac catheterization in patients with open coronary arteries. A comprehensive treatment approach aimed at risk factor managment, including lifestyle counseling regarding smoking cessation, nutrition and physical activity should be initiated. Current pharmacotherapy for MCD can include the treatment of microvascular endothelial dysfunction (statins, angiotensin-converting enzyme inhibitor, low dose aspirin), as well as treatment for angina and myocardial ischemia (beta blockers, calcium channel blockers, nitrates, ranolazine). Additional symptom management techniques can include tri-cyclic medication, enhanced external counterpulsation, autogenic training, and spinal cord stimulation. While our current therapies are effective in the treatment

  3. Association of Microvascular Dysfunction With Late-Life Depression

    DEFF Research Database (Denmark)

    van Agtmaal, Marnix J M; Houben, Alfons J H M; Pouwer, Frans

    2017-01-01

    Importance: The etiologic factors of late-life depression are still poorly understood. Recent evidence suggests that microvascular dysfunction is associated with depression, which may have implications for prevention and treatment. However, this association has not been systematically reviewed....... Objective: To examine the associations of peripheral and cerebral microvascular dysfunction with late-life depression. Data Sources: A systematic literature search was conducted in MEDLINE and EMBASE for and longitudinal studies published since inception to October 16, 2016, that assessed the associations...... between microvascular dysfunction and depression. Study Selection: Three independent researchers performed the study selection based on consensus. Inclusion criteria were a study population 40 years of age or older, a validated method of detecting depression, and validated measures of microvascular...

  4. Invasive assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy: the index of microvascular resistance

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    Gutiérrez-Barrios, Alejandro, E-mail: aleklos@hotmail.com [Cardiology Department, Jerez Hospital, Jerez (Spain); Camacho-Jurado, Francisco [Cardiology Department, Punta Europa Hospital, Algeciras (Spain); Díaz-Retamino, Enrique; Gamaza-Chulián, Sergio; Agarrado-Luna, Antonio; Oneto-Otero, Jesús; Del Rio-Lechuga, Ana; Benezet-Mazuecos, Javier [Cardiology Department, Jerez Hospital, Jerez (Spain)

    2015-10-15

    Summary: We present a review of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and an interesting case of a symptomatic familial HCM patient with inducible ischemia by single photon emission computed tomography. Coronary angiography revealed normal epicardial arteries. Pressure wire measurements of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) demonstrated a significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR. The measurement of IMR, a novel marker of microcirculatory dysfunction, provides novel insights into the pathophysiology of this condition. - Highlights: • Microvascular dysfunction is a common feature in hypertrophic cardiomyopathy (HCM) and represents a strong predictor of unfavorable outcome and cardiovascular mortality. • The index of microvascular resistance (IMR) is a new method for invasively assessing the state of the coronary microcirculation using a single pressure-temperature sensor-tipped coronary wire. • However assessment of IMR in HCM has not been previously reported. We report a case in which microvascular dysfunction is assessed by IMR. This index may be useful in future researches of HCM.

  5. Reversible microvascular dysfunction coupled with persistent myocardial dysfunction: implications for post‐infarct left ventricular remodelling

    Science.gov (United States)

    Galiuto, Leonarda; Gabrielli, Francesca A; Lombardo, Antonella; Torre, Giuseppe La; Scarà, Antonio; Rebuzzi, Antonio G; Crea, Filippo

    2007-01-01

    Background Recent studies have shown that microvascular dysfunction after myocardial infarction is a dynamic phenomenon. Aims To evaluate the implications of dynamic changes in microvascular dysfunction on contractile recovery and left ventricular remodelling, and to identify the ideal timing of assessment of such microvascular dysfunction. Methods and results In 39 patients with a first myocardial infarction who underwent successful percutaneous coronary intervention, microvascular dysfunction was studied by myocardial contrast echocardiography (MCE) at 24 h, 1 week and 3 months after the procedure. Real‐time MCE was performed by contrast pulse sequencing and intravenous Sonovue. 14 patients exhibited left ventricular remodelling at 3 months (>20% increase in left ventricular end‐diastolic volume, group B), whereas 25 did not (group A). Microvascular dysfunction was similar in the two groups at 24 h and improved in group A only, being significantly better than that of group B at 1 week (p<0.05) and 3 months (p<0.005). Improvement in microvascular dysfunction was not associated with improvement in wall motion in the same segments. With multivariate analysis including all echocardiographic variables, microvascular dysfunction at 1 week was found to be the only independent predictor of left ventricular remodelling (p<0.01). With a cut‐off value of 1.4, 1‐week microvascular dysfunction predicts left ventricular remodelling with sensitivity and specificity of 73%. Conclusions Improvement in microvascular dysfunction occurs early after myocardial infarction, although it is not associated with a parallel improvement in wall motion but is beneficial in preventing left ventricular remodelling. Accordingly, 1‐week microvascular dysfunction is a powerful and independent predictor of left ventricular remodelling. PMID:16980514

  6. Treatment strategies in coronary microvascular dysfunction

    DEFF Research Database (Denmark)

    Suhrs, Hannah E; Michelsen, Marie M; Prescott, Eva

    2017-01-01

    . No restrictions were made regarding the study design (randomized, placebo-controlled/ randomized with active comparators/ non-randomized with or without a control group), the cardiac condition studied or the coronary microvascular function at baseline. An electronic database search yielded 4,485 records of which...... 80 studies met our inclusion criteria. Included studies were sorted according to intervention and study design. Studies were small and heterogeneous in methodology and only few were placebo controlled. Although some treatments looked promising, we found that no specific treatment was sufficiently...... well-documented to be recommended in any patient groups. There is a need for larger well-designed clinical trials and we suggest that future studies stratify study populations according to pathogenic mechanisms, thereby investigating whether an individualized treatment approach would be more successful...

  7. ABCD1 dysfunction alters white matter microvascular perfusion.

    Science.gov (United States)

    Lauer, Arne; Da, Xiao; Hansen, Mikkel Bo; Boulouis, Gregoire; Ou, Yangming; Cai, Xuezhu; Liberato Celso Pedrotti, Afonso; Kalpathy-Cramer, Jayashree; Caruso, Paul; Hayden, Douglas L; Rost, Natalia; Mouridsen, Kim; Eichler, Florian S; Rosen, Bruce; Musolino, Patricia L

    2017-12-01

    Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability of the blood-brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic resonance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased capillary flow heterogeneity in asymptomatic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease. In subjects with ongoing inflammatory demyelination we observed a sequence of increased capillary flow heterogeneity followed by blood-brain barrier permeability changes in the perilesional white matter, which predicts lesion progression. These white matter microvascular alterations normalize within 1 year after treatment with haematopoietic stem cell transplantation. For the first time in vivo, our studies unveil a model to assess how ABCD1 alters white matter microvascular function and explores its potential as an earlier biomarker for monitoring disease progression and response to treatment. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  8. ABCD1 dysfunction alters white matter microvascular perfusion

    DEFF Research Database (Denmark)

    Lauer, Arne; Da, Xiao; Hansen, Mikkel Bo

    2017-01-01

    Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability...... of the blood–brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic reson- ance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased...... capillary flow heterogeneity in asymptom- atic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease. In subjects with ongoing inflammatory demyelination we observed a sequence of increased capillary flow hetero...

  9. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

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    Maria Giovanna Scioli

    Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

  10. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

    Science.gov (United States)

    Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

    2015-01-01

    Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and pharmacological

  11. [Recent advances on pericytes in microvascular dysfunction and traditional Chinese medicine prevention].

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    Liu, Lei; Liu, Jian-Xun; Guo, Hao; Ren, Jian-Xun

    2017-08-01

    Pericytesis a kind of widespread vascular mural cells embedded within the vascular basement membrane of blood microvessels, constituting the barrier of capillaries and tissue spaces together with endothelial cells. Pericytes communicate with microvascular endothelial cells through cell connections or paracrine signals, playing an important role in important physiological processes such as blood flow, vascular permeability and vascular formation. Pericytes dysfunction may participate in some microvascular dysfunction, and also mediate pathological repair process, therefore pericytes attracted more and more attention. Traditional Chinese medicine suggests that microvascular dysfunction belongs to the collaterals disease; Qi stagnation and blood stasis in collaterals result in function imbalance of internal organs. Traditional Chinese medicine (TCM) has shown effects on pericytes in microvascular dysfunction, for example qi reinforcing blood-circulation activating medicines can reduce the damage of retinal pericytes in diabetic retinopathy. However, there are some limitations of research fields, inaccuracy of research techniques and methods, and lack of mechanism elaboration depth in the study of microvascular lesion pericytes. This paper reviewed the biological characteristics of pericytes and pericytes in microvascular dysfunction, as well as the intervention study of TCM on pericytes. The article aims to provide reference for the research of pericytes in microvascular dysfunction and the TCM study on pericytes. Copyright© by the Chinese Pharmaceutical Association.

  12. Takotsubo Cardiomyopathy: One More Angiographic Evidence of Microvascular Dysfunction

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    Marco Loffi

    2018-01-01

    Full Text Available Background. Takotsubo cardiomyopathy (TC aetiology has not been completely understood yet. One proposed pathogenic mechanism was coronary microvascular dysfunction (MVD. This study compared coronary flow and myocardial perfusion in patients with TC, microvascular angina (MVA, and a control group (CG. Methods. Out of 42 consecutive patients presented to our centre with TC from 2013 to 2017; we retrospectively selected 27 patients. We compared them with a sex- and age-matched group of 27 MVA cases and 27 patients with normal coronary arteries (CG. The flow was evaluated in the three coronary arteries as TIMI flow and TIMI frame count (TFC. Myocardial perfusion was studied with Blush-Score and Quantitative Blush Evaluator (QuBE. Results. TFC, in TC, revealed flow impairment in the three arteries compared to the CG (left anterior descending artery (LAD: 22±8, 15±4; p=0.001 (right coronary artery: 12±4, 10±3; p=0,025 (left circumflex: 14±4, CG 11±3; p=0,006. QuBE showed myocardial perfusion impairment in the LAD territory in TC comparing with both the CG (8,9 (7,2–11,5 versus 11,4 (10–15,7; p=0,008 and the MVA group (8,9 (7,2–11,5 versus 13,5 (10–16; p=0,006. Conclusions. Our study confirmed that coronary flow is impaired in TC, reflecting a MVD. Myocardial perfusion defect was detected only in the LAD area.

  13. Microvascular Injury in Ketamine-Induced Bladder Dysfunction.

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    Chih-Chieh Lin

    Full Text Available The pathogenesis of ketamine-induced cystitis (KC remains unclear. In this study, bladder microvascular injury was investigated as a possible contributing mechanism. A total of 36 KC patients with exposure to ketamine for more than 6 months, and 9 control subjects, were prospectively recruited. All participants completed questionnaires, including the O'Leary-Sant interstitial cystitis symptom index (ICSI and the interstitial cystitis problem index (ICPI. All KC patients received a urodynamic study and radiological exams. Bladder tissues were obtained from cystoscopic biopsies in the control group and after hydrodistention in the KC group. Double-immunofluorescence staining of N-methyl-d-aspartate receptor subunit 1 (NMDAR1 and the endothelial marker, cluster of differentiation 31 (CD31, was performed to reveal the existence of NMDAR1 on the endothelium. Electron microscopy (EM was applied to assess the microvascular change in the urinary bladder and to measure the thickening of the basement membrane (BM. A proximity ligation assay (PLA was used to quantify the co-localization of the endothelial CD31 receptor and the mesenchymal marker [fibroblast-specific protein 1 (FSP-1]. The Mann-Whitney U test and Spearman's correlation coefficient were used for statistical analysis. The mean ICSI [14.38 (± 4.16] and ICPI [12.67 (± 3.54] scores of the KC group were significantly higher than those (0 and 0, respectively of the control group (both p < 0.001. The KC patients had decreasing cystometric bladder capacity (CBC with a mean volume of 65.38 (± 48.67 mL. NMDAR1 was expressed on endothelial cells in both groups under immunofluorescence staining. Moreover, KC patients had significant BM duplication of microvessels in the mucosa of the urinary bladder under EM. The co-expression of the endothelial marker CD31 and mesenchymal marker FSP1 was significantly stained and calculated under PLA. In conclusion, microvascular injury and mesenchymal phenotypic

  14. Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults.

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    Seliger, Stephen L; Salimi, Shabnam; Pierre, Valerie; Giffuni, Jamie; Katzel, Leslie; Parsa, Afshin

    2016-07-13

    Impairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria. We conducted a cross-sectional study among older hypertensive male veterans with stage 1-4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser-Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders. Among 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m(2); 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (β= - 0.42, p = 0.009 and β= -0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD. Microvascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD.

  15. Targeting the dominant mechanism of coronary microvascular dysfunction with intracoronary physiology tests

    NARCIS (Netherlands)

    Mejia-Renteria, H.; Hoeven, N. van der; Hoef, T.P. van de; Heemelaar, J.; Ryan, N.; Lerman, A.; Royen, N. van; Escaned, J.

    2017-01-01

    The coronary microcirculation plays a key role in modulating blood supply to the myocardium. Several factors like myocardial oxygen demands, endothelial and neurogenic conditions determine its function. Although there is available evidence supporting microvascular dysfunction as an important cause

  16. Microvascular dysfunction in nonfailing arrhythmogenic right ventricular cardiomyopathy

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    Paul, Matthias [University Hospital Muenster, Department of Cardiology and Angiology, Muenster (Germany); University Hospital Muenster, Institute for Genetics of Heart Diseases, Muenster (Germany); Rahbar, Kambiz; Kies, Peter; Schober, Otmar [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Gerss, Joachim [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Schaefers, Klaus; Schaefers, Michael [University of Muenster, European Institute for Molecular Imaging - EIMI, Muenster (Germany); Breithardt, Guenter [University Hospital Muenster, Department of Cardiology and Angiology, Muenster (Germany); Schulze-Bahr, Eric [University Hospital Muenster, Institute for Genetics of Heart Diseases, Muenster (Germany); Wichter, Thomas [Marienhospital Osnabrueck, Department of Cardiology, Niels-Stensen-Kliniken, Osnabrueck (Germany)

    2012-03-15

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a nonischaemic cardiomyopathy and leading cause of sudden death in the young. It has been shown that microvascular dysfunction reflected by an impaired myocardial blood flow (MBF) response to stress is present in patients with other forms of nonischaemic cardiomyopathy, e.g. dilated cardiomyopathy, and that the reduced MBF may be related to a poor prognosis. Therefore, we quantified MBF, coronary flow reserve and coronary vascular resistance in patients with nonfailing ARVC using H{sub 2}{sup 15} O and PET. In ten male patients with ARVC (mean age 49 {+-} 14 years), MBF was quantified at rest and during adenosine-induced hyperaemia using H{sub 2}{sup 15} O PET. Results were compared with those obtained in 20 age-matched healthy male control subjects (mean age 46 {+-} 14 years). Resting MBF was not significantly different between patients with ARVC and controls (MBF{sub rest} 1.19 {+-} 0.29 vs. 1.12 {+-} 0.20 ml/min/ml). However, hyperaemic MBF was significantly lower in patients with ARVC than in controls (2.60 {+-} 0.96 vs. 3.68 {+-} 0.84 ml/min/ml; p = 0.005). Consequently, patients with ARVC had a significantly lower coronary flow reserve than control subjects (2.41 {+-} 1.34 vs. 3.39 {+-} 0.93; p = 0.030). In addition, hyperaemic coronary vascular resistance was increased in patients with ARVC (36.79 {+-} 12.91 vs. 26.31 {+-} 6.49 mmHg x ml{sup -1} x min x ml; p = 0.007), but was found to be unchanged at rest. In this small well-characterized cohort of patients with nonfailing ARVC, we found a significantly reduced hyperaemic MBF and increased coronary vascular resistance. Further studies are necessary to corroborate this potential new functional aspect of the pathophysiological mechanisms underlying ARVC. (orig.)

  17. Microvascular coronary dysfunction and ischemic heart disease: where are we in 2014?

    Science.gov (United States)

    Petersen, John W; Pepine, Carl J

    2015-02-01

    Many patients with angina and signs of myocardial ischemia on stress testing have no significant obstructive epicardial coronary disease. There are many potential coronary and non-coronary mechanisms for ischemia without obstructive epicardial coronary disease, and prominent among these is coronary microvascular and/or endothelial dysfunction. Patients with coronary microvascular and/or endothelial dysfunction are often at increased risk of adverse cardiovascular events, including ischemic events and heart failure despite preserved ventricular systolic function. In this article, we will review the diagnosis and treatment of coronary microvascular and endothelial dysfunction, discuss their potential contribution to heart failure with preserved ejection fraction, and highlight recent advances in the evaluation of atherosclerotic morphology in these patients, many of whom have non-obstructive epicardial disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction

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    Qiu, Gui-Zhen [Department of Health, Linyi People' s Hospital, Shandong University, Shandong (China); Tian, Wei [Department of Nursing, Linyi Oncosurgical Hospital, Shandong (China); Fu, Hai-Tao [Department of Ophthalmology, Linyi People' s Hospital, Shandong University, Shandong (China); Li, Chao-Peng, E-mail: lcpcn@163.com [Eye Institute of Xuzhou, Jiangsu (China); Liu, Ban, E-mail: liuban@126.com [Department of Cardiology, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai (China)

    2016-02-26

    Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. - Highlights: • LncRNA-MEG3 level is down-regulated upon diabetic stress. • MEG3 knockdown aggravates retinal vascular dysfunction in vivo. • MEG3 regulates retinal endothelial cell function in vitro. • MEG3 regulates endothelial cell function through PI3k/Akt signaling.

  19. Diagnosis of coronary microvascular dysfunction – Present status

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    S.R. Mittal

    2015-11-01

    Full Text Available Definite clinical diagnosis of microvascular angina is not possible with the existing knowledge. Resting electrocardiogram may be normal, and exercise electrocardiogram may be unremarkable. Echocardiography usually does not show regional wall motion abnormalities. Transthoracic Doppler echocardiography can satisfactorily evaluate only left anterior descending coronary artery and that too in some patients. Radio-isotope imaging can detect only severe localized disease. Noninvasive diagnosis needs high index of suspicion. At present, definite diagnosis is based on documentation of normal epicardial coronaries, coronary flow reserve less than 2.5 on adenosine induced hyperemia, and absence of spasm of epicardial coronaries on acetylcholine provocation. Invasive evaluation is costly, needs sophisticated equipments and expertise. Therapeutic and prognostic implications of various parameters remains to be evaluated. At present invasive evaluation is recommended only for patients with intractable symptoms with unconfirmed diagnosis, requiring repeated hospitalization and evaluation with failure of empirical therapy.

  20. Bench-to-bedside review: microvascular dysfunction in sepsis--hemodynamics, oxygen transport, and nitric oxide.

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    Bateman, Ryon M; Sharpe, Michael D; Ellis, Christopher G

    2003-10-01

    The microcirculation is a complex and integrated system that supplies and distributes oxygen throughout the tissues. The red blood cell (RBC) facilitates convective oxygen transport via co-operative binding with hemoglobin. In the microcirculation oxygen diffuses from the RBC into neighboring tissues, where it is consumed by mitochondria. Evidence suggests that the RBC acts as deliverer of oxygen and 'sensor' of local oxygen gradients. Within vascular beds RBCs are distributed actively by arteriolar tone and passively by rheologic factors, including vessel geometry and RBC deformability. Microvascular oxygen transport is determined by microvascular geometry, hemodynamics, and RBC hemoglobin oxygen saturation. Sepsis causes abnormal microvascular oxygen transport as significant numbers of capillaries stop flowing and the microcirculation fails to compensate for decreased functional capillary density. The resulting maldistribution of RBC flow results in a mismatch of oxygen delivery with oxygen demand that affects both critical oxygen delivery and oxygen extraction ratio. Nitric oxide (NO) maintains microvascular homeostasis by regulating arteriolar tone, RBC deformability, leukocyte and platelet adhesion to endothelial cells, and blood volume. NO also regulates mitochondrial respiration. During sepsis, NO over-production mediates systemic hypotension and microvascular reactivity, and is seemingly protective of microvascular blood flow.

  1. Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia.

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    Stanhewicz, Anna E; Jandu, Sandeep; Santhanam, Lakshmi; Alexander, Lacy M

    2017-08-01

    Women who have had preeclampsia have increased cardiovascular disease risk; however, the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist postpartum. The putative mechanisms mediating this dysfunction include a reduction in NO-dependent dilation and an increased sensitivity to angiotensin II. In this study, we evaluated endothelium-dependent dilation, angiotensin II sensitivity, and the therapeutic effect of angiotensin II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (n=12) and control women who had a healthy pregnancy (n=12). We hypothesized that preeclampsia would have (1) reduced endothelium-dependent dilation, (2) reduced NO-mediated dilation, and (3) increased sensitivity to angiotensin II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in preeclampsia. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (acetylcholine; 10 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME ( N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 µmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50 ; P Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P =0.006). Angiotensin II type I receptor inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in preeclampsia but had no effect in healthy pregnancy. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction postpartum

  2. Uric acid is associated with inflammation, coronary microvascular dysfunction, and adverse outcomes in postmenopausal women

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    Prasad, Megha; Matteson, Eric L.; Herrmann, Joerg; Gulati, Rajiv; Rihal, Charanjit S.; Lerman, Lilach O.; Lerman, Amir

    2016-01-01

    Uric acid is a risk factor for coronary artery disease (CAD) in postmenopausal women but the association with inflammation and coronary microvascular endothelial dysfunction (CED) is not well-defined. The aim of this study was to determine the relationship of serum uric acid (SUA), inflammatory markers and CED. In this prospective cohort study, serum uric acid, hsCRP levels, and neutrophil count were measured in 229 postmenopausal women who underwent diagnostic catheterization, were found to have no obstructive CAD and underwent coronary microvascular function testing, to measure coronary blood flow (CBF) response to intracoronary acetylcholine. The average age was 58 years (IQR 52, 66) years. Hypertension was present in 48%, type 2 diabetes mellitus in 5.6%, and hyperlipidemia in 61.8%. CED was diagnosed in 59% of postmenopausal women. Mean uric acid level was 4.7 ± 1.3 mg/dL. Postmenopausal women with CED had significantly higher SUA compared to patients without CED (4.9 ± 1.3 vs. 4.4 ± 1.3 mg/dL; p=0.02). There was a significant correlation between SUA and % change in CBF to acetylcholine (p=0.009), and this correlation persisted in multivariable analysis. SUA levels were significantly associated with increased neutrophil count (p=0.02) and hsCRP levels (p=0.006) among patients with CED, but not those without CED. Serum uric acid is associated with coronary microvascular endothelial dysfunction in postmenopausal women and may be related to inflammation. These findings link serum uric acid levels to early coronary atherosclerosis in postmenopausal women. PMID:27993955

  3. The association of systemic microvascular changes with lung function and lung density: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bianca Harris

    Full Text Available Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1 (P<0.001 and FEV(1/forced vital capacity (FVC ratio (P = 0.04. Albumin-to-creatinine ratio was inversely associated with FEV(1 (P = 0.002 but not FEV(1/FVC. Myocardial blood flow (n = 126 was associated with lower FEV(1 (P = 0.02, lower FEV(1/FVC (P = 0.001 and greater percentage LAA (P = 0.04. Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.

  4. Altered retinal flicker response indicates microvascular dysfunction in women with preeclampsia.

    Science.gov (United States)

    Brückmann, Andreas; Seeliger, Christin; Lehmann, Thomas; Schleußner, Ekkehard; Schlembach, Dietmar

    2015-10-01

    Flicker-induced dilatation is reduced in patients with cardiovascular risk, and the following arteriolar constriction is reduced with aging, leading to a reduced arteriolar amplitude and, thereby, indicating microvascular endothelial dysfunction. As endothelial dysfunction is associated with preeclampsia, we assessed retinal flicker response during pregnancy and postpartum. Between 2006 and 2013, women were recruited from University Hospital Jena and Prenatal Diagnostic Center Erfurt, Germany, of which 34 women with preeclampsia, 45 women with normal pregnancy, and 22 nonpregnant controls were included in the study. Women with normal pregnancy were matched for age, nulliparity, smoking, previous gestational hypertensive disorders, and family history of cardiovascular disease. Nonpregnant women were age-matched, nulliparous, nonsmoking, without family history of cardiovascular disease. Retinal vessel measurement using Dynamic Vessel Analyzer consisted of 50-seconds baseline acquisition, followed by three 20-second flicker and 80-second relaxation periods. Arteriolar constriction and arteriolar amplitude were reduced during pregnancy (P=0.001 and P=0.008) and postpartum (P=0.018 and P=0.034) in women with preeclampsia, adjusted for age, body mass index, mean arterial pressure, baseline diameter, and family history of cardiovascular disease. Flicker-induced dilatation was unchanged within the groups and throughout the study period. The unchanged flicker-induced dilatation may support a preserved autoregulatory competence of the microvasculature, and the diminished arteriolar amplitude, mainly because of the absence of the arteriolar constriction, indicates a commenced retinal microvascular dysfunction in women with preeclampsia during pregnancy and postpartum. Mechanisms responsible for altered retinal flicker response in preeclampsia need to be clarified in further studies. © 2015 American Heart Association, Inc.

  5. [Advances in animal model and traditional Chinese medicine prevention in coronary microvascular dysfunction].

    Science.gov (United States)

    Li, Lei; Liu, Jian-Xun; Ren, Jian-Xun; Guo, Hao; Lin, Cheng-Ren

    2017-01-01

    Coronary microvascular dysfunction (CMD) is a common mechanism for some heart disease like cardiac X syndrome and no-reflow phenomenon after percutaneous coronary intervention(PCI). With the development of medical imageology, CMD has received increased attention. Animal model of CMD is indispensable tool for the research of pathogenesis and treatment evaluation, therefor choose an appropriate animal model is the first issue to carry out CMD research. Experimental and clinical studies have shown unique effectiveness of traditional Chinese medicine(TCM) in CMD therapy. Clarifying of the TCM therapeutic effect mechanisms and seeking an optimal solution of combination of traditional Chinese and western medicine will be the focus of future research. This paper reviewed the establishment and evaluation of CMD animal model, as well as the intervention study of TCM on CMD. The article aims to provide reference for the basic research of CMD and the TCM experimental study on CMD. Copyright© by the Chinese Pharmaceutical Association.

  6. Effects of Riot Control Training on Systemic Microvascular Reactivity and Capillary Density.

    Science.gov (United States)

    Pereira, Flavio; de Moraes, Roger; Van Bavel, Diogo; De Lorenzo, Andrea; Tibirica, Eduardo

    2018-03-14

    The main aim of the present study is to evaluate the effects of strenuous exercise, related to special military training for riot control, on systemic microvascular endothelial function and skin capillary density. Endothelium-dependent microvascular reactivity was evaluated in the forearm skin of healthy military trainees (age 23.4 ± 2.3 yr; n = 15) using laser speckle contrast imaging coupled with cutaneous acetylcholine (ACh) iontophoresis and post-occlusive reactive hyperemia (PORH). Functional capillary density was assessed using high-resolution, intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using PORH. Microcirculatory tests were performed before and after a 5-wk special military training for riot control. Microvascular endothelium-dependent vasodilatory responses were markedly and significantly reduced after training, compared with values obtained before training. The peak values of microvascular conductance obtained during iontophoresis of ACh or PORH before training (0.84 ± 0.22 and 0.94 ± 0.72 APU/mmHg, respectively) were markedly reduced after training (0.47 ± 0.11 and 0.71 ± 0.14 APU/mmHg; p < 0.0001 and p = 0.0037, respectively). Endothelium-dependent capillary recruitment was significantly reduced after training (before 101 ± 9 and after 95 ± 8 capillaries/mm2; p = 0.0007). The present study showed that a 5-wk strenuous military training, performed in unfavorable climatic conditions, induces marked systemic microvascular dysfunction, mainly characterized by reduced endothelium-dependent microvascular vasodilation and blunted capillary recruitment.

  7. Microvascular dysfunction affects the development and prognosis of sudden idiopathic hearing loss.

    Science.gov (United States)

    Koçak, H E; Filiz Acıpayam, A Ş; Acıpayam, H; Çakıl Erdoğan, B; Alakhras, W M E; Kıral, M N; Keskin, M; Kayhan, F T

    2017-06-01

    The aim of our study is to investigate whether systemic microvascular function affects the development and prognosis of sudden idiopathic hearing loss (SHL). A prospective case-control study. Fifty patients diagnosed with SHL at our hospital between September 2015 and May 2016 were included as the SHL group, and 50 healthy volunteers who came to the hospital for medical screening were included in the control group. Thirty-one patients from the SHL group who responded to treatment and 19 patients who did not respond to treatment were identified according to the Siegel criteria and were grouped. Patients with comorbid disorders were excluded from the study. To determine microvascular function, the videocapillaroscopic examination was conducted from the nailfold, measuring the capillary density (CD) and post-occlusive reactive hyperaemia (PORH) values and statistical analysis was performed between the groups. While CD was an average of 83.1 ± 6 in the SHL group, it was measured as 96.2 ± 10 in the control group. The CD value was significantly lower in the SHL group than the control group (P 0.05) between the group that responded to treatment (83.4 ± 5.5) and the group that did not respond to treatment (82.7 ± 6.9). The PORH value was significantly lower (P < 0.05) in the group that did not respond to treatment (75.2 ± 7.9) than the group that did (83.8 ± 5.6). To our best knowledge, our study is the first study in the literature. Although the role of specific mechanisms in SHL is not entirely understood, the capillaroscopic examination can show the importance of microvascular function in SHL. CD and PORH values were found to be low in SHL patients, and a low PORH value was found to be a factor of poor prognosis. © 2016 John Wiley & Sons Ltd.

  8. Carriers of the hypertrophic cardiomyopathy MYBPC3 mutation are characterized by reduced myocardial efficiency in the absence of hypertrophy and microvascular dysfunction

    NARCIS (Netherlands)

    Timmer, Stefan A. J.; Germans, Tjeerd; Brouwer, Wessel P.; Lubberink, Mark; van der Velden, Jolanda; Wilde, Arthur A. M.; Christiaans, Imke; Lammertsma, Adriaan A.; Knaapen, Paul; van Rossum, Albert C.

    2011-01-01

    Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk

  9. Elevated plasma plasminogen activator inhibitor type-1 is an independent predictor of coronary microvascular dysfunction in hypertension

    International Nuclear Information System (INIS)

    Naya, Masanao; Tsukamoto, Takahiro; Inubushi, Masayuki; Morita, Koichi; Katoh, Chietsugu; Furumoto, Tomoo; Fujii, Satoshi; Tsutsui, Hiroyuki; Tamaki, Nagara

    2007-01-01

    Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is related to cardiovascular events, but its role in subclinical coronary microvascular dysfunction remains unknown. Thus, in the present study it was investigated whether elevated plasma PAI-1 activity is associated with coronary microvascular dysfunction in hypertensive patients. Thirty patients with untreated essential hypertension and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using 15 O-water positron emission tomography. Clinical variables associated with atherosclerosis (low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, homeostasis model assessment (HOMA-IR), and PAI-1 activity) were assessed to determine their involvement in coronary microvascular dysfunction. Adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) were significantly lower in hypertensive patients than in healthy controls (ATP-induced MBF: 2.77±0.82 vs 3.49±0.71 ml·g -1 ·min -1 ; p<0.02 and CFR: 2.95±1.06 vs 4.25±0.69; p<0.001). By univariate analysis, CFR was positively correlated with HDL-cholesterol (r=0.46, p<0.02), and inversely with HOMA-IR (r=-0.39, p<0.05) and PAI-1 activity (r=-0.61, p<0.001). By multivariate analysis, elevated PAI-1 activity remained a significant independent determinant of diminished CFR. Elevated plasma PAI-1 activity was independently associated with coronary microvascular dysfunction, which suggests that plasma PAI-1 activity is an important clue linking hypofibrinolysis to the development of atherosclerosis. (author)

  10. Bench-to-bedside review: Microvascular dysfunction in sepsis –hemodynamics, oxygen transport, and nitric oxide

    Science.gov (United States)

    Bateman, Ryon M; Sharpe, Michael D; Ellis, Christopher G

    2003-01-01

    The microcirculation is a complex and integrated system that supplies and distributes oxygen throughout the tissues. The red blood cell (RBC) facilitates convective oxygen transport via co-operative binding with hemoglobin. In the microcirculation oxygen diffuses from the RBC into neighboring tissues, where it is consumed by mitochondria. Evidence suggests that the RBC acts as deliverer of oxygen and 'sensor' of local oxygen gradients. Within vascular beds RBCs are distributed actively by arteriolar tone and passively by rheologic factors, including vessel geometry and RBC deformability. Microvascular oxygen transport is determined by microvascular geometry, hemodynamics, and RBC hemoglobin oxygen saturation. Sepsis causes abnormal microvascular oxygen transport as significant numbers of capillaries stop flowing and the microcirculation fails to compensate for decreased functional capillary density. The resulting maldistribution of RBC flow results in a mismatch of oxygen delivery with oxygen demand that affects both critical oxygen delivery and oxygen extraction ratio. Nitric oxide (NO) maintains microvascular homeostasis by regulating arteriolar tone, RBC deformability, leukocyte and platelet adhesion to endothelial cells, and blood volume. NO also regulates mitochondrial respiration. During sepsis, NO over-production mediates systemic hypotension and microvascular reactivity, and is seemingly protective of microvascular blood flow. PMID:12974969

  11. Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction

    Science.gov (United States)

    DelloStritto, Daniel J.; Connell, Patrick J.; Dick, Gregory M.; Fancher, Ibra S.; Klarich, Brittany; Fahmy, Joseph N.; Kang, Patrick T.; Chen, Yeong-Renn; Damron, Derek S.; Thodeti, Charles K.

    2016-01-01

    We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791-sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes. PMID:26907473

  12. Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population-based prospective study.

    Science.gov (United States)

    Holm, H; Nägga, K; Nilsson, E D; Ricci, F; Melander, O; Hansson, O; Bachus, E; Magnusson, M; Fedorowski, A

    2017-07-01

    Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults. A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis. Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L -1 vs. Q1, 22-77 pmol L -1 : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L -1 (Q3-Q4, 68-432 pmol L -1 vs. Q1-Q2,4-68 pmol L -1 ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors. Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia. © 2017 The Association for the Publication of the

  13. Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction

    DEFF Research Database (Denmark)

    Michelsen, Marie Mide; Mygind, Naja Dam; Pena, Adam

    2017-01-01

    BACKGROUND: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard...

  14. Coronary microvascular dysfunction and myocardial contractile reserve in women with angina and no obstructive coronary artery disease

    DEFF Research Database (Denmark)

    Michelsen, Marie M; Pena, Adam; Mygind, Naja D

    2018-01-01

    BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically......) was measured in 919 women of whom 26% had CMD (defined as CFVR CMD) was associated with higher age and a higher resting heart rate. Women with CMD had a reduced GLS reserve (P = .005), while we found no association between CFVR and LVEF at rest, GLS at rest...... dysfunction measured by echocardiography at rest. CONCLUSION: The GLS reserve was significantly lower in women with CMD. The mechanisms underlying the association between CMD and GLS reserve warrant further study....

  15. Harnessing systems biology approaches to engineer functional microvascular networks.

    Science.gov (United States)

    Sefcik, Lauren S; Wilson, Jennifer L; Papin, Jason A; Botchwey, Edward A

    2010-06-01

    Microvascular remodeling is a complex process that includes many cell types and molecular signals. Despite a continued growth in the understanding of signaling pathways involved in the formation and maturation of new blood vessels, approximately half of all compounds entering clinical trials will fail, resulting in the loss of much time, money, and resources. Most pro-angiogenic clinical trials to date have focused on increasing neovascularization via the delivery of a single growth factor or gene. Alternatively, a focus on the concerted regulation of whole networks of genes may lead to greater insight into the underlying physiology since the coordinated response is greater than the sum of its parts. Systems biology offers a comprehensive network view of the processes of angiogenesis and arteriogenesis that might enable the prediction of drug targets and whether or not activation of the targets elicits the desired outcome. Systems biology integrates complex biological data from a variety of experimental sources (-omics) and analyzes how the interactions of the system components can give rise to the function and behavior of that system. This review focuses on how systems biology approaches have been applied to microvascular growth and remodeling, and how network analysis tools can be utilized to aid novel pro-angiogenic drug discovery.

  16. The Ubiquitin-Proteasome System and Microvascular Complications of Diabetes

    Directory of Open Access Journals (Sweden)

    Saeed Yadranji Aghdam

    2013-01-01

    Full Text Available The ubiquitin-proteasome system (UPS is the mainstay of protein quality control which regulates cell cycle, differentiation and various signal transduction pathways in eukaryotic cells. The timely and selective degradation of surplus and/or aberrant proteins by the UPS is essential for normal cellular physiology. Any disturbance, delay or exaggeration in the process of selection, sequestration, labeling for degradation and degradation of target proteins by the UPS will compromise cellular and tissue homeostasis. High blood glucose or hyperglycemia caused by diabetes disrupts normal vascular function in several target organs including the retina and kidney resulting in the development of diabetic retinopathy (DR and diabetic nephropathy (DN. We and others have shown that hyperglycemia and oxidative stress modulate UPS activity in the retina and kidney. The majority of studies have focused on the kidney and provided insights into the contribution of dysregulated UPS to microvascular damage in DN. The eye is a unique organ in which a semi-fluid medium, the vitreous humor, separates the neural retina and its anastomosed blood vessels from the semi-solid lens tissue. The complexity of the cellular and molecular components of the eye may require a normal functioning and well tuned UPS for healthy vision. Altered UPS activity may contribute to the development of retinal microvascular complications of diabetes. A better understanding of the molecular nature of the ocular UPS function under normal and diabetic conditions is essential for development of novel strategies targeting its activity. This review will discuss the association of retinal vascular cell UPS activity with microvascular damage in DR with emphasis on alterations of the PA28 subunits of the UPS.

  17. Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach

    Directory of Open Access Journals (Sweden)

    Panazzolo Diogo G

    2012-11-01

    Full Text Available Abstract Background We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. Methods Data from 189 female subjects (34.0±15.5 years, 30.5±7.1 kg/m2, who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA. PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI, waist circumference, systolic and diastolic blood pressure (BP, fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c, triglycerides (TG, insulin, C-reactive protein (CRP, and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV at rest and peak after 1 min of arterial occlusion (RBCVmax, and the time taken to reach RBCVmax (TRBCVmax. Results A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCVmax varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCVmax, but in the opposite way. Principal component 3 was

  18. Cardiorenal disease connection during post-menopause: The protective role of estrogen in uremic toxins induced microvascular dysfunction.

    Science.gov (United States)

    Pei, Jiayi; Harakalova, Magdalena; den Ruijter, Hester; Pasterkamp, Gerard; Duncker, Dirk J; Verhaar, Marianne C; Asselbergs, Folkert W; Cheng, Caroline

    2017-07-01

    Female gender, post-menopause, chronic kidney disease (CKD) and (CKD linked) microvascular disease are important risk factors for developing heart failure with preserved ejection fraction (HFpEF). Enhancing our understanding of the interrelation between these risk factors could greatly benefit the identification of new drug targets for future therapy. This review discusses the evidence for the protective role of estradiol (E 2 ) in CKD-associated microvascular disease and related HFpEF. Elevated circulating levels of uremic toxins (UTs) during CKD may act in synergy with hormonal changes during post-menopause and could lead to coronary microvascular endothelial dysfunction in HFpEF. To elucidate the molecular mechanism involved, published transcriptome datasets of indoxyl sulfate (IS), high inorganic phosphate (HP) or E 2 treated human derived endothelial cells from the NCBI Gene Expression Omnibus database were analyzed. In total, 36 genes overlapped in both IS- and HP-activated gene sets, 188 genes were increased by UTs (HP and/or IS) and decreased by E 2 , and 572 genes were decreased by UTs and increased by E 2 . Based on a comprehensive in silico analysis and literature studies of collected gene sets, we conclude that CKD-accumulated UTs could negatively impact renal and cardiac endothelial homeostasis by triggering extensive inflammatory responses and initiating dysregulation of angiogenesis. E 2 may protect (myo)endothelium by inhibiting UTs-induced inflammation and ameliorating UTs-related uremic bleeding and thrombotic diathesis via restored coagulation capacity and hemostasis in injured vessels. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Acute phase reactant dynamics and incidence of microvascular dysfunctions in type 2 diabetes mellitus

    Science.gov (United States)

    Azenabor, Alfred; Ogbera, Anthonia O.; Adejumo, Ngozi E.; Adejare, Adejimi O.

    2011-01-01

    BACKGROUND: Acute Phase Reactants (APRs) have a wide range of activities that contribute to host defense. The aim of this report was to evaluate the dynamics and magnitude of these proteins in various microvascular complications in diabetes mellitus (DM). We also sought to assess the predictive values of APRs and other clinical variables for microvascular complications in DM. METHODS: This was a case control study carried out in 200 Nigerian subjects with type 2 DM and 100 sex and age matched healthy controls. The studied APRs included C-reactive protein, beta 2 microglobulin, fibrinogen and lipoprotein (a). RESULTS: The mean values of the APRs were significantly higher in type 2 DM compared with the controls and were observed in higher concentrations in those with microvascular complications, except beta 2 microglobulin. Presence of microvascular complications was observed in those with dilated fundus examination (retinopathy), symptom score of 3.0 (neuropathy), urea and creatinine levels above 50mg% and 1.5mg%, respectively, with significant proteinuria (nephropathy). Significant increase in mean ± SEM values of lipoprotein (a) was observed in diabetic retinopathy in comparison with those without complications (25.76 ± 1.13 mg/dl vs. 22.37 ± 0.73 mg/dl, p = 0.005). Elevated C-reactive protein was observed in diabetic neuropathy in comparison with those without complications (11.43 ± 2.33 u/ml vs. 8.30 ± 1.15 u/ml, p = 0.048). Increased beta 2 microglobulin levels were observed in patients with diabetic foot ulcers in comparison with those without complications (3.04 ± 0.51 mg/dl vs. 2.54 ± 0.14 mg/dl, p = 0.049). Circulating levels of Lipoprotein (a) predicted retinopathy in DM with both good and poor long-term glycemic control while duration of DM predicted the occurrence of foot ulcers.. CONCLUSIONS: Increased level of APRs was associated with a number of microvascular complications and may play a role in the pathogenesis. PMID:22973323

  20. Hypertension management and microvascular insulin resistance in diabetes.

    Science.gov (United States)

    Ko, Seung-Hyun; Cao, Wenhong; Liu, Zhenqi

    2010-08-01

    Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to impaired insulin signaling, reduced nitric oxide availability, and vasoconstriction. Conversely, it acts on the type 2 receptors to cause vasodilatation. Because substrate and hormonal exchanges occur in the microvasculature, antihypertensive agents targeted to improve microvascular insulin sensitivity and function may have beneficial effects beyond their capacity to lower blood pressure in patients with diabetes.

  1. The Human Brain Intracerebral Microvascular System: Development, Structure and Function

    Directory of Open Access Journals (Sweden)

    Miguel eMarín-Padilla

    2012-09-01

    Full Text Available The capillary from the meningeal inner pial lamella play a crucial role in the development and structural organization of the cerebral cortex extrinsic and intrinsic microvascular compartments. Only pial capillaries are capable of perforating through the cortex external glial limiting membrane (EGLM to enter into the nervous tissue, although incapable of perforating the membrane to exit the brain. Circulatory dynamics and functional demands determine which capillaries become arterial and which capillaries become venous. The perforation of the cortex EGLM by pial capillaries is a complex process characterized by three fundamental stages: a pial capillary contact with the EGLM with fusion of vascular and glial basal laminae at the contact site, b endothelial cell filopodium penetration through the fussed laminae with the formation of a funnel between them that accompanies it into the nervous tissue while remaining open to the meningeal interstitium and, c penetration of the whole capillary carrying the open funnel with it and establishing an extravascular Virchow-Robin Compartment (V-RC that maintains the perforating vessel extrinsic (outside the nervous tissue through its entire length. The V-RC is walled internally by the vascular basal lamina and externally by the basal lamina of joined glial cells endfeet. The VRC outer glial wall appear as an extension of the cortex superficial EGLM. All the perforating vessels within the V-RCs constitute the cerebral cortex extrinsic microvascular compartment. These perforating vessels are the only one capable of responding to inflammatory insults. The V-RC remains open (for life to the meningeal interstitium permitting the exchanges of fluid and of cells between brain and meninges. The V-RC function as the brain sole drainage (prelymphatic system in both physiological as well as pathological situations.

  2. Effects of nisoldipine and lisinopril on microvascular dysfunction in hypertensive Type I diabetes patients with nephropathy

    DEFF Research Database (Denmark)

    Sørensen, V B; Rossing, P; Tarnow, L

    1998-01-01

    1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2....... We performed a 1-year double-blind, double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive Type I diabetes patients with diabetic nephropathy. For comparison, 22 age-matched normotensive healthy control subjects...... were included. Measurements were performed at baseline and after 1 year of antihypertensive treatment. The minimal vascular resistance and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method.3. Mean arterial pressure...

  3. Effects of nisoldipine and lisinopril on microvascular dysfunction in hypertensive Type I diabetes patients with nephropathy

    DEFF Research Database (Denmark)

    Sørensen, V B; Rossing, P; Tarnow, L

    1998-01-01

    1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2...... were included. Measurements were performed at baseline and after 1 year of antihypertensive treatment. The minimal vascular resistance and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method.3. Mean arterial pressure....... We performed a 1-year double-blind, double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive Type I diabetes patients with diabetic nephropathy. For comparison, 22 age-matched normotensive healthy control subjects...

  4. Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sandra Beer

    2008-12-01

    vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls.Conclusion: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state.Keywords: skin microcirculation, iontophoresis, pulse wave velocity, type 2 diabetes, hemostatic markers

  5. 2,3,7,8-TCDD exposure, endothelial dysfunction and impaired microvascular reactivity

    Czech Academy of Sciences Publication Activity Database

    Pelclová, D.; Prázdný, M.; Škrha, J.; Fenclová, Z.; Kalousová, M.; Urban, P.; Navrátil, Tomáš; Šenholdová, Z.; Šmerhovský, Z.

    2007-01-01

    Roč. 26, - (2007), s. 705-713 ISSN 0960-3271 Institutional research plan: CEZ:AV0Z40400503 Keywords : 2,3,7,8-TCDD * endothelial dysfunction * oxidative stress * superoxide dismutase Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.335, year: 2007

  6. The role of coronary microvascular dysfunction in the genesis of cardiovascular diseases

    International Nuclear Information System (INIS)

    Parodi, O.; Sambuceti, G.

    1996-01-01

    Using PET, myocardial perfusion abnormalities secondary to microvascular disorders have beeen investigated in arterial hypertension (AH), dilated and hypertrophic cardiomyopathy (CM), as well as in ischemic heart disease (CAD). In AH, regional perfusion at rest is within the normal range, while the coronary reserve and flow response to increase in metabolic demand are blunted. Both dilated and hypertrophic CM demonstrate abnormal vasodilaing capability, wich as bee schown to be presented in the subclinical form of dilated DM; the reduction of coronary reserve is not related to the presence and extent of the hemodynamic impairment in dilated CM, and involved also nonhypertropied myocardium in asymmetric hypertropic CM. These finding indicate a primary involvement of coronary microcirculation in non advanced forms of dilated and hypertrophic CM. Finally, in patients with CAD, myocardia teritories supplied by angiographically normal coronary arteries schow abnormal coronary reserve and flow during pacing, tachycardia, indicating that, even in absence of epicardial coronary artery obstruction, microcirculation is impaired in subject with coronary atherosclerosis. this abnormally can smooth perfusion differences, between control andd jeopardized regions. Although the agreement with the angiographic documantation of coronary artery disease has been frequently considered to characterize the diagnostic reliability of these techiques, the evaluation of myocardial perfusion provides an independent tool for the functional assessment of patient with heart disease. The possibility of obtain measurement of regional myocardial blood flow, provided by positron emission thermography, helps to identify the mechanisms affecting flow regulation in the myocardium. This tool thus provides a new rationale for the application of perfusion imaging, to obtain a more precise characterization of these patients, beyond the agreement with the morphological angiographic picture

  7. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  8. Which side of the balance determines the frequency of vaso-occlusive crises in children with sickle cell anemia: Blood viscosity or microvascular dysfunction?

    Science.gov (United States)

    Charlot, Keyne; Romana, Marc; Moeckesch, Berenike; Jumet, Stéphane; Waltz, Xavier; Divialle-Doumdo, Lydia; Hardy-Dessources, Marie-Dominique; Petras, Marie; Tressières, Benoît; Tarer, Vanessa; Hue, Olivier; Etienne-Julan, Maryse; Antoine-Jonville, Sophie; Connes, Philippe

    2016-01-01

    Vascular resistance and tissue perfusion may be both affected by impaired vascular function and increased blood viscosity. Little is known about the effects of vascular function on the occurrence of painful vaso-occlusive crises (VOC) in children with sickle cell anemia (SCA). The aim of the present study was to determine which side of the balance (blood viscosity or vascular function) is the most deleterious in SCA and increases the risk for frequent hospitalized VOC. Microvascular function, microcirculatory oxygenation and blood viscosity were determined in a group of 22 SCA children/adolescents at steady state and a group of 13 healthy children/adolescents. Univariate analyses demonstrated blunted microvascular reactivity during local thermal heating test and decreased microcirculatory oxygenation in SCA children compared to controls. Multivariate analysis revealed that increased blood viscosity and decreased microcirculatory oxygenation were independent risk factors of frequent VOC in SCA. In contrast, the level of microvascular dysfunction does not predict VOC rate. In conclusion, increased blood viscosity is usually well supported in healthy individuals where vascular function is not impaired. However, in the context of SCA, microvascular function is impaired and any increase of blood viscosity or decrease in microcirculatory oxygenation would increase the risks for frequent VOC. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Adiponectin-deficiency exaggerates sepsis-induced microvascular dysfunction in the mouse brain.

    Science.gov (United States)

    Vachharajani, Vidula; Cunningham, Christie; Yoza, Barbara; Carson, John; Vachharajani, Tushar J; McCall, Charles

    2012-03-01

    Obesity increases circulating cell-endothelial cell interactions; an early marker of inflammation in laboratory model of sepsis, but little is known about the effect of different adipokines. Adiponectin is an anti-inflammatory adipokine secreted by adipocytes. Adiponectin deficiency is implicated in exaggerated proinflammatory phenotype in both obesity and sepsis via increased proinflammatory cytokine expression. However the effect of adiponectin deficiency on circulating cell-endothelial cell interactions in polymicrobial sepsis is unknown. Furthermore although brain dysfunction in septic patients is a known predictor of death, the pathophysiology involved is unknown. In the current study, we examined the effects of adiponectin deficiency on leukocyte (LA) and platelet adhesion (PA) in cerebral microcirculation of septic mice. Adiponectin deficient (Adipoq(-/-): Adko) and background strain C57Bl/6 (wild type (WT)) mice were used. Sepsis was induced using cecal ligation and puncture (CLP). We studied LA and PA in the cerebral microcirculation using intravital fluorescent video microscopy (IVM), blood brain barrier (BBB) dysfunction using Evans Blue (EB) leakage method and E-selectin expression using dual radiolabeling technique in different WT and Adko mice with CLP. Adiponectin deficiency significantly exaggerated LA (WT-CLP:201 ± 17; Adko-CLP: ± 53 cells/mm(2); P < 0.05) and PA (WT-CLP:125 ± 17; Adko-CLP:188 ± 20 cells/mm(2); P < 0.05) in cerebral microcirculation, EB leakage (WT-CLP:10 ± 3.7; Adko-CLP:24 ± 4.3 ng/g × µl plasma; P < 0.05) and E-selectin expression (WT-CLP:0.06 ± 0.11; Adko-CLP:0.44 ± 0.053 ng/g; P < 0.05) in the brain tissue of the mice with CLP. Furthermore, E-selectin monoclonal antibody (mAb) treatment attenuated cell adhesion and BBB dysfunction of Adko-CLP mice. Adiponectin deficiency is associated with exaggerated leukocyte and PA in cerebral microcirculation of mice with CLP via modulation of E-selectin expression.

  10. High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular Dysfunction in Patients with Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    David C. Tong

    2018-01-01

    Full Text Available BackgroundInflammation and microvascular dysfunction (MVD are independently associated with adverse cardiovascular outcomes in patients with ischemic heart disease. This study aimed to assess the relationship between inflammation, MVD, and myocardial injury.MethodsCoronary microvascular function was assessed in 74 patients undergoing percutaneous coronary intervention (PCI using the index of microvascular resistance (IMR by a pressure–temperature sensor-tipped wire. Serum high-sensitivity C-reactive protein (hsCRP level was quantified by rate turbidimetry. Severe MVD was defined as IMR ≥ 30. Pearson correlation was computed to assess the relationships between hsCRP, troponin, and IMR of culprit vessel. Predictors of severe MVD were assessed by regression analysis.ResultsAcute coronary syndromes (ACSs represented 49% of the total cohort. Study cohort was divided into low C-reactive protein (CRP (hsCRP < 3 mg/L and high CRP (hsCRP ≥ 3 mg/L groups. There was higher representation of smokers (78 vs. 52%, diabetics (39 vs. 18%, and ACS (61 vs. 33%, as well as higher body mass index (29.4 ± 4.6 vs. 27.2 ± 4.1 in the high CRP group. Pre-PCI and post-PCI IMR were significantly elevated in the high CRP group compared to the low CRP group (pre-PCI IMR: 29.0 ± 13.9 vs. 17.4 ± 11.1, p < 0.0001; post-PCI IMR: 23.0 ± 16.8 vs. 15.5 ± 8.4, p = 0.02. Peak troponin levels were significantly raised in the high CRP group (9.96 ± 17.19 vs. 1.17 ± 3.00 μg/L, p = 0.002. There was a strong positive correlation between hsCRP and pre-PCI IMR (r = 0.85, p < 0.0001. Pre- and post-PCI IMR levels were correlated with peak troponin level (r = 0.45, p < 0.0001; r = 0.33, p = 0.005, respectively. Predictors of severe MVD include male gender (OR 3.0, diabetes (OR 3.7, smoking history (OR 4.0, ACS presentation (OR 8.5, and hsCRP ≥ 3 mg/L (OR 5.6.ConclusionhsCRP is a

  11. Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

    2017-01-01

    This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

  12. Correlation of microvascular abnormalities and endothelial dysfunction in Type-1 Diabetes Mellitus (T1DM): a real-time intravital microscopy study.

    Science.gov (United States)

    Cheung, Anthony T W; Tomic, M Meighan Smith; Chen, Peter C Y; Miguelino, Eric; Li, Chin-Shang; Devaraj, Sridevi

    2009-01-01

    We hypothesize that real-time in vivo microvascular abnormalities should correlate with biochemical markers of inflammation/endothelial dysfunction in T1DM. Real-time quantification of T1DM and healthy non-diabetic control microcirculation was conducted utilizing computer-assisted intravital microscopy. Selected biochemical markers (high sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecules (sVCAM), soluble intercellular adhesion molecules (sICAM), soluble E-selectin (sE-selectin), nitrotyrosine, superoxide anion (O2-), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha)) were used for correlation. The severity of microvascular abnormalities, as reflected by the arithmetic severity index (SI), was significantly increased in T1DM vs. controls (5.89 +/- 1.47 vs. 2.34 +/- 1.48; Pprogression and therapeutic efficacy studies.

  13. Microvascular dysfunction is associated with plasma osteoprotegerin levels in patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2013-01-01

    Osteoprotegerin (OPG) is a glycoprotein that inhibits nuclear factor-κB's regulatory effects on inflammation, skeletal, and vascular systems, and is a potential biomarker of atherosclerosis and seems to be involved in vascular calcifications. The objective of this study was to assess the relation......Osteoprotegerin (OPG) is a glycoprotein that inhibits nuclear factor-κB's regulatory effects on inflammation, skeletal, and vascular systems, and is a potential biomarker of atherosclerosis and seems to be involved in vascular calcifications. The objective of this study was to assess...

  14. Coronary microvascular dysfunction is not associated with a history of reproductive risk factors in women with angina pectoris-An iPOWER substudy

    DEFF Research Database (Denmark)

    Suhrs, Hannah Elena; Kristensen, Anna Meta; Rask, Anna Bay

    2018-01-01

    BACKGROUND: Reproductive risk factors such as preeclampsia and recurrent miscarriages have been associated with adverse cardiovascular (CV) events. Underlying coronary microvascular dysfunction (CMD) may be a common denominator. PURPOSE: We investigated whether a history of reproductive risk...... factors was associated with CMD in women with angina pectoris and no obstructive coronary artery disease (CAD). METHODS: Participants from the iPOWER study, including women with angina pectoris and no obstructive CAD (... risk factors: recurrent miscarriages, gestational diabetes, preeclampsia, rhesus immunity, polycystic ovary syndrome and menopausal status as well as migraine and Raynaud phenomenon. CMD was assessed by transthoracic Doppler echocardiography with measurement of coronary flow velocity reserve (CFVR...

  15. Microvascular damage evaluation in systemic sclerosis: the role of nailfold videocapillaroscopy and laser techniques

    Directory of Open Access Journals (Sweden)

    B. Ruaro

    2017-12-01

    Full Text Available Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment.

  16. Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Marini, Cecilia [CNR Institute of Bioimages and Molecular Physiology, Milan, Section of Genoa (Italy); Bezante, GianPaolo; Modonesi, Elisa; Rollando, Daniela; Balbi, Manrico; Brunelli, Claudio [University of Genoa, Department of Internal Medicine, Cardiology, Genoa (Italy); Gandolfo, Patrizia; Morbelli, Silvia D.; Armonino, Riccardo [University of Genoa, Department of Internal Medicine, Nuclear Medicine, Genoa (Italy); DePascale, Angelo; Maggi, Davide; Albertelli, Manuela; Cordera, Renzo [University of Genoa, Department of Endocrinological Metabolic Sciences, Diabetology, Genoa (Italy); Sambuceti, Gianmario [University of Genoa, Department of Internal Medicine, Nuclear Medicine, Genoa (Italy); Advanced Biotechnology Center, Genoa (Italy)

    2010-02-15

    The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2). A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using {sup 99m}Tc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session. Estimated MPR was higher in control subjects than in patients (3.36 {+-} 0.66 vs 1.91 {+-} 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 {+-} 0.78 vs 1.93 {+-} 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 {+-} 0.71 vs 1.83 {+-} 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = -0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = -0.51, p < 0.01). LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects. (orig.)

  17. 3.0 T magnetic resonance myocardial perfusion imaging for semi-quantitative evaluation of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Yin, Liang; Xu, Hai-Yan; Zheng, Sui-Sheng; Zhu, Ying; Xiao, Jiang-Xi; Zhou, Wei; Yu, Si-Si; Gong, Liang-Geng

    2017-12-01

    This study aimed to assess coronary microvascular dysfunction (CMD) differences in hypertrophic cardiomyopathy (HCM) patients using cardiac magnetic resonance (CMR) first-pass perfusion and late gadolinium enhancement imaging. Forty-seven patients with HCM and twenty-one healthy volunteers underwent CMR at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late gadolinium enhancement (LGE). Left ventricular end-diastolic wall thickness (EDTH), LGE, time to peak (T peak ), maximal up-slope (Slope max ), and peak signal intensity (SI peak ) were assessed for each myocardial segment. The HCM myocardial segments were grouped by the degree of LGE and hypertrophy. T peak , SI peak , Slope max and EDTH in multiple groups were assessed and compared by ANOVA test/Kruskal-Wallis test. The Spearman correlation test was used to determine the relationships between EDTH, LGE and perfusion parameters (T peak , Slope max and SI peak ). Compared to control group segments, T peak increased while Slope max and SI peak decreased in non-LGE/non-hypertrophic segments and LGE/hypertrophic segments in the HCM group, while T peak increased more significantly in LGE/hypertrophic segments (all p hypertrophic segments of HCM patients, and it may be helpful in the early diagnosis of coronary microvascular dysfunction in HCM. This abnormal perfusion is associated with the severity of myocardial fibrosis and the degree of hypertrophy.

  18. Cardiorenal disease connection during post-menopause: The protective role of estrogen in uremic toxins induced microvascular dysfunction

    NARCIS (Netherlands)

    Pei, J. (Jiayi); M. Harakalova (Magdalena); H.M. den Ruijter (Hester ); G. Pasterkamp (Gerard); D.J.G.M. Duncker (Dirk); M.C. Verhaar (Marianne); F.W. Asselbergs (Folkert); C. Cheng (Caroline)

    2017-01-01

    textabstractFemale gender, post-menopause, chronic kidney disease (CKD) and (CKD linked) microvascular disease are important risk factors for developing heart failure with preserved ejection fraction (HFpEF). Enhancing our understanding of the interrelation between these risk factors could greatly

  19. Cardiorenal disease connection during post-menopause : The protective role of estrogen in uremic toxins induced microvascular dysfunction

    NARCIS (Netherlands)

    Pei, Jiayi; Harakalova, Magdalena; den Ruijter, Hester; Pasterkamp, Gerard; Duncker, Dirk J.; Verhaar, Marianne C.; Asselbergs, Folkert W.; Cheng, Caroline

    2017-01-01

    Female gender, post-menopause, chronic kidney disease (CKD) and (CKD linked) microvascular disease are important risk factors for developing heart failure with preserved ejection fraction (HFpEF). Enhancing our understanding of the interrelation between these risk factors could greatly benefit the

  20. The role of cyclo-oxygenase-1 in high-salt diet-induced microvascular dysfunction in humans.

    Science.gov (United States)

    Cavka, Ana; Cosic, Anita; Jukic, Ivana; Jelakovic, Bojan; Lombard, Julian H; Phillips, Shane A; Seric, Vatroslav; Mihaljevic, Ivan; Drenjancevic, Ines

    2015-12-15

    Recent studies have shown that some of the deleterious effects of a high-salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function. Increased generation of cyclo-oxygenase (COX-1 and COX-2)-derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading. The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX-1 and COX-2 in normotensive subjects on a short-term HS diet. The present study demonstrates the important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet. These results help to explain how even short-term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX-1 could play a role in this impaired tissue blood flow. The present study aimed to assess the effect of a 1-week high-salt (HS) diet on the role of cyclo-oxygenases (COX-1 and COX-2) and the vasoconstrictor prostaglandins, thromboxane A2 (TXA2 ) and prostaglandin F2α (PGF2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n = 54) were assigned to either the HS diet group (N = 30) (∼14 g day(-1) NaCl ) or low-salt (LS) diet group (N = 24) (diet protocols. One HS diet group subset received 100 mg of indomethacin (non-selective COX-1 and COX-2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX-2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty-four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and

  1. Focus on focus: lack of coherence between systemic and microvascular indices of oedema formation.

    Science.gov (United States)

    Ten Tusscher, Birkitt; Gudden, Corien; van Vliet, Suus; Smit, Bob; Ince, Can; Boerma, E Christiaan; de Grooth, Harm-Jan S; Elbers, Paul W G

    2017-01-01

    Fluid therapy remains a cornerstone of therapy in shock states. However, fluid overloading ultimately results in oedema formation which is related to excess morbidity and mortality. Handheld microscopes are now frequently used to study the sublingual microcirculation. As a corollary, these devices measure focal distance, or surface to capillary distance. Physiologically, this could represent a microvascular index of oedema formation and could have the potential to guide fluid therapy. This potential tool should be investigated, especially given the frequently reported lack of coherence between systemic and microvascular parameters in the critically ill. Therefore, we set out to assess the correlation between microvascular focal distance and systemic indices of oedema formation, specifically fluid balance and weight gain. Following ex vivo testing of focal distance measurement reliability, we conducted a prospective observational cohort study in patients admitted to the intensive care unit of our university teaching hospital. We determined surface to capillary distance using sidestream dark field (SDF) and incident dark field (IDF) imaging by assessing the focal distance point or object distance range at which a sharp recording could be made. Measurements were performed in post-cardiac surgery patients and in patients following emergency admission at two time points separated by at least several hours. Data on fluid balance, weight and weight gain were collected simultaneously. Sixty patients were included. The focal setting, focus point for SDF and the object distance range for IDF did not differ significantly between time points. Focus was not correlated with difference in fluid balance or weight gain. There is a lack of coherence between surface to capillary distance as determined by SDF or IDF imaging and fluid balance or weight gain. Thus, focal distance as a microvascular index of oedema formation cannot currently be used as a proxy for systemic indices of

  2. Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction: The iPOWER study.

    Science.gov (United States)

    Michelsen, Marie Mide; Mygind, Naja Dam; Pena, Adam; Olsen, Rasmus Huan; Christensen, Thomas Emil; Ghotbi, Adam Ali; Hasbak, Philip; Kjaer, Andreas; Gustafsson, Ida; Hansen, Peter Riis; Hansen, Henrik Steen; Høst, Nis; Kastrup, Jens; Prescott, Eva

    2017-02-01

    Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively. CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Coronary microvascular dysfunction is not associated with a history of reproductive risk factors in women with angina pectoris-An iPOWER substudy.

    Science.gov (United States)

    Suhrs, Hannah Elena; Kristensen, Anna Meta; Rask, Anna Bay; Michelsen, Marie Mide; Frestad, Daria; Mygind, Naja Dam; Bové, Kira; Prescott, Eva

    2018-01-01

    Reproductive risk factors such as preeclampsia and recurrent miscarriages have been associated with adverse cardiovascular (CV) events. Underlying coronary microvascular dysfunction (CMD) may be a common denominator. We investigated whether a history of reproductive risk factors was associated with CMD in women with angina pectoris and no obstructive coronary artery disease (CAD). Participants from the iPOWER study, including women with angina pectoris and no obstructive CAD (<50% stenosis), were invited to complete an electronic survey regarding reproductive risk factors: recurrent miscarriages, gestational diabetes, preeclampsia, rhesus immunity, polycystic ovary syndrome and menopausal status as well as migraine and Raynaud phenomenon. CMD was assessed by transthoracic Doppler echocardiography with measurement of coronary flow velocity reserve (CFVR) during high-dose dipyridamole infusion, and analyzed in three categories with cut-off points at 2.0 and 2.5. Associations between CFVR and a history of reproductive risk factors were examined by age-adjusted trend test. The questionnaire was completed by 613 women (73% of those invited), of whom 550 had a successful CFVR measurement. There was no significant difference in baseline characteristics between participants and non-participants. Median (interquartile range (IQR)) age was 62.8 (54.8; 68.7) years, median (IQR) BMI 26.2 (23.2; 29.8) kg/m 2 , and 81.5% were postmenopausal. We did not find any significant associations between any of the reproductive risk factors, Raynaud's phenomenon or migraine and CFVR. The lack of association between coronary microvascular function and a history of reproductive risk factors, migraine and Raynaud's phenomenon suggests that a common vascular pathophysiological mechanism underlying these conditions is unlikely. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Opium addiction as an independent risk factor for coronary microvascular dysfunction: A case-control study of 250 consecutive patients with slow-flow angina.

    Science.gov (United States)

    Esmaeili Nadimi, Ali; Pour Amiri, Farah; Sheikh Fathollahi, Mahmood; Hassanshahi, Gholamhossien; Ahmadi, Zahra; Sayadi, Ahmad Reza

    2016-09-15

    Approximately 20% to 30% of patients who undergo coronary angiography for assessment of typical cardiac chest pain display microvascular coronary dysfunction (MCD). This study aimed to determine potential relationships between baseline clinical characteristics and likelihood of MCD diagnosis in a large group of patients with stable angina symptoms, positive exercise test and angiographic ally normal epicardial coronary arteries. This cross-sectional study included 250 Iranian with documented evidence of cardiac ischemia on exercise testing, class I or II indication for coronary angiography, and either: (1) angiographically normal coronary arteries and diagnosis of MCD with slow-flow phenomenon, or (2) normal angiogram and no evidence of MCD. All patients completed a questionnaire designed to capture key data including clinical demographics, past medical history, and social factors. Data was evaluated using single and multivariable logistic regression models to identify potential individual patient factors that might help to predict a diagnosis of MCD. 125 (11.2% of total) patients were subsequently diagnosed with MCD. 125 consecutive control subjects were selected for comparison. The mean age was similar among the two groups (52.38 vs. 53.26%, p=ns), but there was a higher proportion of men in the study group compared to control (42.4 vs. 27.2%, p=0.012). No significant relationships were observed between traditional cardiovascular risk factors (diabetes, hypertension, and dyslipidemia) or body mass index (BMI), and likelihood of MCD diagnosis. However, opium addiction was found to be an independent predictor of MCD on single and multivariable logistic regression model (OR=3.575, 95%CI: 1.418-9.016; p=0.0069). We observed a significant relationship between opium addiction and microvascular angina. This novel finding provides a potential mechanistic insight into the pathogenesis of MCD with slow-flow phenomenon. Copyright © 2016 Elsevier Ireland Ltd. All rights

  5. The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease

    DEFF Research Database (Denmark)

    Brainin, Philip; Frestad, Daria; Prescott, Eva

    2018-01-01

    AIMS: Coronary vascular dysfunction is linked with poor cardiovascular prognosis in patients without obstructive coronary artery disease (CAD) but a critical appraisal of the literature is lacking. METHODS AND RESULTS: We performed a systematic review and meta-analysis to quantify...

  6. Circulating microRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation.

    Science.gov (United States)

    Bijkerk, R; Duijs, J M G J; Khairoun, M; Ter Horst, C J H; van der Pol, P; Mallat, M J; Rotmans, J I; de Vries, A P J; de Koning, E J; de Fijter, J W; Rabelink, T J; van Zonneveld, A J; Reinders, M E J

    2015-04-01

    Because microvascular disease is one of the most important drivers of diabetic complications, early monitoring of microvascular integrity may be of clinical value. By assessing profiles of circulating microRNAs (miRNAs), known regulators of microvascular pathophysiology, in healthy controls and diabetic nephropathy (DN) patients before and after simultaneous pancreas-kidney transplantation (SPK), we aimed to identify differentially expressed miRNAs that associate with microvascular impairment. Following a pilot study, we selected 13 candidate miRNAs and determined their circulating levels in DN (n = 21), SPK-patients (n = 37), healthy controls (n = 19), type 1 diabetes mellitus patients (n = 15) and DN patients with a kidney transplant (n = 15). For validation of selected miRNAs, 14 DN patients were studied longitudinally up to 12 months after SPK. We demonstrated a direct association of miR-25, -27a, -126, -130b, -132, -152, -181a, -223, -320, -326, -340, -574-3p and -660 with DN. Of those, miR-25, -27a, -130b, -132, -152, -320, -326, -340, -574-3p and -660 normalized after SPK. Importantly, circulating levels of some of these miRNAs tightly associate with microvascular impairment as they relate to aberrant capillary tortuosity, angiopoietin-2/angiopoietin-1 ratios, circulating levels of soluble-thrombomodulin and insulin-like growth factor. Taken together, circulating miRNA profiles associate with DN and systemic microvascular damage, and might serve to identify individuals at risk of experiencing microvascular complications, as well as give insight into underlying pathologies. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  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. Tetrastarch sustains pulmonary microvascular perfusion and gas exchange during systemic inflammation.

    Science.gov (United States)

    Heckel, Kai; Winkelmann, Bjoern; Strunden, Mike S; Basedow, Annika; Schuster, Anke; Schumacher, Udo; Kiefmann, Rainer; Reuter, Daniel A; Goetz, Alwin E

    2012-02-01

    According to Fick's law of diffusion, gas exchange depends on the size and thickness of the blood perfused alveolocapillary membrane. Impairment of either one is tenuous. No data are available concerning the impact of hydroxyethyl starches and saline on pulmonary microperfusion and gas exchange during systemic inflammation. Prospective, randomized, controlled experimental study. University research laboratory. Thirty-two anesthetized rabbits assigned to four groups (n = 8). Except for the control group, systemic inflammation was induced by lipopolysaccharide. Fluid resuscitation was performed with saline alone or in conjunction with tetrastarch or pentastarch. Pulmonary microcirculation was analyzed at 0 hr and 2 hrs using intravital microscopy. Thickness of the alveolocapillary membrane was measured using electron microscopy. Macrohemodynamics were stable in all groups. In pulmonary arterioles, lipopolysaccharide reduced the erythrocyte velocity and impeded the microvascular decrease of the hematocrit in the saline and pentastarch group. In contrast, infusion of tetrastarch normalized these perfusion parameters. In capillaries, lipopolysaccharide decreased the functional capillary segment density and the capillary perfusion index, which was prevented by both starches. However, compared with saline and pentastarch, treatment with tetrastarch prevented the lipopolysaccharide-induced reduction of the capillary erythrocyte flux and inversely reduced the erythrocyte capillary transit time. Thickening of alveolocapillary septae after lipopolysaccharide application was solely observed in the saline and pentastarch group. In contrast to pentastarch and saline, the application of tetrastarch prevented the lipopolysaccharide-induced increase of the alveoloarterial oxygen difference. Tetrastarch sustains pulmonary gas exchange during experimental systemic inflammation more effectively than saline and pentastarch by protecting the diffusion distance and the size of the

  9. Prefrontal system dysfunction and credit card debt.

    Science.gov (United States)

    Spinella, Marcello; Yang, Bijou; Lester, David

    2004-10-01

    Credit card use often involves a disadvantageous allocation of finances because they allow for spending beyond means and buying on impulse. Accordingly they are associated with increased bankruptcy, anxiety, stress, and health problems. Mounting evidence from functional neuroimaging and clinical studies implicates prefrontal-subcortical systems in processing financial information. This study examined the relationship of credit card debt and executive functions using the Frontal System Behavior Scale (FRSBE). After removing the influences of demographic variables (age, sex, education, and income), credit card debt was associated with the Executive Dysfunction scale, but not the Apathy or Disinhibition scales. This suggests that processes of conceptualizing and organizing finances are most relevant to credit card debt, and implicates dorsolateral prefrontal dysfunction.

  10. Coronary microvascular dysfunction assessed by intracoronary acetylcholine provocation testing is a frequent cause of ischemia and angina in patients with exercise-induced electrocardiographic changes and unobstructed coronary arteries.

    Science.gov (United States)

    Ong, Peter; Athanasiadis, Anastasios; Hill, Stephan; Schäufele, Tim; Mahrholdt, Heiko; Sechtem, Udo

    2014-08-01

    The exercise electrocardiogram (ECG) is a standard examination in patients with suspected coronary artery disease. However, despite a pathologic result, many patients undergoing diagnostic coronary angiography do not have any significant epicardial stenosis. In this study, we assessed the relation between a pathologic exercise ECG and coronary microvascular dysfunction in response to intracoronary acetylcholine (ACh) provocation in patients without any relevant epicardial stenosis. Coronary microvascular dysfunction is significantly more often in patients with angina, unobstructed coronary arteries and a pathologic exercise stress test compared to those without pathologic stress test. This study recruited 137 consecutive patients with exertional angina pectoris who underwent diagnostic coronary angiography between September 2008 and April 2011 (68% women; mean age, 63 ± 10 years). In none of the patients was there a stenosis of >50%. All patients underwent an exercise ECG before angiography and intracoronary ACh provocation testing for assessment of coronary vasomotor responses directly after angiography. The exercise ECG showed an abnormal result in 69 patients (50%; ST-segment depression ≥0.1 mV and/or reproduction of the patient's usual symptoms). The ACh test revealed a coronary vasomotor abnormality (reproduction of the patient's symptoms, ischemic ECG shifts ± diffuse distal vasoconstriction) in 87 patients (64%). Such a result was significantly more often found in patients with a pathologic exercise ECG (50/69 [72%] vs 19/69 [28%], P = 0.034). There were no other statistically significant differences between patients with and those without pathologic exercise ECG. Coronary microvascular dysfunction is frequently found in patients with exertional angina pectoris and unobstructed coronary arteries. Such a finding is found significantly more often in presence of a pathologic exercise ECG. © 2014 Wiley Periodicals, Inc.

  11. Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results

    Directory of Open Access Journals (Sweden)

    C. Pizzorni

    2011-06-01

    Full Text Available Objectives: Systemic sclerosis (SSc is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Methods: 27 SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns (“Early”, “Active”, “Late”. LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36°C. Statistical evaluation was carried out by non-parametric procedures. Results: Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05. The heating of the probe to 36°C induced a significant increase in peripheral blood flow in all subjects compared to baseline (p <0.05, however, the amount of variation was significantly lower in patients with SSc, compared with healthy controls (p <0.05. The SSc patients with NVC “Late” pattern, showed lower values of peripheral blood flow than patients with NVC “Active” or “Early” patterns (p<0.05. Moreover, a negative correlation between the tissue perfusion score and the progression of the SSc microangiopathy was observed, as well as between the tissue perfusion and the duration of the Raynaud’s phenomenon (p <0.03. Conclusions: LDF can be employed to evaluate blood perfusion in the microvascular circulation in SSc patients. The blood flow changes observed with the LDF seem to correlate with the severity of microvascular damage in SSc as detected by NVC.

  12. Systemic immune dysfunction in pancreatic cancer patients.

    Science.gov (United States)

    Poch, Bertram; Lotspeich, Errki; Ramadani, Marco; Gansauge, Susanne; Beger, Hans G; Gansauge, Frank

    2007-05-01

    We investigated the immune status in 32 pancreatic cancer patients (PC) in comparison with healthy controls (HC). Using flow cytometry, peripheral blood lymphocytes (PBL) were characterized by the expression of surface markers for T helper cells (CD4), T suppressor cells (CD8), B cells (CD19) and NK cells (CD56). The blastogenic response of PBL was analyzed after stimulation with concavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and anti-CD3 antibodies. The serum levels of TNF-alpha, IL-1beta, IL-2, IL-10, IL-12, IL-18, IL-1RA, sIL-2R and TGF-beta were determined by ELISA. No differences in the distribution of peripheral immunocytes in PC were found, whereas the blastogenic response of peripheral blood lymphocytes (PBL) after stimulation with PHA or anti-CD3 antibodies was significantly decreased in PC. In PC, we found reduced serum levels of IL-2 and significantly elevated levels of TNF-alpha, TGF-beta1, IL-10, IL-2R, IL-1beta and IL-1RA. These data provide evidence for a systemic immune dysfunction in pancreatic cancer patients characterized by a shift towards a T helper cell type 2 cytokine profile, a significant elevation of substances related to T cell suppression and a reduced blastogenic response to PHA and anti-CD3 antibodies of PBL.

  13. Microvascular resuscitation as a therapeutic goal in severe sepsis.

    Science.gov (United States)

    Bateman, Ryon M; Walley, Keith R

    2005-01-01

    Sepsis causes microvascular dysfunction. Increased heterogeneity of capillary blood flow results in local tissue hypoxia, which can cause local tissue inflammation, impaired oxygen extraction, and, ultimately, organ dysfunction. Microvascular dysfunction is clinically relevant because it is a marker for mortality: it improves rapidly in survivors of sepsis but fails to improve in nonsurvivors. This, along with the fact that resuscitation of mean arterial pressure and cardiac output alone fails to improve microvascular function, means that microvascular resuscitation is therefore a therapeutic goal. In animal studies of sepsis, volume resuscitation improves microvascular permeability and tissue oxygenation, and leads to improved organ function, including a reduction in myocardial dysfunction. Microvascular resuscitation strategies include hemodynamic resuscitation using the linked combination of volume resuscitation, judicious vasopressor use, and inotropes and vasodilators. Alternative vasoactive agents, such as vasopressin, may improve microcirculatory function to a greater degree than conventional vasopressors. Successful modulation of inflammation has a positive impact on endothelial function. Finally, targeted treatment of the endothelium, using activated protein C, also improves microvascular function and ultimately increases survival. Thus, attention must be paid to the microcirculation in patients with sepsis, and therapeutic strategies should be employed to resuscitate the microcirculation in order to avoid organ dysfunction and to reduce mortality.

  14. Reduced Microvascular Density in Omental Biopsies of Children with Chronic Kidney Disease.

    Science.gov (United States)

    Burkhardt, Dorothea; Bartosova, Maria; Schaefer, Betti; Grabe, Niels; Lahrmann, Bernd; Nasser, Hamoud; Freise, Christian; Schneider, Axel; Lingnau, Anja; Degenhardt, Petra; Ranchin, Bruno; Sallay, Peter; Cerkauskiene, Rimante; Malina, Michal; Ariceta, Gema; Schmitt, Claus Peter; Querfeld, Uwe

    2016-01-01

    Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD. Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2. Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, pchildren (p = 0.01). Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease.

  15. Complicações microvasculares e disfunção autonômica cardíaca em pacientes com diabete melito tipo 1 Complicaciones microvasculares y disfunción autonómica cardíaca en pacientes con diabetes mellittus tipo 1 Microvascular complications and cardiac autonomic dysfunction in patients with diabetes mellitus type 1

    Directory of Open Access Journals (Sweden)

    Fernando K Almeida

    2011-06-01

    Full Text Available FUNDAMENTO: A presença de neuropatia autonômica cardíaca (NAC em pacientes com diabete melito (DM está associada a aumento da mortalidade e a complicações crônicas microvasculares do diabete. OBJETIVO: Investigar uma possível associação entre achados sugestivos de NAC durante a realização do teste ergométrico (TE e nefropatia e retinopatia em pacientes com DM tipo 1. MÉTODOS: Realizamos um estudo transversal com 84 pacientes com DM tipo 1. Todos os pacientes foram submetidos à avaliação clínica e laboratorial e realizaram TE, sendo que aqueles que apresentaram achados sugestivos de isquemia miocárdica foram excluídos da análise dos dados (n = 3. A avaliação de complicações microvasculares (retinopatia e nefropatia foi realizada na amostra. RESULTADOS: Os pacientes com nefropatia e aqueles com retinopatia atingiram uma frequência cardíaca (FC durante o pico de exercício (FC máxima menor e apresentaram aumento menor da FC em relação ao repouso (ΔFC pico quando comparados com aqueles sem estas complicações. Esses pacientes também apresentaram menor redução da FC no segundo e 4º minutos após o final do teste (ΔFC recuperação dois e 4 minutos. Após realização de análise multivariada com controle para os possíveis fatores de confusão, os ΔFC recuperação em dois e 4 minutos, FC máxima e o ΔFC pico permaneceram significativamente associados à retinopatia; e os ΔFC recuperação no segundo e 4º minutos permaneceram associados à presença de nefropatia. CONCLUSÃO: O TE pode ser considerado um instrumento adicional para a detecção precoce de NAC e para identificar pacientes em maior risco para complicações microvasculares do diabete.BACKGROUND: LA presencia de neuropatía autonómica cardíaca (NAC en pacientes con diabetes mellittus (DM está asociada a aumento de la mortalidad y a complicaciones crónicas microvasculares de diabetes. OBJECTIVE: Investigar una posible asociación entre

  16. The regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy patients with or without left ventricular outflow tract obstruction: Assessment with first-pass perfusion imaging using 3.0-T cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hua-yan [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Yang, Zhi-gang, E-mail: yangzg666@163.com [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Sun, Jia-yu; Wen, Ling-yi; Zhang, Ge; Zhang, Shuai [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Guo, Ying-kun [Department of Radiology, West China Second University Hospital, Sichuan University (China)

    2014-04-15

    Purpose: To assess regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction using 3.0-T cardiac magnetic resonance (CMR) first-pass perfusion imaging. Materials and methods: Forty-two HCM patients, including 25 HCM patients with left ventricular outflow tract obstruction (HOCM), 17 HCM patients without left ventricular outflow tract obstruction (NOHCM), and 14 healthy subjects underwent CMR. The left ventricular (LV) function, left ventricular end-diastolic wall thickness (EDTH), and diameter of left ventricular outflow tract (LVOT) were measured and calculated. Based on the signal–time curve of the first-pass myocardium perfusion imaging, perfusion parameters including upslope, time to peak, and peak intensity, were assessed and compared by using one-way analysis of variance and independent t tests. Results: On the first-pass perfusion imaging, lower upslope and peak intensity and longer time to peak were found in HCM patients compared with normal subjects (all p < 0.05). In contrast to the NOHCM group, the average time to peak of the HOCM group was increased (13.30 ± 4.82 s vs 16.28 ± 4.90 s, p < 0.05), but first-pass perfusion upslope was reduced (4.96 ± 2.55 vs 2.58 ± 0.77, p < 0.05). According to the bull's-eye model, the HOCM group's average thickness of basal segments was thicker than the NOHCM group, especially the anteroseptal, inferolateral, and anterior wall values, with a corresponding lower first-pass perfusion upslope than the NOHCM group (all p < 0.05). A significant correlation was observed between first-pass perfusion upslope and LV EDTH (r = −0.551, p < 0.001) and LVOT diameter (r = 0.472, p < 0.001). Conclusions: The regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction can be detected with first-pass perfusion CMR

  17. Body mass index is associated with microvascular endothelial dysfunction in patients with treated metabolic risk factors and suspected coronary artery disease

    NARCIS (Netherlands)

    D.J. Van Der Heijden (Dirk J.); M.A.H. van Leeuwen (Maarten); G.N. Janssens (Gladys N.); M.J. Lenzen (Mattie); P.M. van de Ven (Peter); E.C. Eringa (Etto ); N. van Royen (Niels)

    2017-01-01

    textabstractBackground--Obesity is key feature of the metabolic syndrome and is associated with high cardiovascular morbidity and mortality. Obesity is associated with macrovascular endothelial dysfunction, a determinant of outcome in patients with coronary artery disease. Here, we compared the

  18. Autonomic dysfunction in different subtypes of multiple system atrophy.

    Science.gov (United States)

    Schmidt, Claudia; Herting, Birgit; Prieur, Silke; Junghanns, Susann; Schweitzer, Katherine; Globas, Christoph; Schöls, Ludger; Reichmann, Heinz; Berg, Daniela; Ziemssen, Tjalf

    2008-09-15

    Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA-C and 26 with MSA-P in comparison with 27 age- and sex-matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA-P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA-C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. (c) 2007 Movement Disorder Society.

  19. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  20. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...... the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...

  1. Disruption of microvascular flow-patterns in Alzheimer's disease correlates with neurodegeneration and cognitive decline

    DEFF Research Database (Denmark)

    Nielsen, Rune Bæksager; Egefjord, Lærke; Eskildsen, Simon Fristed

    BACKGROUND: The capillary dysfunction hypothesis of Alzheimer’s disease (AD) proposes that changes in capillary morphology and function disrupts microvascular flow-patterns, consequently, limiting oxygen delivery, causing tissue-hypoxia and neurodegeneration. Capillary dysfunction is characterized...

  2. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Deng Xiaolu

    2011-04-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

  3. Immune System Dysfunction in the Elderly.

    Science.gov (United States)

    Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

    2017-01-01

    Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

  4. Suture-free technique for canine ureteral resection-anastomosis using a microvascular anastomotic system: a cadaveric study.

    Science.gov (United States)

    Wavreille, Vincent; Adin, Christopher A; Arango, Johnattan; Ham, Kathleen L; Byron, Julie K; McLoughlin, Mary A

    2015-01-01

    To describe a suture-free technique for canine ureteral resection-anastomosis using a microvascular anastomotic system (MAS) and to compare surgical time and burst pressure of hand-sewn (HS) ureteral end-to-end anastomosis with the MAS technique. Experimental ex vivo study. Canine cadavers (n = 8). For each cadaver, 1 ureter was randomly assigned to undergo HS anastomosis and the contralateral ureter had MAS anastomosis. The first 3 cadavers (6 ureters) were used to refine the MAS technique. In the other 5 dogs, surgical time and ureteral burst pressure were compared between groups (n = 5 ureters/group). Preliminary procedures showed that selective impaling of the mucosa and submucosa (without muscularis and adventitia) is necessary to allow complete mechanical interlock of the anastomotic rings for the MAS technique. Median anastomotic time was significantly shorter for MAS (7.6 min) than HS (16.6 min; p = .029) and burst pressure higher for MAS (393 cm H2 O) than HS (180 cm H2 O; p = .012). This study demonstrated the feasibility of a suture-free technique of canine ureteral resection-anastomosis using a commercially available MAS. The MAS anastomosis was faster and had higher burst strength compared with the HS anastomosis. © Copyright 2014 by The American College of Veterinary Surgeons.

  5. Renal microvascular disease in an aging population: a reversible process?

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2008-01-01

    Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

  6. Neurodevelopment, GABA System Dysfunction, and Schizophrenia

    Science.gov (United States)

    Schmidt, Martin J; Mirnics, Karoly

    2015-01-01

    The origins of schizophrenia have eluded clinicians and researchers since Kraepelin and Bleuler began documenting their findings. However, large clinical research efforts in recent decades have identified numerous genetic and environmental risk factors for schizophrenia. The combined data strongly support the neurodevelopmental hypothesis of schizophrenia and underscore the importance of the common converging effects of diverse insults. In this review, we discuss the evidence that genetic and environmental risk factors that predispose to schizophrenia disrupt the development and normal functioning of the GABAergic system. PMID:24759129

  7. Imaging Systemic Dysfunction in Parkinson's Disease.

    Science.gov (United States)

    Borghammer, Per; Knudsen, Karoline; Brooks, David J

    2016-06-01

    Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease.

  8. A Simple, Visually Oriented Communication System to Improve Postoperative Care Following Microvascular Free Tissue Transfer: Development, Results, and Implications.

    Science.gov (United States)

    Henderson, Peter W; Landford, Wilmina; Gardenier, Jason; Otterburn, David M; Rohde, Christine H; Spector, Jason A

    2016-07-01

    Background Communication, particularly transmission of information between the surgical and nursing teams, has been identified as one of the most crucial determinants of patient outcomes. Nonetheless, transfer of information among and between the physician and nursing teams in the immediate postoperative period is often informal, verbal, and inconsistent. Methods An iterative process of multidisciplinary information gathering was undertaken to create a novel postoperative communication system (the "Pop-form"). Once developed, nurses were surveyed on multiple measures regarding the perceived likelihood that it would improve their ability to provide directed patient care. Data were quantified using a Likert scale (0-10), and statistically analyzed. Results The Pop-form records and transfers operative details, specific anatomic monitoring parameters, and senior physician contact information. Sixty-eight nurses completed surveys. The perceived usefulness of different components of the Pop-form system was as follows: 8.9 for the description of the procedure; 9.3 for the operative diagram; 9.4 for the monitoring details and parameters; and 9.4 for the direct contact information for the appropriate surgical team member. All respondents were in favor of widespread adoption of the Pop-form. Conclusion This uniform, visual communication system requires less than 1 minute to compose, yet formalizes and standardizes inter-team communication, and therefore shows promise for improving outcomes following microvascular free tissue transfer. We believe that this simple, innovative communication tool has the potential to be more broadly applied to many other health care settings. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Study of audiovestibular dysfunction in children with systemic lupus erythematosus.

    Science.gov (United States)

    Gad, Ghada Ibrahim; Mohamed, Somaia Tawfik; Awwad, Khaled Salah; Mohamed, Rehab Fetoh

    2013-09-01

    Inner ear dysfunction in systemic lupus erythematosis patients has been reported but audiovestibular involvement is not well documented especially in pediatrics. This study was designed to evaluate silent audiovestibular dysfunction among SLE children. Case control study examined in allergy and immunology clinic; pediatrics hospital and audiovestibular clinic; Ain Shams University from January 2009 to December 2010. Thirty-five systemic lupus erythematosus children (diagnosed according to American College of Rheumatology); age group 8-16 years, were randomly selected. Five of them were excluded due to one or more exclusion criteria (previous otitis media, stroke, lupus cerebritis, meningitis or encephalitis, audiovestibular symptom). Ten of them refused enrollment or could not complete full battery. Seventeen females and three males, mean age 12.9 ± 2.6 years, completed the study. Control group included 20 normal subjects, age and sex matched. Full clinical assessment, basic audiological evaluation and vestibular testing (videonystagmography VNG and computerized dynamic posturography CDP) were conducted for children included in the study. Five systemic lupus erythematosus patients had sensorineural hearing loss strongly associated with +ve antiphospholipid antibody and two had conductive hearing loss. Two children in control group had conductive hearing loss (p=0.05). Abnormal VNG findings was significantly higher among systemic lupus erythematosus children (40%) compared to controls (0%) and associated with +ve antiphospholipid antibodies (χ(2)=10, p=0.002, Fisher exact test=0.003). Twenty-five percentage of systemic lupus erythematosus children had abnormal CDP findings reflecting impaired balance function associated with positive antiphospholipid antibodies showing significant statistical difference compared to controls (0% affection) (χ(2)=5.7, p=0.017, Fisher exact test=0.047). Silent audiovestibular dysfunction is prevalent among systemic lupus

  10. [Affection of cardiovascular system in diabetic patients with thyroid dysfunctions].

    Science.gov (United States)

    Schroner, Z; Lazúrová, I

    2006-11-01

    Affection of cardiovascular system is one of the most frequent and--especially in higher age groups--the most serious clinical manifestations of thyroid dysfunction. Moreover, diabetics, mainly type 2 diabetes patients, have a marked predisposition to cardiovascular diseases, especially to atherosclerosis and its visceral complications. Simultaneous occurrence of diabetes mellitus (DM) and thyroid dysfunctions involves a very high risk of development and progression of various forms of cardiovascular diseases. There are two basal aspects of the influence of hypothyreosis on cardiovascular system. Decreasing basal metabolism in the whole organism reduces requirements on the cardiovsuclar system. The second aspect of the influence of hypothyreosis on the cardiovascular system is its atherogenic effect. Hypothyreosis in diabetics accelerates the development of chronic, primarily macroangiopathic complications. As opposed to hypothyreosis, the clinical picture of which is not characterised by cardiovascular system disorders, cardiac involvement in patients with hyperthyreosis is more pronounced. In older diabetics hyperthyreosis is often manifested only by cardiovascular symptomatology. Subclinical hyperthyreosis in DM patients may stimulate cardiac function and increase the risk of atrial fibrillation.

  11. Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet

    NARCIS (Netherlands)

    van Haare, Judith; Kooi, M. Eline; Vink, Hans; Post, Mark J.; van Teeffelen, Jurgen W. G. E.; Slenter, Jos; Munts, Chantal; Cobelens, Hanneke; Strijkers, Gustav J.; Koehn, Dennis; van Bilsen, Marc

    2015-01-01

    It remains to be established if, and to what extent, the coronary microcirculation becomes compromised during the development of obesity and insulin resistance. Recent studies suggest that changes in endothelial glycocalyx properties contribute to microvascular dysfunction under (pre-)diabetic

  12. Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

    Science.gov (United States)

    Murray, Sara G; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A; Trupin, Laura; Yelin, Edward H; Katz, Patricia P; Julian, Laura J

    2012-09-01

    Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk. Copyright © 2012 by the American College of Rheumatology.

  13. System dynamics and dysfunctionalities: levers for overcoming emergency department overcrowding.

    Science.gov (United States)

    Schiff, Gordon D

    2011-12-01

    Overcrowding of U.S. emergency departments (EDs) is a widely recognized and growing problem. This presentation offers the perspectives of a primary care physician (PCP) examining the problem at three levels: global health policy, quality process improvement, and more intimate clinical caring. It posits that ED overcrowding is actually a symptom of 10 more fundamental problems in U.S. health care and EDs: variations/supply-demand mismatch; primary care provider shortfalls; limited after-hours access; admission throughput challenges; clinical challenges related to discontinuity patients; clinical challenges related to those with special needs; interruptions; testing logistical challenges; suboptimal information systems; and fragmented/dysfunctional health insurance system, leaving many un- and underinsured. © 2011 by the Society for Academic Emergency Medicine.

  14. A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging

    International Nuclear Information System (INIS)

    Borges, J.P.; Lopes, G.O.; Verri, V.; Coelho, M.P.; Nascimento, P.M.C.; Kopiler, D.A.; Tibirica, E.

    2016-01-01

    Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men

  15. A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Borges, J.P. [Laboratório de Atividade Física e Promoção è Saúde, Departamento de Desporto Coletivo, Instituto de Educação Física e Desportos, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Lopes, G.O. [Laboratório de Atividade Física e Promoção è Saúde, Departamento de Desporto Coletivo, Instituto de Educação Física e Desportos, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Instituto Nacional de Cardiologia, Rio de Janeiro, RJ (Brazil); Verri, V.; Coelho, M.P.; Nascimento, P.M.C.; Kopiler, D.A. [Instituto Nacional de Cardiologia, Rio de Janeiro, RJ (Brazil); Tibirica, E. [Instituto Nacional de Cardiologia, Rio de Janeiro, RJ (Brazil); Laboratório de Investigação Cardiovascular, Departamento Osório de Almeida, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ (Brazil)

    2016-09-01

    Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.

  16. (Dysfunctional relations between knowledge quality and education system

    Directory of Open Access Journals (Sweden)

    Avramović Zoran

    2011-01-01

    Full Text Available Functional analysis of the relation between knowledge and education system from the viewpoint of quality is used in the paper. It is proved that it is not necessarily true that there is a correspondence between knowledge quality and construction of the education system, i.e. that the former quality is not an inevitable condition of the latter. In the first part of the paper, we distinguish the concept of quality from non-quality knowledge. Out of 19 indicators, five knowledge qualities are normative (exceptional sense, and the others descriptive (specific sense characteristics. In the second part, the conceptual approach to education system focuses on its (dysfunctional and non-functional connections. The tradition of national knowledge, the character of social relations established between the actors within the system and the influence of implicit knowledge on teacher and student actions in education system are discussed. All these factors can influence positively and negatively the direction and content of knowledge quality in education system. Knowledge quality in school curricula and textbooks may be ensured and then (not realized due to the influence of traditional, social and implicit factors on educational interaction. The concept of constellation is used to explain the favorable and unfavorable relation between knowledge quality and education system. In the concluding part, the author argues that education system cannot ensure complete realization of knowledge quality since it is, to a considerable extent, conditioned by school and non-school factors.

  17. In diabetic Charcot neuroarthropathy impaired microvascular function is related to long lasting metabolic control and low grade inflammatory process.

    Science.gov (United States)

    Araszkiewicz, Aleksandra; Soska, Jacek; Borucka, Katarzyna; Olszewska, Marta; Niedzwiecki, Pawel; Wierusz-Wysocka, Bogna; Zozulinska-Ziolkiewicz, Dorota

    2015-09-01

    The aim of this study was to assess microvascular function associated with the occurrence of Charcot neuroarthropathy (CN) in patients with diabetes. We evaluated 70 diabetic patients (54 men) with Charcot neuroarthropathy (CN-DM), median age 59 (IQR: 51-62), mean disease duration 16±8years. The control group were 70 subjects with diabetes and without Charcot neuroarthropathy (DM), 54 men, median age 60 (54-62), mean diabetes duration 15±7years. We assessed metabolic control of diabetes, serum C-reactive protein concentration (CRP) and cardiovascular autonomic neuropathy (CAN). We used AGE-Reader to measure skin autofluorescence (AF) associated with accumulation of advanced glycation end products that reflects long lasting metabolic control. Microvascular function was examined by laser Doppler flowmetry (PERIFLUX 5000) with thermal hyperemia (TH) and postocclusive reactive hyperemia (PORH). CN-DM patients as compared to DM subjects had lower HbA1c level [7.6 (6.6-8.4) vs 8.4 (7.3-9.7)%, plevel (Rs=0.42, plevel (Rs=-0.23, p=0.04). Deterioration of microvascular function and autonomic system dysfunction are present in Charcot neuroarthropathy. Impaired microvascular reactivity is associated with worse long lasting metabolic control of diabetes and low grade inflammatory process. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice.

    Science.gov (United States)

    Steven, Sebastian; Jurk, Kerstin; Kopp, Maximilian; Kröller-Schön, Swenja; Mikhed, Yuliya; Schwierczek, Kathrin; Roohani, Siyer; Kashani, Fatemeh; Oelze, Matthias; Klein, Thomas; Tokalov, Sergey; Danckwardt, Sven; Strand, Susanne; Wenzel, Philip; Münzel, Thomas; Daiber, Andreas

    2017-06-01

    Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether inhibition of dipeptidyl peptidase-4 (DPP-4) and supplementation with glucagon-like peptide-1 (GLP-1) receptor agonists improved endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. Endotoxaemia was induced in C57BL/6J mice by a single injection of LPS (17.5 mg kg -1 for survival and 10 mg kg -1 for all other studies). For survival studies, treatment was started 6 h after LPS injection. For all other studies, drugs were injected 48 h before LPS treatment. Mice treated with LPS alone showed severe thrombocytopenia, microvascular thrombosis in the pulmonary circulation (fluorescence imaging), increased LDH activity, endothelial dysfunction and increased markers of inflammation in aorta and whole blood (leukocyte-dependent oxidative burst, nitrosyl-iron haemoglobin, a marker of nitrosative stress, and expression of inducible NOS). Treatment with the DPP-4 inhibitor linagliptin or the GLP-1 receptor agonist liraglutide, as well as genetic deletion of DPP-4 (DPP4 -/- mice) improved all these parameters. In GLP-1 receptor-deficient mice, both linagliptin and liraglutide lost their beneficial effects and improvement of prognosis. Incubation of platelets and cultured monocytes (containing GLP-1 receptor protein) with GLP-1 receptor agonists inhibited the monocytic oxidative burst and platelet activation, with a GLP-1 receptor-dependent elevation of cAMP levels and PKA activation. GLP-1 receptor activation in platelets by linagliptin and liraglutide strongly attenuated endotoxaemia-induced microvascular thrombosis and mortality by a cAMP/PKA-dependent mechanism, preventing systemic inflammation, vascular dysfunction and end organ damage. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other

  19. Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients.

    Science.gov (United States)

    Barboni, Mirella Telles Salgueiro; Bueno, Clarissa; Nagy, Balázs Vince; Maia, Patrícia Lobo; Vidal, Kallene Summer Moreira; Alves, Rosana Cardoso; Reiter, Russel J; do Amaral, Fernanda Gaspar; Cipolla-Neto, José; Ventura, Dora Fix

    2018-01-01

    Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to an abnormal melatonin profile. It is not clear how the genomic disorder leads to a disturbed synchronization of the sleep/wake rhythm in SMS patients. To evaluate the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMS patients. Subjects were SMS patients (n = 5), with molecular diagnosis and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC activation), followed by a 470-nm blue light, near the melanopsin peak absorption region (direct ipRGC activation). Blue flashes produce a sustained pupillary constriction (ipRGC driven) followed by baseline return, while red flashes produce faster recovery. Pupillary light responses to 640-nm red flash were normal in SMS patients. In response to 470-nm blue flash, SMS patients had altered sustained responses shown by faster recovery to baseline. SMS patients showed impairment in the expected melatonin production suppression during the day, confirming previous reports. SMS patients show dysfunction in the sustained component of the PLR to blue light. It could explain their well-known abnormal melatonin profile and elevated circulating melatonin levels during the day. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. This retinal dysfunction might be related to a deficit in melanopsin-based photoreception, but a deficit in rod function is also possible.

  20. Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo.

    Science.gov (United States)

    Gill, Sean E; Rohan, Marta; Mehta, Sanjay

    2015-09-16

    Sepsis remains a common and serious condition with significant morbidity and mortality due to multiple organ dysfunction, especially acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Sepsis-induced ALI is characterized by injury and dysfunction of the pulmonary microvasculature and pulmonary microvascular endothelial cells (PMVEC), resulting in enhanced pulmonary microvascular sequestration and pulmonary infiltration of polymorphonuclear leukocytes (PMN) as well as disruption of the normal alveolo-capillary permeability barrier with leak of albumin-rich edema fluid into pulmonary interstitium and alveoli. The role of PMVEC death and specifically apoptosis in septic pulmonary microvascular dysfunction in vivo has not been established. In a murine cecal ligation/perforation (CLP) model of sepsis, we quantified and correlated time-dependent changes in pulmonary microvascular Evans blue (EB)-labeled albumin permeability with (1) PMVEC death (propidium iodide [PI]-staining) by both fluorescent intravital videomicroscopy (IVVM) and histology, and (2) PMVEC apoptosis using histologic fluorescent microscopic assessment of a panel of 3 markers: cell surface phosphatidylserine (detected by Annexin V binding), caspase activation (detected by FLIVO labeling), and DNA fragmentation (TUNEL labeling). Compared to sham mice, CLP-sepsis resulted in pulmonary microvascular barrier dysfunction, quantified by increased EB-albumin leak, and PMVEC death (PI+ staining) as early as 2 h and more marked by 4 h after CLP. Septic PMVEC also exhibited increased presence of all 3 markers of apoptosis (Annexin V+, FLIVO+, TUNEL+) as early as 30 mins--1 h after CLP-sepsis, which all similarly increased markedly until 4 h. The time-dependent changes in septic pulmonary microvascular albumin-permeability barrier dysfunction were highly correlated with PMVEC death (PI+; r = 0.976, p pulmonary microvascular dysfunction, including both albumin-permeability barrier dysfunction and

  1. Use of Laser Speckle Contrast Imaging to Assess Digital Microvascular Function in Primary Raynaud Phenomenon and Systemic Sclerosis: A Comparison Using the Raynaud Condition Score Diary.

    Science.gov (United States)

    Pauling, John D; Shipley, Jacqueline A; Hart, Darren J; McGrogan, Anita; McHugh, Neil J

    2015-07-01

    Evaluate objective assessment of digital microvascular function using laser speckle contrast imaging (LSCI) in a cross-sectional study of patients with primary Raynaud phenomenon (RP) and systemic sclerosis (SSc), comparing LSCI with both infrared thermography (IRT) and subjective assessment using the Raynaud Condition Score (RCS) diary. Patients with SSc (n = 25) and primary RP (n = 18) underwent simultaneous assessment of digital perfusion using LSCI and IRT with a cold challenge on 2 occasions, 2 weeks apart. The RCS diary was completed between assessments. The relationship between objective and subjective assessments of RP was evaluated. Reproducibility of LSCI/IRT was assessed, along with differences between primary RP and SSc, and the effect of sex. There was moderate-to-good correlation between LSCI and IRT (Spearman rho 0.58-0.84, p 0.05 for all analyses). Reproducibility of IRT and LSCI was moderate at baseline (ICC 0.51-0.63) and immediately following cold challenge (ICC 0.56-0.86), but lower during reperfusion (ICC 0.3-0.7). Neither subjective nor objective assessments differentiated between primary RP and SSc. Men reported lower median daily frequency of RP attacks (0.82 vs 1.93, p = 0.03). Perfusion using LSCI/IRT was higher in men for the majority of assessments. Objective and subjective methods provide differing information on microvascular function in RP. There is good convergent validity of LSCI with IRT and acceptable reproducibility of both modalities. Neither subjective nor objective assessments could differentiate between primary RP and SSc. Influence of sex on subjective and objective assessment of RP warrants further evaluation.

  2. Microvascular Anastomosis Training in Neurosurgery: A Review

    Directory of Open Access Journals (Sweden)

    Vadim A. Byvaltsev

    2018-01-01

    Full Text Available Cerebrovascular diseases are among the most widespread diseases in the world, which largely determine the structure of morbidity and mortality rates. Microvascular anastomosis techniques are important for revascularization surgeries on brachiocephalic and carotid arteries and complex cerebral aneurysms and even during resection of brain tumors that obstruct major cerebral arteries. Training in microvascular surgery became even more difficult with less case exposure and growth of the use of endovascular techniques. In this text we will briefly discuss the history of microvascular surgery, review current literature on simulation models with the emphasis on their merits and shortcomings, and describe the views and opinions on the future of the microvascular training in neurosurgery. In “dry” microsurgical training, various models created from artificial materials that simulate biological tissues are used. The next stage in training more experienced surgeons is to work with nonliving tissue models. Microvascular training using live models is considered to be the most relevant due to presence of the blood flow. Training on laboratory animals has high indicators of face and constructive validity. One of the future directions in the development of microsurgical techniques is the use of robotic systems. Robotic systems may play a role in teaching future generations of microsurgeons. Modern technologies allow access to highly accurate learning environments that are extremely similar to real environment. Additionally, assessment of microsurgical skills should become a fundamental part of the current evaluation of competence within a microneurosurgical training program. Such an assessment tool could be utilized to ensure a constant level of surgical competence within the recertification process. It is important that this evaluation be based on validated models.

  3. Anxiety, depression and autonomic nervous system dysfunction in hypertension.

    Science.gov (United States)

    Bajkó, Zoltán; Szekeres, Csilla-Cecília; Kovács, Katalin Réka; Csapó, Krisztina; Molnár, Sándor; Soltész, Pál; Nyitrai, Erika; Magyar, Mária Tünde; Oláh, László; Bereczki, Dániel; Csiba, László

    2012-06-15

    This study examined the relationship between autonomic nervous system dysfunction, anxiety and depression in untreated hypertension. 86 newly diagnosed hypertensive patients and 98 healthy volunteers were included in the study. The psychological parameters were assessed with Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory by a skilled psychologist. Autonomic parameters were examined during tilt table examination (10min lying position, 10min passive tilt). Heart rate variability (HRV) was calculated by autoregressive methods. Baroreflex sensitivity (BRS) was calculated by non-invasive sequence method from the recorded beat to beat blood pressure values and RR intervals. Significantly higher state (42.6±9.3 vs. 39.6±10.7 p=0.05) and trait (40.1±8.9 vs. 35.1±8.6, p<0.0001) anxiety scores were found in the hypertension group. There was no statistically significant difference in the depression level. LF-RRI (Low Frequency-RR interval) of HRV in passive tilt (377.3±430.6 vs. 494.1±547, p=0.049) and mean BRS slope (11.4±5.5 vs. 13.2±6.4, p=0.07) in lying position were lower in hypertensives. Trait anxiety score correlates significantly with sympatho/vagal balance (LF/HF-RRI) in passive tilt position (Spearman R=-0.286, p=0.01). Anxiety could play a more important role than depression in the development of hypertension. Altered autonomic control of the heart could be one of the pathophysiological links between hypertension and psychological factors. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Cardiovascular risk factors as determinants of retinal and skin microvascular function: The Maastricht Study

    Science.gov (United States)

    Houben, Alfons J. H. M.; Berendschot, Tos T. J. M.; Schouten, Jan S. A. G.; Kroon, Abraham A.; van der Kallen, Carla J. H.; Henry, Ronald M. A.; Koster, Annemarie; Dagnelie, Pieter C.; Schaper, Nicolaas C.; Schram, Miranda T.; Stehouwer, Coen D. A.

    2017-01-01

    Objective Microvascular dysfunction is an important underlying mechanism of microvascular diseases. Determinants (age, sex, hypertension, dyslipidemia, hyperglycemia, obesity, and smoking) of macrovascular diseases affect large-artery endothelial function. These risk factors also associate with microvascular diseases. We hypothesized that they are also determinants of microvascular (endothelial) function. Methods In The Maastricht Study, a type 2 diabetes-enriched population-based cohort study (n = 1991, 51% men, aged 59.7±8.2 years), we determined microvascular function as flicker light-induced retinal arteriolar %-dilation and heat-induced skin %-hyperemia. Multiple linear regression analyses were used to assess the associations of cardiovascular risk factors (age, sex, waist circumference, total-to-high-density lipoprotein (HDL) cholesterol ratio, fasting plasma glucose (FPG), 24-h systolic blood pressure, and cigarette smoking) with retinal and skin microvascular function. Results In multivariate analyses, age and FPG were inversely associated with retinal and skin microvascular function (regression coefficients per standard deviation (SD) were -0.11SD (95%CI: -0.15;-0.06) and -0.12SD (-0.17;-0.07) for retinal arteriolar %-dilation and -0.10SD (-0.16;-0.05) and -0.11SD (-0.17;-0.06) for skin %-hyperemia, respectively. Men and current smokers had -0.43SD (-0.58;-0.27) and -0.32SD (-0.49;-0.15) lower skin %-hyperemia, respectively. 24-h systolic blood pressure, waist circumference, and total-to-HDL cholesterol ratio were not statistically significantly associated with these microvascular functions. Conclusions Associations between cardiovascular risk factors and retinal and skin microvascular function show a pattern that is partly similar to the associations between cardiovascular risk factors and macrovascular function. Impairment of microvascular function may constitute a pathway through which an adverse cardiovascular risk factor pattern may increase risk of

  5. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    Directory of Open Access Journals (Sweden)

    Jaime M. Ross

    2015-08-01

    Full Text Available Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing.

  6. SU-E-J-197: A Novel Optical Interstitial Fiber Spectroscopic System for Real-Time Tissue Micro-Vascular Hemodynamics Monitoring.

    Science.gov (United States)

    Zhao, D; Campos, D; Yan, Y; Kimple, R; Jacques, S; van der Kogel, A; Kissick, M

    2012-06-01

    To demonstrate a novel interstitial optical fiber spectroscopic system, based on diffuse optical spectroscopies with spectral fitting, for the simultaneous monitoring of tumor blood volume and oxygen tension. The technique provides real-time, minimally-invasive and quantification of tissue micro-vascular hemodynamics. An optical fiber prototype probe characterizesthe optical transport in tissue between two large Numerical Aperture (NA) fibers of 200μm core diameter (BFH37-200, ThorLabs) spaced 3-mm apart. Two 21-Ga medical needles are used to protect fiber ends and to facilitate tissue penetration with minimum local blunt trauma in nude mice with xenografts. A 20W white light source (HL-2000-HP, Ocean Optics) is coupled to one fiber with SMA adapter. The other fiber is used to collect light, which is coupled into the spectrometer (QE65000 with Spectrasuite Operating software and OmniDriver, Ocean Optics). The wavelength response of the probe depends on the wavelength dependence of the light source, and of the light signal collection that includes considerable scatter, modeled with Monte-Carlo techniques (S. Jacques 2010 J. of Innov. Opt. Health Sci. 2 123-9). Measured spectra of tissue are normalized by a measured spectrum of a white standard, yielding the transmission spectrum. A head-and-neck xenograft on the flank of a live mouse is used for development. The optical fiber probe delivers and collects light at an arbitrary depth in the tumor. By spectral fitting of the measured transmission spectrum, an analysis of blood volume and oxygen tension is obtained from the fitting parameters in real time. A newly developed optical fiber spectroscopic system with an optical fiber probe takes spectroscopic techniques to a much deeper level in a tumor, which has potential applications for real-time monitoring hypoxic cell population dynamics for an eventual adaptive therapy metric of particular use in hypofractionated radiotherapy. © 2012 American Association of

  7. Leydig cell dysfunction, systemic inflammation and metabolic syndrome in long-term testicular cancer survivors.

    Science.gov (United States)

    Bandak, M; Jørgensen, N; Juul, A; Lauritsen, J; Oturai, P S; Mortensen, J; Hojman, P; Helge, J W; Daugaard, G

    2017-10-01

    Twenty to thirty percent of testicular cancer (TC) survivors have elevated serum levels of luteinising hormone (LH) with or without corresponding low testosterone levels (Leydig cell dysfunction) during clinical follow-up for TC. However, it remains to be clarified if this subgroup of TC survivors has an increased long-term risk of systemic inflammation and metabolic syndrome (MetS) when compared with TC survivors with normal Leydig cell function during follow-up. TC survivors with Leydig cell dysfunction and a control group of TC survivors with normal Leydig cell function during follow-up were eligible for participation in the study. Markers of systemic inflammation and prevalence of MetS were compared between TC survivors with Leydig cell dysfunction and the control group. Of 158 included TC survivors, 28 (18%) had uncompensated Leydig cell dysfunction, 59 (37%) had compensated Leydig cell dysfunction and 71 (45%) had normal Leydig cell function during follow-up. MetS and markers of systemic inflammation were evaluated at a median follow-up of 9.7 years (interquartile range 4.1-17.1) after TC treatment. The prevalence of MetS was significantly lower among patients with compensated Leydig cell dysfunction during follow-up (12% versus 27%, p = 0.04), whereas there was no difference between TC survivors with uncompensated Leydig cell dysfunction and controls (33% versus 27%, p = 0.5). Apart from high-sensitivity C-reactive protein which was higher in TC survivors with uncompensated Leydig cell dysfunction during follow-up, there was no evidence of increased systemic inflammation in patients with Leydig cell dysfunction during clinical follow-up. Total testosterone at follow-up was significantly associated with MetS, whereas there was no association between LH and MetS. We did not find evidence that TC survivors with Leydig cell dysfunction during clinical follow-up had increased long-term risk of MetS. Total testosterone at follow-up was significantly associated

  8. Dysfunctional Neurotransmitter Systems in Fibromyalgia, Their Role in Central Stress Circuitry and Pharmacological Actions on These Systems

    Directory of Open Access Journals (Sweden)

    Susanne Becker

    2012-01-01

    Full Text Available Fibromyalgia is considered a stress-related disorder, and hypo- as well as hyperactive stress systems (sympathetic nervous system and hypothalamic-pituitary-adrenal axis have been found. Some observations raise doubts on the view that alterations in these stress systems are solely responsible for fibromyalgia symptoms. Cumulative evidence points at dysfunctional transmitter systems that may underlie the major symptoms of the condition. In addition, all transmitter systems found to be altered in fibromyalgia influence the body's stress systems. Since both transmitter and stress systems change during chronic stress, it is conceivable that both systems change in parallel, interact, and contribute to the phenotype of fibromyalgia. As we outline in this paper, subgroups of patients might exhibit varying degrees and types of transmitter dysfunction, explaining differences in symptomatoloy and contributing to the heterogeneity of fibromyalgia. The finding that not all fibromyalgia patients respond to the same medications, targeting dysfunctional transmitter systems, further supports this hypothesis.

  9. Arterial vasculopathy in systemic sclerosis: Computerized tomography (CT) angiographic features of macrovascular and microvascular upper limbs arteries

    NARCIS (Netherlands)

    Emad, Y.; Al-Sherbeni, H.; Ragab, Y.; Abo-El-Youn, I.; El-Shaarawy, N.; Nassar, D.Y.; Fathy, A.; Al-Hanafi, H.; Rasker, Johannes J.

    2014-01-01

    Objective To describe the CT angiographic findings of arterial vasculopathy in the major vessels as well as medium and micro vascular affection of the whole upper limbs arterial tree in patients with systemic sclerosis (SSc) with and without digital ulceration. Methods Twenty-two cases with systemic

  10. Motor system dysfunction in the schizophrenia diathesis: Neural systems to neurotransmitters.

    Science.gov (United States)

    Abboud, R; Noronha, C; Diwadkar, V A

    2017-07-01

    Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary motor area, dorsal anterior cingulate cortex, the prefrontal cortex, the basal ganglia, and cerebellum. Notably all of these regions are associated in some manner to the pathophysiology of schizophrenia. At the molecular scale, both dopamine and γ-Aminobutyric Acid (GABA) abnormalities have been associated with working memory dysfunction, but particularly relating to the basal ganglia and the prefrontal cortex respectively. As evidence from multiple scales (behavioral, regional and molecular) converges, here we provide a synthesis of the bio-behavioral relevance of motor dysfunction in schizophrenia, and its consistency across scales. We believe that the selective compendium we provide can supplement calls arguing for renewed interest in studying the motor system in schizophrenia. We believe that in addition to being a highly relevant target for the study of schizophrenia related pathways in the brain, such focus provides tractable behavioral probes for in vivo imaging studies in the illness. Our assessment is that the motor system is a highly valuable research domain for the study of schizophrenia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Tydén, Helena; Lood, Christian; Gullstrand, Birgitta

    2017-01-01

    Objectives Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated...... the interplay between endothelial dysfunction, platelets and type I IFN in SLE. Methods We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs). Type I IFN activity was assessed with a reporter cell assay and platelet activation by flow cytometry. Endothelial dysfunction...... with activation of platelets and the type I IFN system. We suggest that an interplay between the type I IFN system, injured endothelium and activated platelets may contribute to development of CVD in SLE....

  12. Digestive system dysfunction in cystic fibrosis: challenges for nutrition therapy.

    Science.gov (United States)

    Li, Li; Somerset, Shawn

    2014-10-01

    Cystic fibrosis can affect food digestion and nutrient absorption. The underlying mutation of the cystic fibrosis trans-membrane regulator gene depletes functional cystic fibrosis trans-membrane regulator on the surface of epithelial cells lining the digestive tract and associated organs, where Cl(-) secretion and subsequently secretion of water and other ions are impaired. This alters pH and dehydrates secretions that precipitate and obstruct the lumen, causing inflammation and the eventual degradation of the pancreas, liver, gallbladder and intestine. Associated conditions include exocrine pancreatic insufficiency, impaired bicarbonate and bile acid secretion and aberrant mucus formation, commonly leading to maldigestion and malabsorption, particularly of fat and fat-soluble vitamins. Pancreatic enzyme replacement therapy is used to address this insufficiency. The susceptibility of pancreatic lipase to acidic and enzymatic inactivation and decreased bile availability often impedes its efficacy. Brush border digestive enzyme activity and intestinal uptake of certain disaccharides and amino acids await clarification. Other complications that may contribute to maldigestion/malabsorption include small intestine bacterial overgrowth, enteric circular muscle dysfunction, abnormal intestinal mucus, and intestinal inflammation. However, there is some evidence that gastric digestive enzymes, colonic microflora, correction of fatty acid abnormalities using dietary n-3 polyunsaturated fatty acid supplementation and emerging intestinal biomarkers can complement nutrition management in cystic fibrosis. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Leydig cell dysfunction, systemic inflammation and metabolic syndrome in long-term testicular cancer survivors

    DEFF Research Database (Denmark)

    Bandak, M; Jørgensen, N; Juul, A

    2017-01-01

    BACKGROUND: Twenty to thirty percent of testicular cancer (TC) survivors have elevated serum levels of luteinising hormone (LH) with or without corresponding low testosterone levels (Leydig cell dysfunction) during clinical follow-up for TC. However, it remains to be clarified if this subgroup...... of TC survivors has an increased long-term risk of systemic inflammation and metabolic syndrome (MetS) when compared with TC survivors with normal Leydig cell function during follow-up. PATIENTS AND METHODS: TC survivors with Leydig cell dysfunction and a control group of TC survivors with normal Leydig...... cell function during follow-up were eligible for participation in the study. Markers of systemic inflammation and prevalence of MetS were compared between TC survivors with Leydig cell dysfunction and the control group. RESULTS: Of 158 included TC survivors, 28 (18%) had uncompensated Leydig cell...

  14. Compact dual-mode diffuse optical system for blood perfusion monitoring in a porcine model of microvascular tissue flaps

    Science.gov (United States)

    Lee, Seung Yup; Pakela, Julia M.; Helton, Michael C.; Vishwanath, Karthik; Chung, Yooree G.; Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Christian, James F.; O'Reilly, Jameson; Farkas, Dana; Ward, Brent B.; Feinberg, Stephen E.; Mycek, Mary-Ann

    2017-12-01

    In reconstructive surgery, the ability to detect blood flow interruptions to grafted tissue represents a critical step in preventing postsurgical complications. We have developed and pilot tested a compact, fiber-based device that combines two complimentary modalities-diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy-to quantitatively monitor blood perfusion. We present a proof-of-concept study on an in vivo porcine model (n=8). With a controllable arterial blood flow supply, occlusion studies (n=4) were performed on surgically isolated free flaps while the device simultaneously monitored blood flow through the supplying artery as well as flap perfusion from three orientations: the distal side of the flap and two transdermal channels. Further studies featuring long-term monitoring, arterial failure simulations, and venous failure simulations were performed on flaps that had undergone an anastomosis procedure (n=4). Additionally, benchtop verification of the DCS system was performed on liquid flow phantoms. Data revealed relationships between diffuse optical measures and state of occlusion as well as the ability to detect arterial and venous compromise. The compact construction of the device, along with its noninvasive and quantitative nature, would make this technology suitable for clinical translation.

  15. Birth weight relates to blood pressure and microvascular function in normal subjects

    NARCIS (Netherlands)

    Serne, EH; Stehouwer, CDA; ter Maaten, JC; ter Wee, PM; Gans, ROB

    2000-01-01

    Objective The relationship between low birth weight and elevated blood pressure in adult life is well established but presently unexplained. Both microvascular dysfunction and insulin resistance have been proposed as a possible explanation. We have examined the relation between birth weight and

  16. Intravascular Stenting in Microvascular Anastomoses

    DEFF Research Database (Denmark)

    Assersen, Kristine; Sørensen, Jens

    2015-01-01

    Background The effect of intravascular stenting (IVaS) on microvascular anastomoses has given adverse results. For experienced microsurgeons the benefit of IVaS is doubtful. We have investigated the potential benefit of the IVaS technique for two groups of inexperienced microsurgeons with differe...

  17. Dysfunction and Failure in Open Family Systems, I: Application of a Unified Theory.

    Science.gov (United States)

    Constantine, Larry L.

    1983-01-01

    Develops a detailed profile of dysfunction and disablement in the open family system: its intrinsic defects, response to crisis, and likely process of breakdown when overstressed. Suggests that somatic symptoms of stress in children may grow out of accelerated independence combined with parental overinvolvement. (JAC)

  18. Modeling of respiratory system dysfunction among nuclear workers: a preliminary study.

    Science.gov (United States)

    Belyaeva, Z D; Osovets, S V; Scott, B R; Zhuntova, G V; Grigoryeva, E S

    2008-01-01

    Numerous studies have reported on cancers among Mayak Production Association (PA) nuclear workers. Other studies have reported on serious deterministic effects of large radiation doses for the same population. This study relates to deterministic effects (respiratory system dysfunction) in Mayak workers after relatively small chronic radiation doses (alpha plus gamma). Because cigarette smoke is a confounding factor, we also account for smoking effects. Here we present a new empirical mathematical model that was introduced for simultaneous assessment of radiation and cigarette-smoking-related damage to the respiratory system. The model incorporates absolute thresholds for smoking- and radiation-induced respiratory system dysfunction. As the alpha radiation dose to the lung increased from 0 to 4.36 Gy, respiratory function indices studied decreased, although remaining in the normal range. The data were consistent with the view that alpha radiation doses to the lung above a relatively small threshold (0.15 to 0.39 Gy) cause some respiratory system dysfunction. Respiratory function indices were not found to be influenced by total-body gamma radiation doses in the range 0-3.8 Gy when delivered at low rates over years. However, significant decreases in airway conductance were found to be associated with cigarette smoking. Whether the indicated cigarette smoking and alpha radiation associated dysfunction is debilitating is unclear.

  19. Language Disorders due to Posterior System Strokes - An Ignored Dysfunction

    Science.gov (United States)

    ÖZTÜRK, Şerefnur; EGE, Fahrettin; EKMEKÇİ, Hakan

    2014-01-01

    The anterior system is primarily responsible for the clinical picture in a patient that presents with clinical aphasia. However, recent reports have shown that injuries to posterior structures, the cerebellum in particular, may have a role in language processing. Herein, we will look first at the linguistic role of the cerebellum in light of the literature, then of the thalamus and some described clinical syndromes, and finally, specific syndromes resulting from occipital lobe lesions, all of which are supported by the posterior vascular system. The human brain is such a complex organization that in addition to the thalamus and occipital cortex, we can see the involvement of the cerebellum in high cognitive functions. Posterior system strokes may lead to clinical findings of cognitive deficits, including neurolinguistic components. Determining these defects in stroke patients may precipitate changes in current management strategies. PMID:28360648

  20. Active cooling of microvascular composites for battery packaging

    Science.gov (United States)

    Pety, Stephen J.; Chia, Patrick X. L.; Carrington, Stephen M.; White, Scott R.

    2017-10-01

    Batteries in electric vehicles (EVs) require a packaging system that provides both thermal regulation and crash protection. A novel packaging scheme is presented that uses active cooling of microvascular carbon fiber reinforced composites to accomplish this multifunctional objective. Microvascular carbon fiber/epoxy composite panels were fabricated and their cooling performance assessed over a range of thermal loads and experimental conditions. Tests were performed for different values of coolant flow rate, channel spacing, panel thermal conductivity, and applied heat flux. More efficient cooling occurs when the coolant flow rate is increased, channel spacing is reduced, and thermal conductivity of the host composite is increased. Computational fluid dynamics (CFD) simulations were also performed and correlate well with the experimental data. CFD simulations of a typical EV battery pack confirm that microvascular composite panels can adequately cool battery cells generating 500 W m-2 heat flux below 40 °C.

  1. Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

    Science.gov (United States)

    Ahmed, R G

    2016-09-01

    Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

    Science.gov (United States)

    Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

    2015-11-01

    See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Cholinergic function and dysfunction in the visual system.

    Science.gov (United States)

    Beelke, M; Sannita, W G

    2002-01-01

    Acetylcholine (ACh) function is thought not only to play a significant role in memory, learning and other cognitive processes, but studies at a cellular level and in vivo indicate an important role for ACh in vision as well, especially for visual information processing. A suitable experimental model of geriatric memory impairment and Alzheimer dementia that pharmacologically blocks the brain muscarinic transmission has been proposed. This model has been extensively used also as an attempt to test cholinergic drugs in the absence of detailed knowledge of sites and mechanisms of ACh action and as test condition in the investigation of the role of ACh in visual information processing. Alzheimer's dementia results from complex neuron alterations, rather than simply reflecting ACh impoverishment, also involving the visual system, with substantial loss of retinal ganglion cells and alterations in visual information processing. Viewing all these data as a whole, nonspecific ACh actions on cognition, such as arousal or attention, contribute in modulating the function-specific action of ACh in information processing, both at cognitive and visual level.

  4. Prevalence of thyroid dysfunctions in systemic lupus erythematosus.

    Science.gov (United States)

    Antonelli, Alessandro; Fallahi, Poupak; Mosca, Marta; Ferrari, Silvia Martina; Ruffilli, Ilaria; Corti, Alessandro; Panicucci, Erica; Neri, Rossella; Bombardieri, Stefano

    2010-06-01

    The association of systemic lupus erythematosus (SLE) and thyroid autoimmunity has been reported by several studies in a wide range of variability. However, from a review of the literature, discrepant results have been reported. The aim of the study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with SLE vs sex- and age-matched controls. Thyroid hormones and the presence of antithyroid antibodies were tested and thyroid ultrasonography was performed in 213 patients with SLE vs 426 sex- and age-matched controls, from the same geographic area, with a well-defined status of iodine intake. The odds ratio for subclinical hypothyroidism for female patients with SLE with respect to controls was 4.5 (95% confidence interval [CI], 2.5-8.4); for antithyroid peroxidase antibody (AbTPO) positivity, it was 2.6 (95% CI, 1.7-4.1); and for thyroid autoimmunity, it was 2.9 (95% CI, 2.0-4.4). The mean values of thyroid-stimulating hormone and AbTPO were higher in female SLE patients than in controls (P illness syndrome" vs 0 control. Thyroid function and AbTPOs should be tested and ultrasonography should be performed as part of the clinical profile in SLE patients. Subjects at high risk (women, positive AbTPOs, hypoechoic, and small thyroid) should have thyroid function follow-up and appropriate treatment in due course. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Evaluation of the portal venous system using MR angiography in patients with severe liver dysfunction

    International Nuclear Information System (INIS)

    Fukatsu, Hiroshi; Ando, Yoko; Yamakawa, Koji; Ishigaki, Takeo

    1994-01-01

    Fifteen patients of chronic liver dysfunction were examined with 2D TOF MR angiography to assess the portal venous system condition. All of the collateral pathways except esophageal varices were clearly demonstrated in all cases, portal vein thromboses were accurately diagnosed in two cases. Portal vein visualization index were determined as follows: good delineation of the main portal vein only; good delineation of the first tributaries of the intrahepatic portal vein; good delineation of the second or further tributaries. This index showed good correlation with the clinical stage proposed by Japan liver cancer study group. These results suggested that MR angiography has a potential for the evaluation of the portal system in patients with severe liver dysfunction. (author)

  6. Renal tubular dysfunction presenting as recurrent hypokalemic periodic quadriparesis in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    D Prasad

    2014-01-01

    Full Text Available We report recurrent hypokalemic periodic quadriparesis in a 30-year-old woman. Patient had also symptoms of multiple large and small joint pain, recurrent oral ulceration, photosensitivity and hair loss that were persisting since last 6 months and investigations revealed systemic lupus erythematosus (SLE with distal tubular acidosis. Our patient was successfully treated with oral potassium chloride, sodium bicarbonate, hydroxychloroquine and a short course of steroids. Thus, tubular dysfunction should be carefully assessed in patients with SLE.

  7. Modeling of Respiratory System Dysfunction Among Nuclear Workers: A Preliminary Study

    OpenAIRE

    Belyaeva, Z.D.; Osovets, S.V.; Scott, B.R.; Zhuntova, G.V.; Grigoryeva, E.S.

    2008-01-01

    Numerous studies have reported on cancers among Mayak Production Association (PA) nuclear workers. Other studies have reported on serious deterministic effects of large radiation doses for the same population. This study relates to deterministic effects (respiratory system dysfunction) in Mayak workers after relatively small chronic radiation doses (alpha plus gamma). Because cigarette smoke is a confounding factor, we also account for smoking effects. Here we present a new empirical mathemat...

  8. Lower urinary tract dysfunction in patients with peripheral nervous system lesions.

    Science.gov (United States)

    Podnar, Simon; Vodušek, David B

    2015-01-01

    The prevalence of lower urinary tract (LUT) dysfunction in peripheral nervous system (PNS) disorders is larger than in comparable control populations. This is particularly true for polyneuropathies with autonomic nervous system involvement, and for localized lesions with LUT innervation. LUT symptoms may be the guide to the diagnosis of processes localized in the lumbosacral spinal canal (as in cauda equina syndrome), and in the pelvis. Typical LUT dysfunctions (LUTD) caused by PNS involvement include bladder and sphincter hypoactivity with poor emptying, and incontinence. Paradoxically, bladder overactivity may also occur in pure PNS lesions. The acute cauda equina syndrome is an emergency requiring magnetic resonance imaging and surgery; in chronic neurogenic LUTD due to PNS involvement, the diagnosis of the lesion may be clarified by clinical neurophysiologic testing. Other important causes of neurogenic LUT dysfunction are perineoabdominal and pelvic surgeries. Surgeons are devising nerve-sparing techniques to prevent such major and often persistent complications in patients who are otherwise cured of the underlying disease. LUTD significantly affects the quality of life in patients and may lead to recurring urinary infections and upper urinary tract involvement. Thorough assessment of LUT function by urodynamics may be necessary in patients who are not improved by simple conservative measures. © 2015 Elsevier B.V. All rights reserved.

  9. Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation.

    Science.gov (United States)

    Andersen, Kirstin; Kesper, Marie Sophie; Marschner, Julian A; Konrad, Lukas; Ryu, Mi; Kumar Vr, Santhosh; Kulkarni, Onkar P; Mulay, Shrikant R; Romoli, Simone; Demleitner, Jana; Schiller, Patrick; Dietrich, Alexander; Müller, Susanna; Gross, Oliver; Ruscheweyh, Hans-Joachim; Huson, Daniel H; Stecher, Bärbel; Anders, Hans-Joachim

    2017-01-01

    CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences. Copyright © 2016 by the American Society of Nephrology.

  10. Microvascular function in pre-eclampsia is influenced by insulin resistance and an imbalance of angiogenic mediators.

    Science.gov (United States)

    Ghosh, Anshuman; Freestone, Nicholas S; Anim-Nyame, Nicholas; Arrigoni, Francesca I F

    2017-04-01

    In preeclampsia, maternal microvascular function is disrupted and angiogenesis is dysfunctional. Insulin resistance that occurs in some pregnancies also pathologically affects microvascular function. We wished to examine the relationship of angiogenic mediators and insulin resistance on microvascular health in pregnancy. We performed a nested, case-control study of 16 women who developed preeclampsia with 17 normal pregnant controls. We hypothesized that the impaired microvascular blood flow in preeclamptic women associated with an increased ratio of the antiangiogenic factors; (s-endoglin [sEng] and soluble fms-like tyrosine kinase-1 [sFlt-1]) and proangiogenic molecule (placental growth factor [PlGF]) could be influenced by insulin resistance. Serum samples taken after 28 weeks of gestation were measured for the angiogenic factors, insulin, and glucose alongside the inflammatory marker; tumor necrosis factor-α and endothelial activation, namely; soluble vascular cell adhesion molecule 1, intercellular adhesion molecule-1, and e-selectin. Maternal microvascular blood flow, measured by strain gauge plethysmography, correlated with ratios of pro- and antiangiogenic mediators independently of preeclampsia. Decreased microvascular function measured in preeclampsia strongly correlated with both the antiangiogenic factor (sFlt-1 + sEng): PlGF ratio and high levels of insulin resistance, and combining insulin resistance with antiangiogenic factor ratios further strengthened this relationship. In pregnancy, microvascular blood flow is strongly associated with perturbations in pro- and antiangiogenic mediators. In preeclampsia, the relationship of maternal microvascular dysfunction with antiangiogenic mediators is strengthened when combined with insulin resistance. © 2017 Kingston University. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  11. Microvascularization on collared peccary placenta

    DEFF Research Database (Denmark)

    Santos, Tatiana Carlesso; Oliveira, Moacir Franco; Dantzer, Vibeke

    2012-01-01

    into a microvascular network wall in a basket-like fashion. At the base of these baskets venules were formed. On the fetal side, arterioles branched centrally in the fetal rugae into a capillary network in a bulbous form, complementary to the opposite maternal depressions forming the baskets. At the base...... of the bulbous protrusions, the fetal venules arise. The blood vessel orientation in the materno-fetal interface of the placentae of collared peccaries suggests a blood flow pattern of the type countercurrent to cross current. The same pattern has been reported in domestic swine demonstrating that, even after 38...

  12. Brainstem and Autonomic Nervous System Dysfunction: A Neurosurgical Point of View.

    Science.gov (United States)

    Martín-Gallego, A; González-García, L; Carrasco-Brenes, A; Segura-Fernández-Nogueras, M; Delgado-Babiano, A; Ros-Sanjuán, A; Romero-Moreno, L; Domínguez-Páez, M; Dawid-Milner, M S; Arráez-Sánchez, M A

    2017-01-01

    Central autonomic control nuclei and pathways are mainly integrated within the brainstem, especially in the medulla oblongata. Lesions within these structures can lead to central dysautonomia.Central autonomic control structures can be damaged by tumors, during surgery, or by other neurosurgical pathologies. These may elicit clinical or subclinical autonomic complications that can constitute a serious clinical problem.The authors present a broad review of the central autonomic nervous system, its possible dysfunctions, and the relation between neurosurgery and this "not-well-known system". Preliminary results of an autonomic study of brainstem lesions that is currently being carried out by the authors are also shown.

  13. Cognitive dysfunction in systemic lupus erythematosus in relation to disease activity and damage

    Directory of Open Access Journals (Sweden)

    Guido Dorman

    2017-08-01

    Full Text Available Systemic lupus erythematosus (SLE is a rheumatic disease, which during its evolution may present neurocognitive dysfunction with fronto-subcortical compromise. However, there is no enough published evidence regarding the relationship between cognitive dysfunction and SLE activity and SLE induced damage. The objective of the study was to analyze this association. We designed an observational cross-sectional study including 84 patients with SLE. We used the SLEDAI index to evaluate activity and the SLICC index to evaluate cumulative damage. We used neuropsychological tests to assess the presence of cognitive symptoms, global cognitive function, verbal and visual memory, visual-construction, semantic verbal fluency, processing speed and working memory. Scores more than 1.5 standard deviations below adjusted normal values were considered as cognitive dysfunction. We observed a statistically significant association between the higher value of SLEDAI and working memory impairment and a higher value of SLICC and viso-construction and semantic verbal fluency impairment. The association observed in SLE patients between disease activity or damage and some cognitive domains may be involving different pathophysiological brain mechanisms of different areas with different degrees of severity and vulnerability

  14. C3 Glomerulopathy and Atypical Hemolytic Uremic Syndrome: Two Important Manifestations of Complement System Dysfunction

    Directory of Open Access Journals (Sweden)

    Ravneet Bajwa

    2018-02-01

    Full Text Available The advances in our understanding of the alternative pathway have emphasized that uncontrolled hyperactivity of this pathway causes 2 distinct disorders that adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome (aHUS, renal dysfunction occurs along with thrombocytopenia, anemia, and target organ injury to multiple organs, most commonly the kidney. On the other hand, in the so-termed C3 glomerulopathy, kidney involvement is not associated with thrombocytopenia, anemia, or other system involvement. In this report, we present 2 cases of alternative pathway dysfunction. The 60-year-old female patient had biopsy-proven C3 glomerulopathy, while the 32-year-old female patient was diagnosed with aHUS based on renal dysfunction, thrombocytopenia, anemia, and normal ADAMTS-13 level. The aHUS patient was successfully treated with the monoclonal antibody (eculizumab for complement blockade. The patient with C3 glomerulopathy did not receive the monoclonal antibody. In this patient, management focused on blood pressure and proteinuria control with an angiotensin-converting enzyme inhibitor. This article focuses on the clinical differences, pathophysiology, and treatment of aHUS and C3 glomerulopathy.

  15. Endothelial dysfunction

    OpenAIRE

    Yaylalı, Yalın Tolga; Küçükaslan, Mete

    2011-01-01

    Endothelium is a multi-functional cluster of cells within the vascular system consisting of a single layer ofsquamous epithelium. Physiologically, endothelium performs various arrangement and protection functions.However, when these functions are disturbed toward derangement, endothelium also mediates pathologicalfunctions with negative effects on the body. Endothelial dysfunction is mediated by several mediators (nitricoxide, endothelins, prostaglandins, angiotensin 2, etc). Endothelial dysf...

  16. Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Ewers, Michael

    2012-02-01

    Sporadic Alzheimer\\'s disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.

  17. Probiotics (VSL#3 prevent endothelial dysfunction in rats with portal hypertension: role of the angiotensin system.

    Directory of Open Access Journals (Sweden)

    Sherzad K Rashid

    Full Text Available AIMS: Portal hypertension characterized by generalized vasodilatation with endothelial dysfunction affecting nitric oxide (NO and endothelium-dependent hyperpolarization (EDH has been suggested to involve bacterial translocation and/or the angiotensin system. The possibility that ingestion of probiotics prevents endothelial dysfunction in rats following common bile duct ligation (CBDL was evaluated. METHODS: Rats received either control drinking water or the probiotic VSL#3 solution (50 billion bacteria.kg body wt⁻¹.day⁻¹ for 7 weeks. After 3 weeks, rats underwent surgery with either resection of the common bile duct or sham surgery. The reactivity of mesenteric artery rings was assessed in organ chambers, expression of proteins by immunofluorescence and Western blot analysis, oxidative stress using dihydroethidium, and plasma pro-inflammatory cytokine levels by flow cytometry. RESULTS: Both NO- and EDH-mediated relaxations to acetylcholine were reduced in the CBDL group compared to the sham group, and associated with a reduced expression of Cx37, Cx40, Cx43, IKCa and SKCa and an increased expression of endothelial NO synthase (eNOS. In aortic sections, increased expression of NADPH oxidase subunits, angiotensin converting enzyme, AT1 receptors and angiotensin II, and formation of ROS and peroxynitrite were observed. VSL#3 prevented the deleterious effect of CBDL on EDH-mediated relaxations, vascular expression of connexins, IKCa, SKCa and eNOS, oxidative stress, and the angiotensin system. VSL#3 prevented the CBDL-induced increased plasma TNF-α, IL-1α and MCP-1 levels. CONCLUSIONS: These findings indicate that VSL#3 ingestion prevents endothelial dysfunction in the mesenteric artery of CBDL rats, and this effect is associated with an improved vascular oxidative stress most likely by reducing bacterial translocation and the local angiotensin system.

  18. [The role of dysfunction of the autonomic nervous system in idiopathic overactive urinary bladder in women].

    Science.gov (United States)

    Borisov, V V; Akarachkova, E S; Shvarkov, S B; Grigorashvili, I I; Romikh, V V

    2012-01-01

    A complex urological and neurological examination of female patients with idiopathic overactive bladder (IOAB) has detected clinical signs and neurophysiological correlates of vegetative dysfunction in the form of disturbed sympatho-parasympathic interrelations, failure of segmental and compensatory enhancement of suprasegmental mechanisms of regulation of lower urinary tract activity. The treatment with selective inhibitors of serotonin re-entry reduced severity ofpsychovegetative syndrome and symptoms of the lower urinary tract. This confirms an essential role of the autonomic nervous system in pathogenetic mechanisms of IOAB development and gives grounds for recommending selective inhibitors of serotonin re-entry for combined treatment of IOAB patients.

  19. Obligatory role of hyperaemia and shear stress in microvascular adaptation to repeated heating in humans.

    Science.gov (United States)

    Green, Daniel J; Carter, Howard H; Fitzsimons, Matthew G; Cable, N Timothy; Thijssen, Dick H J; Naylor, Louise H

    2010-05-01

    The endothelium, a single layer of cells lining the entire circulatory system, plays a key role in maintaining vascular health. Endothelial dysfunction independently predicts cardiovascular events and improvement in endothelial function is associated with decreased vascular risk. Previous studies have suggested that exercise training improves endothelial function in macrovessels, a benefit mediated via repeated episodic increases in shear stress. However, less is known of the effects of shear stress modulation in microvessels. In the present study we examined the hypothesis that repeated skin heating improves cutaneous microvascular vasodilator function via a shear stress-dependent mechanism. We recruited 10 recreationally active males who underwent bilateral forearm immersion in warm water (42 degrees C), 3 times per week for 30 min. During these immersion sessions, shear stress was manipulated in one arm by inflating a pneumatic cuff to 100 mmHg, whilst the other arm remained uncuffed. Vasodilatation to local heating, a NO-dependent response assessed using laser Doppler, improved across the 8 week intervention period in the uncuffed arm (cutaneous vascular conductance week 0 vs. week 4 at 41 degrees C: 1.37 +/- 0.45 vs. 2.0 +/- 0.91 units, P = 0.04; 42 degrees C: 2.06 +/- 0.45 vs. 2.68 +/- 0.83 units; P = 0.04), whereas no significant changes were evident in the cuffed arm. We conclude that increased blood flow, and the likely attendant increase in shear stress, is a key physiological stimulus for enhancing microvascular vasodilator function in humans.

  20. Parasympathetic nervous system dysfunction, as identified by pupil light reflex, and its possible connection to hearing impairment

    OpenAIRE

    Wang, Yang; Zekveld, Adriana A.; Naylor, Graham; Ohlenforst, Barbara; Jansma, Elise P.; Lorens, Artur; Lunner, Thomas; Kramer, Sophia E.

    2016-01-01

    Context\\ud Although the pupil light reflex has been widely used as a clinical diagnostic tool for autonomic nervous system dysfunction, there is no systematic review available to summarize the evidence that the pupil light reflex is a sensitive method to detect parasympathetic dysfunction. Meanwhile, the relationship between parasympathetic functioning and hearing impairment is relatively unknown.\\ud \\ud Objectives\\ud To 1) review the evidence for the pupil light reflex being a sensitive meth...

  1. Outcomes and organ dysfunctions of critically ill patients with systemic lupus erythematosus and other systemic rheumatic diseases

    Directory of Open Access Journals (Sweden)

    O.T. Ranzani

    2011-11-01

    Full Text Available Our objective was to compare the pattern of organ dysfunctions and outcomes of critically ill patients with systemic lupus erythematosus (SLE with patients with other systemic rheumatic diseases (SRD. We studied 116 critically ill SRD patients, 59 SLE and 57 other-SRD patients. The SLE group was younger and included more women. Respiratory failure (61% and shock (39% were the most common causes of ICU admission for other-SRD and SLE groups, respectively. ICU length-of-stay was similar for the two groups. The 60-day survival adjusted for the groups’ baseline imbalances was not different (P = 0.792. Total SOFA scores were equal for the two groups at admission and during ICU stay, although respiratory function was worse in the other-SRD group at admission and renal and hematological functions were worse in the SLE group at admission. The incidence of severe respiratory dysfunction (respiratory SOFA >2 at admission was higher in the other-SRD group, whereas severe hematological dysfunction (hematological SOFA >2 during ICU stay was higher in the SLE group. SLE patients were younger and displayed a decreased incidence of respiratory failure compared to patients with other-SRDs. However, the incidences of renal and hematological failure and the presence of shock at admission were higher in the SLE group. The 60-day survival rates were similar.

  2. The effect of γ-linolenic acid-α-lipoic acid on functional deficits in the peripheral and central nervous system of streptozotocin- diabetic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Smale, S.; Duis, S.E.; Kamal, A.

    2001-01-01

    Diabetes mellitus can lead to functional and structural deficits in both the peripheral and central nervous system. The pathogenesis of these deficits is multifactorial, probably involving, among others, microvascular dysfunction and oxidative stress. The present study examined the effects of 12

  3. Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study

    DEFF Research Database (Denmark)

    Mygind, Naja Dam; Michelsen, Marie Mide; Pena, Adam

    2016-01-01

    Background-The majority of women with angina-like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary...... microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing. Methods and Results-After screening 3568 women, 963 women with angina-like chest pain and a diagnostic coronary angiogram without significant coronary...... testing. Conclusion-Impaired CFVR was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris. CFVR was associated with few cardiovascular risk factors, suggesting that CFVR is an independent parameter in the risk...

  4. PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

    Directory of Open Access Journals (Sweden)

    Beatrice M. Girard

    2017-12-01

    Full Text Available Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1 and its cognate receptor, PAC1 (Adcyap1r1, have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction.

  5. A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

    Science.gov (United States)

    Kiehl, Kent A

    2006-06-15

    Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

  6. Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine Treatment

    Directory of Open Access Journals (Sweden)

    Sriranjini Sitaram Jaideep

    2014-01-01

    Full Text Available Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory (mean age 39.26 ± 9.88 years; male 43, female 7 were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I or Ayurveda treatment (Group II for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS. Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F=8.16, P=0.007, F=9.73, P=0.004, F=13.51, and P=0.001, resp.. The BRS too increased following the treatment period (F=10.129, P=0.004. Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted.

  7. Shear Stress Inhibits Apoptosis of Ischemic Brain Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xiafeng Shen

    2013-01-01

    Full Text Available As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF is the most fundamental option. Laminar shear stress (LS, as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs. In order to study whether LS was a protective factor in stroke, we investigated LS-intervented ischemic apoptosis of rat BMECs (rBMECs through PE Annexin V/7-AAD, JC-1 and Hoechst 33258 staining to observe the membranous, mitochondrial and nuclear dysfunction. Real-time PCR and western blot were also used to test the gene and protein expressions of Tie-2, Bcl-2 and Akt, which were respectively related to maintain membranous, mitochondrial and nuclear norm. The results showed that LS could be a helpful stimulus for ischemic rBMECs survival. Simultaneously, membranous, mitochondrial and nuclear regulation played an important role in this process.

  8. Chlorine gas exposure causes systemic endothelial dysfunction by inhibiting endothelial nitric oxide synthase-dependent signaling.

    Science.gov (United States)

    Honavar, Jaideep; Samal, Andrey A; Bradley, Kelley M; Brandon, Angela; Balanay, Joann; Squadrito, Giuseppe L; MohanKumar, Krishnan; Maheshwari, Akhil; Postlethwait, Edward M; Matalon, Sadis; Patel, Rakesh P

    2011-08-01

    Chlorine gas (Cl(2)) exposure during accidents or in the military setting results primarily in injury to the lungs. However, the potential for Cl(2) exposure to promote injury to the systemic vasculature leading to compromised vascular function has not been studied. We hypothesized that Cl(2) promotes extrapulmonary endothelial dysfunction characterized by a loss of endothelial nitric oxide synthase (eNOS)-derived signaling. Male Sprague Dawley rats were exposed to Cl(2) for 30 minutes, and eNOS-dependent vasodilation of aorta as a function of Cl(2) dose (0-400 ppm) and time after exposure (0-48 h) were determined. Exposure to Cl(2) (250-400 ppm) significantly inhibited eNOS-dependent vasodilation (stimulated by acetycholine) at 24 to 48 hours after exposure without affecting constriction responses to phenylephrine or vasodilation responses to an NO donor, suggesting decreased NO formation. Consistent with this hypothesis, eNOS protein expression was significantly decreased (∼ 60%) in aorta isolated from Cl(2)-exposed versus air-exposed rats. Moreover, inducible nitric oxide synthase (iNOS) mRNA was up-regulated in circulating leukocytes and aorta isolated 24 hours after Cl(2) exposure, suggesting stimulation of inflammation in the systemic vasculature. Despite decreased eNOS expression and activity, no changes in mean arterial blood pressure were observed. However, injection of 1400W, a selective inhibitor of iNOS, increased mean arterial blood pressure only in Cl(2)-exposed animals, suggesting that iNOS-derived NO compensates for decreased eNOS-derived NO. These results highlight the potential for Cl(2) exposure to promote postexposure systemic endothelial dysfunction via disruption of vascular NO homeostasis mechanisms.

  9. Chlorine Gas Exposure Causes Systemic Endothelial Dysfunction by Inhibiting Endothelial Nitric Oxide Synthase–Dependent Signaling

    Science.gov (United States)

    Honavar, Jaideep; Samal, Andrey A.; Bradley, Kelley M.; Brandon, Angela; Balanay, Joann; Squadrito, Giuseppe L.; MohanKumar, Krishnan; Maheshwari, Akhil; Postlethwait, Edward M.; Matalon, Sadis; Patel, Rakesh P.

    2011-01-01

    Chlorine gas (Cl2) exposure during accidents or in the military setting results primarily in injury to the lungs. However, the potential for Cl2 exposure to promote injury to the systemic vasculature leading to compromised vascular function has not been studied. We hypothesized that Cl2 promotes extrapulmonary endothelial dysfunction characterized by a loss of endothelial nitric oxide synthase (eNOS)-derived signaling. Male Sprague Dawley rats were exposed to Cl2 for 30 minutes, and eNOS-dependent vasodilation of aorta as a function of Cl2 dose (0–400 ppm) and time after exposure (0–48 h) were determined. Exposure to Cl2 (250–400 ppm) significantly inhibited eNOS-dependent vasodilation (stimulated by acetycholine) at 24 to 48 hours after exposure without affecting constriction responses to phenylephrine or vasodilation responses to an NO donor, suggesting decreased NO formation. Consistent with this hypothesis, eNOS protein expression was significantly decreased (∼ 60%) in aorta isolated from Cl2–exposed versus air-exposed rats. Moreover, inducible nitric oxide synthase (iNOS) mRNA was up-regulated in circulating leukocytes and aorta isolated 24 hours after Cl2 exposure, suggesting stimulation of inflammation in the systemic vasculature. Despite decreased eNOS expression and activity, no changes in mean arterial blood pressure were observed. However, injection of 1400W, a selective inhibitor of iNOS, increased mean arterial blood pressure only in Cl2–exposed animals, suggesting that iNOS-derived NO compensates for decreased eNOS-derived NO. These results highlight the potential for Cl2 exposure to promote postexposure systemic endothelial dysfunction via disruption of vascular NO homeostasis mechanisms. PMID:21131444

  10. Patient satisfaction for levonorgestrel intrauterine system and norethisterone for treatment of dysfunctional uterine bleeding

    International Nuclear Information System (INIS)

    Naqaish, T.; Rizvi, F.; Khan, A.; Afzal, M.

    2012-01-01

    Background: Dysfunctional uterine bleeding (DUB) is a common problem with complex management. It can be quite harrowing for the physicians as in most instances they are unable to pinpoint the cause of abnormal bleeding even after a thorough history and physical examination. Aim was to compare patient satisfaction for Levonorgestrel intra uterine system (LNG-IUS) and Norethisterone for the treatment of Dysfunctional Uterine Bleeding (DUB). It is Descriptive case series conducted in Department Obstetrics and Gynaecology, Shifa International Hospital, Islamabad from September, 2011 to September, 2012. Methods: One hundred and nineteen (119) female patients of reproductive age Group with DUB were selected by consecutive sampling. Informed written consent was obtained. A structural patient satisfaction questionnaire (PSQ) was used to collect information regarding age of patients, type of method used for treatment of DUB (Levonorgestrel or Norethisterone), treatment outcome in terms of patient satisfaction scale, and decrease in bleeding after 6 months. Results: The mean age of the patients was 41.03+-4.415 year ranging from 28-60 years. The mean parity of women in the study was 3.22+-1.188 with a range of 1-7. The satisfaction level was significantly (p<0.05) greater (90% versus 20%) in Group A (levonorgesterol-releasing intrauterine system) as compared with Group B (Norethisterone). The blood loss was significantly (p<0.05) decreased in Group A (98%) as compared with Group B (80%). The preference of continuing the method as well as recommendation to a friend was significantly greater in Group A as compared to Group B. Conclusion: The levonorgesterol-releasing intrauterine system (LNG-IUS) is a better choice as compared to Norethisterone, for treatment of DUB with 90% patients highly satisfied. (author)

  11. A cognitive neuroscience perspective on psychopathy: Evidence for paralimbic system dysfunction

    Science.gov (United States)

    Kiehl, Kent A.

    2009-01-01

    Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed ‘the paralimbic system’. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy. PMID:16712954

  12. The effects of Chinese medicines on cAMP/PKA signaling in central nervous system dysfunction.

    Science.gov (United States)

    Li, Lin; Fan, Xiang; Zhang, Xi-Ting; Yue, Shao-Qian; Sun, Zuo-Yan; Zhu, Jin-Qiang; Zhang, Jun-Hua; Gao, Xiu-Mei; Zhang, Han

    2017-06-01

    Neuropathological injury in the mammalian adult central nervous system (CNS) may cause axon disruption, neuronal death and lasting neurological deficits. Failure of axon regeneration is one of the major challenges for CNS functional recovery. Recently, the cAMP/PKA signaling pathway has been proven to be a critical regulator for neuronal regeneration, neuroplasticity, learning and memory. Also, previous studies have shown the effects of Chinese medicines on the prevention and treatment of CNS dysfunction mediated in part by cAMP/PKA signaling. In this review, the authors discuss current knowledge of the role of cAMP/PKA signaling pathway in neuronal regeneration and provide an overview of the Chinese medicines that may enable CNS functional recovery via this signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus.

    Science.gov (United States)

    Brooks, W M; Jung, R E; Ford, C C; Greinel, E J; Sibbitt, W L

    1999-01-01

    To determine the relationship between neurochemical markers of brain injury and brain dysfunction associated with systemic lupus erythematosus (SLE). Patients with SLE (n = 12) were studied using magnetic resonance spectroscopic imaging at 1.5 Tesla to determine neurochemistry and a neurocognitive testing battery to determine brain dysfunction. N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) concentrations were measured in white (WM) and gray (GM) matter and expressed as the ratios NAA/Cho, NAA/Cre, and Cho/Cre. Neurocognitive testing results were expressed as a composite z score. Disease activity was quantified by SLE Disease Activity Index (SLEDAI) and disease injury by Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index. Neurochemical measures of brain injury were correlated with neurocognitive testing z scores: NAA/Cho in WM (r = 0.77, p = 0.003) and GM (r = 0.67, p = 0.017); WM Cho/Cre also correlated with total z score (r = -0.74, p = 0.006). Neurometabolite ratios and SLICC were correlated: GM NAA/Cho (r = -0.70, p = 0.011 ) and NAA/Cre (r = -0.71, p = 0.01) and WM Cho/Cre (r = 0.66, p = 0.02). Correlations between neurometabolite ratios and SLEDAI did not reach significance. Brain function is closely correlated with brain injury assessed noninvasively by proton magnetic resonance spectroscopy. This important finding further supports the use of magnetic resonance spectroscopy to evaluate brain injury in SLE.

  14. No evidence for mirror system dysfunction in schizophrenia from a multimodal TMS/EEG study.

    Science.gov (United States)

    Andrews, Sophie C; Enticott, Peter G; Hoy, Kate E; Thomson, Richard H; Fitzgerald, Paul B

    2015-08-30

    Dysfunctional mirror neuron systems have been proposed to contribute to the social cognitive deficits observed in schizophrenia. A few studies have explored mirror systems in schizophrenia using various techniques such as TMS (levels of motor resonance) or EEG (levels of mu suppression), with mixed results. This study aimed to use a novel multimodal approach (i.e. concurrent TMS and EEG) to further investigate mirror systems and social cognition in schizophrenia. Nineteen individuals with schizophrenia or schizoaffective disorder and 19 healthy controls participated. Single-pulse TMS was applied to M1 during the observation of hand movements designed to elicit mirror system activity. Single EEG electrodes (C3, CZ, C4) recorded brain activity. Participants also completed facial affect recognition and theory of mind tasks. The schizophrenia group showed significant deficits in facial affect recognition and higher level theory of mind compared to healthy controls. A significant positive relationship was revealed between mu suppression and motor resonance for the overall sample, indicating concurrent validity of these measures. Levels of mu suppression and motor resonance were not significantly different between groups. These findings indicate that in stable outpatients with schizophrenia, mirror system functioning is intact, and therefore their social cognitive difficulties may be caused by alternative pathophysiology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Engineering Blood and Lymphatic Microvascular Networks in Fibrin Matrices.

    Science.gov (United States)

    Knezevic, Lea; Schaupper, Mira; Mühleder, Severin; Schimek, Katharina; Hasenberg, Tobias; Marx, Uwe; Priglinger, Eleni; Redl, Heinz; Holnthoner, Wolfgang

    2017-01-01

    Vascular network engineering is essential for nutrient delivery to tissue-engineered constructs and, consequently, their survival. In addition, the functionality of tissues also depends on tissue drainage and immune cell accessibility, which are the main functions of the lymphatic system. Engineering both the blood and lymphatic microvasculature would advance the survival and functionality of tissue-engineered constructs. The aim of this study was to isolate pure populations of lymphatic endothelial cells (LEC) and blood vascular endothelial cells (BEC) from human dermal microvascular endothelial cells and to study their network formation in our previously described coculture model with adipose-derived stromal cells (ASC) in fibrin scaffolds. We could follow the network development over a period of 4 weeks by fluorescently labeling the cells. We show that LEC and BEC form separate networks, which are morphologically distinguishable and sustainable over several weeks. In addition, lymphatic network development was dependent on vascular endothelial growth factor (VEGF)-C, resulting in denser networks with increasing VEGF-C concentration. Finally, we confirm the necessity of cell-cell contact between endothelial cells and ASC for the formation of both blood and lymphatic microvascular networks. This model represents a valuable platform for in vitro drug testing and for the future in vivo studies on lymphatic and blood microvascularization.

  16. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  17. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  18. Salivary dysfunction associated with systemic diseases: systematic review and clinical management recommendations.

    Science.gov (United States)

    von Bültzingslöwen, Inger; Sollecito, Thomas P; Fox, Philip C; Daniels, Troy; Jonsson, Roland; Lockhart, Peter B; Wray, David; Brennan, Michael T; Carrozzo, Marco; Gandera, Beatrice; Fujibayashi, Takashi; Navazesh, Mahvash; Rhodus, Nelson L; Schiødt, Morten

    2007-03-01

    The objective of this study was to identify systemic diseases associated with hyposalivation and xerostomia and develop evidence-based management recommendations for hyposalivation/xerostomia. Literature searches covered the English language medical literature from 1966 to 2005. An evidence-based review process was applied to management studies published from 2002 to 2005. Several systemic diseases were identified. From studies published 2002 to 2005, 15 were identified as high-quality studies and were used to support management recommendations: pilocarpine and cevimeline are recommended for treating hyposalivation and xerostomia in primary and secondary Sjögren's syndrome (SS). IFN-alpha lozenges may enhance saliva flow in primary SS patients. Anti-TNF-alpha agents, such as infliximab or etanercept, are not recommended to treat hyposalivation in SS. Dehydroepiandrosterone is not recommended to relieve hyposalivation or xerostomia in primary SS. There was not enough evidence to support any recommendations for the use of local stimulants, lubricants, and protectants for hyposalivation/xerostomia. However, professional judgment and patient preferences may support the use of a specific product for an individual patient. These evidence-based management recommendations should guide the clinician's management decisions for patients with salivary dysfunction related to systemic disease. Future treatment strategies may include new formulations of existing drugs, e.g., local application of pilocarpine. Recent discoveries on gene expression and a better understanding of the etiopathogenesis of SS may open new treatment options in the future.

  19. Magnetoencephalography study of right parietal lobe dysfunction of the evoked mirror neuron system in antipsychotic-free schizophrenia.

    Directory of Open Access Journals (Sweden)

    Yutaka Kato

    Full Text Available INTRODUCTION: Patients with schizophrenia commonly exhibit deficits of non-verbal communication in social contexts, which may be related to cognitive dysfunction that impairs recognition of biological motion. Although perception of biological motion is known to be mediated by the mirror neuron system, there have been few empirical studies of this system in patients with schizophrenia. METHODS: Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement of another individual. RESULTS: Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase-locking factors and gamma-synchronization predominantly in right parietal cortex. CONCLUSIONS: Our findings demonstrate that untreated patients with schizophrenia exhibit aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization in the right parietal lobe during observation of biological motion.

  20. Autonomic nervous system dysfunction and serum levels of neurotoxic and neurotrophic cytokines in patients with cobalamin deficiency

    Directory of Open Access Journals (Sweden)

    Özcan Çeneli

    2010-12-01

    Full Text Available neurotrophiccytokines epidermal growth factor (EGF and interleukin-6 (IL-6 plays a role in the pathogenesisof cobalamin (Cbl deficiency-induced neuropathy. The aim of this study was to evaluate autonomicnervous system dysfunction and to look for any relationship between autonomic nervous systemdisturbances and serum cytokine levels (TNF-

  1. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R

    1995-01-01

    insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 18.2 +/- 1.4 mg.kg fat-free mass [FFM]-1.min-1, P metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P ...Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...

  2. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    Directory of Open Access Journals (Sweden)

    Daniele Caligiore

    2017-03-01

    Full Text Available Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  3. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    Science.gov (United States)

    Caligiore, Daniele; Mannella, Francesco; Arbib, Michael A; Baldassarre, Gianluca

    2017-03-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  4. NAP reduces murine microvascular endothelial cells proliferation induced by hyperglycemia.

    Science.gov (United States)

    D'Amico, Agata Grazia; Scuderi, Soraya; Maugeri, Grazia; Cavallaro, Sebastiano; Drago, Filippo; D'Agata, Velia

    2014-11-01

    Hyperglycemia has been identified as a risk factor responsible for micro- and macrovascular complications in diabetes. NAP (Davunetide) is a peptide whose neuroprotective actions are widely demonstrated, although its biological role on endothelial dysfunctions induced by hyperglycemia remains uninvestigated. In the present study we hypothesized that NAP could play a protective role on hyperglycemia-induced endothelial cell proliferation. To this end we investigated the effects of NAP on an in vitro model of murine microvascular endothelial cells grown in high glucose for 7 days. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and cyclin D1 protein expression analysis revealed that NAP treatment significantly reduces viability and proliferation of the cells. Hyperglycemia induced the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase and/or phosphatidylinositol-3 kinase/Akt pathways in a time-dependent manner. NAP treatment reduced the phosphorylation levels of ERK and AKT in cells grown in high glucose. These evidences suggest that NAP might be effective in the regulation of endothelial dysfunction induced by hyperglycemia.

  5. Parasympathetic Nervous System Dysfunction, as Identified by Pupil Light Reflex, and Its Possible Connection to Hearing Impairment.

    Directory of Open Access Journals (Sweden)

    Yang Wang

    Full Text Available Although the pupil light reflex has been widely used as a clinical diagnostic tool for autonomic nervous system dysfunction, there is no systematic review available to summarize the evidence that the pupil light reflex is a sensitive method to detect parasympathetic dysfunction. Meanwhile, the relationship between parasympathetic functioning and hearing impairment is relatively unknown.To 1 review the evidence for the pupil light reflex being a sensitive method to evaluate parasympathetic dysfunction, 2 review the evidence relating hearing impairment and parasympathetic activity and 3 seek evidence of possible connections between hearing impairment and the pupil light reflex.Literature searches were performed in five electronic databases. All selected articles were categorized into three sections: pupil light reflex and parasympathetic dysfunction, hearing impairment and parasympathetic activity, pupil light reflex and hearing impairment.Thirty-eight articles were included in this review. Among them, 36 articles addressed the pupil light reflex and parasympathetic dysfunction. We summarized the information in these data according to different types of parasympathetic-related diseases. Most of the studies showed a difference on at least one pupil light reflex parameter between patients and healthy controls. Two articles discussed the relationship between hearing impairment and parasympathetic activity. Both studies reported a reduced parasympathetic activity in the hearing impaired groups. The searches identified no results for pupil light reflex and hearing impairment.As the first systematic review of the evidence, our findings suggest that the pupil light reflex is a sensitive tool to assess the presence of parasympathetic dysfunction. Maximum constriction velocity and relative constriction amplitude appear to be the most sensitive parameters. There are only two studies investigating the relationship between parasympathetic activity and hearing

  6. Parasympathetic Nervous System Dysfunction, as Identified by Pupil Light Reflex, and Its Possible Connection to Hearing Impairment.

    Science.gov (United States)

    Wang, Yang; Zekveld, Adriana A; Naylor, Graham; Ohlenforst, Barbara; Jansma, Elise P; Lorens, Artur; Lunner, Thomas; Kramer, Sophia E

    2016-01-01

    Although the pupil light reflex has been widely used as a clinical diagnostic tool for autonomic nervous system dysfunction, there is no systematic review available to summarize the evidence that the pupil light reflex is a sensitive method to detect parasympathetic dysfunction. Meanwhile, the relationship between parasympathetic functioning and hearing impairment is relatively unknown. To 1) review the evidence for the pupil light reflex being a sensitive method to evaluate parasympathetic dysfunction, 2) review the evidence relating hearing impairment and parasympathetic activity and 3) seek evidence of possible connections between hearing impairment and the pupil light reflex. Literature searches were performed in five electronic databases. All selected articles were categorized into three sections: pupil light reflex and parasympathetic dysfunction, hearing impairment and parasympathetic activity, pupil light reflex and hearing impairment. Thirty-eight articles were included in this review. Among them, 36 articles addressed the pupil light reflex and parasympathetic dysfunction. We summarized the information in these data according to different types of parasympathetic-related diseases. Most of the studies showed a difference on at least one pupil light reflex parameter between patients and healthy controls. Two articles discussed the relationship between hearing impairment and parasympathetic activity. Both studies reported a reduced parasympathetic activity in the hearing impaired groups. The searches identified no results for pupil light reflex and hearing impairment. As the first systematic review of the evidence, our findings suggest that the pupil light reflex is a sensitive tool to assess the presence of parasympathetic dysfunction. Maximum constriction velocity and relative constriction amplitude appear to be the most sensitive parameters. There are only two studies investigating the relationship between parasympathetic activity and hearing impairment

  7. Microvascular decompression for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Khan, S.A.; Khan, B.; Khan, A.A.; Afridi, E.A.A.; Mehmood, S.; Muhammad, G.; Hussain, I.; Zadran, K.K.; Bhatti, S.N.

    2015-01-01

    Background: Trigeminal Neuralgia (TGN) is the most frequently diagnosed type of facial pain. In idiopathic type of TGN it is caused by the neuro-vascular conflict involving trigeminal nerve. Microvascular decompression (MVD) aims at addressing this basic pathology in the idiopathic type of TGN. This study was conducted to determine the outcome and complications of patients with idiopathic TGN undergoing MVD. Method: In a descriptive case series patients with idiopathic TGN undergoing MVD were included in consecutive manner. Patients were diagnosed on the basis of detailed history and clinical examination. Retromastoid approach with craniectomy was used to access cerebellopontine angle (CP-angle) and microsurgical decompression was done. Patients were followed up for 6 months. Results: A total of 53 patients underwent MVD with mean age of 51.6±4.2 years and male predominance. In majority of cases (58.4 percentage) both Maxillary and Mandibular divisions were involved. Per-operatively superior cerebellar artery (SCA) was causing the neuro-vascular conflict in 33 (62.2 percentage) of the cases, anterior inferior cerebellar artery (AICA) in 6 (11.3 percentage) cases, both CSA and AICA in 3 (5.6 percentage) cases, venous compressions in only 1 (1.8percentage) patient and thick arachnoid adhesions were seen in 10 (18.9 percentage) patients. Postoperatively, 33 (68 percentage) patients were pain free, in 14 (26.45 percentage) patients pain was significantly improved whereas in 3 (5.6 percentage) patients there was mild improvement in symptoms. Three (5.6 percentage) patients did not improve after the primary surgery. Cerebrospinal fluid (CSF) leak was encountered in 7 (13.2 percentage) patients post-operatively, 4 (7.5 percentage) patients developed wound infection and 1 (1.8 percentage) patient developed aseptic meningitis. Three (5.6 percentage) patients had transient VII nerve palsy while one patient developed permanent VII nerve palsy. Conclusion: MVD is a safe and

  8. Executive Dysfunction

    Science.gov (United States)

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  9. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-01-01

    Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle

  10. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  11. Diabetes-Induced Dysfunction of Mitochondria and Stem Cells in Skeletal Muscle and the Nervous System

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2017-10-01

    Full Text Available Diabetes mellitus is one of the most common metabolic diseases spread all over the world, which results in hyperglycemia caused by the breakdown of insulin secretion or insulin action or both. Diabetes has been reported to disrupt the functions and dynamics of mitochondria, which play a fundamental role in regulating metabolic pathways and are crucial to maintain appropriate energy balance. Similar to mitochondria, the functions and the abilities of stem cells are attenuated under diabetic condition in several tissues. In recent years, several studies have suggested that the regulation of mitochondria functions and dynamics is critical for the precise differentiation of stem cells. Importantly, physical exercise is very useful for preventing the diabetic alteration by improving the functions of both mitochondria and stem cells. In the present review, we provide an overview of the diabetic alterations of mitochondria and stem cells and the preventive effects of physical exercise on diabetes, focused on skeletal muscle and the nervous system. We propose physical exercise as a countermeasure for the dysfunction of mitochondria and stem cells in several target tissues under diabetes complication and to improve the physiological function of patients with diabetes, resulting in their quality of life being maintained.

  12. Machine learning-based assessment tool for imbalance and vestibular dysfunction with virtual reality rehabilitation system.

    Science.gov (United States)

    Yeh, Shih-Ching; Huang, Ming-Chun; Wang, Pa-Chun; Fang, Te-Yung; Su, Mu-Chun; Tsai, Po-Yi; Rizzo, Albert

    2014-10-01

    Dizziness is a major consequence of imbalance and vestibular dysfunction. Compared to surgery and drug treatments, balance training is non-invasive and more desired. However, training exercises are usually tedious and the assessment tool is insufficient to diagnose patient's severity rapidly. An interactive virtual reality (VR) game-based rehabilitation program that adopted Cawthorne-Cooksey exercises, and a sensor-based measuring system were introduced. To verify the therapeutic effect, a clinical experiment with 48 patients and 36 normal subjects was conducted. Quantified balance indices were measured and analyzed by statistical tools and a Support Vector Machine (SVM) classifier. In terms of balance indices, patients who completed the training process are progressed and the difference between normal subjects and patients is obvious. Further analysis by SVM classifier show that the accuracy of recognizing the differences between patients and normal subject is feasible, and these results can be used to evaluate patients' severity and make rapid assessment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Is there a dysfunction in the visual system of depressed patients?

    Directory of Open Access Journals (Sweden)

    Iacovides Apostolos

    2005-03-01

    Full Text Available Abstract Background The aim of the current study was to identify a possible locus of dysfunction in the visual system of depressed patients. Materials and Methods Fifty Major Depressive patients aged 21–60 years and 15 age-matched controls took part in the study The diagnosis was obtained with the SCAN v 2.0. The psychometric assessment included the HDRS, the HAS, the Newcastle Scales, the Diagnostic Melancholia Scale and the GAF scale. Flash Electroretinogram and Electrooculogram were performed in all subjects. The statistical analysis included ANCOVA, Student's t-test and Pearson Product Moment Correlation Coefficient were used. Results The Electro-oculographic findings suggested that all subtypes of depressed patients had lower dark trough and light peak values in comparison to controls (p Discussion The findings of the current study provide empirical data in order to assist in the understanding of the international literature and to explain the mechanism of action of therapies like sleep deprivation and light therapy.

  14. Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy

    NARCIS (Netherlands)

    van Duinkerken, Eelco; Ijzerman, Richard G.; Klein, Martin; Moll, Annette C.; Snoek, Frank J.; Scheltens, Philip; Pouwels, Petra J. W.; Barkhof, Frederik; Diamant, Michaela; Tijms, Betty M.

    2016-01-01

    Type 1 diabetes mellitus (T1DM) patients, especially with concomitant microvascular disease, such as proliferative retinopathy, have an increased risk of cognitive deficits. Local cortical gray matter volume reductions only partially explain these cognitive dysfunctions, possibly because volume

  15. Nitric oxide-mediated cutaneous microvascular function is impaired in polycystic ovary sydrome but can be improved by exercise training.

    Science.gov (United States)

    Sprung, V S; Cuthbertson, D J; Pugh, C J A; Daousi, C; Atkinson, G; Aziz, N F; Kemp, G J; Green, D J; Cable, N T; Jones, H

    2013-03-15

    Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease. The contribution of the nitric oxide (NO) dilator system to cutaneous endothelial dysfunction is currently unknown in PCOS. Our aim was to examine whether women with PCOS demonstrate impaired cutaneous microvascular NO function and whether exercise training can ameliorate any impairment. Eleven women with PCOS (age, 29 ± 7 years; body mass index, 34 ± 6 kg m(-2)) were compared with six healthy obese control women (age, 29 ± 7 years; body mass index, 34 ± 5 kg m(-2)). Six women with PCOS (30 ± 7 years; 31 ± 6 kg m(-2)) then completed 16 weeks of exercise training. Laser Doppler flowmetry, combined with intradermal microdialysis of l-N(G)-monomethyl-l-arginine, a nitric oxide antagonist, in response to incremental local heating of the forearm was assessed in women with PCOS and control women, and again in women with PCOS following exercise training. Cardiorespiratory fitness, homeostasis model assessment for insulin resistance, hormone and lipid profiles were also assessed. Differences between women with PCOS and control women and changes with exercise were analysed using Student's unpaired t tests. Differences in the contribution of NO to cutaneous blood flow [expressed as a percentage of maximal cutaneous vasodilatation (CVCmax)] were analysed using general linear models. At 42°C heating, cutaneous NO-mediated vasodilatation was attenuated by 17.5%CVCmax (95% confidence interval, 33.3, 1.7; P = 0.03) in women with PCOS vs. control women. Exercise training improved cardiorespiratory fitness by 5.0 ml kg(-1) min(-1) (95% confidence interval, 0.9, 9.2; P = 0.03) and NO-mediated cutaneous vasodilatation at 42°C heating by 19.6% CVCmax (95% confidence interval, 4.3, 34.9; P = 0.02). Cutaneous microvascular NO function is impaired in women with PCOS compared with obese matched control women but can be improved with exercise training.

  16. Microvascular and immunological studies in Raynaud's phenomenon.

    NARCIS (Netherlands)

    Houtman, Pieternella Maria

    1985-01-01

    The purpose of this thesis was to investigate the diagnostic significance of microvascular abnormalities - as observed in the nailfold - in patients with RP with respect to the presence or development of a connective tissue disease. In addition, we investigated whether the observed abnormalities

  17. Cognitive and autonomic dysfunction in presymptomatic and early Huntington's disease.

    Science.gov (United States)

    Kobal, Jan; Melik, Ziva; Cankar, Ksenija; Strucl, Martin

    2014-06-01

    Huntington's disease is characterized by disorders of movement, cognition and behavior. Individuals with Huntington's disease display aberrant changes in the autonomic nervous system that are detected even before the onset of other symptoms. Subtle cognitive dysfunction may start before other clinical manifestations. The aim of the present study was to investigate the autonomic nervous system response to mental arithmetic and the relationship between the autonomic and cognitive/motor function in presymptomatic and early Huntington's disease. We examined 15 presymptomatic Huntington's disease gene carriers (PHD), 15 early Huntington's disease patients (EHD) and 30 healthy controls. PHD and EHD groups were determined according to Unified Huntington's Disease Rating Scale (UHDRS) motor score. ECG, heart rate, systolic and diastolic blood pressure, and cutaneous laser Doppler flux were measured during rest and during a simple mental arithmetic test. UHDRS cognitive test battery was applied to determine cognitive dysfunction. During mental arithmetic, the heart rate of PHD/EHD increased significantly less than that of controls. Decreased microvascular response to mental arithmetic was found in EHD. Significant correlations for the PHD/EHD group were found between laser Doppler flux response and Symbol Digit Modalities Test score, and between laser Doppler flux response and UHDRS motor score. It seems that central autonomic dysregulation of cardiovascular system in Huntington's disease goes along with the degeneration of other central neuronal systems. This finding is relevant as it could enable simple and noninvasive testing of disease progression.

  18. MEDICAL AND PSYCHOLOGICAL CORRECTION AND REHABILITATION OF PREGNANT WOMEN WITH SOMATOFORM DYSFUNCTION OF VEGETATIVE NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    V. G. Syusyuka

    2014-02-01

    Full Text Available Introduction Neurocirculatory dystonia (NCD takes one of the leading positions among different extragenital diseases in pregnant women, and it promotes complications of pregnancy, labor and postpartum period. NCD which is included into the diagnostic section “Somatoform vegetative dysfunction” – is polyetiologic functional disease of cardiovascular system based on disorders of neuroendocrine regulation with multiple and various clinical signs that become worse in stress influence. Object of the work – is to estimate influence of medical and psychological correction program on the psycho-emotional state and rate of gestation complications in pregnant women with somatoform dysfunction of vegetative nervous system (SDVNS. Materials and methods of investigations There 56 pregnant women with NCD and it is the evidence of somatoform dysfunction of vegetative nervous system within gestation period of 12-34 weeks were examined in the study. Presence of this extragenital pathology was clinically proved by therapeutist. I group included 29 pregnant women who participated in the complex program of medical and psychological correction and sanatorium rehabilitation. II group included 27 pregnant women having rehabilitation in accord with standards of sanatorium-resort therapy. Control group comprised 24 somatically healthy pregnant women. Level of trait and state anxiety were estimated under methods of Spielberg-Hanin. Estimation of type of attitude towards the disease and of other associated personal attitudes was carried out using Personality Questionnaire of the V.M. Bekhterev Institute (PQBI. Results and their discussion. High rate of combination of SDVNS with various somatic pathology both in group I and group II was found (86.2% and 85.2% correspondingly. By comparing the results before sanatorium health improvement it was defined that average and high levels of state anxiety were dominating in all groups (group І - 91.7%, group II – 85% and

  19. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Severe acute pancreatitis (SAP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS can lead to multiple organ dysfunction syndrome (MODS during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  20. The role of tissue renin angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness

    Directory of Open Access Journals (Sweden)

    Annayya R Aroor

    2013-10-01

    Full Text Available Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin angiotensin aldosterone system (RAAS in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.

  1. Features of renal dysfunction in children with systemic lupus erythematosus and juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    L.F. Bogmat

    2017-09-01

    had microproteinuria (66.6 % and a decrease in the concentration function of the kidneys (33.3 %. When studying the function of the kidneys depending on the activity of the pathological process, attention was paid to the increase in the level of microproteinuria (p < 0.01 and reduction of glomerular filtration in the group with III degree of activity (p < 0.01. There is also an increase in the level of proteinuria in the group with the duration of the disease for more than 3 years. Thus, it has been found that kidney damage is associated with a significant decrease in glomerular filtration and proteinuria, that is, a dysfunction of the glomerular kidney system. In patients with SLE, in a group with the duration of the disease from 1 to 3 years, in 68.1 % of cases there was proteinuria, and in rare cases — changes in glome­rular filtration rate. In the group of children with the duration of the pathological process over 3 years, deeper changes in the function of the kidneys have been detected. Thus, almost all patients had proteinuria (90.4 %, the incidence of reduction in glomerular filtration rate increased to 19.0 %, and in 14.2 % of cases, a reduction in the concentration function of kidneys has been detected. When analyzing the incidence of renal dysfunction depending on the activity of SLE, attention was paid to the increase in the level of proteinuria (p < 0.05 and the decrease in glomerular filtration rate (p < 0.02, especially in patients with II degree of disease activity. In the study of kidney function indicators depending on the duration of SLE, it was found that in the group with the duration of the disease for more than 3 years, there was a decrease in glomerular filtration rate (p < 0.03, increase in the level of microalbuminuria (p < 0.03 and a reduction in maximum urinary gravity (p < 0.03. When studying the indicators of kidney function depending on the activity of the pathological process, an increase in the level of microalbumi­nuria with II

  2. Kidney dysfunction, systemic inflammation and mental well-being in elderly post-myocardial infarction patients

    NARCIS (Netherlands)

    Heeres, Rick H.M.; Hoogeveen, Ellen K.; Geleijnse, Marianne; Goede, De Janette; Kromhout, Daan; Giltay, Erik J.

    2017-01-01

    Background The aim was to investigate whether mild kidney dysfunction and low-grade inflammation in post-myocardial infarction patients are independently associated with markers of mental well-being (i.e. depressive and apathy symptoms, and dispositional optimism). Methods In post-myocardial

  3. Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

    Science.gov (United States)

    Bokma, Jouke P; Winter, Michiel M; van Dijk, Arie P; Vliegen, Hubert W; van Melle, Joost P; Meijboom, Folkert J; Post, Martijn C; Berbee, Jacqueline K; Boekholdt, S Matthijs; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; Bouma, Berto J

    2018-04-03

    The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] 0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EFtetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905. © 2017 American Heart Association, Inc.

  4. Effects of hyperoxia on microvascular cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    D' Amore, P.A.; Sweet, E.

    1987-02-01

    Microvascular cells are most vulnerable to direct oxygen damage. Using an in vitro model system we have investigated the effect of elevated oxygen on the proliferation, morphology, and integrity of microvascular endothelial cells (EC) and pericytes. Cultivation of these cells at oxygen concentrations of 40% for 1 wk resulted in the inhibition of EC proliferation but had no effect on the growth of the pericytes. Similarly, hyperoxia induced a dramatic change in the shape of the EC, increasing their spread area by close to six-fold. Under the same conditions, the spread area of the pericytes was unaffected. To understand the effect of the hyperoxic treatment on the cells, the integrity of various membrane systems was assessed. /sup 51/Cr release was used to monitor plasma membrane integrity. There was no difference in chromium release by EC and pericytes over the 7 d of growth under normoxic and hyperoxic conditions. Mitochondrial integrity was examined by staining the cells with Rhodamine 123, which is selectively accumulated by the mitochondria. The staining pattern of the mitochondria of both EC and pericytes was altered by growth in the elevated oxygen. Finally, the lysosomes were visualized using acridine orange. The acridine orange staining pattern revealed enlarged and perinuclear lysosomes in the EC but no change in the pericyte lysosomal staining pattern. Thus, the cells of the microvasculature seem to be differentially affected by hyperoxia, a fact that may be significant in the etiology of reperfusion injury, ischemic disease, and pathologies associated with prematurity.

  5. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.

    Science.gov (United States)

    Mohammed, Selma F; Hussain, Saad; Mirzoyev, Sultan A; Edwards, William D; Maleszewski, Joseph J; Redfield, Margaret M

    2015-02-10

    Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology. We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size-expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm(2)) than control (PHeart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD. In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF. © 2014 American Heart Association, Inc.

  6. Hypothalamic pituitary dysfunction in acute nonmycobacterial infections of central nervous system

    Directory of Open Access Journals (Sweden)

    Dinesh K Dhanwal

    2011-01-01

    Full Text Available Background and Objective: Acute and chronic central nervous system (CNS infections are not uncommon in tropical countries and are associated with high morbidity and mortality if specific targeted therapy is not instituted in time. Effects of tubercular meningitis, a form of chronic meningitis on hypothalamic pituitary axis, are well known both at the time of diagnosis and after few months to years of illness. However, there are few reports of pituitary dysfunction in subjects with acute CNS infections. Therefore, this study was aimed at evaluating the pituitary hormonal profile in patients with nonmycobacterial acute meningitis at the time of presentation. Materials and Methods: This prospective case series study included 30 untreated adult patients with acute meningitis, meningoencephalitis, or encephalitis, due to various nonmycobacterial agents, admitted and registered with Lok Nayak Hospital, Maulana Aazd Medical College, New Delhi, between September 2007 and March 2009. Patients with preexisting endocrine diseases, tubercular meningitis and patients on steroids were carefully excluded from the study. The basal pituitary hormonal profile was measured by the electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH, follicular stimulating hormone (FSH, prolactin (PRL, thyrotropin (TSH, free tri-iodothyronine (fT3, and free thyroxine (fT4. Results: The cases (n = 30 comprised of patients with acute pyogenic meningitis (n = 23, viral meningoencephalitis (n = 4, brain abscess (n = 2, and cryptococcal meningitis (n = 1. The mean age of patients was 28.97 ± 11.306 years. Out of 30 patients, 14 (46.7% were males and 16 (58.1% were females. Adrenal insufficiency both absolute and relative was seen in seven (23.3% and hyperprolactinemia was seen in nine (30.0% of the patients. One study subject had central hypothyroidism and seven (23.3 showed low levels of LH and/or FSH. None of patients showed clinical features suggestive of

  7. Bowel Dysfunction

    Science.gov (United States)

    ... to PCF? Featured Fundraise for PCF: Many vs Cancer Contact Us Bowel Dysfunction The broad term of bowel dysfunction includes ... immodium) can be used to help with loose bowel movements. Increasing fiber intake through whole grains, ... mission 82% Join the fight against prostate ...

  8. New insights into the pathogenesis of cystic fibrosis: pivotal role of glutathione system dysfunction and implications for therapy.

    Science.gov (United States)

    Hudson, Valerie M

    2004-01-01

    The cystic fibrosis transmembrane regulator (CFTR) should no longer be viewed primarily as a 'chloride channel' but recognized as a channel that also controls the efflux of other physiologically important anions, such as glutathione (GSH) and bicarbonate. More effective approaches to cystic fibrosis treatment may result from this reconceptualization of the CFTR by researchers and clinicians. For example, oxidant damage in cystic fibrosis has been assumed to be a significant part of the pathophysiology of the disease. Generally speaking, antioxidant status in cystic fibrosis is compromised. However, until recently this was seen as secondary to the excessive chemoattraction of neutrophils in this disease caused by mutation of the CFTR protein, leading to a high oxidant burden. New findings suggest that the cystic fibrosis mutations in fact cause a primary dysfunction in the system of one of the body's most important antioxidant and immune-signaling substances: the reduced GSH system. Cystic fibrosis mutations significantly decrease GSH efflux from cells without redundant channels to the CFTR; this leads to deficiency of GSH in the epithelial lining fluid of the lung, as well as in other compartments, including immune system cells and the gastrointestinal tract. This deficiency is exaggerated over time as the higher-than-normal oxidant burden of cystic fibrosis leads to successively larger decrements in GSH without the normal opportunity to fully recover physiologic levels. This GSH system dysfunction may be the trigger for initial depletion of other antioxidants and may also play a role in initiating the over-inflammation characteristic of cystic fibrosis. Proper GSH system functioning also affects immune system competence and mucus viscosity, both of relevance to cystic fibrosis pathophysiology. In a way, cystic fibrosis may be thought of as the first identified disease with GSH system dysfunction.This overview provides a review of the most pertinent recent research

  9. Radionuclide assessment of pulmonary microvascular permeability

    Energy Technology Data Exchange (ETDEWEB)

    Groeneveld, A.B.J. [Medical Intensive Care Unit, Department of Internal Medicine, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam (Netherlands)

    1997-04-01

    The literature has been reviewed to evaluate the technique and clinical value of radionuclide measurements of microvascular permeability and oedema formation in the lungs. Methodology, modelling and interpretation vary widely among studies. Nevertheless, most studies agree on the fact that the measurement of permeability via pulmonary radioactivity measurements of intravenously injected radiolabelled proteins versus that in the blood pool, the so-called pulmonary protein transport rate (PTR), can assist the clinician in discriminating between permeability oedema of the lungs associated with the adult respiratory distress syndrome (ARDS) and oedema caused by an increased filtration pressure, for instance in the course of cardiac disease, i.e. pressure-induced pulmonary oedema. Some of the techniques used to measure PTR are also able to detect subclinical forms of lung microvascular injury not yet complicated by permeability oedema. This may occur after cardiopulmonary bypass and major vascular surgery, for instance. By paralleling the clinical severity and course of the ARDS, the PTR method may also serve as a tool to evaluate new therapies for the syndrome. Taken together, the currently available radionuclide methods, which are applicable at the bedside in the intensive care unit, may provide a gold standard for detecting minor and major forms of acute microvascular lung injury, and for evaluating the severity, course and response to treatment. (orig.). With 2 tabs.

  10. Diabetes and sexual dysfunction: current perspectives

    Directory of Open Access Journals (Sweden)

    Maiorino MI

    2014-03-01

    Full Text Available Maria Ida Maiorino,1 Giuseppe Bellastella,1 Katherine Esposito2 1Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy; 2Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Abstract: Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes. Keywords: diabetes mellitus, diabetes complications, erectile dysfunction, female sexual dysfunction, lifestyle changes

  11. Obesity is associated with lower coronary microvascular density.

    Directory of Open Access Journals (Sweden)

    Duncan J Campbell

    Full Text Available BACKGROUND: Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure. METHODS: We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy. RESULTS: Non-obese (body mass index, BMI, ≤ 30 kg/m(2, n=33 and obese patients (BMI >30 kg/m(2, n=24 did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145 ± 239, mean ± SD, vs. 1371 ± 333 mm/mm(3, P=0.007 and higher diffusion radius (16.9 ± 1.5 vs. 15.6 ± 2.0 μm, P=0.012, in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73 ± 0.11 μm/μm was not significantly different from that of non-obese patients (0.71 ± 0.11 μm/μm, suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001, and lower capillary length density was associated with both increased BMI (P=0.043 and increased PCWP (P=0.016. CONCLUSIONS: Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.

  12. Uptake of Single-Walled Carbon Nanotubes Conjugated with DNA by Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Harvey

    2012-01-01

    Full Text Available Single-walled carbon nanotubes (SWCNTs have been proposed to have great therapeutic potential. SWCNTs conjugated with drugs or genes travel in the systemic circulation to reach target cells or tissues following extravasation from microvessels although the interaction between SWCNT conjugates and the microvascular endothelial cells (ECs remains unknown. We hypothesized that SWCNT-DNA conjugates would be taken up by microvascular ECs and that this process would be facilitated by SWCNTs compared to facilitation by DNA alone. ECs were treated with various concentrations of SWCNT-DNA-FITC conjugates, and the uptake and intracellular distribution of these conjugates were determined by a confocal microscope imaging system followed by quantitative analysis of fluorescence intensity. The uptake of SWCNT-DNA-FITC conjugates (2 μg/mL by microvascular ECs was significantly greater than that of DNA-FITC (2 μg/mL, observed at 6 hrs after treatment. For the intracellular distribution, SWCNT-DNA-FITC conjugates were detected in the nucleus of ECs, while DNA-FITC was restricted to the cytoplasm. The fluorescence intensity and distribution of SWCNTs were concentration and time independent. The findings demonstrate that SWCNTs facilitate DNA delivery into microvascular ECs, thus suggesting that SWCNTs serving as drug and gene vehicles have therapeutic potential.

  13. Disruption of microvascular flow-patterns in Alzheimer's disease correlates with neurodegeneration and cognitive decline

    DEFF Research Database (Denmark)

    Nielsen, Rune Bæksager; Egefjord, Lærke; Eskildsen, Simon Fristed

    BACKGROUND: The capillary dysfunction hypothesis of Alzheimer’s disease (AD) proposes that changes in capillary morphology and function disrupts microvascular flow-patterns, consequently, limiting oxygen delivery, causing tissue-hypoxia and neurodegeneration. Capillary dysfunction is characterized...... and neurodegeneration in AD. METHOD: 24 patients diagnosed with AD were assessed at inclusion and after six months. Using perfusion magnetic resonance imaging (MRI), we estimated CTH, flow-normalized CTH termed relative transit time heterogeneity (RTH), OEFmax and relative cerebral blood flow (rCBF). Neurodegeneration...... by elevated capillary transit time heterogeneity (CTH) and accompanying raised maximum oxygen extraction fraction (OEFmax), which theoretically reflects weakened tissue oxygen-tension. AIM: We tested whether the severity of CTH and the level of OEFmax correlated with the severity of cognitive symptoms...

  14. Habitual aerobic exercise does not protect against micro- or macrovascular endothelial dysfunction in healthy estrogen-deficient postmenopausal women.

    Science.gov (United States)

    Santos-Parker, Jessica R; Strahler, Talia R; Vorwald, Victoria M; Pierce, Gary L; Seals, Douglas R

    2017-01-01

    Aging causes micro- and macrovascular endothelial dysfunction, as assessed by endothelium-dependent dilation (EDD), which can be prevented and reversed by habitual aerobic exercise (AE) in men. However, in estrogen-deficient postmenopausal women, whole forearm microvascular EDD has not been studied, and a beneficial effect of AE on macrovascular EDD has not been consistently shown. We assessed forearm blood flow in response to brachial artery infusions of acetylcholine (FBF ACh ), a measure of whole forearm microvascular EDD, and brachial artery flow-mediated dilation (FMD), a measure of macrovascular EDD, in 12 premenopausal sedentary women (Pre-S; 24 ± 1 yr; V̇o 2max = 37.5 ± 1.6 ml·kg -1 ·min -1 ), 25 estrogen-deficient postmenopausal sedentary women (Post-S; 62 ± 1 yr; V̇o 2max = 24.7 ± 0.9 ml·kg -1 ·min -1 ), and 16 estrogen-deficient postmenopausal AE-trained women (Post-AE; 59 ± 1 yr; V̇o 2max = 40.4 ± 1.4 ml·kg -1 ·min -1 ). FBF ACh was lower in Post-S and Post-AE compared with Pre-S women (135 ± 9 and 116 ± 17 vs. 193 ± 21 AUC, respectively, both P healthy nonobese estrogen-deficient postmenopausal women, despite being associated with lower systemic markers of inflammation and oxidative stress. This is the first study to demonstrate that habitual aerobic exercise may not protect against age/menopause-related whole forearm microvascular endothelial dysfunction in healthy nonobese estrogen-deficient postmenopausal women, consistent with recent findings regarding macrovascular endothelial function. This is in contrast to what is observed in healthy middle-aged and older aerobic exercise-trained men. Copyright © 2017 the American Physiological Society.

  15. Erectile Dysfunction

    Science.gov (United States)

    ... rigid. Medications The oral medications for erectile dysfunction, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), relax the muscles ... to begin working; the erection helping effects of sildenafil and vardenafil last for about 8 hours and ...

  16. Ultraharmonic VUS Imaging of Microvascularization

    NARCIS (Netherlands)

    D. Maresca (David)

    2013-01-01

    textabstractThe coronary arteries are major blood vessels branching along the heart surface to convey nutrients and oxygen carried in the blood to the heart muscle cells. In turn, the heart ensures the perpetual transportation of blood throughout the other organs of the circulatory system.

  17. Pathways for insulin access to the brain: the role of the microvascular endothelial cell.

    Science.gov (United States)

    Meijer, Rick I; Gray, Sarah M; Aylor, Kevin W; Barrett, Eugene J

    2016-11-01

    Insulin affects multiple important central nervous system (CNS) functions including memory and appetite, yet the pathway(s) by which insulin reaches brain interstitial fluid (bISF) has not been clarified. Recent studies demonstrate that to reach bISF, subarachnoid cerebrospinal fluid (CSF) courses through the Virchow-Robin space (VRS) which sheaths penetrating pial vessels down to the capillary level. Whether insulin predominantly enters the VRS and bISF by local transport through the blood-brain barrier, or by being secreted into the CSF by the choroid plexus, is unknown. We injected 125 I-TyrA14-insulin or regular insulin intravenously and compared the rates of insulin reaching subarachnoid CSF with its plasma clearance by brain tissue samples (an index of microvascular endothelial cell binding/uptake/transport). The latter process was more than 40-fold more rapid. We then showed that selective insulin receptor blockade or 4 wk of high-fat feeding each inhibited microvascular brain 125 I-TyrA14-insulin clearance. We further confirmed that 125 I-TyrA14-insulin was internalized by brain microvascular endothelial cells, indicating that the in vivo tissue association reflected cellular transport, not simply microvascular tracer binding. Copyright © 2016 the American Physiological Society.

  18. Optimal hematocrit in an artificial microvascular network.

    Science.gov (United States)

    Piety, Nathaniel Z; Reinhart, Walter H; Stutz, Julianne; Shevkoplyas, Sergey S

    2017-09-01

    Higher hematocrit increases the oxygen-carrying capacity of blood but also increases blood viscosity, thus decreasing blood flow through the microvasculature and reducing the oxygen delivery to tissues. Therefore, an optimal value of hematocrit that maximizes tissue oxygenation must exist. We used viscometry and an artificial microvascular network device to determine the optimal hematocrit in vitro. Suspensions of fresh red blood cells (RBCs) in plasma, normal saline, or a protein-containing buffer and suspensions of stored red blood cells (at Week 6 of standard hypothermic storage) in plasma with hematocrits ranging from 10 to 80% were evaluated. For viscometry, optimal hematocrits were 10, 25.2, 31.9, 37.1, and 37.5% for fresh RBCs in plasma at shear rates of 3.2 or less, 11.0, 27.7, 69.5, and 128.5 inverse seconds. For the artificial microvascular network, optimal hematocrits were 51.1, 55.6, 59.2, 60.9, 62.3, and 64.6% for fresh RBCs in plasma and 46.4, 48.1, 54.8, 61.4, 65.7, and 66.5% for stored RBCs in plasma at pressures of 2.5, 5, 10, 20, 40, and 60 cm H 2 O. Although exact optimal hematocrit values may depend on specific microvascular architecture, our results suggest that the optimal hematocrit for oxygen delivery in the microvasculature depends on perfusion pressure. Therefore, anemia in chronic disorders may represent a beneficial physiological response to reduced perfusion pressure resulting from decreased heart function and/or vascular stenosis. Our results may help explain why a therapeutically increasing hematocrit in such conditions with RBC transfusion frequently leads to worse clinical outcomes. © 2017 AABB.

  19. Design, manufacture and in-vitro evaluation of a new microvascular anastomotic device.

    Science.gov (United States)

    Huang, Shao-Fu; Wang, Tien-Hsiang; Wang, Hsuan-Wen; Huang, Shu-Wei; Lin, Chun-Li; Kuo, Hsien-Nan; Yu, Tsung-Chih

    2013-01-01

    Many microvascular anastomoses have been proposed for use with physical assisted methods, such as cuff, ring-pin, stapler, clip to the anastomose blood vessel. The ring-pin type anastomotic device (e.g., 3M Microvascular Anastomotic System) is the most commonly used worldwide because the anastomotic procedure can be conducted more rapidly and with fewer traumas than using sutures. However, problems including vessel leakage, ring slippage, high cost and high surgical skill demand need to be resolved. The aim of this study is to design and manufacture a new anastomotic device for microvascular anastomosis surgery and validate the device functions with in-vitro testing. The new device includes one pair of pinned rings and a set of semi-automatic flap apparatus designed and made using computer-aided design / computer-aided manufacture program. A pair of pinned rings was used to impale vessel walls and establish fluid communication with rings joined. The semi-automatic flap apparatus was used to assist the surgeon to invert the vessel walls and impale onto each ring pin, then turning the apparatus knob to bring the rings together. The device was revised until it became acceptable for clinical requires. An in-vitro test was performed using a custom-made seepage micro-fluid system to detect the leakage of the anastomotic rings. The variation between input and output flow for microvascular anastomoses was evaluated. The new microvascular anastomotic device was convenient and easy to use. It requires less time than sutures to invert and impale vessel walls onto the pinned rings using the semi-automatic flap apparatus. The in-vitro test data showed that there were no tears from the joined rings seam during the procedures. The new anastomotic devices are effective even with some limitations still remaining. This device can be helpful to simplify the anastomosis procedure and reduce the surgery time.

  20. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Science.gov (United States)

    Penetration of the brain microvascular endothelial layer is one of the routes L. monocytogenes use to breach the blood-brain barrier. Because host factors in the blood severely limit direct invasion of human brain microvascular endothelial cells (HBMECs) by L. monocytogenes, alternative mechanisms m...

  1. Increased systemic Th17 cytokines are associated with diastolic dysfunction in children and adolescents with diabetic ketoacidosis.

    Directory of Open Access Journals (Sweden)

    William H Hoffman

    Full Text Available Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA. Twenty seven of the 39 measured cytokines/chemokines were elevated at 6-12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17 are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA.

  2. Longterm outcomes and damage accrual in patients with childhood systemic lupus erythematosus with psychosis and severe cognitive dysfunction.

    Science.gov (United States)

    Lim, Lily Siok Hoon; Lefebvre, Arlette; Benseler, Susanne; Silverman, Earl D

    2013-04-01

    (1) To describe the clinical course and response to treatment; and (2) to evaluate and compare damage accrual of distinct phenotypic subgroups of patients with clinically important psychiatric illness of pediatric systemic lupus erythematosus (pSLE). A single-center cohort study of patients with pSLE followed at a pediatric lupus clinic from 1985 to July 2009. Clinical course and response to treatment were studied. Remission was defined by absence of psychiatric/cognitive symptoms while receiving minimal doses of prednisone. Disease activity and damage were measured using SLE Disease Activity Index and SLE Damage Index. Fifty-three children were included: 40 with psychosis and cognitive dysfunction (PSYC group) and 13 with isolated cognitive dysfunction (COG group). All received immunosuppressive treatment. Eighteen of 32 treated with azathioprine required a change to cyclophosphamide for poor response but none on cyclophosphamide required a change. The median times to remission were 72 weeks (PSYC) and 70 weeks (COG). Eight patients (7 PSYC, 1 COG) experienced flare following response/remission. New damage was noted in 50% of children at a median of 11 months: 57% of PSYC group, 31% of COG group. Persistent cognitive dysfunction was seen in 16% of PSYC patients and 15% of COG patients. Most patients responded to immunosuppressive treatment, although median time to remission was > 1 year. Roughly half the patients acquired a new damage item, most of which did not interfere with functional abilities. Fewer than 20% of patients developed neuropsychiatric damage. Both phenotypes of psychiatric pSLE responded equally well to current treatment.

  3. Anatomical evaluation of penile venous system by CT cavernosography in patients with erectile dysfunction and venous leakage

    Directory of Open Access Journals (Sweden)

    Ghafoori M

    2012-11-01

    Full Text Available Background: Erectile dysfunction is an important problem in men and an organic cause is found in about 50% of cases. When a vasculogenic etiology is suspected, imaging assessments are of great help. Cavernosography is traditionally recognized as an imaging modality for evaluation of venous leakage in men with impotency. We employed CT cavernosography as a novel technique for demonstrating penile venous anatomy and leaking veins.Methods: In the present case series study, we recruited 45 patients with erectile dysfunction by convenient sampling at Hazrat Rasoul Akram Hospital in Tehran, Iran, during one year (1390. The patients had previously been diagnosed with venous incompetency by Doppler study. After intracavernosal injection of prostaglandin E1, we injected sterile normal saline into the corpora cavernosa to achieve penile erection. Later, we injected contrast media into the corpus cavernosum, which was followed by CT scan of the penis and pelvic area to show the venous anatomy and leakage sites.Results: The mean age of the patients was 35.8±8.9 years. 36 (80% patients had venous leakage in crural veins, 27 (60% in cavernosal veins, 27 (60% in circumflex veins, 24 (52.3% in urethral veins, 21 (46.7% in deep dorsal vein, 3 (6.7% in para-arterial veins and 3 (6.7% in corpus spongiosum. Conclusion: The results of this study show the high prevalence of venous leakage in patients referring for erectile dysfunction. Moreover, CT cavernosography was shown to be a useful method for evaluating penile venous system and its related leakage sites which are important for surgical planning.

  4. Aspiration of activated charcoal elicits an increase in lung microvascular permeability.

    Science.gov (United States)

    Arnold, T C; Willis, B H; Xiao, F; Conrad, S A; Carden, D L

    1999-01-01

    Gastric decontamination with orally administered activated charcoal is the recommended treatment for many poisonings. However, ingestion of central nervous system depressants resulting in loss of protective airway reflexes may result in pulmonary aspiration of activated charcoal. Although activated charcoal has been reported to be an inert substance, evidence suggests that pulmonary aspiration of charcoal is associated with lung edema formation and pulmonary compromise. This study tested the hypothesis that intratracheal instillation of activated charcoal disrupts the integrity of the lung microvascular barrier. The capillary filtration coefficient (Kf,c), a sensitive measure of lung microvascular permeability, was determined isogravimetrically prior to and after intratracheal instillation of activated charcoal 0.04 g/kg (12% weight/vol solution, pH 7.4) or an equal volume of sterile water in isolated, perfused rat lungs. Arterial blood gas analysis was determined prior to and after tracheal instillation of activated charcoal or sterile water in a separate group of animals. Intratracheal instillation of activated charcoal resulted in a significant increase in pulmonary microvascular permeability compared to lungs treated with sterile water or control lungs (delta Kf,c = +0.21 +/- 0.076; -0.014 +/- 0.04; and -0.041 +/- 0.02 mL/min/cm H2O/100 g lung tissue, respectively, p animals administered activated charcoal compared to time-matched controls and animals administered sterile water. Intratracheal instillation of activated charcoal is associated with a significant increase in lung microvascular permeability and arterial blood gas derangements. The effects of activated charcoal on pulmonary microvascular barrier integrity may contribute to the lung edema formation and pulmonary compromise observed following clinical aspiration of activated charcoal.

  5. Lidocaine Prevents Oxidative Stress-Induced Endothelial Dysfunction of the Systemic Artery in Rats With Intermittent Periodontal Inflammation.

    Science.gov (United States)

    Saito, Takumi; Yamamoto, Yasuhiro; Feng, Guo-Gang; Kazaoka, Yoshiaki; Fujiwara, Yoshihiro; Kinoshita, Hiroyuki

    2017-06-01

    Periodontal inflammation causes endothelial dysfunction of the systemic artery. However, it is unknown whether the use of local anesthetics during painful dental procedures alleviates periodontal inflammation and systemic endothelial function. This study was designed to examine whether the gingival or systemic injection of lidocaine prevents oxidative stress-induced endothelial dysfunction of the systemic artery in rats with intermittent periodontal inflammation caused by lipopolysaccharides (LPS). Some rats received 1500 µg LPS injections to the gingiva during a week interval from the age of 8 to 11 weeks (LPS group). Lidocaine (3 mg/kg), LPS + lidocaine (3 mg/kg), LPS + lidocaine (1.5 mg/kg), and LPS + lidocaine (3 mg/kg, IP) groups simultaneously received gingival 1.5 or 3 mg/kg or IP 3 mg/kg injection of lidocaine on the same schedule as the gingival LPS. Isolated aortas or mandibles were subjected to the evaluation of histopathologic change, isometric force recording, reactive oxygen species, and Western immunoblotting. Mean blood pressure and heart rate did not differ among the control, LPS, LPS + lidocaine (3 mg/kg), and lidocaine (3 mg/kg) groups. LPS application reduced acetylcholine (ACh, 10 to 10 mol/L)-induced relaxation (29% difference at ACh 3 × 10 mol/L, P = .01), which was restored by catalase. Gingival lidocaine (1.5 and 3 mg/kg) dose dependently prevented the endothelial dysfunction caused by LPS application (24.5%-31.1% difference at ACh 3 × 10 mol/L, P = .006 or .001, respectively). Similar to the gingival application, the IP injection of lidocaine (3 mg/kg) restored the ACh-induced dilation of isolated aortas from rats with the LPS application (27.5% difference at ACh 3 × 10 mol/L, P lidocaine (3 mg/kg), or the combination. The LPS induced a 4-fold increase in the protein expression of tumor necrosis factor-α in the periodontal tissue (P lidocaine (3 mg/kg) coadministration partly reduced the levels. Lidocaine application also decreased

  6. Impaired coronary microvascular function in diabetics

    International Nuclear Information System (INIS)

    Tsujimoto, Go

    2000-01-01

    Global and regional myocardial uptake was determined with technetium-99m tetrofosmin and a 4 hour exercise (370 MBq iv) and rest (740 MBq iv) protocol, in 24 patients with non-insulin dependent diabetes mellitus and in 22 control subjects. The purpose of this study was to evaluate impaired coronary microvascular function in diabetics by measurement of % uptake increase in myocardial counts. The parameter of % uptake increase (ΔMTU) was calculated as the ratio of exercise counts to rest myocardial counts with correction of myocardial uptake for dose administered and physical decay between the exercise study and the rest study. Global ΔMTU was significantly lower in the diabetics than in control subjects (14.4±5.4% vs. 21.7±8.5%, p<0.01). Regional ΔMTU in each of 4 left ventricular regions (anterior, septal, inferior, posterolateral) was significantly lower in the diabetic group than in the control group (p<0.01) respectively, but there were no significant differences between ΔMTU in the 4 left ventricular regions in the same group. ΔMTU was useful as a non-invasive means of evaluating impaired coronary microvascular function in diabetics. (author)

  7. The Role of Dysfunctional Myths in a Decision-Making Process under Bounded Rationality: A Complex Dynamical Systems Perspective.

    Science.gov (United States)

    Stamovlasis, Dimitrios; Vaiopoulou, Julie

    2017-07-01

    The present study examines the factors influencing a decision-making process, with specific focus on the role of dysfunctional myths (DM). DM are thoughts or beliefs that are rather irrational, however influential to people's decisions. In this paper a decision-making process regarding the career choice of university students majoring in natural sciences and education (N=496) is examined by analyzing survey data taken via Career Decision Making Difficulties Questionnaire (CDDQ). The difficulty of making the choice and the certainty about one's decision were the state variables, while the independent variables were factors related to the lack of information or knowledge needed, which actually reflect a bounded rationality. Cusp catastrophe analysis, based on both least squares and maximum likelihood procedures, showed that the nonlinear models predicting the two state variables were superior to linear alternatives. Factors related to lack of knowledge about the steps involved in the process of career decision-making, lack of information about the various occupations, lack of information about self and lack of motivation acted as asymmetry, while dysfunctional myths acted as bifurcation factor for both state variables. The catastrophe model, grounded in empirical data, revealed a unique role for DM and a better interpretation within the context of complexity and the notion of bounded rationality. The analysis opens the nonlinear dynamical systems (NDS) perspective in studying decision-making processes. Theoretical and practical implications are discussed.

  8. Cutaneous microvascular perfusion responses to insulin iontophoresis are differentially affected by insulin resistance after spinal cord injury.

    Science.gov (United States)

    La Fountaine, Michael F; Cirnigliaro, Christopher M; Azarelo, Frank; Hobson, Joshua C; Tascione, Oriana; Swonger, Kirsten N; Dyson-Hudson, Trevor; Bauman, William A

    2017-09-01

    What is the central question of this study? What impact does insulin resistance have on cutaneous perfusion responses to insulin iontophoresis in vascular beds with markedly reduced or functionally ablated sympathetic nervous system vasomotor function resulting from spinal cord injury? What is the main finding and its importance? Persons with spinal cord injury have sublesional microvascular endothelial dysfunction, as indicated by a blunted cutaneous perfusion response to acetylcholine iontophoresis, and the presence of insulin resistance has a further confounding effect on endothelium-mediated changes to cutaneous perfusion in the lower extremities. Endothelium-mediated mechanisms that regulate skin blood flow might play an integral role in optimizing skin perfusion in vascular beds with sympathetic nervous system vasomotor impairment, such as in spinal cord injury (SCI). Insulin is a vasoactive hormone and second messenger of nitric oxide that facilitates endothelium-mediated dilatation. The effects of insulin resistance (IR) on sublesional cutaneous perfusion responses to insulin provocation have yet to be described in persons with SCI. Persons with SCI and an able-bodied (AB) cohort were divided into subgroups based upon fasting plasma insulin concentration cut-offs for IR (≥13.13 mIU ml -1 ) or insulin sensitivity (IS; insulin, acetylcholine or placebo iontophoresis in the lower extremities; BPU responses were log 10 transformed to facilitate comparisons, and the net insulin response (NetIns) BPU response was calculated (insulin minus placebo BPU response). The NetIns was significantly greater in both IS groups compared with their corresponding IR group. The acetylcholine-mediated BPU responses in the SCI subgroups were significantly lower than those in the ABIS group. The proportional BPU responses of NetIns to acetylcholine in the IS cohorts (i.e. ABIS and SCIS) were significantly greater (P < 0.05) than that of each IR subgroup. The presence of IR

  9. Erectile Dysfunction

    Science.gov (United States)

    ... cut out alcohol. Excess alcohol can contribute to erectile dysfunction. If you choose to drink alcohol, do so in moderation. For healthy adults, that means up to one drink a day for men older than age 65, and up to two drinks ...

  10. Cognitive dysfunction in body dysmorphic disorder: new implications for nosological systems and neurobiological models.

    Science.gov (United States)

    Jefferies-Sewell, Kiri; Chamberlain, Samuel R; Fineberg, Naomi A; Laws, Keith R

    2017-02-01

    Introduction Body dysmorphic disorder (BDD) is a debilitating disorder, characterized by obsessions and compulsions relating specifically to perceived appearance, and which has been newly classified within the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder. Participants with BDD (n=12) and participants without BDD (n=16) were tested using a computerized neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task), and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ, and education. In comparison to controls, patients with BDD showed significantly impaired attentional set-shifting, abnormal decision-making, impaired response inhibition, and greater omission and commission errors on the emotional processing task. Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity, and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the reclassification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD.

  11. Cognitive dysfunction in Body Dysmorphic Disorder: New implications for nosological systems & neurobiological models

    Science.gov (United States)

    Jefferies-Sewell, K; Chamberlain, SR; Fineberg, NA; Laws, KR

    2017-01-01

    Background Body dysmorphic disorder (BDD) is a debilitating disorder, characterised by obsessions and compulsions relating specifically to perceived appearance, newly classified within the DSM-5 Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder. Materials and Methods Participants with BDD (n=12) and healthy controls (n=16) were tested using a computerised neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task) and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ and education. Results In comparison to controls, patients with BDD showed significantly impaired attentional set shifting, abnormal decision-making, impaired response inhibition and greater omission and commission errors on the emotional processing task. Conclusions Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the re-classification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD. PMID:27899165

  12. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System

    Directory of Open Access Journals (Sweden)

    Qing-Qing Xu

    2016-01-01

    Full Text Available Sodium Tanshinone IIA sulfonate (STS is a derivative of Tanshinone IIA (Tan IIA. Tan IIA has been reported to possess neuroprotective effects against Alzheimer’s disease (AD. However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP- induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE and increased the activity of choline acetyltransferase (ChAT in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD and decreased the levels of malondialdehyde (MDA and reactive oxygen species (ROS in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3. STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

  13. Dysfunctional family systems: relationships to disordered eating behaviors among university women.

    Science.gov (United States)

    Lundholm, J K; Waters, J E

    1991-01-01

    Clinicians have speculated that the appearance and maintainance of eating-disordered behavior may be attributed to certain familial characteristics which predispose vulnerable individuals to the development of these behaviors. However, few empirical studies exist to substantiate these speculations. This study compared the responses of 190 female university students on three self-report instruments: the Disordered Eating and Weight Control Instrument (DEWCI), the Eating Disorders Instrument (EDI), and the Family Adaptability and Cohesion Evaluation Scale (FACES III) to identify potential relationships between eating-disordered behavior and family types. Subjects were classified, on the basis of their scores on the FACES III, into one of three family types: balanced, midrange, or extreme. A one-way analysis of variance with main effect for family type was applied to the eating-behavior subscales. A Turkey multiple comparison test was applied to the significant main effects. Women classified in the extreme family type scored significantly higher (p less than .05) on several measures of eating-disordered behavior. A Distance From Center (DFC) linear score also was computed and correlated with the eating-disordered subscales. All but 4 of the 18 measures correlated significantly (p less than .05). These findings support speculation, particularly that of family theorists, that eating-disordered behavior may be a symptom response and/or coping strategy for women in dysfunctional families.

  14. Human stem cell-derived neurons: a system to study human tau function and dysfunction.

    Directory of Open Access Journals (Sweden)

    Mariangela Iovino

    2010-11-01

    Full Text Available Intracellular filamentous deposits containing microtubule-associated protein tau constitute a defining characteristic of many neurodegenerative disorders. Current experimental models to study tau pathology in vitro do not usually recapitulate the tau expression pattern characteristic of adult human brain. In this study, we have investigated whether human embryonic stem cell-derived neurons could be a good model to study human tau distribution, function and dysfunction.Using RT-PCR, immunohistochemistry, western blotting and cell transfections we have investigated whether all 6 adult human brain tau isoforms are expressed in neurons derived from human embryonic and fetal stem cells and whether 4 repeat tau over-expression alone, or with the F3 tau repeat fragment, (amino acid 258-380 of the 2N4R tau isoform with the ΔK280 mutation affects tau distribution. We found that the shortest 3 repeat tau isoform, similarly to human brain, is the first to be expressed during neuronal differentiation while the other 5 tau isoforms are expressed later. Over expression of tau with 4 repeats affects tau cellular distribution and the short tau F3 fragment appears to increase tau phosphorylation but this effect does not appear to be toxic for the cell.Our results indicate that human embryonic stem cell-derived neurons express all 6 tau isoforms and are a good model in which to study tau physiology and pathology.

  15. Endothelial dysfunction and reduced heart rate variability in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Elena Nikolaevna Smirnova

    2018-03-01

    Full Text Available According to experts of the World Health Organization (WHO, metabolic syndrome (MS can be considered as pandemy of the XXI century, because its prevalence among the population of developed countries is about 25-35%. In this study with the purpose of complex investigation of the autonomic nervous system and endothelial function we included 66 patients with MS between the ages of 25 and 61 (46.9±9.9 years. A comparison group of apparently healthy individuals (16 individuals, average age of 45.3±2.3 years; P>0.05 was studied. To evaluate the response of microvascular tone, we used the method of wavelet analysis of skin temperature oscillations during cooling of the limb. All patients underwent the study of heart rate variability. The levels of insulin, endothelin-1, and vascular endothelial growth factor were determined using enzyme immunoassay. Patients with MS had significant differences in all metabolic parameters. Our study showed that in the group of MS there is a decrease of the variability of heart rhythm compared with the healthy group. Conducting cold test revealed signs of endothelial dysfunction in the MS group, which was manifested by the decrease of the index of vasodilation in the endothelial and neurogenic frequency range. In the study group we determined the increase in biochemical markers of endothelial dysfunction, which correlated with parameters of vasodilation. Also, the presence of endothelial dysfunction significantly correlated with signs of reduction of the variability of the heart rhythm.

  16. Differentiation state determines neural effects on microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Muffley, Lara A., E-mail: muffley@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: pansc@mail.ncku.edu.tw [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: gnaunderwater@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: marga16@uw.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

    2012-10-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

  17. Mandibular reconstruction with composite microvascular tissue transfer

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, J.J. III; Wooden, W.A. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1990-10-01

    Microvascular free tissue transfer has provided a variety of methods of restoring vascularized bone and soft tissue to difficult defects created by tumor resection and trauma. Over 7 years, 26 patients have undergone 28 free flaps for mandibular reconstruction, 15 for primary squamous cell carcinoma of the floor of the mouth or tongue, 7 for recurrent tumor, and 6 for other reasons (lymphangioma (1), infection (1), gunshot wound (1), and osteoradionecrosis (3)). Primary reconstruction was performed in 19 cases and secondary in 9. All repairs were composite flaps including 12 scapula, 5 radial forearm, 3 fibula, 2 serratus, and 6 deep circumflex iliac artery. Mandibular defects included the symphysis alone (7), symphysis and body (5), symphysis-body-ramus condyle (2), body or ramus (13), and bilateral body (1). Fourteen patients had received prior radiotherapy to adjuvant or curative doses. Eight received postoperative radiotherapy. All patients had initially successful vascularized reconstruction by clinical examination (28) and positive radionuclide scan (22 of 22). Bony stability was achieved in 25 of 26 patients and oral continence in 24 of 26. One complete flap loss occurred at 14 days. Complications of some degree developed in 22 patients including partial skin necrosis (3), orocutaneous fistula (3), plate exposure (1), donor site infection (3), fracture of reconstruction (1), and fracture of the radius (1). Microvascular transfer of bone and soft tissue allows a reliable reconstruction--despite previous radiotherapy, infection, foreign body, or surgery--in almost every situation in which mandible and soft tissue are absent. Bony union, a healed wound, and reasonable function and appearance are likely despite early fistula, skin loss, or metal plate or bone exposure.

  18. TRANSFUSION RESTORES BLOOD VISCOSITY AND REINSTATES MICROVASCULAR CONDITIONS FROM HEMORRHAGIC SHOCK INDEPENDENT OF OXYGEN CARRYING CAPACITY

    OpenAIRE

    Cabrales, Pedro; Intaglietta, Marcos; Tsai, Amy G.

    2007-01-01

    Systemic and microvascular hemodynamic responses to transfusion of oxygen using functional and non-functional packed fresh red blood cells (RBCs) from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of RBCs on rheological and oxygen transport properties. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of the blood volume, and a hypovolemic state was maintained for one hour. Volume restitution was performed by infus...

  19. Endothelial and non-endothelial coronary blood flow reserve and left ventricular dysfunction in systemic hypertension

    Directory of Open Access Journals (Sweden)

    Aloísio Marchi Rocha

    2009-04-01

    Full Text Available OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has been proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS. Group 1 (FS >0.25: n=8, FS=0.29 ± 0.03; Group 2 (FS <0.25: n=10, FS= 0.17 ± 0.03. RESULTS: Baseline coronary blood flow was similar in both groups (Group 1: 80.15 ± 26.41 mL/min, Group 2: 100.09 ± 21.51 mL/min, p=NS. In response to adenosine, coronary blood flow increased to 265.1 ± 100.2 mL/min in Group 1 and to 300.8 ± 113.6 mL/min (p <0.05 in Group 2. Endothelium-independent coronary blood flow reserve was similar in both groups (Group 1: 3.31 ± 0.68 and Group 2: 2.97 ± 0.80, p=NS. In response to acetylcholine, coronary blood flow increased to 156.08 ± 36.79 mL/min in Group 1 and to 177.8 ± 83.6 mL/min in Group 2 (p <0.05. Endothelium-dependent coronary blood flow reserve was similar in the two groups (Group 1: 2.08 ± 0.74 and group Group 2: 1.76 ± 0.61, p=NS. Peak acetylcholine/peak adenosine coronary blood flow response (Group 1: 0.65 ± 0.27 and Group 2: 0.60 ± 0.17 and minimal coronary vascular resistance (Group 1: 0.48 ± 0.21 mmHg/mL/min and Group 2: 0.34 ± 0.12 mmHg/mL/min were similar in both groups (p= NS. Casual diastolic blood pressure and end-systolic left ventricular stress were independently associated with FS. CONCLUSIONS: In our hypertensive patients, endothelium-dependent and endothelium-independent coronary blood flow reserve vasodilator administrations had similar effects in patients with either normal or decreased left

  20. Nosography of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome in internal medicine patients

    Directory of Open Access Journals (Sweden)

    Silvia Spoto

    2015-09-01

    Full Text Available Sepsis is defined by the presence of at least two systemic inflammatory response syndrome criteria associated with an infection microbiologically or clinically evidenced. In Italy sepsis is responsible for 80,000 hospital admissions per year and, in the last decades, severe sepsis and septic shock cases are increasing, in correlation with the increased prevalence of multi-drugresistant microbial strains. The predominant etiologic agents are Gram-positive and Gram-negative bacteria, but sepsis caused by fungi is increasing. The host response with both inflammatory and anti-inflammatory processes is responsible for organic failures, which complicate the syndrome, and for the susceptibility to secondary infections. The impairment of one or more organs or systems may be the onset clinical presentation. The organ dysfunctions complicating sepsis involve mainly cardiorespiratory system, kidneys, hemostatis and central nervous system. Fever or hypothermia, tachycardia, tachypnea, leukocytosis or leukopenia, elevated blood levels of lactate and procalcitonin, hypotension are diagnostically sensitive findings for sepsis. Definitive diagnosis requires isolation of the pathogen from blood sample or from the focus of infection. Therapeutic success against sepsis depends on the appropriate use of antibiotics, on the treatment of hemodynamic and respiratory disorder and on general supportive care. In some cases the use of activated protein C is to take in consideration.

  1. THE CARDIOVASCULAR SYSTEM IN TYPE 2 DIABETES MELLITUS AND THYROID DISORDERS IN THE ABSENCE OF THYROID GLAND DYSFUNCTION.

    Science.gov (United States)

    Ballyizek, M F; Ignat'eva Pa

    The state of the cardiovascular system was studied in patients with type 2 diabetes mellitus and thyroid disorders in the absence of thyroid gland dysfunction. 76.9% of the 302 patients with DM2 had thyroid pathology; in 23,8% it was not previously diagnosed. We compared euthyroid patients with DM2 without thy'ropathies and with diffuse-nodular changes largely in the form of difuse- multinodular non-toxic goiter and autoinnnune thyroiditis (AIT). It was demonstrated that enhanced frequency of thyroid disorders is related to DM2 duration and vascular complications. The predominant thyroid pathology in DM2 was diffuse-multinodular non-toxic goiter followed by autoimnune thvroiditis. Nodular forms in AIT without DM2 are rare whereas multinodularformns in the patients with DM2 and AIT occur much more fequently. Node formation is related to such DM2 complications as diabetic nephropathy, angiopathy, and retinopathy. The study showed that the frequency of both non-specific clinical changes characteristic of thyroid dysfunction and of specific cardiological manifestations in euthyroid patients with DM2 and thyroid pathology signficantly increases especially in the presence of AIT and anti-thyreoperoxidase antibodies, regardless the form of thyropathy. It may be due to imimuno-inflammatory cross talk between thyroid and myocardial tissues. Patients with DM2 and diffuse-nodular changes in the thyroid gland more frequently presented with dif ferent forms of atrial fibrillation and high-grade ventricular extrasystole than patients with AIT or DM2 without thyropathies. It is concluded that euthyroid patients with DM2 need their thyroid function to be regularly monitored. The development of examination algorithm is an object of further studies.

  2. Retinal microvascular abnormalities and stroke: a systematic review

    NARCIS (Netherlands)

    Doubal, F.N.; Hokke, P.E.; Wardlaw, J.M.

    2009-01-01

    Background: Lacunar strokes account for 25% of ischaemic strokes, but their precise aetiology is unknown. Similarities between the retinal and cerebral small vessels mean that clarification of the exact relationship between retinal microvascular abnormalities and stroke, and particularly with stroke

  3. Capillaries within compartments: microvascular interpretation of dynamic positron emission tomography data

    DEFF Research Database (Denmark)

    Munk, O L; Keiding, S; Bass, L

    2003-01-01

    estimation of parameters in models with more physiological realism. We explore the standard compartmental model and find that incorporation of blood flow leads to paradoxes, such as kinetic rate constants being time-dependent, and tracers being cleared from a capillary faster than they can be supplied...... single- and multi-capillary systems and include effects of non-exchanging vessels. They are suitable for analysing dynamic PET data from any capillary bed using either intravascular or diffusible tracers, in terms of physiological parameters which include regional blood flow. Udgivelsesdato: 2003-Nov-7...... by blood flow. The inability of the standard model to incorporate blood flow consequently raises a need for models that include more physiology, and we develop microvascular models which remove the inconsistencies. The microvascular models can be regarded as a revision of the input function. Whereas...

  4. Neurogenic voiding dysfunction.

    Science.gov (United States)

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

    This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments. Despite the extended evidence base on NLUTD, there is a paucity of high-quality new research concerning voiding dysfunction as opposed to storage problems. The update aims to inform clinicians about new developments in clinical practice, as well as ignite discussion for further clinical and basic research in the aforementioned areas of NLUTD.

  5. Coherence and Coupling Functions Reveal Microvascular Impairment in Treated Hypertension

    Directory of Open Access Journals (Sweden)

    Valentina Ticcinelli

    2017-10-01

    Full Text Available The complex interactions that give rise to heart rate variability (HRV involve coupled physiological oscillators operating over a wide range of different frequencies and length-scales. Based on the premise that interactions are key to the functioning of complex systems, the time-dependent deterministic coupling parameters underlying cardiac, respiratory and vascular regulation have been investigated at both the central and microvascular levels. Hypertension was considered as an example of a globally altered state of the complex dynamics of the cardiovascular system. Its effects were established through analysis of simultaneous recordings of the electrocardiogram (ECG, respiratory effort, and microvascular blood flow [by laser Doppler flowmetry (LDF]. The signals were analyzed by methods developed to capture time-dependent dynamics, including the wavelet transform, wavelet-based phase coherence, non-linear mode decomposition, and dynamical Bayesian inference, all of which can encompass the inherent frequency and coupling variability of living systems. Phases of oscillatory modes corresponding to the cardiac (around 1.0 Hz, respiratory (around 0.25 Hz, and vascular myogenic activities (around 0.1 Hz were extracted and combined into two coupled networks describing the central and peripheral systems, respectively. The corresponding spectral powers and coupling functions were computed. The same measurements and analyses were performed for three groups of subjects: healthy young (Y group, 24.4 ± 3.4 y, healthy aged (A group, 71.1 ± 6.6 y, and aged treated hypertensive patients (ATH group, 70.3 ± 6.7 y. It was established that the degree of coherence between low-frequency oscillations near 0.1 Hz in blood flow and in HRV time series differs markedly between the groups, declining with age and nearly disappearing in treated hypertension. Comparing the two healthy groups it was found that the couplings to the cardiac rhythm from both respiration and

  6. Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus.

    Science.gov (United States)

    Massardo, L; Bravo-Zehnder, M; Calderón, J; Flores, P; Padilla, O; Aguirre, J M; Scoriels, L; González, A

    2015-05-01

    Autoantibodies against N-methyl-D-aspartate receptor (anti-NMDAR) and ribosomal-P (anti-P) antigens are potential pathogenic factors in the frequently observed diffuse brain dysfunctions in patients with systemic lupus erythematosus (SLE). Although studies have been conducted in this area, the role of anti-NMDAR antibodies in SLE cognitive dysfunction remains elusive. Moreover, the specific contribution of anti-P antibodies has not been reported yet. The present study attempts to clarify the contribution of anti-NMDAR and anti-P antibodies to cognitive dysfunction in SLE. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess a wide range of cognitive function areas in 133 Chilean women with SLE. ANCOVA models included autoantibodies, patient and disease features. Cognitive deficit was found in 20%. Higher SLEDAI-2K scores were associated with impairment in spatial memory and learning abilities, whereas both anti-NMDAR and anti-P antibodies contributed to deficits in attention and spatial planning abilities, which reflect fronto-parietal cortex dysfunctions. These results reveal an association of active disease together with specific circulating autoantibodies, such as anti-NMDAR and anti-P, with cognitive dysfunction in SLE patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. Primary graft dysfunction; possible evaluation by high resolution computed tomography, and suggestions for a scoring system

    DEFF Research Database (Denmark)

    Belmaati, Esther; Jensen, Claus; Kofoed, Klaus F

    2009-01-01

    and appears to have many morphological features similar to what is found in PGD, and might, therefore, be usefully extrapolated to PGD. Principles of HRCT, scoring systems based on HRCT and various terms describing PGD were reviewed and summarized. The sensitivity, inter-intra observer variability......, and reproducibility of these systems were discussed. Lastly, the future perspectives for 64-multi-slice computed tomography (MSCT) in relation to PGD were discussed. Few studies on scoring systems of lung tissue by HRCT in ARDS patients and idiopathic pulmonary fibrosis (IPF) patients were found. Most studies were...... of minimal influence. Studies have reported on how lung tissue images, derived by HRCT, can be scored and graded. There does not seem to be a golden standard for evaluating these images, which makes comparison between methods challenging. These scoring systems assess the presence, severity, and extent...

  8. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting.

    Science.gov (United States)

    Cade, W Todd

    2008-11-01

    Physical therapists commonly treat people with diabetes for a wide variety of diabetes-associated impairments, including those from diabetes-related vascular disease. Diabetes is associated with both microvascular and macrovascular diseases affecting several organs, including muscle, skin, heart, brain, and kidneys. A common etiology links the different types of diabetes-associated vascular disease. Common risk factors for vascular disease in people with diabetes, specifically type 2 diabetes, include hyperglycemia, insulin resistance, dyslipidemia, hypertension, tobacco use, and obesity. Mechanisms for vascular disease in diabetes include the pathologic effects of advanced glycation end product accumulation, impaired vasodilatory response attributable to nitric oxide inhibition, smooth muscle cell dysfunction, overproduction of endothelial growth factors, chronic inflammation, hemodynamic dysregulation, impaired fibrinolytic ability, and enhanced platelet aggregation. It is becoming increasingly important for physical therapists to be aware of diabetes-related vascular complications as more patients present with insulin resistance and diabetes. The opportunities for effective physical therapy interventions (such as exercise) are significant.

  9. Improving diagnosis and treatment of women with angina pectoris and microvascular disease

    DEFF Research Database (Denmark)

    Prescott, Eva; Abildstrøm, Steen Zabell; Aziz, Ahmed

    2014-01-01

    BACKGROUND: The iPOWER study aims at determining whether routine assessment of coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease is feasible and identifies women at risk. METHODS: All women with angina referred to invasive angiographic......, advanced echocardiographic modalities at rest and during stress, and invasive measures of CFR and coronary vascular reactivity. The study will include 2000 women who will be followed for 5 years for cardiovascular outcomes. RESULTS: By May 2013, 1685 women have been screened, 759 eligible patients...... identified, 530 contacted, and 299 (56%) agreed to participate. Among the first 50 patients, Doppler CFR was successfully measured in 49 (98%). CONCLUSIONS: Among women with suspected ischemic heart disease and no obstructive coronary artery disease, non-invasive Doppler CFR is feasible as a routine...

  10. (Dysfunctionality of accounting cost systems in manufacturing companies of Tuzla canton

    Directory of Open Access Journals (Sweden)

    Sado Puškarević

    2014-12-01

    Full Text Available This paper shows the results of the conducted primary survey on functionality of cost systems in manufacturing companies of Tuzla Canton (hereinafter “TC”. This paper assesses their adequacy to the needs of these companies: the present needs, and the ones that will be brought by the changes in the environment. These systems have to be up-to-date, as they influence the process of cost management, which is the key factor of companies’ adaptation to the conditions of a modern market. Cost management, which is based on the information of a cost system, enables the company to take the adequate stand towards customers on markets and toward their competition. Also, the quality cost information is a precondition for effective and efficient allocation of limited resources in a transitional period of society development. Therefore, only quality designed cost system in transitional economy will enable recovery, and then, growth and development of a company. This emphasizes the importance of research of the stated issues for transitional countries. The research results should also help to persuade the management about the need to modernize the operation organization, primarily the accounting function, mainly in the part of cost system organization. The determined defects, as well as deviances in relation to current needs for information about costs, are guidelines for an adequate process of redesigning cost systems in companies of transitional economy.

  11. Absolute coronary blood flow measurement and microvascular resistance in ST-elevation myocardial infarction in the acute and subacute phase

    Energy Technology Data Exchange (ETDEWEB)

    Wijnbergen, Inge; Veer, Marcel van ' t [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven (Netherlands); Lammers, Jeroen; Ubachs, Joey [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Pijls, Nico H.J., E-mail: nico.pijls@cze.nl [Department of Cardiology, Catharina Hospital, Eindhoven (Netherlands); Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven (Netherlands)

    2016-03-15

    Background/Purpose: In a number of patients with acute myocardial infarction (AMI), myocardial hypoperfusion, known as the no-reflow phenomenon, persists after primary percutaneous intervention (PPCI). The aim of this study was to evaluate the feasibility and safety of a new quantitative method of measuring absolute blood flow and resistance within the perfusion bed of an infarct-related artery. Furthermore, we sought to study no-reflow by correlating these measurements to the index of microvascular resistance (IMR) and the area at risk (AR) as determined by cardiac magnetic resonance imaging (CMR). Methods: Measurements of absolute flow and myocardial resistance were performed in 20 patients with ST-segment elevation myocardial infarction (STEMI), first immediately following PPCI and then again after 3–5 days. These measurements used the technique of thermodilution during a continuous infusion of saline. Flow was expressed in ml/min per gram of tissue within the area at risk. Results: The average time needed for measurement of absolute flow, resistance and IMR was 20 min, and all measurements could be performed without complication. A higher flow supplying the AR correlated with a lower IMR in the acute phase. Absolute flow increased from 3.14 to 3.68 ml/min/g (p = 0.25) and absolute resistance decreased from 1317 to 1099 dyne.sec.cm-5/g (p = 0.40) between the first day and fifth day after STEMI. Conclusions: Measurement of absolute flow and microvascular resistance is safe and feasible in STEMI patients and may allow for a better understanding of microvascular (dys)function in the early phase of AMI. - Highlights: • We measured absolute coronary blood flow and microvascular resistance in STEMI patients in the acute phase and in the subacute phase, using the technique of thermodilution with low grade intracoronary continuous infusion of saline. • These measurements are safe and feasible during PPCI in STEMI patients. • In STEMI patients, absolute flow

  12. Renal dysfunction prevalence and clinical impact in heart failure

    Directory of Open Access Journals (Sweden)

    Palazzuoli A

    2011-09-01

    Full Text Available Alberto Palazzuoli, Susanna Benincasa, Stefanie Grothgar, Pasquale Di Sipio, Giovanni Paganini, Marco Pellegrini, Ranuccio NutiDepartment of Internal Medicine and Metabolic Diseases, Cardiology Section, Le Scotte Hospital, University of Siena, ItalyAbstract: Chronic kidney disease (CKD is associated with a significant increase in death and cardiovascular mortality. However the exact mechanism by which CKD impairs the cardiovascular outcome is not well established. Some reasons may lie in the association of CKD with several other cardiovascular and noncardiovascular disorders including accelerated systemic atherosclerosis, endothelial dysfunction, increased levels of inflammatory factors, anemic status, bone mineral dysfunction, electrolyte imbalance, and renin–angiotensin–aldosterone system (RAAS activation. Therefore several risk factors such as hypertension, diabetes, lipid disorders, and older age are common in both conditions. In patients affected with heart failure (HF a key role is represented by the neurohormonal activation. This condition causes fluid and sodium retention, peripheral vasoconstriction, as well as increased congestion and cardiac workload. Moreover, HF during the decompensated phases is often associated with a worsening renal function that leads to further RAAS activation, microvascular damage, and intrarenal flow redistribution. In order to clarify the interactions between these factors, several questions need to be answered: the universal definition of “worsening renal function,” the identification of the best laboratory parameters to investigate renal function in terms of sensitivity and specificity, and a better definition of the comorbidities’ role in the determination of the outcome, especially in patients with chronic HF. A clarification of these key points could lead to the individualization of new specific therapeutic targets and to a reduction in mortality and hospitalization in patients with HF and

  13. Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications.

    Science.gov (United States)

    Cho, Y H; Craig, M E; Januszewski, A S; Benitez-Aguirre, P; Hing, S; Jenkins, A J; Donaghue, K C

    2017-04-01

    To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA 1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. Skin autofluorescence was significantly associated with age (R 2 = 0.15; P skin autofluorescence was associated with concurrent HbA 1c (R 2 = 0.32; P skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R 2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R 2 = 0.11; P = 0.006). Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications. © 2016 Diabetes UK.

  14. The concept of depression as a dysfunction of the immune system

    OpenAIRE

    Leonard, Brian E.

    2010-01-01

    Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis and the immune system, acts as a trigger for anxiety and depression. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids, as occurs in chronically stressful situations and in depression, contribute to the behavioural changes associated with depression.

  15. Dysfunctional astrocytes as key players in the pathogenesis of central nervous system disorders

    NARCIS (Netherlands)

    De Keyser, Jacques; Mostert, Jop P.; Koch, Marcus W.

    2008-01-01

    Once considered little more than the glue that holds neurons in place, astrocytes are now becoming appreciated for the key roles they play in central nervous system functions. They supply neurons and oligodendrocytes with substrates for energy metabolism, control extracellular water and electrolyte

  16. The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function

    International Nuclear Information System (INIS)

    Bakkum, M.J.; Danad, I.; Romijn, M.A.J.; Stuijfzand, W.J.A.; Leonora, R.M.; Rossum, A.C. van; Knaapen, P.; Tulevski, I.I.; Somsen, G.A.; Lammertsma, A.A.; Kuijk, C. van; Raijmakers, P.G.

    2015-01-01

    Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function. A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [ 15 O]H 2 O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow. Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg x ml -1 x min -1 x g -1 , p < 0.01) as compared to nonobese patients. Male gender (β = 40.7, p < 0.001), BMI (β = 1.61, p < 0.001), smoking (β = 6.29, p = 0.03) and EAT volume (β = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR. EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors. (orig.)

  17. The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function

    Energy Technology Data Exchange (ETDEWEB)

    Bakkum, M.J.; Danad, I.; Romijn, M.A.J.; Stuijfzand, W.J.A.; Leonora, R.M.; Rossum, A.C. van; Knaapen, P. [VU University Medical Center, Department of Cardiology, Amsterdam (Netherlands); Tulevski, I.I.; Somsen, G.A. [Cardiology Centers of the Netherlands, Amsterdam (Netherlands); Lammertsma, A.A.; Kuijk, C. van; Raijmakers, P.G. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands)

    2015-09-15

    Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function. A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [{sup 15}O]H{sub 2}O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow. Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg x ml{sup -1} x min{sup -1} x g{sup -1}, p < 0.01) as compared to nonobese patients. Male gender (β = 40.7, p < 0.001), BMI (β = 1.61, p < 0.001), smoking (β = 6.29, p = 0.03) and EAT volume (β = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR. EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors. (orig.)

  18. DETECTION OF MICROVASCULAR COMPLICATIONS OF TYPE 2 DIABETES BY EZSCAN AND ITS COMPARISON WITH STANDARD SCREENING METHODS

    Directory of Open Access Journals (Sweden)

    Sarita Bajaj

    2016-08-01

    Full Text Available BACKGROUND EZSCAN is a new, noninvasive technique to detect sudomotor dysfunction and thus neuropathy in diabetes patients at an early stage. It further predicts chances of development of other microvascular complications. In this study, we evaluated EZSCAN for detection of microvascular complications in Type 2 diabetes patients and compared accuracy of EZSCAN with standard screening methods. MATERIALS AND METHODS 104 known diabetes patients, 56 males and 48 females, were studied. All cases underwent the EZSCAN test, Nerve Conduction Study (NCS test, Vibration perception threshold test (VPT, Monofilament test, Fundus examination and Urine micral test. The results of EZSCAN were compared with standard screening methods. The data has been analysed and assessed by applying appropriate statistical tests within different groups. RESULTS Mean age of the subjects was 53.5 ± 11.4 years. For detection of diabetic neuropathy, sensitivity and specificity of EZSCAN was found to be 77.0 % and 95.3%, respectively. Odd’s ratio (OR was 68.82 with p < 0.0001. AUC in ROC curve was 0.930. Sensitivity and specificity of EZSCAN for detection of nephropathy were 67.1% and 94.1%, respectively. OR = 32.69 with p < 0.0001. AUC was 0.926. Sensitivity of EZSCAN for detection of retinopathy was 90% while specificity is 70.3%. OR = 21.27; p< 0.0001. AUC came out to be 0.920. CONCLUSION Results of EZSCAN test compared significantly to the standard screening methods for the detection of microvascular complications of diabetes and can be used as a simple, noninvasive and quick method to detect microvascular complications of diabetes.

  19. Does dysfunction of the mirror neuron system contribute to symptoms in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Eisen, Andrew; Lemon, Roger; Kiernan, Matthew C; Hornberger, Michael; Turner, Martin R

    2015-07-01

    There is growing evidence that mirror neurons, initially discovered over two decades ago in the monkey, are present in the human brain. In the monkey, mirror neurons characteristically fire not only when it is performing an action, such as grasping an object, but also when observing a similar action performed by another agent (human or monkey). In this review we discuss the origin, cortical distribution and possible functions of mirror neurons as a background to exploring their potential relevance in amyotrophic lateral sclerosis (ALS). We have recently proposed that ALS (and the related condition of frontotemporal dementia) may be viewed as a failure of interlinked functional complexes having their origins in key evolutionary adaptations. This can include loss of the direct projections from the corticospinal tract, and this is at least part of the explanation for impaired motor control in ALS. Since, in the monkey, corticospinal neurons also show mirror properties, ALS in humans might also affect the mirror neuron system. We speculate that a defective mirror neuron system might contribute to other ALS deficits affecting motor imagery, gesture, language and empathy. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Influence of Different Doses of Levofloxacin on Antioxidant Defense Systems and Markers of Renal and Hepatic Dysfunctions in Rats

    Directory of Open Access Journals (Sweden)

    Ebenezer Tunde Olayinka

    2015-01-01

    Full Text Available Levofloxacin (LFX is a broad spectrum fluoroquinolone antibiotic used in the treatment of infections such as pneumonia, chronic bronchitis, and sinusitis. The present study assessed the likely toxic effect of LFX on hepatic and renal tissues in rats. Twenty male Wistar rats were randomly divided into four treatment groups: A: control, B: 5 mg/kg bw LFX (half therapeutic dose, C: 10 mg/kg bw LFX (therapeutic dose, and D: 20 mg/kg bw LFX (double therapeutic dose. After seven days of administration, result indicated significant (P<0.05 increase in plasma ALT, AST, and ALP activities in the treated groups compared to control. Also, there was a significant increase in plasma creatinine, urea, and total bilirubin in the treated groups relative to control. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides also increased significantly in the treated groups relative to control. Also, hepatic MDA level increased significantly in all the treated groups. However, hepatic SOD, catalase, and GST activities were significantly reduced in the LFX-treated animals. Moreover, GSH and ascorbic acid levels were significantly decreased in the LFX-treated groups relative to control. In conclusion, three doses of levofloxacin depleted antioxidant defense system and induced oxidative stress and hepatic and renal dysfunctions in rats.

  1. In vitro analysis of human periodontal microvascular endothelial cells.

    Science.gov (United States)

    Tsubokawa, Mizuki; Sato, Soh

    2014-08-01

    Endothelial cells (ECs) participate in key aspects of vascular biology, such as maintenance of capillary permeability, initiation of coagulation, and regulation of inflammation. According to previous reports, ECs have revealed highly specific characteristics depending on the organs and tissues. However, some reports have described the characteristics of the capillaries formed by human periodontal ECs. Therefore, the aim of the present study is to examine the functional characteristics of the periodontal microvascular ECs in vitro. Human periodontal ligament-endothelial cells (HPDL-ECs) and human gingiva-endothelial cells (HG-ECs) were isolated by immunoprecipitation with magnetic beads conjugated to a monoclonal anti-CD31 antibody. The isolated HPDL-ECs and HG-ECs were characterized to definitively demonstrate that these cell cultures represented pure ECs. Human umbilical-vein ECs and human dermal microvascular ECs were used for comparison. These cells were compared according to the proliferation potential, the formation of capillary-like tubes, the transendothelial electric resistance (TEER), and the expression of tight junction proteins. HPDL-ECs and HG-ECs with characteristic cobblestone monolayer morphology were obtained, as determined by light microscopy at confluence. Furthermore, the HPDL-ECs and HG-ECs expressed the EC markers platelet endothelial cell adhesion molecule-1 (also known as CD31), von Willebrand factor, and Ulex europaeus agglutinin 1, and the cells stained strongly positive for CD31 and CD309. In addition, the HPDL-ECs and HG-ECs were observed to form capillary-like tubes, and they demonstrated uptake of acetylated low-density lipoprotein. Functional analyses of the HPDL-ECs and HG-ECs showed that, compared to the control cells, tube formation persisted for only a brief period of time, and TEER was substantially reduced at confluence. Furthermore, the cells exhibited delocalization of zonula occludens-1 and occludin at cell-cell contact sites

  2. Relationship of endothelial dysfunction and kidney functional state in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    A M Basova

    2009-01-01

    Full Text Available Objective. To study vasoregulatory function of vascular wall in pts with systemic sclerosis (SS and chronic scleroderma-related renal disease (SRD and determine relationship with main measures of kidney functional state. Material and methods. 25 pts with SS (24 female with mean age 46,4±10,7 years and mean disease duration 7,5±4,7 years were included. 24 pts (96% had diffuse form and 17 pts (68% – generalized stage of SS. 22 pts (88% had chronic course of the disease with typical damage of vessels, heart, lungs and skin. SRD was revealed in 17 pts (68%. Sonographic method of Celermejer D. et al. (1992 was used for assessment of vascular endothelial function. 15 healthy persons without SS were included in control group. Results. Most prominent changes of brachial artery reactivity with insufficient vasodilatation and paradoxical vasoconstriction to reactive hyperemia were revealed in most pts with moderate and severe SRD. Conclusion. These changes of endothelium dependent and endothelium independent parameters in pts with SRD pointed to irreversible probably scleroderma-related vascular wall damage.

  3. New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis

    Science.gov (United States)

    Orellana, Juan A.; Cerpa, Waldo; Carvajal, Maria F.; Lerma-Cabrera, José M.; Karahanian, Eduardo; Osorio-Fuentealba, Cesar; Quintanilla, Rodrigo A.

    2017-01-01

    Alcohol dependence causes physical, social, and moral harms and currently represents an important public health concern. According to the World Health Organization (WHO), alcoholism is the third leading cause of death worldwide, after tobacco consumption and hypertension. Recent epidemiologic studies have shown a growing trend in alcohol abuse among adolescents, characterized by the consumption of large doses of alcohol over a short time period. Since brain development is an ongoing process during adolescence, short- and long-term brain damage associated with drinking behavior could lead to serious consequences for health and wellbeing. Accumulating evidence indicates that alcohol impairs the function of different components of the melanocortin system, a major player involved in the consolidation of addictive behaviors during adolescence and adulthood. Here, we hypothesize the possible implications of melanocortins and glial cells in the onset and progression of alcohol addiction. In particular, we propose that alcohol-induced decrease in α-MSH levels may trigger a cascade of glial inflammatory pathways that culminate in altered gliotransmission in the ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate dopaminergic drive in the NAc, contributing to increase the vulnerability to alcohol dependence and addiction in the adolescence and adulthood. PMID:28424592

  4. Organizational Dysfunctions: Sources and Areas

    Directory of Open Access Journals (Sweden)

    Jacek Pasieczny

    2016-12-01

    Full Text Available Objective:The purpose of this article is to identify and describe various types and sources of organizational dysfunctions. Research Design & Methods: The findings are based on literature review and an ongoing empirical research project conducted in private sector organisations. The empirical study can be situated within interpretative approach. In this qualitative project open interviews and observations were used to collect data. Findings: The study indicates that various types and sources of organizational dysfunctions can be identified in organizations operating in Poland. The sources of dysfunctions may be found both within the organization and its environment. Regardless of its specific features, most of the dysfunctions may be interpreted as an undesirable goal displacement. Very often areas of these dysfunctions are strongly interconnected and create a system that hinders organizational performance. Yet, it is difficult to study these phenomena as respondents are unwilling, for various reasons, to disclose the problems faced by their organizations. Implications & Recommendations: The results imply that the issue of organisational dysfunctions requires open, long-lasting and comparative studies. Recommendations for further studies are formulated in the last section of the paper. Contribution & Value Added: The paper provides insight into "the dark side of organising" by identifying sources and areas of dysfunctions. It also reveals difficulties connected with conducting research on dysfunctions in the Polish context.

  5. Autonomic Dysfunction Predicts Early Cardiac Affection in Patients with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Khaled M. Othman

    2010-01-01

    Full Text Available Objective To detect the early preclinical alterations in cardiac autonomic control as well as altered cardiac function in systemic sclerosis (SSc patients and their relevance to the clinical features of the disease using noninvasive methods. Methods 30 SSc patients and 15 healthy controls matched for age and sex underwent clinical examination, serological analysis, and echocardiographic assessment including Doppler flow imaging to evaluate cardiac function, and 24-hour Holter monitoring analyzed for arrhythmia and heart rate variability (HRV in the time and frequency domains. Results The trans-mitral Doppler of early to atrial wave (E/A ratio was reversed in five patients (16.6% and the tricuspid E/A ratio was reversed in 10 patients (33.3%. Holter analysis for SSc patients revealed an increased prevalence of premature ventricular contractions (PVC ≥ 10/h ( P = 0.02, supra-ventricular tachycardias (SVTs ( P = 0.2, and total PVC count ( P = 0.0000. Highly significant ( P = 0.000 impairment in all HRV parameters was demonstrated in the SSc patients. Total skin thickness score (TSS, Raynaud's phenomenon and anti-scleroderma 70 (anti-SCL70 showed significant positive correlations with all arrhythmia parameters, while showing a significant negative correlation with the impaired ventricular diastolic function and various HRV parameters. No correlation was found between arrhythmia and HRV parameters and disease duration, disease type, or presence of anti-centromere antibodies. Conclusion Low heart rate variability, increased TSS and the presence of anti-SCL70 are correlated with preclinical cardiac involvement in SSc patients and may predict the likelihood of malignant arrhythmia and sudden cardiac death. Therefore, noninvasive HRV evaluation before clinical cardiac involvement in these patients might be beneficial when added to the clinical and laboratory assessments in detecting high-risk patients, and may allow for implementation of preventive

  6. Postirradiation cardiovascular dysfunction

    International Nuclear Information System (INIS)

    Hawkins, R.N.; Cockerham, L.G.

    1987-01-01

    Cardiovascular dysfunction may be defined as the inability of any element of the cardiovascular system to perform adequately upon demand, leading to inadequate performance and nutritive insufficiency of various parts of the body. Exposure to supralethal doses of radiation (accidental and therapeutic) has been show to induce significant alterations in cardiovascular function in man. These findings indicate that, after irradiation, cardiovascular function is a major determinant of continued performance and even survival. For the two persons who received massive radiation doses (45 and 88 Gy, respectively) in criticality accidents, the inability to maintain systematic arterial blood pressure (AP) was the immediate cause of death. In a study of cancer patients given partial-body irradiation, two acute lethalities were attributed to myocardial infarction after an acute hypotensive episode during the first few hours postexposure. Although radiation-induced cardiovascular dysfunction has been observed in many species, its severity, duration, and even etiology may vary with the species, level of exposure, and dose rate. For this reason, our consideration of the effects of radiation on cardiovascular performance is limited to the circulatory derangements that occur in rat, dog, and monkey after supralethal doses and lead to radiation-induced cardiovascular dysfunction in these experimental models. The authors consider other recent data as they pertain to the etiology of cardiovascular dysfunction in irradiated animals

  7. Value of microvascular surgery in academic oral and maxillofacial surgery.

    Science.gov (United States)

    Fattahi, Tirbod; Fernandes, Rui

    2013-01-01

    The specialty of oral and maxillofacial surgery has witnessed a large trend of inclusion of maxillofacial oncology and microvascular reconstructive surgery within its scope of practice in recent years. The purpose of this report is to describe the authors' experience with a very active oncologic and microvascular reconstructive surgical service within an academic oral and maxillofacial surgical program at a large university teaching hospital. The operative log from July 1, 2010, to June 30, 2011, of 325 operations devoted to head and neck oncology and reconstruction was examined. Thirty-nine patients (group A) received a pedicled flap for head and neck reconstruction. Sixty-three patients (group B) received a microvascular free tissue transfer for head and neck reconstruction. Financial records of 20 consecutive patients who underwent simultaneous ablative and reconstructive procedures in each group were then reviewed for total hospital charges, including direct (surgical fees) and indirect (hospital stay, operating room expenses, and ancillary services) charges, and length of stay. Total hospital charges and direct surgical fees, were higher for the microvascular reconstruction group (group B). Length of hospital stay was not statistically different between the two groups. Microvascular reconstructive surgery performed within an academic oral and maxillofacial surgical program has many financial and intangible benefits within a medical center. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Pilot study on microvascular anastomosis: performance and future educational prospects.

    Science.gov (United States)

    Berretti, G; Colletti, G; Parrinello, G; Iavarone, A; Vannucchi, P; Deganello, A

    2017-11-30

    The introduction of microvascular free flaps has revolutionised modern reconstructive surgery. Unfortunately, access to training opportunities at standardised training courses is limited and expensive. We designed a pilot study on microvascular anastomoses with the aim of verifying if a short course, easily reproducible, could transmit microvascular skills to participants; if the chosen pre-test was predictive of final performance; and if age could influence the outcome. A total of 30 participants (10 students, 10 residents and 10 surgeons) without any previous microvascular experience were instructed and tested during a single 3 to 5 hour course. The two microanastomoses evaluated were the first ever performed by each participant. More than the half of the cohort was able to produce both patent microanastomoses in less than 2 hours; two-thirds of the attempted microanastomoses were patent. The pretest predicted decent scores from poor performances with a sensitivity of 61.5%, specificity of 100%, positive predictive value of 100% and negative predictive value of 40%. Students and residents obtained significantly higher scores than surgeons. Since our course model is short, cost-effective and highly reproducible, it could be introduced and implemented anywhere as an educational prospect for preselecting young residents showing talent and natural predisposition and having ambitions towards microvascular reconstructive surgery. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale.

  9. Sirtuin 2 Regulates Microvascular Inflammation during Sepsis

    Directory of Open Access Journals (Sweden)

    Nancy Buechler

    2017-01-01

    Full Text Available Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1–7, epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT, SIRT2 knockout (SIRT2KO, and SIRT2 overexpressing (SIRT2KI mice by cecal ligation and puncture (CLP. We studied leukocyte/platelet adhesion using intravital microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small intestine with immunohistochemistry (IHC six hours post-CLP/sham surgery. We also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice. Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice show attenuation of cellular adhesion with sepsis in the small intestine. We also show that the small intestinal E-selectin and ICAM-1 expressions increased in SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and affects survival.

  10. Endothelial dysfunction in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hadi AR Hadi

    2008-01-01

    Full Text Available Hadi AR Hadi, Jassim Al SuwaidiDepartment of Cardiology and Cardiovascular Surgery, Hamad General Hospital – Hamad Medical Corporation, Doha, State of Qatar; Department of Cardioscience, Sheikh Khalifa Medical City, Abu Dhabi, UAEAbstract: Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain

  11. Free and microvascular bone grafting in the irradiated dog mandible

    International Nuclear Information System (INIS)

    Altobelli, D.E.; Lorente, C.A.; Handren, J.H. Jr.; Young, J.; Donoff, R.B.; May, J.W. Jr.

    1987-01-01

    Microvascular and free rib grafts were placed in 4.5 cm defects in an edentate mandibular body defect 18 to 28 days after completion of 50 Gy of irradiation from a 60 Co source. The animals were sacrificed from two to forty weeks postoperatively and evaluated clinically, radiographically, and histologically. There was a marked difference in the alveolar mucosal viability with the two grafts. Mucosal dehiscence was not observed over any of the microvascular grafts, but was present in seven-eighths of the free grafts. Union of the microvascular bone graft to the host bone occurred within six weeks. In contrast, after six weeks the free graft was sequestered in all the animals. An unexpected finding with both types of graft was the marked subperiosteal bone formation. This bone appeared to be derived from the host bed, stabilizing and bridging the defects bilaterally. The results suggest that radiated periosteum may play an important role in osteogenesis

  12. Bevacizumab-Related Microvascular Angina and Its Management with Nicorandil.

    Science.gov (United States)

    Katoh, Manami; Takeda, Norihiko; Arimoto, Takahide; Abe, Hajime; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki; Komuro, Issei

    2017-10-21

    Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF)-A, is currently used to treat patients with ovarian or colon cancer. While several cardiovascular toxicities related to bevacizumab-containing regimens have been reported, the effect of bevacizumab on the coronary microcirculation has not been fully elucidated. Here we report a case of 54-year-old female patient who developed microvascular angina after a series of bevacizumab-containing chemotherapeutic regimen. The discontinuation of bevacizumab and nicorandil administration was effective in alleviating her chest discomfort and the ischemic changes on her ECG. This highlights the possibility that coronary microvascular angina can be induced in patients treated with bevacizumab-containing chemotherapy. It should also be noted that nicorandil can be effective in managing microvascular angina.

  13. Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2013-01-01

    Full Text Available Because histopathological changes in the lungs of patients with systemic sclerosis (SSc are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO and plasminogen activator inhibitor-1 (PAI-1 synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP. We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS related significantly to staining of septal cells for interleukin (IL-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04, septal IL-13 (P=0.03, and septal basic fibroblast growth factor (bFGF; P=0.02. Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

  14. Obesity, inflammation and endothelial dysfunction.

    Science.gov (United States)

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

  15. Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits

    Directory of Open Access Journals (Sweden)

    Ryan G. Lim

    2017-05-01

    Full Text Available Brain microvascular endothelial cells (BMECs are an essential component of the blood-brain barrier (BBB that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington’s disease (HD, it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC-derived BMECs (iBMEC from HD patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic abnormalities in angiogenesis and barrier properties, as well as in signaling pathways governing these processes. Thus, our findings provide an iPSC-derived BBB model for a neurodegenerative disease and demonstrate autonomous neurovascular deficits that may underlie HD pathology with implications for therapeutics and drug delivery.

  16. Aging alters reactivity of microvascular resistance networks in mouse gluteus maximus muscle.

    Science.gov (United States)

    Sinkler, Shenghua Y; Segal, Steven S

    2014-09-15

    Aging occurs with enhanced sympathetic nerve activity and endothelial dysfunction; however, little is known of how successive branches of microvascular resistance networks are affected in vivo. We questioned whether vascular reactivity is altered differentially along resistance networks with advanced age. The left gluteus maximus muscle of anesthetized 4-mo-old and 24-mo-old male C57BL/6 mice (Young and Old, respectively) was exposed for intravital microscopy and superfused with physiological salt solution (3 ml/min; pH 7.4, 34°C). Spontaneous vasomotor tone increased progressively from proximal feed arteries (FA) and first-order (1A) arterioles through distal second-order (2A) and third-order (3A) arterioles and was ~15% greater in 2A and 3A of Old versus Young. Vasoconstriction during elevated superfusion Po2 increased with branch order and to a greater extent in Young. Peak constrictions to phenylephrine [α1 adrenoreceptor (α1AR) agonist] were similar for FA and 1A of both ages and ~20% greater for 2A and 3A of Young. Across arterioles (but not FA), constrictions to UK 14304 (α2AR agonist) were depressed ~30% in Old versus Young. Thus advanced age attenuated vasoconstriction to O2 throughout networks while blunting vasoconstriction to α1AR and α2AR activation in arterioles. With ACh, endothelium-dependent dilation (EDD) was ~20% greater in FA of Young yet was approximately twofold greater for 2A and 3A of Old. Sodium nitroprusside evoked maximal dilations similar to ACh. Thus, with advanced age, EDD was attenuated in FA while robust in distal arterioles having enhanced vasomotor tone. We conclude that advanced age differentially alters reactivity among branches of microvascular resistance networks. Copyright © 2014 the American Physiological Society.

  17. Novel Genetic Loci Associated with Retinal Microvascular Diameter

    NARCIS (Netherlands)

    R.A. Jensen (Richard); X. Sim (Xueling); G.D. Smith; X. Li (Xiaohui); M. Jakobsdottir (Margret); C-Y. Cheng (Ching-Yu); J. Brody (Jennifer); M.F. Cotch (Mary Frances); B. McKnight (Barbara); R. Klein (Ronald); J.J. Wang (Jie Jin); A. Kifley (Annette); T.B. Harris (Tamara); L.J. Launer (Lenore); K.D. Taylor (Kent D.); B.E.K. Klein (Barbara); L.J. Raffel (Leslie); X. Li (Xiang); M.A. Ikram (Arfan); C.C.W. Klaver (Caroline); S.J. van der Lee (Sven); U. Mutlu (Unal); A. Hofman (Albert); A.G. Uitterlinden (André); C. Liu (Chunyu); A. Kraja (Aldi); P. Mitchell (Paul); V. Gudnason (Vilmundur); J.I. Rotter (Jerome I.); E.A. Boerwinkle (Eric); C.M. van Duijn (Cornelia); B.M. Psaty (Bruce); T.Y. Wong (Tien Yin)

    2016-01-01

    textabstractBackground-There is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic

  18. Towards clinical application of microvascular endothelial cell seeding

    NARCIS (Netherlands)

    Arts, C.H.P. (Catharina Henrica Paulina)

    2002-01-01

    The central question in this thesis is whether microvascular endothelial cells (MVEC) from subcutaneous fat tissue are suitable for the seeding of prosthetic vascular grafts and deendothelialized surfaces. The aim of the application of endothelial cells (EC) is the inhibition of thrombogenicity and

  19. Effect of Erythropoietin on Microvascular Anastomosis in Rat ...

    African Journals Online (AJOL)

    Purpose: To investigate the re-endothelialization potential of erythropoietin (EPO) following microvascular anastomosis in rat femoral artery. Methods: Ninety-six male Sprague-Dawley rats weighing between 300 g and 320 g were allocated randomly into two groups (control and EPO, n = 48). Left femoral artery ...

  20. Renal and cardiac microvascular endothelium: injury and repair

    NARCIS (Netherlands)

    Oosterhuis, NR

    2016-01-01

    Injury to the capillary endothelium can be devastating for renal and cardiac function. To halt the progression of chronic kidney disease (CKD) and heart failure (HF) preservation of the microvascular endothelial cell (EC) function and structure is of great importance.1 Increasing knowledge about

  1. Risk factor profile and the occurrence of microvascular ...

    African Journals Online (AJOL)

    Background: Type 2 diabetes has a long pre-clinical period before diagnosis, during which there may be development of complications, both of microvascular and macrovascular types. Objective: To determine the risk factor profile of hyperglycaemia, hypertension and dyslipidaemia in patients with short-term (=/< 2 years) ...

  2. Correlates of time to microvascular complications among diabetes ...

    African Journals Online (AJOL)

    Correlates of time to microvascular complications among diabetes mellitus patients using parametric and non-parametric approaches: a case study of Ayder referral hospital, Ethiopia. ... A retrospective follow up study was conducted on diabetic patients during this treatment period of 3 years. Using simple random sampling ...

  3. Effect of Erythropoietin on Microvascular Anastomosis in Rat

    African Journals Online (AJOL)

    Purpose: To investigate the re-endothelialization potential of erythropoietin (EPO) following microvascular anastomosis in rat femoral artery. Methods: Ninety-six male Sprague-Dawley rats weighing between 300 g and 320 g were allocated randomly into two groups (control and EPO, n = 48). Left femoral artery ...

  4. Ventricular repolarization alterations in women with angina pectoris and suspected coronary microvascular dysfunction

    DEFF Research Database (Denmark)

    Dose, Nynne; Michelsen, Marie Mide; Mygind, Naja Dam

    2018-01-01

    OBJECTIVES: CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. METHODS: Women with angina...... pectoris and no obstructive coronary artery disease (n=138) and age-matched controls were compared in regard to QTc interval and morphology combination score (MCS) based on T-wave asymmetry, flatness and presence of T-wave notch. CMD was assessed as a coronary flow velocity reserve (CFVR) by transthoracic...... was attenuated after multivariable adjustment (p=0.08). CONCLUSION: This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation....

  5. Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes

    NARCIS (Netherlands)

    Heuvel, van den M.; Sorop, O.; Koopmans, S.J.; Dekker, R.A.; Vries, de R.; Beusekom, H.M.M.; Eringa, E.C.; Duncker, D.J.; Danser, A.H.J.; Giessen, W.J.

    2012-01-01

    Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics.

  6. Proximate Mediators of Microvascular Dysfunction at the Blood-Brain Barrier: Neuroinflammatory Pathways to Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Barry W. Festoff

    2017-01-01

    Full Text Available Current projections are that by 2050 the numbers of people aged 65 and older with Alzheimer’s disease (AD in the US may increase threefold while dementia is projected to double every 20 years reaching ~115 million by 2050. AD is clinically characterized by progressive dementia and neuropathologically by neuronal and synapse loss, accumulation of amyloid plaques, and neurofibrillary tangles (NFTs in specific brain regions. The preclinical or presymptomatic stage of AD-related brain changes may begin over 20 years before symptoms occur, making development of noninvasive biomarkers essential. Distinct from neuroimaging and cerebrospinal fluid biomarkers, plasma or serum biomarkers can be analyzed to assess (i the presence/absence of AD, (ii the risk of developing AD, (iii the progression of AD, or (iv AD response to treatment. No unifying theory fully explains the neurodegenerative brain lesions but neuroinflammation (a lethal stressor for healthy neurons is universally present. Current consensus is that the earlier the diagnosis, the better the chance to develop treatments that influence disease progression. In this article we provide a detailed review and analysis of the role of the blood-brain barrier (BBB and damage-associated molecular patterns (DAMPs as well as coagulation molecules in the onset and progression of these neurodegenerative disorders.

  7. Vascular Endothelial Growth Factor Receptor 1 Contributes to Escherichia coli K1 Invasion of Human Brain Microvascular Endothelial Cells through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway▿ †

    OpenAIRE

    Zhao, Wei-Dong; Liu, Wei; Fang, Wen-Gang; Kim, Kwang Sik; Chen, Yu-Hua

    2010-01-01

    Escherichia coli is the most common Gram-negative organism causing neonatal meningitis. Previous studies demonstrated that E. coli K1 invasion of brain microvascular endothelial cells (BMEC) is required for penetration into the central nervous system, but the microbe-host interactions that are involved in this process remain incompletely understood. Here we report the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) expressed on human brain microvascular endothelial cells...

  8. Mitochondrial dysfunction in obesity.

    Science.gov (United States)

    de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

    2018-01-01

    Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Dysregulation of microRNAs and renin-angiotensin system in high salt diet-induced cardiac dysfunction in uninephrectomized rats.

    Science.gov (United States)

    Amara, Venkateswara Rao; Surapaneni, Sunil Kumar; Tikoo, Kulbhushan

    2017-01-01

    Uninephrectomy is not associated with major adverse events in cardiovascular and renal functions of live kidney donors. The effect of high salt diet on the quality of life of live kidney donors is largely unknown. Hence in this study, we aimed to determine the effect of high salt diet on the alterations of renin-angiotensin system and microRNAs leading to CV and renal dysfunction in uninephrectomized rats. In order to mimic clinical scenario, uninephrectomized male Sprague Dawley rats were fed initially with normal pellet diet for 12 weeks and then for 20 weeks with high salt (10% w/w NaCl) diet. At the end of the study, biochemical, functional, histological and molecular parameters were measured. High salt diet feeding resulted in renal dysfunction & fibrosis, decreased baroreflex sensitivity, increased in vivo cardiovascular reactivity to angiotensin II owing to upregulation of angiotensin II type 1 receptors and L-type calcium channels leading to cardiovascular dysfunction in uninephrectomized rats (UNX+HSD) worse than that of normal (binephric) rats fed with high salt diet (HSD). Protein expression of functional and hypertrophic protein markers revealed decreased SERCA, p-AMPK and increased p-AKT. Interestingly, levels of miR-25, miR-451 and miR-155 increased and miR-99 decreased in heart of uninephrectomized rats fed with high salt. However, circulating miR-25 and miR-451 levels decreased and miR-99b increased in these animals. Our study points out that since tissue and circulating levels of miRNAs are not similar, caution must be exercised during the usage of miRs as diagnostic or prognostic biomarkers. To our knowledge, we are the first to show that epigenetic alterations result in cardiac dysfunction in uninephrectomized rats fed with high salt diet.

  10. Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction.

    Science.gov (United States)

    Campbell, Duncan J; Somaratne, Jithendra B; Jenkins, Alicia J; Prior, David L; Yii, Michael; Kenny, James F; Newcomb, Andrew E; Kelly, Darren J; Black, Mary Jane

    2013-08-10

    Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study.

    Science.gov (United States)

    Mygind, Naja Dam; Michelsen, Marie Mide; Pena, Adam; Frestad, Daria; Dose, Nynne; Aziz, Ahmed; Faber, Rebekka; Høst, Nis; Gustafsson, Ida; Hansen, Peter Riis; Hansen, Henrik Steen; Bairey Merz, C Noel; Kastrup, Jens; Prescott, Eva

    2016-03-15

    The majority of women with angina-like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing. After screening 3568 women, 963 women with angina-like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age (SD) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high-dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve (CFVR) by Doppler examination of the left anterior descending coronary artery. CFVR was successfully measured in 919 (95%) women. Median (IQR) CFVR was 2.33 (1.98-2.76), and 241 (26%) had markedly impaired CFVR (<2). In multivariable regression analysis, predictors of impaired CFVR were age (P<0.01), hypertension (P=0.02), current smoking (P<0.01), elevated heart rate (P<0.01), and low high-density lipoprotein cholesterol (P=0.02), but these variables explained only a little of the CFVR variation (r(2)=0.09). CFVR was not associated with chest pain characteristics or results from diagnostic stress testing. Impaired CFVR was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris. CFVR was associated with few cardiovascular risk factors, suggesting that CFVR is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired CFVR. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley

  12. Effect of mesenchymal precursor cells on the systemic inflammatory response and endothelial dysfunction in an ovine model of collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Laura M Dooley

    Full Text Available Mesenchymal precursor cells (MPC are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced arthritis model has been previously developed which demonstrates local joint inflammation and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model.Arthritis was induced in sixteen adult sheep by administration of bovine type II collagen into the hock joint following initial sensitisation. After 24h, sheep were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic inflammation, along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following arthritis induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess endothelial dysfunction.Arthritic sheep treated with MPC demonstrated a marked spike in plasma IL-10, 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA sheep treated with MPCs demonstrated a significantly greater maximal relaxation to bradykinin when compared to untreated RA sheep (253.6 ± 17.1% of pre-contracted tone vs. 182.3 ± 27.3% in controls, and digital arteries also demonstrated greater endothelium-dependent vasodilation. This study demonstrated that MPCs

  13. Imaging for evaluation of erectile dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Hyup [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2001-03-15

    Penile erection is a complex phenomenon that includes coordinated intraaction of the nervous, arterial, venous, and sinusoidal systems. A defect in any of these systems may result in erectile dysfunction. Erectile dysfunction is defined as the consistent inability to generate or maintain an erection of sufficient rigidity for sexual intercourse. Although the introduction of sildenafil citrate made the information from imaging studies less critical in the management of the patients with erectile dysfunction, still the imaging studies such as Doppler US, penile arteriography, and cavemosonetry/cavemosography remain the major modalities in the evaluation of erectile dysfunction.

  14. Hypertrophic cardiomyopathy: Cardiac structural and microvascular abnormalities as evaluated with multi-parametric MRI

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu-Dong, E-mail: njmu_zyd@163.com [Department of Radiology, the First Affiliated Hospital with Nanjing Medical University (China); Li, Meijiao, E-mail: newgljyk@163.com [Department of Radiology, Peking University First Hospital (China); Qi, Liang, E-mail: qiliang1120@126.com [Department of Radiology, the First Affiliated Hospital with Nanjing Medical University (China); Wu, Chen-Jiang, E-mail: njmu_wcj@163.com [Department of Radiology, the First Affiliated Hospital with Nanjing Medical University (China); Wang, Xiaoying, E-mail: cjr.wangxiaoying@vip.163.com [Department of Radiology, Peking University First Hospital (China)

    2015-08-15

    Highlights: • LGE-present HCM had lower K{sup trans}, higher V{sub e} and MTT against LGE-absent HCM and normal group. • LGE-absent had significantly higher V{sub e} and MTT against normal group. • K{sup trans} was not changed between LGE-absent and normal group Microcirculatory dysfunction in HCM closely correlated to structural abnormality. - Abstract: Purpose: To determine the relationship between myocardial structural and microvascular abnormality in hypertrophic cardiomyopathy (HCM) by multi-parametric cardiac MRI. Materials and methods: Twenty-four HCM and eighteen controls were retrospectively included. Left ventricle mass (LVM), LV end-systolic and end-diastolic volume (LVESV, LVEDV), LV ejection fraction (LVEF), and 16-segment wall thickness at ES and ED (SESWT, SEDWT) were assessed with a 2D cine-MRI. Myocardial perfusion (reflected by K{sup trans}), interstitial volume (V{sub e}) and mean transmit time (MTT) were evaluated with a model-dependent dynamic contrast-enhanced MRI. Myocardial fibrosis was assessed with late gadolinium enhancement (LGE) imaging. Results: K{sup trans} was significantly decreased in LGE-present (0.74 ± 0.15 mL/g/min) against LGE-absent (0.55 ± 0.14 mL/g/min, p = 0.030) and normal group (0.81 ± 0.32 mL/g/min, p < 0.001), but was unchanged in LGE-absent against normal group (p > 0.05). V{sub e} and MTT were significantly increased in LGE-present (V{sub e}: 26.7 ± 15.7%; MTT: 28.6 ± 21.3 s) against LGE-absent (37.6 ± 18.3%; 49.8 ± 30.5 s) and normal group (19.7 ± 6.9%; 15.1 ± 3.9 s; all p < 0.001), and were significantly increased in LGE-absent against normal group (p < 0.001). LGE significantly correlated to K{sup trans}, V{sub e}, MTT, and SESWT (ρ = 0.232, −0.247, −0.443, and −0.207, respectively). K{sup trans} negatively correlated to SEDWT and SESWT (ρ = −0.224 and −0.231). V{sub e} and MTT positively correlated to SEDWT (V{sub e}: ρ = 0.223; MTT: ρ = 0.239) and SESWT (V{sub e}: ρ = 0.248; MTT:

  15. Polyphenol-Rich Blackcurrant Juice Prevents Endothelial Dysfunction in the Mesenteric Artery of Cirrhotic Rats with Portal Hypertension: Role of Oxidative Stress and the Angiotensin System.

    Science.gov (United States)

    Rashid, Sherzad; Idris-Khodja, Noureddine; Auger, Cyril; Kevers, Claire; Pincemail, Joël; Alhosin, Mahmoud; Boehm, Nelly; Oswald-Mammosser, Monique; Schini-Kerth, Valérie B

    2018-04-01

    Chronic liver diseases with portal hypertension are characterized by a progressive vasodilatation, endothelial dysfunction, and NADPH oxidase-derived vascular oxidative stress, which have been suggested to involve the angiotensin system. This study evaluated the possibility that oral intake of polyphenol-rich blackcurrant juice (PRBJ), a rich natural source of antioxidants, prevents endothelial dysfunction in a rat model of cirrhosis induced by chronic bile duct ligation (CBDL), and, if so, determined the underlying mechanism. Male Wistar rats received either control drinking water or water containing 60 mg/kg gallic acid equivalents of PRBJ for 3 weeks before undergoing surgery with CBDL or sham surgery. After 4 weeks, vascular reactivity was assessed in mesenteric artery rings using organ chambers. Both the acetylcholine-induced nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric artery rings were significantly reduced in CBDL rats compared to sham rats. An increased level of oxidative stress and expression of NADPH oxidase subunits, COX-2, NOS, and of the vascular angiotensin system are observed in arterial sections in the CBDL group. Chronic intake of PRBJ prevented the CBDL-induced impaired EDH-mediated relaxation, oxidative stress, and expression of the different target proteins in the arterial wall. In addition, PRBJ prevented the CBDL-induced increase in the plasma level of proinflammatory cytokines (interleukin [IL]-1α, monocyte chemotactic protein 1, and tumor necrosis factor α) and the decrease of the anti-inflammatory cytokine, IL-4. Altogether, these observations indicate that regular ingestion of PRBJ prevents the CBDL-induced endothelial dysfunction in the mesenteric artery most likely by normalizing the level of vascular oxidative stress and the angiotensin system.

  16. Grape-derived polyphenols improve aging-related endothelial dysfunction in rat mesenteric artery: role of oxidative stress and the angiotensin system.

    Directory of Open Access Journals (Sweden)

    Noureddine Idris Khodja

    Full Text Available Aging is characterized by the development of an endothelial dysfunction, which affects both the nitric oxide (NO- and the endothelium-derived hyperpolarizing factor (EDHF-mediated relaxations, associated with vascular oxidative stress and the activation of the angiotensin system. This study investigated whether red wine polyphenols (RWPs, antioxidants and potent stimulators of NO- and EDHF-mediated relaxations improve aging-related endothelial dysfunction, and, if so, examined the underlying mechanism. Mesenteric artery reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX staining, and expression of target proteins by immunohistochemical staining. Control young rats (16 weeks received solvent (ethanol, 3% v/v, and middle-aged rats (46 weeks either solvent or RWPs (100 mg/kg/day in the drinking water. The acetylcholine-induced endothelium-dependent NO component was slightly reduced whereas the EDHF component was markedly blunted in rings of middle-aged rats compared to young rats. The endothelial dysfunction was associated with oxidative stress, an upregulation of angiotensin II and AT1 receptors and a down-regulation of SK(Ca, IK(Ca, and angiotensin converting enzyme. Intake of RWPs for either one or two weeks improved the NO and the EDHF components of the relaxation, and normalized oxidative stress, the expression of SK(Ca, IK(Ca and the components of the angiotensin system. The protective effect of the 2-week RWPs treatment persisted for one and two weeks following stopping intake of RWPs. Thus, intake of RWPs caused a persistent improvement of the endothelial function, particularly the EDHF component, in middle-aged rats and this effect seems to involve the normalization of the expression of SK(Ca, IK(Ca and the angiotensin system.

  17. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

    Suda, Koichi; Tsuruta, Masashi; Eom, Jihyoun

    2011-01-01

    Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down......-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were...... the rise in the systemic expression of IL-6 (P cardiovascular dysfunction related to LPS, and pretreatment with budesonide/formoterol reduces the systemic expression of IL-6 and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular...

  18. Stress affects a gastrin-releasing peptide system in the spinal cord that mediates sexual function: implications for psychogenic erectile dysfunction.

    Directory of Open Access Journals (Sweden)

    Hirotaka Sakamoto

    Full Text Available Many men suffering from stress, including post-traumatic stress disorder (PTSD, report sexual dysfunction, which is traditionally treated via psychological counseling. Recently, we identified a gastrin-releasing peptide (GRP system in the lumbar spinal cord that is a primary mediator for male reproductive functions.To ask whether an acute severe stress could alter the male specific GRP system, we used a single-prolonged stress (SPS, a putative rat model for PTSD in the present study. Exposure of SPS to male rats decreases both the local content and axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Remarkably, pharmacological stimulation of GRP receptors restores penile reflexes in SPS-exposed males, and induces spontaneous ejaculation in a dose-dependent manner. Furthermore, although the level of plasma testosterone is normal 7 days after SPS exposure, we found a significant decrease in the expression of androgen receptor protein in this spinal center.We conclude that the spinal GRP system appears to be a stress-vulnerable center for male reproductive functions, which may provide new insight into a clinical target for the treatment of erectile dysfunction triggered by stress and psychiatric disorders.

  19. Female Sexual Dysfunction

    Science.gov (United States)

    ... medically as female sexual dysfunction. Many women experience problems with sexual function at some point. Female sexual dysfunction can occur at any stage of life. It can be lifelong or be acquired later in life. It can ...

  20. Clustering of microvascular complications in Type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Bjerg, Lasse; Hulman, Adam; Charles, Morten

    2018-01-01

    AIMS: To describe to what extent microvascular complications exhibit clustering in persons with Type 1 diabetes, and to assess whether the presence of one complication modified the strength of the association between the other two. METHODS: We conducted a cross-sectional analysis of the electronic...... duration and HbA1c, persons with neuropathy had an OR of 2.15 (95% CI: 1.73-2.66) for concurrent diabetic kidney disease. Those with retinopathy had an OR of 2.49 (1.92-3.24) for diabetic kidney disease and of 2.66 (1.94-3.64) for neuropathy. CONCLUSIONS: Microvascular complications in persons with Type 1...... medical records of 2276 persons with Type 1 diabetes treated in a specialized care hospital in Denmark in 2013. We used log-linear analysis to describe associations between diabetic kidney disease, neuropathy and retinopathy and logistic regression models to quantify the magnitude of associations...

  1. Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H₁ and H₂ receptors in vitro.

    Science.gov (United States)

    Zhang, Luyi; Yao, Ke; Fan, Yanying; He, Ping; Wang, Xiaofen; Hu, Weiwei; Chen, Zhong

    2012-12-01

    findings suggest that carnosine may be beneficial in the treatment of microvascular endothelial dysfunction induced by oxidative stress. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

  2. Microvascular free tissue transfer: results in 57 consecutive cases.

    Science.gov (United States)

    Fowler, J D; Degner, D A; Walshaw, R; Walker, D

    1998-01-01

    To evaluate the outcomes and complications in a consecutive series of animals undergoing microvascular reconstructive procedures at two veterinary institutions. Retrospective study. A total of 44 client-owned dogs and one red-necked wallaby. The medical records of all animals undergoing reconstructive microsurgical procedures at the Western College of Veterinary Medicine and Michigan State University were reviewed. Microvascular flap survival and related complications were described. Statistical analysis was performed to determine the significance of relationships between operative factors and outcome. A total of 57 microvascular procedures were performed on 55 animals. Reconstruction was required after trauma in 42 animals, after ablative cancer surgery in 11 animals and for correction of congenital tissue aplasia in I animal. Donor tissues included the superficial cervical cutaneous, medial saphenous fasciocutaneous or musculofasciocutaneous, caudal superficial epigastric cutaneous, trapezius muscle or musculocutaneous, caudal sartorius muscle, latissimus dorsi muscle or musculocutaneous, cranial abdominal myoperitoneal, carpal footpad, digital footpad, and vascularized ulnar bone flaps. A total of 53 of 57 flaps (93%) survived. There was a significant relationship between flap failure and level of assistant surgeon experience (P flaps were significantly more likely to fail when compared with pooled data from all other flap types (P flaps was not likely caused by an inherently deficient flap design, but was more likely attributed to the location and severity of trauma at the recipient site, the difficulty in isolating suitable recipient vessels for anastomosis or the absence of a trained assistant surgeon during these procedures. Clinical Relevance-This retrospective study documents the successful application of microvascular technique in a series of clinical cases requiring tissue reconstruction.

  3. Postanesthetic temporomandibular joint dysfunction.

    OpenAIRE

    Knibbe, M. A.; Carter, J. B.; Frokjer, G. M.

    1989-01-01

    Internal derangements, myofascial pain dysfunction, and chronic dislocation of the temporomandibular joint (TMJ) are three common sequelae resulting from mandibular trauma. Etiologic factors include prolonged dental and otolaryngologic procedures, and intraoperative use of the laryngoscope and bronchoscope. Three cases are reported to document postanesthetic TMJ dysfunction arising from normal preoperative joints. Four types of TMJ dysfunction are discussed: anterior meniscus dislocation with...

  4. [Nursing cooperation on circulation restore during microvascular submandibular gland transfer].

    Science.gov (United States)

    Kang, Xiao-Wei; Rong, Chen; Liu, Jie

    2011-06-01

    To summarize the cooperative measures on circulation restore during the operation of microvascular submandibular gland transfer. Fifty-six cases of microvascular submandibular gland transfer were performed in Peking University School & Hospital of Stomatology from January 2005 to March 2009. The related data was collected retrospectively and the cooperative measures on circulation restore during the operation were summarized. The circulation restore of transferred glands were satisfied in all 56 cases when the submandibular gland transfer operation finished. Thrombosis happened in 7 cases within the postoperative 48 hours and the secondary emergency operations were done. At last 6 glands were salvaged and the final successful rate was 98.21%. Successful circulation restore was one of the key points on microvascular submandibular gland transfer. The most important mission of the nursing during the operation was the prevention of vascular crisis. The main measures include persistent wet packing using narceine, fomentation using warm saline and special nursing on postoperative complications. Our experience proves that it is beneficial to the success of operation.

  5. Cell proliferation along vascular islands during microvascular network growth

    Directory of Open Access Journals (Sweden)

    Kelly-Goss Molly R

    2012-06-01

    Full Text Available Abstract Background Observations in our laboratory provide evidence of vascular islands, defined as disconnected endothelial cell segments, in the adult microcirculation. The objective of this study was to determine if vascular islands are involved in angiogenesis during microvascular network growth. Results Mesenteric tissues, which allow visualization of entire microvascular networks at a single cell level, were harvested from unstimulated adult male Wistar rats and Wistar rats 3 and 10 days post angiogenesis stimulation by mast cell degranulation with compound 48/80. Tissues were immunolabeled for PECAM and BRDU. Identification of vessel lumens via injection of FITC-dextran confirmed that endothelial cell segments were disconnected from nearby patent networks. Stimulated networks displayed increases in vascular area, length density, and capillary sprouting. On day 3, the percentage of islands with at least one BRDU-positive cell increased compared to the unstimulated level and was equal to the percentage of capillary sprouts with at least one BRDU-positive cell. At day 10, the number of vascular islands per vascular area dramatically decreased compared to unstimulated and day 3 levels. Conclusions These results show that vascular islands have the ability to proliferate and suggest that they are able to incorporate into the microcirculation during the initial stages of microvascular network growth.

  6. Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient.

    Science.gov (United States)

    Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M

    2011-06-01

    Microvascular permeability to water is characterized by the microvascular filtration coefficient (K(f)). Conventional gravimetric techniques to estimate K(f) rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate K(f) estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce K(f) from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to K(f) and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of K(f) in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique.

  7. Preventing microvascular complications in type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Vijay Viswanathan

    2015-01-01

    Full Text Available Patients with complications of diabetes such as retinopathy, nephropathy, and cardiovascular complications have increased hospital stay with greater economic burden. Prevention of complications should be started before the onset of type 1 diabetes mellitus (T1DM by working on risk factors and thereafter by intervention upon confirmatory diagnosis which can prevent further damage to β-cells. The actual risk of getting microvascular complications like microalbuminuria and retinopathy progression starts at glycated hemoglobin (HbA1c level of 7%. As per the American Diabetes Association, a new pediatric glycemic control target of HbA1c 20 years as compared to patients <10 years of age. Screening of these complications should be done regularly, and appropriate preventive strategies should be followed. Angiotensin converting enzyme inhibitors and angiotensin II receptor blocker reduce progression from microalbuminuria to macroalbuminuria and increase the regression rate to normoalbuminuria. Diabetic microvascular complications can be controlled with tight glycemic therapy, dyslipidemia management and blood pressure control along with renal function monitoring, lifestyle changes, including smoking cessation and low-protein diet. An integrated and personalized care would reduce the risk of development of microvascular complications in T1DM patients. The child with diabetes who receives limited care is more likely to develop long-term complications at an earlier age. Screening for subclinical complications and early interventions with intensive therapy is the need of the hour.

  8. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

    Directory of Open Access Journals (Sweden)

    Cai-Guo Yu

    2016-01-01

    Full Text Available Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

  9. Microvascular Remodeling and Wound Healing: A Role for Pericytes

    Science.gov (United States)

    Dulmovits, Brian M.; Herman, Ira M.

    2012-01-01

    Physiologic wound healing is highly dependent on the coordinated functions of vascular and non-vascular cells. Resolution of tissue injury involves coagulation, inflammation, formation of granulation tissue, remodeling and scarring. Angiogenesis, the growth of microvessels the size of capillaries, is crucial for these processes, delivering blood-borne cells, nutrients and oxygen to actively remodeling areas. Central to angiogenic induction and regulation is microvascular remodeling, which is dependent upon capillary endothelial cell and pericyte interactions. Despite our growing knowledge of pericyte-endothelial cell crosstalk, it is unclear how the interplay among pericytes, inflammatory cells, glia and connective tissue elements shape microvascular injury response. Here, we consider the relationships that pericytes form with the cellular effectors of healing in normal and diabetic environments, including repair following injury and vascular complications of diabetes, such as diabetic macular edema and proliferative diabetic retinopathy. In addition, pericytes and stem cells possessing “pericyte-like” characteristics are gaining considerable attention in experimental and clinical efforts aimed at promoting healing or eradicating ocular vascular proliferative disorders. As the origin, identification and characterization of microvascular pericyte progenitor populations remains somewhat ambiguous, the molecular markers, structural and functional characteristics of pericytes will be briefly reviewed. PMID:22750474

  10. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

    Science.gov (United States)

    Yu, Cai-Guo; Zhang, Ning; Yuan, Sha-Sha; Ma, Yan; Yang, Long-Yan; Feng, Ying-Mei; Zhao, Dong

    2016-01-01

    Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on "VEGF uncoupling with nitric oxide" and "competitive angiopoietin 1/angiopoietin 2" mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

  11. 4D microvascular imaging based on ultrafast Doppler tomography.

    Science.gov (United States)

    Demené, Charlie; Tiran, Elodie; Sieu, Lim-Anna; Bergel, Antoine; Gennisson, Jean Luc; Pernot, Mathieu; Deffieux, Thomas; Cohen, Ivan; Tanter, Mickael

    2016-02-15

    4D ultrasound microvascular imaging was demonstrated by applying ultrafast Doppler tomography (UFD-T) to the imaging of brain hemodynamics in rodents. In vivo real-time imaging of the rat brain was performed using ultrasonic plane wave transmissions at very high frame rates (18,000 frames per second). Such ultrafast frame rates allow for highly sensitive and wide-field-of-view 2D Doppler imaging of blood vessels far beyond conventional ultrasonography. Voxel anisotropy (100 μm × 100 μm × 500 μm) was corrected for by using a tomographic approach, which consisted of ultrafast acquisitions repeated for different imaging plane orientations over multiple cardiac cycles. UFT-D allows for 4D dynamic microvascular imaging of deep-seated vasculature (up to 20 mm) with a very high 4D resolution (respectively 100 μm × 100 μm × 100 μm and 10 ms) and high sensitivity to flow in small vessels (>1 mm/s) for a whole-brain imaging technique without requiring any contrast agent. 4D ultrasound microvascular imaging in vivo could become a valuable tool for the study of brain hemodynamics, such as cerebral flow autoregulation or vascular remodeling after ischemic stroke recovery, and, more generally, tumor vasculature response to therapeutic treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

    Science.gov (United States)

    Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A

    2017-02-01

    Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response

  13. Computer-assisted and fractal-based morphometric assessment of microvascularity in histological specimens of gliomas

    Science.gov (United States)

    Di Ieva, Antonio; Bruner, Emiliano; Widhalm, Georg; Minchev, Georgi; Tschabitscher, Manfred; Grizzi, Fabio

    2012-01-01

    Fractal analysis is widely applied to investigate the vascular system in physiological as well as pathological states. We propose and examine a computer-aided and fractal-based image analysis technique to quantify the microvascularity in histological specimens of WHO grade II and III gliomas. A computer-aided and fractal-based analysis was used to describe the microvessels and to quantify their geometrical complexity in histological specimens collected from 17 patients. The statistical analysis showed that the fractal-based indexes are the most discriminant parameters to describe the microvessels. The computer-aided quantitative analysis also showed that grade III gliomas are generally more vascularized than grade II gliomas. The fractal parameters are reliable quantitative indicators of the neoplastic microvasculature, making them potential surrogate biomarkers. The qualitative evaluation currently performed by the neuropathologist can be combined with the computer-assisted quantitative analysis of the microvascularity to improve the diagnosis and optimize the treatment of patients with brain cancer. PMID:22645645

  14. Study of microvascular non-Newtonian blood flow modulated by electroosmosis.

    Science.gov (United States)

    Tripathi, Dharmendra; Yadav, Ashu; Anwar Bég, O; Kumar, Rakesh

    2018-05-01

    An analytical study of microvascular non-Newtonian blood flow is conducted incorporating the electro-osmosis phenomenon. Blood is considered as a Bingham rheological aqueous ionic solution. An externally applied static axial electrical field is imposed on the system. The Poisson-Boltzmann equation for electrical potential distribution is implemented to accommodate the electrical double layer in the microvascular regime. With long wavelength, lubrication and Debye-Hückel approximations, the boundary value problem is rendered non-dimensional. Analytical solutions are derived for the axial velocity, volumetric flow rate, pressure gradient, volumetric flow rate, averaged volumetric flow rate along one time period, pressure rise along one wavelength and stream function. A plug swidth is featured in the solutions. Via symbolic software (Mathematica), graphical plots are generated for the influence of Bingham plug flow width parameter, electrical Debye length and Helmholtz-Smoluchowski velocity (maximum electro-osmotic velocity) on the key hydrodynamic variables. This study reveals that blood flow rate accelerates with decreasing the plug width (i.e. viscoplastic nature of fluids) and also with increasing the Debye length parameter. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Distinct effects of blood flow and temperature on cutaneous microvascular adaptation.

    Science.gov (United States)

    Carter, Howard H; Spence, Angela L; Atkinson, Ceri L; Pugh, Christopher J A; Cable, N Timothy; Thijssen, Dick H J; Naylor, Louise H; Green, Daniel J

    2014-11-01

    We performed two experiments to determine whether cutaneous microvascular adaptations in response to repeated core temperature (Tc) elevation are mediated by increases in skin blood flow (SkBF) and/or skin temperature. Healthy subjects participated for 8 wk in thrice-weekly bouts of 30-min lower limb heating (40°C). In study 1, both forearms were "clamped" at basal skin temperature throughout each heating bout (n = 9). Study 2 involved identical lower limb heating, with the forearms under ambient conditions (unclamped, n = 10). In both studies, a cuff was inflated around one forearm during the heating bouts to assess the contribution of SkBF and temperature responses. We assessed forearm SkBF responses to both lower limb (systemic reflex) heating and to local heating of the forearm skin, pre- and postintervention. Acutely, lower limb heating increased Tc (study 1, 0.63°C ± 0.15°C; study 2, 0.69°C ± 0.19°C; P heating decreased in study 1 (clamped forearms; week 0 vs week 8, 1.46 ± 0.52 vs 0.99 ± 0.44 CVC; P heating, whereas repeated increases in SkBF in the absence of change in skin temperature induced the opposite response. Repeated increases in Tc induce intrinsic microvascular changes, the nature of which are dependent upon both SkBF and skin temperature.

  16. Influence of eNOS gene 4a/bVNTR polymorphism on development of endothelial dysfunction and respiratory system disorders in children - residents of radioactively contaminated areas

    International Nuclear Information System (INIS)

    Stepanova, Je.Yi.; Kolpakov, Yi.Je.; Zigalo, V.M.; And Others

    2015-01-01

    Total of 184 children were examined to determine the possible associative links between eNOS gene intron 4m polymorphism and indices characterizing the functional state of the endothelium and the bronchopulmonary system. Of them the main group of children consisted of 135 childrenresidents of radioactively contaminated areas, the control group - of 49 healthy children who lived in ''clean'' regions by the radioactive con tamination and were not belonging to victims of the Chernobyl accident contingents. The molecular genetic study determining the eNOS gene intron 4 polymorphism was performed. Children of the main group did not differ from that of control and literature data by the frequency of geno types 4a/b and eNOS gene allele polymorphism. An increase in the duration of circulation restoration up to the ini tial level after occlusion test was noted in children of the main group with genotype 4a/4b comparing to children with genotype 4b/4b ; a decrease in the nitrite content was observed in blood serum. The integral indices of elastic ity and tensility of the lung tissue, respiratory permeability were decreased; the signs of bronchospasm were record ed 1.5 times more often. These adverse effects were associated with the presence of genotype allele 4a , the signs of endothelial dysfunction and the level of the incorporated 137 Cs. More pronounced changes in vascular endothelial reaction to occlusion and the significant decrease of serum nitrite level in allele 4a carriers, especially in children who live in adverse ecological conditions, give the right to include them into the risk group for the development of endothelial dysfunction, and to conside pulmonary dysfunction as one of its manifestations

  17. Unravelling Endogenous MicroRNA System Dysfunction as a New Pathophysiological Mechanism in Machado-Joseph Disease.

    Science.gov (United States)

    Carmona, Vitor; Cunha-Santos, Janete; Onofre, Isabel; Simões, Ana Teresa; Vijayakumar, Udaya; Davidson, Beverly L; Pereira de Almeida, Luís

    2017-04-05

    Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3' UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3' UTR and whether they can alleviate MJD neuropathology in vivo. Our results demonstrate that endogenous miRNAs, by targeting sequences in the 3' UTR, robustly reduce ATXN3 expression and aggregation in vitro and neurodegeneration and neuroinflammation in vivo. Importantly, we found an abnormal MJD-associated downregulation of genes involved in miRNA biogenesis and silencing activity. Finally, we identified three miRNAs-mir-9, mir-181a, and mir-494-that interact with the ATXN3-3' UTR and whose expression is dysregulated in human MJD neurons and in other MJD cell and animal models. Furthermore, overexpression of these miRNAs in mice resulted in reduction of mutATXN3 levels, aggregate counts, and neuronal dysfunction. Altogether, these findings indicate that endogenous miRNAs and the 3' UTR of ATXN3 play a crucial role in MJD pathogenesis and provide a promising opportunity for MJD treatment. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  18. White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

    Science.gov (United States)

    Cannerfelt, B; Nystedt, J; Jönsen, A; Lätt, J; van Westen, D; Lilja, A; Bengtsson, A; Nilsson, P; Mårtensson, J; Sundgren, P C

    2018-01-01

    Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

  19. Autonomic dysfunction in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Dümcke, Christine Winkler; Møller, Søren

    2008-01-01

    Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non-alcoholic liver cirrhosis and increases wit...

  20. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies.

    Science.gov (United States)

    Martínez-Martínez, Laura-Aline; Mora, Tania; Vargas, Angélica; Fuentes-Iniestra, Mario; Martínez-Lavín, Manuel

    2014-04-01

    Fibromyalgia often coexists and overlaps with other syndromes such as chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Chronic stress has been implicated in the pathogenesis of these illnesses. The sympathetic nervous system is a key element of the stress response system. Sympathetic dysfunction has been reported in these syndromes, raising the possibility that such dysautonomia could be their common clustering underlying pathogenesis. The objective of this study was to carry out a review of all published comparative case-control studies investigating sympathetic nervous system performance in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. Online databases PubMed and EMBASE were accessed using the following key words: autonomic (OR) sympathetic (AND) fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. All entries up to December 10th 2012 were reviewed by 2 independent investigators searching for case-control studies in humans. The Method for Evaluating Research and Guidelines Evidence adapted to the Scottish Intercollegiate Guidelines Network was used to rank the level of evidence contained in the selected articles. A total of 196 articles are included in this review. The most often used methods to assess sympathetic functionality were heart rate variability analysis, sympathetic skin response, tilt table testing, and genetic studies. The majority of studies (65%) described sympathetic nervous system predominance in these overlapping syndromes. In contrast, 7% of the studies found parasympathetic predominance. This review demonstrates that sympathetic nervous system predominance is common in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. This concordance raises the possibility that sympathetic dysfunction could be their common underlying pathogenesis that brings on overlapping clinical features. The recognition of

  1. Circulating brain microvascular endothelial cells (cBMECs as potential biomarkers of the blood-brain barrier disorders caused by microbial and non-microbial factors.

    Directory of Open Access Journals (Sweden)

    Sheng-He Huang

    Full Text Available Despite aggressive research, central nervous system (CNS disorders, including blood-brain barrier (BBB injury caused by microbial infection, stroke, abused drugs [e.g., methamphetamine (METH and nicotine], and other pathogenic insults, remain the world's leading cause of disabilities. In our previous work, we found that dysfunction of brain microvascular endothelial cells (BMECs, which are a major component of the BBB, could be caused by nicotine, meningitic pathogens and microbial factors, including HIV-1 virulence factors gp41 and gp120. One of the most challenging issues in this area is that there are no available cell-based biomarkers in peripheral blood for BBB disorders caused by microbial and non-microbial insults. To identify such cellular biomarkers for BBB injuries, our studies have shown that mice treated with nicotine, METH and gp120 resulted in increased blood levels of CD146+(endothelial marker/S100B+ (brain marker circulating BMECs (cBMECs and CD133+[progenitor cell (PC marker]/CD146+ endothelial PCs (EPCs, along with enhanced Evans blue and albumin extravasation into the brain. Nicotine and gp120 were able to significantly increase the serum levels of ubiquitin C-terminal hydrolase 1 (UCHL1 (a new BBB marker as well as S100B in mice, which are correlated with the changes in cBMECs and EPCs. Nicotine- and meningitic E. coli K1-induced enhancement of cBMEC levels, leukocyte migration across the BBB and albumin extravasation into the brain were significantly reduced in alpha7 nAChR knockout mice, suggesting that this inflammatory regulator plays an important role in CNS inflammation and BBB disorders caused by microbial and non-microbial factors. These results demonstrated that cBMECs as well as EPCs may be used as potential cell-based biomarkers for indexing of BBB injury.

  2. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.

    Science.gov (United States)

    Alvarez, Roger A; Miller, Megan P; Hahn, Scott A; Galley, Joseph C; Bauer, Eileen; Bachman, Timothy; Hu, Jian; Sembrat, John; Goncharov, Dmitry; Mora, Ana L; Rojas, Mauricio; Goncharova, Elena; Straub, Adam C

    2017-12-01

    Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells (ECs) express hemoglobin (Hb) α to control nitric oxide (NO) diffusion, but the role of this system in pulmonary circulation has not been evaluated. We hypothesized that up-regulation of Hb α in pulmonary ECs contributes to NO depletion and pulmonary vascular dysfunction in pulmonary hypertension. Primary distal pulmonary arterial vascular smooth muscle cells, lung tissue sections from unused donor (control) and idiopathic pulmonary artery (PA) hypertension lungs, and rat and mouse models of SU5416/hypoxia-induced pulmonary hypertension (PH) were used. Immunohistochemical, immunocytochemical, and immunoblot analyses and transfection, infection, DNA synthesis, apoptosis, migration, cell count, and protein activity assays were performed in this study. Cocultures of human pulmonary microvascular ECs and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced PH were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study. We find increased expression of Hb α in pulmonary endothelium from humans and mice with PH compared with controls. In addition, we show up-regulation of Hb α in human pulmonary ECs cocultured with PA smooth muscle cells in hypoxia. We treated pulmonary ECs with a Hb α mimetic peptide that disrupts the association of Hb α with endothelial NO synthase, and found that cells treated with the peptide exhibited increased NO signaling compared with a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the Hb α mimetic peptide enhanced vasodilation in response to acetylcholine. Our findings reveal that endothelial Hb α functions as an endogenous scavenger of NO in the pulmonary endothelium

  3. Gene expression of proteolytic systems and growth regulators of skeletal muscle in horses with myopathy associated with pituitary pars intermedia dysfunction.

    Science.gov (United States)

    Aleman, Monica; Nieto, Jorge E

    2010-06-01

    To investigate gene expression of the major proteolytic systems and growth regulators in skeletal muscle of horses with myopathy associated with pituitary pars intermedia dysfunction (PPID). 14 horses with PPID-associated myopathy and 7 healthy control horses. Horses with PPID and controls were age matched (15 to 28 years old). Muscle biopsy specimens were collected from both groups and processed for RNA and cDNA extraction. Validation of the most stable housekeeping genes for skeletal muscle was performed and used to compare gene expression of the following proteolytic systems: cysteine aspartate protease-dependent systems (caspases), lysosomal-dependent systems (cathepsins), non-lysosomal calcium protease-dependent systems (calpains), and ubiquitin-proteasome-dependent systems (ubiquitins). Gene expression of negative regulators of muscle growth (myostatin and inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) was also determined. No significant difference between groups was detected in expression of the major proteolytic systems except for m-calpain, which was greater in horses with PPID. No differences in gene expression of myostatin and interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were detected between groups. Greater expression of m-calpain may suggest that calpains play an important role in development of muscle atrophy in horses with PPID. However, because posttranslational events may alter protein activation, inactivation, and functions not studied here, other mechanisms of muscle atrophy cannot be excluded.

  4. Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans.

    Science.gov (United States)

    Hurr, Chansol; Patik, Jordan C; Kim, KiYoung; Christmas, Kevin M; Brothers, R Matthew

    2018-03-01

    What is the central question of this study? The purpose was to determine whether there is a difference between African Americans and Caucasians in cutaneous microvascular function and whether this difference is attributable to elevated oxidative stress. What is the main finding and its importance? The main finding is that African Americans have an attenuated cutaneous vasodilatation during local heating relative to Caucasians that is restored with local infusion of the superoxide dismutase mimetic, tempol. This suggests that superoxide mediates microvascular dysfunction and might contribute to the greater prevalence of cardiovascular disease in this population. African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that the cutaneous hyperaemic response to local heating is reduced in young AA relative to Caucasian Americans (CA) and that this is attributable to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibres received lactated Ringer solution (control), 10 mm ascorbic acid or 10 μm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) at a rate of 2.0 μl min -1 . Cutaneous vascular conductance (CVC) was calculated as the red blood cell flux divided by mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVC max ) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23 ± 4 years old) subjects participated. During 39°C heating, the %CVC max was lower in AA at the control (CA, 65 ± 20% versus AA, 47 ± 15%; P tempol site, there were no differences between groups. This was followed by infusion of 10 mm l-NAME at all sites to assess the contribution of nitric oxide to vasodilatation during local heating. The contribution of nitric oxide was lower in AA relative to CA at 39°C; however, this was restored with

  5. Microvascular injury and the kidney in hypertension.

    Science.gov (United States)

    Ruiz-Hurtado, G; Ruilope, L M

    Renal macrocirculation participates in the development of arterial hypertension. The elevation in systemic blood pressure (BP) can damage the kidney starting in the microcirculation. Established arterial hypertension impinge upon the large arteries and stiffness develops. As a consequence central BP raises and BP pulsatility appear and contribute to further damage renal microcirculation by direct transmission of the elevated BP. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Postanesthetic temporomandibular joint dysfunction.

    Science.gov (United States)

    Knibbe, M. A.; Carter, J. B.; Frokjer, G. M.

    1989-01-01

    Internal derangements, myofascial pain dysfunction, and chronic dislocation of the temporomandibular joint (TMJ) are three common sequelae resulting from mandibular trauma. Etiologic factors include prolonged dental and otolaryngologic procedures, and intraoperative use of the laryngoscope and bronchoscope. Three cases are reported to document postanesthetic TMJ dysfunction arising from normal preoperative joints. Four types of TMJ dysfunction are discussed: anterior meniscus dislocation with reduction, anterior meniscus dislocation without reduction, dislocation/subluxation of the mandibular condyle, and myofascial pain dysfunction syndrome. Preoperative screening of mandibular function is recommended in identifying patients as either normal or having potential TMJ dysfunction. Failure to recognize postoperative TMJ dysfunction can lead to long-term symptoms that are difficult to alleviate. Litigation is a common sequel in these cases. Images Figure 3 PMID:2604053

  7. Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Ryuji Sakakibara

    2011-01-01

    Full Text Available Bladder dysfunction (urinary urgency/frequency, bowel dysfunction (constipation, and sexual dysfunction (erectile dysfunction (also called “pelvic organ” dysfunctions are common nonmotor disorders in Parkinson's disease (PD. In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

  8. Prostaglandin E1 protects coronary microvascular function via the glycogen synthase kinase 3β-mitochondrial permeability transition pore pathway in rat hearts subjected to sodium laurate-induced coronary microembolization.

    Science.gov (United States)

    Zhu, Houyong; Ding, Yu; Xu, Xiaoqun; Li, Meiya; Fang, Yangliang; Gao, Beibei; Mao, Hengyi; Tong, Guoxin; Zhou, Liang; Huang, Jinyu

    2017-01-01

    Prostaglandin E1 (PGE1) is used as a pretreatment for ischemia reperfusion injury in many biological systems. However, its value as a pretreatment for coronary microembolization (CME) is unknown. The goal of this study was to determine whether PGE1 would protect against CME. In a CME rat model, we observed microthrombi and early myocardial ischemia, with endothelium appearing exfoliated and mitochondria having irregular morphology and decreased internal complexity. The level of fibrinogen-like protein 2 prothrombinase was increased and superoxide dismutase and catalase levels were decreased. Moreover, mitochondria copy number and mitochondrial permeability transition pore (mPTP) opening were increased. Pretreatment with PGE1 (1 or 2 μg/kg) significantly improved these cardiological deficits, acting via the glycogen synthase kinase 3β (GSK-3β)-mPTP pathway. Unexpectedly, the phosphorylation of Akt at Ser473 decreased in the PGE1 at high dose. Overall, our findings suggested an important role for PGE1 in pretreatment of coronary microvascular dysfunction.

  9. Oral health and erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Vijendra P Singh

    2017-01-01

    Full Text Available Ample evidence strongly supports the fact that periodontal disease is a major risk factor for various systemic diseases namely cardio-vascular disease, diabetes mellitus, etc. Recently, investigators focussed on exploring the link between chronic periodontitis (CP and erectile dysfunction (ED by contributing to the endothelial dysfunction. Both the diseases share common risk factors. Various studies conducted in different parts of the world in recent years reported the evidence linking this relationship as well as improvement in ED with periodontal treatment. Systemic exposure to the periodontal pathogen and periodontal infection-induced systemic inflammation was thought to associate with these conditions. The objective of this review was to highlight the evidence of the link between CP and ED and the importance of oral health in preventing the systemic conditions.

  10. Vitamin D levels and microvascular complications in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sarita Bajaj

    2014-01-01

    Full Text Available Background: Vitamin D has important actions on glucose metabolism. These include improved insulin exocytosis, direct stimulation of insulin receptor, improved uptake of glucose by peripheral tissues, improving insulin resistance. It has got various pleiotropic effects like suppression of cell mediated immunity, regulation of cell proliferation, stimulation of neurotropic factors such as nerve growth factor, Glial cell line-derived neurotrophic factor, neurotropin, suppression of RAAS, reduction of albuminuria, immunomodulatory effects, and anti-inflammatory effects. Thus, vitamin D is implicated in many ways in the pathogenesis of retinopathy, neuropathy and nephropathy. Objectives: To study the correlation of vitamin D levels with microvascular complications in type 2 diabetes. Materials and Methods: Cross-sectional case-control study of 18 patients (18-70 years, who met the American Diabetes Association 2011 criteria for type 2 diabetes, was conducted. Age and sex matched healthy controls were taken. Subjects were evaluated for the presence of microvascular complications by clinical evaluation, urine examination, fundus examination, nerve conduction studies, and various biochemical tests. 25-OH cholecalciferol levels were done for each. Cut off level for vitamin D deficiency was 20 ng/ml. Results: Mean vitamin D was lower in type 2 diabetics than healthy subjects (19.046 vs. 27.186 ng/ml. Prevalence of vitamin D deficiency and insufficiency was found to significantly higher in diabetics when compared to healthy subjects (P = 0.0001. Vitamin D deficiency was found to be significantly associated with neuropathy (χ2 = 5.39, df = 1, P = 0.020, retinopathy, (χ2 = 6.6, df = 1, P = 0.010 and nephropathy (χ2 = 10. 52, df = 1, P = 0.001. Lower levels of vitamin D were found to be associated with increasing prevalence of combinations of microvascular complications namely neuropathy with retinopathy (P = 0.036, neuropathy with nephropathy (P = 0

  11. Burden of Sexual Dysfunction.

    Science.gov (United States)

    Balon, Richard

    2017-01-02

    Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at £53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self-esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society.

  12. [Functional, mechanical, and structural demands in microvascular prostheses (author's transl)].

    Science.gov (United States)

    Tizian, C H

    1980-01-01

    Fundamental conclusions can be made based on initial experimental experiences concerning microvascular prostheses. Beside having high durability, the microprostheses need to be compatible with other tissues and easy to handle. They must have a microporous structure to allow tissue ingrowth. Negative surface charge, hydrophobic property, and inertness of the synthetic material contribute to avoiding thrombosis. The isodiametric relationship between vessel and micrograft appears to create an optimal hemodynamic situation. For insertion, the use of microsurgical techniques is necessary in determining the future of the implanted micrograft. By performing everting continuous over-and-over suture, the end-to-end anastomosis showed excellent results.

  13. Microvascular alterations and the role of complement in dermatomyositis.

    Science.gov (United States)

    Lahoria, Rajat; Selcen, Duygu; Engel, Andrew G

    2016-07-01

    Different mechanisms have been proposed to explain the pathological basis of perifascicular muscle fibre atrophy in dermatomyositis. These include ischaemia due to immune-mediated microvascular injury, enhanced expression of type 1 interferon-induced gene transcripts in perifascicular capillaries and muscle fibres, and occlusion of larger perimysial blood vessels. Microvascular complement deposition is a feature of dermatomyositis pathology but the trigger for complement activation, the predominant complement pathway involved, or its role in the pathogenesis of the disease, has not been clearly defined. In the first step of this study we examined the density of capillaries and transverse vessels and searched for occlusion or depletion of larger perimysial blood vessels in 10 patients with dermatomyositis. This revealed an invariable association of perifascicular atrophy with capillary and transverse vessel depletion. The capillary and transverse vessel densities in non-atrophic fibre regions were not significantly different from those in muscle specimens of 10 age-matched controls. Next, in the same 10, as well as in 40 additional dermatomyositis patients, we searched for vascular deposits of IgG, IgM, and the C5b-9 complement membrane attack complex. Thirty-one of 50 dermatomyositis specimens contained C5b-9 reactive endomysial microvessels but none of these or other vessels reacted for IgG. Ten of 50 specimens harboured IgM-positive capillaries but only a few of these reacted for C5b-9. Finally, we analysed and compared different pathways of complement activation in dermatomyositis, lupus nephritis, and necrotic muscle fibres in Duchenne dystrophy. In lupus nephritis, C5-b9 deposits co-localized with IgG, IgM, C1q, and C4d, consistent with immune complex dependent activation of the classical complement pathway. In both dermatomyositis and Duchenne dystrophy, C5-b9 deposits co-localized with C1q and C4d and rarely with IgM indicating activation of the classical

  14. Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women

    Science.gov (United States)

    Sara, Jaskanwal D; Zhang, Ming; Gharib, Hossein; Lerman, Lilach O; Lerman, Amir

    2015-01-01

    Background Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and Results In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3hypothyroidism had a significantly lower % Δ CBF Ach (48.26 [80.66] versus 64.58 [128.30]) compared to patients with euthyroidism, while the % Δ CAD Ach did not vary significantly between groups. After adjusting for covariates, females with hypothyroidism still had a significantly lower % Δ CBF Ach (estimated difference in % Δ CBF Ach [SE]: −16.79 [8.18]). Conclusions Hypothyroidism in women is associated with microvascular endothelial dysfunction, even after adjusting for confounders, and may explain some of the increased risk of cardiovascular disease in these patients. PMID:26224049

  15. Sleep quality and duration are related to microvascular function: the Amsterdam Growth and Health Longitudinal Study

    NARCIS (Netherlands)

    Bonsen, T.; Wijnstok, N.J.; Hoekstra, T.; Eringa, E.C.; Serne, E.H.; Smulders, Y.M.; Twisk, J.W.R.

    2015-01-01

    Sleep and sleep disorders are related to cardiovascular disease, and microvascular function is an early cardiovascular disease marker. Therefore, the relationship of sleep (measured in sleep quality and duration) with microvascular function was examined in healthy adults. Sleep quality was assessed

  16. Perioperative antibiotics in the setting of microvascular free tissue transfer: current practices

    NARCIS (Netherlands)

    Reiffel, Alyssa J.; Kamdar, Mehul R.; Kadouch, Daniel J. M.; Rohde, Christine H.; Spector, Jason A.

    2010-01-01

    Microvascular free tissue transfer is a ubiquitous and routine method of restoring anatomic defects. There is a paucity of data regarding the role of perioperative antibiotics in free tissue transfer. We designed a survey to explore usage patterns among microvascular surgeons and thereby define a

  17. Rapid automatic assessment of microvascular density in sidestream dark field images

    NARCIS (Netherlands)

    R. Bezemer (Rick); J.G. Dobbe (Johannes); S.A. Bartels (Sebastiaan); E. Christiaan Boerma (E.); P.W.G. Elbers (Paul W.); M. Heger (Michal); C. Ince (Can)

    2011-01-01

    textabstractThe purpose of this study was to develop a rapid and fully automatic method for the assessment of microvascular density and perfusion in sidestream dark field (SDF) images. We modified algorithms previously developed by our group for microvascular density assessment and introduced a new

  18. Microvascular oxygen pressure in the pig intestine during haemorrhagic shock and resuscitation

    NARCIS (Netherlands)

    Sinaasappel, M.; van Iterson, M.; Ince, C.

    1999-01-01

    1. The aim of this study was to investigate the relation between microvascular and venous oxygen pressures during haemorrhagic shock and resuscitation in the pig intestine. To this end microvascular PO2 (microPO2) was measured by quenching of Pd-porphyrin phosphorescence by oxygen and validated for

  19. Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

    Science.gov (United States)

    Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

    2001-01-01

    OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

  20. Linking erectile dysfunction and coronary artery disease.

    Science.gov (United States)

    Rodriguez, J J; Al Dashti, R; Schwarz, E R

    2005-12-01

    Coronary artery disease (CAD) and erectile dysfunction (ED) are both highly prevalent conditions that frequently coexist. Additionally, they share mutual vascular risk factors, suggesting that they are both manifestations of systemic vascular disease. The role of endothelial dysfunction in CAD is well established. Normal erectile function is primarily a vascular event that relies heavily on endothelially derived, nitric oxide-induced vasodilation. Accordingly, endothelial dysfunction appears to be a common pathological etiology and mechanism of disease progression between CAD and ED. The risk factors of diabetes mellitus, hypertension, hyperlipidemia, obesity and tobacco abuse contribute to endothelial dysfunction. This article reviews the role of vascular endothelium in health, the abnormalities resulting from vascular risk factors, and clinical trials evaluating the role of endothelial dysfunction in ED.

  1. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  2. The Microvascular Gap Junction Channel: A Route to Deliver MicroRNAs for Neurological Disease Treatment

    Directory of Open Access Journals (Sweden)

    Dominique Thuringer

    2017-08-01

    Full Text Available Brain microvascular endothelial cells (BMECs separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell. It was also shown that, when altered, BMEC could be regenerated by endothelial cells derived from pluripotent stem cells. Here, we discuss the transfer of microRNA through gap junctions between BMEC, the regeneration of BMEC from induced pluripotent stem cells that could be engineered to express specific microRNA, and how such an innovative approach could benefit to the treatment of glioblastoma and other neurological diseases.

  3. Human microvascular endothelial cell seeding on Cr-DLC thin films for heart valve applications

    Science.gov (United States)

    Ali, N.; Kousar, Y.; Gracio, J.; Titus, E.; Okpalugo, T. I.; Singh, V.; Pease, M.; Ogwu, A. A.; Meletis, E. I.; Ahmed, W.; Jackson, M. J.

    2006-04-01

    In this investigation, Cr-modified diamond-like carbon (Cr-DLC) films were studied for potential applications in mechanical heart valves. Three Cr-DLC samples were prepared using a magnetron sputtering technique employing an intensified plasma-assisted processing (IPAP) system. The three samples consisted of the following Cr contents: 1, 5, and 10 at.%. The biological response of human microvascular endothelial cells (HMV-EC), seeded on Cr-DLC films, was evaluated in terms of initial cell attachment and growth. The Cr-DLC films were characterized using Raman spectroscopy, x-ray diffraction, scanning electron microscopy, secondary ion mass spectroscopy, and by the contact angle technique. Endothelial cell adhesion and growth were found to be affected by changing the Cr content of Cr-DLC films.

  4. Valsartan-induced improvement in insulin sensitivity is not paralleled by changes in microvascular function in individuals with impaired glucose metabolism.

    Science.gov (United States)

    van der Zijl, Nynke J; Serné, Erik H; Goossens, Gijs H; Moors, Chantalle C M; Ijzerman, Richard G; Blaak, Ellen E; Diamant, Michaela

    2011-10-01

    Individuals with impaired glucose metabolism (IGM) are at high risk of developing type 2 diabetes (T2DM). The renin-angiotensin system (RAS) is activated in insulin-resistant states and its inhibition resulted in delayed onset of T2DM. The underlying mechanisms may include improvement in microvascular structure and function, which may increase glucose and insulin delivery to insulin-sensitive tissues. We hypothesized that functional and structural capillary density is impaired in insulin-resistant individuals with IGM and that treatment with the angiotensin-receptor blocker valsartan (VAL) will improve insulin sensitivity and microvascular function. In this randomized controlled trial, individuals with IGM (n = 48) underwent a hyperinsulinaemic-euglycaemic clamp to assess insulin sensitivity (M-value) and capillaroscopy to examine baseline skin capillary density (BCD), capillary density after arterial occlusion (PRH) and capillary density during venous occlusion (VEN) before and after 26 weeks of VAL or placebo (PLB). Sixteen BMI-matched individuals with normal glucose metabolism (NGM) served as controls. Individuals with IGM were more insulin resistant (P < 0.001) and had impaired microvascular function compared with those with NGM (all P < 0.01). Univariate associations were found for microvascular function (BCD, PRH, VEN) and M-value (all P < 0.005). The relations were independent of age, sex and BMI. VAL improved insulin sensitivity (P = 0.034) and lowered blood pressure as compared with PLB, whereas microvascular function remained unchanged. In insulin-resistant individuals with IGM, impaired functional and structural capillary density was inversely associated with insulin sensitivity. VAL improved insulin sensitivity without affecting the functional and structural capillary density, indicating that other mechanisms may be stronger determinants in the VAL-mediated insulin-sensitizing effect.

  5. Erectile Dysfunction (ED)

    Science.gov (United States)

    ... men older than 75 years of age. Is erectile dysfunction just a part of old age? ED doesn’t have to be a part of getting older. It’s true that as you get older, you may need more ... Symptoms of erectile dysfunction The primary symptom of ED is not ...

  6. Loneliness and Sexual Dysfunctions.

    Science.gov (United States)

    Mijuskovic, Ben

    1987-01-01

    Argues that sexual dysfunctions result from early childhood experiences which were originally nonsexual in nature. Contends that psychological difficulties centered around problems of loneliness tend to generate certain sexual dysfunctions. Extends and explores suggestion that genesis of sexual conflicts is in nonsexual infant separation anxiety…

  7. Localised cutaneous microvascular adaptation to exercise training in humans.

    Science.gov (United States)

    Atkinson, Ceri L; Carter, Howard H; Thijssen, Dick H J; Birk, Gurpreet K; Cable, N Timothy; Low, David A; Kerstens, Floortje; Meeuwis, Iris; Dawson, Ellen A; Green, Daniel J

    2018-02-07

    Exercise training induces adaptation in conduit and resistance arteries in humans, partly as a consequence of repeated elevation in blood flow and shear stress. The stimuli associated with intrinsic cutaneous microvascular adaptation to exercise training have been less comprehensively studied. We studied 14 subjects who completed 8-weeks cycle ergometer training, with partial cuff inflation on one forearm to unilaterally attenuate cutaneous blood flow responses during each exercise-training bout. Before and after training, bilateral forearm skin microvascular dilation was determined using cutaneous vascular conductance (CVC: skin flux/blood pressure) responses to gradual localised heater disk stimulation performed at rest (33, 40, 42 and 44 °C). Cycle exercise induced significant increases in forearm cutaneous flux and temperature, which were attenuated in the cuffed arm (2-way ANOVA interaction-effect; P < 0.01). We found that forearm CVC at 42 and 44 °C was significantly lower in the uncuffed arm following 8-weeks of cycle training (P < 0.01), whereas no changes were apparent in the contralateral cuffed arm (P = 0.77, interaction-effect P = 0.01). Lower limb exercise training in healthy young men leads to lower CVC-responses to a local heating stimulus, an adaptation mediated, at least partly, by a mechanism related to episodic increases in skin blood flow and/or skin temperature.

  8. Clustering of microvascular complications in Type 1 diabetes mellitus.

    Science.gov (United States)

    Bjerg, Lasse; Hulman, Adam; Charles, Morten; Jørgensen, Marit Eika; Witte, Daniel Rinse

    2018-04-01

    To describe to what extent microvascular complications exhibit clustering in persons with Type 1 diabetes, and to assess whether the presence of one complication modified the strength of the association between the other two. We conducted a cross-sectional analysis of the electronic medical records of 2276 persons with Type 1 diabetes treated in a specialized care hospital in Denmark in 2013. We used log-linear analysis to describe associations between diabetic kidney disease, neuropathy and retinopathy and logistic regression models to quantify the magnitude of associations adjusting for potential confounders. The median duration of diabetes was 24 years and median HbA1c was 63 mmol/mol (7.9%). We found strong indication of clustering and found no evidence that presence of one complication modified the association between the other two. In models adjusted for diabetes duration and HbA 1c , persons with neuropathy had an OR of 2.15 (95% CI: 1.73-2.66) for concurrent diabetic kidney disease. Those with retinopathy had an OR of 2.49 (1.92-3.24) for diabetic kidney disease and of 2.66 (1.94-3.64) for neuropathy. Microvascular complications in persons with Type 1 diabetes exhibit strong clustering. However, the association between any pair of complications is not modified by the presence of the third. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. The role of the microvascular tortuosity in tumor transport phenomena.

    Science.gov (United States)

    Penta, R; Ambrosi, D

    2015-01-07

    The role of the microvascular network geometry in transport phenomena in solid tumors and its interplay with the leakage and pressure drop across the vessels is qualitatively and quantitatively discussed. Our starting point is a multiscale homogenization, suggested by the sharp length scale separation that exists between the characteristic vessels and the tumor tissue spatial scales, referred to as the microscale and the macroscale, respectively. The coupling between interstitial and capillary compartment is described by a double Darcy model on the macroscale, whereas the geometric information on the microvascular structure is encoded in the effective hydraulic conductivities, which are numerically computed by solving classical differential problems on the microscale representative cell. Then, microscale information is injected into the macroscopic model, which is analytically solved in a prototypical geometry and compared with previous experimentally validated, phenomenological models. In this way, we are able to capture the role of the standard blood flow determinants in the tumor, such as tumor radius, tissue hydraulic conductivity and vessels permeability, as well as influence of the vascular tortuosity on fluid convection. The results quantitatively confirm that transport of blood (and, as a consequence, of any advected anti-cancer drug) can be dramatically impaired by increasing the geometrical complexity of the microvasculature. Hence, our quantitative analysis supports the argument that geometric regularization of the capillary network improves blood transport and drug delivery in the tumor mass. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Towards an analysis of dysfunctional grammar.

    Science.gov (United States)

    Rigaudeau-McKenna, B

    2005-01-01

    This article applies Systemic Functional Linguistics (SFL) to the study of language dysfunction. It demonstrates the potential that Systemic Functional analysis can offer to one aspect of the analysis of language dysfunction--the failure to realise complexes of clauses. For the purpose of analysis, new concepts and new measures have been created. The newly defined concepts and measures are illustrated in the discourse data of normally developing children and adolescents with brain injury.

  11. Sodium arsanilate-induced vestibular dysfunction in rats: effects on open-field behavior and spontaneous activity in the automated digiscan monitoring system.

    Science.gov (United States)

    Ossenkopp, K P; Prkacin, A; Hargreaves, E L

    1990-08-01

    Vestibular dysfunction was chemically induced in Long-Evans rats by intratympanic injections (30 mg per side) of sodium arsanilate (atoxyl). Following a one-week recovery period the rats were behaviorally assayed for integrity of the labyrinthine systems. All subjects were tested for presence of the air-righting reflex, the contact-righting reflex (by lightly holding a sheet of Plexiglas against the soles of the rat's feet), and body rotation-induced nystagmus. All animals were then tested for their ability to remain on a small (15 x 15 cm) platform. Next, the subjects were given two 10-min open-field tests during which ambulation, rearing, grooming, and defecation responses were recorded. Four to five weeks later all rats were tested twice (60 min per session) in the automated Digiscan Activity Monitor which provides a multivariate assessment of spontaneous motor activity. The rats with vestibular dysfunction (Group VNX) took significantly less time to fall off the platform (p less than 0.01). They also exhibited significantly more open-field ambulation but fewer rearing responses (ps less than 0.01). An examination of group correlation coefficients for open-field variables and the platform test scores revealed some interesting group differences (ps less than 0.05). In the Digiscan tests the atoxyl-treated rats exhibited fewer number of horizontal movements, but increased speed for these movements (ps less than 0.05). Vertical movements did not differ significantly in incidence, but these movements were greatly reduced in duration (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  13. The passage of a diffusible indicator through a microvascular system

    Directory of Open Access Journals (Sweden)

    Kislukhin Victor V

    2013-02-01

    Full Text Available Abstract The aim. (1 To develop a mathematical model of the passage of a diffusible indicator through microcirculation based on a stochastic description of diffusion and flow; (2 To use Goresky transform of the dilution curves of the diffusible indicators for the estimation of the permeability of a tissue-capillary barrier. The method. We assume that there are two causes for flow to be stochastic: (a All microvessels are divided between open and closed microvessels. There exists random exchange between the two groups. (b The flow through open microvessels is also random. We assume that each diffusing tracer has a probability to leave the intravascular space, and has a probability to return. We also assume that all considered processes are stationary (stability of microcirculation. Conclusion. (a The distribution of the time to pass microcirculation by diffusing indicator is given by a compound Poisson distribution; (b The permeability of tissue-capillary barrier can be obtained from the means, delay, and dispersions of the dilutions of intravascular and diffusing traces.

  14. Effect of noise stress on cardiovascular system in adult male albino rat: implication of stress hormones, endothelial dysfunction and oxidative stress.

    Science.gov (United States)

    Said, Mona A; El-Gohary, Ola A

    2016-07-01

    Noise pollution has been realized as an environmental stressor associated with modern life style that affects our health without being consciously aware of it. The present study investigated the effect of acute, chronic intermittent and chronic continuous exposure to noise of intensity 80-100 dB on heart rate and mean systemic arterial blood pressure in rats and the possible underlying mechanisms. Noise stress causes significant increase in heart rate, mean systemic arterial blood pressure as well as significant increase in plasma levels of corticosterone, adrenaline, noradrenaline, endothelin-1, nitric oxide and malondialdehyde with significant decrease in superoxide dismutase and these values are significantly more worse in chronic continuous exposure to noise than acute or chronic intermittent exposure. These findings suggest that noise stress has many adverse effects on cardiovascular system via increasing plasma levels of stress hormones, oxidative stress and endothelial dysfunction. These findings have major implication in the management of adverse cardiovascular reactions of people subjected to daily noise stress.

  15. Improving diagnosis and treatment of women with angina pectoris and microvascular disease: the iPOWER study design and rationale.

    Science.gov (United States)

    Prescott, Eva; Abildstrøm, Steen Zabell; Aziz, Ahmed; Merz, Noel Bairey; Gustafsson, Ida; Halcox, Julian; Hansen, Henrik Steen; Hansen, Peter Riis; Kastrup, Jens; Michelsen, Marie; Mygind, Naja Dam; Ong, Peter; Pena, Adam; Rosengren, Annika; Sechtem, Udo; Søgaard, Peter

    2014-04-01

    The iPOWER study aims at determining whether routine assessment of coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease is feasible and identifies women at risk. All women with angina referred to invasive angiographic assessment in Eastern Denmark are invited to join the study according to in- and exclusion criteria. Assessment includes demographic, clinical and psychosocial data, symptoms, electrocardiogram, blood- and urine samples and transthoracic echocardiography during rest and dipyridamol stress with measurement of coronary flow reserve (CFR) by Doppler of the left anterior descending artery. In substudies CMD will be assessed by positron emission tomography, peripheral endothelial function, magnetic resonance imaging-and computed tomography derived myocardial perfusion scans, angiographic corrected TIMI frame counts, advanced echocardiographic modalities at rest and during stress, and invasive measures of CFR and coronary vascular reactivity. The study will include 2000 women who will be followed for 5 years for cardiovascular outcomes. By May 2013, 1685 women have been screened, 759 eligible patients identified, 530 contacted, and 299 (56%) agreed to participate. Among the first 50 patients, Doppler CFR was successfully measured in 49 (98%). Among women with suspected ischemic heart disease and no obstructive coronary artery disease, non-invasive Doppler CFR is feasible as a routine assessment. The study will provide information on methods to diagnose CMD and determine the prognostic value of routine non-invasive assessment of microvascular function. Future study will provide women identified with CMD participation in interventional substudies designed to test treatment strategies. Copyright © 2014 Mosby, Inc. All rights reserved.

  16. Genetics Home Reference: surfactant dysfunction

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Surfactant dysfunction Surfactant dysfunction Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Surfactant dysfunction is a lung disorder that causes breathing ...

  17. The complement system is dysfunctional in metabolic disease: Evidences in plasma and adipose tissue from obese and insulin resistant subjects.

    Science.gov (United States)

    Moreno-Navarrete, José María; Fernández-Real, José Manuel

    2017-10-26

    The relationship between chronic low-grade inflammation, insulin resistance and other obesity-associated metabolic disturbances is increasingly recognized. The possible mechanisms that trigger these immunologic alterations remain to be fully understood. The complement system is a crucial element of immune defense system, being important in the activation of innate and adaptative immune response, promoting the clearance of apoptotic and damaged endogenous cells and participating in processes of tissue development, degeneration, and regeneration. Circulating components of the complement system appear to be dysregulated in obesity-associated metabolic disturbances. The activation of the complement system is also evident in adipose tissue from obese subjects, in association with subclinical inflammation and alterations in glucose metabolism. The possible contribution of some components of the complement system in the development of insulin resistance and obesity-associated metabolic disturbances, and the possible role of complement system in adipose tissue physiology is reviewed here. The modulation of the complement system could constitute a potential target in the pathophysiology and therapy of obesity and associated metabolic disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Diastolic dysfunction characterizes cirrhotic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Piyush O. Somani

    2014-11-01

    Conclusions: Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS.

  19. Omega-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption Enhances Microvascular Reactivity in Young Healthy Individuals.

    Science.gov (United States)

    Stupin, Ana; Rasic, Lidija; Matic, Anita; Stupin, Marko; Kralik, Zlata; Kralik, Gordana; Grcevic, Manuela; Drenjancevic, Ines

    2018-04-10

    Whilst the beneficial effect of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on cardiovascular (CV) system is well supported in CV patients, the effect of consumption of omega-3 PUFAs enriched functional food in healthy individuals is still not fully elucidated. This study aimed to determine the effect of consumption of omega-3 PUFAs enriched hen eggs on microvascular reactivity (primary outcome), blood pressure (BP) and serum lipid profile in young healthy individuals. Control group (N=16) ate three ordinary hen eggs (277 mg omega-3 PUFAs/day), and OMEGA-3 group (N=20) ate three omega-3 PUFAs enriched eggs containing 259 mg of omega-3 PUFAs/egg daily (ALA 167 mg/egg, EPA 7 mg/egg, DHA 84 mg/egg) for 3 weeks (777 mg omega-3 PUFAs/day). Post-occlusive reactive hyperemia (PORH) in skin microcirculation assessed by laser Doppler flowmetry, serum lipid profile, fasting blood glucose, high-sensitivity C-reactive protein (hsCRP) and arterial BP were measured in all subjects before and after the protocol. PORH was significantly enhanced, and triglycerides, hsCRP and BP were significantly decreased in OMEGA-3 group compared to baseline measurement, while there was no significant difference in Control group after the protocol compared to baseline. This is the first study to demonstrate that consumption of a mixture of omega-3 PUFAs (ALA+EPA+DHA), provided via enriched hen eggs, elicits changes in microvascular reactivity, BP and triglycerides level in healthy subjects that are associated with CV benefits, thus suggesting that daily consumption of omega-3 PUFAs enriched eggs in healthy individuals may potentially contribute to CV risk factors attenuation and disease prevention.

  20. Reduced toxicity polyester resins and microvascular pre-preg tapes for advanced composites manufacturing

    Science.gov (United States)

    Poillucci, Richard

    Advanced composites manufacturing broadly encapsulates topics ranging from matrix chemistries to automated machines that lay-up fiber-reinforced materials. Environmental regulations are stimulating research to reduce matrix resin formulation toxicity. At present, composites fabricated with polyester resins expose workers to the risk of contact with and inhalation of styrene monomer, which is a potential carcinogen, neurotoxin, and respiratory irritant. The first primary goal of this thesis is to reduce the toxicity associated with polyester resins by: (1) identification of potential monomers to replace styrene, (2) determination of monomer solubility within the polyester, and (3) investigation of approaches to rapidly screen a large resin composition parameter space. Monomers are identified based on their ability to react with polyester and their toxicity as determined by the Globally Harmonized System (GHS) and a green screen method. Solubilities were determined by the Hoftyzer -- Van Krevelen method, Hansen solubility parameter database, and experimental mixing of monomers. A combinatorial microfluidic mixing device is designed and tested to obtain distinct resin compositions from two input chemistries. The push for safer materials is complemented by a thrust for multifunctional composites. The second primary goal of this thesis is to design and implement the manufacture of sacrificial fiber materials suitable for use in automated fiber placement of microvascaular multifunctional composites. Two key advancements are required to achieve this goal: (1) development of a roll-to-roll method to place sacrificial fibers onto carbon fiber pre-preg tape; and (2) demonstration of feasible manufacture of microvascular carbon fiber plates with automated fiber placement. An automated method for placing sacrificial fibers onto carbon fiber tapes is designed and a prototype implemented. Carbon fiber tows with manual placement of sacrificial fibers is implemented within an

  1. BMPRII influences the response of pulmonary microvascular endothelial cells to inflammatory mediators.

    Science.gov (United States)

    Vengethasamy, Leanda; Hautefort, Aurélie; Tielemans, Birger; Belge, Catharina; Perros, Frédéric; Verleden, Stijn; Fadel, Elie; Van Raemdonck, Dirk; Delcroix, Marion; Quarck, Rozenn

    2016-11-01

    Mutations in the bone morphogenetic protein receptor (BMPR2) gene have been observed in 70 % of patients with heritable pulmonary arterial hypertension (HPAH) and in 11-40 % with idiopathic PAH (IPAH). However, carriers of a BMPR2 mutation have only 20 % risk of developing PAH. Since inflammatory mediators are increased and predict survival in PAH, they could act as a second hit inducing the development of pulmonary hypertension in BMPR2 mutation carriers. Our specific aim was to determine whether inflammatory mediators could contribute to pulmonary vascular cell dysfunction in PAH patients with and without a BMPR2 mutation. Pulmonary microvascular endothelial cells (PMEC) and arterial smooth muscle cells (PASMC) were isolated from lung parenchyma of transplanted PAH patients, carriers of a BMPR2 mutation or not, and from lobectomy patients or lung donors. The effects of CRP and TNFα on mitogenic activity, adhesiveness capacity, and expression of adhesion molecules were investigated in PMECs and PASMCs. PMECs from BMPR2 mutation carriers induced an increase in PASMC mitogenic activity; moreover, endothelin-1 secretion by PMECs from carriers was higher than by PMECs from non-carriers. Recruitment of monocytes by PMECs isolated from carriers was higher compared to PMECs from non-carriers and from controls, with an elevated ICAM-1 expression. CRP increased adhesion of monocytes to PMECs in carriers and non-carriers, and TNFα only in carriers. PMEC from BMPR2 mutation carriers have enhanced adhesiveness for monocytes in response to inflammatory mediators, suggesting that BMPR2 mutation could generate susceptibility to an inflammatory insult in PAH.

  2. Vocal cord dysfunction.

    Science.gov (United States)

    Deckert, James; Deckert, Linda

    2010-01-15

    Vocal cord dysfunction involves inappropriate vocal cord motion that produces partial airway obstruction. Patients may present with respiratory distress that is often mistakenly diagnosed as asthma. Exercise, psychological conditions, airborne irritants, rhinosinusitis, gastroesophageal reflux disease, or use of certain medications may trigger vocal cord dysfunction. The differential diagnosis includes asthma, angioedema, vocal cord tumors, and vocal cord paralysis. Pulmonary function testing with a flow-volume loop and flexible laryngoscopy are valuable diagnostic tests for confirming vocal cord dysfunction. Treatment of acute episodes includes reassurance, breathing instruction, and use of a helium and oxygen mixture (heliox). Long-term management strategies include treatment for symptom triggers and speech therapy.

  3. Wide-area mapping of resting state hemodynamic correlations at microvascular resolution with multi-contrast optical imaging (Conference Presentation)

    Science.gov (United States)

    Senarathna, Janaka; Hadjiabadi, Darian; Gil, Stacy; Thakor, Nitish V.; Pathak, Arvind P.

    2017-02-01

    Different brain regions exhibit complex information processing even at rest. Therefore, assessing temporal correlations between regions permits task-free visualization of their `resting state connectivity'. Although functional MRI (fMRI) is widely used for mapping resting state connectivity in the human brain, it is not well suited for `microvascular scale' imaging in rodents because of its limited spatial resolution. Moreover, co-registered cerebral blood flow (CBF) and total hemoglobin (HbT) data are often unavailable in conventional fMRI experiments. Therefore, we built a customized system that combines laser speckle contrast imaging (LSCI), intrinsic optical signal (IOS) imaging and fluorescence imaging (FI) to generate multi-contrast functional connectivity maps at a spatial resolution of 10 μm. This system comprised of three illumination sources: a 632 nm HeNe laser (for LSCI), a 570 nm ± 5 nm filtered white light source (for IOS), and a 473 nm blue laser (for FI), as well as a sensitive CCD camera operating at 10 frames per second for image acquisition. The acquired data enabled visualization of changes in resting state neurophysiology at microvascular spatial scales. Moreover, concurrent mapping of CBF and HbT-based temporal correlations enabled in vivo mapping of how resting brain regions were linked in terms of their hemodynamics. Additionally, we complemented this approach by exploiting the transit times of a fluorescent tracer (Dextran-FITC) to distinguish arterial from venous perfusion. Overall, we demonstrated the feasibility of wide area mapping of resting state connectivity at microvascular resolution and created a new toolbox for interrogating neurovascular function.

  4. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

    Science.gov (United States)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-06-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

  5. 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,

  6. Comparisons of severity classification systems for oropharyngeal dysfunction in children with cerebral palsy: Relations with other functional profiles.

    Science.gov (United States)

    Goh, Yu-Ra; Choi, Ja Young; Kim, Seon Ah; Park, Jieun; Park, Eun Sook

    2018-01-01

    This study aimed to investigate the relationships between various classification systems assessing the severity of oropharyngeal dysphagia and communication function and other functional profiles in children with cerebral palsy (CP). This is a prospective, cross-sectional, study in a university-affiliated, tertiary-care hospital. We recruited 151 children with CP (mean age 6.11 years, SD 3.42, range 3-18yr). The Eating and Drinking Ability Classification System (EDACS) and the dysphagia scales of Functional Oral Intake Scale (FOIS), Swallow Function Scales (SFS), and Food Intake Level Scale (FILS) were used. The Communication Function Classification System (CFCS) and Viking Speech Scale (VSS) were employed to classify communication function and speech intelligibility, respectively. The Pediatric Evaluation of Disability Inventory (PEDI) with the Gross Motor Function Classification System (GFMCS) and the Manual Ability Classification System (MACS) level were also assessed. Spearman correlation analysis to investigate the associations between measures and univariate and multivariate logistic regression models to identify significant factors were used. Median GMFCS level of participants was III (interquartile range II-IV). Significant dysphagia based on EDACS level III-V was noted in 23 children (15.2%). There were strong to very strong relationships between the EDACS level with the dysphagia scales. The EDACS presented strong associations with MACS, CFCS, and VSS, a moderate association with GMFCS level, and a moderate to strong association with each domain of the PEDI. In multivariate analysis, poor functioning in EDACS were associated with poor functioning in gross motor and communication functions. Copyright © 2017. Published by Elsevier Ltd.

  7. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  8. Chronic pelvic floor dysfunction.

    Science.gov (United States)

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Sexual Dysfunction in Urogynaecology

    NARCIS (Netherlands)

    A.M.E. Roos (Anne-Marie)

    2014-01-01

    markdownabstract__abstract__ This thesis is dedicated to enhance understanding of sexual dysfunction in the field of urogynaecology, focussing on the prevalence of sexual problems in urogynaecology clinics, the clinical attention of the urogynaecologist to female sexual dyfunction, the impact

  10. HIV and thyroid dysfunction.

    Science.gov (United States)

    Parsa, Alan A; Bhangoo, Amrit

    2013-06-01

    Human Immunodeficiency virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are associated with dysfunction of many endocrine organs and their axis. HIV infectivity leads to altered metabolism, poor oral intake and increased prevalence of weight loss and wasting which may have a role in thyroid dysfunction. Overt thyroid dysfunction occurs at similar rates as the general population while subclinical disease such as nonthyroidal illness (sick euthyroid syndrome), subclinical hypothyroidism and isolated low T4 levels are more frequent. Moreover, HAART therapy can complicate thyroid function further through drug interactions and the immune reconstitution inflammatory syndrome (IRIS). In this review we report the common thyroid dysfunctions associated with HIV before and after HAART therapy. We discuss presentation, diagnostic work up, treatment and follow up in each condition.

  11. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

    International Nuclear Information System (INIS)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-01-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

  12. Free microvascular transplantation of the trapezius musculocutaneous flap in dogs.

    Science.gov (United States)

    Philibert, D; Fowler, J D; Clapson, J B

    1992-01-01

    A musculocutaneous flap based on the prescapular branch of the superficial cervical artery and including the cervical part of the trapezius muscle and overlying skin was transplanted over a defect created on the medial side of the contralateral tibia in four dogs by using microvascular technique. The donor and recipient sites in three dogs were examined clinically for 21 days, after which they were examined angiographically and histologically. All dogs were free of lameness by hour 48. Seromas formed at the donor site between days 7 and 15. One vascular pedicle was traumatized at hour 40, and the dog was euthanatized. Three flaps survived with minimal necrosis. Edema of the flaps was severe from days 5 to 11. Angiograms showed complete perfusion of the flaps, and survival was confirmed histologically. Esthetic appearance and function were good in one dog at month 7.

  13. CMR of microvascular obstruction and hemorrhage in myocardial infarction

    Directory of Open Access Journals (Sweden)

    Wu Katherine C

    2012-09-01

    Full Text Available Abstract Microvascular obstruction (MO or no-reflow phenomenon is an established complication of coronary reperfusion therapy for acute myocardial infarction. It is increasingly recognized as a poor prognostic indicator and marker of subsequent adverse LV remodeling. Although MO can be assessed using various imaging modalities including electrocardiography, myocardial contrast echocardiography, nuclear scintigraphy, and coronary angiography, evaluation by cardiovascular magnetic resonance (CMR is particularly useful in enhancing its detection, diagnosis, and quantification, as well as following its subsequent effects on infarct evolution and healing. MO assessment has become a routine component of the CMR evaluation of acute myocardial infarction and will increasingly play a role in clinical trials of adjunctive reperfusion agents and strategies. This review will summarize the pathophysiology of MO, current CMR approaches to diagnosis, clinical implications, and future directions needed for improving our understanding of this common clinical problem.

  14. Novel brain model for training of deep microvascular anastomosis.

    Science.gov (United States)

    Ishikawa, Tatsuya; Yasui, Nobuyuki; Ono, Hidenori

    2010-01-01

    Models of the brain and skull were developed using a selective laser sintering method for training in the procedures of deep microvascular anastomosis. Model A has an artificial skull with two craniotomies, providing fronto-temporal-subtemporal and suboccipital windows. The brain in Model A is soft and elastic, and consists of the brainstem and a hemispheric part with a detailed surface. Rehearsals or training for anastomosis to the insular part of the middle cerebral artery, superior cerebellar artery, posterior cerebral artery, and posterior inferior cerebellar artery can be performed through the craniotomies. Model B has an artificial skull with a bifrontal craniotomy and an artificial brain consisting of the bilateral frontal lobes with an interhemispheric fissure and corpus callosum. Rehearsals or training for anastomosis of the callosal segment of the anterior cerebral artery can be practiced through this craniotomy. These realistic models will help to develop skills for deep vascular anastomosis, which remains a challenging neurosurgical procedure, even for experienced neurosurgeons.

  15. An Unusual Case of Suspected Microvascular Angina in a Newborn

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    Stefania Cataldo

    2012-01-01

    Full Text Available Myocardial ischemia in pediatric population is uncommon and usually due to congenital heart disease or extracardiac conditions leading to poor coronary perfusion. A 6-day-old newborn presented with respiratory distress and signs of heart failure. ECG, echocardiography, and laboratory results were consistent with myocardial ischemia. Coronary angiography was performed to exclude anomalous origin of coronary arteries, showing normal coronary artery origin and course. Thrombophilia and extra-cardiac causes were ruled out. Clinical conditions improved with mechanical ventilation and diuretics, enzyme levels lowered, repolarisation and systolic function abnormalities regressed, but ischemic electrocardiographic and echocardiographic signs still presented during intense crying. Becaues of suspicion of microvascular angina, therapy with ASA and beta-blocker was started. At 5 month followup, the baby was in good clinical condition and no more episodes were recorded. We believe it is an interesting case, as no similar cases have been recorded till now.

  16. Statin use before diabetes diagnosis and risk of microvascular disease

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G

    2014-01-01

    BACKGROUND: The role of statins in the development of microvascular disease in patients with diabetes is unknown. We tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes...... Statistics. We randomly selected 15,679 individuals from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47,037 individuals who had never used statins before diagnosis (non-statin users). Our primary outcome was to compare...... the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address...

  17. Auditory Dysfunction in Patients with Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Sadaharu Tabuchi

    2014-01-01

    Full Text Available Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

  18. Gut dysfunction in Parkinson's disease.

    Science.gov (United States)

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-07-07

    Early involvement of gut is observed in Parkinson's disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.

  19. Comprehensive Analysis of Chicken Vessels as Microvascular Anastomosis Training Model

    Directory of Open Access Journals (Sweden)

    Bo Young Kang

    2017-01-01

    Full Text Available BackgroundNonliving chickens are commonly used as a microvascular anastomosis training model. However, previous studies have investigated only a few types of vessel, and no study has compared the characteristics of the various vessels. The present study evaluated the anatomic characteristics of various chicken vessels as a training model.MethodsEight vessels—the brachial artery, basilic vein, radial artery, ulnar artery, ischiatic artery and vein, cranial tibial artery, and common dorsal metatarsal artery—were evaluated in 26 fresh chickens and 30 chicken feet for external diameter (ED and thicknesses of the tunica adventitia and media. The dissection time from skin incision to application of vessel clamps was also measured.ResultsThe EDs of the vessels varied. The ischiatic vein had the largest ED of 2.69±0.33 mm, followed by the basilic vein (1.88±0.36 mm, ischiatic artery (1.68±0.24 mm, common dorsal metatarsal artery (1.23±0.23 mm, cranial tibial artery (1.18±0.19 mm, brachial artery (1.08±0.15 mm, ulnar artery (0.82±0.13 mm, and radial artery (0.56±0.12 mm, and the order of size was consistent across all subjects. Thicknesses of the tunica adventitia and media were also diverse, ranging from 74.09±19.91 µm to 158.66±40.25 µm (adventitia and from 31.2±7.13 µm to 154.15±46.48 µm (media, respectively. Mean dissection time was <3 minutes for all vessels.ConclusionsOur results suggest that nonliving chickens can provide various vessels with different anatomic characteristics, which can allow trainees the choice of an appropriate microvascular anastomosis training model depending on their purpose and skillfulness.

  20. Immediate pain relief by microvascular decompression for idiopathic trigeminal neuralagia

    International Nuclear Information System (INIS)

    Haq, N.U.; Ali, M.; Khan, H.M.; Ishaq, M.; Khattak, M.I.

    2016-01-01

    Background: Trigeminal neuralgia is a common entity which is managed by neurosurgeons in day to day practice. Up-till now many treatment options have been adopted for it but micro-vascular decompression is much impressive in terms of pain control and recurrence rate in all of them. The objective of study was known the efficacy of micro vascular decompression for idiopathic trigeminal neuralgia by using muscle patch in terms of immediate pain relief. Methods: This descriptive study was carried out in Neurosurgery Department lady reading hospital, Peshawar from January 2010 to December 2012. All patients who underwent micro vascular decompression for idiopathic trigeminal neuralgia were included in the study. Patients were assessed 72 hours after the surgery by borrow neurological institute pain scale (BNIP scale) for pain relief and findings were documented on predesigned proforma. Data was analysed by SPSS-17. Results: Total 52 patients were included in this study. Among these 32 (61.53 percentage) were female and 20 (38.46 percentage) were males having age from 22-76 years (mean 49 years). Right side was involved in 36 (69.23 percentage) and left side in 16 (30.76 percentage) patients. Duration of symptoms ranged from 6 months to 16 years (mean 8 years). History of dental extraction and peripheral neurectomy was present in 20 (38 percentage) and 3(5.76 percentage) patients while V3 was most commonly involved branch with 28(57.69 percentage) frequency and combined V2,V3 involvement was 1 (11.53 percentage). Superior cerebellar artery was most common offending vessel in 46(88.46 percentage) while arachnoid adhesions were in 2(3.84 percentage) patients. We assessed patient immediate postoperatively using BNIP pain scale. Conclusion: Micro-vascular decompression is most effective mode of treatment for trigeminal neuralgia in terms of immediate pain relief. (author)

  1. Spontaneous oscillations of capillary blood flow in artificial microvascular networks.

    Science.gov (United States)

    Forouzan, Omid; Yang, Xiaoxi; Sosa, Jose M; Burns, Jennie M; Shevkoplyas, Sergey S

    2012-09-01

    Previous computational studies have suggested that the capillary blood flow oscillations frequently observed in vivo can originate spontaneously from the non-linear rheological properties of blood, without any regulatory input. Testing this hypothesis definitively in experiments involving real microvasculature has been difficult because in vivo the blood flow in capillaries is always actively controlled by the host. The objective of this study was to test the hypothesis experimentally and to investigate the relative contribution of different blood cells to the capillary blood flow dynamics under static boundary conditions and in complete isolation from the active regulatory mechanisms mediated by the blood vessels in vivo. To accomplish this objective, we passed whole blood and re-constituted blood samples (purified red blood cells suspended in buffer or in autologous plasma) through an artificial microvascular network (AMVN) comprising completely inert, microfabricated vessels with the architecture inspired by the real microvasculature. We found that the flow of blood in capillaries of the AMVN indeed oscillates with characteristic frequencies in the range of 0-0.6 Hz, which is in a very good agreement with previous computational studies and in vivo observations. We also found that the traffic of leukocytes through the network (typically neglected in computational modeling) plays an important role in generating the oscillations. This study represents the key piece of experimental evidence in support of the hypothesis that spontaneous, self-sustained oscillations of capillary blood flow can be generated solely by the non-linear rheological properties of blood flowing through microvascular networks, and provides an insight into the mechanism of this fundamentally important microcirculatory phenomenon. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  3. Subclinical right ventricle systolic dysfunction in childhood-onset systemic lupus erythematosus: insights from two-dimensional speckle-tracking echocardiography.

    Science.gov (United States)

    Leal, G N; Silva, K F; França, C M P; Lianza, A C; Andrade, J L; Campos, L M A; Bonfá, E; Silva, C A

    2015-05-01

    The objective of this article is to evaluate right ventricle strain imaging by two-dimensional speckle-tracking (2DST) in childhood-onset systemic lupus erythematosus (c-SLE). Thirty-five c-SLE patients with no signs or symptoms of heart failure and 33 healthy volunteers were evaluated by standard echocardiogram and 2DST. Conventional parameters included tricuspid annular plane systolic excursion (TAPSE), RV tissue-Doppler-derived Tei index and systolic pulmonary artery pressure. Global peak longitudinal systolic strain (PLSS) and strain rate (PLSSR) of RV were obtained by 2DST. Demographic/clinical features, SLEDAI-2K/SLICC/ACR-DI and treatment were also assessed. The median current age was similar in patients and controls (14.75 vs. 14.88 years, p = 0.62). RV PLSS was significantly reduced in c-SLE (-24.5 ± 5.09 vs. -27.62 ± 3.02%, p = 0.003). Similar findings were observed after excluding patients with pulmonary hypertension (-24.62 ± 4.87% vs. -27.62 ± 3.02%, p = 0.0041). RV PLSS was positively correlated with TAPSE (r = +0.49, p = 0.0027) and negatively correlated with Tei index (r = -0.34, p = 0.04) in c-SLE. RV PLSSR was not different comparing patients and controls (-0.65 s(-1 )± 0.47 vs. -1.87 ± 0.49 s(-1), p = 0.07). Further analysis of c-SLE patients revealed higher frequencies of neuropsychiatric manifestations (39% vs. 0%, p = 0.007) and antiphospholipid antibodies (55% vs. 18%, p = 0.035) in those with RV PLSS ≤ -23.7% vs >-23.7%. No differences were evidenced in demographic data, disease activity/damage or treatments (p > 0.05). The present study, using a new and more sensitive technique, revealed subclinical RV systolic dysfunction in c-SLE patients that may have future prognostic implications. The novel association of asymptomatic RV dysfunction with neuropsychiatric manifestations and antiphospholipid antibodies may suggest common physiopathological pathways.

  4. Effects of stress on gastrointestinal function: interactions of neural and endocrine systems in mediating stress-induced intestinal dysfunction in rats

    International Nuclear Information System (INIS)

    Williams, C.L.

    1987-01-01

    The etiology of stress-induced intestinal dysfunction is completely unresolved, and the lack of an appropriate animal model has hindered studies of causality. We compared a number of stressors and their resultant effects on intestinal transit, a measure of the propulsive motor activity of the gut, in the rat. We found that the response of the intestine to stress, and the neural systems activated by stress, were dependent on the type and duration of stress, as well as the animal strain, and gender. We developed a model, acute wrapping restraint stress, to fully characterize the effects of stress on intestinal transit. Wrap restraint stress is a nonulcerogenic model in which rats are subjected to acute restraint by wrapping them in a harness of paper tape to restrict, but not prevent movement of the upper body and forelimbs. Transit was evaluated by the geometric center method, in which a radiomarker ( 51 Cr) is instilled directly into the proximal duodenum and proximal colon via a surgically placed intestinal cannula, in fasted, adult female Sprague Dawley rats

  5. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

  6. DYSFUNCTIONS IN THE APPLICATION OF THE MANAGERIAL CONTROL SYSTEMS IN ROMANIAN PUBLIC INSTITUTIONS: THE REPORTING IMPROPRIETIES, THE INFORMATION AND THE COMMUNICATION STANDARDS

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    CRĂCIUN Liviu

    2014-07-01

    Full Text Available The development level of managerial control systems in the Romanian public entities is not a remarkable one, on the contrary, some institutions do not understand the real usefulness of the internal control system and the related set of standards; the compliance is determined only by the regulatory norms. The practice of implementing the internal control proves that the perception of executives and middle managers regarding that system is not a favourable and supporting one. The managers face difficulties caused by the ambiguity of some of the standards, poorly understood, and for which the body of laws does not provide advices. Thus, some institutions report the high compliance of standards, although the reality shows numerous inconsistencies. Other public institutions assess their own level of implementation only partially, but do not identify improvement solutions. Because of the lacking of benchmarking initiatives and knowledge transferring between institutions, the picture of this situation indicates dysfunctions that influence the efficiency of the activities and the achievement of the objectives. In this paper, we will analyze the correlation between the observed shortcomings in the implementation of three of the most important standards, namely the Reporting improprieties, the Information and the Communication. The methodology used is an analytical and exploratory one and critically examines the implementation status of these three standards in more than 40 public institutions in Dolj County, Romania. Also, by analyzing the answers to the questionnaire, our study identifies differences in interpretation and implementation of these standards between certain types of organizations (given the heterogeneity of the investigated sample. The results show a high interdependence between this control standards and our proposals focus on the strengthening of the interpersonal skills and the personal relationships. Our study is directed toward the

  7. Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz

    2007-01-01

    examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured......: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate...

  8. Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies.

    Science.gov (United States)

    Burks, Tyesha N; Marx, Ruth; Powell, Laura; Rucker, Jasma; Bedja, Djahida; Heacock, Elisa; Smith, Barbara J; Foster, D Brian; Kass, David; O'Rourke, Brian; Walston, Jeremy D; Abadir, Peter M

    2015-05-20

    Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

  9. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  10. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE

    Science.gov (United States)

    SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE.PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti. US EPA, ORD, NHEERL, ETD, PTB, Research Triangle Park, NC USA. Environmental particles (PM...

  11. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

    Directory of Open Access Journals (Sweden)

    R. Andrew Shanely

    2016-08-01

    Full Text Available Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125. Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05, however, the rating of perceived exertion was greater during the WM trial (p > 0.05. WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05, but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine, antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function.

  12. Striated muscle microvascular response to silver implants: A comparative in vivo study with titanium and stainless steel.

    Science.gov (United States)

    Kraft, C N; Hansis, M; Arens, S; Menger, M D; Vollmar, B

    2000-02-01

    Local microvascular perfusion is the primary line of defense of tissue against microorganisms and plays a considerable role in reparative processes. The impairment of the microcirculation by a biomaterial may therefore have profound consequences. Silver is known to have excellent antimicrobial activity and, although regional and systemic toxic effects have been described, silver is regularly discussed as an implant material in bone surgery. Because little is known about the influence of silver implants on the adjacent host tissue microvasculature, we studied in vivo nutritive perfusion and leukocytic response, and compared these results with those of the conventionally used materials titanium and stainless steel. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, the implantation of a commercially pure silver sample led to a distinct and persistent activation of leukocytes combined with a marked disruption of the microvascular endothelial integrity, massive leukocyte extravasation, and considerable venular dilation. Whereas animals with stainless-steel implants showed a moderate increase in these parameters with a tendency to recuperate, titanium implants caused only a transient increase of leukocyte-endothelial cell interaction within the first 120 min and no significant change in macromolecular leakage, leukocyte extravasation and venular diameter. After 3 days, five of six preparations with silver samples showed severe inflammation and massive edema. Thus, the use of silver as an implant material should be critically judged despite its bactericidal properties. The implant material titanium seems to be well tolerated by the local vascular system and currently represents the golden standard. Copyright 2000 John Wiley & Sons, Inc.

  13. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission

    OpenAIRE

    Zhou, Hao; Wang, Shuyi; Zhu, Pingjun; Hu, Shunying; Chen, Yundai; Ren, Jun

    2017-01-01

    Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism in...

  14. Improved myocardial perfusion after transmyocardial laser revascularization in a patient with microvascular coronary artery disease

    Directory of Open Access Journals (Sweden)

    Peyman Mesbah Oskui

    2014-03-01

    Full Text Available We report the case of a 59-year-old woman who presented with symptoms of angina that was refractory to medical management. Although her cardiac catheterization revealed microvascular coronary artery disease, her symptoms were refractory to optimal medical management that included ranolazine. After undergoing transmyocardial revascularization, her myocardial ischemia completely resolved and her symptoms dramatically improved. This case suggests that combination of ranolazine and transmyocardial revascularization can be applied to patients with microvascular coronary artery disease.

  15. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

    Directory of Open Access Journals (Sweden)

    Ingmar Lundquist

    Full Text Available Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided.

  16. Liver dysfunction assessed by model for end-stage liver disease excluding INR (MELD-XI scoring system predicts adverse prognosis in heart failure.

    Directory of Open Access Journals (Sweden)

    Satoshi Abe

    Full Text Available AIMS: Liver dysfunction due to heart failure (HF is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. METHODS AND RESULTS: We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289 and Group H (MELD-XI ≥10, n = 273. We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days, 104 deaths (62 cardiac deaths and 42 non-cardiac deaths were observed. The event (cardiac death, non-cardiac death, all-cause death-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively. In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively. CONCLUSIONS: The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF.

  17. Small Spacecraft Active Thermal Control: Micro-Vascular Composites Enable Small Satellite Cooling

    Science.gov (United States)

    Ghosh, Alexander

    2016-01-01

    The Small Spacecraft Integrated Power System with Active Thermal Control project endeavors to achieve active thermal control for small spacecraft in a practical and lightweight structure by circulating a coolant through embedded micro-vascular channels in deployable composite panels. Typically, small spacecraft rely on small body mounted passive radiators to discard heat. This limits cooling capacity and leads to the necessity to design for limited mission operations. These restrictions severely limit the ability of the system to dissipate large amounts of heat from radios, propulsion systems, etc. An actively pumped cooling system combined with a large deployable radiator brings two key advantages over the state of the art for small spacecraft: capacity and flexibility. The use of a large deployable radiator increases the surface area of the spacecraft and allows the radiation surface to be pointed in a direction allowing the most cooling, drastically increasing cooling capacity. With active coolant circulation, throttling of the coolant flow can enable high heat transfer rates during periods of increased heat load, or isolate the radiator during periods of low heat dissipation.

  18. Voiding dysfunction - A review

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    Sripathi V

    2005-01-01

    Full Text Available In a child who is toilet trained the sudden onset of daytime wetting with frequency or urgency is alarming to the parents. Initially this subject was subdivided into a number of descriptive clinical conditions which led to a lot of confusion in recognition and management. Subsequently, the term elimination dysfunction was coined by Stephen Koff to emphasise the association between recurrent urinary infection, wetting, constipation and bladder overactivity. From a urodynamic point of view, in voiding dysfunction, there is either detrusor overactivity during bladder filling or dyssynergic action between the detrusor and the external sphincter during voiding. Identifying a given condition as a ′filling phase dysfunction′ or ′voiding phase dysfunction′ helps to provide appropriate therapy. Objective clinical criteria should be used to define voiding dysfunction. These include bladder wall thickening, large capacity bladder and infrequent voiding, bladder trabeculation and spinning top deformity of the urethra and a clinically demonstrated Vincent′s curtsy. The recognition and treatment of constipation is central to the adequate treatment of voiding dysfunction. Transcutaneous electric nerve stimuation for the treatment of detrusor overactivity, biofeedback with uroflow EMG to correct dyssynergic voiding, and behavioral therapy all serve to correct voiding dysfunction in its early stages. In established neurogenic bladder disease the use of Botulinum Toxin A injections into the detrusor or the external sphincter may help in restoring continence especially in those refractory to drug therapy. However in those children in whom the upper tracts are threatened, augmentation of the bladder may still be needed.

  19. Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion.

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    Dae Hyun Lee

    Full Text Available Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals. Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion and perfused boundary region (PBR, a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm, was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031. We conclude that microvascular beds with a thick ("healthy" glycocalyx (low PBR, reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk" glycocalyx (high PBR is associated with a less efficient and defective microvascular perfusion.

  20. Thiel embalming technique: a valuable method for microvascular exercise and teaching of flap raising.

    Science.gov (United States)

    Wolff, Klaus-D; Kesting, Marco; Mücke, Thomas; Rau, Andrea; Hölzle, Frank

    2008-01-01

    Because of its high requirements on dexterity and microsurgical skills and the need of complete understanding of flap anatomy, microvascular free flap transfer belongs to the most demanding surgical procedures. Therefore, courses for flap raising and microvascular exercise are considered a prerequisite to prepare for clinical practise. To achieve teaching conditions as realistic as possible we used a novel cadaver embalming method enabling tissue dissection comparable to the living body. Thirty cadavers which were offered to us by the Institute of Anatomy for the purpose of running flap raising courses were embalmed in the technique described by Thiel. On each cadaver, nine free flaps were dissected according to a structured protocol by each course participant and afterwards used for microvascular exercise. The conservation of fine vascular structures and the suitability of the embalmed tissue for microvascular suturing were observed and photographically documented. The Thiel embalming technique provided flap raising procedures to be performed under realistic conditions similar to the living body. Vessels and nerves could be exposed and dissected up to a diameter of 1 mm and allowed for microvascular suturing even after weeks like fresh specimens. The Thiel embalming method is a unique technique and ideally suited to teach flap raising and microvascular suturing on human material. (c) 2008 Wiley-Liss, Inc. Microsurgery, 2008

  1. Effects of Dietary Supplementation with Brazil Nuts on Microvascular Endothelial Function in Hypertensive and Dyslipidemic Patients: A Randomized Crossover Placebo-Controlled Trial.

    Science.gov (United States)

    Huguenin, Grazielle V B; Moreira, Annie S B; Siant'Pierre, Tatiana D; Gonçalves, Rodrigo A; Rosa, Glorimar; Oliveira, Glaucia M M; Luiz, Ronir R; Tibirica, Eduardo

    2015-11-01

    To investigate the effects of dietary supplementation with GBNs on microvascular endothelial function in hypertensive and dyslipidemic patients. Ninety-one patients of both sexes aged 62.1 ± 9.3 years received 13 g/day of GBNs or a placebo for three months with a washout period of one month between treatments. Microvascular endothelial function was assessed using LSCI coupled with iontophoresis of ACh and PORH. We also used skin video capillaroscopy to measure capillary density and recruitment at rest and during PORH. Plasma concentrations of NOx were also measured as a marker of nitric oxide bioavailability. Supplementation with GBNs significantly increased the plasma levels of Se (p 0.05), and GBNs did not improve capillary density at baseline or recruitment during PORH (p > 0.05). Supplementation with GBNs induced significant increases in the plasma Se concentration and systemic bioavailability of nitric oxide. Nevertheless, GBN supplementation did not lead to any improvement in systemic microvascular reactivity or density in patients with arterial hypertension and dyslipidemia who were undergoing multiple drug therapies. © 2015 John Wiley & Sons Ltd.

  2. Carotid Artery Intima-Media Thickness and Cutaneous Microvascular Function are Associated With Vitamin C Levels in Young Patients With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Odermarsky, Michal; Lykkesfeldt, Jens; Liuba, Petru

    2008-01-01

    and plasma ascorbate remained significant after adjustment for age, diabetes duration, body mass index, and HbA1c (r=-0.28; p=0.05, and r=0.35, p=0.01, respectively). No association was observed between plasma ascorbate and the inflammatory and lipid variables (p>0.2). Conclusion: In juvenile type 1 diabetes......Background: Vascular endothelial dysfunction and accelerated thickening of arterial intima contribute to increased cardiovascular morbidity in type 1 diabetes. Although vitamin C has important antioxidant functions, and increased oxidative stress is a central mechanism of vascular abnormalities......-phosphoric acid-stabilized EDTA-plasma by high-performance liquid chromatography. Results: In univariate regression analysis, both cIMT and skin microvascular response to ACH correlated with ascorbate levels (r=-0.29; p=0.04, and r=0.43; p=0.004 respectively). The relationships between these vascular indexes...

  3. Carotid Artery Intima-Media Thickness and Cutaneous Microvascular Function are Associated With Vitamin C Levels in Young Patients With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Odermarsky, Michal; Lykkesfeldt, Jens; Liuba, Petru

    2008-01-01

    Background: Vascular endothelial dysfunction and accelerated thickening of arterial intima contribute to increased cardiovascular morbidity in type 1 diabetes. Although vitamin C has important antioxidant functions, and increased oxidative stress is a central mechanism of vascular abnormalities......, lower plasma levels of vitamin C appears to predispose to more pronounced adverse changes in both microcirculation and peripheral arteries. Further studies are needed to investigate whether dietary supplementation with vitamin C could retard the development of microvasculopathy and atherosclerosis...... in diabetes, the relationship between these two in young patients with this disease has not been yet investigated. Methods: Carotid artery intima-media thickness (cIMT) and cutaneous microvascular reactivity to endothelium-dependent (acetylcholine, ACH) and independent (sodium nitroprusside, SNP) were...

  4. Sepsis and myocardial dysfunction

    Directory of Open Access Journals (Sweden)

    Rafaela Deczka Morsch

    2006-12-01

    Full Text Available Sepsis and septic shock are prevalent in the intensive care setting,accounting for more than 40% of mortality in this scenario. Theappropriate management and recognition of sepsis-inducedmyocardial dysfunction are paramount for its proper treatmentand probably impact mortality rates. The objective of this articleis to review its definition, pathophysiologic mechanisms, possibletreatments and current research on the subject according to acritical view.Cellular signaling involved in myocardial depression is not fullyunderstood. Disturbances in calcium homeostasis,cardiodepressant circulating factors, inflammatory mediators,nitric oxide and apoptosis act as synergistic pathways that leadto severely depressed cardiac function. The diagnosis ofmyocardial dysfunction during sepsis carries a worse prognosisand increased mortality.Myocardial dysfunction plays an important role in morbidity andmortality rate of critically ill patients. Current research in thisarea will continue to evolve; we will, therefore, soon have moreinsights into potential novel therapies that can change its mortalityrates.

  5. Apraxia and motor dysfunction in corticobasal syndrome.

    Science.gov (United States)

    Burrell, James R; Hornberger, Michael; Vucic, Steve; Kiernan, Matthew C; Hodges, John R

    2014-01-01

    Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS. Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM. In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold apraxia correlated with atrophy of the pre-motor and parietal cortices. Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy.

  6. Systemic not just mesenteric lymph causes acute lung injury following hemorrhagic shock.

    Science.gov (United States)

    Diebel, Lawrence N; Liberati, David M; Ledgerwood, Anna M; Lucas, Charles E

    2008-10-01

    Recent studies have demonstrated a significant role for factor(s) present in mesenteric lymph following hemorrhagic shock in the etiology of post-hemorrhagic shock acute lung injury (ALI). Earlier studies have shown that ischemia-reperfusion insults to systemic tissue beds can also result in ALI. We therefore hypothesized that factors in systemic lymph may cause lung injury after hemorrhagic shock; this was studied in vitro. Confluent human pulmonary microvascular endothelial cells (HMVEC) maintained in a 2-chamber cell culture system were exposed to systemic lymph obtained from dogs exposed to sham operation or hemorrhagic shock and resuscitation. HMVEC injury was indexed by apoptosis (% Apo, Hoechst staining) and permeability to albumin (microL/min). HMVEC activation was indexed by surface expression of intracellular adhesion molecule-1 (ICAM-1) expressed as mean fluorescence intensity using flow cytometry. There was a 2-fold increase in HMVEC permeability and apoptotic rate after incubation with postshock systemic lymph. A similar effect was noted with ICAM expression, which was 2.5 fold higher after incubation with postshock lymph. These biologic effects were first noted with the 120-minute postresuscitation lymph. Lymph obtained during shock or from sham animals had no effect. Pulmonary microvascular endothelial dysfunction is evident after exposure to lymph obtained from systemic sites after hemorrhagic shock. The "unique" properties ascribed to post-hemorrhagic shock mesenteric lymph in causing ALI seem to be shared by lymph from systemic sites as well.

  7. Studies of pathological dynamics after microvascular injury using nonlinear optical methods

    Science.gov (United States)

    Rosidi, Nathanael L.

    Microvascular lesions are a common feature in the aging brain and clinical evidence has correlated microvascular pathology with the development of neurodegenerative diseases such as Alzheimer's disease and dementia. Traditional animal models that replicate hemorrhagic and ischemic lesions in the brain typically affect large regions in the cortex and do not reproduce the small-scale lesions linked to neurodegeneration that likely stem from injuries to single microvessels. Due in part to this lack of small-scale injury animal models, there remains an incomplete understanding of the cellular and pathophysiological dynamics following small-scale vascular lesions, making progress on therapeutic strategies difficult. We used tightly focused femtosecond laser pulses to injure single penetrating arterioles (PA) (i.e., arterioles that plunge into the brain) in the cortex of live anesthetized rodents and used two-photon excited fluorescence (2PEF) imaging to quantify blood flow changes and to determine the time course of pathological consequences in the brain after injury. We find that after ischemic occlusion of a PA, nearby pial and penetrating arterioles do not actively compensate for the reduction of blood flow observed near the occluded blood vessel. We find that capillaries connected downstream to the clotted vessel dilate but other capillaries in the vicinity do not, suggesting that any compensatory signal that results in a physiological response travels vascularly. We ruptured individual PAs to induce microhemorrhages that resulted in extravasation of blood into the parenchyma. We find that tissue compression due to the hematoma does not collapse capillaries and cause acute ischemia. 2PEF imaging of mice expressing yellow fluorescent protein (YFP) in a subset of cortical neurons revealed no dendrite degeneration out to seven days after microhemorrhage. However, we did observe an inflammatory response by microglia/macrophages as quickly as 1.5-hrs after

  8. Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system.

    Science.gov (United States)

    Lonnemann, G; Floege, J; Kliem, V; Brunkhorst, R; Koch, K M

    2000-08-01

    In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius((R))) for the treatment of acute renal failure in patients with MODS in the intensive care unit. Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments. Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28 degrees C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (dialysis using the Genius((R)) system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent

  9. Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.

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    Vivekanandhan Aravindhan

    Full Text Available Lipopolysaccharide (LPS/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM and its complications. Endotoxin core antibodies (EndoCAb, LPS binding protein (LBP and soluble CD14 (sCD14 act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF.A total of 197 subjects (64 normal glucose tolerance (NGT subjects, 97 T1DM subjects without MVC and 36 with MVC were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays.Compared to NGT, T1DM subjects (both with and without MVC had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p<0.05. No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC.Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications.

  10. Early detection of cardiac involvement in systemic sclerosis assessed by tissue-Doppler echocardiography: relationship with neurohormonal activation and endothelial dysfunction.

    Science.gov (United States)

    Dimitroulas, Theodoros; Giannakoulas, Georgios; Papadopoulou, Klio; Karvounis, Haralambos; Dimitroula, Hara; Koliakos, Georgios; Karamitsos, Theodoros; Parcharidou, Despoina; Settas, Loukas

    2010-05-01

    Cardiopulmonary complications are common in patients with systemic sclerosis (SSc). We assessed cardiac involvement in patients with SSc using echocardiography and investigated the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) with echocardiographic measures of myocardial function in sera of patients with SSc who had no symptoms of heart failure. We prospectively studied 52 patients with SSc (mean age 55.7 +/- 10.1 yrs, 51 women), with conventional and tissue-Doppler echocardiography. Plasma NT-proBNP and ADMA levels were measured in all patients. Data were compared with those obtained from 25 healthy controls comparable for age and sex. Patients with SSc had impaired left ventricular (LV) and right ventricular diastolic function expressed by inverted ratio of peak early to peak late transmitral (Mit E/A) and transtricuspid velocity and increased left atrial diameter compared with controls. Peak systolic mitral lateral annular motion velocity and peak early diastolic mitral lateral annular motion velocity (LV Em) were lower, while LV E/Em ratio was higher, in patients with SSc compared to controls. ADMA was significantly related with LV Em and E/Em ratio. NT-proBNP was associated with Mit E, Mit E/A ratio and mitral deceleration time. Significant correlation was also observed between NT-proBNP and ADMA levels. Depressed cardiac function is common, even in asymptomatic patients with SSc. NT-proBNP and ADMA are significantly correlated with echocardiographic abnormalities, providing a potent link for cardiac function, neuroendocrine derangement, and endothelial dysfunction in patients with SSc who have cardiac disease.

  11. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial.

    Science.gov (United States)

    McMurray, John J V; Ezekowitz, Justin A; Lewis, Basil S; Gersh, Bernard J; van Diepen, Sean; Amerena, John; Bartunek, Jozef; Commerford, Patrick; Oh, Byung-Hee; Harjola, Veli-Pekka; Al-Khatib, Sana M; Hanna, Michael; Alexander, John H; Lopes, Renato D; Wojdyla, Daniel M; Wallentin, Lars; Granger, Christopher B

    2013-05-01

    We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison PARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

  12. Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging.

    Science.gov (United States)

    Toth, Peter; Tarantini, Stefano; Csiszar, Anna; Ungvari, Zoltan

    2017-01-01

    Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. Copyright © 2017 the American Physiological Society.

  13. Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging

    Science.gov (United States)

    Toth, Peter; Tarantini, Stefano; Csiszar, Anna

    2017-01-01

    Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. PMID:27793855

  14. The effect of L-arginine on microvascular reactivity in normotensive subjects with a family history of hypertension

    Directory of Open Access Journals (Sweden)

    Polona Zaletel

    2014-06-01

    Full Text Available Background: An increasing number of studies support the hypothesis that endothelial dysfunction due to reduced availability of nitric oxide plays a key role in initiation, development and progression of essential hypertension. The aim of our study was to determine whether the ingestion of L-arginine actually improves microvascular function in normotensive subjects with a family history of hypertension.Methods: 30 normotensive healthy men, aged 20–30 years, were divided into two groups according to the family history of hypertension. We measured ECG, heart rate, systolic and diastolic arterial pressure, cardiac output, stroke volume, total peripheral resistance (Task Force Monitor and laser Doppler (LD flux in the microvessels of the skin on the forearm at rest, before and after the administration of 0.9 g L-arginine. The endothelium-dependent vasodilation was assessed by iontophoresis of acetylcholine and the endothelium-independent vasodilation by iontophoresis of sodium nitroprusside.Results: After the ingestion of L-arginine the heart rate and the cardiac output statistically significantly decreased in both groups (paired t-test, p < 0.05. Arterial pressure did not change significantly. Stroke volume decreased and total peripheral resistance increased only in the group of subjects with a family history of hypertension (paired t-test, p < 0.05 The ingestion of L-arginine in predisposed normotensive subjects acutely improved the endothelium-dependent vasodilation (Dunnett’s test, p < 0.05, which is consistent with the assumption that endothelial dysfunction is already present in these subjects.Conclusions: In subjects with a family history of hypertension L-arginine improved endothelial function. This justifies L-arginine as a potential agent for the prevention and/or treatment of arterial hypertension.

  15. Quantitative and qualitative retinal microvascular characteristics and blood pressure.

    Science.gov (United States)

    Cheung, Carol Y; Tay, Wan T; Mitchell, Paul; Wang, Jie J; Hsu, Wynne; Lee, Mong L; Lau, Qiangfeng P; Zhu, Ai L; Klein, Ronald; Saw, Seang M; Wong, Tien Y

    2011-07-01

    The present study examined the effects of blood pressure on a spectrum of quantitative and qualitative retinal microvascular signs. Retinal photographs from the Singapore Malay Eye Study, a population-based cross-sectional study of 3280 (78.7% response) persons aged 40-80 years, were analyzed. Quantitative changes in the retinal vasculature (branching angle, vascular tortuosity, fractal dimension, and vascular caliber) were measured using a semi-automated computer-based program. Qualitative signs, including focal arteriolar narrowing (FAN), arteriovenous nicking (AVN), opacification of the arteriolar wall (OAW), and retinopathy (e.g., microaneurysms, retinal hemorrhages), were assessed from photographs by trained technicians. After excluding persons with diabetes and ungradable photographs, 1913 persons provided data for this analysis. In multivariable linear regression models controlling for age, sex, BMI, use of antihypertensive medication, and other factors, retinal arteriolar branching asymmetry ratio, arteriolar tortuosity, venular tortuosity, fractal dimension, arteriolar caliber, venular caliber, FAN, AVN, and retinopathy were independently associated with mean arterial blood pressure. In contrast, arteriolar/venular branching angle, venular branching asymmetry ratio and OAW were not related to blood pressure. Retinal arteriolar caliber (sβ = -0.277) and FAN (sβ = 0.170) had the strongest associations with mean arterial blood pressure, and higher blood pressure levels were associated with increasing number of both quantitative and qualitative retinal vascular signs (P trend qualitative retinal vascular signs, with the number of signs increasing with higher blood pressure levels.

  16. Preoperative assessment of microvascular invasion in hepatocellular carcinoma

    Science.gov (United States)

    Chakraborty, Jayasree; Zheng, Jian; Gönen, Mithat; Jarnagin, William R.; DeMatteo, Ronald P.; Do, Richard K. G.; Simpson, Amber L.

    2017-03-01

    Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer-related death worldwide.1 Resection or liver transplantation may be curative in patients with early-stage HCC but early recurrence is common.2, 3 Microvascular invasion (MVI) is one of the most important predictors of early recurrence.3 The identification of MVI prior to surgery would optimally select patients for potentially curative resection or liver transplant. However, MVI can only be diagnosed by microscopic assessment of the resected tumor. The aim of the present study is to apply CT-based texture analysis to identify pre-operative imaging predictors of MVI in patients with HCC. Texture features are derived from CT and analyzed individually as well as in combination, to evaluate their ability to predict MVI. A two-stage classification is employed: HCC tumors are automatically categorized into uniform or heterogenous groups followed by classification into the presence or absence of MVI. We achieve an area under the receiver operating characteristic curve (AUC) of 0.76 and accuracy of 76.7% for uniform lesions and AUC of 0.79 and accuracy of 74.06% for heterogeneous tumors. These results suggest that MVI can be accurately and objectively predicted from preoperative CT scans.

  17. Biomarker for early renal microvascular and diabetic kidney diseases.

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2017-11-01

    Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

  18. Hypertension and sexual dysfunction

    African Journals Online (AJOL)

    Review Article: Hypertension and sexual dysfunction. 117. Vol 54 No 2. S Afr Fam Pract 2012. Introduction. Hypertension is a major independent cardiovascular risk factor, and also a marker of survival risk. Quality of life during the treatment of hypertension is an important health issue, as one in every five treated patients ...

  19. Temporomandibular Joint Dysfunction

    Science.gov (United States)

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to talk, chew, and yawn. For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that travels through the face, jaw, ...

  20. Female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Wåhlin-Jacobsen, Sarah

    2016-01-01

    Female sexual dysfunction (FSD) is a controversial condition, which has prompted much debate regarding its aetiology, components, and even its existence. Our inability to work together as clinicians, psychologists, patients, and advocates hinders our understanding of FSD, and we will only improve...

  1. Mitochondrial dysfunction in epilepsy

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Kunz, W.S.

    2012-01-01

    Roč. 12, č. 1 (2012), s. 35-40 ISSN 1567-7249 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR GA309/08/0292 Institutional research plan: CEZ:AV0Z50110509 Keywords : epilepsy * mitochondrial dysfunction * neurodegeneration Subject RIV: FH - Neurology Impact factor: 4.025, year: 2012

  2. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227 ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  3. Increased prevalence of microvascular complications in type 2 diabetes patients with the metabolic syndrome.

    Science.gov (United States)

    Abdul-Ghani, Muhammad; Nawaf, Gamal; Nawaf, Fawaz; Itzhak, Baruch; Minuchin, Oscar; Vardi, Pnina

    2006-06-01

    Microvascular complications of diabetes contribute significantly to the disease morbidity. The metabolic syndrome is common among subjects with diabetes and is a very important risk factor for macrovascular complications. However, its contribution to the microvascular complication has not been assessed. To assess the risk of microvascular complications associated with the metabolic syndrome in diabetes subjects. The study group comprised 415 diabetic subjects attending a primary care clinic. The prevalence of microvascular complications was compared between 270 diabetic subjects with metabolic syndrome (NCEP-III criteria) and 145 diabetic patients without. We found that as a group, diabetic subjects with metabolic syndrome had a significantly higher frequency of microvascular-related complications than diabetic subjects without the syndrome (46.6% and 26.8% respectively, P= 0.0005). These include microalbuminuria (41.5% vs. 23.9%, P= 0.013), neuropathy (10.4% vs. 7.5%, P = 0.38), retinopathy (9.6% vs. 4.1%, P = 0.046) and leg ulcers (7.9% vs. 2.8%, P = 0.044). After adjustment for age, gender, glycemic control, disease duration, lipid profile and blood pressure, metabolic syndrome was associated with a significantly higher risk of microvascular complications: odds ratio (95% confidence interval) for nephropathy 2.27 (1.53-3.34), neuropathy 1.77 (0.79-4.0), retinopathy 3.42 (1.2-9.87), and leg ulcers 3.57 (1.08-11.95). In addition to hyperglycemia and disease duration, the metabolic syndrome is a significant risk factor for the development of microvascular complications in diabetic subjects.

  4. Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

    Science.gov (United States)

    Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

    2017-05-12

    Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were

  5. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    Directory of Open Access Journals (Sweden)

    Almeida A

    2011-08-01

    Full Text Available Laurinda Lemos1,2, Carlos Alegria3, Joana Oliveira3, Ana Machado2, Pedro Oliveira4, Armando Almeida11Life and Health Sciences Research Institute (ICVS, School of Health Sciences, Campus de Gualtar, University of Minho, Braga, Portugal; 2Hospital Center of Alto Ave, Unit of Fafe, Fafe, Portugal; 3Department of Neurosurgery, Hospital São Marcos; 4Products and Systems Engineering, Campus de Azurém, University of Minho, Guimarães, PortugalAbstract: In idiopathic trigeminal neuralgia (TN the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1 a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol], (2 the association of gabapentin (GBP and analgesic block of trigger-points with ropivacaine (ROP (GBP+ROP protocol, and (3 a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol. Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols from cases of idiopathic TN, or selected for MVD surgery (n = 22 due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug

  6. Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

    Science.gov (United States)

    Baydemir, Canan; Ural, Dilek; Karaüzüm, Kurtuluş; Balci, Sibel; Argan, Onur; Karaüzüm, Irem; Kozdağ, Güliz; Ağır, Ayşen A

    2017-07-10

    BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

  7. Dysfunctions in public psychiatric bureaucracies.

    Science.gov (United States)

    Marcos, L R

    1988-03-01

    The author describes common dysfunctions in public psychiatric organizations according to the model of bureaucracy articulated by Max Weber. Dysfunctions are divided into the categories of goal displacement, outside interference, unclear authority structure and hierarchy, and informal relations in the work place. The author emphasizes the bureaucratic nature of public psychiatry and the need for mental health professionals to understand the dysfunctions of the organizations in which they work, including the impact of these dysfunctions on the provision of quality care.

  8. Radiation induced microvascular damage in the rat spinal cord: cellular and secretory factors

    International Nuclear Information System (INIS)

    Pfeffer, M. Raphael; Siegal, Tali; Meltzer, A; Shezen, E; Ovadia, Haim

    1996-01-01

    Purpose/Objective: To investigate the short and long-term effect of radiation on micro vessel permeability, endothelin and nitric oxide production, and cellular profile in the spinal cord of rats and to evaluate the influence of recombinant human manganese superoxide dismutase (r-hMnSOD) on these effects. Materials and Methods: The thoracolumbar spinal cord of Fischer rats was irradiated to a dose of 15 Gy. At various times afterwards the rats were killed and the spinal cord was excised. Endothelin and nitric oxide synthase (NOS) activity and microvascular permeability were assayed quantitatively. Astrocytes, microglia, vascular basal membrane and neuro filaments were immunohistochemically evaluated. Results: None of the rats developed signs of neurological dysfunction. Endothelin concentrations in the spinal cord were significantly reduced 18 hours after irradiation and continued to decrease until after 10 days (p=<0.007). After 56 days endothelin concentration returned to normal and then rose to markedly elevated levels at 120 and 180 days (p=<0.002). NOS activity was reduced soon after irradiation and remained very low throughout the period of observation despite the changes in endothelin. Vascular permeability was markedly increased after 18 hours and again after 120 and 180 days. Treatment with r-hMnSOD had no effect on normal vascular permeability but abolished the increase in vascular permeability seen after irradiation. Standard microscopic examination revealed no changes in the irradiated spinal cord. Immunohistochemical stains showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p=<0.0003). An increase in astrocytic cells was seen after 180 days with an earlier short lasting peak after 14 days. No abnormalities were found in blood vessel configuration, density and diameter. Vascular basal membrane and neuro filaments were unchanged throughout the study. Conclusions: Following radiation to the spinal cord there

  9. Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney.

    Science.gov (United States)

    Kelsen, Silvia; He, Xiaochen; Chade, Alejandro R

    2012-08-15

    Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution

  10. The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function.

    Science.gov (United States)

    Al-Tahami, Belqes Abdullah Mohammad; Ismail, Ab Aziz Al-Safi; Bee, Yvonne Tee Get; Awang, Siti Azima; Salha Wan Abdul Rani, Wan Rimei; Sanip, Zulkefli; Rasool, Aida Hanum Ghulam

    2015-01-01

    Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR). 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations. 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group. 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.

  11. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission.

    Science.gov (United States)

    Zhou, Hao; Wang, Shuyi; Zhu, Pingjun; Hu, Shunying; Chen, Yundai; Ren, Jun

    2018-05-01

    Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria. Our data revealed that empagliflozin improved diabetic myocardial structure and function, preserved cardiac microvascular barrier function and integrity, sustained eNOS phosphorylation and endothelium-dependent relaxation, as well as improved microvessel density and perfusion. Further study suggested that empagliflozin exerted its effects through inhibition of mitochondrial fission in an adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent manner. Empagliflozin restored AMP-to-ATP ratio to trigger AMPK activation, suppressed Drp1 S616 phosphorylation, and increased Drp1 S637 phosphorylation, ultimately leading to inhibition of mitochondrial fission. The empagliflozin-induced inhibition of mitochondrial fission preserved cardiac microvascular endothelial cell (CMEC) barrier function through suppressed mitochondrial reactive oxygen species (mtROS) production and subsequently oxidative stress to impede CMEC senescence. Empagliflozin-induced fission loss also favored angiogenesis by promoting CMEC migration through amelioration of F-actin depolymerization. Taken together, these results indicated the therapeutic promises of empagliflozin in the treatment of pathological microvascular changes in diabetes. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission

    Directory of Open Access Journals (Sweden)

    Hao Zhou

    2018-05-01

    Full Text Available Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2 inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria. Our data revealed that empagliflozin improved diabetic myocardial structure and function, preserved cardiac microvascular barrier function and integrity, sustained eNOS phosphorylation and endothelium-dependent relaxation, as well as improved microvessel density and perfusion. Further study suggested that empagliflozin exerted its effects through inhibition of mitochondrial fission in an adenosine monophosphate (AMP-activated protein kinase (AMPK-dependent manner. Empagliflozin restored AMP-to-ATP ratio to trigger AMPK activation, suppressed Drp1S616 phosphorylation, and increased Drp1S637 phosphorylation, ultimately leading to inhibition of mitochondrial fission. The empagliflozin-induced inhibition of mitochondrial fission preserved cardiac microvascular endothelial cell (CMEC barrier function through suppressed mitochondrial reactive oxygen species (mtROS production and subsequently oxidative stress to impede CMEC senescence. Empagliflozin-induced fission loss also favored angiogenesis by promoting CMEC migration through amelioration of F-actin depolymerization. Taken together, these results indicated the therapeutic promises of empagliflozin in the treatment of pathological microvascular changes in diabetes.

  13. Is There an Association between Vitamin D Level and Microvascular Complications of Type 2 Diabetes Mellitus?

    Directory of Open Access Journals (Sweden)

    Y Simsek

    2015-09-01

    Full Text Available Objective: Vitamin D deficiency is associated with impaired glucose tolerance and the development of Type 1 and 2 diabetes mellitus.The aim of this study was to compare the 25-hydroxyvitamin D (25-OH-vitamin D levels between Type 2 diabetic patients with and without microvascular complications and healthy subjects to identify any possible associations with vitamin D levels and microvascular complications. Methods: One hundred and one patients with microvascular complications (nephropathy, retinopathy or neuropathy, 102 patients without microvascular complications and 81 healthy subjects were compared in terms of serum levels of 25-OH-vitamin-D, calcium, phosphorus, parathyroid hormone (PTH, and glycated haemoglobin (HbA1c. Results: No significant differences were found among the three groups with respect to serum calcium, phosphorus and PTH levels, and no correlation was identified between HbA1c and 25-OH-vitamin D levels. The healthy group had higher vitamin D levels than both diabetic groups, while the vitamin D levels were similar in the diabetic groups. Conclusion: Although vitamin D deficiency is more common in patients with Type 2 diabetes mellitus than healthy subjects, no relationship between vitamin D deficiency and microvascular complications of diabetes was found.

  14. Effect of acetylsalicylic acid on microvascular thrombosis in autologous breast reconstruction.

    Science.gov (United States)

    Enajat, Morteza; Aziz Mohammadi, Mujzgan; Debeij, Jan; van der Hulst, Rene R W J; Mureau, Marc A M

    2014-01-01

    Although advances in microsurgery have increased success rates of autologous breast reconstruction, microvascular thrombosis still remains a major concern as a cause of flap failure. At present, no evidence-based guidelines on pharmacological prevention of microvascular thrombosis exist. This study investigates the effect of acetylsalicylic acid on the incidence of microvascular complications in patients undergoing autologous breast reconstruction. Patients undergoing deep inferior epigastric artery perforator or free transverse rectus abdominis myocutaneous flap breast reconstruction at two academic centers in the Netherlands between 2005 and 2011 were included. Patients at one center received once daily 0.6 mL of nadroparine and 40 mg acetylsalicylic acid, while patients at the other center received 0.6 mL nadroparine only. A total of 430 consecutive patients underwent 592 breast reconstructions. No statistically significant differences were found between the two groups in the incidence of flap failure (2.8 and 2.5%), microvascular thromboembolic complications (2.6 and 3.8%), venous congestion (3.4 and 2.8%), or overall complications (28.0 and 32.3%). Hematoma tended to occur more often in the group receiving acetylsalicylic acid (9.2 and 4.7%).It was found that no protective effect of acetylsalicylic acid on microvascular complications was present. Given its known risks and the somewhat increased occurrence of hematoma in the present study, we stopped to routinely administer acetylsalicylic acid after autologous breast reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Plasmalemmal V-H+-ATPases regulate intracellular pH in human lung microvascular endothelial cells

    International Nuclear Information System (INIS)

    Rojas, Jose D.; Sennoune, Souad R.; Maiti, Debasish; Martinez, Gloria M.; Bakunts, Karina; Wesson, Donald E.; Martinez-Zaguilan, Raul

    2004-01-01

    The lung endothelium layer is exposed to continuous CO 2 transit which exposes the endothelium to a substantial acid load that could be detrimental to cell function. The Na + /H + exchanger and HCO 3 - -dependent H + -transporting mechanisms regulate intracellular pH (pH cyt ) in most cells. Cells that cope with high acid loads might require additional primary energy-dependent mechanisms. V-H + -ATPases localized at the plasma membranes (pmV-ATPases) have emerged as a novel pH regulatory system. We hypothesized that human lung microvascular endothelial (HLMVE) cells use pmV-ATPases, in addition to Na + /H + exchanger and HCO 3 - -based H + -transporting mechanisms, to maintain pH cyt homeostasis. Immunocytochemical studies revealed V-H + -ATPase at the plasma membrane, in addition to the predicted distribution in vacuolar compartments. Acid-loaded HLMVE cells exhibited proton fluxes in the absence of Na + and HCO 3 - that were similar to those observed in the presence of either Na + , or Na + and HCO 3 - . The Na + - and HCO 3 - -independent pH cyt recovery was inhibited by bafilomycin A 1 , a V-H + -ATPase inhibitor. These studies show a Na + - and HCO 3 - -independent pH cyt regulatory mechanism in HLMVE cells that is mediated by pmV-ATPases

  16. Zika Virus Infects, Activates, and Crosses Brain Microvascular Endothelial Cells, without Barrier Disruption

    Directory of Open Access Journals (Sweden)

    Michelle P. Papa

    2017-12-01

    Full Text Available Zika virus (ZIKV has been associated to central nervous system (CNS harm, and virus was detected in the brain and cerebrospinal fluids of microcephaly and meningoencephalitis cases. However, the mechanism by which the virus reaches the CNS is unclear. Here, we addressed the effects of ZIKV replication in human brain microvascular endothelial cells (HBMECs, as an in vitro model of blood brain barrier (BBB, and evaluated virus extravasation and BBB integrity in an in vivo mouse experimental model. HBMECs were productively infected by African and Brazilian ZIKV strains (ZIKVMR766 and ZIKVPE243, which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKVMR766 promoted earlier cellular death, in comparison to ZIKVPE243, but infection with either strain did not result in enhanced endothelial permeability. Despite the maintenance of endothelial integrity, infectious virus particles crossed the monolayer by endocytosis/exocytosis-dependent replication pathway or by transcytosis. Remarkably, both viruses' strains infected IFNAR deficient mice, with high viral load being detected in the brains, without BBB disruption, which was only detected at later time points after infection. These data suggest that ZIKV infects and activates endothelial cells, and might reach the CNS through basolateral release, transcytosis or transinfection processes. These findings further improve the current knowledge regarding ZIKV dissemination pathways.

  17. Segmental and total microvascular resistances during hemorrhagic hypotension in rabbit omentum.

    Science.gov (United States)

    Firrell, J C; Lipowsky, H H; Usami, S; Chien, S

    1984-09-01

    Single input-output microvascular modules in the rabbit omentum were studied to quantitate total modular resistance (RT) and the changes in resistance of successive serial segments (Rseg) during hemorrhagic hypotension (55 mmHg for 1 h). RT was calculated from the pressure drop between input and output vessels and the total flow through the module. Changes in Rseg were estimated from alterations in single microvessel hindrance (1/diam4) for selected microvessels within a module together with a correction for flow redistribution within each segment derived from changes in the proportion of total flow. Mean RT increased to 2.1 times control within the first 10 min of systemic hypotension and gradually declined over 1 h. Response of Rseg varied in different generations of microvessels (arterioles and venules subdivided by size). Rseg for arterioles and venules less than 30 microns, but not that for arterioles and venules greater than 30 microns, showed comparable or greater changes than RT. Calculated differences between RT and the summed Rseg of measured segments suggest that the unmeasured Rseg in capillaries and blood rheological parameters may have significantly influenced changes in RT during hemorrhagic hypotension.

  18. Organic anion transporting polypeptide 2 transports valproic acid in rat brain microvascular endothelial cells.

    Science.gov (United States)

    Guo, Yi; Jiang, Li

    2016-07-01

    Abnormal drug transporter expression or function in the brain may lead to decreased concentrations of antiepileptic drugs (AEDs) in the central nervous system in patients with drug-resistant epilepsy. We previously showed the influx transporter organic anion transport polypeptide 2 (Oatp2) was expressed in rat brain microvascular endothelial cells (BMECs). Seizures decrease expression of Oatp2, but it remains unclear whether Oatp2 transports AEDs. In this study, we utilized rat BMECs as an in vitro model of the blood-brain barrier (BBB) to study Oatp2-mediated transport of valproic acid (VPA), the most common clinically used AEDs. In vivo injection of pregnenolone-16-carbonitrile was used to induce high expression of Oatp2 in isolated BMECs. Small interfering RNA treatment was used to silence Oatp2, and uptake of VPA was assessed. Increased expression of Oatp2 in BMECs increased the uptake of VPA, while inhibition of Oatp2 reduced VPA uptake. This study indicates Oatp2 transports VPA across the BBB, and suggests altered Oatp2 expression may contribute to resistance to VPA in patients with drug-resistant epilepsy.

  19. Clinical correlates of the spectrum of lung microvascular injury in human noncardiac edema

    International Nuclear Information System (INIS)

    Sibbald, W.J.; Driedger, A.A.; Wells, G.A.; Koval, J.J.

    1983-01-01

    Researchers measured the clearance from blood to pulmonary edema fluid of a small molecular researchersight hydrophilic radiotracer, Indium-111-DTPA (In-DTPA) and a larger molecular researchrsight radiotracer, Iodine-125-HSA (I-HSA), in patients with pulmonary edema on either a cardiac or noncardiac (permeability) basis. In previous investigations, researchers had noted an apparent relationship between the magnitude of clearance of I-HSA across the alveolocapillary membrane and the severity of noncardiac pulmonary edema. In this study, researchers were able to distinguish at least 2 distinct groups of patients with noncardiac pulmonary edema. Patients with the greatest damage to the alveolo-capillary exchanging membrane, defined by the flux of I-HSA from blood to edema fluid, were significantly differentiated from those with a lesser microvascular injury on the basis of higher mean heart rate (HR), temperature, cardiac index (CI), pulmonary artery pressures, right ventricular stroke work index (RVSWI), and a lower mean total white blood cell count (WBC), among others. Therefore, noncardiac pulmonary edema is characterized by a spectrum of permeability injury to the pulmonary microvasculature which seems to parallel other measurable indices of the severity of the systemic response to the illness

  20. Zika Virus Infects, Activates, and Crosses Brain Microvascular Endothelial Cells, without Barrier Disruption

    Science.gov (United States)

    Papa, Michelle P.; Meuren, Lana M.; Coelho, Sharton V. A.; Lucas, Carolina G. de Oliveira; Mustafá, Yasmin M.; Lemos Matassoli, Flavio; Silveira, Paola P.; Frost, Paula S.; Pezzuto, Paula; Ribeiro, Milene R.; Tanuri, Amilcar; Nogueira, Mauricio L.; Campanati, Loraine; Bozza, Marcelo T.; Paula Neto, Heitor A.; Pimentel-Coelho, Pedro M.; Figueiredo, Claudia P.; de Aguiar, Renato S.; de Arruda, Luciana B.

    2017-01-01

    Zika virus (ZIKV) has been associated to central nervous system (CNS) harm, and virus was detected in the brain and cerebrospinal fluids of microcephaly and meningoencephalitis cases. However, the mechanism by which the virus reaches the CNS is unclear. Here, we addressed the effects of ZIKV replication in human brain microvascular endothelial cells (HBMECs), as an in vitro model of blood brain barrier (BBB), and evaluated virus extravasation and BBB integrity in an in vivo mouse experimental model. HBMECs were productively infected by African and Brazilian ZIKV strains (ZIKVMR766 and ZIKVPE243), which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKVMR766 promoted earlier cellular death, in comparison to ZIKVPE243, but infection with either strain did not result in enhanced endothelial permeability. Despite the maintenance of endothelial integrity, infectious virus particles crossed the monolayer by endocytosis/exocytosis-dependent replication pathway or by transcytosis. Remarkably, both viruses' strains infected IFNAR deficient mice, with high viral load being detected in the brains, without BBB disruption, which was only detected at later time points after infection. These data suggest that ZIKV infects and activates endothelial cells, and might reach the CNS through basolateral release, transcytosis or transinfection processes. These findings further improve the current knowledge regarding ZIKV dissemination pathways. PMID:29312238

  1. Interactive virtual simulation using a 3D computer graphics model for microvascular decompression surgery.

    Science.gov (United States)

    Oishi, Makoto; Fukuda, Masafumi; Hiraishi, Tetsuya; Yajima, Naoki; Sato, Yosuke; Fujii, Yukihiko

    2012-09-01

    The purpose of this paper is to report on the authors' advanced presurgical interactive virtual simulation technique using a 3D computer graphics model for microvascular decompression (MVD) surgery. The authors performed interactive virtual simulation prior to surgery in 26 patients with trigeminal neuralgia or hemifacial spasm. The 3D computer graphics models for interactive virtual simulation were composed of the brainstem, cerebellum, cranial nerves, vessels, and skull individually created by the image analysis, including segmentation, surface rendering, and data fusion for data collected by 3-T MRI and 64-row multidetector CT systems. Interactive virtual simulation was performed by employing novel computer-aided design software with manipulation of a haptic device to imitate the surgical procedures of bone drilling and retraction of the cerebellum. The findings were compared with intraoperative findings. In all patients, interactive virtual simulation provided detailed and realistic surgical perspectives, of sufficient quality, representing the lateral suboccipital route. The causes of trigeminal neuralgia or hemifacial spasm determined by observing 3D computer graphics models were concordant with those identified intraoperatively in 25 (96%) of 26 patients, which was a significantly higher rate than the 73% concordance rate (concordance in 19 of 26 patients) obtained by review of 2D images only (p computer graphics model provided a realistic environment for performing virtual simulations prior to MVD surgery and enabled us to ascertain complex microsurgical anatomy.

  2. Red blood cell count as an indicator of microvascular complications in Chinese patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Wang ZS

    2013-05-01

    Full Text Available Zhan-Sheng Wang,1,2 Zhan-Chun Song,1 Jing-Hui Bai,1 Fei Li,3 Tao Wu,1 Ji Qi,2 Jian Hu11Department of Cardiology, First Affiliated Hospital of China Medical University, 2Second Department of Cardiology, Fourth People's Hospital of Shenyang, Shenyang, 3Department of Cardiology, Shenzhou Hospital of Shenyang Medical College, Shenyang, People's Republic of ChinaBackground: Rheological disorders of red blood cells (RBC and decreased RBC deformability have been involved in the development of diabetic microangiopathy. However, few studies have evaluated the association of RBC count with microvascular complications in patients with type 2 diabetes mellitus (T2DM. The purpose of this study was to investigate the association of RBC count with microvascular complications in patients with T2DM.Methods: This study involved 369 patients with T2DM: 243 with one or more microvascular complications and 126 without microvascular complications. Anticoagulated blood was collected and analyzed in an automated blood cell counter. The presence of risk factors for microvascular complications was determined.Results: The proportion of patients with microvascular complications increased as the RBC count decreased (P < 0.001. After adjustment for known risk factors for microvascular complications by logistic regression analysis, lower quartiles of RBC count were associated with a higher risk of microvascular complications compared with the reference group composed of the highest quartile (first quartile, odds ratio 4.98, 95% confidence interval 1.54–6.19, P = 0.008; second quartile, odds ratio 3.21, 95% confidence interval 1.17–5.28, P = 0.024.Conclusion: A decreased RBC count is associated with microvascular complications in Chinese patients with T2DM. The RBC count is a potential marker to improve further the ability to identify diabetic patients at high risk of microvascular complications.Keywords: red blood cell count, microvascular complication, type 2 diabetes

  3. Renin-angiotensin-aldosterone system blockers for heart failure with reduced ejection fraction or left ventricular dysfunction: Network meta-analysis.

    Science.gov (United States)

    Xie, Wuxiang; Zheng, Fanfan; Song, Xiaoyu; Zhong, Baoliang; Yan, Li

    2016-02-15

    Renin-angiotensin-aldosterone system (RAAS) blockers are effective therapies for heart failure and reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVD). We aimed to assess the efficacy and safety of RAAS blockers in these patients. We searched MEDLINE, EMBASE, and Cochrane Library in May 2015. Twenty-one double-blind randomized controlled trials (RCTs) with 69,229 patients were included this network meta-analysis. Compared with placebo, an angiotensin receptor-neprilysin inhibitor (ARNI) had the highest probability of reducing all-cause mortality (odds ratio [OR]=0.67, 95% credible interval [CrI]: 0.48-0.86), followed by an aldosterone receptor antagonist (ARA, OR=0.74, 95% CrI: 0.62-0.88) and an angiotensin-converting enzyme inhibitor (ACEI, OR=0.80, 95% CrI: 0.71-0.89). The most efficacious therapy for preventing heart failure hospitalization was ARNI (OR=0.55, 95% CrI: 0.40-0.71), followed by combination therapy with an angiotensin II receptor blocker (ARB) plus an ACEI (OR=0.61, 95% CrI: 0.49-0.75), then an ACEI alone (OR=0.69, 95% CrI: 0.61-0.77). Sensitivity analysis restricted to nine RCTs with a high background use of ACEI and/or ARB (>80%) indicated that adding an ARA to current standard therapy significantly reduced mortality (OR=0.73, 95% CrI: 0.51-0.95) and hospitalization risk (OR=0.67, 95% CrI: 0.47-0.87), but did not significantly increase the discontinuation risk (OR=1.29, 95% CrI: 0.83-2.31). ARNI has the highest probability of being the most efficacious therapy for HFrEF in reducing death and hospitalization for heart failure. ARA has the most favorable benefit-risk profile as an adjunct to background ACEI and/or ARB therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. ASSOCIATION OF GENE POLYMORPHISMS OF THE RENIN-ANGIOTENSIN SYSTEM AND ENDOTHELIAL DYSFUNCTION WITH DEVELOPMENT AND SEVERITY OF PORTAL HYPERTENSION IN PATIENTS WITH CHRONIC HEPATITIS C

    Directory of Open Access Journals (Sweden)

    O. V. Taratina

    2016-01-01

    Full Text Available Background: At present, much attention is paid to genetic factors explaining the clinical course of chronic hepatitis C. Aim: To evaluate an association of the gene polymorphisms involved in the formation of endothelial dysfunction (NOS3 894G/T, CYBA 242C/T, MTHFR 677C/T and encoding components of the renin-angiotensin system (ATR1 1166A/C, AGT (-6G/T and 235M/T with development and severity of portal hypertension syndrome in patients with chronic hepatitis C. Materials and methods: 162 patients with chronic hepatitis C and HCV-related cirrhosis (114 women and 48 men were divided into the following groups: no portal hypertension (n = 98, "compensated" (n = 19 and "decompensated" (n = 45 portal hypertension. The gene polymorphisms were assessed by molecular genetic methods. Results: TT genotype of CYBA was more common in patients with portal hypertension than in those without (odds ratio (OR for TT = 3.59, p = 0.031. This difference becomes larger when comparing the decompensated portal hypertension group with the no portal hypertension group (OR TT = 5.46, p = 0.009. Other gene polymorphisms were not associated with development or decompensation of portal hypertension. Multivariate analysis of the impact of genetic, clinical and demographic factors showed that portal hypertension was associated primarily with patients age at the time of the study (Wald's х2 = 14.99 and with their body mass index (Wald's х2 = 4.35. After exclusion of these population-wide risk factors from the model, the development of portal hypertension correlated with the carriage of 235TT genotype of CYBA (Wald's х2 = 6.07, OR = 4.29 and (-6AA genotype AGT (Wald's х2 = 4.73, OR = 4.13, as well as with the lack of protective 235TT genotype AGT (Wald's х2 = 4.06, OR = 0.33. The combined effects of the studied gene polymorphisms on decompensation of the portal hypertension in patients with chronic HCV infection were similar. Conclusion: The development and increase in

  5. [Thyroid dysfunction and amiodarone].

    Science.gov (United States)

    Lima, Jandira; Carvalho, Patrícia; Molina, M Auxiliadora; Rebelo, Marta; Dias, Patrícia; Vieira, José Diniz; Costa, José M Nascimento

    2013-02-01

    Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

  6. What is regressive autism and why does it occur? Is it the consequence of multi-systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature?

    Science.gov (United States)

    Ewing, Graham E

    2009-07-01

    There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the excretory system influences elimination of heavy metals and facilitates their accumulation and subsequent manifestation as neurotoxins: the long-term consequences of which would lead to neurodegeneration, cognitive and developmental problems. It may also influence regulation of neural hyperthermia. This article explores the issues and concludes that sensory dysfunction and systemic failure, manifested as autism, is the inevitable consequence arising from subtle DNA alteration and consequently from the overuse of vaccines.

  7. [Macrovascular and microvascular complications in type 2 diabetes patients].

    Science.gov (United States)

    Rosolová, H; Petrlová, B; Simon, J; Sifalda, P; Sípová, I; Sefrna, F

    2008-03-01

    The prevalence of chronic vascular complications is higher in patients with type 2 diabetes mellitus (DM2). The objective of our cross-sectional study was to assess the incidence and types of macrovascular (MVC) and microvascular (mvc) complications and to analyse their relation to the different risk factors and biomarkers in order to improve their prevention. 415 patients (219 men and 196 women) with an average age of 66 +/- 9 years enrolled in the study. A total of 95% of patients with DM2 had a history of hypertension, 27% had MVC (of which 55% had ischaemic heart disease), and 54% had mvc (ofwhich 95% had diabetic nephropathy). The patients with vascular complications were significantly older and had a longer history of DM2; they did not differ for their systolic blood pressure, but had a higher pulse pressure and took more antihypertensives. They did not differ for their lipid levels or the respective therapy. Diabetic patients with MVC and mvc had higher insulin resistance, higher plasmatic levels of total homocysteine and a higher incidence ofalbuminuria or proteinuria. The factors which significantly and independently associated with MVC were male gender, age over 60 years, higher hs-C-reactive protein (hs-CRP) exceeding 1 mg/l, glycaemia over 5.6 mmol/l, lower diastolic blood pressure and lower HDL-cholesterol; mvc associated with higher age over 60 years, a history of DM2 exceeding 8 years, and hs-CRP above 1 mg/l. Our results show that patients with DM2 have a high incidence ofvascular complications significantly associated with age, DM2 history and higher hs-CRP, irrespective of the other monitored parametres.

  8. Teflon granulomas mimicking cerebellopontine angle tumors following microvascular decompression.

    Science.gov (United States)

    Deep, Nicholas L; Graffeo, Christopher S; Copeland, William R; Link, Michael J; Atkinson, John L; Neff, Brian A; Raghunathan, Aditya; Carlson, Matthew L

    2017-03-01

    To report two patients with a history of microvascular decompression (MVD) for hemifacial spasm who presented with Teflon granulomas (TG) mimicking cerebellopontine angle (CPA) tumors and to perform a systematic review of the English-language literature. Case series at a single tertiary academic referral center and systematic review. Retrospective chart review with analysis of clinical, radiological, and histopathological findings. Systematic review using PubMed, Embase, MEDLINE, and Web of Science databases. Two patients with large skull base TGs mimicking CPA tumors clinically and radiographically were managed at the authors' institution. The first presented 4 years after MVD with asymmetrical sensorineural hearing loss, multiple progressive cranial neuropathies, and brainstem edema due to a growing TG. Reoperation with resection of the granuloma confirmed a foreign-body reaction consisting of multinucleated giant cells containing intracytoplasmic Teflon particles. The second patient presented 11 years after MVD with asymmetrical sensorineural hearing loss and recurrent hemifacial spasm. No growth was noted over 2 years, and the patient has been managed expectantly. Only one prior case of TG after MVD for hemifacial spasm has been reported in the English literature. TG is a rare complication of MVD for hemifacial spasm. The diagnosis should be suspected in patients presenting with a new-onset enhancing mass of the CPA after MVD, even when performed decades earlier. A thorough clinical and surgical history is critical toward establishing an accurate diagnosis to guide management and prevent unnecessary morbidity. Surgical intervention is not required unless progressive neurologic complications ensue. 4 Laryngoscope, 127:715-719, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Reperfusion ventricular arrhythmia bursts identify larger infarct size in spite of optimal epicardial and microvascular reperfusion using cardiac magnetic resonance imaging

    NARCIS (Netherlands)

    van der Weg, Kirian; Kuijt, Wichert J.; Bekkers, Sebastiaan C. A. M.; Tijssen, Jan G. P.; Green, Cynthia L.; Lemmert, Miguel E.; Krucoff, Mitchell W.; Gorgels, Anton P. M.

    2017-01-01

    Ventricular arrhythmia (VA) bursts following recanalisation in acute ST-elevation myocardial infarction (STEMI) are related to larger infarct size (IS). Inadequate microvascular reperfusion, as determined by microvascular obstruction (MVO) using cardiac magnetic resonance imaging (CMR), is also

  10. Pattern of Presentation of Multiple Organ Dysfunction Syndrome in ...

    African Journals Online (AJOL)

    Background: Multiple organ dysfunction syndrome is the sequential failure of several organ systems after a trigger event, like sepsis, massive transfusions, burns, trauma and cardiogenic shock. Aim and Objectives- The pattern of presentation of multiple organ dysfunction and the risk factors associated with multiple organ ...

  11. Postinjury Inflammation and Organ Dysfunction.

    Science.gov (United States)

    Sauaia, Angela; Moore, Frederick A; Moore, Ernest E

    2017-01-01

    The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early proinflammation via innate immune system activation may cause early OD, whereas antiinflammation, via inhibition of the adaptive immune system and apoptosis, may induce immunoparalysis, impaired healing, infections, and late OD. Patients discharged with low-level OD may develop the persistent inflammation-immunosuppression catabolism syndrome. Although the incidence of multiple organ failure has decreased over time, it remains morbid, lethal, and resource intensive. However, single OD, especially acute lung injury, remains frequent. Treatment is limited, and prevention remains the mainstay strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Microvascular Branching as a Determinant of Blood Flow by Intravital Particle Imaging Velocimetry

    Science.gov (United States)

    Parsons-Wingerter, Patricia; McKay, Terri L.; Vickerman, Mary B.; Wernet, Mark P.; Myers, Jerry G.; Radhakrishnan, Krishnan

    2007-01-01

    The effects of microvascular branching on blood flow were investigated in vivo by microscopic particle imaging velocimetry (micro-PIV). We use micro-PIV to measure blood flow by tracking red blood cells (RBC) as the moving particles. Velocity flow fields, including flow pulsatility, were analyzed for the first four branching orders of capillaries, postcapillary venules and small veins of the microvascular network within the developing avian yolksac at embryonic day 5 (E5). Increasing volumetric flowrates were obtained from parabolic laminar flow profiles as a function of increasing vessel diameter and branching order. Maximum flow velocities increased approximately twenty-fold as the function of increasing vessel diameter and branching order compared to flow velocities of 100 - 150 micron/sec in the capillaries. Results from our study will be useful for the increased understanding of blood flow within anastomotic, heterogeneous microvascular networks.

  13. Microvascular Complications Associated With Rapid Improvements in Glycemic Control in Diabetes.

    Science.gov (United States)

    Gibbons, Christopher H; Goebel-Fabbri, Ann

    2017-07-01

    Aggressive glycemic control has become the standard clinical approach to diabetes care. Unintended consequences have included the development of microvascular complications that are related to the rapidity of glycemic improvement. Diabetic neuropathy may develop in up to 10% of individuals secondary to aggressive glycemic control. The neuropathy is predominantly small fiber sensory and autonomic, and the severity of the neuropathy is tied to the change in the glycosylated hemoglobin A1C. Other microvascular complications such as retinopathy and nephropathy are common and may occur in parallel with the neuropathy. Eating disorders are a common comorbid risk factor. Individuals with uncontrolled diabetes for prolonged periods, particularly those with a history of eating disorders involving insulin restriction for calorie purging, are at high risk for developing treatment-induced microvascular complications. Gradual glycemic improvements should be encouraged but future research is needed to optimize treatment and prevention strategies.

  14. Dysfunctional uterine bleedings of a climacteric period

    International Nuclear Information System (INIS)

    Prilepskaya, V.N.

    1993-01-01

    Climacteric period of some women is complicated by dysfunctional uterine bleedings (DUB). Bearing in mind the fact that DUBS are caused by disorder of estrin rhysmic secretion, the paper presents the methods of differential diagnostics for investigations into functional disorders in the hypothalamus -hypophysis - ovaries - uterus system. The preference is given to roentgenologic and radioimmunologic diagnostic methods

  15. The effect of exercise training on cutaneous microvascular reactivity: A systematic review and meta-analysis.

    Science.gov (United States)

    Lanting, Sean M; Johnson, Nathan A; Baker, Michael K; Caterson, Ian D; Chuter, Vivienne H

    2017-02-01

    This study aimed to review the efficacy of exercise training for improving cutaneous microvascular reactivity in response to local stimulus in human adults. Systematic review with meta-analysis. A systematic search of Medline, Cinahl, AMED, Web of Science, Scopus, and Embase was conducted up to June 2015. Included studies were controlled trials assessing the effect of an exercise training intervention on cutaneous microvascular reactivity as instigated by local stimulus such as local heating, iontophoresis and post-occlusive reactive hyperaemia. Studies where the control was only measured at baseline or which included participants with vasospastic disorders were excluded. Two authors independently reviewed and selected relevant controlled trials and extracted data. Quality was assessed using the Downs and Black checklist. Seven trials were included, with six showing a benefit of exercise training but only two reaching statistical significance with effect size ranging from -0.14 to 1.03. The meta-analysis revealed that aerobic exercise had a moderate statistically significant effect on improving cutaneous microvascular reactivity (effect size (ES)=0.43, 95% CI: 0.08-0.78, p=0.015). Individual studies employing an exercise training intervention have tended to have small sample sizes and hence lacked sufficient power to detect clinically meaningful benefits to cutaneous microvascular reactivity. Pooled analysis revealed a clear benefit of exercise training on improving cutaneous microvascular reactivity in older and previously inactive adult cohorts. Exercise training may provide a cost-effective option for improving cutaneous microvascular reactivity in adults and may be of benefit to those with cardiovascular disease and metabolic disorders such as diabetes. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  16. The effects of Secondhand Smoke (SHS) exposure on microvascular endothelial function among healthy women.

    Science.gov (United States)

    Sanip, Zulkefli; Hanaffi, Siti Hajar Mohd; Ahmad, Imran; Yusoff, Siti Suhaila Mohd; Rasool, Aida Hanum Ghulam; Yusoff, Harmy Mohamed

    2015-01-01

    Studies have demonstrated that secondhand smoke (SHS) exposure could impair endothelial function. However, the effect of SHS exposure specifically on microvascular endothelial function is not well understood. This study aimed to determine the effects of SHS exposure on microvascular endothelial function among non-smoking, generally healthy women. We studied 127 women; and based on their hair nicotine levels measured using gas chromatography-mass spectrometry, 25 of them were categorized as having higher hair nicotine levels, 25 were grouped as having lower hair nicotine and 77 women were grouped into the non-detected group. The non-detected group did not have detectable levels of hair nicotine. Anthropometry, blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured accordingly. Microvascular endothelial function was assessed non-invasively using laser Doppler fluximetry and the process of iontophoresis involving acetylcholine and sodium nitroprusside as endothelium-dependent and endothelium-independent vasodilators respectively. The mean hair nicotine levels for higher and lower hair nicotine groups were 0.74 (1.04) and 0.05 (0.01) ng/mg respectively. There were no significant differences in anthropometry, BP, lipid profile and hsCRP between these groups. There were also no significant differences in the microvascular perfusion and endothelial function between these groups. In this study, generally healthy non-smoking women who have higher, lower and non-detected hair nicotine levels did not show significant differences in their microvascular endothelial function. Low levels of SHS exposure among generally healthy non-smoking women may not significantly impair their microvascular endothelial function.

  17. Microvascular endothelial function and cognitive performance: The ELSA-Brasil cohort study.

    Science.gov (United States)

    Brant, Luisa; Bos, Daniel; Araujo, Larissa Fortunato; Ikram, M Arfan; Ribeiro, Antonio Lp; Barreto, Sandhi M

    2018-02-01

    Impaired microvascular endothelial function may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent. Our objective is to investigate the relation of microvascular endothelial function to cognitive performance in the ELSA-Brasil cohort study. A total of 1521 participants from ELSA-Brasil free of dementia underwent peripheral arterial tonometry (PAT) to quantify microvascular endothelial function (PAT-ratio and mean baseline pulse amplitude (BPA)) and cognitive tests that covered the domains of memory, verbal fluency, and executive function at baseline. Cognitive tests in participants aged 55 years old and above were repeated during the second examination (mean follow-up: 3.5 (0.3) years). Linear regression and generalized linear models were used to evaluate the association between endothelial function, global cognitive performance, and performance on specific cognitive domains. In unadjusted cross-sectional analyses, we found that BPA and PAT-ratio were associated with worse global cognitive performance (mean difference for BPA: -0.07, 95% CI: -0.11; -0.03, p<0.01; mean difference for PAT-ratio: 0.11, 95% CI: 0.01; 0.20, p=0.02), worse performance on learning, recall, and word recognition tests (BPA: -0.87, 95% CI: -1.21; -0.52, p<0.01; PAT-ratio: 1.58, 95% CI: 0.80; 2.36, p<0.01), and only BPA was associated with worse performance in verbal fluency tests (-0.70, 95% CI: -1.19; -0.21, p<0.01). Adjustments for age, sex, and level of education rendered the associations statistically non-significant. Longitudinally, there was no association between microvascular endothelial and cognitive functions. The associations between microvascular endothelial function and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may be of limited value with regard to preclinical cognitive deficits.

  18. Tibia Bone Microvascular Flow Dynamics as Compared to Anterior Tibial Artery Flow During Body Tilt.

    Science.gov (United States)

    Becker, Rachel L; Siamwala, Jamila H; Macias, Brandon R; Hargens, Alan R

    2018-04-01

    We compared microvascular and macrovascular blood flows of the tibia and anterior tibial artery during graded whole-body tilt. We hypothesized equal responses for bone microvascular and macrovascular blood flows during varying angles of tilt. There were 18 volunteers who were randomly positioned in the following postures: supine, 15° head-up tilt, 6° head-up tilt, 6° head-down tilt, and 15° head-down tilt using an inversion table with reference to seated posture (baseline control). Ultrasonography quantified anterior tibial arterial diameter and peak systolic velocity, enabling calculation of macrovascular blood flow to the tibia. Tibial bone microvascular blood flow was measured noninvasively using photoplethysmography in the same leg. Transitioning from a seated position to a supine position, macrovascular blood flow did not change significantly (1.81 ± 1.18 to 2.80 ± 1.74cm 3 · s-1). However, bone microvascular flow increased significantly (0.36 ± 0.23 to 1.11 ± 0.79 V) from the seated to the supine position. Transitioning from a seated posture to 15° head-down tilt, both arterial macrovascular and bone microvascular flows increased significantly (1.81 ± 1.18 to 3.32 ± 2.08 cm3 · s-1 and 0.36 ± 0.23 V to 2.99 ± 2.71 V, respectively). The normalized flow for microvascular blood flow as a function of body tilt was significantly greater than that for macrovascular blood flow at 6° and 15° head-down tilt. These data do not support our hypothesis that bone microvascular flow and arterial macrovascular flow share equal responses to altered body tilt. Therefore, for a given decrease in local blood pressure in the leg with head-down body tilt, the magnitude of increase in blood flow is greater in the microcirculation as compared to the feeding artery.Becker RL, Siamwala JH, Macias BR, Hargens AR. Tibia bone microvascular flow dynamics as compared to anterior tibial artery flow during body tilt. Aerosp Med Hum Perform. 2018; 89(4):357-364.

  19. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

    2014-01-01

    The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

  20. Up-to-date Doppler techniques for breast tumor vascularity: superb microvascular imaging and contrast-enhanced ultrasound.

    Science.gov (United States)

    Park, Ah Young; Seo, Bo Kyoung

    2018-04-01

    Ultrasonographic Doppler techniques have improved greatly over the years, allowing more sophisticated evaluation of breast tumor vascularity. Superb microvascular imaging (SMI) and contrast-enhanced ultrasound (CEUS) with second-generation contrast agents are two representative up-to-date techniques. SMI is a sensitive Doppler technique that adopts an intelligent filter system to separate low-flow signals from artifacts. With the development of second-generation contrast agents, CEUS has also emerged as a useful Doppler technique for evaluating tumor microcirculation. Both techniques can improve the diagnostic performance of gray-scale ultrasonography by providing vascular information useful not only for the morphologic assessment of microvessels, but also for the quantitative analysis of perfusion. In this review, we explain the imaging principles and previous research underlying these two vascular techniques, and describe our clinical experiences.

  1. Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

    DEFF Research Database (Denmark)

    Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf

    2015-01-01

    migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation......, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface....... Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. RESULTS: We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS...

  2. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Erickson Michelle A

    2011-10-01

    LRP-1 were upregulated by LPS. Conclusions Our results show that cultured mouse brain microvascular pericytes secrete cytokines, chemokines, and nitric oxide and respond to the innate immune system stimulator LPS. These immune properties of pericytes are likely important in their communication within the neurovascular unit and provide a mechanism by which they participate in neuroinflammatory processes in brain infections and neurodegenerative diseases.

  3. Diastolic dysfunction in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Wiese, Signe Skovgaard; Halgreen, Hanne

    2016-01-01

    stiffness of the cirrhotic heart may decrease the compliance and result in DD. The prevalence of DD in cirrhotic patients averages about 50 %. It can be evaluated by transmitral Doppler echocardiography, tissue Doppler echocardiography, and cardiac magnetic resonance imaging. There seems to be a relation...... between DD and the severity of liver dysfunction and the presence of ascites. After liver transplantation, DD worsens the prognosis and increases the risk of graft rejection, but DD improves after few months. Insertion of a transjugular intrahepatic portosystemic shunt increases left ventricular diastolic...

  4. GABAergic dysfunction in pediatric neuro-developmental disorders

    Directory of Open Access Journals (Sweden)

    Constance L Smith-Hicks

    2013-12-01

    Full Text Available The GABAergic system is central to the development and functional maturation of the nervous system. Emerging evidence support the role of GABAergic dysfunction in neuro-developmental disorders. This review presents the molecules and mechanisms that underlie GABA system dysfunction in several neuro-developmental disorders presenting in childhood. The impact on synaptic plasticity, neuronal circuit function and behavior, followed by targeted treatment strategies are discussed.

  5. Managing female sexual dysfunction.

    Science.gov (United States)

    Buster, John E

    2013-10-01

    Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article's most important note: how to initiate the conversation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-κB pathway in mouse brain microvascular endothelial cells

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    Lin Chih-Chung

    2013-01-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 is a proinflammatory mediator and elevated in the regions of several brain injury and inflammatory diseases. The deleterious effects of ET-1 on endothelial cells may aggravate brain inflammation mediated through the regulation of cyclooxygenase-2 (COX-2/prostaglandin E2 (PGE2 system in various cell types. However, the signaling mechanisms underlying ET-1-induced COX-2 expression in brain microvascular endothelial cells remain unclear. Herein we investigated the effects of ET-1 in COX-2 regulation in mouse brain microvascular endothelial (bEnd.3 cells. Results The data obtained with Western blotting, RT-PCR, and immunofluorescent staining analyses showed that ET-1-induced COX-2 expression was mediated through an ETB-dependent transcriptional activation. Engagement of Gi- and Gq-protein-coupled ETB receptors by ET-1 led to phosphorylation of ERK1/2, p38 MAPK, and JNK1/2 and then activated transcription factor NF-κB. Moreover, the data of chromatin immunoprecipitation (ChIP and promoter reporter assay demonstrated that the activated NF-κB was translocated into nucleus and bound to its corresponding binding sites in COX-2 promoter, thereby turning on COX-2 gene transcription. Finally, up-regulation of COX-2 by ET-1 promoted PGE2 release in these cells. Conclusions These results suggested that in mouse bEnd.3 cells, activation of NF-κB by ETB-dependent MAPK cascades is essential for ET-1-induced up-regulation of COX-2/PGE2 system. Understanding the mechanisms of COX-2 expression and PGE2 release regulated by ET-1/ETB system on brain microvascular endothelial cells may provide rationally therapeutic interventions for brain injury or inflammatory diseases.

  7. Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells.

    Science.gov (United States)

    McCarthy, Ryan C; Kosman, Daniel J

    2014-01-01

    We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a cell-derived barrier. We found that iron efflux from hBMVEC through the ferrous iron permease ferroportin (Fpn) was stimulated by secretion of the soluble form of the multi-copper ferroxidase, ceruloplasmin (sCp) from the co-cultured C6 cells. Reciprocally, expression of sCp mRNA in the C6 cells was increased by neighboring hBMVEC. In addition, data indicate that C6 cell-secreted hepcidin stimulates internalization of hBMVEC Fpn but only when the end-feet projections characteristic of this glia-derived cell line are proximal to the endothelial cells. This hepcidin-dependent loss of Fpn correlated with knock-down of iron efflux from the hBMVEC; this result was consistent with the mechanism by which hepcidin regulates iron efflux in mammalian cells. In summary, the data support a model of iron trafficking across the BBB in which the capillary endothelium induce the underlying astrocytes to produce the ferroxidase activity needed to support Fpn-mediated iron efflux. Reciprocally, astrocyte proximity modulates the effective concentration of hepcidin at the endothelial cell membrane and thus the surface expression of hBMVEC Fpn. These results are independent of the source of hBMVEC iron (transferrin or non-transferrin bound) indicating that the model developed here is broadly applicable to brain iron homeostasis.

  8. Hepatitis C Virus-Induced Mitochondrial Dysfunctions

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    Birke Bartosch

    2013-03-01

    Full Text Available Chronic hepatitis C is characterized by metabolic disorders and a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that lead in the long term to hepatocellular carcinoma. Many lines of evidence suggest that mitochondrial dysfunctions, including modification of metabolic fluxes, generation and elimination of oxidative stress, Ca2+ signaling and apoptosis, play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV proteins localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory, probably due to the use of artificial expression and replication systems. In vivo studies are hampered by the fact that innate and adaptive immune responses will overlay mitochondrial dysfunctions induced directly in the hepatocyte by HCV. Thus, the molecular aspects underlying HCV-induced mitochondrial dysfunctions and their roles in viral replication and the associated pathology need yet to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems.

  9. Client attributions for sexual dysfunction.

    Science.gov (United States)

    Fichten, C S; Spector, I; Libman, E

    1988-01-01

    This investigation examined attributions for sexual dysfunctions made by 63 individuals and 21 of their partners who presented at a sex therapy service for the following problems: erectile dysfunction, premature ejaculation, and female orgasmic dysfunctions. All participants completed measures of marital adjustment, locus of control, depression and a questionnaire which assessed: attributions of responsibility for the sexual problem, perceived control over sexual functioning, distress, effort made to improve the sexual relationship, and expectations about the efficacy of sex therapy for the problem. Results indicate that both identified patients and their partners, regardless of the dysfunction, blamed the sexual problem on the "dysfunctional individual" rather than on the circumstances or the partner. With respect to the partners, husbands of women with orgasmic dysfunction were more likely to blame themselves than the circumstances, while the opposite was true for wives of males with erectile difficulties. Individuals experiencing the dysfunction perceived themselves and their partners as having little, but equal control over the identified patient's sexuality. Correlational analyses indicate that in identified patients, the better the quality of the marital relationship, the greater the self-blame and the lower the partner blame. Those with happy marriages also made greater efforts to improve their sexual relationship and had higher expectations of success with therapy. The implications of the results for research on the role of attributions in sexual dysfunction and for assessment of cognitive factors in sexually dysfunctional individuals and their partners is discussed.

  10. Dynamic tracking of magnetic nanoparticles for mapping microvascular networks using a clinical 1.5 T magnetic resonance scanner

    Science.gov (United States)

    Olamaei, Nina; Cheriet, Farida; Deschênes, Sylvain; Martel, Sylvain

    2014-05-01

    Being able to visualize blood vessels with an inner diameter of less than 150 μm is the present limit of modern medical imaging modalities and it becomes an important issue to advance state-of-the-art medical imaging, diagnostics, surgery, and targeted interventions. In cancer therapy, such capability would provide the information required for new delivery methods such as magnetic resonance navigation to navigate therapeutic agents along a planned trajectory deeper in the vasculature and hence closer to the region to be treated for enhancing the therapeutic index. To demonstrate the possibility of gathering images of microvascular networks dynamically and beyond the limitation of medical imaging modalities, the susceptibility artifact was used as the contrast mechanism in magnetic resonance imaging (MRI) to detect magnetic micro-aggregations of iron-oxide nanoparticles (150 ± 20 μm in diameter) as they were injected in a 2D synthetic microvascular network. Magnetic entities cause susceptibility artifacts in the images by disrupting the MRI's homogeneous magnetic field in a much larger scale than their actual size. The position of the artifact reflects the position of the aggregations in the vascular system. The calculated positions of discrete-time scans were extracted and assembled to build up the distribution of the vascular network. The results suggest that this method could be used to gather images of blood vessels beyond the spatial resolution of clinical medical imaging modalities with a measured average error confirmed on a 2D reconstruction of the micro-vessels of approximately half of a pixel's size.

  11. An ex vivo model for anti-angiogenic drug testing on intact microvascular networks.

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    Mohammad S Azimi

    Full Text Available New models of angiogenesis that mimic the complexity of real microvascular networks are needed. Recently, our laboratory demonstrated that cultured rat mesentery tissues contain viable microvascular networks and could be used to probe pericyte-endothelial cell interactions. The objective of this study was to demonstrate the efficacy of the rat mesentery culture model for anti-angiogenic drug testing by time-lapse quantification of network growth. Mesenteric windows were harvested from adult rats, secured in place with an insert, and cultured for 3 days according to 3 experimental groups: 1 10% serum (angiogenesis control, 2 10% serum + sunitinib (SU11248, and 3 10% serum + bevacizumab. Labeling with FITC conjugated BSI-lectin on Day 0 and 3 identified endothelial cells along blood and lymphatic microvascular networks. Comparison between day 0 (before and 3 (after in networks stimulated by 10% serum demonstrated a dramatic increase in vascular density and capillary sprouting. Growing networks contained proliferating endothelial cells and NG2+ vascular pericytes. Media supplementation with sunitinib (SU11248 or bevacizumab both inhibited the network angiogenic responses. The comparison of the same networks before and after treatment enabled the identification of tissue specific responses. Our results establish, for the first time, the ability to evaluate an anti-angiogenic drug based on time-lapse imaging on an intact microvascular network in an ex vivo scenario.

  12. Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke.

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    Nadine Schleicher

    Full Text Available Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model.We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group: control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography.Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p0.1.Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.

  13. GLP-1-based therapies have no microvascular effects in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Smits, Mark M.; Tonneijck, Lennart; Muskiet, Marcel H.A.; Hoekstra, Trynke; Kramer, Mark H.H.; Diamant, Michaela; Serné, Erik H.; Van Raalte, Daniël H.

    2016-01-01

    Objective - To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus. Approach and Results - We studied 57 patients with type 2 diabetes mellitus

  14. Perioperative antibiotics in the setting of microvascular free tissue transfer: current practices.

    Science.gov (United States)

    Reiffel, Alyssa J; Kamdar, Mehul R; Kadouch, Daniel J M; Rohde, Christine H; Spector, Jason A

    2010-08-01

    Microvascular free tissue transfer is a ubiquitous and routine method of restoring anatomic defects. There is a paucity of data regarding the role of perioperative antibiotics in free tissue transfer. We designed a survey to explore usage patterns among microvascular surgeons and thereby define a standard of care. A 24-question survey regarding the perioperative antibiotic use in microvascular head and neck, breast, and lower extremity reconstruction was sent to all those members of the American Society for Reconstructive Microsurgery who had registered e-mail addresses ( N = 450). Ninety-nine members responded. A first-generation cephalosporin is the most frequent choice of perioperative antibiotics across most categories: 93.5% for breast, 59.2% for head and neck, 91.1% for nontraumatic lower extremity, and 84.9% for traumatic noninfected lower extremity reconstruction. In penicillin-allergic patients, clindamycin is the most common choice. For traumatic lower extremity reconstruction in the presence of soft tissue infection or osteomyelitis, culture and sensitivity results determine the selection of perioperative antibiotics in 74%. A first-generation cephalosporin is the standard of care for perioperative antibiotic use in microvascular breast, head and neck, nontraumatic lower extremity, and traumatic noninfected lower extremity reconstruction. No consensus exists regarding the appropriate duration of coverage. These data may serve as a guide until a large controlled prospective trial is performed and a standard of care is established. (c) Thieme Medical Publishers.

  15. Microvascularized 3D Breast Cancer Constructs for Drug Testing and Development

    Science.gov (United States)

    2014-10-01

    Biomedical Engineering Symposium, Birmingham, AL, April 2014. Marshall LE, Frost AR, Berry JL. Microvascularized 3D Breast Cancer Constructs for Drug... cancer , prostate cancer , testicular cancer , uterine cancer , cervical cancer , thyroid cancer , gastric cancer , brain stem glioma, cerebellar...In embodiments, the tissue constructs of the present disclosure can be used to screen potential breast cancer therapeutic compounds. The compounds

  16. Tumor microvascular changes in antiangiogenic treatment : Assessment by magnetic resonance contrast media of different molecular weights

    NARCIS (Netherlands)

    Turetschek, K; Preda, A; Novikov, [No Value; Brasch, RC; Weinmann, HJ; Wunderbaldinger, P; Roberts, TPL

    Purpose: To test magnetic resonance (MR) contrast media of different molecular weights (MWs) for their potential to characterize noninvasively microvascular changes in an experimental tumor treatment model. Materials and Methods: MD-MBA-435, a poorly differentiated human breast cancer cell line, was

  17. Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

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    MW Laschke

    2014-10-01

    Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

  18. Retinal Vascular Fractals and Microvascular and Macrovascular Complications in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Grauslund, Jakob; Green, Anders; Kawasaki, Ryo

    2010-01-01

    PURPOSE: Fractal analysis is a method to quantify the geometric pattern and complexity of the retinal vessels. This study examined the association of retinal fractal dimension (D(f)) and microvascular and macrovascular complications in a population-based cohort of Danish patients with type 1 diab...

  19. Usability of the internal mammary recipient vessels in microvascular breast reconstruction.

    Science.gov (United States)

    O'Neill, Anne C; Hayward, Victoria; Zhong, Toni; Hofer, Stefan O P

    2016-07-01

    Although the internal mammary vessels are, for many surgeons, the recipient vessels of choice in microvascular breast reconstruction, there continues to be some debate regarding their use. The reliability of these vessels, particularly the vein, has been called into question, with high rates of conversion to alternative vessels being reported. This study investigates the true usability rate of the internal mammary vessels in a large series of consecutive patients without preselection. A review of all patients who underwent microvascular breast reconstruction at the University Health Network between September 2007 and December 2013 was conducted, and the conversion rate to alternative vessels was determined. A total of 759 microvascular breast reconstructions were performed in 515 patients. The internal mammary vessels were explored in all cases and found to be suitable for anastomosis in 756 of 759 reconstructions. Conversion to the thoracodorsal vessels was required in three reconstructions (0.4%) due to unusable internal mammary arteries. There was no significant increase in unusable vessels with timing or laterality of reconstruction or other factors such as smoking, vascular co-morbidities and adjuvant chemotherapy or radiotherapy. Total flap failure occurred in four reconstructions (0.5%), whereas partial flap loss occurred in five (0.6%). The internal mammary vessels can be safely and reliably used in almost all patients undergoing microsurgical breast reconstruction with low rates of microvascular complications. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. Spumiform capillary basement membrane swelling : A new type of microvascular degeneration in senescent hamster

    NARCIS (Netherlands)

    Gerrits, P.O.; Kortekaas, R.; de Weerd, H.; Veenstra-Algra, A.; Luiten, P.G.M.; van der Want, J.J.L.; Veening, Jan

    Brain microvasculature plays a critical role in the regulation of homeostasis of neural tissues. The present study focuses on characteristic microvascular basement membrane (bm) aberrations in the midbrain periaqueductal gray matter (PAG) and their relation to aging. The PAG can be considered a

  1. Spumiform capillary basement membrane swelling: a new type of microvascular degeneration in senescent hamster.

    NARCIS (Netherlands)

    Gerrits, P.O.; Kortekaas, R.; Weerd, H. de; Veenstra-Algra, A.; Luiten, P.G.M.; Want, J.J. van der; Veening, J.G.

    2013-01-01

    Brain microvasculature plays a critical role in the regulation of homeostasis of neural tissues. The present study focuses on characteristic microvascular basement membrane (bm) aberrations in the midbrain periaqueductal gray matter (PAG) and their relation to aging. The PAG can be considered a

  2. Preservation of intestinal microvascular Po2 during normovolemic hemodilution in a rat model

    NARCIS (Netherlands)

    van Bommel, J.; Siegemund, M.; Henny, C. P.; van den Heuvel, D. A.; Trouwborst, A.; Ince, C.

    2000-01-01

    The effect of hemodilution on the intestinal microcirculatory oxygenation is not clear. The aim of this study was to determine the effect of moderate normovolemic hemodilution on intestinal microvascular partial oxygen pressure (Po2) and its relation to the mesenteric venous Po2 (Pmvo2).

  3. Laser speckle contrast imaging for monitoring changes in microvascular blood flow

    DEFF Research Database (Denmark)

    Ambrus, Rikard; Strandby, Rune B.; Svendsen, Lars Bo

    2016-01-01

    BACKGROUND/AIMS: Microvascular blood flow is essential for healing and predicts surgical outcome. The aim of the current study was to investigate the relation between fluxes measured with the laser speckle contrast imaging (LSCI) technique and changes in absolute blood flow. In addition, we studied...

  4. In vivo transluminal microvascular endothelial cell seeding on balloon injured rabbit arteries.

    NARCIS (Netherlands)

    Arts, C.H.; Groot, P.G. de; Attevelt, N.; Heijnen-Snyder, G.J.; Verhagen, H.J.; Eikelboom, B.C.; Blankensteijn, J.D.

    2004-01-01

    AIM: Seeding venous endothelial cells (EC) onto damaged vascular surfaces attenuates the development of intimal hyperplasia. Unlike venous EC, fat derived microvascular endothelial cells (MVEC) do not require a culture step to increase the yield. The authors investigated whether fat derived MVEC are

  5. Hemifacial spasm : Intraoperative electromyographic monitoring as a guide for microvascular decompression

    NARCIS (Netherlands)

    Mooij, JJA; Mustafa, MK; van Weerden, TW

    2001-01-01

    OBJECTIVE: Microvascular decompression is the logical and well-accepted treatment of choice for hemifacial spasm (HFS). In experienced hands, good to excellent results can be obtained. However, sometimes the exact site of the vascular compression is unclear. The aim of this study was to analyze

  6. Distinct effects of blood flow and temperature on cutaneous microvascular adaptation.

    NARCIS (Netherlands)

    Carter, H.H.; Spence, A.L.; Atkinson, C.L.; Pugh, C.J.; Cable, N.T.; Thijssen, D.H.J.; Naylor, L.H.; Green, D.J.

    2014-01-01

    PURPOSE: We performed two experiments to determine whether cutaneous microvascular adaptations in response to repeated core temperature (Tc) elevation are mediated by increases in skin blood flow (SkBF) and/or skin temperature. METHODS: Healthy subjects participated for 8 wk in thrice-weekly bouts

  7. Microvascular reactivity differences between the two legs of patients with unilateral lower limb ischaemia

    NARCIS (Netherlands)

    Ubbink, D. T.; Jacobs, M. J.; Slaaf, D. W.; Tangelder, G. J.; Reneman, R. S.

    1992-01-01

    Posturally induced microvascular constriction in the skin of the leg is disturbed in severe ischaemia. It is unknown whether this disturbance is of local or central origin and whether the stage of ischaemia at which this disturbance occurs differs when the nutritive and thermoregulatory flow levels

  8. Retinal Photoreceptors and Microvascular Changes in Prediabetes Measured with Adaptive Optics (rtx1™: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Anna Zaleska-Żmijewska

    2017-01-01

    Full Text Available Background. Patients with prediabetes are at risk for diabetes, cardiovascular events, and microvascular complications. The rtx1 (Imagine Eyes, France permits early detection of changes in the retinal photoreceptors and vessels. Objective. Cone parameters and retinal microvasculature were analyzed with the rtx1 in 12 prediabetic patients and 22 healthy subjects. The analysis was based on cone density (DM, interphotoreceptor distance (SM, cone packing regularity, and retinal vessel parameters: wall thickness, lumen diameter (LD, wall-to-lumen ratio (WLR, and cross-sectional area of the vascular wall. Results. DM in the prediabetic group was not significantly lower than that in the control group (18,935 ± 1713 cells/mm2 and 19,900 ± 2375 cells/mm2, respectively; p=0.0928. The LD and WLR means differed significantly between the prediabetic and the control groups (LD 94.3 ± 10.9 versus 101.2 ± 15, p=0.022; WLR 0.29 ± 0.05 versus 0.22 ± 0.03, p<0.05. A multivariate regression analysis showed that the WLR was significantly correlated with BMI and total cholesterol. Conclusions. Abnormalities found in rtx1 examinations indicated early signs of arteriolar dysfunction, prior to impaired glucose tolerance progressing to diabetes. The rtx1 retinal image analysis offers noninvasive measurement of early changes in the vasculature that routine clinical examination cannot detect.

  9. High glucose induced oxidative stress and apoptosis in cardiac microvascular endothelial cells are regulated by FoxO3a.

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    Chaoming Peng

    Full Text Available Cardiac microvascular endothelial cells (CMECs dysfunction contributes to cardiovascular complications in diabetes, whereas, the underlying mechanism is not fully clarified. FoxO transcription factors are involved in apoptosis and reactive oxygen species (ROS production. Therefore, the present study was designed to elucidate the potential role of FoxO3a on the CMECs injury induced by high glucose.CMECs were isolated from hearts of adult rats and cultured in normal or high glucose medium for 6 h, 12 h and 24 h respectively. To down-regulate FoxO3a expression, CMECs were transfected with FoxO3a siRNA. ROS accumulation and apoptosis in CMECs were assessed by dihydroethidine (DHE staining and TUNEL assay respectively. Moreover, the expressions of Akt, FoxO3a, Bim and BclxL in CMECs were assessed by Western blotting assay.ROS accumulation in CMECs was significantly increased after high glucose incubation for 6 to 24 h. Meanwhile, high glucose also increased apoptosis in CMECs, correlated with decreased the phosphorylation expressions of Akt and FoxO3a. Moreover, high glucose incubation increased the expression of Bim, whereas increased anti-apoptotic protein BclxL. Furthermore, siRNA target FoxO3a silencing enhanced the ROS accumulation, whereas suppressed apoptosis in CMECs. FoxO3a silencing also abolished the disturbance of Bcl-2 proteins induced by high glucose in CMECs.Our data provide evidence that high glucose induced FoxO3a activation which suppressed ROS accumulation, and in parallel, resulted in apoptosis of CMECs.

  10. Sexual dysfunction in women partners of men with erectile dysfunction.

    Science.gov (United States)

    Greenstein, A; Abramov, L; Matzkin, H; Chen, J

    2006-01-01

    We evaluated 113 female partners of men with erectile dysfunction (ED) attending a sexual dysfunction clinic in order to define sexual dysfunction among these women. In all, 51 (45%) women denied having any sexual dysfunction. The other 62 (55%) responded to questions classifying their complaint(s) according to the international classification of female sexual dysfunction (FSD) in the following topics (40/62, 65%, reported having more than one problem): decreased sexual desire (n=35, 56%), sexual aversion (none), arousal (n=23, 37%) and orgasmic disorders (n=39, 63%), dyspareunia (n=19, 31%), vaginismus (n=3, 5%), and noncoital sexual pain (none). Many female partners of men with ED report having some form of sexual disorder, mostly orgasmic problems and decreased sexual desire. Therefore, for optimal outcome of ED treatment, evaluation and treatment of male and FSD should be addressed as one unit within the context of the couple, and be incorporated into one clinic of sexual medicine.

  11. Sexual dysfunction, depression, and the impact of antidepressants.

    Science.gov (United States)

    Kennedy, Sidney H; Rizvi, Sakina

    2009-04-01

    Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.