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Sample records for coronary microvascular serotonin

  1. Treatment of Angina and Microvascular Coronary Dysfunction

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    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

  2. 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)

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

    International Nuclear Information System (INIS)

    Gutiérrez-Barrios, Alejandro; Camacho-Jurado, Francisco; Díaz-Retamino, Enrique; Gamaza-Chulián, Sergio; Agarrado-Luna, Antonio; Oneto-Otero, Jesús; Del Rio-Lechuga, Ana; Benezet-Mazuecos, Javier

    2015-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease

    DEFF Research Database (Denmark)

    Mygind, Naja Dam; Michelsen, Marie Mide; Peña, 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.......01), hypertension (P=0.02), current smoking (Ppain characteristics or results from diagnostic stress testing...

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Quantitative evaluation of capillaroscopic microvascular changes in patients with established coronary heart disease.

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    Sanchez-Garcia, M Esther; Ramirez-Lara, Irene; Gomez-Delgado, Francisco; Yubero-Serrano, Elena M; Leon-Acuña, Ana; Marin, Carmen; Alcala-Diaz, Juan F; Camargo, Antonio; Lopez-Moreno, Javier; Perez-Martinez, Pablo; Tinahones, Francisco José; Ordovas, Jose M; Caballero, Javier; Blanco-Molina, Angeles; Lopez-Miranda, Jose; Delgado-Lista, Javier

    2018-02-23

    Microcirculation disturbances have been associated to most of the cardiovascular risk factors as well as to multiple inflammatory diseases. However, whether these abnormalities are specifically augmented in patients with coronary heart disease is still unknown. We aimed to evaluate if there is a relationship between the presence of coronary heart disease and the existence of functional and structural capillary abnormalities evaluated in the cutaneous microcirculation by videocapillaroscopy. Two matched samples of 30 participants with and without coronary heart disease but with similar clinical and anthropometric characteristics were evaluated by videocapillaroscopy at the dorsal skin of the third finger of the non-dominant hand. We calculated basal capillary density as well as capillary density after a period of arterial and venous occlusion in order to evaluate functionality and maximum capillary density. We also measured capillary recruitment. Microvascular capillary density at rest was significantly lower in patients suffering from coronary heart disease than in controls. This fact was also found after dynamic tests (arterial and venous occlusion), suggesting functional impairments. Capillary recruitment of the samples was not different in our sample. In our study, patients with coronary heart disease exhibit functional and structural microvascular disturbances. Although this is a very preliminary study, these findings open the door for further studying the microvascular functionality in coronary patients and how it relates to the response to treatment and/or the prognosis of the disease. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  11. Microvascular dysfunction in the immediate aftermath of chronic total coronary occlusion recanalization.

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    Ladwiniec, Andrew; Cunnington, Michael S; Rossington, Jennifer; Thackray, Simon; Alamgir, Farquad; Hoye, Angela

    2016-05-01

    The aim of this study was to compare microvascular resistance under both baseline and hyperemic conditions immediately after percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) with an unobstructed reference vessel in the same patient Microvascular dysfunction has been reported to be prevalent immediately after CTO PCI. However, previous studies have not made comparison with a reference vessel. Patients with a CTO may have global microvascular and/or endothelial dysfunction, making comparison with established normal values misleading. After successful CTO PCI in 21 consecutive patients, coronary pressure and flow velocity were measured at baseline and hyperemia in distal segments of the CTO/target vessel and an unobstructed reference vessel. Hemodynamics including hyperemic microvascular resistance (HMR), basal microvascular resistance (BMR), and instantaneous minimal microvascular resistance at baseline and hyperemia were calculated and compared between reference and target/CTO vessels. After CTO PCI, BMR was reduced in the target/CTO vessel compared with the reference vessel: 3.58 mm Hg/cm/s vs 4.94 mm Hg/cm/s, difference -1.36 mm Hg/cm/s (-2.33 to -0.39, p = 0.008). We did not detect a difference in HMR: 1.82 mm Hg/cm/s vs 2.01 mm Hg/cm/s, difference -0.20 (-0.78 to 0.39, p = 0.49). Instantaneous minimal microvascular resistance correlated strongly with the length of stented segment at baseline (r = 0.63, p = 0.005) and hyperemia (r = 0.68, p = 0.002). BMR is reduced in a recanalized CTO in the immediate aftermath of PCI compared to an unobstructed reference vessel; however, HMR appears to be preserved. A longer stented segment is associated with increased microvascular resistance. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Coronary microvascular function, insulin sensitivity and body composition in predicting exercise capacity in overweight patients with coronary artery disease

    DEFF Research Database (Denmark)

    Jürs, Anders; Pedersen, Lene Rørholm; Olsen, Rasmus Huan

    2015-01-01

    BACKGROUND: Coronary artery disease (CAD) has a negative impact on exercise capacity. The aim of this study was to determine how coronary microvascular function, glucose metabolism and body composition contribute to exercise capacity in overweight patients with CAD and without diabetes. METHODS...... by a cardiopulmonary exercise test. Body composition was determined by whole body dual-energy X-ray absorptiometry scan and magnetic resonance imaging. Coronary flow reserve (CFR) assessed by transthoracic Doppler echocardiography was used as a measure of microvascular function. RESULTS: Median BMI was 31.3 and 72...... metabolism and body composition. CFR, EDV and LVEF remained independent predictors of VO2peak in multivariable regression analysis. CONCLUSION: The study established CFR, EDV and LVEF as independent predictors of VO2peak in overweight CAD patients with no or only mild functional symptoms and a LVEF > 35...

  13. Long-term effects of bariatric surgery on peripheral endothelial function and coronary microvascular function.

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    Tarzia, Pierpaolo; Lanza, Gaetano A; Sestito, Alfonso; Villano, Angelo; Russo, Giulio; Figliozzi, Stefano; Lamendola, Priscilla; De Vita, Antonio; Crea, Filippo

    We previously demonstrated that bariatric surgery (BS) leads to a short-term significant improvement of endothelial function and coronary microvascular function. In this study we assessed whether BS maintains its beneficial effect at long-term follow up. We studied 19 morbidly obese patients (age 43±9years, 12 women) without any evidence of cardiovascular disease who underwent BS. Patients were studied before BS, at 3 months and at 4.0±1.5years follow up. Peripheral vascular function was assessed by flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), i.e., brachial artery diameter changes in response to post-ischemic forearm hyperhaemia and to nitroglycerin administration, respectively. Coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to intravenous adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery. Together with improvement of anthropometric and metabolic profile, at long-term follow-up patients showed a significant improvement of FMD (6.43±2.88 vs. 8.21±1.73%, p=0.018), and CBF response to both adenosine (1.73±0.48 vs. 2.58±0.54; pfunction and on coronary microvascular dilator function. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  14. Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus

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    Momose, Mitsuru; Neverve, Jodi; Nekolla, Stephan G.; Schwaiger, Markus; Bengel, Frank M. [Nuklearmedizinische Klinik und Poliklinik der Technischen Universitaet Muenchen, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich (Germany); Abletshauser, Claudia [Department of Medicine, Novartis Pharma GmbH, Nuernberg (Germany); Schnell, Oliver; Standl, Eberhard [Institut fuer Diabetesforschung, Munich (Germany)

    2002-12-01

    In diabetic patients, a number of studies have suggested an impairment of vascular reactivity in response to vasodilatory stimuli. The pattern of dysregulation at the coronary microcirculatory level, however, has not been clearly defined. Thus, it was the aim of this study to characterise coronary microvascular function non-invasively in a homogeneous group of asymptomatic type 2 diabetic patients. In 46 patients with type 2 diabetes, myocardial blood flow (MBF) was quantified at baseline, in response to cold pressor test (CPT) and during adenosine-mediated vasodilation using positron emission tomography and nitrogen-13 ammonia. None of the patients had been treated with insulin, and none had symptoms of cardiac disease. Decreased MBF during CPT, indicating microvascular dysregulation, was observed in 16 patients (CPT-), while 30 patients demonstrated increased MBF during CPT (CPT+). Response to CPT was mildly, but significantly correlated with response to adenosine (r=0.44, P=0.0035). There was no difference in HbA1c, serum lipid levels or serum endothelial markers between the groups. Microvascular dysregulation in the CPT- group was associated with elevated baseline MBF (P<0.0001), reduced baseline vascular resistance (P=0.0026) and an abnormal increase in resistance during CPT (P=0.0002). In conclusion, coronary microvascular dysregulation is present in approximately one-third of asymptomatic, non-insulin-treated type 2 diabetic patients. Elevated baseline blood flow and reduced microvascular resistance at rest are characteristics of this dysregulation. These data suggest a state of activation of endothelial-dependent vasodilation at baseline which appears to limit the flow response to stress conditions. (orig.)

  15. 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

  16. Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

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    Wyss, Christophe A.; Koepfli, Pascal; Namdar, Mehdi; Siegrist, Patrick T.; Kaufmann, Philipp A. [University Hospital, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Luscher, Thomas F. [University Hospital, Division of Cardiology, Cardiovascular Center, Zurich (Switzerland); Camici, Paolo G. [Hammersmith Hospital, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London (United Kingdom)

    2005-01-01

    Tetrahydrobiopterin (BH{sub 4}) is an essential co-factor for the synthesis of nitric oxide (NO), and BH{sub 4} deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH{sub 4} deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. Myocardial blood flow (MBF; ml min{sup -1} g{sup -1}) was measured at rest, during adenosine-induced (140 {mu}g kg{sup -1} min{sup -1} over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using {sup 15}O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH{sub 4} (10 mg kg{sup -1} body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. BH{sub 4} increased exercise-induced hyperaemia in controls (2.96{+-}0.58 vs 3.41{+-}0.73 ml min{sup -1} g{sup -1}, p<0.05) and hypercholesterolaemic subjects (2.47{+-}0.78 vs 2.70{+-}0.72 ml min{sup -1} g{sup -1}, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52{+-}1.10 vs 4.85{+-}0.45 ml min{sup -1} g{sup -1}, p=NS) or hypercholesterolaemic subjects (4.86{+-}1.18 vs 4.53{+-}0.93 ml min{sup -1} g{sup -1}, p=NS). Flow reserve utilisation remained unchanged in controls (70{+-}17% vs 71{+-}19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53{+-}15% vs 66{+-}14%, p<0.05). BH{sub 4} restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH{sub 4} deficiency may contribute to coronary

  17. 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

  18. [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.

  19. Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

    Science.gov (United States)

    Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

    2015-01-01

    Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

  20. Microvascular resistance of the culprit coronary artery in acute ST-elevation myocardial infarction

    Science.gov (United States)

    Carrick, David; Haig, Caroline; Carberry, Jaclyn; McCartney, Peter; Welsh, Paul; Ahmed, Nadeem; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Lindsay, Mitchell; Hood, Stuart; Watkins, Stuart; Rauhalammi, Samuli M.O.; Mordi, Ify; Ford, Ian; Radjenovic, Aleksandra; Sattar, Naveed; Oldroyd, Keith G.

    2016-01-01

    BACKGROUND. Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS. IMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire–based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days). RESULTS. Myocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0–33.0] vs. 17 [13.0–39.0] vs. 37 [21.0–63.0], P < 0.001; CFR: 1.7 [1.4–2.5] vs. 1.5 [1.1–1.8] vs. 1.4 [1.0–1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS. IMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR. TRIAL REGISTRATION. NCT02072850. FUNDING. A

  1. 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.)

  2. 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.)

  3. 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)

  4. A randomised trial comparing the effect of exercise training and weight loss on microvascular function in coronary artery disease

    DEFF Research Database (Denmark)

    Olsen, Rasmus Huan; Pedersen, Lene Rørholm; Jürs, Anders

    2015-01-01

    BACKGROUND: Coronary microvascular function is associated with outcome and is reduced in coronary artery disease (CAD) and obesity. We compared the effect of aerobic interval training (AIT) and weight loss on coronary flow reserve (CFR) and peripheral vascular function in revascularised obese CAD...... patients. METHODS AND RESULTS: Seventy non-diabetic patients (BMI 28-40 kg × m(-2), age 45-75 years) were randomised to 12 weeks' AIT (three weekly sessions lasting 38 min with ≈ 16 min at 85-90% of VO2peak) or low energy diet (LED, 800-1000 kcal/day). Per protocol adherence was defined by training......-attendance ≥ 60% and weight loss ≥ 5%, respectively. CFR was assessed by Doppler echocardiography of the LAD. Peripheral vascular function was assessed by arterial tonometry as reactive hyperaemia index (RHI) and augmentation index. Most participants had impaired CFR with a mean CFR of 2.38 (SD 0.59). Twenty...

  5. Local heart irradiation of ApoE−/− mice induces microvascular and endocardial damage and accelerates coronary atherosclerosis

    International Nuclear Information System (INIS)

    Gabriels, Karen; Hoving, Saske; Seemann, Ingar; Visser, Nils L.; Gijbels, Marion J.; Pol, Jeffrey F.; Daemen, Mat J.; Stewart, Fiona A.; Heeneman, Sylvia

    2012-01-01

    Background and purpose: Radiotherapy of thoracic and chest-wall tumors increases the long-term risk of radiation-induced heart disease, like a myocardial infarct. Cancer patients commonly have additional risk factors for cardiovascular disease, such as hypercholesterolemia. The goal of this study is to define the interaction of irradiation with such cardiovascular risk factors in radiation-induced damage to the heart and coronary arteries. Material and methods: Hypercholesterolemic and atherosclerosis-prone ApoE −/− mice received local heart irradiation with a single dose of 0, 2, 8 or 16 Gy. Histopathological changes, microvascular damage and functional alterations were assessed after 20 and 40 weeks. Results: Inflammatory cells were significantly increased in the left ventricular myocardium at 20 and 40 weeks after 8 and 16 Gy. Microvascular density decreased at both follow-up time-points after 8 and 16 Gy. Remaining vessels had decreased alkaline phosphatase activity (2–16 Gy) and increased von Willebrand Factor expression (16 Gy), indicative of endothelial cell damage. The endocardium was extensively damaged after 16 Gy, with foam cell accumulations at 20 weeks, and fibrosis and protein leakage at 40 weeks. Despite an accelerated coronary atherosclerotic lesion development at 20 weeks after 16 Gy, gated SPECT and ultrasound measurements showed only minor changes in functional cardiac parameters at 20 weeks. Conclusions: The combination of hypercholesterolemia and local cardiac irradiation induced an inflammatory response, microvascular and endocardial damage, and accelerated the development of coronary atherosclerosis. Despite these pronounced effects, cardiac function of ApoE −/− mice was maintained.

  6. Syndrome of diminished vasodilator reserve of the coronary microcirculation (microvascular angina or syndrome X): Diagnosis by combined atrial pacing and thallium 201 imaging--a case report

    International Nuclear Information System (INIS)

    Magarian, G.J.; Palac, R.; Reinhart, S.

    1990-01-01

    Patients with angina-like chest pain without evidence of epicardial coronary artery disease or coronary arterial vasospasm are becoming increasingly recognized. These are often related to noncardiac causes including esophageal, musculoskeletal, and hyperventilatory or panic states. However, recently a subgroup of such patients are being recognized as having true myocardial ischemia and chest pain on the basis of diminished coronary microvascular vasodilatory reserve (microvascular ischemia or Syndrome X). The authors describe such a patient who was found to have replication of anginal pain associated with a reversible ischemic defect on thallium 201 imaging during atrial pacing, suggesting ischemia in this myocardial segment. Resolution of angina and ST segment electrocardiographic changes of ischemia occurred with cessation of pacing. We believe this is the first report of a patient with this form of myocardial ischemia diagnosed by this method and should be considered in patients with anginal chest pain after significant coronary artery disease and coronary vasospasm have been excluded

  7. Peripheral Reactive Hyperemia Index and Coronary Microvascular Function in Women With no Obstructive CAD

    DEFF Research Database (Denmark)

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

    2016-01-01

    and the endothelial-independent aspect of CMD assessed as a coronary flow velocity reserve (CFVR). METHODS: We included 339 women with chest pain suggestive of angina pectoris and a diagnostic invasive coronary angiogram without significant coronary artery stenosis (

  8. Catheter-Based Measurements of Absolute Coronary Blood Flow and Microvascular Resistance: Feasibility, Safety, and Reproducibility in Humans.

    Science.gov (United States)

    Xaplanteris, Panagiotis; Fournier, Stephane; Keulards, Daniëlle C J; Adjedj, Julien; Ciccarelli, Giovanni; Milkas, Anastasios; Pellicano, Mariano; Van't Veer, Marcel; Barbato, Emanuele; Pijls, Nico H J; De Bruyne, Bernard

    2018-03-01

    The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans. Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (ρ=0.841, P <0.001; intraclass correlation coefficient=0.89, P <0.001) and R (ρ=0.780, P <0.001; intraclass correlation coefficient=0.89, P <0.001). In Bland-Altman plots, there was no significant bias or asymmetry. Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation. © 2018 American Heart Association, Inc.

  9. 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

  10. 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...

  11. A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings

    DEFF Research Database (Denmark)

    Pries, A.R.; Habazettl, H.; Ambrosio, G.

    2008-01-01

    -will certainly result in more rational diagnostic and therapeutic interventions for patients with ischaemic heart disease. Specifically targeted research based on improved assessment modalities is needed to improve the diagnosis of CMD and to translate current molecular, cellular, and physiological knowledge......Obstructive disease of the large coronary arteries is the prominent cause for angina pectoris. However, angina may also occur in the absence of significant coronary atherosclerosis or coronary artery spasm, especially in women. Myocardial ischaemia in these patients is often associated...

  12. 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.

  13. 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

  14. Influence of abnormal glucose metabolism on coronary microvascular function after a recent myocardial infarction

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVES: This study sought to assess the association between abnormal glucose metabolism and abnormal coronary flow reserve (CFR) in patients with a recent acute myocardial infarction (AMI). BACKGROUND: Mortality and morbidity after AMI is high among patients with abnormal glucose metabolism, ...... (140 microg/kg/min) to obtain the hyperemic flow profiles. The CFR was defined as the ratio of hyperemic to baseline peak diastolic coronary flow velocities. RESULTS: Median CFR was 1.9 (interquartile range [IQR] 1.4 to 2.4], and 109 (60%) patients had a CFR...

  15. Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Mancini, M.; Petretto, E.; Kleinert, C.; Scavone, A.; De, T.; Cook, S.; Šilhavý, Jan; Zídek, Václav; Pravenec, Michal; d´Amati, G.; Camici, P.G.

    2013-01-01

    Roč. 108, č. 1 (2013), s. 316 ISSN 0300-8428 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : arterial hypertension * coronary circulation * myocardial ischemia * spontaneously hypertensive rat * recombinant inbred strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.955, year: 2013

  16. Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease

    DEFF Research Database (Denmark)

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

    2016-01-01

    had focal fibrosis. Median (IQR) CFVR was 2.3 (1.9; 2.7), 23 (36 %) had CFVR significant correlations were found between CFVR and ECV or native T1 (R (2)  = 0.02; p = 0.......27 and R (2)  = 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 (R (2)  = 0.1; p = 0.13 and R (2)  = 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate. CONCLUSION: In women with angina and no obstructive coronary...

  17. 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.)

  18. 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

    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. RESULTS: MBFR was systematically higher...... 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...

  19. Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with Ranolazine

    Science.gov (United States)

    Nelson, Michael D.; Sharif, Behzad; Shaw, Jaime L.; Cook-Wiens, Galen; Wei, Janet; Shufelt, Chrisandra; Mehta, Puja K.; Thomson, Louise EJ; Berman, Daniel S.; Thompson, Richard B.; Handberg, Eileen M.; Pepine, Carl J.; Li, Debiao; Bairey Merz, C. Noel

    2016-01-01

    Background Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine—a late-sodium current inhibitor—improves diastolic function in animal models, and subjects with obstructive CAD. We hypothesized that ranolazine would beneficially alter diastolic function in CMD. Methods To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images: a) acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD, and b) from 43 healthy reference controls. Results Diastolic strain rate was impaired in CMD vs. controls (circumferential diastolic strain rate: 99.9 ± 2.5%/s vs. 120.1 ± 4.0%/s, p=0.0003; radial diastolic strain rate: −199.5 ± 5.5%/s vs. −243.1 ± 9.6%/s, p=0.0008, case vs. control). Moreover, peak systolic circumferential (CS) and radial (RS) strain were also impaired in cases vs. controls (CS: −18.8 ± 0.3% vs. −20.7 ± 0.3%; RS: 35.8 ± 0.7% vs. 41.4 ± 0.9%; respectively; both p < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis however, we observed no significant changes in left ventricular diastolic function in CMD cases after two weeks of ranolazine vs. placebo. Conclusions The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have sub-clinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD. PMID:28004395

  20. 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

  1. Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction.

    Science.gov (United States)

    Cuculi, Florim; De Maria, Giovanni Luigi; Meier, Pascal; Dall'Armellina, Erica; de Caterina, Alberto R; Channon, Keith M; Prendergast, Bernard D; Choudhury, Robin P; Choudhury, Robin C; Forfar, John C; Kharbanda, Rajesh K; Banning, Adrian P

    2014-11-04

    Invasive assessment of coronary physiology (IACP) offers important prognostic insights in ST-segment elevation myocardial infarction (STEMI) but the dynamics of coronary recovery are poorly understood. This study sought to examine the evolution of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), ratio of distal coronary pressure (Pd) to mean aortic pressure (Pa), and fractional flow reserve (FFR) in patients undergoing primary percutaneous coronary intervention (PPCI). 82 patients with STEMI underwent IACP at PPCI. Repeat IACP was performed in 61 patients (74%) at day 1 and in 46 patients (56%) at 6 months. Contrast-enhanced cardiac magnetic resonance imaging (CMR) was performed in 45 patients (55%) at day 1 and in 41 patients (50%) at 6 months. Changes in IACP were compared between patients with and without microvascular obstruction (MVO) on CMR. MVO was present in 21 of 45 patients (47%). Patients with MVO had lower CFR at PPCI and day 1 (p < 0.05) and a trend toward higher IMR values (p = 0.07). At 6 months, CFR and IMR were not significantly different between the groups. Baseline flow and Pd/Pa remained stable over time but FFR reduced significantly between PPCI and 6 months (p = 0.008); this reduction was mainly observed in patients with MVO (p = 0.006) but not in those without MVO (p = 0.21). In PPCI-treated patients with STEMI, coronary microcirculation begins to recover within 24 h and recovery progresses further by 6 months. FFR significantly reduces from baseline to 6 months. The presence of MVO indicates a highly dysfunctional microcirculation. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Treatment of depression in acute coronary syndromes with selective serotonin reuptake inhibitors

    NARCIS (Netherlands)

    van Melle, Joost P.; de Jonge, Peter; van den Berg, Maarten P.; Pot, Harm J.; van Veldhuisen, Dirk J.

    2006-01-01

    Depression in patients with acute coronary syndromes (ACS) is common and associated with impaired cardiovascular prognosis in terms of cardiac mortality and new cardiovascular events. It remains unclear whether antidepressant treatment may reverse these effects. In this review, the literature is

  3. Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.

    Science.gov (United States)

    Liou, Kevin; Jepson, Nigel; Buckley, Nicolas; Chen, Vivien; Thomas, Shane; Russell, Elizabeth Anne; Ooi, Sze-Yuan

    2016-04-01

    Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.

  4. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  5. What Is Coronary Microvascular Disease?

    Science.gov (United States)

    ... the results explained to you: Blood pressure measurement. Fasting blood glucose. This test is for diabetes. Lipoprotein ... weight and height to check for overweight or obesity . He or she also may recommend tests for ...

  6. Microvascular Cranial Nerve Palsy

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Microvascular Cranial Nerve Palsy Sections What Is Microvascular Cranial Nerve Palsy? ... Microvascular Cranial Nerve Palsy Treatment What Is Microvascular Cranial Nerve Palsy? Leer en Español: ¿Qué es una parálisis ...

  7. 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

    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 (

  8. 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

  9. Value of a new multiparametric score for prediction of microvascular obstruction lesions in ST-segment elevation myocardial infarction revascularized by percutaneous coronary intervention.

    Science.gov (United States)

    Amabile, Nicolas; Jacquier, Alexis; Gaudart, Jean; Sarran, Anthony; Shuaib, Anes; Panuel, Michel; Moulin, Guy; Bartoli, Jean-Michel; Paganelli, Franck

    2010-10-01

    Despite improvement in revascularization strategies, microvascular obstruction (MO) lesions remain associated with poor outcome after ST-segment elevation myocardial infarction (STEMI). To establish a bedside-available score for predicting MO lesions in STEMI, with cardiac magnetic resonance imaging (CMR) as the reference standard, and to test its prognostic value for clinical outcome. Patients with STEMI of4 accurately identified microcirculatory injuries (sensitivity 84%; specificity 82%) and independently predicted the presence of MO lesions on CMR. MO score>4 predicted adverse cardiovascular events during the first year after STEMI (relative risk 2.60 [1.10-6.60], p=0.03). MO lesions are frequent in PCI-treated STEMI and are associated with larger MIs. MO score accurately predicted MO lesions and identified patients with poor outcome post-STEMI. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  10. Serotonin Test

    Science.gov (United States)

    ... microscope. (For more, see the article on Anatomic Pathology .) See More Common Questions See Less Common Questions ... tumor. Accessed December 2010. Vorvick, L. (Updated 2009 March 14). Serum serotonin level. MedlinePlus Medical Encyclopedia [On- ...

  11. Coronary Flow Velocity Reserve Assessed by Transthoracic Doppler

    DEFF Research Database (Denmark)

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

    2016-01-01

    the feasibility and factors associated with the quality of CFVR obtained in a large prospective study of women suspected of having microvascular disease. METHODS: Women with angina-like chest pain and no obstructive coronary artery disease on coronary angiography (

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

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R

    1995-01-01

    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 exa......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...... metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P

  13. The minimum coronary artery diameter in which coronary spasm can be identified by synchrotron radiation coronary angiography

    International Nuclear Information System (INIS)

    Matsushita, Shonosuke; Hyodo, Kazuyuki; Imazuru, Tomohiro; Tokunaga, Chiho; Sato, Fujio; Enomoto, Yoshiharu; Hiramatsu, Yuji; Sakakibara, Yuzuru

    2008-01-01

    Background: Coronary vasospasm is defined as a temporary, intense narrowing of the coronary conduit artery. It brings about ischemic chest pain and becomes one of the causes of myocardial infarction. Coronary spasms are divided into two categories. One is the coronary spasm of the conduit artery and the other is the coronary microvascular spasm. Although coronary spasms are diagnosed with the images of coronary angiography, microvascular spasms cannot be diagnosed because of the limitations of conventional angiographic systems. However, synchrotron radiation coronary angiography (SRCA) can identify coronary arteries down to 100 μm in diameter in the beating heart and 50 μm in arrested heart. Aim: The purpose of this study was to confirm whether microvascular spasms could be identified or not using SRCA, and then down that size identification was possible. Methods: The Langendorff perfusion system with isolated rat hearts was employed. Krebs-Henseleit solution (KH solution) was used as a perfusate. 10 mM of 4-aminopyridine (4-AP: a voltage-gated potassium channel blocker; spasm inducer) was added to the KH solution and maintained for 5 min. SRCA was performed at pre-, during and 10 min after cessation of the KH solution with 4-AP. Coronary spasms were defined as a temporal 75% reduction of coronary arterial diameter. Results and conclusion: Multiple sizes of coronary arteries showed coronary spasms. The minimum stenosed coronary artery size was 100 μm. Since coronary microvascular spasms are seen in the arterioles (50-400 μm), coronary microvascular spasms may be diagnosed with the use of synchrotron radiation coronary angiography

  14. 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 assess...

  15. Peripheral Endothelial Function and Coronary Flow Velocity Reserve Are Not Associated in Women with Angina and No Obstructive Coronary Artery Disease

    DEFF Research Database (Denmark)

    Flintholm Raft, Kristoffer; Frestad, Daria; Michelsen, Marie Mide

    2017-01-01

    PURPOSE: We investigated whether impaired flow-mediated dilation (FMD) and plasma biomarkers reflecting endothelial dysfunction are associated with coronary microvascular dysfunction (CMD) in women with angina and no obstructive coronary artery disease (CAD). METHODS: Patients (n = 194) were rand...

  16. Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes – a randomized, single-blinded, cross-over pilot study

    DEFF Research Database (Denmark)

    Faber, Rebekka; Zander, Mette; Pena, Adam

    2015-01-01

    dipyridamole induced stress. Peripheral microvascular endothelial function was assessed by Endo-PAT2000®. Interventions were compared by two-sample t-test after ensuring no carry over effect. RESULTS: A total of 24 patients were included. Twenty patients completed the study (15 male; mean age 57 ± 9; mean BMI...

  17. Regulation of Coronary Blood Flow in Health and Ischemic Heart Disease

    Science.gov (United States)

    Duncker, Dirk J.; Koller, Akos; Merkus, Daphne; Canty, John M.

    2018-01-01

    The major factors determining myocardial perfusion and oxygen delivery have been elucidated over the past several decades, and this knowledge has been incorporated into the management of patients with ischemic heart disease (IHD). The basic understanding of the fluid mechanical behavior of coronary stenoses has also been translated to the cardiac catheterization laboratory where measurements of coronary pressure distal to a stenosis and coronary flow are routinely obtained. However, the role of perturbations in coronary microvascular structure and function, due to myocardial hypertrophy or coronary microvascular dysfunction, in IHD is becoming increasingly recognized. Future studies should therefore be aimed at further improving our understanding of the integrated coronary microvascular mechanisms that control coronary blood flow, and of the underlying causes and mechanisms of coronary microvascular dysfunction. This knowledge will be essential to further improve the treatment of patients with IHD. PMID:25475073

  18. Cardiac rehabilitation: a good measure to improve quality of life in peri- and postmenopausal women with microvascular angina

    OpenAIRE

    Wojciech Szot; Joanna Zając; Magdalena Kostkiewicz; Jakub Owoc; Iwona Bojar

    2015-01-01

    Cardiac Syndrome X (CSX) was considered a stable coronary syndrome, yet due to its nature, CSX symptoms often have a great impact on patients’ Quality of Life (QoL). According to ESC 2013 stable coronary artery disease criteria, CSX was replaced by Microvascular Angina (MA).Unfortunately, most CSX or MA patients, after classical angina (involving main coronary vessels) has been ruled out, often do not receive proper treatment. Indications for pharmacological treatment of MA patients were intr...

  19. Microvascular inflammation in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Laura Vitiello

    2014-06-01

    Full Text Available Atherogenesis is the pathogenetic process leading to formation of the atheroma lesion. It is associated to a chronic inflammatory state initially stimulated by an aberrant accumulation of lipid molecules beyond the endothelial barrier. This event triggers a cascade of deleterious events mainly through immune cell stimulation with the consequent liberation of potent pro-inflammatory and tissue damaging mediators. The atherogenetic process implies marked modifications of endothelial cell functions and a radical change in the endothelial–leukocyte interaction pattern. Moreover, accumulating evidence shows an important link between microvascular and inflammatory responses and major cardiovascular risk factors. This review illustrates the current knowledge on the effects of obesity, hypercholesterolemia and diabetes on microcirculation; their pathophysiological implications will be discussed.

  20. 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...

  1. 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.

  2. 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.

  3. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review.

    Science.gov (United States)

    Gillman, P Ken

    2010-02-01

    The US Food and Drug Administration (FDA) have suggested that fatal serotonin syndrome (SS) is possible with selective serotonin reuptake inhibitors (SSRIs) and triptans: this warning affects millions of patients as these drugs are frequently given simultaneously. SS is a complex topic about which there is much misinformation. The misconception that 5-HT1A receptors can cause serious SS is still widely perpetuated, despite quality evidence that it is activation of the 5-HT2A receptor that is required for serious SS. This review considers SS involving serotonin agonists: ergotamine, lysergic acid diethylamide, bromocriptine, and buspirone, as well as triptans, and reviews the experimental foundation underpinning the latest understanding of SS. It is concluded that there is neither significant clinical evidence, nor theoretical reason, to entertain speculation about serious SS from triptans and SSRIs. The misunderstandings about SS exhibited by the FDA, and shared by the UK Medicines and Healthcare products Regulatory Agency (in relation to methylene blue), are an important issue with wide ramifications.

  4. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  5. Radioprotective action of serotonin

    Energy Technology Data Exchange (ETDEWEB)

    Vodop' yanova, L G; Vinogradova, M F [Leningradskij Gosudarstvennyj Univ. (USSR). Biologicheskij Nauchno-Issledovatel' skij Inst.

    1975-09-01

    Tests in vitro were performed to study the effect of serotonin on oxidative phosphorylation in the mitochondria of rat liver. Serotonin (2.10/sup -4/ M) was shown to suppress oxidation of ..cap alpha..-ketoglutaric acid without significantly changing succinic acid consumption. A comparison of the results obtained with those from the literature allowed to assume that the radioprotective effect of serotonin was based not only on its previously known ability to cause tissue hypoxia, but also on its ability to affect oxidation processes in mitochondria.

  6. Comparison of Myocardial Perfusion Scintigraphy and Coronary Angiography Results

    Directory of Open Access Journals (Sweden)

    Umut Elboga

    2017-05-01

    Full Text Available Aim: Coronary artery disease (CAD is one of the most frequent causes of mortality and morbidity worldwide. Coronary angiography is the gold standard for the anatomical diagnosis of coronary artery stenosis. Myocardial Perfusion Scintigraphy (MPS is a non-invasive imaging modality used for the diagnosis of CAD. In this study, we aimed to compare the findings of MPS and coronary angiogram. Material and Method: Eighty-one patients (37 males, 44 females; mean age 55 ± 10.95 years with angina and detected perfusion defects on MPS were included in this study. All of the patients underwent coronary angiogram. A narrowing %u2265 50% was considered pathological on the coronary angiography. Results: Findings of the coronary angiogram and MPS were compared and found consistent in 51 (63% patients. A coronary narrowing < 50% was detected by coronary angiogram in 4 (5% of the remaining patients. Coronary angiogram was found to be normal in the remaining 26 patients (32% and these patients were evaluated as cardiac syndrome X (CSX known as microvascular angina (MA. Discussion: The findings showed that MPS is superior to coronary angiogram in the early diagnosis of myocardial perfusion disorders at the microvascular level. Therefore, we concluded that MPS should be the primary diagnostic tool to begin treatment before an anatomically large narrowing occurs in the coronaries.

  7. Microvascularization on collared peccary placenta

    DEFF Research Database (Denmark)

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

    2012-01-01

    and fetal compartments of the placentae. The immunolocalization of vimentin in the vascular endothelium and in the smooth muscle cells of blood vessels showed indented capillaries along the uterine epithelium and the trophoblast at the sides of complementary maternal and fetal microfolds, or rugae...... 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...

  8. Coronary flow reserve in patients with diabetes mellitus and prediabetes.

    Science.gov (United States)

    Atar, Asli I; Altuner, Tugba Kayhan; Bozbas, Huseyin; Korkmaz, Mehmet E

    2012-07-01

    Abnormalities of coronary microcirculation have been reported in patients with diabetes mellitus (DM) even in the presence of normal coronary arteries. It is unknown when the microvascular effects on coronary arteries begin to appear in the DM disease course. Coronary flow reserve (CFR), determined by pharmacological stress transthoracic Doppler echocardiography, is a reliable indicator of coronary microvascular function. We sought to determine the coronary microvascular function of prediabetic patients compared to DM patients and normal population. Seventy-four subjects with normal coronary arteries were enrolled. DM and prediabetes were diagnosed according to American Diabetes Association criteria. All subjects had Doppler recordings of the left anterior descending artery with adenosine infusion at a rate of 0.014 mg/kg per minute. The demographical characteristics and laboratory findings of the three groups were similar (DM group: n = 25, mean age 62 ± 7 years, 19 females; prediabetic group: n = 25, mean age 64 ± 12 years, 21 females; control group: n = 24, mean age 63 ± 7 years, 15 females) except fasting glucose levels. CFR values of the three groups were significantly different (DM group: CFR = 1.75 ± 0.50; prediabetic group: CFR = 2.24 ± 0.43; control group: CFR = 2.38 ± 0.32, P < 0.001). CFR values of DM group were lower than those of prediabetic and control groups (DM vs. prediabetic: P < 0.001, DM vs. control: P < 0.001). However, CFR levels of prediabetic group were not different from those of the control group (P = 0.481). DM was an independent factor predictive of CFR < 2 (OR, 22.69; 95% CI, 6.47-79.51; P < 0.001). Coronary microvascular function seems to be normal in the prediabetic state, but dysfunction appears after DM becomes overt. © 2012, Wiley Periodicals, Inc.

  9. Serotonin metabolism in rat brain

    International Nuclear Information System (INIS)

    Schutte, H.H.

    1976-01-01

    The metabolism of serotonin in rat brain was studied by measuring specific activities of tryptophan in plasma and of serotonin, 5-hydroxyindole acetic acid and tryptophan in the brain after intravenous injection of tritiated tryptophan. For a detailed analysis of the specific activities, a computer simulation technique was used. It was found that only a minor part of serotonin in rat brain is synthesized from tryptophan rapidly transported from the blood. It is suggested that the brain tryptophan originates from brain proteins. It was also found that the serotonin in rat brain is divided into more than one metabolic compartment

  10. Experimental diode laser-assisted microvascular anastomosis.

    Science.gov (United States)

    Reali, U M; Gelli, R; Giannotti, V; Gori, F; Pratesi, R; Pini, R

    1993-05-01

    An experimental study to evaluate a diode-laser approach to microvascular end-to-end anastomoses is reported. Studies were carried out on the femoral arteries and veins of Wistar rats, and effective welding of vessel tissue was obtained at low laser power, by enhancing laser absorption with indocyanine green (Cardio-green) solution. The histologic and surgical effects of this laser technique were examined and compared with those of conventional microvascular sutured anastomoses.

  11. The Effects of Serotonin in Immune Cells

    OpenAIRE

    Herr, Nadine; Bode, Christoph; Duerschmied, Daniel

    2017-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express...

  12. Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

    DEFF Research Database (Denmark)

    Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...... in cardiac output and was associated with the appearance of areas with myocardial necrosis in the regional left ventricular wall. The myocardial plasma flow rate and maximum plasma flow rate in response to a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease in the myocardial...... ng/kg for 60 min) on myocardial microvascular transport of a small hydrophilic indicator was examined by the single-injection, residue-detection method. Intracoronary infusion of rTNF-alpha increased myocardial microvascular transport after 120 min. This increase was preceded by a sustained decline...

  13. Coronary Flow Reserve Predicts Cardiopulmonary Fitness in Patients with Coronary Artery Disease Independently of Systolic and Diastolic Function

    DEFF Research Database (Denmark)

    Snoer, Martin; Olsen, Rasmus Huan; Monk-Hansen, Tea

    2014-01-01

    Aims Despite revascularization and optimal medical treatment, patients with coronary artery disease (CAD) have reduced exercise capacity. In the absence of coronary artery stenosis, coronary flow reserve (CFR) is a measure of coronary microvascular function, and a marker of future poor outcome...... in CAD patients. The aim of this study was to examine the relationship among CFR, systolic and diastolic function, peripheral vascular function, and cardiopulmonary fitness in CAD patients. Methods and Results Forty patients with median left ventricular ejection fraction (LVEF) 49 (interquartile 46....... Conclusions Coronary flow reserve measured noninvasively predicts cardiopulmonary fitness independently of resting systolic and diastolic function in CAD patients, indicating that cardiac output during maximal exercise is dependent on the ability of the coronary circulation to adapt to the higher metabolic...

  14. Microvascular pericytes in healthy and diseased kidneys

    Science.gov (United States)

    Pan, Szu-Yu; Chang, Yu-Ting; Lin, Shuei-Liong

    2014-01-01

    Pericytes are interstitial mesenchymal cells found in many major organs. In the kidney, microvascular pericytes are defined anatomically as extensively branched, collagen-producing cells in close contact with endothelial cells. Although many molecular markers have been proposed, none of them can identify the pericytes with satisfactory specificity or sensitivity. The roles of microvascular pericytes in kidneys were poorly understood in the past. Recently, by using genetic lineage tracing to label collagen-producing cells or mesenchymal cells, the elusive characteristics of the pericytes have been illuminated. The purpose of this article is to review recent advances in the understanding of microvascular pericytes in the kidneys. In healthy kidney, the pericytes are found to take part in the maintenance of microvascular stability. Detachment of the pericytes from the microvasculature and loss of the close contact with endothelial cells have been observed during renal insult. Renal microvascular pericytes have been shown to be the major source of scar-forming myofibroblasts in fibrogenic kidney disease. Targeting the crosstalk between pericytes and neighboring endothelial cells or tubular epithelial cells may inhibit the pericyte–myofibroblast transition, prevent peritubular capillary rarefaction, and attenuate renal fibrosis. In addition, renal pericytes deserve attention for their potential to produce erythropoietin in healthy kidneys as pericytes stand in the front line, sensing the change of oxygenation and hemoglobin concentration. Further delineation of the mechanisms underlying the reduced erythropoietin production occurring during pericyte–myofibroblast transition may be promising for the development of new treatment strategies for anemia in chronic kidney disease. PMID:24465134

  15. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

    Science.gov (United States)

    Corcoran, David

    2018-01-01

    The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

  16. Graft microvascular disease in solid organ transplantation.

    Science.gov (United States)

    Jiang, Xinguo; Sung, Yon K; Tian, Wen; Qian, Jin; Semenza, Gregg L; Nicolls, Mark R

    2014-08-01

    Alloimmune inflammation damages the microvasculature of solid organ transplants during acute rejection. Although immunosuppressive drugs diminish the inflammatory response, they do not directly promote vascular repair. Repetitive microvascular injury with insufficient regeneration results in prolonged tissue hypoxia and fibrotic remodeling. While clinical studies show that a loss of the microvascular circulation precedes and may act as an initiating factor for the development of chronic rejection, preclinical studies demonstrate that improved microvascular perfusion during acute rejection delays and attenuates tissue fibrosis. Therefore, preservation of a functional microvasculature may represent an effective therapeutic strategy for preventing chronic rejection. Here, we review recent advances in our understanding of the role of the microvasculature in the long-term survival of transplanted solid organs. We also highlight microvessel-centered therapeutic strategies for prolonging the survival of solid organ transplants.

  17. 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

  18. Serotonin and decision making processes.

    NARCIS (Netherlands)

    Homberg, J.R.

    2012-01-01

    Serotonin (5-HT) is an important player in decision making. Serotonergic antidepressant, anxiolytic and antipsychotic drugs are extensively used in the treatment of neuropsychiatric disorders characterized by impaired decision making, and exert both beneficial and harmful effects in patients.

  19. Corrected thrombolysis in myocardial infarction frame counts in diabetic patients with angiographically normal coronary arteries

    International Nuclear Information System (INIS)

    Turkoglu, S.; Ozdemir, M.; Tacoy, G.; Tavil, Y.; Abaci, A.; Timurkaynak, T.; Cengel, A.

    2008-01-01

    Objective was to evaluate corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) in patients with angiographically normal coronary arteries and diabetes mellitus, a condition known to be associated with microvascular dysfunction. Patients who underwent coronary angiography in Gazi University Hospital, Ankara, Turkey between January 2000 and January 2005 were studied. Corrected TIMI frame count was left circumflex (Cx) and right coronary arteries (RCA) in 118 diabetic and 122 non-diabetic patients with normal coronary angiogram. The mean CTFC values of the LAD, Cx and the RCA were similar in diabetics and nondiabetics (21.0+-7.5 versus 21.3+-9.6, 23.3+-9.7 versus 23.5+-10.8, 17.9+-6.7 versus 18.7+-7.4 respectively, p>0.05 for all comparisons). In stepwise multivariate linear regression analysis, body surface area had a significant correlation with CTFC of all the 3 coronary arteries. We conclude that CTFC in diabetics and non-diabetics with angiographically normal coronary arteries is similar. Since microvascular disease is an inherent component of diabetes, our finding may reflect the inadequacy of CTFC in predicting microvascular disease in diabetic patients with normal coronary angiograms. (author)

  20. Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications.

    Science.gov (United States)

    Vecchiati, Alessandra; Tellatin, Sara; Angelini, Annalisa; Iliceto, Sabino; Tona, Francesco

    2014-06-24

    Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy (CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries (50-20 μm), arterioles (20-10 μm), and capillaries (system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcirculatory resistance during maximal hyperemia, which is calculated by dividing pressure by flow (distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.

  1. 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.

  2. Sex-Related Differences in Vasomotor Function in Patients With Angina and Unobstructed Coronary Arteries

    DEFF Research Database (Denmark)

    Aziz, Ahmed; Hansen, Henrik Steen; Sechtem, Udo

    2017-01-01

    BACKGROUND Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries. OBJECTIVES The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population...... and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test). METHODS Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular...... dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression. RESULTS The mean patient age was 62 years, and 42% were male. There were 813 patients (59 with a pathological ACH test, 33% for CMD...

  3. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.J.A.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; Bruin, A. de

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  4. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; de Bruin, A.

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  5. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

    Science.gov (United States)

    Serotonin and norepinephrine reuptake inhibitors (SNRIs) Antidepressant SNRIs help relieve depression symptoms, such as irritability and sadness, ... effects they may cause. By Mayo Clinic Staff Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class ...

  6. Microvascular lesions of the true vocal fold.

    Science.gov (United States)

    Postma, G N; Courey, M S; Ossoff, R H

    1998-06-01

    Microvascular lesions, also called varices or capillary ectasias, in contrast to vocal fold polyps with telangiectatic vessels, are relatively small lesions arising from the microcirculation of the vocal fold. Varices are most commonly seen in female professional vocalists and may be secondary to repetitive trauma, hormonal variations, or repeated inflammation. Microvascular lesions may either be asymptomatic or cause frank dysphonia by interrupting the normal vibratory pattern, mass, or closure of the vocal folds. They may also lead to vocal fold hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in determining the functional significance of vocal fold varices. Management of patients with a varix includes medical therapy, speech therapy, and occasionally surgical vaporization. Indications for surgery are recurrent hemorrhage, enlargement of the varix, development of a mass in conjunction with the varix or hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy due to a functionally significant varix.

  7. Microvascular Anastomosis: Proposition of a Learning Curve.

    Science.gov (United States)

    Mokhtari, Pooneh; Tayebi Meybodi, Ali; Benet, Arnau; Lawton, Michael T

    2018-04-14

    Learning to perform a microvascular anastomosis is one of the most difficult tasks in cerebrovascular surgery. Previous studies offer little regarding the optimal protocols to maximize learning efficiency. This failure stems mainly from lack of knowledge about the learning curve of this task. To delineate this learning curve and provide information about its various features including acquisition, improvement, consistency, stability, and recall. Five neurosurgeons with an average surgical experience history of 5 yr and without any experience in bypass surgery performed microscopic anastomosis on progressively smaller-caliber silastic tubes (Biomet, Palm Beach Gardens, Florida) during 24 consecutive sessions. After a 1-, 2-, and 8-wk retention interval, they performed recall test on 0.7-mm silastic tubes. The anastomoses were rated based on anastomosis patency and presence of any leaks. Improvement rate was faster during initial sessions compared to the final practice sessions. Performance decline was observed in the first session of working on a smaller-caliber tube. However, this rapidly improved during the following sessions of practice. Temporary plateaus were seen in certain segments of the curve. The retention interval between the acquisition and recall phase did not cause a regression to the prepractice performance level. Learning the fine motor task of microvascular anastomosis adapts to the basic rules of learning such as the "power law of practice." Our results also support the improvement of performance during consecutive sessions of practice. The objective evidence provided may help in developing optimized learning protocols for microvascular anastomosis.

  8. 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.

  9. Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Helena U Westergren

    Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

  10. [Involvement of thrombophilia in coronary thrombosis].

    Science.gov (United States)

    Bal Dit Sollier, C; Drouet, L

    2017-12-01

    This review of thrombophilia and coronary thrombosis takes into account the "classical" thrombophilia commonly found in venous pathology and the conditions under which their research may be useful in certain forms of arterial thrombosis especially coronary thrombosis. In addition to the classical thrombophilia, exceptional thrombophilia are evoked, which are both factors of venous thrombosis but also arterial thrombosis. There are also thrombophilia that are more specific to the arterial system such as - homocystein which is potentially both a thrombosis factor but also an agent of arterial parietal lesion or - serotonin which is a factor of arterial spasm and especially coronary spasm. Finally, under the term thrombophilia, it is possible to include thrombophilic conditions, in particular cancers and inflammatory conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Serotonin and Blood Pressure Regulation

    Science.gov (United States)

    Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

    2012-01-01

    5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

  12. ROLE OF SEROTONIN IN FISH REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Parvathy ePrasad

    2015-06-01

    Full Text Available The neuroendocrine mechanism regulates reproduction through the hypothalamo-pituitary-gonadal (HPG axis which is evolutionarily conserved in vertebrates. The HPG axis is regulated by a variety of internal as well as external factors. Serotonin, a monoamine neurotransmitter, is involved in a wide range of reproductive functions. In mammals, serotonin regulates sexual behaviours, gonadotropin release and gonadotropin-release hormone (GnRH secretion. However, the serotonin system in teleost may play unique role in the control of reproduction as the mechanism of reproductive control in teleosts is not always the same as in the mammalian models. In fish, the serotonin system is also regulated by natural environmental factors as well as chemical substances. In particular, selective serotonin reuptake inhibitors (SSRIs are commonly detected as pharmaceutical contaminants in the natural environment. Those factors may influence fish reproductive functions via the serotonin system. This review summarizes the functional significance of serotonin in the teleosts reproduction.

  13. Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin

    DEFF Research Database (Denmark)

    Nielsen, Kirsten; Brask, Dorthe; Knudsen, Gitte M.

    2006-01-01

    Tracking serotonergic pathways in the brain through immunodetection of serotonin has widely been used for the anatomical characterization of the serotonergic system. Immunostaining for serotonin is also frequently applied for the visualization of individual serotonin containing fibers...... and quantification of serotonin positive fibers has been widely used to detect changes in the serotonergic innervation. However, particularly in conditions with enhanced serotonin metabolism the detection level of serotonin may lead to an underestimation of the true number of serotonergic fibers. The serotonin...... immunostained for serotonin and SERT protein and colocalization was quantified in several brain areas by confocal microscopy. In comparison with untreated rats, MAO inhibitor treated rats had a significantly higher number (almost 200% increase) of serotonin immunopositive fibers whereas no difference...

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

    African Journals Online (AJOL)

    Socio-demographic and clinical factors have been known to affect the time to microvascular complications and survival probabilities of diabetes mellitus patients. The objective of this study was to identify risk factors and estimate average survival times for the time to the development of microvascular complications of ...

  15. Serotonin-induced down-regulation of cell surface serotonin transporter

    DEFF Research Database (Denmark)

    Jørgensen, Trine Nygaard; Christensen, Peter Møller; Gether, Ulrik

    2014-01-01

    The serotonin transporter (SERT) terminates serotonergic signaling and enables refilling of synaptic vesicles by mediating reuptake of serotonin (5-HT) released into the synaptic cleft. The molecular and cellular mechanisms controlling SERT activity and surface expression are not fully understood...

  16. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

  17. What can we learn about treating heart failure from the heart's response to acute exercise? Focus on the coronary microcirculation.

    Science.gov (United States)

    Heinonen, Ilkka; Sorop, Oana; de Beer, Vincent J; Duncker, Dirk J; Merkus, Daphne

    2015-10-15

    Coronary microvascular function and cardiac function are closely related in that proper cardiac function requires adequate oxygen delivery through the coronary microvasculature. Because of the close proximity of cardiomyocytes and coronary microvascular endothelium, cardiomyocytes not only communicate their metabolic needs to the coronary microvasculature, but endothelium-derived factors also directly modulate cardiac function. This review summarizes evidence that the myocardial oxygen balance is disturbed in the failing heart because of increased extravascular compressive forces and coronary microvascular dysfunction. The perturbations in myocardial oxygen balance are exaggerated during exercise and are due to alterations in neurohumoral influences, endothelial function, and oxidative stress. Although there is some evidence from animal studies that the myocardial oxygen balance can partly be restored by exercise training, it is largely unknown to what extent the beneficial effects of exercise training include improvements in endothelial function and/or oxidative stress in the coronary microvasculature and how these improvements are impacted by risk factors such as diabetes, obesity, and hypercholesterolemia. Copyright © 2015 the American Physiological Society.

  18. Automated mass spectrometric analysis of urinary and plasma serotonin

    NARCIS (Netherlands)

    de Jong, Wilhelmina H. A.; Wilkens, Marianne H. L. I.; de Vries, Elisabeth G. E.; Kema, Ido P.

    Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated in liver cell regeneration and bone formation. The aim

  19. 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

  20. Differentiation state determines neural effects on microvascular endothelial cells

    International Nuclear Information System (INIS)

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-01-01

    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: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

  1. Management standards for stable coronary artery disease in India

    Directory of Open Access Journals (Sweden)

    Sundeep Mishra

    2016-12-01

    Full Text Available Coronary artery disease (CAD is one of the important causes of cardiovascular morbidity and mortality globally, giving rise to more than 7 million deaths annually. An increasing burden of CAD in India is a major cause of concern with angina being the leading manifestation. Stable coronary artery disease (SCAD is characterised by episodes of transient central chest pain (angina pectoris, often triggered by exercise, emotion or other forms of stress, generally triggered by a reversible mismatch between myocardial oxygen demand and supply resulting in myocardial ischemia or hypoxia. A stabilised, frequently asymptomatic phase following an acute coronary syndrome (ACS is also classified as SCAD. This definition of SCAD also encompasses vasospastic and microvascular angina under the common umbrella.

  2. Mandibular reconstruction with composite microvascular tissue transfer

    International Nuclear Information System (INIS)

    Coleman, J.J. III; Wooden, W.A.

    1990-01-01

    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

  3. 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.

  4. Serotonin shapes risky decision making in monkeys

    OpenAIRE

    Long, Arwen B.; Kuhn, Cynthia M.; Platt, Michael L.

    2009-01-01

    Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in ...

  5. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  6. Serotonin: Modulator of a Drive to Withdraw

    Science.gov (United States)

    Tops, Mattie; Russo, Sascha; Boksem, Maarten A. S.; Tucker, Don M.

    2009-01-01

    Serotonin is a fundamental neuromodulator in both vertebrate and invertebrate nervous systems, with a suspected role in many human mental disorders. Yet, because of the complexity of serotonergic function, researchers have been unable to agree on a general theory. One function suggested for serotonin systems is the avoidance of threat. We propose…

  7. Vasospastic angina and microvascular angina are differentially influenced by PON1 A632G polymorphism in the Japanese.

    Science.gov (United States)

    Mashiba, Junko; Koike, George; Kamiunten, Hitoshi; Ikeda, Manami; Sunagawa, Kenji

    2005-12-01

    Ethnicity and smoking are well-known risk factors for the pathogenesis of coronary vasospasm. Oxidative stress induced by smoking plays a crucial role in coronary vasospasm, but is not enough to account for the pathogenesis of coronary vasospasm, indicating that genetic factors are strongly involved. The study group comprised 162 vasospastic angina patients (VSAs), 61 microvascular angina patients (MVAs) and 61 non-responders (NRs) diagnosed by acetylcholine provocation test. Four polymorphisms of the oxidative stress related genes, cytochrome b-245, alpha polypeptide gene (CYBA) C242T and A640G, paraoxonase 1 gene (PON1) A632G, phospholipase A2 group VII gene (PLA2G7) G994T were genotyped. Allele frequency of PON1 632-G was significantly higher in both the VSA with dominant fashion and the MVA with recessive fashion compared with NR. This association was strongly influenced by gender in the MVA only. There were no significant associations between the other polymorphisms and coronary vasospasm. In addition, the allele frequency of PON1 632-G in the Japanese was higher than in Caucasians. There was a significant association between PON1 A632G polymorphism and MVA as well as VSA, but the impact of this on VSA and MVA is different in the Japanese.

  8. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  9. 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.

  10. Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules

    OpenAIRE

    Zhang, Wujie; Choi, Jung K.; He, Xiaoming

    2017-01-01

    Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. ...

  11. Concomitant macro and microvascular complications in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Alwakeel Jamal

    2009-01-01

    Full Text Available To determine the prevalence of concomitant microvascular and macrovascular complica-tions of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1% patients (294 (47% were males who developed diabetic nephropathy. Their mean age was 66.9 ± 11.4 years, mean duration of diabetes was 15.4 ± 7.5 years, mean age at the onset of nephropathy was 61.5 ± 12.4 years, and mean duration of nephropathy was 3.9 ± 3.8 years. Concomitant diabetic complications included cataract (38.2%, acute coronary syndrome (36.1%, peripheral neuropathy (24.9%, myocardial infarction (24.1%, background retinopathy (22.4%, stroke (17.6%, proliferative retinopathy (11.7%, foot infection (7.3%, limb amputation (3.7% and blindness (3%. Hypertension was documented in 577 (92.2% patients, dyslipidemia in 266 (42.5% and mortality from all causes in 86 (13.7%. There were 148 (23.6% patients with one complication, 81 (12.9% with two, 83 (13.3% with three, and 61 (9.7% with four or more. Dete-rioration of glomerular filtration rate was observed in 464 (74% patients and doubling of serum creatinine in 250 (39.9%, while 95 (15.2% developed end-stage renal disease (ESRD at the end of study and 79 (12.6% required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05. Relative risks of developing com-plications were significant after the onset of nephropathy; ACS (1.41, MI (1.49, stroke (1.48, diabetic foot (1.6, amputation (1.58 and death (1.93. We conclude that complications of diabetes are aggre-ssive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate progression

  12. Concomitant macro and microvascular complications in diabetic nephropathy

    International Nuclear Information System (INIS)

    Alwakeel, Jamal S; AlSuwaida, Abdulkareem; Isnani, Arthur C; AlHarbi, Ali; Alam Awatif

    2009-01-01

    To determine the prevalence of concomitant microvascular and macro vascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 + -11.4 years, mean duration of diabetes was 15.4 + -7.5 years, mean age at the onset of nephropathy was 61.5 + - 12.4 years, and mean duration of nephropathy was 3.9 + - 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate

  13. Concomitant macro and microvascular complications in diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Alwakeel, Jamal S; AlSuwaida, Abdulkareem [Div. of Nephrology, Dept. of Medicine, King Khalid Univ., Hospital, Riyadh (Saudi Arabia); Isnani, Arthur C [Dept. of Family and Community Medicine, King Khalid Univ. Hospital, Riyadh (Saudi Arabia); AlHarbi, Ali [Coll. of Medicine and Research Center, King Khalid Univ. Hospital, Riyadh (Saudi Arabia); Awatif, Alam [Div. of Nephrology, Dept. of Medicine, Security Forces Hospital, Riyadh (Saudi Arabia)

    2009-07-01

    To determine the prevalence of concomitant microvascular and macro vascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 + -11.4 years, mean duration of diabetes was 15.4 + -7.5 years, mean age at the onset of nephropathy was 61.5 + - 12.4 years, and mean duration of nephropathy was 3.9 + - 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate

  14. Serotonin shapes risky decision making in monkeys.

    Science.gov (United States)

    Long, Arwen B; Kuhn, Cynthia M; Platt, Michael L

    2009-12-01

    Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in part due to the lack of a good animal model. We used dietary rapid tryptophan depletion (RTD) to acutely lower brain serotonin in three macaques performing a simple gambling task for fluid rewards. To confirm the efficacy of RTD experiments, we measured total plasma tryptophan using high-performance liquid chromatography (HPLC) with electrochemical detection. Reducing brain serotonin synthesis decreased preference for the safe option in a gambling task. Moreover, lowering brain serotonin function significantly decreased the premium required for monkeys to switch their preference to the risky option, suggesting that diminished serotonin signaling enhances the relative subjective value of the risky option. These results implicate serotonin in risk-sensitive decision making and, further, suggest pharmacological therapies for treating pathological risk preferences in disorders such as problem gambling and addiction.

  15. Preparation and evaluation of serotonin labelled with 125I

    International Nuclear Information System (INIS)

    Sivaprasad, N.; Geetha, R.; Ghodke, A.S.; Karmalkar, C.P.; Pilkhwal, N.S.; Sarnaik, J.S.; Borkute, S.D.; Nadkarni, G.D.

    1999-01-01

    Radiolabelled serotonin is an important tool for studying serotonin receptors and estimating serotonin levels in plants and animals. In this paper we report the synthesis of serotonin - 125 I. Tyrosine Methyl Ester (TME) was first labelled with 125 I using chloramine-T method. 125 I-TME was then conjugated with serotonin using carbodimide. The labelled conjugate was purified using gel filtration. Yield and radiochemical purity were estimated using electrophoresis and ITLC in different solvent systems. The binding of the purified tracer to serotonin receptors and serotonin antibodies was studied. (author)

  16. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  17. Measurement of microvascular function in patients presenting with thrombolysis for ST elevation myocardial infarction, and PCI for non-ST elevation myocardial infarction.

    Science.gov (United States)

    Palmer, Sonny; Layland, Jamie; Adams, Heath; Ashokkumar, Srikkumar; Williams, Paul D; Judkins, Christopher; La Gerche, Andre; Burns, Andrew T; Whitbourn, Robert J; MacIsaac, Andrew I; Wilson, Andrew M

    2018-04-12

    In this prospective study, we compared the invasive measures of microvascular function in two subsets: patients with pharmacoinvasive thrombolysis for STEMI, and patients undergoing percutaneous coronary intervention (PCI) for NSTEMI. The study consisted of 17 patients with STEMI referred for cardiac catheterisation post thrombolysis, and 20 patients with NSTEMI. Coronary physiological indexes were measured in each patient before and after PCI. The median pre-PCI index of microcirculatory function (IMR) at baseline was significantly higher in the STEMI group than the NSTEMI group (26 units vs. 15 units, p = 0.02). Following PCI, IMR decreased in both groups (STEMI 20 units vs. NSTEMI 14 units, p = 0.10). There was an inverse correlation between post PCI IMR and left ventricular ejection fraction (LVEF) (r = -0.52, p = 0.001). Furthermore, post PCI IMR was an independent predictor of index admission LVEF in the total population (β = -0.388, p = 0.02). Invasive measures of microvascular function are inferior in a pharmacoinvasive STEMI group compared to a clinically stable NSTEMI group. In the STEMI population, the IMR following coronary intervention appears to predict LVEF. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases. A future tool for the analysis of microvascular heart involvement?

    Science.gov (United States)

    Cutolo, M; Sulli, A; Secchi, M E; Paolino, S; Pizzorni, C

    2006-10-01

    Raynaud's phenomenon (RP) represents the most frequent clinical aspect of cardio/microvascular involvement and is a key feature of several autoimmune rheumatic diseases. Moreover, RP is associated in a statistically significant manner with many coronary diseases. In normal conditions or in primary RP (excluding during the cold-exposure test), the normal nailfold capillaroscopic pattern shows a regular disposition of the capillary loops along with the nailbed. On the contrary, in subjects suffering from secondary RP, one or more alterations of the capillaroscopic findings should alert the physician of the possibility of a connective tissue disease not yet detected. Nailfold capillaroscopy (NV) represents the best method to analyse microvascular abnormalities in autoimmune rheumatic diseases. Architectural disorganization, giant capillaries, haemorrhages, loss of capillaries, angiogenesis and avascular areas characterize >95% of patients with overt scleroderma (SSc). The term 'SSc pattern' includes, all together, these sequential capillaroscopic changes typical to the microvascular involvement in SSc. The capillaroscopic aspects observed in dermatomyositis and in the undifferentiated connective tissue disease are generally reported as 'SSc-like pattern'. Effectively, and early in the disease, the peripheral microangiopathy may be well recognized and studied by nailfold capillaroscopy, or better with nailfold video capillaroscopy (NVC). The early differential diagnosis between primary and secondary RP is the best advantage NVC may offer. In addition, interesting capillaroscopic changes have been observed in systemic lupus erythematosus, anti-phospholipid syndrome and Sjogren's syndrome. Further epidemiological and clinical studies are needed to better standardize the NCV patterns. In future, the evaluation of nailfold capillaroscopy in autoimmune rheumatic diseases might represent a tool for the prediction of microvascular heart involvement by considering the systemic

  19. 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

  20. The influence of serotonin on fear learning.

    Directory of Open Access Journals (Sweden)

    Catherine Hindi Attar

    Full Text Available Learning of associations between aversive stimuli and predictive cues is the basis of Pavlovian fear conditioning and is driven by a mismatch between expectation and outcome. To investigate whether serotonin modulates the formation of such aversive cue-outcome associations, we used functional magnetic resonance imaging (fMRI and dietary tryptophan depletion to reduce brain serotonin (5-HT levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT depleted subjects compared to a non-depleted control group exhibited attenuated autonomic responses to cues indicating the upcoming of an aversive event. These results were closely paralleled by reduced aversive learning signals in the amygdala and the orbitofrontal cortex, two prominent structures of the neural fear circuit. In agreement with current theories of serotonin as a motivational opponent system to dopamine in fear learning, our data provide first empirical evidence for a role of serotonin in representing formally derived learning signals for aversive events.

  1. [Metabolism of serotonin in autism in children].

    Science.gov (United States)

    Bursztejn, C; Ferrari, P; Dreux, C; Braconnier, A; Lancrenon, S

    1988-01-01

    In this controlled study of 22 autistic children and 22 normal controls matched for age and sex, the frequency of hyperserotonemia in infantile autism was confirmed. Platelet serotonin was elevated in patients. Comparative to controls, serotonin was also high in urine of autistic patients, while, on the contrary there was no difference for the urinary excretion of 5-HIAA. No difference was observed either for serotonin uptake and efflux or for MAO activity, in isolated platelets. The elevation of plasma free tryptophan - significant only with the Kolmogorov Smirnov test - suggests that 5-HT biosynthesis might be enhanced. In the group of patient reported in this study, disorders of serotonin metabolism are associated with disturbances of platelet catecholamines, and also with elevated immunoglobulins and enhanced cellular immunity reactions.

  2. Correlation Factor Analysis of Retinal Microvascular Changes in Patients With Essential Hypertension

    Institute of Scientific and Technical Information of China (English)

    Huang Duru; Huang Zhongning

    2006-01-01

    Objectives To investigate correlation between retinal microvascular signs and essential hypertension classification. Methods The retinal microvascular signs in patients with essential hypertension were assessed with the indirect biomicroscopy lens, the direct and the indirect ophthalmoscopes were used to determine the hypertensive retinopathy grades and retinal arteriosclerosis grades.The rank correlation analysis was used to analysis the correlation these grades with the risk factors concerned with hypertension. Results Of 72 cases with essential hypertension, 28 cases complicated with coronary disease, 20 cases diabetes, 41 cases stroke,17 cases renal malfunction. Varying extent retinal arterioscleroses were found in 71 cases, 1 case with retinal hemorrhage, 2 cases with retina edema, 4 cases with retinal hard exudation, 5 cases with retinal hemorrhage complicated by hard exudation, 2 cases with retinal hemorrhage complicated by hard exudation and cotton wool spot, 1 case with retinal hemorrhage complicated by hard exudation and microaneurysms,1 case with retinal edema and hard exudation, 1 case with retinal microaneurysms, 1 case with branch retinal vein occlusion. The rank correlation analysis showed that either hypertensive retinopathy grades or retinal arteriosclerosis grades were correlated with risk factor lamination of hypertension (r=0.25 or 0.31, P<0.05), other correlation factors included age and blood high density lipoprotein concerned about hypertensive retinopathy grades or retinal arteriosclerosis grades, but other parameters, namely systolic or diastolic pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, fasting blood glucose,blood urea nitrogen and blood creatinine were not confirmed in this correlation analysis (P > 0.05).Conclusions Either hypertensive retinopathy grade or retinal arteriosclerosis grade is close with the hypertension risk factor lamination, suggesting that the fundus examination of patients with

  3. [Evaluation and Optimization of Microvascular Arterial Anastomoses by Transit Time Flow Measurement].

    Science.gov (United States)

    Herberhold, S; Röttker, J; Bartmann, D; Solbach, A; Keiner, S; Welz, A; Bootz, F; Laffers, W

    2016-03-01

    INDRODUCTION: The regular application of transit time flow measurement in microvascular anastomoses during heart surgery has lead to improvements of the outcome of coronary artery bypass grafts. Our study was meant to discover whether this measurement method was also applicable for evaluation and optimization of microvascular arterial anastomoses of radial forearm flaps. In this prospective examination a combining ultrasound imaging and transit time flow measurement device (VeriQ, MediStim) was used during surgery to assess anastomotic quality of 15 radial forearm flaps. Pulsatility index (PI) and mean blood flow were measured immediately after opening the arterial anastomosis as well as 15 min afterwards. Furthermore, application time and description of handling were recorded seperately for every assessment. Mean blood flow immediately after opening the anastomosis and 15 min later were 3.9 and 3.4 ml/min resepectively showing no statistically significant difference (p=0.96). There was no significance in the increase of pulsatility index from 22.1 to 27.2 (p=0.09) during the same time range, either. Due to measurement results showing atypical pulse curves in 2 cases decision for surgical revision of the anastomoses was made. All forearm flaps showed good vascularisation during follow-up. Time for device set up, probe placement and measurements was about 20 min. Handling was described to be uncomplicated without exception. There were no noteworthy problems. Transit time flow measurement contributes to the improvement of anastomotic quality and therefore to the overall outcome of radial forearm flaps. The examined measurement method provides objective results and is useful for documentation purposes. © Georg Thieme Verlag KG Stuttgart · New York.

  4. 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.

  5. Integral diagnosis of coronary atherosclerosis by coronary multidetector computed tomography and by invasive coronary angiography

    International Nuclear Information System (INIS)

    Llerena Rojas, Luis Roberto; Llerena Rojas, Lorenzo D; Mendoza Rodriguez, Vladimir

    2013-01-01

    Coronary angiography by multidetector computed tomography (CMDCT) visualizes the wall and lumen of coronary arteries. Invasive coronary angiography (INVCA) only visualizes the arterial lumen but with better resolution

  6. Brain microvascular function during cardiopulmonary bypass

    International Nuclear Information System (INIS)

    Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

    1987-01-01

    Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass

  7. Transthoracic Doppler echocardiography – noninvasive diagnostic window for coronary flow reserve assessment

    Directory of Open Access Journals (Sweden)

    Dimitrow Paweł

    2003-04-01

    Full Text Available Abstract This review focuses on transthoracic Doppler echocardiography as noninvasive method used to assess coronary flow reserve (CFR in a wide spectrum of clinical settings. Transthoracic Doppler echocardiography is rapidly gaining appreciation as popular tool to measure CFR both in stenosed and normal epicardial coronary arteries (predominantly in left anterior descending coronary artery. Post-stenotic CFR measurement is helpful in: functional assessment of moderate stenosis, detection of significant or critical stenosis, monitoring of restenosis after revascularization. In the absence of stenosis in the epicardial coronary artery, decreased CFR enable to detect impaired microvascular vasodilatation in: reperfused myocardial infarct, arterial hypertension with or without left ventricular hypertrophy, diabetes mellitus, hypercholesterolemia, syndrome X, hypertrophic cardiomyopathy. In these diseases, noninvasive transthoracic Doppler echocardiography allows for serial CFR evaluations to explore the effect of various pharmacological therapies.

  8. Gap filling of 3-D microvascular networks by tensor voting.

    Science.gov (United States)

    Risser, L; Plouraboue, F; Descombes, X

    2008-05-01

    We present a new algorithm which merges discontinuities in 3-D images of tubular structures presenting undesirable gaps. The application of the proposed method is mainly associated to large 3-D images of microvascular networks. In order to recover the real network topology, we need to fill the gaps between the closest discontinuous vessels. The algorithm presented in this paper aims at achieving this goal. This algorithm is based on the skeletonization of the segmented network followed by a tensor voting method. It permits to merge the most common kinds of discontinuities found in microvascular networks. It is robust, easy to use, and relatively fast. The microvascular network images were obtained using synchrotron tomography imaging at the European Synchrotron Radiation Facility. These images exhibit samples of intracortical networks. Representative results are illustrated.

  9. 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

  10. 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.

  11. Therapeutic Effects of PPARα on Neuronal Death and Microvascular Impairment

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Moran

    2015-01-01

    Full Text Available Peroxisome-proliferator activated receptor-alpha (PPARα is a broadly expressed nuclear hormone receptor and is a transcription factor for diverse target genes possessing a PPAR response element (PPRE in the promoter region. The PPRE is highly conserved, and PPARs thus regulate transcription of an extensive array of target genes involved in energy metabolism, vascular function, oxidative stress, inflammation, and many other biological processes. PPARα has potent protective effects against neuronal cell death and microvascular impairment, which have been attributed in part to its antioxidant and anti-inflammatory properties. Here we discuss PPARα’s effects in neurodegenerative and microvascular diseases and also recent clinical findings that identified therapeutic effects of a PPARα agonist in diabetic microvascular complications.

  12. Serotonin Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2018-01-01

    Full Text Available Serotonin Syndrome (SS is a potentially fatal iatrogenic condition that occurs as a result of an over-stimulation of the serotonergic receptors. Its typical presentation consists of the triad altered mental status, autonomic hyperactivity and neuromuscular alterations, although the clinical condition is highly variable. Despite being potentially treatable, many cases per year are underdiagnosed, a fact that has been mainly attributed to the lack of knowledge of this condition by the physicians. SS treatment relies on four pillars: removal of the precipitating agent and supportive therapy, antagonism of 5-HT2A receptors, and control of agitation, autonomic instability and hyperthermia. It is expected that its incidence will accompany the growth of the prescription of antidepressants, andincreasing physician’s awareness about its occurrence, could contribute to a timely diagnosis and to the success of the treatment. We present a clinical case of a patient diagnosed with Bipolar Affective Disorder, hospitalized for a depressive episode with a psychotic component, which developed a SS compatible condition. Based on this case report the authors undertake a theoretical review of this condition.

  13. Serotonin and decision making processes.

    Science.gov (United States)

    Homberg, Judith R

    2012-01-01

    Serotonin (5-HT) is an important player in decision making. Serotonergic antidepressant, anxiolytic and antipsychotic drugs are extensively used in the treatment of neuropsychiatric disorders characterized by impaired decision making, and exert both beneficial and harmful effects in patients. Detailed insight into the serotonergic mechanisms underlying decision making is needed to strengthen the first and weaken the latter. Although much remains to be done to achieve this, accumulating studies begin to deliver a coherent view. Thus, high central 5-HT levels are generally associated with improved reversal learning, improved attentional set shifting, decreased delay discounting, and increased response inhibition, but a failure to use outcome representations. Based on 5-HT's evolutionary role, I hypothesize that 5-HT integrates expected, or changes in, relevant sensory and emotional internal/external information, leading to vigilance behaviour affecting various decision making processes. 5-HT receptor subtypes play distinctive roles in decision making. 5-HT(2A) agonists and 5-HT2c antagonists decrease compulsivity, whereas 5-HT(2A) antagonists and 5-HT(2C) agonists decrease impulsivity. 5-HT(6) antagonists univocally affect decision making processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Immunomodulatory Effects Mediated by Serotonin

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2015-01-01

    Full Text Available Serotonin (5-HT induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b downstream signaling transduction proteins; and (c enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

  15. Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules.

    Science.gov (United States)

    Zhang, Wujie; Choi, Jung K; He, Xiaoming

    2017-02-01

    Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. This approach provides an alternative and promising method for constructing vascularized tissues.

  16. Apolipoprotein B level and diabetic microvascular complications ( is there a correlation?

    Directory of Open Access Journals (Sweden)

    Mary N. Rizk

    2013-01-01

    Conclusion Apo B levels are strongly correlated to diabetic microvascular complications. The higher the degree of nephropathy, the higher the Apo B level. The presence of more than one microvascular complication correlates positively with high levels of Apo B. This suggests the possible use of Apo B as a sensitive biomarker of the presence of early diabetic microvascular complications.

  17. Salivary serotonin does not correlate with central serotonin turnover in adult phenylketonuria (PKU patients

    Directory of Open Access Journals (Sweden)

    Joseph Leung

    2018-06-01

    Full Text Available Introduction: Phenylketonuria (PKU is an inborn error of metabolism associated with an increased risk of behavioural and mood disorders. There are currently no reliable markers for monitoring mood in PKU. The purpose of this study was to evaluate salivary serotonin as a possible non-invasive marker of long-term mood symptoms and central serotonin activity in patients with PKU. Methods: 20 patients were recruited from our Adult Metabolic Diseases Clinic. Age, sex, plasma phenylalanine (Phe level, DASS (Depression Anxiety Stress Scales depression score, DASS anxiety score, BMI, salivary serotonin, salivary cortisol, 2-year average Phe, 2-year average tyrosine (Tyr, and 2-year average Phe:Tyr ratio were collected for each patient. Spearman's ρ correlation analysis was used to determine if there was any relationship between any of the parameters. Results: There were positive correlations between DASS anxiety and DASS depression scores (Spearman's ρ = 0.8708, p-value < 0.0001, BMI and plasma Phe level (Spearman's ρ = 0.6228, p-value = .0034, and 2-year average Phe and BMI (Spearman's ρ = 0.5448, p-value = .0130. There was also a negative correlation between salivary cortisol and plasma Phe level (Spearman's ρ = −0.5018, p-value = .0338. All other correlations were not statistically significant. Conclusion: Salivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, implying that salivary serotonin does not reflect central serotonin turnover. Additionally, this study suggests that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU. Synopsis: Salivary serotonin does not correlate with peripheral phenylalanine levels, DASS depression scale scores, or DASS anxiety scale scores, suggesting that salivary serotonin is not a suitable marker for monitoring dietary control, mood, or anxiety in PKU

  18. Effect of a Tibetan herbal mixture on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation.

    Science.gov (United States)

    Schäfer, Daniela; Lambrecht, Julia; Radtke, Thomas; Wilhelm, Matthias; Saner, Hugo

    2015-08-01

    In this 6-week prospective, randomized, placebo-controlled and double-blind study, we investigated the effects of a natural herbal remedy based on a recipe from Tibet (Padma® 28), on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation in 80 coronary artery disease (CAD) patients (age 66 ± 8 years) on guideline-based medication for secondary prevention. We found no significant effects of Padma 28 and conclude that the addition of Padma 28 to guideline-based secondary prevention treatment of CAD did not lead to significant effects on important surrogate markers in elderly male CAD patients. © The European Society of Cardiology 2014.

  19. Coronary heart disease

    Science.gov (United States)

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...

  20. Oscillatory serotonin function in depression.

    Science.gov (United States)

    Salomon, Ronald M; Cowan, Ronald L

    2013-11-01

    Oscillations in brain activities with periods of minutes to hours may be critical for normal mood behaviors. Ultradian (faster than circadian) rhythms of mood behaviors and associated central nervous system activities are altered in depression. Recent data suggest that ultradian rhythms in serotonin (5HT) function also change in depression. In two separate studies, 5HT metabolites in cerebrospinal fluid (CSF) were measured every 10 min for 24 h before and after chronic antidepressant treatment. Antidepressant treatments were associated with enhanced ultradian amplitudes of CSF metabolite levels. Another study used resting-state functional magnetic resonance imaging (fMRI) to measure amplitudes of dorsal raphé activation cycles following sham or active dietary depletions of the 5HT precursor (tryptophan). During depletion, amplitudes of dorsal raphé activation cycles increased with rapid 6 s periods (about 0.18 Hz) while functional connectivity weakened between dorsal raphé and thalamus at slower periods of 20 s (0.05 Hz). A third approach studied MDMA (ecstasy, 3,4-methylenedioxy-N-methylamphetamine) users because of their chronically diminished 5HT function compared with non-MDMA polysubstance users (Karageorgiou et al., 2009). Compared with a non-MDMA using cohort, MDMA users showed diminished fMRI intra-regional coherence in motor regions along with altered functional connectivity, again suggesting effects of altered 5HT oscillatory function. These data support a hypothesis that qualities of ultradian oscillations in 5HT function may critically influence moods and behaviors. Dysfunctional 5HT rhythms in depression may be a common endpoint and biomarker for depression, linking dysfunction of slow brain network oscillators to 5HT mechanisms affected by commonly available treatments. 5HT oscillatory dysfunction may define illness subtypes and predict responses to serotonergic agents. Further studies of 5HT oscillations in depression are indicated. Copyright

  1. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  2. Microvascular imaging: techniques and opportunities for clinical physiological measurements

    International Nuclear Information System (INIS)

    Allen, John; Howell, Kevin

    2014-01-01

    The microvasculature presents a particular challenge in physiological measurement because the vessel structure is spatially inhomogeneous and perfusion can exhibit high variability over time. This review describes, with a clinical focus, the wide variety of methods now available for imaging of the microvasculature and their key applications. Laser Doppler perfusion imaging and laser speckle contrast imaging are established, commercially-available techniques for determining microvascular perfusion, with proven clinical utility for applications such as burn-depth assessment. Nailfold capillaroscopy is also commercially available, with significant published literature that supports its use for detecting microangiopathy secondary to specific connective tissue diseases in patients with Raynaud's phenomenon. Infrared thermography measures skin temperature and not perfusion directly, and it has only gained acceptance for some surgical and peripheral microvascular applications. Other emerging technologies including imaging photoplethysmography, optical coherence tomography, photoacoustic tomography, hyperspectral imaging, and tissue viability imaging are also described to show their potential as techniques that could become established tools for clinical microvascular assessment. Growing interest in the microcirculation has helped drive the rapid development in perfusion imaging of the microvessels, bringing exciting opportunities in microvascular research. (topical review)

  3. The serotonin transporter in psychiatric disorders

    DEFF Research Database (Denmark)

    Spies, Marie; Knudsen, Karen Birgitte Moos; Lanzenberger, Rupert

    2015-01-01

    Over the past 20 years, psychotropics affecting the serotonergic system have been used extensively in the treatment of psychiatric disorders. Molecular imaging, in particular PET, has allowed for elucidation of the essential contribution of the serotonin transporter to the pathophysiology...... of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application...... of this neuroimaging method in clinical practice. Although results from individual studies diverge, meta-analysis indicates a trend towards reduced serotonin transporter availability in patients with major depressive disorder. Inconsistencies in results might suggest symptom heterogeneity in major depressive disorder...

  4. Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder

    NARCIS (Netherlands)

    Ruhé, Henricus G.; Ooteman, Wendy; Booij, Jan; Michel, Martin C.; Moeton, Martina; Baas, Frank; Schene, Aart H.

    2009-01-01

    BACKGROUND: In major depressive disorder, selective serotonin reuptake inhibitors target the serotonin transporter (SERT). Their response rates (30-50%) are modified by SERT promotor polymorphisms (5-HTTLPR). OBJECTIVES: To quantify the relationship between SERT occupancy and response, and whether

  5. Serotonin: Is it a marker for the diagnosis of hepatocellular ...

    African Journals Online (AJOL)

    Impaired metabolic function in liver cirrhosis and slow uptake and storage of serotonin by the platelets is a sequelae of kinetic change of serotonin transport mechanisms or abnormal serotonin release from dense granules of activated platelets is a condition defined as ''platelet exhaustion'', contributes to elevated plasma ...

  6. Regulation of Pituitary Beta Endorphin Release: Role of Serotonin Neurons

    Science.gov (United States)

    1983-12-15

    endogenous) may be related to pain and its transmission in the nervous system. Areas known to have a large number of opiate receptors both in primates and...serotonin meta- bolite 5-hydroxytrvptamine; serotonin 5-hydroxtryptophan; serotonin precursor intra- cerebro -ventricular administration intermediate lobe

  7. Verocytotoxin-induced apoptosis of human microvascular endothelial cells.

    Science.gov (United States)

    Pijpers, A H; van Setten, P A; van den Heuvel, L P; Assmann, K J; Dijkman, H B; Pennings, A H; Monnens, L A; van Hinsbergh, V W

    2001-04-01

    The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-alpha interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-alpha-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.

  8. 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.

  9. Major prognostic impact of persistent microvascular obstruction as assessed by contrast-enhanced cardiac magnetic resonance in reperfused acute myocardial infarction

    International Nuclear Information System (INIS)

    Cochet, Alexandre A.; Lalande, Alain; Walker, Paul M.; Touzery, Claude; Brunotte, Francois; Lorgis, Luc; Beer, Jean-Claude; Cottin, Yves; Zeller, Marianne; Wolf, Jean-Eric

    2009-01-01

    The aim of this study was to compare the prognostic significance of microvascular obstruction (MO) and persistent microvascular obstruction (PMO) as assessed by cardiac magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). CMR was performed in 184 patients within the week following successfully reperfused first AMI. First-pass images were performed to evaluate extent of MO and late gadolinium-enhanced images to assess PMO and infarct size (IS). Major adverse cardiac events (MACE) were collected at 1-year follow-up. MO and PMO were found in 127 (69%) and 87 (47%) patients, respectively. By using univariate logistic regression analysis, high Global Registry of Acute Coronary Events (GRACE) risk score (odds ratio [OR] 95% confidence interval [CI]: 3.6 [1.8-7.4], p < 0.001), IS greater than 10% (OR [95% CI]: 2.7 [1.1-6.9], p = 0.036), left ventricular ejection fraction less than 40% (OR [95% CI]: 2.4 [1.1-5.2], p = 0.027), presence of MO (OR [95% CI]: 3.1 [1.3-7.3], p = 0.004) and presence of PMO (OR [95% CI]:10 [4.1-23.9], p < 0.001) were shown to be significantly associated with the outcome. By using multivariate analysis, presence of MO (OR [95% CI]: 2.5 [1.0-6.2], p = 0.045) or of PMO (OR [95% CI]: 8.7 [3.6-21.1], p < 0.001), associated with GRACE score, were predictors of MACE. Presence of microvascular obstruction and persistent microvascular obstruction is very common in AMI patients even after successful reperfusion and is associated with a dramatically higher risk of subsequent cardiovascular events, beyond established prognostic markers. Moreover, our data suggest that the prognostic impact of PMO might be superior to MO. (orig.)

  10. 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...... echocardiography. RESULTS: Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p... 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....

  11. Thyroid hormone promotes remodeling of coronary resistance vessels.

    Directory of Open Access Journals (Sweden)

    Olga V Savinova

    Full Text Available Low thyroid hormone (TH function has been linked to impaired coronary blood flow, reduced density of small arterioles, and heart failure. Nonetheless, little is known about the mechanisms by which THs regulate coronary microvascular remodeling. The current study examined the initial cellular events associated with coronary remodeling induced by triiodothyronine (T3 in hypothyroid rats. Rats with established hypothyroidism, eight weeks after surgical thyroidectomy (TX, were treated with T3 for 36 or 72 hours. The early effects of T3 treatment on coronary microvasculature were examined morphometrically. Gene expression changes in the heart were assessed by quantitative PCR Array. Hypothyroidism resulted in arteriolar atrophy in the left ventricle. T3 treatment rapidly induced small arteriolar muscularization and, within 72 hours, restored arteriolar density to control levels. Total length of the capillary network was not affected by TX or T3 treatment. T3 treatment resulted in the coordinate regulation of Angiopoietin 1 and 2 expression. The response of Angiopoietins was consistent with vessel enlargement. In addition to the well known effects of THs on vasoreactivity, these results suggest that THs may affect function of small resistance arteries by phenotypic remodeling of vascular smooth muscle cells (VSMC.

  12. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig...... is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue...... average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT₄ receptor binding in nucleus accumbens, but did not alter 5-HT(1A) and 5-HT(2A) receptor...

  13. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig...... is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue...... average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT4 receptor binding in nucleus accumbens, but did not alter 5-HT(1A) and 5-HT(2A) receptor...

  14. Cross-talk between cardiac muscle and coronary vasculature.

    Science.gov (United States)

    Westerhof, Nico; Boer, Christa; Lamberts, Regis R; Sipkema, Pieter

    2006-10-01

    The cardiac muscle and the coronary vasculature are in close proximity to each other, and a two-way interaction, called cross-talk, exists. Here we focus on the mechanical aspects of cross-talk including the role of the extracellular matrix. Cardiac muscle affects the coronary vasculature. In diastole, the effect of the cardiac muscle on the coronary vasculature depends on the (changes in) muscle length but appears to be small. In systole, coronary artery inflow is impeded, or even reversed, and venous outflow is augmented. These systolic effects are explained by two mechanisms. The waterfall model and the intramyocardial pump model are based on an intramyocardial pressure, assumed to be proportional to ventricular pressure. They explain the global effects of contraction on coronary flow and the effects of contraction in the layers of the heart wall. The varying elastance model, the muscle shortening and thickening model, and the vascular deformation model are based on direct contact between muscles and vessels. They predict global effects as well as differences on flow in layers and flow heterogeneity due to contraction. The relative contributions of these two mechanisms depend on the wall layer (epi- or endocardial) and type of contraction (isovolumic or shortening). Intramyocardial pressure results from (local) muscle contraction and to what extent the interstitial cavity contracts isovolumically. This explains why small arterioles and venules do not collapse in systole. Coronary vasculature affects the cardiac muscle. In diastole, at physiological ventricular volumes, an increase in coronary perfusion pressure increases ventricular stiffness, but the effect is small. In systole, there are two mechanisms by which coronary perfusion affects cardiac contractility. Increased perfusion pressure increases microvascular volume, thereby opening stretch-activated ion channels, resulting in an increased intracellular Ca2+ transient, which is followed by an increase in Ca

  15. Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

    Science.gov (United States)

    Aguilera, A; Selgas, R; Codoceo, R; Bajo, A

    2000-01-01

    Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

  16. Measuring the serotonin uptake site using [3H]paroxetine--a new serotonin uptake inhibitor

    International Nuclear Information System (INIS)

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand

  17. BLOOD CHEMISTRY AND PLATELET SEROTONIN UPTAKE AS ...

    African Journals Online (AJOL)

    A cross sectional study was conducted to investigate the blood chemistry and platelet serotonin uptake as alternative method of determining HIV disease stage in HIV/AIDS patients. Whole blood was taken from subjects at the Human Virology of the Nigerian Institute of Medical Research. Subjects were judged suitable for ...

  18. Modulation of defensive reflex conditioning in snails by serotonin

    Science.gov (United States)

    Andrianov, Vyatcheslav V.; Bogodvid, Tatiana K.; Deryabina, Irina B.; Golovchenko, Aleksandra N.; Muranova, Lyudmila N.; Tagirova, Roza R.; Vinarskaya, Aliya K.; Gainutdinov, Khalil L.

    2015-01-01

    Highlights Daily injection of serotonin before a training session accelerated defensive reflex conditioning in snails.Daily injection of 5-hydroxytryptophan before a training session in snails with a deficiency of serotonin induced by the “neurotoxic” analog of serotonin 5,7-dihydroxytryptamine, restored the ability of snails to learn.After injection of the “neurotoxic” analogs of serotonin 5,6- and 5,7-dihydroxytryptamine as well as serotonin, depolarization of the membrane and decrease of the threshold potential of premotor interneurons was observed. We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the “neurotoxic” analogs of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT) were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within 2 weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail's ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3. PMID:26557063

  19. Complete blood cell count components and coronary slow-flow phenomenon

    Directory of Open Access Journals (Sweden)

    Arjmand N

    2016-12-01

    Full Text Available Nasim Arjmand, Mohammad Reza Dehghani Department of Cardiology, Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IranDespite the implementation of preventive strategies, ischemic heart disease and stroke remain the main causes of mortality and morbidity worldwide.1,2 Of the cardiovascular diseases, coronary slow-flow phenomenon (CSFP, with a prevalence rate of 1%–7% among patients undergoing diagnostic coronary angiography, has been found to be associated with cardiovascular events, including cardiac arrhythmia and acute coronary syndrome.3–5 However, the potential mechanisms involved in the pathogenesis of CSFP remain unknown. Microvascular and endothelial dysfunctions, inflammation, diffuse atherosclerosis, and increased platelet aggregability have been reported to be the main possible etiologies for CSFP.6,7View original paper by Atlas and colleagues.

  20. Positive regulation of raphe serotonin neurons by serotonin 2B receptors.

    Science.gov (United States)

    Belmer, Arnauld; Quentin, Emily; Diaz, Silvina L; Guiard, Bruno P; Fernandez, Sebastian P; Doly, Stéphane; Banas, Sophie M; Pitychoutis, Pothitos M; Moutkine, Imane; Muzerelle, Aude; Tchenio, Anna; Roumier, Anne; Mameli, Manuel; Maroteaux, Luc

    2018-06-01

    Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT 2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT 2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serotonin releasers, and selective serotonin reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5-HT 2B receptors directly and positively regulate raphe serotonin neuron activity. By ex vivo electrophysiological recordings, we report that stimulation by the 5-HT 2B receptor agonist, BW723C86, increased the firing frequency of serotonin Pet1-positive neurons. Viral overexpression of 5-HT 2B receptors in these neurons increased their excitability. Furthermore, in vivo 5-HT 2B -receptor stimulation by BW723C86 counteracted 5-HT 1A autoreceptor-dependent reduction in firing rate and hypothermic response in wild-type mice. By a conditional genetic ablation that eliminates 5-HT 2B receptor expression specifically and exclusively from Pet1-positive serotonin neurons (Htr2b 5-HTKO mice), we demonstrated that behavioral and sensitizing effects of MDMA (3,4-methylenedioxy-methamphetamine), as well as acute behavioral and chronic neurogenic effects of the antidepressant fluoxetine, require 5-HT 2B receptor expression in serotonergic neurons. In Htr2b 5-HTKO mice, dorsal raphe serotonin neurons displayed a lower firing frequency compared to control Htr2b lox/lox mice as assessed by in vivo extracellular recordings and a stronger hypothermic effect of 5-HT 1A -autoreceptor stimulation was observed. The increase in head-twitch response to DOI (2,5-dimethoxy-4-iodoamphetamine) further confirmed the lower serotonergic tone resulting from the absence of 5-HT 2B receptors in serotonin neurons. Together, these observations indicate that the 5-HT 2B receptor acts as a direct positive modulator of serotonin Pet1

  1. Preventing microvascular complications in type 1 diabetes mellitus

    OpenAIRE

    Viswanathan, Vijay

    2015-01-01

    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 progressi...

  2. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

    Science.gov (United States)

    Salmon, Andrew H J; Satchell, Simon C

    2012-03-01

    Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

  3. Coronary Physiology During Exercise and Vasodilation in the Healthy Heart and in Severe Aortic Stenosis.

    Science.gov (United States)

    Lumley, Matthew; Williams, Rupert; Asrress, Kaleab N; Arri, Satpal; Briceno, Natalia; Ellis, Howard; Rajani, Ronak; Siebes, Maria; Piek, Jan J; Clapp, Brian; Redwood, Simon R; Marber, Michael S; Chambers, John B; Perera, Divaka

    2016-08-16

    Severe aortic stenosis (AS) can manifest as exertional angina even in the presence of unobstructed coronary arteries. The authors describe coronary physiological changes during exercise and hyperemia in the healthy heart and in patients with severe AS. Simultaneous intracoronary pressure and flow velocity recordings were made in unobstructed coronary arteries of 22 patients with severe AS (mean effective orifice area 0.7 cm(2)) and 38 controls, at rest, during supine bicycle exercise, and during hyperemia. Stress echocardiography was performed to estimate myocardial work. Wave intensity analysis was used to quantify waves that accelerate and decelerate coronary blood flow (CBF). Despite a greater myocardial workload in AS patients compared with controls at rest (12,721 vs. 9,707 mm Hg/min(-1); p = 0.003) and during exercise (27,467 vs. 20,841 mm Hg/min(-1); p = 0.02), CBF was similar in both groups. Hyperemic CBF was less in AS compared with controls (2,170 vs. 2,716 cm/min(-1); p = 0.05). Diastolic time fraction was greater in AS compared with controls, but minimum microvascular resistance was similar. With exercise and hyperemia, efficiency of perfusion improved in the healthy heart, demonstrated by an increase in the relative contribution of accelerating waves. By contrast, in AS, perfusion efficiency decreased due to augmentation of early systolic deceleration and an attenuated rise in systolic acceleration waves. Invasive coronary physiological evaluation can be safely performed during exercise and hyperemia in patients with severe aortic stenosis. Ischemia in AS is not related to microvascular disease; rather, it is driven by abnormal cardiac-coronary coupling. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. 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

  5. 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.

  6. [Microvascular decompression for hemifacial spasm. Ten years of experience].

    Science.gov (United States)

    Revuelta-Gutiérrez, Rogelio; Vales-Hidalgo, Lourdes Olivia; Arvizu-Saldaña, Emiliano; Hinojosa-González, Ramón; Reyes-Moreno, Ignacio

    2003-01-01

    Hemifacial spasm characterized by involuntary paroxistic contractions of the face is more frequent on left side and in females. Evolution is progressive and in a few cases may disappear. Management includes medical treatment, botulinum toxin, and microvascular decompression of the nerve. We present the results of 116 microvascular decompressions performed in 88 patients over 10 years. All patients had previous medical treatment. All patients were operated on with microsurgical technique by asterional craniotomy. Vascular compression was present in all cases with one exception. Follow-up was from 1 month to 133 months. Were achieved excellent results in 70.45% of cases after first operation, good results in 9.09%, and poor results in 20.45% of patients. Long-term results were excellent in 81.82%, good in 6.82%, and poor in 11.36% of patients. Hypoacusia and transitory facial palsy were the main complications. Hemifacial spasm is a painless but disabling entity. Medical treatment is effective in a limited fashion. Injection of botulinum toxin has good response but benefit is transitory. Microvascular decompression is treatment of choice because it is minimally invasive, not destructive, requires minimum technical support, and yields best long-term results.

  7. Microvascular Architecture of Hepatic Metastases in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Darshini Kuruppu

    1997-01-01

    Full Text Available Development of effective treatment for hepatic metastases can be initiated by a better understanding of tumour vasculature and blood supply. This study was designed to characterise the microvascular architecture of hepatic metastases and observe the source of contributory blood supply from the host. Metastases were induced in mice by an intrasplenic injection of colon carcinoma cells (106 cells/ml. Vascularization of tumours was studied over a three week period by scanning electron microscopy of microvascular corrosion casts. Metastatic liver involvement was observed initially within a week post induction, as areas approximately 100 μm in diameter not perfused by the casting resin. On histology these spaces corresponded to tumour cell aggregates. The following weeks highlighted the angiogenesis phase of these tumours as they received a vascular supply from adjacent hepatic sinusoids. Direct sinusoidal supply of metastases was maintained throughout tumour growth. At the tumour periphery most sinusoids were compressed to form a sheath demarcating the tumour from the hepatic vasculature. No direct supply from the hepatic artery or the portal vein was observed. Dilated vessels termed vascular lakes dominated the complex microvascular architecture of the tumours, most tapering as they traversed towards the periphery. Four vascular branching patterns could be identified as true loops, bifurcations and trifurcations, spirals and capillary networks. The most significant observation in this study was the direct sinusoidal supply of metastases, together with the vascular lakes and the peripheral sinusoidal sheaths of the tumour microculature.

  8. Preventing microvascular complications in type 1 diabetes mellitus

    Science.gov (United States)

    Viswanathan, Vijay

    2015-01-01

    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. PMID:25941647

  9. Microvascular transplantation and replantation of the dog submandibular gland.

    Science.gov (United States)

    Su, Wan Fu; Jen, Yee Min; Chen, Shyi Gen; Nieh, Shin; Wang, Chih-Hung

    2006-05-01

    Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function.

  10. 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.

  11. Coronary artery aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Koischwitz, D.; Harder, T.; Schuppan, U.; Thurn, P.

    1982-04-01

    Seven saccular coronary artery aneurysms have been demonstrated in the course of 1452 selective coronary artery angiograms. In six patients they were arterio-sclerotic; in one patient the aneurysm must have been congenital or of mycotic-embolic origin. The differential diagnosis between true aneurysms and other causes of vascular dilatation is discussed. Coronary artery aneurysms have a poor prognosis because of the possibility of rupture with resultant cardiac tamponade, or the development of thrombo-embolic myocardial infarction. These aneurysms can only be diagnosed by means of coronary angiography and require appropriate treatment.

  12. Indications for coronary angiography

    International Nuclear Information System (INIS)

    Kaltenbach, M.; Vallbracht, C.

    1985-01-01

    Today selective coronary angiography, introduced by Sones in 1957, is used as clinical routine for diagnosing morphological changes in the coronary arteries. Hitherto, more recent techniques such as digital subtraction angiography cannot provide comparable information. Strict criteria for its indication depending on possible therapeutic consequences, have to be applied, although the risk is low with a letality of 0.01 to 0.05 percent. Radionuclear investigations can be used as additional tool in selected cases. The careful indication for coronary angiography usually implies the possible need for coronary bypass graft surgery of balloon angioplasty. (orig./MG) [de

  13. Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

    Science.gov (United States)

    Guo, Yue-Ping; Commons, Kathryn G.

    2017-01-01

    The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

  14. Cardiac rehabilitation: a good measure to improve quality of life in peri- and postmenopausal women with microvascular angina

    Directory of Open Access Journals (Sweden)

    Wojciech Szot

    2015-05-01

    Full Text Available Cardiac Syndrome X (CSX was considered a stable coronary syndrome, yet due to its nature, CSX symptoms often have a great impact on patients’ Quality of Life (QoL. According to ESC 2013 stable coronary artery disease criteria, CSX was replaced by Microvascular Angina (MA.Unfortunately, most CSX or MA patients, after classical angina (involving main coronary vessels has been ruled out, often do not receive proper treatment. Indications for pharmacological treatment of MA patients were introduced only recently. Another problematic issue is that scientists describing the pathophysiology of both CSX and MA stress a lack of a deeper insight into the multifactorial etiology of the source of pain associated with this disease. In the presented article we have attempted to study the influence of cardiac rehabilitation (3 months programme on the QoL of patients recognized as suffering from MA, as well as to check if changes in myocardial perfusion in these patients at baseline and after completion of cardiac rehabilitation match changes in their QoL. Therefore, after screening 436 women for MA, we studied 55 of them who were confirmed as having MA and who agreed to participate in the study. Exercise tests, Myocardial Perfusion Imaging, and QoL questionnaires were studied at baseline and after completing 3 months period of cardiac rehabilitation. Results were subsequently compared, which showed a link between improved perfusion score in SPECT study and improved overall physical capacity, on one hand, and improved QoL score on the other. These results confirm that cardiac rehabilitation is a very useful treatment option for MA patients. It seems that training during cardiac rehabilitation is a very important factor (improved physical efficiency –> increase in self-belief, and that taking into consideration the multifactor pathophysiology of pain, it is connected with a better quality of life for MA patients.

  15. Cardiac rehabilitation: a good measure to improve quality of life in peri- and postmenopausal women with microvascular angina

    Directory of Open Access Journals (Sweden)

    Wojciech Szot

    2015-05-01

    Full Text Available Cardiac Syndrome X (CSX was considered a stable coronary syndrome, yet due to its nature, CSX symptoms often have a great impact on patients’ Quality of Life (QoL. According to ESC 2013 stable coronary artery disease criteria, CSX was replaced by Microvascular Angina (MA.Unfortunately, most CSX or MA patients, after classical angina (involving main coronary vessels has been ruled out, often do not receive proper treatment. Indications for pharmacological treatment of MA patients were introduced only recently. Another problematic issue is that scientists describing the pathophysiology of both CSX and MA stress a lack of a deeper insight into the multifactorial etiology of the source of pain associated with this disease. In the presented article we have attempted to study the influence of cardiac rehabilitation (3 months programme on the QoL of patients recognized as suffering from MA, as well as to check if changes in myocardial perfusion in these patients at baseline and after completion of cardiac rehabilitation match changes in their QoL. Therefore, after screening 436 women for MA, we studied 55 of them who were confirmed as having MA and who agreed to participate in the study. Exercise tests, Myocardial Perfusion Imaging, and QoL questionnaires were studied at baseline and after completing 3 months period of cardiac rehabilitation. Results were subsequently compared, which showed a link between improved perfusion score in SPECT study and improved overall physical capacity, on one hand, and improved QoL score on the other. These results confirm that cardiac rehabilitation is a very useful treatment option for MA patients. It seems that training during cardiac rehabilitation is a very important factor (improved physical efficiency –> increase in self-belief, and that taking into consideration the multifactor pathophysiology of pain, it is connected with a better quality of life for MA patients.

  16. Tramadol: seizures, serotonin syndrome, and coadministered antidepressants.

    Science.gov (United States)

    Sansone, Randy A; Sansone, Lori A

    2009-04-01

    This ongoing column is dedicated to the challenging clinical interface between psychiatry and primary care-two fields that are inexorably linked.Tramadol (Ultram(®)) is a commonly prescribed analgesic because of its relatively lower risk of addiction and better safety profile in comparison with other opiates. However, two significant adverse reactions are known to potentially occur with tramadol-seizures and serotonin syndrome. These two adverse reactions may develop during tramadol monotherapy, but appear much more likely to emerge during misuse/overdose as well as with the coadministration of other drugs, particularly antidepressants. In this article, we review the data relating to tramadol, seizures, and serotonin syndrome. This pharmacologic intersection is of clear relevance to both psychiatrists and primary care clinicians.

  17. Binding of Serotonin to Lipid Membranes

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Wang, Chunhua; Cruys-Bagger, Nicolaj

    2013-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a prevalent neurotransmitter throughout the animal kingdom. It exerts its effect through the specific binding to the serotonin receptor, but recent research has suggested that neural transmission may also be affected by its nonspecific interactions...... with the lipid matrix of the synaptic membrane. However, membrane–5-HT interactions remain controversial and superficially investigated. Fundamental knowledge of this interaction appears vital in discussions of putative roles of 5-HT, and we have addressed this by thermodynamic measurements and molecular...... dynamics (MD) simulations. 5-HT was found to interact strongly with lipid bilayers (partitioning coefficient ∼1200 in mole fraction units), and this is highly unusual for a hydrophilic solute like 5-HT which has a bulk, oil–water partitioning coefficient well below unity. It follows that membrane affinity...

  18. Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

    Science.gov (United States)

    Namkung, Jun; Kim, Hail; Park, Sangkyu

    2015-01-01

    Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

  19. Coronary atherosclerosis in sudden cardiac death: An autopsy study

    Directory of Open Access Journals (Sweden)

    Sudha M

    2009-10-01

    Full Text Available Background: The incidence of ischemic heart disease (IHD has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. Materials and Methods: Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000um 2 were assessed. The statistical significance was estimated. Results and Conclusions: Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

  20. Serotonin projection patterns to the cochlear nucleus.

    Science.gov (United States)

    Thompson, A M; Thompson, G C

    2001-07-13

    The cochlear nucleus is well known as an obligatory relay center for primary auditory nerve fibers. Perhaps not so well known is the neural input to the cochlear nucleus from cells containing serotonin that reside near the midline in the midbrain raphe region. Although the specific locations of the main, if not sole, sources of serotonin within the dorsal cochlear nucleus subdivision are known to be the dorsal and median raphe nuclei, sources of serotonin located within other cochlear nucleus subdivisions are not currently known. Anterograde tract tracing was used to label fibers originating from the dorsal and median raphe nuclei while fluorescence immunohistochemistry was used to simultaneously label specific serotonin fibers in cat. Biotinylated dextran amine was injected into the dorsal and median raphe nuclei and was visualized with Texas Red, while serotonin was visualized with fluorescein. Thus, double-labeled fibers were unequivocally identified as serotoninergic and originating from one of the labeled neurons within the dorsal and median raphe nuclei. Double-labeled fiber segments, typically of fine caliber with oval varicosities, were observed in many areas of the cochlear nucleus. They were found in the molecular layer of the dorsal cochlear nucleus, in the small cell cap region, and in the granule cell and external regions of the cochlear nuclei, bilaterally, of all cats. However, the density of these double-labeled fiber segments varied considerably depending upon the exact region in which they were found. Fiber segments were most dense in the dorsal cochlear nucleus (especially in the molecular layer) and the large spherical cell area of the anteroventral cochlear nucleus; they were moderately dense in the small cell cap region; and fiber segments were least dense in the octopus and multipolar cell regions of the posteroventral cochlear nucleus. Because of the presence of labeled fiber segments in subdivisions of the cochlear nucleus other than the

  1. Large coronary intramural hematomas

    DEFF Research Database (Denmark)

    Antonsen, Lisbeth; Thayssen, Per; Jensen, Lisette Okkels

    2015-01-01

    Isolated spontaneous coronary intramural hematoma is a unique subset of spontaneous coronary artery dissection that is characterized by a hemorrhage limited to the medial-adventitial layers, causing subsequent hematoma formation without visible intimal flaps. It is an infrequent and serious...... diagnostics and treatment strategy. Coronary intramural hematomas can also occur iatrogenically, as a complication to percutaneous coronary intervention (PCI). Coronary angiography (CAG) has limited diagnostic value in the absence of intimal dissections, and lesions are often angiographically ambiguous....... Intravascular ultrasound (IVUS) is an important diagnostic tool in establishing the correct diagnosis, as it provides a complete vessel wall assessment, and enables morphometric information regarding the magnitude and severity of the underlying hematoma. Due to the rarity of this clinical scenario...

  2. Can the inflammatory response be evaluated using 18F-FDG within zones of microvascular obstruction after myocardial infarction?

    Science.gov (United States)

    Prato, Frank S; Butler, John; Sykes, Jane; Keenliside, Lynn; Blackwood, Kimberley J; Thompson, R Terry; White, James A; Mikami, Yoko; Thiessen, Jonathan D; Wisenberg, Gerald

    2015-02-01

    Inflammation that occurs after acute myocardial infarction plays a pivotal role in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is taken up avidly by macrophages, has been proposed as a marker of cell-based inflammation. However, its reliability as an accurate indicator of inflammation has not been established, particularly in the early postinfarction period when regional myocardial perfusion is often severely compromised. Nine adult dogs underwent left anterior descending coronary occlusion with or without reperfusion. Animals were imaged between 7 and 21 d after infarction with PET/MR imaging after bolus injection of gadolinium-diethylenetriaminepentaacetic acid (DTPA), bolus injection of (18)F-FDG, bolus injection of (99)Tc-DTPA to simulate the distribution of gadolinium-DTPA (which represents its partition coefficient in well-perfused tissue), and injection of (111)In-labeled white blood cells 24 h earlier. After sacrifice, myocardial tissue concentrations of (18)F, (111)In, and (99)Tc were determined in a well counter. Linear regression analysis evaluated the relationships between the concentrations of (111)In and (18)F and the dependence of the ratio of (111)In/(18)F to the apparent distribution volume of (99m)Tc-DTPA. In 7 of 9 animals, (111)In increased as (18)F increased with the other 2 animals, showing weak negative slopes. With respect to the dependence of (111)In/(18)F with partition coefficient, 4 animals showed no dependence and 4 showed a weak positive slope, with 1 animal showing a negative slope. Further, in regions of extensive microvascular obstruction, (18)F significantly underestimated the extent of the presence of (111)In. In the early post-myocardial infarction period, (18)F-FDG PET imaging after a single bolus administration may underestimate the extent and degree of inflammation within regions of microvascular obstruction. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  3. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...

  4. Serotonin synthesis, release and reuptake in terminals: a mathematical model

    Directory of Open Access Journals (Sweden)

    Best Janet

    2010-08-01

    Full Text Available Abstract Background Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. Methods We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. Results We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to

  5. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yinxia Li

    Full Text Available Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  6. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yinxia; Zhao, Yunli; Huang, Xu; Lin, Xingfeng; Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  7. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  8. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  9. Plasma serotonin in horses undergoing surgery for small intestinal colic

    Science.gov (United States)

    Torfs, Sara C.; Maes, An A.; Delesalle, Catherine J.; Pardon, Bart; Croubels, Siska M.; Deprez, Piet

    2015-01-01

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were significantly lower (P serotonin was not a suitable prognostic factor in horses with SI surgical colic. PMID:25694668

  10. Stimulation of aortic smooth muscle cell mitogenesis by serotonin

    International Nuclear Information System (INIS)

    Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.; Moskowitz, M.A.

    1986-01-01

    Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 μM serotonin with increased incorporation of [ 3 H]thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 μM. At a concentration of 1 μM, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was ≅ 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors

  11. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  12. Rotavirus and Serotonin Cross-Talk in Diarrhoea

    Science.gov (United States)

    Nordgren, Johan; Karlsson, Thommie; Sharma, Sumit; Magnusson, Karl-Eric; Svensson, Lennart

    2016-01-01

    Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p serotonin receptor antagonist significantly (p serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron. PMID:27459372

  13. Ca++ dependent bistability induced by serotonin in spinal motoneurons

    DEFF Research Database (Denmark)

    Hounsgaard, J.; Kiehn, O.

    1985-01-01

    The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly...... to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude...... that serotonin controls the expression of a Ca++ dependent plateau potential in motoneurons....

  14. Serotonin Control of Thermotaxis Memory Behavior in Nematode Caenorhabditis elegans

    Science.gov (United States)

    Guo, Yuling; Wang, Daoyong; Li, Chaojun; Wang, Dayong

    2013-01-01

    Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans. PMID:24223727

  15. Serotonin and conditioning: focus on Pavlovian psychostimulant drug conditioning.

    Science.gov (United States)

    Carey, Robert J; Damianopoulos, Ernest N

    2015-04-01

    Serotonin containing neurons are located in nuclei deep in the brainstem and send axons throughout the central nervous system from the spinal cord to the cerebral cortex. The vast scope of these connections and interactions enable serotonin and serotonin analogs to have profound effects upon sensory/motor processes. In that conditioning represents a neuroplastic process that leads to new sensory/motor connections, it is apparent that the serotonin system has the potential for a critical role in conditioning. In this article we review the basics of conditioning as well as the serotonergic system and point up the number of non-associative ways in which manipulations of serotonin neurotransmission have an impact upon conditioning. We focus upon psychostimulant drug conditioning and review the contribution of drug stimuli in the use of serotonin drugs to investigate drug conditioning and the important impact drug stimuli can have on conditioning by introducing new sensory stimuli that can create or mask a CS. We also review the ways in which experimental manipulations of serotonin can disrupt conditioned behavioral effects but not the associative processes in conditioning. In addition, we propose the use of the recently developed memory re-consolidation model of conditioning as an approach to assess the possible role of serotonin in associative processes without the complexities of performance effects related to serotonin treatment induced alterations in sensory/motor systems. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across...... the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes...

  17. [Endarterectomy of the coronary arteries].

    Science.gov (United States)

    Fischer, V; Simkovic, I; Holoman, M; Verchvodko, P; Janotík, P; Galbánek, J; Hulman, M; Kostelnicák, J; Jurco, R; Slezák, J

    1992-02-01

    The authors analyze 50 patients with endarterectomy of the coronary arteries during the periods of 1972-1974 and 1988-1990. The results of endarterectomy of the right and left coronary artery provide evidence of its justification in indicated cases whereby contrary to some departments the results of endarterectomy of the left coronary artery are comparable with endarterectomy of the right coronary artery.

  18. Soluble Flt-1 links microvascular disease with heart failure in CKD.

    Science.gov (United States)

    Di Marco, Giovana S; Kentrup, Dominik; Reuter, Stefan; Mayer, Anna B; Golle, Lina; Tiemann, Klaus; Fobker, Manfred; Engelbertz, Christiane; Breithardt, Günter; Brand, Eva; Reinecke, Holger; Pavenstädt, Hermann; Brand, Marcus

    2015-05-01

    Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.

  19. 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

  20. 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.

  1. Coronary wave energy: a novel predictor of functional recovery after myocardial infarction.

    Science.gov (United States)

    De Silva, Kalpa; Foster, Paul; Guilcher, Antoine; Bandara, Asela; Jogiya, Roy; Lockie, Tim; Chowiencyzk, Phil; Nagel, Eike; Marber, Michael; Redwood, Simon; Plein, Sven; Perera, Divaka

    2013-04-01

    Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=-0.81; Pwave threshold of 2.8 W m(-2) s(-2)×10(5) predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=-0.34; P=0.07). The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

  2. Selective coronary scintigraphy

    International Nuclear Information System (INIS)

    Gambini, D.-J.

    1975-01-01

    Isotopic techniques occupy a leading place amongst examinations practicable on coronary patients because of their reliability and the safety and simplicity of their use. The present work reviews the possible applications of selective coronary scintigraphy in pathology. After a brief discussion on scintigraphy, isotopic techniques for myocardium research, coronarography and other methods to study local myocardium perfusion the theoretical bases for the use of the exploration are studied, the techniques and methods employed are reported and the results discussed. Coronary scintigraphy consists of selective injection in the two coronary arteries previously catheterized during a coronarography, of two different populations of microspheres labelled with two physically short-lived indicators: 15μ 99m Tc-labelled serumalbumin microspheres, 10 to 15μ In-labelled siderophiline microspheres. Various studies have shown the complete harmlessness of the exploration when certain precautions are taken regarding the size and number of the spheres. The microspheres disperse into the downstream arterial territory proportionally to the number of capillaries present in the different parts of the irrigated region, and are temporarily stopped in the precapillaries. The preparation of the different images needed to interpret the Face and OAG examination for the left coronary, then for the right coronary, is carried out at the end of the coronarography and lasts about 45 minutes. It is also possible by selective injection in the aorta-coronary bridges to judge their functional condition by observation of the regions they irrigate. 56 patients of the Necker hospital cardiological clinic have been examined [fr

  3. Congenital coronary artery fistula

    International Nuclear Information System (INIS)

    Oh, Yeon Hee; Kim, Hong; Zeon, Seoc Kil; Suh, Soo Jhi

    1986-01-01

    Congenital coronary artery fistula (CCAF) is communication of a coronary artery or its main branch with one of the atria or ventricles, the coronary sinus, the superior vena cava, or the pulmonary artery. In Korean peoples, only 4 cases of the CCAF were reported as rare as worldwide and authors want to report another case of CCAF, confirmed by operation. 10-year-old girl shows a fistula between sinus node artery of the right coronary artery and right atrium on root aortogram with left-to-right shunt and Qp/Qs=1.58, in which simple ligation of the sinus node artery from right coronary artery was performed. All of the 5 Korean CCAF (4 were previously reported and 1 of authors) were originated from right coronary artery, and of which 4 were opening into right ventricle and 1 of authors were into right atrium. Associated cardiac anomaly was noted in only 1 case as single coronary artery. Ages were from 9 months of age to 10 years old and no adult left case were found. 3 were female and 2 were male patients.

  4. 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

  5. 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

  6. 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

  7. Profile of Microvascular Disease in Type 2 Diabetes in a Tertiary ...

    African Journals Online (AJOL)

    Background: Diabetes mellitus (DM) is a metabolic disorder complicated by microvascular and macrovascular diseases. The clinical profile of these complications has not been adequately studied in many tertiary health care centers in India. Aim: The authors studied the clinical profile of microvascular diabetes ...

  8. Regulation of serotonin release from enterochromaffin cells of rat cecum mucosa

    International Nuclear Information System (INIS)

    Simon, C.; Ternaux, J.P.

    1990-01-01

    The release of endogenous serotonin or previously taken up tritiated serotonin from isolated strips of rat cecum mucosa containing enterochromaffin cells was studied in vitro. Release of tritiated serotonin was increased by potassium depolarization and was decreased by tetrodotoxin, veratridine and the absence of calcium. Endogenous serotonin was released at a lower rate than tritiated serotonin; endogenous serotonin release was stimulated by potassium depolarization but was unaffected by tetrodotoxin, veratridine or the absence of calcium. Carbachol, norepinephrine, clonidine and isoproterenol decreased release of tritiated serotonin but had less or reverse effect on release of endogenous serotonin. The results suggest two different serotoninergic pools within the enterochromaffin cell population

  9. Mutational scanning of the human serotonin transporter reveals fast translocating serotonin transporter mutants

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Larsen, Mads B; Johnsen, Laust B

    2004-01-01

    The serotonin transporter (SERT) belongs to a family of sodium-chloride-dependent transporters responsible for uptake of amino acids and biogenic amines from the extracellular space. SERT represents a major pharmacological target in the treatment of several clinical conditions, including depressi...

  10. Serotonin-S2 and dopamine-D2 receptors are the same size in membranes

    International Nuclear Information System (INIS)

    Brann, M.R.

    1985-01-01

    Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor

  11. No link of serotonin 2C receptor editing to serotonin transporter genotype

    NARCIS (Netherlands)

    Lyddon, R.; Cuppen, E.; Haroutunian, V.; Siever, L.J.; Dracheva, S.

    2010-01-01

    RNA editing is a post-transcriptional process, which has the potential to alter the function of encoded proteins. In particular, serotonin 2C receptor (5-HT2cR) mRNA editing can produce 24 protein isoforms of varying functionality. Rodent studies have shown that 5-HT2cR editing is dynamically

  12. Coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2009-07-01

    Coronary CT angiography has attained increasing scientific attention at academic institutions and has become a highly accurate diagnostic modality. Extending this knowledge into a practice setting is the purpose of 'Coronary CT Angiography'. This book will assist you in integrating cardiac CT into your daily practice, while also giving an overview of the current technical status and applications. The specific features of scanners from all four main vendors are also presented providing an objective overview of noninvasive coronary angiography using CT. (orig.)

  13. Coronary flow velocity reserve by echocardiography

    DEFF Research Database (Denmark)

    Olsen, Rasmus Huan; Pedersen, Lene Rørholm; Snoer, Martin

    2016-01-01

    BACKGROUND: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography of the LAD is used to assess microvascular function but validation studies in clinical settings are lacking. We aimed to assess feasibility, reproducibility and agreement with myocardial flow...... performed within a week (1-week) and for all scans regardless of time gap (total) and to account for scar tissue for patients with and without previous myocardial infarction (MI). RESULTS: Eighty-six patients with median BMI 30.9 (IQR 29.4-32.9) kg × m(-2) and CFVR 2.29 (1.90-2.63) were included. CFVR...... was feasible in 83 (97 %) using a contrast agent in 14 %. For reproducibility overall (n = 21) limits of agreement (LOA) were (-0.75;0.71), within-subjects coefficient of variation (CV) 11 %, and reliability 0.84. For reproducibility within 1-week (n = 13) LOA were (-0.33;0.25), within-subjects CV 5...

  14. Acute effects of chewing tobacco on coronary microcirculation and hemodynamics in habitual tobacco chewers

    Directory of Open Access Journals (Sweden)

    Vikas Thakran

    2015-01-01

    Full Text Available Background: Long-term adverse cardiovascular effects of smokeless tobacco are well established, however, the effect of chewing tobacco on coronary microcirculation and hemodynamic have not been studied. We intended to analyze the acute effect of chewing tobacco on coronary microcirculation and hemodynamics in habitual tobacco chewers with stable coronary artery disease undergoing elective percutaneous coronary intervention (PCI. Materials and Methods: We prospectively enrolled seven habitual tobacco chewers with stable coronary artery disease with single vessel disease or double vessel disease satisfying the criteria for elective PCI. Patients were instructed to keep 1 g of crushed dried tobacco leaves in the mouth after a successful PCI. Lesion in last stented vessels was evaluated for fractional flow reserve (FFR, coronary flow reserve (CFR, and index of microcirculatory resistance (IMR post-PCI, after 15 min and 30 min of tobacco chewing along with the measurement of serum cotinine levels. Results: Oral tobacco led to high levels of cotinine in the majority of patients. There was an insignificant rise in heart rate, systolic and diastolic blood pressure following tobacco consumption. Baseline CFR (median 1.6, range 1.1–5.5 was low in tobacco chewers after PCI even after optimum FFR (0.9 ± 0.05 in the majority of patients suggesting abnormal microvascular hemodynamics (high IMR in 3 patients, overall median 14.2, range 7–36.2. However, there was no significant change in the estimated CFR or IMR values following tobacco chewing. One patient had bradycardia and hypotension which may be related to vagal reaction or acute nicotine poisoning. Conclusion: Tobacco chewers have abnormal coronary microcirculation hemodynamics even following a successful PCI. However, the coronary micocirculation and hemodynamics do not change acutely following tobacco chewing despite high serum cotinine concentrations.

  15. Looking on the bright side of serotonin transporter gene variation.

    NARCIS (Netherlands)

    Homberg, J.R.; Lesch, K.P.

    2011-01-01

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for

  16. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    Rationale The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  17. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    RATIONALE: The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  18. Effect of serotonin infusions on the mean plasma concentrations of ...

    African Journals Online (AJOL)

    SERVER

    hhazali@hotmail.com, tabeshyarnoor@yahoo.com. neurotransmitters. It has been shown that neurons secreting serotonin may be co-locolized with neurons secreting GHRH and TRH (Bujatti et al., 1976; Bulsa et al., 1998; Savard et al., 1986; Savard et al., 1983). This indicate that serotonin as a neurotransmitter may control.

  19. Serotonin synthesis rate and the tryptophan hydroxylase-2

    DEFF Research Database (Denmark)

    Furmark, Tomas; Marteinsdottir, Ina; Frick, Andreas

    2016-01-01

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohor...

  20. Brain serotonin content - Increase following ingestion of carbohydrate diet.

    Science.gov (United States)

    Fernstrom, J. D.; Wurtman, R. J.

    1971-01-01

    In the rat, the injection of insulin or the consumption of carbohydrate causes sequential increases in the concentrations of tryptophan in the plasma and the brain and of serotonin in the brain. Serotonin-containing neurons may thus participate in systems whereby the rat brain integrates information about the metabolic state in its relation to control of homeostasis and behavior.

  1. Capture and retention of tritiated serotonin by the chick notochord

    International Nuclear Information System (INIS)

    Gerard, Anne; Gerard, Hubert; Dollander, Alexis

    1978-01-01

    The 3 day old chick notochord capacity to fix tritiated serotonin is maximal in its axis and in cephalic region. Observations permitting to find, the intracellular serotonin binding sites, contribute to an explanation of the capture mechanism and suggest a special direct role of the notochord on the monoaminergic neuron cytodifferentiation [fr

  2. Interaction of antidepressants with the serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Sørensen, Lena; Andersen, Jacob; Thomsen, Mette

    2012-01-01

    The serotonin transporter (SERT) and the norepinephrine transporter (NET) are sodium-dependent neurotransmitter transporters responsible for reuptake of released serotonin and norepinephrine, respectively, into nerve terminals in the brain. A wide range of inhibitors of SERT and NET are used...

  3. The rat frontal cortex serotonin receptors. Influence of supraletal irradiation

    International Nuclear Information System (INIS)

    Chanez, P.O.; Timmermans, R.; Gerber, G.B.

    1984-01-01

    The density of the frontal cortex serotonin-2 receptors was determined after a supralethal irradiation (20 Gy) in Wistar rat. Using spiperone as ligand, we observed an important decrease in the density of serotonin-2 receptor and an increase in the dissociation constant receptor-ligand, 3 days after exposure [fr

  4. Optically measured microvascular blood flow contrast of malignant breast tumors.

    Directory of Open Access Journals (Sweden)

    Regine Choe

    Full Text Available Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS, a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63; tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66, and using normal tissue in the contralateral breast was 2.27 (1.90-2.70. Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography.

  5. Acute Coronary Syndrome

    Science.gov (United States)

    ... heart cells are dying. An electrocardiogram (ECG or EKG) can diagnose an acute coronary syndrome by measuring ... Privacy Policy Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  6. Coronary artery fistula

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2015:chap 84. Friedman AH, Silverman NH. Congenital anomalies of the coronary arteries. In: ... provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  7. Coronary Artery Disease

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh

    2017-01-01

    A family history of coronary artery disease (CAD) is an important risk factor for adverse coronary events, in particular if the disease has an early onset. The risk of CAD is influenced by genetic and environmental factors with a greater genetic contribution earlier in life. Through recent years......), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early- onset CAD were recruited from the Western Denmark Heart...... Registry and risk factor control was evaluated. The study revealed that risk factors are common in early-onset CAD and that a large room for risk factor improvement remains. In study II, we used coronary computed tomography angiography to compare the coronary plaque burden and characteristics between 88...

  8. Auxetic coronary stent endoprosthesis

    DEFF Research Database (Denmark)

    Amin, Faisal; Ali, Murtaza Najabat; Ansari, Umar

    2014-01-01

    BACKGROUND: Cardiovascular heart disease is one of the leading health issues in the present era and requires considerable health care resources to prevent it. The present study was focused on the development of a new coronary stent based on novel auxetic geometry which enables the stent to exhibit...... a negative Poisson's ratio. Commercially available coronary stents have isotropic properties, whereas the vascular system of the body shows anisotropic characteristics. This results in a mismatch between anisotropic-isotropic properties of the stent and arterial wall, and this in turn is not favorable...... for mechanical adhesion of the commercially available coronary stents with the arterial wall. It is believed that an auxetic coronary stent with inherent anisotropic mechanical properties and negative Poisson's ratio will have good mechanical adhesion with the arterial wall. METHODS: The auxetic design...

  9. Acute coronary syndrome

    Science.gov (United States)

    ... Have plenty of fruits, veggies, whole grains, and lean meats. Try to limit foods high in cholesterol ... et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary ...

  10. Coronary hemodynamics in vasospastic angina

    International Nuclear Information System (INIS)

    Matsumura, Kentaro; Kubota, Shinobu; Serizawa, Takashi; Nakase, Emiko; Kawai, Ichiro; Saito, Takayuki

    1991-01-01

    To evaluate the coronary circulation and myocardial perfusion dynamics, we performed left coronary digital subtraction angiography (DSA) in 35 patients with vasospastic angina. The left coronary circulation time (CCT) measured from the proximal left coronary artery to the coronary sinus was 5.77±0.86 sec, and the left epicardial conducting artery transmission time (CAT) measured from the proximal left coronary artery to the apical area was 2.65±0.82 sec in normal controls. The CCT and CAT were significantly prolonged in patients with vasospastic angina, indicating that the coronary peripheral vascular resistance is probably greater after the cessation of nitrates and Ca ++ -antagonists. After the intracoronary injection of ergonovine malate, the CCT was slightly shortened, but the apical T 1/2 was significantly prolonged in patients with vasospastic angina. This suggested that coronary vasospasm is present not only in the epicardial arteries but also in coronary arteries with peripheral resistance. These phenomena were not observed in normal controls. We performed left coronary DSA after conventional left coronary cineangiography. When the CCT exceeded 6.7 sec, we considered that the coronary circulation was significantly impaired. We concluded that the coronary DSA is very useful for evaluating abnormal coronary circulation in patients with vasospastic angina during myocardial perfusion. (author)

  11. A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

    Science.gov (United States)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

  12. Melatonin and serotonin effects on gastrointestinal motility.

    Science.gov (United States)

    Thor, P J; Krolczyk, G; Gil, K; Zurowski, D; Nowak, L

    2007-12-01

    The gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin (M) suggests that this hormone is somehow involved in digestive pathophysiology. Release of GI melatonin from serotonin-rich enterochromaffin EC cells of the GI mucosa suggest close antagonistic relationship with serotonin (S) and seem to be related to periodicity of food intake. Food deprivation resulted in an increase of tissue and plasma concentrations of M. Its also act as an autocrine and paracrine hormone affecting not only epithelium and immune system but also smooth muscle of the digestive tract. Low doses M improve gastrointestinal transit and affect MMC. M reinforce MMCs cyclic pattern but inhibits spiking bowel activity. Pharmacological doses of M delay gastric emptying via mechanisms that involve CCK2 and 5HT3 receptors. M released in response to lipid infusion exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying. On isolated bowel S induces dose dependent increase in tone and reduction in amplitude of contraction which is affected by M. M reduced the tone but not amplitude or frequency of contraction. M is a promising therapeutic agent for IBS with activities independent of its effects on sleep, anxiety or depression. Since of its unique properties M could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers and irritable bowel syndrome.

  13. Coronary tortuosity: a long and winding road.

    NARCIS (Netherlands)

    Zegers, E.S.; Meursing, B.T.J.; Oude Ophuis, A.J.M.

    2007-01-01

    Coronary tortuosity is a phenomenon often encountered by cardiologists performing coronary angiography. The aetiology and clinical importance of coronary tortuosity are still unclear. Coronary tortuosity without fixed atherosclerotic stenosis in patients with angina pectoris and an abnormal exercise

  14. Coronary Artery Anomalies in Animals

    Directory of Open Access Journals (Sweden)

    Brian A. Scansen

    2017-04-01

    Full Text Available Coronary artery anomalies represent a disease spectrum from incidental to life-threatening. Anomalies of coronary artery origin and course are well-recognized in human medicine, but have received limited attention in veterinary medicine. Coronary artery anomalies are best described in the dog, hamster, and cow though reports also exist in the horse and pig. The most well-known anomaly in veterinary medicine is anomalous coronary artery origin with a prepulmonary course in dogs, which limits treatment of pulmonary valve stenosis. A categorization scheme for coronary artery anomalies in animals is suggested, dividing these anomalies into those of major or minor clinical significance. A review of coronary artery development, anatomy, and reported anomalies in domesticated species is provided and four novel canine examples of anomalous coronary artery origin are described: an English bulldog with single left coronary ostium and a retroaortic right coronary artery; an English bulldog with single right coronary ostium and transseptal left coronary artery; an English bulldog with single right coronary ostium and absent left coronary artery with a prepulmonary paraconal interventricular branch and an interarterial circumflex branch; and a mixed-breed dog with tetralogy of Fallot and anomalous origin of all coronary branches from the brachiocephalic trunk. Coronary arterial fistulae are also described including a coronary cameral fistula in a llama cria and an English bulldog with coronary artery aneurysm and anomalous shunting vessels from the right coronary artery to the pulmonary trunk. These examples are provided with the intent to raise awareness and improve understanding of such defects.

  15. Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

    Energy Technology Data Exchange (ETDEWEB)

    Stapleton, P.A.; McBride, C.R.; Yi, J.; Nurkiewicz, T.R., E-mail: tnurkiewicz@hsc.wvu.edu

    2015-11-01

    With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO{sub 2} aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m{sup 3}, 5 h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10{sup −4} M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated. - Highlights: • Female reproductive health associated with nanomaterial exposure is understudied. • We examined uterine microvascular alterations 24-hours after nano

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

    Science.gov (United States)

    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.

  17. Calcified Plaque of Coronary Artery: Factors Influencing Overestimation of Coronary Artery Stenosis on Coronary CT Angiography

    International Nuclear Information System (INIS)

    Kim, Mok Hee; Kim, Yun Hyeon; Choi, Song; Seon, Hyun Ju; Jeong, Gwang Woo; Park, Jin Gyoon; Kang, Heoung Keun; Ko, Joon Seok

    2010-01-01

    To assess the influence of calcified plaque characteristics on the overestimation of coronary arterial stenosis on a coronary CT angiography (CCTA). The study included 271 coronary arteries with calcified plaques identified by CCTA, and based on 928 coronary arteries from 232 patients who underwent both CCTA and invasive coronary angiography (ICA). Individual coronary arteries were classified into two groups by agreement based on the degree of stenosis from each CCTA and ICA: 1) group A includes patients with concordant CCTA and ICA results and, 2) group B includes patients with an overestimation of CCTA compared to ICA. Parameters including total calcium score, calcium score of an individual coronary artery, calcium burden number of an individual coronary artery, and the density of each calcified plaque (calcium score / number of calcium burden) for each individual coronary artery were compared between the two groups. Of the 271 coronary arteries, 164 (60.5%) were overestimated on CCTA. The left anterior descending artery (LAD) had a significantly low rate of overestimation (47.1%) compared to the other coronary arteries (p=0.001). No significant differences for total calcium score, calcium score of individual coronary artery, and the density of each calcified plaque from individual coronary arteries between two groups was observed. However, a decreasing tendency for the rate of overestimation on CCTA was observed with an increase in calcium burden of individual coronary arteries (p<0.05). The evaluation of coronary arteries suggests that the degree of coronary arterial stenosis had a tendency to be overestimated by calcified plaques on CCTA. However, the rate of overestimation for the degree of coronary arterial stenosis by calcified plaques was not significantly influenced by total calcium score, calcium score of individual coronary artery, and density of each calcified plaque

  18. Invasive angiography and revascularization in patients with stable angina following prior coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Joshi, Francis R; Biasco, Luigi; Pedersen, Frants

    2017-01-01

    . Follow-up data were available for all patients, by means of records linked to each Danish social security number. RESULTS: In patients with prior CABG and stable angina (n = 2,309), diagnostic angiography led to revascularization in 574 (24.9%) cases. Chronic kidney disease (HR 1.93 [1.08-3.44], P = 0......BACKGROUND: There are limited data to guide the optimum approach to patients presenting with angina after coronary artery bypass grafting (CABG). Although often referred for invasive angiography, the effectiveness of this is unknown; angina may also result from diffuse distal or micro......-vascular coronary disease and it is not known how often targets for intervention are identified. METHODS: Retrospective review of 50,460 patients undergoing angiography in East Denmark between January 2010 and December 2014. Clinical and procedural data were prospectively stored in a regional electronic database...

  19. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  20. Association between salivary serotonin and the social sharing of happiness.

    Directory of Open Access Journals (Sweden)

    Masahiro Matsunaga

    Full Text Available Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others, we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative, as well as the presence of a friend (absent, positive, or negative. Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking, which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  1. Selective serotonin reuptake inhibitors and risk for gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Batić-Mujanović Olivera

    2014-01-01

    Full Text Available The most of the known effects of selective serotonin reuptake inhibitors, beneficial or harmful, are associated with the inhibitory action of the serotonin reuptake transporter. This mechanism is present not only in neurons, but also in other cells such as platelets. Serotoninergic mechanism seems to have an important role in hemostasis, which has long been underestimated. Abnormal activation may lead to a prothrombotic state in patients treated with selective serotonin reuptake inhibitors. On one hand there may be an increased risk of bleeding, and on the other hand reduction in thrombotic risk may be possible. Serotonin is critical to maintain a platelet haemostatic function, such as platelet aggregation. Evidences from the studies support the hypothesis that antidepressants with a relevant blockade of action of serotonin reuptake mechanism may increase the risk of bleeding, which can occur anywhere in the body. Epidemiological evidences are, however, the most robust for upper gastrointestinal bleeding. It is estimated that this bleeding can occur in 1 in 100 to 1 in 1.000 patient-years of exposure to the high-affinity selective serotonin reuptake inhibitors, with very old patients at the highest risk. The increased risk may be of particular relevance when selective serotonin reuptake inhibitors are taken simultaneously with nonsteroidal anti-inflammatory drugs, low dose of aspirin or warfarin.

  2. Association between salivary serotonin and the social sharing of happiness.

    Science.gov (United States)

    Matsunaga, Masahiro; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  3. Oscillations and Multiple Equilibria in Microvascular Blood Flow.

    Science.gov (United States)

    Karst, Nathaniel J; Storey, Brian D; Geddes, John B

    2015-07-01

    We investigate the existence of oscillatory dynamics and multiple steady-state flow rates in a network with a simple topology and in vivo microvascular blood flow constitutive laws. Unlike many previous analytic studies, we employ the most biologically relevant models of the physical properties of whole blood. Through a combination of analytic and numeric techniques, we predict in a series of two-parameter bifurcation diagrams a range of dynamical behaviors, including multiple equilibria flow configurations, simple oscillations in volumetric flow rate, and multiple coexistent limit cycles at physically realizable parameters. We show that complexity in network topology is not necessary for complex behaviors to arise and that nonlinear rheology, in particular the plasma skimming effect, is sufficient to support oscillatory dynamics similar to those observed in vivo.

  4. 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...

  5. 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...... 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. RESULTS: 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...

  6. 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...... 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...... diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54-0·66; pdiabetic neuropathy (0·66, 0·57-0·75; p

  7. Distal coronary hemoperfusion during percutaneous transluminal coronary angioplasty

    NARCIS (Netherlands)

    Muinck, Ebo Derk de

    1994-01-01

    In this thesis several aspects of passive and active coronary perfusion during coronary angioplasty are investigated. The autoperfusion balloon catheters that were evaluated are the Stack® and the RX-60® catheters (Advanced Cardiovascular Systems, inc., Santa Clara, California, U.S.A). The coronary

  8. A mathematical model of coronary blood flow control: simulation of patient-specific three-dimensional hemodynamics during exercise

    Science.gov (United States)

    Lau, Kevin D.; Asrress, Kaleab N.; Redwood, Simon R.; Figueroa, C. Alberto

    2016-01-01

    This work presents a mathematical model of the metabolic feedback and adrenergic feedforward control of coronary blood flow that occur during variations in the cardiac workload. It is based on the physiological observations that coronary blood flow closely follows myocardial oxygen demand, that myocardial oxygen debts are repaid, and that control oscillations occur when the system is perturbed and so are phenomenological in nature. Using clinical data, we demonstrate that the model can provide patient-specific estimates of coronary blood flow changes between rest and exercise, requiring only the patient's heart rate and peak aortic pressure as input. The model can be used in zero-dimensional lumped parameter network studies or as a boundary condition for three-dimensional multidomain Navier-Stokes blood flow simulations. For the first time, this model provides feedback control of the coronary vascular resistance, which can be used to enhance the physiological accuracy of any hemodynamic simulation, which includes both a heart model and coronary arteries. This has particular relevance to patient-specific simulation for which heart rate and aortic pressure recordings are available. In addition to providing a simulation tool, under our assumptions, the derivation of our model shows that β-feedforward control of the coronary microvascular resistance is a mathematical necessity and that the metabolic feedback control must be dependent on two error signals: the historical myocardial oxygen debt, and the instantaneous myocardial oxygen deficit. PMID:26945076

  9. A mathematical model of coronary blood flow control: simulation of patient-specific three-dimensional hemodynamics during exercise.

    Science.gov (United States)

    Arthurs, Christopher J; Lau, Kevin D; Asrress, Kaleab N; Redwood, Simon R; Figueroa, C Alberto

    2016-05-01

    This work presents a mathematical model of the metabolic feedback and adrenergic feedforward control of coronary blood flow that occur during variations in the cardiac workload. It is based on the physiological observations that coronary blood flow closely follows myocardial oxygen demand, that myocardial oxygen debts are repaid, and that control oscillations occur when the system is perturbed and so are phenomenological in nature. Using clinical data, we demonstrate that the model can provide patient-specific estimates of coronary blood flow changes between rest and exercise, requiring only the patient's heart rate and peak aortic pressure as input. The model can be used in zero-dimensional lumped parameter network studies or as a boundary condition for three-dimensional multidomain Navier-Stokes blood flow simulations. For the first time, this model provides feedback control of the coronary vascular resistance, which can be used to enhance the physiological accuracy of any hemodynamic simulation, which includes both a heart model and coronary arteries. This has particular relevance to patient-specific simulation for which heart rate and aortic pressure recordings are available. In addition to providing a simulation tool, under our assumptions, the derivation of our model shows that β-feedforward control of the coronary microvascular resistance is a mathematical necessity and that the metabolic feedback control must be dependent on two error signals: the historical myocardial oxygen debt, and the instantaneous myocardial oxygen deficit. Copyright © 2016 the American Physiological Society.

  10. The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.

    Science.gov (United States)

    Cui, Shanyu; Park, Hyewon; Park, Hyelim; Mun, Dasom; Lee, Seung Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui Nam; Lee, Moon Hyoung; Joung, Boyoung

    2018-03-01

    The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP). During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(-/-)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. © Copyright: Yonsei University College of Medicine 2018

  11. 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)

  12. Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

    Directory of Open Access Journals (Sweden)

    Lih eKuo

    2013-08-01

    Full Text Available Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO during oxidative stress and inflammation related to the activation of L-arginine consuming enzyme arginase. Superoxide produced in the vascular wall compromises vasomotor function by not only scavenging endothelium-derived NO but also inhibiting prostacyclin synthesis due to formation of peroxynitrite. The upregulation of arginase contributes to the deficiency of endothelial NO and microvascular dysfunction in various vascular diseases by initiating or following oxidative stress and inflammation. Hydrogen peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function and plays important roles in the physiological regulation of coronary blood flow. In occlusive coronary ischemia, the release of hydrogen peroxide from the microvasculature helps to restore vasomotor function of coronary collateral microvessels with exercise training. However, excessive production and prolonged exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial function by reducing L-arginine availability through hydroxyl radical-dependent upregulation of arginase. The redox signaling can be a double-edged sword in the microcirculation, which helps tissue survival in one way by improving vasomotor regulation and elicits oxidative stress and tissue injury in the other way by causing vascular dysfunction. The impact of vascular arginase on the development of vasomotor dysfunction associated with angiotensin II receptor activation, hypertension, ischemia-reperfusion, hypercholesterolemia and inflammatory insults is discussed.

  13. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors

    International Nuclear Information System (INIS)

    Pazos, A.; Palacios, M.

    1985-01-01

    The distribution of serotonin-1 (5-HT 1 ) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [ 3 H]serotonin (5-[ 3 H]HT), 8-hydroxy-2-[N-dipropylamino- 3 H]tetralin (8-OH-[ 3 H]DPAT), [ 3 H]LSD and [ 3 H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[ 3 H]HT binding by several serotonin-1 agonists led to the identification of brain areas enriched in each one of the three subtypes of 5-HT 1 recognition sites already described. The existence of these 'selective' areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. Very high concentrations of 5-HT 1 receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The distribution of 5-HT 1 receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. (Auth.)

  14. Serotonin syndrome:case report and current concepts.

    LENUS (Irish Health Repository)

    Fennell, J

    2005-05-01

    Selective serotonin reuptake inhibitors (SSRI\\'s) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

  15. The importance of serotonin in the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Jarosław Koza

    2017-12-01

    Description of the current knowledge and conclusions. Serotonin is responsible for some symptoms of carcinoid syndrome. It is the result of higher 5-hydroxytryptamine content in the body. Moreover disrupted serotonin system is found in different gastrointestinal disorders e.g. in gastroesophageal reflux disease, functional heartburn, hypersensitive esophagus, functional dyspepsia, irritable bowel syndrome (both diarrhoea predominant and constipation predominant as well as in inflammatory bowel diseases. Knowledge of changed mechanisms in particular diseases facilitates the optimal choice of treatment. Drugs affecting the serotonin system in gastroenterological clinical practice are useful especially in the case of abnormalities in the brain - gut axis.

  16. Moderation of antidepressant response by the serotonin transporter gene

    DEFF Research Database (Denmark)

    Huezo-Diaz, Patricia; Uher, Rudolf; Smith, Rebecca

    2009-01-01

    Background: There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR...... the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Results: The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more...

  17. Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

    DEFF Research Database (Denmark)

    Ahdidan, Jamila; Foldager, Leslie; Rosenberg, Raben

    2013-01-01

    Objective: The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we...... that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found. Conclusions: The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients...... and the serotonin transporter polymorphism....

  18. Acetylcholine versus cold pressor testing for evaluation of coronary endothelial function.

    Directory of Open Access Journals (Sweden)

    Ahmed AlBadri

    Full Text Available Assessment of coronary endothelial function with intracoronary acetylcholine (IC-Ach provides diagnostic and prognostic data in patients with suspected coronary microvascular dysfunction (CMD, but is often not feasible due in part to the time and expertise needed for pharmacologic mixing. Cold pressor testing (CPT is a simple and safe stimulus useful for either invasive or non-invasive endothelial function testing and myocardial perfusion imaging but has not been specifically evaluated among symptomatic women with signs of ischemic heart disease (IHD who have no obstructive coronary artery disease (CAD.163 women with signs and symptoms of IHD and no obstructive CAD from the NHLBI- Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD study underwent coronary reactivity testing with a Doppler flow wire (FloWire® Volcano, San Diego, CA in the proximal left anterior descending artery. Coronary artery diameter and coronary blood flow (CBF assessed by core lab using QCA before and after IC-Ach (18.2 μg/ml infused over 3 minutes and during CPT.Mean age was 55 ± 12 years. Rate pressure product (RPP in response to IC-Ach did not change (baseline to peak, P = 0.26, but increased during CPT (363±1457; P = 0.0028. CBF in response to CPT was poorly correlated to IC-Ach CBF. Change in coronary artery diameter after IC-Ach correlated with change after CPT (r = 0.59, P<0.001. The correlation coefficient was stronger in subjects with coronary dilation to IC-Ach (r = 0.628, P<0.001 versus those without dilation (r = 0.353, P = 0.002, suggesting that other factors may be important to this relationship when endothelium is abnormal.In women with no obstructive CAD and suspected CMD, coronary diameter changes with IC-Ach and CPT are moderately-well correlated suggesting that CPT testing may be of some use, particularly among patients with normal endothelial function, however, not an alternative to IC-Ach for diagnosis of coronary

  19. Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo.

    Science.gov (United States)

    Nishimiya, Kensuke; Matsumoto, Yasuharu; Shindo, Tomohiko; Hanawa, Kenichiro; Hasebe, Yuhi; Tsuburaya, Ryuji; Shiroto, Takashi; Takahashi, Jun; Ito, Kenta; Ishibashi-Ueda, Hatsue; Yasuda, Satoshi; Shimokawa, Hiroaki

    2015-01-01

    The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined. Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, Pmicro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges. The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.

  20. Nuclear cardiology and coronary surgery

    DEFF Research Database (Denmark)

    Eckardt, R.; Andersen, L.I.; Hesse, B.

    2008-01-01

    Rising age, repeated percutaneous coronary revascularizations, and co-morbidity such as overweight, diabetes, and hypertension, characterize a change over the last 20-30 years in coronary patients referred to coronary artery bypass grafting (CABG). This patient group represents a great part of to...

  1. The serotonin transporter: Examination of the changes in transporter affinity induced by ligand binding

    International Nuclear Information System (INIS)

    Humphreys, C.J.

    1989-01-01

    The plasmalemmal serotonin transporter uses transmembrane gradients of Na + , Cl - and K + to accumulate serotonin within blood platelets. Transport is competitively inhibited by the antidepressant imipramine. Like serotonin transport, imipramine binding requires Na + . Unlike serotonin, however, imipramine does not appear to be transported. To gain insight into the mechanism of serotonin transport the author have analyzed the influences of Na + and Cl - , the two ions cotransported with serotonin, on both serotonin transport and the interaction of imipramine and other antidepressant drugs with the plasmalemmal serotonin transporter of human platelets. Additionally, the author have synthesized, purified and characterized the binding of 2-iodoimipramine to the serotonin transporter. Finally, the author have conducted a preliminary study of the inhibition of serotonin transport and imipramine binding produced by dicyclohexylcarbodiimide. My results reveal many instances of positive heterotropic cooperativity in ligand binding to the serotonin transporter. Na + binding enhances the transporters affinity for imipramine and several other antidepressant drugs, and also increases the affinity for Cl - . Cl - enhances the transporters affinity for imipramine, as well as for Na + . At concentrations in the range of its K M for transport serotonin is a competitive inhibitor of imipramine binding. At much higher concentrations, however, serotonin also inhibits imipramines dissociation rate constant. This latter effect which is Na + -independent and species specific, is apparently produced by serotonin binding at a second, low affinity site on, or near, the transporter complex. Iodoimipramine competitively inhibit both [ 3 H]imipramine binding and [ 3 H]serotonin transport

  2. Serotonin binding in vitro by releasable proteins from human blood platelets

    International Nuclear Information System (INIS)

    Heemstra, V.L.

    1983-11-01

    Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and β-thromboglobulin (βTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified [ 125 I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, βTG, with [ 14 C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric βTG with a dissociation constant of about 4 X 10(sup-8) M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and βTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and βTG may be mediated in part by serotonin-protein associations

  3. [Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer].

    Science.gov (United States)

    Liu, Jin-kang; Wang, Xiao-yi; Xiong, Zeng; Zhou, Hui; Zhou, Jian-hua; Fu, Chun-yan; Li, Bo

    2008-08-01

    To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.

  4. VEGF expression and microvascular density in relation to high-risk ...

    African Journals Online (AJOL)

    Bassma M. El Sabaa

    2012-01-13

    Jan 13, 2012 ... Eleven cases were low grade and 19 were high-grade cases. VEGF expression .... increasing microvascular permeability,26 degradation of extra- ...... soluble receptors in pre-invasive, invasive and recurrent cervical cancer.

  5. Anomalous origin of right coronary artery from left coronary sinus.

    Science.gov (United States)

    Hamzeh, Gadah; Crespo, Alex; Estarán, Rafael; Rodríguez, Miguel A; Voces, Roberto; Aramendi, José I

    2008-08-01

    Anomalous aortic origin of the coronary arteries is uncommon but clinically significant. Manifestations vary from asymptomatic patients to those who present with angina pectoris, myocardial infarction, heart failure, syncope, arrhythmias, and sudden death. We describe 4 patients, aged 34 to 59 years, who were diagnosed with right coronary artery arising from the left sinus of Valsalva, confirmed by coronary angiography, which was surgically repaired. Three patients presented dyspnea and angina, and one with acute myocardial infarction. At operation, the right coronary artery was dissected at the take-off from the intramural course, and reimplanted into the right sinus of Valsalva. There was no mortality. One patient had associated coronary artery disease that required stent placement postoperatively. This reimplantation technique provides a good physiological and anatomical repair, eliminates a slit-like ostium, avoids compression of the coronary artery between the aorta and the pulmonary artery, and gives superior results to coronary artery bypass grafting or the unroofing technique.

  6. The serotonin transporter and early life stress : Translational perspectives

    NARCIS (Netherlands)

    Houwing, Danielle J; Buwalda, Bauke; Zee, van der Eddy; de Boer, Sietse F; Olivier, Jocelien D A

    2017-01-01

    The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human

  7. Serotonin blockade delays learning performance in a cooperative fish.

    Science.gov (United States)

    Soares, Marta C; Paula, José R; Bshary, Redouan

    2016-09-01

    Animals use learning and memorizing to gather information that will help them to make ecologically relevant decisions. Neuro-modulatory adjustments enable them to make associations between stimuli and appropriate behavior. A key candidate for the modulation of cooperative behavior is serotonin. Previous research has shown that modulation of the serotonergic system spontaneously affects the behavior of the cleaner wrasse Labroides dimidiatus during interactions with so-called 'client' reef fish. Here, we asked whether shifts in serotonin function affect the cleaners' associative learning abilities when faced with the task to distinguish two artificial clients that differ in their value as a food source. We found that the administration of serotonin 1A receptor antagonist significantly slowed learning speed in comparison with saline treated fish. As reduced serotonergic signaling typically enhances fear, we discuss the possibility that serotonin may affect how cleaners appraise, acquire information and respond to client-derived stimuli via manipulation of the perception of danger.

  8. Relationships of Whole Blood Serotonin and Plasma Norepinephrine within Families.

    Science.gov (United States)

    Leventhal, Bennett L.; And Others

    1990-01-01

    This study of 47 families of autistic probands found that whole blood serotonin was positively correlated between autistic children and their mothers, fathers, and siblings, but plasma norepinephrine levels were not. (Author/JDD)

  9. Cholinesterase catalyzed hydrolysis of O-acyl derivatives of serotonin

    International Nuclear Information System (INIS)

    Makhaeva, G.F.; Suvorov, N.N.; Ginodman, L.N.; Antonov, V.K.; AN SSSR, Moscow. Inst. Bioorganicheskoj Khimii)

    1977-01-01

    Hydrolysis of O acyl serotonin derivatives containing the residues of monocarbon dicarbon and amino acids under the effect of horse serum butyryl cholinesterase and bull erythrocytic acetylcholinesterase has been studied. It has been established, that acetylcholinesterase hydrolizes O acetylserotonin only; butyrylcholinesterase hydrolizes all the compounds investigated, except for 5,5'-terephthaloildioxytriptamine. The kinetic parameters of hydrolysis were determined. O acyl serotonin derivatives turned out good substrates of butylrylcholinesterase; serotonin and 5.5'-terephtaloildioxytriptamine are effective competitine inhibitors of the enzyme. Estimating of resistance of O acyl serotonin derivatines to blood cholinesterase effect under physiological conditions shows that the compounds investigated with the exception of 5,5'-terephthaloildioxytriptamine must be quickly hydrolyzed under butyrylcholinesterase action. 5,5'-terephthaloildioxytriptamine is suggested as a radioprotective preparation with the prolonged effect, which agrees with the biological test results

  10. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    Kendall, D.A.; Taylor, D.P.; Enna, S.J.

    1983-01-01

    High (17 nM) and low (603 nM) affinity binding sites for [ 3 ]tetrahydrotrazodone ([ 3 ] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [ 3 ]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [ 3 ] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [ 3 ]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  11. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease

    NARCIS (Netherlands)

    P.W.J.C. Serruys (Patrick); M-C. Morice (Marie-Claude); A.P. Kappetein (Arie Pieter); A. Colombo (Antonio); D.R. Holmes Jr (David); M.J. Mack (Michael); E. Stahle (Elisabeth); T.E. Feldman (Ted); M.J.B.M. van den Brand (Marcel); E.J. Bass (Eric); N. van Dyck (Nic); K. Leadly (Katrin); K.D. Dawkins (Keith); F.W. Mohr (Friedrich)

    2009-01-01

    textabstractBACKGROUND Percutaneous coronary intervention (PCI) involving drug-eluting stents is increasingly used to treat complex coronary artery disease, although coronary-artery bypass grafting (CABG) has been the treatment of choice historically. Our trial compared PCI and CABG for treating

  12. Interactions of the gasotransmitters contribute to microvascular tone (dysregulation in the preterm neonate.

    Directory of Open Access Journals (Sweden)

    Rebecca M Dyson

    Full Text Available Hydrogen sulphide (H2S, nitric oxide (NO, and carbon monoxide (CO are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow.90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions.No relationship was observed between NO and CO (p = 0.18, r = 0.18. A positive relationship between NO and H2S (p = 0.008, r = 0.28 and an inverse relationship between CO and H2S (p = 0.01, r = -0.33 exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented.The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.

  13. GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

    Science.gov (United States)

    Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

    2017-11-01

    Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM

  14. In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K

    2011-01-01

    Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....

  15. SEP-225289 serotonin and dopamine transporter occupancy: a PET study.

    Science.gov (United States)

    DeLorenzo, Christine; Lichenstein, Sarah; Schaefer, Karen; Dunn, Judith; Marshall, Randall; Organisak, Lisa; Kharidia, Jahnavi; Robertson, Brigitte; Mann, J John; Parsey, Ramin V

    2011-07-01

    SEP-225289 is a novel compound that, based on in vitro potencies for transporter function, potentially inhibits reuptake at dopamine, norepinephrine, and serotonin transporters. An open-label PET study was conducted during the development of SEP-225289 to investigate its dopamine and serotonin transporter occupancy. Different single doses of SEP-225289 were administered to healthy volunteers in 3 cohorts: 8 mg (n = 7), 12 mg (n = 5), and 16 mg (n = 7). PET was performed before and approximately 24 h after oral administration of SEP-225289, to assess occupancy at trough levels. Dopamine and serotonin transporter occupancies were estimated from PET using (11)C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane ((11)C-PE2I) and (11)C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ((11)C-DASB), respectively. Plasma concentration of SEP-225289 was assessed before ligand injection, and subjects were monitored for adverse events. Average dopamine and serotonin transporter occupancies increased with increasing doses of SEP-225289. Mean dopamine and serotonin transporter occupancies were 33% ± 11% and 2% ± 13%, respectively, for 8 mg; 44% ± 4% and 9% ± 10%, respectively, for 12 mg; and 49% ± 7% and 14% ± 15%, respectively, for 16 mg. On the basis of the relationship between occupancy and plasma concentration, dopamine transporter IC(50) (the plasma concentration of drug at 50% occupancy) was determined (4.5 ng/mL) and maximum dopamine transporter occupancy was extrapolated (85%); however, low serotonin transporter occupancy prevented similar serotonin transporter calculations. No serious adverse events were reported. At the doses evaluated, occupancy of the dopamine transporter was significantly higher than that of the serotonin transporter, despite similar in vitro potencies, confirming that, in addition to in vitro assays, PET occupancy studies can be instrumental to the drug development process by informing early decisions about

  16. Genetics of premenstrual syndrome: investigation of specific serotonin receptor polymorphisms

    OpenAIRE

    Dhingra, Vandana

    2014-01-01

    Premenstrual dysphoric disorder (PMDD) is a distressing and disabling syndrome causing a significant degree of impairment on daily functioning and interpersonal relationships in 3-8% of the women. With the convincing evidence that PMS is inheritable and that serotonin is important in the pathogenesis of PMS, and failure of initial studies to demonstrate significant associations between key genes controlling the synthesis, reuptake and catabolism of serotonin and PMDD, the main aim of this the...

  17. Plasma serotonin in horses undergoing surgery for small intestinal colic

    OpenAIRE

    Torfs, Sara C; Maes, An A; Delesalle, Catherine J; Pardon, Bart; Croubels, Siska M; Deprez, Piet

    2015-01-01

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those fo...

  18. Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

    Science.gov (United States)

    Borges, Juliana Pereira; Mendes, Fernanda de Souza Nogueira Sardinha; Lopes, Gabriella de Oliveira; Sousa, Andréa Silvestre de; Mediano, Mauro Felippe Felix; Tibiriçá, Eduardo

    2018-08-15

    Chronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. Microvascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). Peak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). Endothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  20. Serotonin induces peripheral antinociception via the opioidergic system.

    Science.gov (United States)

    Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda E; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

    2018-01-01

    Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined. The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE 2 (2 μg). Serotonin (250 ng), administered locally to the right paw of animals, produces antinociception in this model. The selective antagonists for mu, delta and kappa opioid receptors, clocinnamox clocinnamox (40 μg), naltrindole (60 μg) and nor-binaltorfimina (200 μg), respectively, inhibited the antinociceptive effect induced by serotonin. Additionally, bestatin (400 μg), an inhibitor of enkephalinases that degrade peptides opioids, enhanced the antinociceptive effect induced by serotonin (low dose of 62.5 ng). These results suggest that serotonin possibly induce peripheral antinociception through the release of endogenous opioid peptides, possible from immune cells or keratinocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Lung damage and pulmonary uptake of serotonin in intact dogs

    International Nuclear Information System (INIS)

    Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

    1985-01-01

    The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [ 3 H]serotonin and the extravascular volume accessible to [ 14 C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage

  2. Serotonin Regulates the Feeding and Reproductive Behaviors of Pratylenchus penetrans.

    Science.gov (United States)

    Han, Ziduan; Boas, Stephanie; Schroeder, Nathan E

    2017-07-01

    The success of all plant-parasitic nematodes is dependent on the completion of several complex behaviors. The lesion nematode Pratylenchus penetrans is an economically important parasite of a diverse range of plant hosts. Unlike the cyst and root-knot nematodes, P. penetrans moves both within and outside of the host roots and can feed from both locations. Adult females of P. penetrans require insemination by actively moving males for reproduction and can lay eggs both within and outside of the host roots. We do not have a complete understanding of the molecular basis for these behaviors. One candidate modulator of these behaviors is the neurotransmitter serotonin. Previous research demonstrated an effect of exogenously applied serotonin on the feeding and male mating behaviors of cyst and root-knot nematodes. However, there are no data on the role of exogenous serotonin on lesion nematodes. Similarly, there are no data on the presence and function of endogenous serotonin in any plant-parasitic nematode. Here, we establish that exogenous serotonin applied to P. penetrans regulates both feeding and sex-specific behaviors. Furthermore, using immunohistochemistry and pharmacological assays, our data suggest that P. penetrans utilizes endogenous serotonin to regulate both feeding and sex-specific behaviors.

  3. Noninvasive measurement of lung carbon-11-serotonin extraction in man

    International Nuclear Information System (INIS)

    Coates, G.; Firnau, G.; Meyer, G.J.; Gratz, K.F.

    1991-01-01

    The fraction of serotonin extracted on a single passage through the lungs is being used as an early indicator of lung endothelial damage but the existing techniques require multiple arterial blood samples. We have developed a noninvasive technique to measure lung serotonin uptake in man. We utilized the double indicator diffusion principle, a positron camera, 11 C-serotonin as the substrate, and 11 CO-erythrocytes as the vascular marker. From regions of interest around each lung, we recorded time-activity curves in 0.5-sec frames for 30 sec after a bolus injection of first the vascular marker 11 CO-erythrocytes and 10 min later 11 C-serotonin. A second uptake measurement was made after imipramine 25-35 mg was infused intravenously. In three normal volunteers, the single-pass uptake of 11 C-serotonin was 63.9% +/- 3.6%. This decreased in all subjects to a mean of 53.6% +/- 1.4% after imipramine. The rate of lung washout of 11 C was also significantly prolonged after imipramine. This noninvasive technique can be used to measure lung serotonin uptake to detect early changes in a variety of conditions that alter the integrity of the pulmonary endothelium

  4. Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

    Science.gov (United States)

    Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P seizure threshold (P seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

  5. INFLUENCE OF A SEROTONIN-RICH AND DOPAMINE-RICH DIET ON PLATELET SEROTONIN CONTENT AND URINARY-EXCRETION OF BIOGENIC-AMINES AND THEIR METABOLITES

    NARCIS (Netherlands)

    KEMA, IP; SCHELLINGS, AMJ; MEIBORG, G; HOPPENBROUWERS, CJM; MUSKIET, FAJ

    Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although

  6. Coronary artery anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)

    2011-12-15

    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

  7. [Pregnancy and coronary artery dissection].

    Science.gov (United States)

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna

    2015-01-01

    Acute myocardial infarction during pregnancy is associated with high maternal and fetal mortality. Coronary atherosclerosis is the most common cause due to an increase in the age of the patients and the association with cardiovascular risk factors such as smoking, hypertension, diabetes mellitus, preeclampsia, and the existence of family history of coronary disease. However, thrombosis, coronary dissection or coronary vasospasms are other causes that may justify it. We report the case of a 33 weeks pregnant first-time mother, without cardiovascular risk factors, who presented an acute coronary event in the context of atherosclerotic disease and coronary dissection after percutaneous coronary intervention. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  8. Coronary MR angiography: current status

    International Nuclear Information System (INIS)

    Danias, P.G.; Manning, W.J.

    2000-01-01

    Since first described in the early 1990s, coronary magnetic resonance angiography (MRA) has evolved as a promising noninvasive modality for imaging of the coronary arteries and evaluation of coronary artery disease. Despite technical limitations, coronary MRA has established value for imaging of anomalous coronary arteries and assessment of bypass graft patency. Current research focuses on the development of optimal respiratory compensation strategies, improved spatial and temporal resolution and faster acquisition of image data. The accurate detection of stenoses and assessment of the severity of coronary atherosclerosis is presently being evaluated with large multi-center studies. With further technique enhancements and more clinical experience, coronary MRA is likely to become the dominant noninvasive modality in clinical cardiology. (orig.) [de

  9. 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

  10. 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

  11. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors.

    Science.gov (United States)

    Dobry, Yuriy; Rice, Timothy; Sher, Leo

    2013-01-01

    At present, there are scarce clinical and basic lab data concerning the risk of acute serotonin toxicity from selective serotonin reuptake inhibitors (SSRIs) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) co-administration. The health care community can strongly benefit from efforts to address the high risks associated with serotonin syndrome from this specific drug combination. The aim of this work is to review the risk of serotonin syndrome in adolescents and young adults prescribed with SSRIs and are concurrently using ecstasy. An electronic search of the major behavioral science bibliographic databases (Pubmed, PsycINFO, Medline) was conducted to retrieve peer-reviewed articles, which detail the clinical characteristics, biological mechanisms and social implications of SSRIs, MDMA, and their potential synergism in causing serotonin syndrome in the pediatric and young adult population. Search terms included "serotonin syndrome", "ecstasy", "MDMA", "pediatric", and "SSRI". Additional references were incorporated from the bibliographies of these retrieved articles. MDMA, in combination with the widely-prescribed SSRI antidepressant class, can lead to rapid, synergistic rise of serotonin (5-HT) concentration in the central nervous system, leading to the acute medical emergency known as serotonin syndrome. This review addresses such complication through an exploration of the theoretical mechanisms and clinical manifestations of this life-threatening pharmacological interaction. The increasing incidences of recreational ecstasy use and SSRI pharmacotherapy among multiple psychiatric disorders in the adolescent population have made this an overlooked yet increasingly relevant danger, which poses a threat to public health. This can be curbed through further research, as well as greater health care provision and attention from a regulatory body owing.

  12. CT coronary angiography vs. invasive coronary angiography in CHD

    Directory of Open Access Journals (Sweden)

    Anja Hagen

    2012-04-01

    Full Text Available Scientific background: Various diagnostic tests including conventional invasive coronary angiography and non-invasive computed tomography (CT coronary angiography are used in the diagnosis of coronary heart disease (CHD. Research questions: The present report aims to evaluate the clinical efficacy, diagnostic accuracy, prognostic value cost-effectiveness as well as the ethical, social and legal implications of CT coronary angiography versus invasive coronary angiography in the diagnosis of CHD. Methods: A systematic literature search was conducted in electronic data bases (MEDLINE, EMBASE etc. in October 2010 and was completed with a manual search. The literature search was restricted to articles published from 2006 in German or English. Two independent reviewers were involved in the selection of the relevant publications. The medical evaluation was based on systematic reviews of diagnostic studies with invasive coronary angiography as the reference standard and on diagnostic studies with intracoronary pressure measurement as the reference standard. Study results were combined in a meta-analysis with 95 % confidence intervals (CI. Additionally, data on radiation doses from current non-systematic reviews were taken into account. A health economic evaluation was performed by modelling from the social perspective with clinical assumptions derived from the meta-analysis and economic assumptions derived from contemporary German sources. Data on special indications (bypass or in-stent-restenosis were not included in the evaluation. Only data obtained using CT scanners with at least 64 slices were considered. Results: No studies were found regarding the clinical efficacy or prognostic value of CT coronary angiography versus conventional invasive coronary angiography in the diagnosis of CHD. Overall, 15 systematic reviews with data from 44 diagnostic studies using invasive coronary angiography as the reference standard (identification of obstructive

  13. Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine

    Directory of Open Access Journals (Sweden)

    O’Connor Erin K

    2012-05-01

    Full Text Available Abstract Background Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine. Methods Pigs received intracoronary infusions of physiologic levels (1–100 nM of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels. Results In vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males. Conclusions Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.

  14. Modulation for emergent networks: serotonin and dopamine.

    Science.gov (United States)

    Weng, Juyang; Paslaski, Stephen; Daly, James; VanDam, Courtland; Brown, Jacob

    2013-05-01

    In autonomous learning, value-sensitive experiences can improve the efficiency of learning. A learning network needs be motivated so that the limited computational resources and the limited lifetime are devoted to events that are of high value for the agent to compete in its environment. The neuromodulatory system of the brain is mainly responsible for developing such a motivation system. Although reinforcement learning has been extensively studied, many existing models are symbolic whose internal nodes or modules have preset meanings. Neural networks have been used to automatically generate internal emergent representations. However, modeling an emergent motivational system for neural networks is still a great challenge. By emergent, we mean that the internal representations emerge autonomously through interactions with the external environments. This work proposes a generic emergent modulatory system for emergent networks, which includes two subsystems - the serotonin system and the dopamine system. The former signals a large class of stimuli that are intrinsically aversive (e.g., stress or pain). The latter signals a large class of stimuli that are intrinsically appetitive (e.g., pleasure or sweet). We experimented with this motivational system for two settings. The first is a visual recognition setting to investigate how such a system can learn through interactions with a teacher, who does not directly give answers, but only punishments and rewards. The second is a setting for wandering in the presence of a friend and a foe. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

    Science.gov (United States)

    Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

    2009-01-01

    The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

  16. 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.

  17. Comparison of tissue processing methods for microvascular visualization in axolotls.

    Science.gov (United States)

    Montoro, Rodrigo; Dickie, Renee

    2017-01-01

    The vascular system, the pipeline for oxygen and nutrient delivery to tissues, is essential for vertebrate development, growth, injury repair, and regeneration. With their capacity to regenerate entire appendages throughout their lifespan, axolotls are an unparalleled model for vertebrate regeneration, but they lack many of the molecular tools that facilitate vascular imaging in other animal models. The determination of vascular metrics requires high quality image data for the discrimination of vessels from background tissue. Quantification of the vasculature using perfused, cleared specimens is well-established in mammalian systems, but has not been widely employed in amphibians. The objective of this study was to optimize tissue preparation methods for the visualization of the microvascular network in axolotls, providing a basis for the quantification of regenerative angiogenesis. To accomplish this aim, we performed intracardiac perfusion of pigment-based contrast agents and evaluated aqueous and non-aqueous clearing techniques. The methods were verified by comparing the quality of the vascular images and the observable vascular density across treatment groups. Simple and inexpensive, these tissue processing techniques will be of use in studies assessing vascular growth and remodeling within the context of regeneration. Advantages of this method include: •Higher contrast of the vasculature within the 3D context of the surrounding tissue •Enhanced detection of microvasculature facilitating vascular quantification •Compatibility with other labeling techniques.

  18. Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.

    Science.gov (United States)

    Freitas, Felipe; Estato, Vanessa; Carvalho, Vinícius Frias; Torres, Rafael Carvalho; Lessa, Marcos Adriano; Tibiriçá, Eduardo

    2013-10-01

    The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model. Male Wistar rats (170-250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively. Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats. Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations. © 2013 John Wiley & Sons Ltd.

  19. 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.

  20. Coronary CT Angiography in the Quantitative Assessment of Coronary Plaques

    Directory of Open Access Journals (Sweden)

    Zhonghua Sun

    2014-01-01

    Full Text Available Coronary computed tomography angiography (CCTA has been recently evaluated for its ability to assess coronary plaque characteristics, including plaque composition. Identification of the relationship between plaque composition by CCTA and patient clinical presentations may provide insight into the pathophysiology of coronary artery plaque, thus assisting identification of vulnerable plaques which are associated with the development of acute coronary syndrome. CCTA-generated 3D visualizations allow evaluation of both coronary lesions and lumen changes, which are considered to enhance the diagnostic performance of CCTA. The purpose of this review is to discuss the recent developments that have occurred in the field of CCTA with regard to its diagnostic accuracy in the quantitative assessment of coronary plaques, with a focus on the characterization of plaque components and identification of vulnerable plaques.

  1. Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.

    Science.gov (United States)

    Kim, Dae Hyun; Grodstein, Francine; Newman, Anne B; Chaves, Paulo H M; Odden, Michelle C; Klein, Ronald; Sarnak, Mark J; Lipsitz, Lewis A

    2015-09-01

    To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). Community. Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication. © 2015, Copyright the Authors Journal compilation © 2015

  2. Microvascular versus macrovascular cerebral vasomotor reactivity in patients with severe internal carotid artery stenosis or occlusion.

    Science.gov (United States)

    Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Martí-Fàbregas, Joan; Durduran, Turgut

    2014-02-01

    In patients with severe internal carotid artery steno-occlusive lesions (ISOL), impaired cerebrovascular reactivity (CVR) is predictive of future ischemic stroke (IS) or transient ischemic attack (TIA). Therefore, the evaluation of CVR in ISOL patients may be a means to evaluate the risk for IS/TIA and decide on an intervention. Our aim was (1) to explore the feasibility of concurrent near-infrared spectroscopy (NIRS-DOS), diffuse correlation spectroscopy, and transcranial Doppler for CVR assessment in ISOL patients, and (2) to compare macrovascular and microvascular CVR in ISOL patients and explore its potential for IS/TIA risk stratification. Twenty-seven ISOL patients were recruited. The changes in continuous microvascular and macrovascular hemodynamics upon acetazolamide injection were used to determine CVR. Oxyhemoglobin (HbO2, by near-infrared spectroscopy), microvascular cerebral blood flow (CBF, by diffuse correlation spectroscopy) and CBF velocity (by transcranial Doppler) showed significant increases upon acetazolamide injection in all subjects (P < .03). Only macrovascular CVR (P = .024) and none of the microvascular measures were significantly dependent on the presence of ISOL. In addition, while CBF was significantly correlated with HbO2, neither of these microvascular measures correlated with macrovascular CBF velocity. We demonstrated the simultaneous, continuous, and noninvasive evaluation of CVR at both the microvasculature and macrovasculature. We found that macrovascular CVR response depends on the presence of ISOL, whereas the microvascular CVR did not significantly depend on the ISOL presence, possibly due to the role of collaterals other than those of the circle of Willis. The concurrent microvascular and macrovascular CVR measurement in the ISOL patients might improve future IS/TIA risk assessment. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  3. Transfer of Learning from Practicing Microvascular Anastomosis on Silastic Tubes to Rat Abdominal Aorta.

    Science.gov (United States)

    Mokhtari, Pooneh; Tayebi Meybodi, Ali; Lawton, Michael T; Payman, Andre; Benet, Arnau

    2017-12-01

    Learning to perform microvascular anastomosis is difficult. Laboratory practice models using artificial vessels are frequently used for this purpose. However, the efficacy of such practice models has not been objectively assessed for the performance of microvascular anastomosis during live surgical settings. This study was conducted to assess the transfer of learning from practicing microvascular anastomosis on tubes to anastomosing rat abdominal aorta. Ten surgeons without any experience in microvascular anastomosis were randomly assigned to an experimental or a control group. Both groups received didactic and visual training on end-to-end microvascular anastomosis. The experimental group received 24 sessions of hands-on training on microanastomosis using Silastic tubes. Next, both groups underwent recall tests on weeks 1, 2, and 8 after training. The recall test consisted of completing an end-to-end anastomosis on the rat's abdominal aorta. Anastomosis score, the time to complete the anastomosis, and the average time to place 1 stitch on the vessel perimeter were compared between the 2 groups. Compared with the control group, the experimental group did significantly better in terms of anastomosis score, total time, and per-stitch time. The measured variables showed stability and did not change significantly between the 3 recall tests. The skill of microvascular anastomosis is transferred from practicing on Silastic tubes to rat's abdominal aorta. Considering the relative advantages of Silastic tubes to live rodent surgeries, such as lower cost and absence of ethical issues, our results support the widespread use of Silastic tubes in training programs for microvascular anastomosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig.

    Science.gov (United States)

    Dyson, Rebecca M; Palliser, Hannah K; Lakkundi, Anil; de Waal, Koert; Latter, Joanna L; Clifton, Vicki L; Wright, Ian M R

    2014-09-17

    Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion-reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29-36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68-71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion-reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  5. Implications of genetic research on the role of the serotonin in depression: emphasis on the serotonin type 1A receptor and the serotonin transporter.

    Science.gov (United States)

    Neumeister, Alexander; Young, Theresa; Stastny, Juergen

    2004-08-01

    Serotonin systems appear to play a key role in the pathophysiology of major depressive disorder. Consequently, ongoing research determines whether serotonin related genes account for the very robust differential behavioral and neural mechanisms that discriminate patients with depression from healthy controls. Serotonin type 1(A) receptors and the serotonin transporters are reduced in depression, and recent genetic research in animals and humans has implicated both in depression. Preclinical studies have utilized a variety of animal models that have been used to explain pathophysiological mechanisms in humans, although it is not clear at all whether these models constitute relevant models for depression in humans. However, data from preclinical studies can generate hypotheses that are tested in humans by combining genetic data with behavioral and physiological challenge paradigms and neuroimaging. These studies will enhance our understanding about combined influences from multiple interacting genes, as well as from environmental factors on brain circuits and their function, and about how these mechanisms may contribute to the pathophysiology of neuropsychiatric disorders.

  6. Myocardial blood flow reserve is impaired in patients with aortic valve calcification and unobstructed epicardial coronary arteries.

    Science.gov (United States)

    Nel, Karen; Nam, Michael C Y; Anstey, Chris; Boos, Christopher J; Carlton, Edward; Senior, Roxy; Kaski, Juan Carlos; Khattab, Ahmed; Shamley, Delva; Byrne, Christopher D; Stanton, Tony; Greaves, Kim

    2017-12-01

    Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation. 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay. Mean (±SD) participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6 (22.2) mm, and median coronary calcification score was 43.5AU. Mean MBFR was 2.20 (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression modelling incorporating demographics, coronary plaque characteristics, MBFR, and inflammatory markers, demonstrated that age (β=0.05, 95% CI: 0.02, 0.08, P=0.007), hs-CRP (β=0.09, CI: 0.02, 0.16, P=0.010) and diabetes (β=1.03, CI: 0.08, 1.98, P=0.033), were positively associated with AVCS. MBFR (β=-0.87, CI: -1.44, -0.30, P=0.003), BMI (β=-0.11, CI: -0.21, -0.01, P=0.033), and LDL (β=-0.32, CI: -0.61, -0.03, P=0.029) were negatively associated with AVCS. TPL and coronary calcium score were not independently associated with AVCS when included in the regression model. Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation. Copyright © 2017 Elsevier B.V. All rights

  7. Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

    Science.gov (United States)

    Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

    2014-01-01

    The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

  8. Percutaneous transluminal coronary angioplasty

    International Nuclear Information System (INIS)

    Przybojewski, J.Z.; Weich, H.F.H.

    1984-01-01

    The purpose of this article is to review PTCA, percutaneous transluminal coronary angioplasty, which can be considered to be a truly revolutionary and fairly simple invasive form of intervention to atherosclerotic obstruction. The 'epidemic' of IHD, ischaemic heart disease, in the Republic of South Africa calls for the employment of this technique, which has already been carried out in a few teaching hospitals in this country. Very recently, modified balloon dilatation catheters have been used percutaneously in the non-operative transluminal correction of congenital coarctation of the aorta in infants and children, congenital pulmonary value stenosis, and hypoplasia and stenosis of the pulmonary arteries. It has also been employed for PTCA and for the simultaneous occlusion of coronary-bronchial artery anastomosis using a detachable balloon. The isotopes thallium 201 and technetium 99 were also used in scintiscanning

  9. Meniscotibial (coronary) ligament tears

    International Nuclear Information System (INIS)

    El-Khoury, G.Y.; Usta, H.Y.; Berger, R.A.

    1984-01-01

    Preservation of the meniscus whenever possible is essential in maintaining knee stability and preventing premature osteoarthritis. Peripheral meniscal tears are the most amenable to surgical repair. This study evaluates the peripheral attachments of the medial meniscus and focuses on a specific tear limited to the meniscotibial ligament (coronary ligament). The diagnosis is made arthrographically when the medial meniscus floats above the tibial plateau without separating completely from the capsule. The lateral meniscus is rarely involved in this type of injury. (orig.)

  10. Serotonin enhances the impact of health information on food choice.

    Science.gov (United States)

    Vlaev, Ivo; Crockett, Molly J; Clark, Luke; Müller, Ulrich; Robbins, Trevor W

    2017-06-01

    Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

  11. Serotonin inhibits low-threshold spike interneurons in the striatum

    Science.gov (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

    2012-01-01

    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μm) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations. These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT2C receptor agonists and reversed by 5-HT2C antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments, XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons. We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT2C receptors and increasing an M type current. PMID:22495583

  12. Baseline High-Sensitivity C-Reactive Protein Predicts Macrovascular and Microvascular Complications of Type 2 Diabetes: A Population-Based Study.

    Science.gov (United States)

    Aryan, Zahra; Ghajar, Alireza; Faghihi-Kashani, Sara; Afarideh, Mohsen; Nakhjavani, Manouchehr; Esteghamati, Alireza

    2018-04-25

    This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024-1.032) for CHD, 1.025 (1.021-1.029) for diabetic neuropathy, 1.037 (1.030-1.043) for diabetic retinopathy, and 1.035 (1.027-1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D. © 2018 S. Karger AG, Basel.

  13. 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.

  14. Emergence of Nonobstructive Coronary Artery Disease: A Woman's Problem and Need for Change in Definition on Angiography

    Science.gov (United States)

    Pepine, Carl J.; Ferdinand, Keith C.; Shaw, Leslee J; Light-McGroary, KellyAnn; Shah, Rashmee U.; Gulati, Martha; Duvernoy, Claire; Walsh, Mary Norine; Bairey Merz, C. Noel

    2015-01-01

    Recognition of ischemic heart disease (IHD) is often delayed or deferred in women. Thus, many at risk for adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. This lack of recognition is related to sex-specific IHD pathophysiology that differs from traditional models using data from men with flow-limiting coronary artery disease (CAD) obstructions. Symptomatic women are less likely to have obstructive CAD than men with similar symptoms, and tend to have coronary microvascular dysfunction, plaque erosion, and thrombus formation. Emerging data document that more extensive, nonobstructive CAD involvement, hypertension, and diabetes are associated with major adverse events similar to those with obstructive CAD. A central emerging paradigm is the concept of nonobstructive CAD as a cause of IHD and related adverse outcomes among women. This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges. PMID:26493665

  15. 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.

  16. Evaluation of Microvascular Perfusion and Resuscitation after Severe Injury.

    Science.gov (United States)

    Lee, Yann-Leei L; Simmons, Jon D; Gillespie, Mark N; Alvarez, Diego F; Gonzalez, Richard P; Brevard, Sidney B; Frotan, Mohammad A; Schneider, Andrew M; Richards, William O

    2015-12-01

    Achieving adequate perfusion is a key goal of treatment in severe trauma; however, tissue perfusion has classically been measured by indirect means. Direct visualization of capillary flow has been applied in sepsis, but application of this technology to the trauma population has been limited. The purpose of this investigation was to compare the efficacy of standard indirect measures of perfusion to direct imaging of the sublingual microcirculatory flow during trauma resuscitation. Patients with injury severity scores >15 were serially examined using a handheld sidestream dark-field video microscope. In addition, measurements were also made from healthy volunteers. The De Backer score, a morphometric capillary density score, and total vessel density (TVD) as cumulative vessel area within the image, were calculated using Automated Vascular Analysis (AVA3.0) software. These indices were compared against clinical and laboratory parameters of organ function and systemic metabolic status as well as mortality. Twenty severely injured patients had lower TVD (X = 14.6 ± 0.22 vs 17.66 ± 0.51) and De Backer scores (X = 9.62 ± 0.16 vs 11.55 ± 0.37) compared with healthy controls. These scores best correlated with serum lactate (TVD R(2) = 0.525, De Backer R(2) = 0.576, P trauma patients, and seems to provide real-time assessment of microcirculatory perfusion. This study suggests that in severe trauma, many indirect measurements of perfusion do not correlate with microvascular perfusion. However, visualized perfusion deficiencies do reflect a shift toward anaerobic metabolism.

  17. [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.

  18. Upcyte® Microvascular Endothelial Cells Repopulate Decellularized Scaffold

    Science.gov (United States)

    Dally, Iris; Hartmann, Nadja; Münst, Bernhard; Braspenning, Joris; Walles, Heike

    2013-01-01

    A general problem in tissue engineering is the poor and insufficient blood supply to guarantee tissue cell survival as well as physiological tissue function. To address this limitation, we have developed an in vitro vascularization model in which a decellularized porcine small bowl segment, representing a capillary network within a collagen matrix (biological vascularized scaffold [BioVaSc]), is reseeded with microvascular endothelial cells (mvECs). However, since the supply of mvECs is limited, in general, and as these cells rapidly dedifferentiate, we have applied a novel technology, which allows the generation of large batches of quasi-primary cells with the ability to proliferate, whilst maintaining their differentiated functionality. These so called upcyte mvECs grew for an additional 15 population doublings (PDs) compared to primary cells. Upcyte mvECs retained endothelial characteristics, such as von Willebrandt Factor (vWF), CD31 and endothelial nitric oxide synthase (eNOS) expression, as well as positive Ulex europaeus agglutinin I staining. Upcyte mvECs also retained biological functionality such as tube formation, cell migration, and low density lipoprotein (LDL) uptake, which were still evident after PD27. Initial experiments using MTT and Live/Dead staining indicate that upcyte mvECs repopulate the BioVaSc Scaffold. As with conventional cultures, these cells also express key endothelial molecules (vWF, CD31, and eNOS) in a custom-made bioreactor system even after a prolonged period of 14 days. The combination of upcyte mvECs and the BioVaSc represents a novel and promising approach toward vascularizing bioreactor models which can better reflect organs, such as the liver. PMID:22799502

  19. Persistent hemifacial spasm after microvascular decompression: a risk assessment model.

    Science.gov (United States)

    Shah, Aalap; Horowitz, Michael

    2017-06-01

    Microvascular decompression (MVD) for hemifacial spasm (HFS) provides resolution of disabling symptoms such as eyelid twitching and muscle contractions of the entire hemiface. The primary aim of this study was to evaluate the predictive value of patient demographics and spasm characteristics on long-term outcomes, with or without intraoperative lateral spread response (LSR) as an additional variable in a risk assessment model. A retrospective study was undertaken to evaluate the associations of pre-operative patient characteristics, as well as intraoperative LSR and need for a staged procedure on the presence of persistent or recurrent HFS at the time of hospital discharge and at follow-up. A risk assessment model was constructed with the inclusion of six clinically or statistically significant variables from the univariate analyses. A receiving operator characteristic curve was generated, and area under the curve was calculated to determine the strength of the predictive model. A risk assessment model was first created consisting of significant pre-operative variables (Model 1) (age >50, female gender, history of botulinum toxin use, platysma muscle involvement). This model demonstrated borderline predictive value for persistent spasm at discharge (AUC .60; p=.045) and fair predictive value at follow-up (AUC .75; p=.001). Intraoperative variables (e.g. LSR persistence) demonstrated little additive value (Model 2) (AUC .67). Patients with a higher risk score (three or greater) demonstrated greater odds of persistent HFS at the time of discharge (OR 1.5 [95%CI 1.16-1.97]; p=.035), as well as greater odds of persistent or recurrent spasm at the time of follow-up (OR 3.0 [95%CI 1.52-5.95]; p=.002) Conclusions: A risk assessment model consisting of pre-operative clinical characteristics is useful in prognosticating HFS persistence at follow-up.

  20. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  1. 3H-spiroperidol labels serotonin receptors in rat cerebral cortex and hippocampus

    International Nuclear Information System (INIS)

    Creese, I.; Snyder, S.H.

    1978-01-01

    It is found that in the cerebral cortex, butaclamol displaceable 3 H-spiroperidol binding labels both dopamine and serotonin receptors. In the hippocampus it is probable that 3 H-spiroperidol binding involves serotonin receptors exclusively. (Auth.)

  2. Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Olivier, J D A; Jans, L A W; Korte-Bouws, G A H; Korte, S M; Deen, P M T; Cools, A R; Ellenbroek, B A; Blokland, A

    2008-01-01

    RATIONALE: Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats. OBJECTIVES: As individual differences exist in central serotonin

  3. Plasma serotonin level is a predictor for recurrence and poor prognosis in colorectal cancer patients.

    Science.gov (United States)

    Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li

    2018-02-01

    To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.

  4. Effects of ageing on serotonin transporters in healthy females

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Tammela, L.; Karhunen, L.; Uusitupa, M.; Bergstroem, K.A.; Tiihonen, J.

    2001-01-01

    The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [ 123 I] nor-β-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [ 123 I] nor-β-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P 123 I] nor-β-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade). (orig.)

  5. How the cerebral serotonin homeostasis predicts environmental changes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Kalbitzer, Urs; Knudsen, Gitte Moos

    2013-01-01

    Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which...... has in several previous studies been linked to an increased risk to develop mood disorders. We argue that long-lasting fluctuations in the cerebral serotonin transmission, which is regulated via the 5-HTT, are responsible for mediating responses to environmental changes based on an assessment...... of cerebral serotonin transmission to seasonal and other forms of environmental change imparts greater behavioral flexibility, at the expense of increased vulnerability to stress. This model may explain the somewhat higher prevalence of the s-allele in some human populations dwelling at geographic latitudes...

  6. Radioimmunoassays for serotonin and 5-hydroxyindole acetic acid

    International Nuclear Information System (INIS)

    Delaage, M.A.; Puizillout, J.J.

    1981-01-01

    Radioimmunoassays for serotonin and 5-hydroxyindole acetic acid were developed. High titer antibodies, having a well-defined high specificity, have been raised by coupling the side-chain of both molecules to human serum albumin. Serotonin is first converted into N-hemisuccinate, and then treated like 5-HIAA, namely, conjugated with HSA for the immunogen. Synthesis of 125 I iodinated analogues was performed by coupling 5-HIAA or N-succinyl serotonin to glycyltyrosine, without any contact between both molecules and the oxidizing reagents. Chemical conversions of biological samples (by succinylation for 5-HT and amidation for 5-HIAA) were carried out. This critical step makes the antigen molecules resemble the immunogen more closely, thus allowing an appreciable gain in specificity and sensitivity. These assays allow the rapid determination of 5-HT and 5-HIAA in small amounts of tissue, blood, cerebral spinal fluid or perfusate without any purification, with a sensitivity threshold of 50 pg

  7. Protonated serotonin: Geometry, electronic structures and photophysical properties

    Science.gov (United States)

    Omidyan, Reza; Amanollahi, Zohreh; Azimi, Gholamhassan

    2017-07-01

    The geometry and electronic structures of protonated serotonin have been investigated by the aim of MP2 and CC2 methods. The relative stabilities, transition energies and geometry of sixteen different protonated isomers of serotonin have been presented. It has been predicted that protonation does not exhibit essential alteration on the S1 ← S0 electronic transition energy of serotonin. Instead, more complicated photophysical nature in respect to its neutral analogue is suggested for protonated system owing to radiative and non-radiative deactivation pathways. In addition to hydrogen detachment (HD), hydrogen/proton transfer (H/PT) processes from ammonium to indole ring along the NH+⋯ π hydrogen bond have been predicted as the most important photophysical consequences of SERH+ at S1 excited state. The PT processes is suggested to be responsible for fluorescence of SERH+ while the HD driving coordinate is proposed for elucidation of its nonradiative deactivation mechanism.

  8. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  9. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  10. Coffee consumption and coronary calcification - The Rotterdam Coronary Calcification Study

    NARCIS (Netherlands)

    van Woudenbergh, Geertruida J.; Vliegenthart, Rozemarijn; van Rooij, Frank J. A.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jacqueline C. M.; Geleijnse, Johanna M.

    Background-The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. Methods and Results-The study involved 1570 older men and women without coronary heart disease who participated in the

  11. Coffee consumption and coronary calcification: The Rotterdam coronary calcification study

    NARCIS (Netherlands)

    G.J. van Woudenbergh (Geertruida); R. Vliegenthart (Rozemarijn); F.J.A. van Rooij (Frank); A. Hofman (Albert); M. Oudkerk (Matthijs); J.C.M. Witteman (Jacqueline); J.M. Geleijnse (Marianne)

    2008-01-01

    textabstractBACKGROUND - The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. METHODS AND RESULTS - The study involved 1570 older men and women without coronary heart disease who

  12. Coffee Consumption and Coronary Calcification: The Rotterdam Coronary Calcification Study

    NARCIS (Netherlands)

    Woudenbergh, van G.J.; Vliegenthart, R.; Rooij, van F.J.A.; Hofman, A.; Oudkerk, M.; Witteman, J.C.M.; Geleijnse, J.M.

    2008-01-01

    Background¿ The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. Methods and Results¿ The study involved 1570 older men and women without coronary heart disease who participated in the

  13. Local heart irradiation of ApoE(-/-) mice induces microvascular and endocardial damage and accelerates coronary atherosclerosis

    NARCIS (Netherlands)

    Gabriels, Karen; Hoving, Saske; Seemann, Ingar; Visser, Nils L.; Gijbels, Marion J.; Pol, Jeffrey F.; Daemen, Mat J.; Stewart, Fiona A.; Heeneman, Sylvia

    2012-01-01

    Radiotherapy of thoracic and chest-wall tumors increases the long-term risk of radiation-induced heart disease, like a myocardial infarct. Cancer patients commonly have additional risk factors for cardiovascular disease, such as hypercholesterolemia. The goal of this study is to define the

  14. Effects of delayed laboratory processing on platelet serotonin levels.

    Science.gov (United States)

    Sanner, Jennifer E; Frazier, Lorraine; Udtha, Malini

    2013-01-01

    Despite the availability of established guidelines for measuring platelet serotonin, these guidelines may be difficult to follow in a hospital setting where time to processing may vary from sample to sample. The purpose of this study was to evaluate the effect of the time to processing of human blood samples on the stability of the enzyme-linked immunosorbent assay (ELISA) for the determination of platelet serotonin levels in human plasma. Human blood samples collected from a convenience sample of eight healthy volunteers were analyzed to determine platelet serotonin levels from plasma collected in ethylene diamine tetra acetic acid (EDTA) tubes and stored at 4°C for 3 hr, 5 hr, 8 hr, and 12 hr. Refrigeration storage at 4°C for 3 hr, 5 hr, 8 hr, and 12 hr altered the platelet serotonin measurement when compared to immediate processing. The bias for the samples stored at 4°C for 3 hr was 102.3 (±217.39 ng/10(9) platelets), for 5 hr was 200.1 (±132.76 ng/10(9) platelets), for 8 hr was 146.9 (±221.41 ng/10(9) platelets), and for 12 hr was -67.6 (±349.60 ng/10(9) platelets). Results from this study show that accurate measurement of platelet serotonin levels is dependent on time to processing. Researchers should therefore follow a standardized laboratory guideline for obtaining immediate platelet serotonin levels after blood sample collection.

  15. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors

    International Nuclear Information System (INIS)

    Pazos, A.; Cortes, R.; Palacios, J.M.

    1985-01-01

    The distribution of serotonin-2 (5-HT 2 ) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with four ligands: [ 3 H]ketanserin, [ 3 H]mesulergine, [ 3 H]LSD and [ 3 H]spiperone, which are reported to show high affinity for 5-HT 2 receptors. Very high concentrations were localized in the claustrum, olfactory tubercle and layer IV of the neocortex. The anterior olfactory nucleus, piriform cortex and layer I of neocortex were also rich in 5-HT 2 receptors. The specificity of the different ligands used is discussed in terms of the other populations of sites recognized by them. The distribution of 5-HT 2 receptors here reported is discussed in correlation with (a) the known distribution of serotoninergic terminals, (b) the specific anatomical systems and (c) the central effects reported to be mediated by 5-HT 2 -selective drugs. (Auth.)

  16. Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

    Science.gov (United States)

    Cheng, A V; Ferrier, I N; Morris, C M; Jabeen, S; Sahgal, A; McKeith, I G; Edwardson, J A; Perry, R H; Perry, E K

    1991-11-01

    The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.

  17. [Developments in percutaneous coronary intervention and coronary stents].

    Science.gov (United States)

    Simsek, C; Daemen, J; Zijlstra, F

    2014-01-01

    In The Netherlands, more than 30.000 patients undergo a percutaneous coronary intervention every year, during which a coronary stent implantation will be performed in 90% of the cases. It is estimated that more than 5 million coronary stent implantations will be performed worldwide this year. While these numbers are impressive, however, coronary stents still have as a limitation the possibility of stent thrombosis. This has been and is an important stimulus for the development of both coronary stents, from a bare metal stent via a drug eluting stent to the present-day development of bio-absorbable stents, and anti-platelet drugs,from acenocoumarol to thieropyridines. The possibility of shortening the period of use of this powerful medication by developing new kinds of non-thrombogenic stents would, for example, make it possible to achieve significant reductions in subsequent bleeding during (dental) procedures.

  18. Microvascular filtration is increased in the forearms of patients with breast cancer-related lymphedema

    DEFF Research Database (Denmark)

    Jensen, Mads Radmer; Simonsen, Lene; Karlsmark, Tonny

    2013-01-01

    -enhanced ultrasound; venous occlusion strain-gauge plethysmography; lower-body negative pressure; noninvasive blood pressure measurements; and skin (99m)Tc-pertechnetate clearance technique. Measurements were performed bilaterally and simultaneously in the forearms, enabling use of the nonedematous forearm...... relative microvascular volume, forearm blood flow, skin blood flow, or central or local sympathetic vascular reflexes. Forearm microvascular filtration is increased in patients with BCRL, and more so in the edematous arm. The vascular sympathetic control mechanisms seem to be preserved. We propose...... with unilateral BCRL, the following aspects of upper extremity peripheral circulation were examined: muscle relative microvascular volume; capillary filtration coefficient; central and local sympathetic vascular reflexes; skin blood flow; and forearm blood flow. These were studied via real-time, contrast...

  19. Significance of determination of bone mineral density and osteocalcin in diabetic patients with diabetic microvascular complications

    International Nuclear Information System (INIS)

    Kong Xianghui; Mu Junqing; Lu Kuan

    2003-01-01

    Objective: To study the influence of diabetic microvascular complications on bone mineral density (BMI) and osteocalcin (BGP). Methods: 60 patients with type 2 diabetes mellitus were studied, including 33 with microvascular complications (retinopathy, nephropathy, neuropathy) (group 1) and 27 without complications (group 2). Fasting blood glucose, serum fructosamine (GSP), total alkaline phosphatase (TALP), calcium (Ca 2+ ) levels were measured by biochemical method; osteocalcin (BGP) level was detected by RIA. BMD of the lumbar spine and femur was measured by dual energy X-ray absorptiometry in all patients. Body mass index (BMI) was calculated from the height and body weight. Results: The BMI, GSP, FBG, TALP and Ca 2+ values in the two groups were not much different, but BGP and BMD in group 1 were significantly lower than those in group 2. Conclusion: Bone mineral density (BMD) and BGP values were closely related to the microvascular complications in diabetes, which could decrease bone formation and increase the frequency of osteoporosis

  20. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  1. Modulation of the intrinsic properties of motoneurons by serotonin

    DEFF Research Database (Denmark)

    Perrier, Jean-François; Rasmussen, Hanne Borger; Christensen, Rasmus Kordt

    2013-01-01

    Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts...... a sustained depolarization and an amplification of synaptic inputs. Under pathological conditions, such as after a spinal cord injury, the promotion of persistent inward currents by serotonin and/or the overexpression of autoactive serotonergic receptors may contribute to motoneuronal excitability, muscle...

  2. Coaction of Stress and Serotonin Transporter Genotype in Predicting Aggression at the Transition to Adulthood

    Science.gov (United States)

    Conway, Christopher C.; Keenan-Miller, Danielle; Hammen, Constance; Lind, Penelope A.; Najman, Jake M.; Brennan, Patricia A.

    2012-01-01

    Despite consistent evidence that serotonin functioning affects stress reactivity and vulnerability to aggression, research on serotonin gene-stress interactions (G x E) in the development of aggression remains limited. The present study investigated variation in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the…

  3. Effect of serotonin on the yield of UV-induced thymine dimers in DNA

    International Nuclear Information System (INIS)

    Frajkin, G.Ya.; Strakhovskaya, M.G.; Ivanova, Eh.V.

    1985-01-01

    Using fluorescence method serotonin interaction with DNA is studied and bond constant Ksub(c)=4.2x10 4 M -1 is defined. It is shown that bound serotonin reduces yield of UV-induced thymine dimers. Value of efficient distance of protective serotonin effect constituting part of DNA chain of 4 base pairs, is determined

  4. 21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

  5. Three-dimensional dynamic contrast-enhanced MRI for the accurate, extensive quantification of microvascular permeability in atherosclerotic plaques

    NARCIS (Netherlands)

    Calcagno, Claudia; Lobatto, Mark E.; Dyvorne, Hadrien; Robson, Philip M.; Millon, Antoine; Senders, Max L.; Lairez, Olivier; Ramachandran, Sarayu; Coolen, Bram F.; Black, Alexandra; Mulder, Willem J. M.; Fayad, Zahi A.

    2015-01-01

    Atherosclerotic plaques that cause stroke and myocardial infarction are characterized by increased microvascular permeability and inflammation. Dynamic contrast-enhanced MRI (DCE-MRI) has been proposed as a method to quantify vessel wall microvascular permeability in vivo. Until now, most DCE-MRI

  6. 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

    2018-06-01

    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.

  7. Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.

    Science.gov (United States)

    Yang, Chuang-Bo; Zhang, Shuang; Jia, Yong-Jun; Yu, Yong; Duan, Hai-Feng; Zhang, Xi-Rong; Ma, Guang-Ming; Ren, Chenglong; Yu, Nan

    2017-10-01

    To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RIC AP-VP : [RIC AP-VP =(IC AP -IC VP )/IC AP ]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RIC AP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all phepatocellular carcinoma with and without microvascular invasion. Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

    Science.gov (United States)

    Chetham, P M; Sefton, W D; Bridges, J P; Stevens, T; McMurtry, I F

    1997-04-01

    Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

  9. Assessment of macrovascular endothelial function using pulse wave analysis and its association with microvascular reactivity in healthy subjects.

    Science.gov (United States)

    Ibrahim, N N I N; Rasool, A H G

    2017-08-01

    Pulse wave analysis (PWA) and laser Doppler fluximetry (LDF) are non-invasive methods of assessing macrovascular endothelial function and microvascular reactivity respectively. The aim of this study was to assess the correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF. 297 healthy and non-smoking subjects (159 females, mean age (±SD) 23.56 ± 4.54 years) underwent microvascular reactivity assessment using LDF followed by macrovascular endothelial function assessments using PWA. Pearson's correlation showed no correlation between macrovascular endothelial function and microvascular reactivity (r = -0.10, P = 0.12). There was no significant correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF in healthy subjects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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...

  11. Decreased uptake of 3H-serotonin and endogenous content of serotonin in blood platelets in hypertensive patients

    International Nuclear Information System (INIS)

    Kamal, L.A.; Le Quan-Bui, K.H.; Meyer, P.

    1984-01-01

    The uptake and content of serotonin in blood platelets were studied in patients with essential hypertension and in five families in which at least one member was hypertensive. Blood was obtained from male and female normotensive volunteers and hypertensive patients who were free of medication. Lineweaver-Burk plots of 3H-serotonin uptake from both control subjects and hypertensive patients were linear, which suggested simple Michaelis-Menten uptake kinetics. The maximal uptake velocity (Vmax) in hypertensive patients was significantly lower than in control subjects (control . 41.7 +/- 3.3 pmol/min/10(8) platelets, n . 17; hypertensive . 26.6 +/- 3.0 pmol/min/10(8) platelets, n . 16; p less than 0.005). The affinity constant (Km) was slightly but significantly lower in hypertensive patients (control . 0.70 +/- 0.08 microM; hypertensive . 0.46 +/- 0.08 microM; p less than 0.05). The serotonin content in blood platelets determined by high pressure liquid chromatography with electrochemical detection was significantly lower in hypertensive patients (control . 165.0 +/- 12.9 nmol/10(11) platelets, n . 29; hypertensive . 105.9 +/- 10.4 nmol/10(11) platelets, n . 27; p less than 0.001). In the five families investigated, the lowered serotonin content was observed in some normotensive members. The reduced number of carriers of serotonin uptake and the slight decrease in the affinity constant observed in platelets of patients with essential hypertension suggest that serotonin metabolism is altered in essential hypertension and that blood platelets may be a useful model in studying the serotonergic modifications at the molecular level

  12. Identifying coronary artery disease in men with type 2 diabetes: osteoprotegerin, pulse wave velocity, and other biomarkers of cardiovascular risk.

    LENUS (Irish Health Repository)

    Davenport, Colin

    2012-02-01

    OBJECTIVES: In patients with type 2 diabetes, high serum levels of osteoprotegerin (OPG) have been associated with a greater risk of cardiovascular events. However, it remains unclear how well OPG performs when compared with traditional biomarkers of cardiovascular risk such as high-sensitivity C-reactive protein (hsCRP). Furthermore, OPG levels are also high in the presence of diabetes-related microvascular disease, and it is unclear whether OPG can distinguish microvascular disease from large-vessel atherosclerosis. The first aim of this study was to compare OPG levels against other biomarkers of cardiovascular risk in the identification of patients with documented multivessel coronary artery disease (CAD). The second aim was to compare OPG levels in patients with microvascular complications (microalbuminuria) against those with established CAD. METHODS: Three groups of male patients with type 2 diabetes were recruited: patients without microvascular complications or large-vessel atherosclerosis (n = 24), patients with microalbuminuria only (n = 23), and patients with microalbuminuria and documented multivessel CAD (n = 25). OPG, hsCRP, interleukin 6, urate, and pulse wave velocity were measured. RESULTS: Serum OPG levels were significantly higher in patients with a combination of microalbuminuria and CAD than in those with microalbuminuria alone. There were no significant differences in any of the other biomarkers between the groups. CONCLUSION: OPG was found to be superior to the other biomarkers studied in identifying patients with documented CAD. The presence of CAD was a greater determinant of serum OPG levels than microalbuminuria in our population. These findings support the use of OPG as a biomarker of cardiovascular risk.

  13. Potential of [11C]DASB for measuring endogenous serotonin with PET: binding studies

    International Nuclear Information System (INIS)

    Lundquist, Pinelopi; Wilking, Helena; Hoeglund, A. Urban; Sandell, Johan; Bergstroem, Mats; Hartvig, Per; Langstroem, Bengt

    2005-01-01

    The serotonin transporter radioligand [ 11 C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, or [ 11 C]DASB, was examined in order to assess its potential for measuring fluctuations in endogenous serotonin concentrations with positron emission tomography. Binding characteristics of [ 11 C]DASB and the propensity for serotonin to displace the tracer were explored in rat brain homogenates. Experiments showed that serotonin displaced [ 11 C]DASB in vitro. Ex vivo experiments performed after tranylcypromine injection (3 or 15 mg/kg) showed a dose-dependent trend in radioactivity uptake and suggested that serotonin may compete with [ 11 C]DASB for transporter binding

  14. Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning : a case report

    NARCIS (Netherlands)

    Hanekamp, BB; Zijlstra, JG; Tulleken, JE; Ligtenberg, JJM; van der Werf, TS; Hofstra, LS

    Newer, more selective, antidepressant agents are increasingly being used as first-line treatment. However, clinical experience in patients after a deliberate overdose is limited. We present a case of venlafaxine intoxication complicated by a late rise in creatine kinase, seizures and serotonin

  15. Tall Fescue Alkaloids Bind Serotonin Receptors in Cattle

    Science.gov (United States)

    The serotonin (5HT) receptor 5HT2A is involved in the tall fescue alkaloid-induced vascular contraction in the bovine periphery. This was determined by evaluating the contractile responses of lateral saphenous veins biopsied from cattle grazing different tall fescue/endophyte combinations. The contr...

  16. Acute serotonin depletion releases motivated inhibition of response vigour.

    Science.gov (United States)

    den Ouden, Hanneke E M; Swart, Jennifer C; Schmidt, Kristin; Fekkes, Durk; Geurts, Dirk E M; Cools, Roshan

    2015-04-01

    The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas, however, has been mixed. In the current study, we aimed to investigate the role of serotonin (5HT) in behavioural vigour as a function of incentive motivation. We employed dietary acute tryptophan depletion (ATD) to lower the 5HT precursor tryptophan during the performance of a speeded visual discrimination task. Feedback valence and feedback probability were manipulated independently and cued prior to target onset. On feedback trials, fast correct responses led to either reward or avoidance of punishment, while slow or incorrect responses led to reward omission or punishment. We show that behavioural responding is inhibited under high incentive motivation (i.e. high-feedback probability) at baseline 5HT levels and that lowering these leads to behavioural disinhibition, while leaving accuracy unaffected. Surprisingly, there were no differential effects of motivational valence, with 5HT depletion releasing behavioural inhibition under both appetitive and aversive motivation. Our findings extend current theories on the role of 5HT in behavioural inhibition by showing that reductions in serotonin lead to increased behavioural vigour only if there is a motivational drive to inhibit behaviour at baseline.

  17. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Witkamp, R.F.; Boekschoten, M.V.; Laak, ter M.C.; Heins, M.S.; Norren, van K.

    2016-01-01

    Background: Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections

  18. Binding-Induced Fluorescence of Serotonin Transporter Ligands

    DEFF Research Database (Denmark)

    Wilson, James; Ladefoged, Lucy Kate; Babinchak, Michael

    2014-01-01

    The binding-induced fluorescence of 4-(4-(dimethylamino)-phenyl)-1-methylpyridinium (APP(+)) and two new serotonin transporter (SERT)-binding fluorescent analogues, 1-butyl-4-[4-(1-dimethylamino)phenyl]-pyridinium bromide (BPP(+)) and 1-methyl-4-[4-(1-piperidinyl)phenyl]-pyridinium (PPP(+)), has...

  19. Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

    Directory of Open Access Journals (Sweden)

    Marco Redaelli

    Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

  20. Use of selective serotonin reuptake inhibitors reduces fertility in men

    DEFF Research Database (Denmark)

    Nørr, L; Bennedsen, Birgit; Fedder, Jens

    2016-01-01

    Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included...

  1. Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs

    NARCIS (Netherlands)

    van Zwieten, P. A.; Blauw, G. J.; van Brummelen, P.

    1990-01-01

    A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT

  2. Purification and fluorescent labeling of the human serotonin transporter

    DEFF Research Database (Denmark)

    Rasmussen, Søren G F; Gether, Ulrik

    2005-01-01

    To establish a purification procedure for the human serotonin transporter (hSERT) we expressed in Sf9 insect cells an epitope-tagged version of the transporter containing a FLAG epitope at the N-terminus and a polyhistidine tail at the C-terminus (FLAG-hSERT-12H). For purification, the transporter...

  3. High brain serotonin levels in migraine between attacks

    DEFF Research Database (Denmark)

    Deen, Marie; Hansen, Hanne D; Hougaard, Anders

    2018-01-01

    Migraine has been hypothesized to be a syndrome of chronic low serotonin (5-HT) levels, but investigations of brain 5-HT levels have given equivocal results. Here, we used positron emission tomography (PET) imaging of the 5-HT4receptor as a proxy for brain 5-HT levels. Given that the 5-HT4receptor...

  4. Effects of Postnatal Serotonin Agonism on Fear Response and Memory

    Science.gov (United States)

    The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter the development of the serotonergic circuitry, altering behaviors mediated by 5-HT signaling, such as memory, fear and aggression. White leghorn chicks...

  5. A new Drosophila octopamine receptor responds to serotonin.

    Science.gov (United States)

    Qi, Yi-Xiang; Xu, Gang; Gu, Gui-Xiang; Mao, Fen; Ye, Gong-Yin; Liu, Weiwei; Huang, Jia

    2017-11-01

    As the counterparts of the vertebrate adrenergic transmitters, octopamine and tyramine are important physiological regulators in invertebrates. They control and modulate many physiological and behavioral functions in insects. In this study, we reported the pharmacological properties of a new α2-adrenergic-like octopamine receptor (CG18208) from Drosophila melanogaster, named DmOctα2R. This new receptor gene encodes two transcripts by alternative splicing. The long isoform DmOctα2R-L differs from the short isoform DmOctα2R-S by the presence of an additional 29 amino acids within the third intracellular loop. When heterologously expressed in mammalian cell lines, both receptors were activated by octopamine, tyramine, epinephrine and norepinephrine, resulting in the inhibition of cAMP production in a dose-dependent manner. The long form is more sensitive to the above ligands than the short form. The adrenergic agonists naphazoline, tolazoline and clonidine can stimulate DmOctα2R as full agonists. Surprisingly, serotonin and serotoninergic agonists can also activate DmOctα2R. Several tested adrenergic antagonists and serotonin antagonists blocked the action of octopamine or serotonin on DmOctα2R. The data presented here reported an adrenergic-like G protein-coupled receptor activated by serotonin, suggesting that the neurotransmission and neuromodulation in the nervous system could be more complex than previously thought. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Brief Report: Platelet-Poor Plasma Serotonin in Autism

    Science.gov (United States)

    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.

    2012-01-01

    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  7. A role for serotonin in piglet preweaning mortality

    Science.gov (United States)

    Improving piglet survivability rate is of high priority for swine production as well as for piglet well-being. Dysfunction in the serotonin system has been associated with growth deficiencies, infant mortality or failure to thrive (FTT) in human infants. The aim of this study was to examine the role...

  8. Serotonin transporter genotype, salivary cortisol, neuroticism and life events

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Kessing, Lars Vedel

    2014-01-01

    OBJECTIVE: To investigate if cortisol alone or in interaction with other risk factors (familial risk, the serotonin transporter genotype, neuroticism and life events (LEs)) predicts onset of psychiatric disorder in healthy individuals at heritable risk. MATRIAL AND METHODS: In a high-risk study...

  9. Serotonin synthesis studied with positron emission tomography, (PET)

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Lundquist, Pinelopi

    Positron emission tomography (PET) has the potential to study the biosynthesis and release of serotonin (5HT) at brain serotonergic neurons. PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes. This section focuses on probes to measure...

  10. Alterations to embryonic serotonin change aggression and fearfulness

    Science.gov (United States)

    Prenatal environment, including maternal hormones, affects the development of the serotonin (5-HT) system, with long-lasting effects on mood and behavioral exhibition in children and adults. The chicken provides a unique animal model to study the effects of embryonic development on childhood and ado...

  11. Plasma serotonin in horses undergoing surgery for small intestinal colic

    NARCIS (Netherlands)

    Torfs, Sara C; Maes, An A; Delesalle, Catherine J; Pardon, Bart; Croubels, Siska M; Deprez, Piet

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI

  12. Serotonin and calcium homeostasis during the transition period.

    Science.gov (United States)

    Weaver, S R; Laporta, J; Moore, S A E; Hernandez, L L

    2016-07-01

    The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently

  13. Therapeutic Application of Diacylglycerol Oil for Obesity: Serotonin Hypothesis

    Directory of Open Access Journals (Sweden)

    Yuji Hirowatari

    2012-01-01

    Full Text Available ABSTRACT: Characteristics for the serum lipid abnormalities in the obesity/metabolic syndrome are elevated fasting, postprandial triglyceride (TG, and decreased high-density lipoprotein-cholesterol (HDL-C. Diacylglycerol (DAG oil ingestion has been reported to ameliorate postprandial hyperlipidemia and prevent obesity by increasing energy expenditure, due to the intestinal physiochemical dynamics that differ from triacylglycerol (TAG. Our study demonstrated that DAG suppresses postprandial increase in TG-rich lipoprotein, very low-density lipoprotein (VLDL, and insulin, as compared with TAG in young, healthy individuals. Interestingly, our study also presented that DAG significantly increases plasma serotonin, which is mostly present in the intestine, and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our other study demonstrated that DAG suppresses postprandial increase in TG, VLDL-C, and remnant-like particle-cholesterol, in comparison with TAG in an apolipoprotein C-II deficient subject, suggesting that DAG suppresses postprandial TG-rich lipoprotein independently of lipoprotein lipase. Further, to understand the molecular mechanisms for DAG-mediated increase in serotonin and energy expenditure, we studied the effects of 1-monoacylglycerol and 2(1:1-10 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells, the human intestinal cell line. We also studied effects of 1- and 2-monoacylglycerol, and serotonin on the expression of mRNA associated with â-oxidation, fatty acids metabolism, and thermogenesis, in the Caco-2 cells. 1-monoacylglycerol significantly increased serotonin release from the Caco-2 cells, compared with 2-monoacylglycerol by approximately 40%. The expression of mRNA of acyl-CoA oxidase (ACO, fatty acid translocase (FAT, and uncoupling protein-2 (UCP-2, was significantly higher in 1-MOG

  14. Selective serotonin reuptake inhibitor (SSRI antidepressants, prolactin and breast cancer

    Directory of Open Access Journals (Sweden)

    Janet eAshbury

    2012-12-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are a widely prescribed class of anti-depressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003-2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with nonusers of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively, regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40 for long-term users of sertraline (≥24 prescriptions, given the small number of exposed cases (n=12, the borderline statistical significance and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.

  15. Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

    Science.gov (United States)

    Lefevre, Arthur; Richard, Nathalie; Jazayeri, Mina; Beuriat, Pierre-Aurélien; Fieux, Sylvain; Zimmer, Luc; Duhamel, Jean-René; Sirigu, Angela

    2017-07-12

    Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT 1A R) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [ 11 C]DASB and [ 18 F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT 1A R, respectively. Oxytocin (1 IU in 20 μl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [ 11 C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [ 18 F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [ 11 C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT 1A R. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT 1A R receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders. SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical

  16. In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin(2A) Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and Hallucinogen Users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frokjaer, Vibe G.; Holst, Klaus K.

    2011-01-01

    Context: Both hallucinogens and 3,4-methylenedioxy-methamphetamine( MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.Objective: ......Context: Both hallucinogens and 3,4-methylenedioxy-methamphetamine( MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin...

  17. A rare anomaly: Double right coronary artery

    Directory of Open Access Journals (Sweden)

    Dursun Çayan Akkoyun

    2013-01-01

    Full Text Available Coronary artery anomalies are rare anomalies. Theseare usually asymptomatic and are discovered incidentally.Double right coronary artery (RCA is a rare coronaryartery anomaly. Although there is controversy aboutidentification and classification of double RCA, it is oftena benign condition, but it can be complicated by atherosclerosisand can lead to serious conditions such asmyocardial infarction (MI and may be accompanied byother anomalies. In our case, double RCA were detectedin coronary angiography for acute anterior MI, and in thenext session successful percutaneous coronary interventionwas performed.Key words: Coronary anomaly, coronary angiography,coronary stenosis

  18. Current status of hybrid coronary revascularization.

    Science.gov (United States)

    Jaik, Nikhil P; Umakanthan, Ramanan; Leacche, Marzia; Solenkova, Natalia; Balaguer, Jorge M; Hoff, Steven J; Ball, Stephen K; Zhao, David X; Byrne, John G

    2011-10-01

    Hybrid coronary revascularization combines coronary artery bypass surgery with percutaneous coronary intervention techniques to treat coronary artery disease. The potential benefits of such a technique are to offer the patients the best available treatments for coronary artery disease while minimizing the risks of the surgery. Hybrid coronary revascularization has resulted in the establishment of new 'hybrid operating suites', which incorporate and integrate the capabilities of a cardiac surgery operating room with that of an interventional cardiology laboratory. Hybrid coronary revascularization has greatly augmented teamwork and cooperation between both fields and has demonstrated encouraging as well as good initial outcomes.

  19. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    Science.gov (United States)

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  20. Non-conventional features of peripheral serotonin signalling - the gut and beyond.

    Science.gov (United States)

    Spohn, Stephanie N; Mawe, Gary M

    2017-07-01

    Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

  1. Non-invasive assessment of coronary calcification

    International Nuclear Information System (INIS)

    Vliegenthart, Rozemarijn; Oei, Hok-Hay S.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jackqueline C. M.

    2004-01-01

    Electron-beam tomography (EBT) and multi-detector computed tomography (MDCT) enable the noninvasive assessment of coronary calcification. The amount of coronary calcification, as detected by EBT, has a close relation with the amount of coronary atherosclerosis, which is the substrate for the occurrence of myocardial infarction and sudden cardiac death. Calcification of the coronary arteries can be seen as a cumulative measure of life-time exposure to cardiovascular risk factors. Several studies have shown that the amount of coronary calcification is associated with the risk of coronary heart disease. Therefore, coronary calcification is a promising method for non-invasive detection of asymptomatic subjects at high risk of developing coronary heart disease. Whether measurement of coronary calcification also increases the predictive power of coronary events based on cardiovascular risk factors is topic of current research

  2. Aborted Sudden Cardiac Death in a Female Patient Presenting with Takotsubo-Like Cardiomyopathy due to Epicardial Coronary Vasospasm

    Directory of Open Access Journals (Sweden)

    Sorin Giusca

    2017-01-01

    Full Text Available Takotsubo cardiomyopathy is characterized by apical ballooning of the left ventricle (LV in the absence of relevant coronary artery stenosis, which typically occurs in elderly women after emotional stress. Catecholamine cardiotoxicity, metabolic disturbance, and coronary microvascular impairment have previously been proposed as underlying pathophysiologic mechanisms of takotsubo cardiomyopathy, whereas myocardial stunning resulting from epicardial coronary artery vasospasm is not generally accepted as a cause of takotsubo cardiomyopathy. The prognosis of takotsubo cardiomyopathy is generally more favourable compared to myocardial infarction; however, severe complications such as rupture of the LV and life-threatening arrhythmias may occur. Herein, we describe a case of an 84-year-old female, who presented with aborted sudden cardiac death due to ventricular fibrillation. Echocardiography suggested LV apical ballooning with severely impaired LV-function, so that takotsubo cardiomyopathy was suspected. However, coronary angiography revealed epicardial spasm of the left anterior ascending, which resolved after intracoronary injection of 0.2 mg nitroglycerine. Cardiac magnetic resonance exhibited subendocardial late enhancement and echocardiography showed normalization of LV dysfunction during follow-up. The patient was put on conservative treatment with nitrates and calcium inhibitors and ICD implantation were deferred.

  3. Exercise and sleep in aging: emphasis on serotonin.

    Science.gov (United States)

    Melancon, M O; Lorrain, D; Dionne, I J

    2014-10-01

    Reductions in central serotonin activity with aging might be involved in sleep-related disorders in later life. Although the beneficial effects of aerobic exercise on sleep are not new, sleep represents a complex recurring state of unconsciousness involving many lines of transmitters which remains only partly clear despite intense ongoing research. It is known that serotonin released into diencephalon and cerebrum might play a key inhibitory role to help promote sleep, likely through an active inhibition of supraspinal neural networks. Several lines of evidence support the stimulatory effects of exercise on higher serotonergic pathways. Hence, exercise has proved to elicit acute elevations in forebrain serotonin concentrations, an effect that waned upon cessation of exercise. While adequate exercise training might lead to adaptations in higher serotonergic networks (desensitization of forebrain receptors), excessive training has been linked to serious brain serotonergic maladaptations accompanied by insomnia. Dietary supplementation of tryptophan (the only serotonin precursor) is known to stimulate serotonergic activity and promote sleep, whereas acute tryptophan depletion causes deleterious effects on sleep. Regarding sleep-wake regulation, exercise has proved to accelerate resynchronization of the biological clock to new light-dark cycles following imposition of phase shifts in laboratory animals. Noteworthy, the effect of increased serotonergic transmission on wake state appears to be biphasic, i.e. promote wake and thereafter drowsiness. Therefore, it might be possible that acute aerobic exercise would act on sleep by increasing activity of ascending brain serotonergic projections, though additional work is warranted to better understand the implication of serotonin in the exercise-sleep axis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus.

    Directory of Open Access Journals (Sweden)

    Cecilia Berg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI fluoxetine (FLU, Prozac® is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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.

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

    International Nuclear Information System (INIS)

    Qiu, Gui-Zhen; Tian, Wei; Fu, Hai-Tao; Li, Chao-Peng; Liu, Ban

    2016-01-01

    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.

  8. 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

  9. 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

  10. My First 100 Consecutive Microvascular Free Flaps: Pearls and Lessons Learned in First Year of Practice

    Directory of Open Access Journals (Sweden)

    Edward I. Chang, MD

    2013-07-01

    Conclusions: As a young plastic surgeon embarking in reconstructive plastic surgery at an academic institution, the challenges and dilemmas presented in the first year of practice have been daunting but also represent opportunities for learning and improvement. Skills and knowledge acquired from time, experience, and mentors are invaluable in optimizing outcomes in microvascular free flap reconstruction.

  11. 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

  12. Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels.

    Science.gov (United States)

    Cuchiara, Michael P; Gould, Daniel J; McHale, Melissa K; Dickinson, Mary E; West, Jennifer L

    2012-11-07

    Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.

  13. Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

    NARCIS (Netherlands)

    Johannes, Tanja; Mik, Egbert G.; Nohé, Boris; Raat, Nicolaas J. H.; Unertl, Klaus E.; Ince, Can

    2006-01-01

    INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (microPO2) and oxygen consumption

  16. PATENCY AND HEALING OF MICROVASCULAR PROSTHESES - A REVIEW OF 10 YEARS OF EXPERIMENTAL WORK IN GRONINGEN

    NARCIS (Netherlands)

    VANDERLEI, B; ROBINSON, PH

    1993-01-01

    From 1982 onwards, in Groningen, The Netherlands, we have worked on the experimental evaluation and development of microvascular prostheses in rats and rabbits. In this review article a systematic overview of this experimental work is presented and the results are discussed with regard to the

  17. Effect of Antimicrobial Compounds on Balamuthia mandrillaris Encystment and Human Brain Microvascular Endothelial Cell Cytopathogenicity▿

    OpenAIRE

    Siddiqui, Ruqaiyyah; Matin, Abdul; Warhurst, David; Stins, Monique; Khan, Naveed Ahmed

    2007-01-01

    Cycloheximide, ketoconazole, or preexposure of organisms to cytochalasin D prevented Balamuthia mandrillaris-associated cytopathogenicity in human brain microvascular endothelial cells, which constitute the blood-brain barrier. In an assay for inhibition of cyst production, these three agents prevented the production of cysts, suggesting that the biosynthesis of proteins and ergosterol and the polymerization of actin are important in cytopathogenicity and encystment.

  18. Hepatitis B and C seroprevalence in patients with diabetes mellitus and its relationship with microvascular complications

    Directory of Open Access Journals (Sweden)

    Kadir Gisi

    2016-12-01

    Full Text Available Introduction: Diabetic patients are susceptible to bacterial, viral and fungal infections because of various deficiencies in the immune system. Aim: To investigate a possible link between hepatitis B/C prevalence and microvascular complications as well as duration of diabetes. Material and methods: In total 1263 diabetic patients (1149 type 2, 114 type 1 were enrolled in the study. The control group consisted of 1482 healthy blood donors who were over 40 years old. All diabetic patients were tested for HBsAg, anti-HBs and anti-HCV beside routine laboratory tests. Diabetic patients were divided into three groups according to their diabetes duration, and all of the patients were scanned for microvascular complications. Demographic data of all patients were recorded. Results : HBsAg seropositivity was 3.7% in diabetic patients and 1.08% in the control group; this difference was statistically significant (p < 0.001. HBsAg positivity rates in type 1 and type 2 diabetics were 0.8% and 4%, respectively (p = 0.09. HCV seropositivity was 2.2% for diabetics and 0.5% for the control group; this difference was statistically significant (p 0.05. Also, no relationship was found between microvascular complications of diabetes and hepatitis B/C seropositivity. Conclusions : Hepatitis B and C seroprevalence was found to be increased in diabetes mellitus; however, there was no relationship between hepatitis seroprevalence and the duration or microvascular complications of diabetes.

  19. The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction

    NARCIS (Netherlands)

    Buise, Marc P.; Ince, Can; Tilanus, Hugo W.; Klein, Jan; Gommers, Diederik; van Bommel, Jasper

    2005-01-01

    Esophagectomy followed by gastric tube reconstruction is the surgical treatment of choice for patients with esophageal cancer. Complications of the cervical anastomosis are associated with impaired microvascular blood flow (MBF) and ischemia in the gastric fundus. The aim of the present study was to

  20. 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

  1. MICROVASCULAR CHANGES IN AGED RAT FOREBRAIN - EFFECTS OF CHRONIC NIMODIPINE TREATMENT

    NARCIS (Netherlands)

    de Jong, Giena; Weerd, H. de; Schuurman, T.; Traber, J.; Luiten, P.G.M.

    1990-01-01

    In the present study the effects of long-term treatment with the 1,4-dihydropyridine calcium antagonist nimodipine on ultrastructural alterations of the microvascular morphology were examined in the frontoparietal cortex, entorhinal cortex and CA1 of the hippocampus in the aged rat. Qualitative

  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. Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice.

    Science.gov (United States)

    Kalueff, A V; Fox, M A; Gallagher, P S; Murphy, D L

    2007-06-01

    Although mice with a targeted disruption of the serotonin transporter (SERT) have been studied extensively using various tests, their complex behavioral phenotype is not yet fully understood. Here we assess in detail the behavior of adult female SERT wild type (+/+), heterozygous (+/-) and knockout (-/-) mice on an isogenic C57BL/6J background subjected to a battery of behavioral paradigms. Overall, there were no differences in the ability to find food or a novel object, nest-building, self-grooming and its sequencing, and horizontal rod balancing, indicating unimpaired sensory functions, motor co-ordination and behavioral sequencing. In contrast, there were striking reductions in exploration and activity in novelty-based tests (novel object, sticky label and open field tests), accompanied by pronounced thigmotaxis, suggesting that combined hypolocomotion and anxiety (rather than purely anxiety) influence the SERT -/- behavioral phenotype. Social interaction behaviors were also markedly reduced. In addition, SERT -/- mice tended to move close to the ground, frequently displayed spontaneous Straub tail, tics, tremor and backward gait - a phenotype generally consistent with 'serotonin syndrome'-like behavior. In line with replicated evidence of much enhanced serotonin availability in SERT -/- mice, this serotonin syndrome-like state may represent a third factor contributing to their behavioral profile. An understanding of the emerging complexity of SERT -/- mouse behavior is crucial for a detailed dissection of their phenotype and for developing further neurobehavioral models using these mice.

  4. Diagnosing coronary artery disease after a positive coronary computed tomography angiography

    DEFF Research Database (Denmark)

    Nissen, L; Winther, S; Westra, J

    2018-01-01

    Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim...

  5. Vessel dilatation in coronary angiograms

    International Nuclear Information System (INIS)

    Hinterauer, L.; Goebel, N.

    1983-01-01

    Amongst 166 patients with aneurysms, ectasia or megaloarteries shown on coronary angiograms, 86.1% had dilated vessels as part of generalised coronary sclerosis (usually in patients with three-vessel disease). In 9%, dilatation was of iatrogenic origin and in 4.8% it was idiopathic. One patient had Marfan's syndrome. Amongst 9 000 patients, there were eight with megalo-arteries without stenosis; six of these had atypical angina and three suffered an infarct. Patients with definite dilatation of the coronary artery and stagnation of contrast flow required treatment. (orig.) [de

  6. Vessel dilatation in coronary angiograms

    Energy Technology Data Exchange (ETDEWEB)

    Hinterauer, L.; Goebel, N.

    1983-11-01

    Amongst 166 patients with aneurysms, ectasia or megaloarteries shown on coronary angiograms, 86.1% had dilated vessels as part of generalised coronary sclerosis (usually in patients with three-vessel disease). In 9%, dilatation was of iatrogenic origin and in 4.8% it was idiopathic. One patient had Marfan's syndrome. Amongst 9 000 patients, there were eight with megalo-arteries without stenosis; six of these had atypical angina and three suffered an infarct. Patients with definite dilatation of the coronary artery and stagnation of contrast flow required treatment.

  7. Management of coronary artery disease

    Science.gov (United States)

    Safri, Z.

    2018-03-01

    Coronary Artery Disease (CAD) is associated with significant morbidity and mortality, therefore it’s important to early and accurate detection and appropriate management. Diagnosis of CAD include clinical examination, noninvasive techniques such as biochemical testing, a resting ECG, possibly ambulatory ECG monitoring, resting echocardiography, chest X-ray in selected patients; and catheterization. Managements of CAD patients include lifestyle modification, control of CAD risk factors, pharmacologic therapy, and patient education. Revascularization consists of percutaneous coronary angioplasty and coronary artery bypass grafting. Cardiac rehabilitation should be considered in all patients with CAD. This comprehensive review highlights strategies of management in patients with CAD.

  8. PLACENTAL GROWTH FACTOR AND CORONARY NEOANGIOGENESIS IN CORONARY HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Tulikov

    2013-01-01

    Full Text Available Neoangiogenesis in coronary heart disease is a protective reaction aimed to improve ischemic myocardial perfusion, by increasing the number and size of arterial collaterals. Placental growth factor (PlGF is one of the key peptides regulating angiogenic processes in atherosclerosis. In particular, a number of investigators have shown that injection of recombinant PlGF into the system or regional blood flow can stimulate neoangiogenesis. On the other hand, there is evidence confirming the involvement of PlGF in the progression of atherosclerosis and in the development of acute coronary syndrome. In this connection, the problem of investigating the efficiency and safety of possible use of PlGF preparations, as well as its place in the diagnosis of coronary heart disease and acute coronary syndrome remains urgent

  9. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Christian Stevns; Hasbak, Philip

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM......). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

  10. Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

    Science.gov (United States)

    Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G

    2017-01-01

    Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions. Copyright © 2017 the American Physiological Society.

  11. 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.

  12. Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training

    Science.gov (United States)

    La Favor, Justin D.; Dubis, Gabriel S.; Yan, Huimin; White, Joseph D.; Nelson, Margaret A.M.; Anderson, Ethan J.; Hickner, Robert C.

    2016-01-01

    Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies. PMID:27765769

  13. Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex.

    Science.gov (United States)

    Basura, Gregory J; Abbas, Atheir I; O'Donohue, Heather; Lauder, Jean M; Roth, Bryan L; Walker, Paul D; Manis, Paul B

    2008-10-01

    Maturation of the mammalian cerebral cortex is, in part, dependent upon multiple coordinated afferent neurotransmitter systems and receptor-mediated cellular linkages during early postnatal development. Given that serotonin (5-HT) is one such system, the present study was designed to specifically evaluate 5-HT tissue content as well as 5-HT(2A) receptor protein levels within the developing auditory cortex (AC). Using high performance liquid chromatography (HPLC), 5-HT and the metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was measured in isolated AC, which demonstrated a developmental dynamic, reaching young adult levels early during the second week of postnatal development. Radioligand binding of 5-HT(2A) receptors with the 5-HT(2A/2C) receptor agonist, (125)I-DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; in the presence of SB206553, a selective 5-HT(2C) receptor antagonist, also demonstrated a developmental trend, whereby receptor protein levels reached young adult levels at the end of the first postnatal week (P8), significantly increased at P10 and at P17, and decreased back to levels not significantly different from P8 thereafter. Immunocytochemical labeling of 5-HT(2A) receptors and confocal microscopy revealed that 5-HT(2A) receptors are largely localized on layer II/III pyramidal cell bodies and apical dendrites within AC. When considered together, the results of the present study suggest that 5-HT, likely through 5-HT(2A) receptors, may play an important role in early postnatal AC development.

  14. The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS)

    DEFF Research Database (Denmark)

    Madsen, Michael Tvilling; Isbrand, Anders; Andersen, Ulla Overgaard

    2017-01-01

    , Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome" trial (MEDACIS) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial. A total of 240 patients with ACS and no depressive symptoms will be included in the trial for treatment with either 25 mg...... melatonin or placebo for a 12-week period. Development and severity of depressive symptoms will be evaluated using Major Depression Inventory every 2 weeks with the purpose of investigating the potential preventive effect of melatonin on depressive symptoms. DISCUSSION: Previously, only selective serotonin...

  15. Selective serotonin reuptake inhibitors for fibromyalgia syndrome

    Science.gov (United States)

    Walitt, Brian; Urrútia, Gerard; Nishishinya, María Betina; Cantrell, Sarah E; Häuser, Winfried

    2016-01-01

    Background Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. Objectives The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. Selection criteria We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. Main results The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional

  16. Selective serotonin reuptake inhibitors for fibromyalgia syndrome

    Directory of Open Access Journals (Sweden)

    Brian Walitt

    Full Text Available ABSTRACT BACKGROUND: Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. OBJECTIVES: To assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs in the treatment of fibromyalgia. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5, MEDLINE (1966 to June 2014, EMBASE (1946 to June 2014, and the reference lists of reviewed articles. Selection criteria: We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis: Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. MAIN RESULTS: The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10% difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6% and placebo (39/171 (22.8% risk difference (RD 0.10, 95% confidence interval (CI 0.01 to 0.20; number needed to treat for an

  17. Coronary angiography using synchrotron radiation

    International Nuclear Information System (INIS)

    Akatsuka, Takao; Hiranaka, Yukio; Takeda, Tohru; Hyodo, Kazuyuki.

    1990-01-01

    Invasive coronary angiography is the imaging technique of choice for diagnosis of ischemic heart disease. Recently, the application of synchrotron radiation in coronary angiography has been investigated in the world, with the aim of developing the noninvasive technique for visualizing the heart. In this article, backgrounds and present situation of coronary angiography using synchrotron radiation are reviewed. Firstly, visual imaging techniques of the cardiovascular system are discussed in terms of angiography and digital subtraction angiography (DSA). Conventional temporal, energy, and hybrid subtraction modes used in DSA are referred to. Secondly, the application of synchrotron radiation is presented, focusing on the property of synchrotron radiation and K-edge subtraction angiography. Two kinds of synchrotron radiation beam methods are outlined. Interpretation of image data and various subtraction procedures remain unestablished. There is much to be done before coronary angiography using synchrotron radiation comes into a clinical practice. (N.K.)

  18. Depression following acute coronary syndrome

    DEFF Research Database (Denmark)

    Joergensen, Terese Sara Hoej; Maartensson, Solvej; Ibfelt, Else Helene

    2016-01-01

    PURPOSE: Depression is common following acute coronary syndrome, and thus, it is important to provide knowledge to improve prevention and detection of depression in this patient group. The objectives of this study were to examine: (1) whether indicators of stressors and coping resources were risk...... factors for developing depression early and later after an acute coronary syndrome and (2) whether prior depression modified these associations. METHODS: The study was a register-based cohort study, which includes 87,118 patients with a first time diagnosis of acute coronary syndrome during the period...... 2001-2009 in Denmark. Cox regression models were used to analyse hazard ratios (HRs) for depression. RESULTS: 1.5 and 9.5 % develop early (≤30 days) and later (31 days-2 years) depression after the acute coronary syndrome. Among all patients with depression, 69.2 % had first onset depression, while 30...

  19. Coronary Computed Tomography Angiography (CTA)

    Science.gov (United States)

    ... coronary arteries, may also be administered as a tablet or spray underneath your tongue. While lying on ... the scanner at one time such as with MRI. If an intravenous contrast material is used, you ...

  20. Pronounced Coronary Arteriosclerosis in Cirrhosis

    DEFF Research Database (Denmark)

    Danielsen, Karen V; Wiese, Signe; Hove, Jens

    2018-01-01

    factors including smoking, type 2 diabetes, hypertension, gender, or hypercholesterolemia. Coronary artery calcium-score was associated with diastolic dysfunction, lateral e´ (p = 0.025), but not with other markers of cardiac dysfunction. During a median follow-up of 25 months 12 patients (21%) died......BACKGROUND: The relation between excessive alcohol consumption and coronary arteriosclerosis has remained controversial. The etiology of cirrhosis has been considered a substantial risk factor for development of arteriosclerotic lesions. The coronary artery calcium-score derived from coronary CT...... and women: 136 vs. 0 HU; p alcohol-related cirrhosis was significantly higher than in nonalcohol-related cirrhosis (362 vs. 46 HU, p 

  1. Physiologic assessment of coronary artery fistula

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, N.C.; Beauvais, J. (Creighton Univ., Omaha, NE (USA))

    1991-01-01

    Coronary artery fistula is an uncommon clinical entity. The most common coronary artery fistula is from the right coronary artery to the right side of the heart, and it is less frequent to the pulmonary artery. The effect of a coronary artery fistula may be physiologically significant because of the steal phenomenon resulting in coronary ischemia. Based on published reports, it is recommended that patients with congenital coronary artery fistulas be considered candidates for elective surgical correction to prevent complications including development of congestive heart failure, angina, subacute bacterial endocarditis, myocardial infarction, and coronary aneurysm formation with rupture or embolization. A patient is presented in whom treadmill-exercise thallium imaging was effective in determining the degree of coronary steal from a coronary artery fistula, leading to successful corrective surgery.

  2. Physiologic assessment of coronary artery fistula

    International Nuclear Information System (INIS)

    Gupta, N.C.; Beauvais, J.

    1991-01-01

    Coronary artery fistula is an uncommon clinical entity. The most common coronary artery fistula is from the right coronary artery to the right side of the heart, and it is less frequent to the pulmonary artery. The effect of a coronary artery fistula may be physiologically significant because of the steal phenomenon resulting in coronary ischemia. Based on published reports, it is recommended that patients with congenital coronary artery fistulas be considered candidates for elective surgical correction to prevent complications including development of congestive heart failure, angina, subacute bacterial endocarditis, myocardial infarction, and coronary aneurysm formation with rupture or embolization. A patient is presented in whom treadmill-exercise thallium imaging was effective in determining the degree of coronary steal from a coronary artery fistula, leading to successful corrective surgery

  3. Ethanol intake and 3H-serotonin uptake I: A study in Fawn-Hooded rats

    International Nuclear Information System (INIS)

    Daoust, M.; Compagnon, P.; Legrand, E.; Boucly, P.

    1991-01-01

    Ethanol intake and synaptosomal 3 H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3 H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces 3 H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system

  4. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

    Science.gov (United States)

    Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

    2013-01-01

    The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

  5. The serotonin system in autism spectrum disorder: from biomarker to animal models

    Science.gov (United States)

    Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

    2015-01-01

    Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker. PMID:26577932

  6. Correlation between coronary computed tomographic angiography and fractional flow reserve

    DEFF Research Database (Denmark)

    Kristensen, Thomas Skaarup; Engstrøm, Thomas; Kelbæk, Henning

    2010-01-01

    Coronary CT angiography (CCTA) has become an important modality to evaluate the presence of coronary artery disease. Coronary artery stenosis of intermediate severity remains a therapeutic dilemma. Measurement of fractional flow reserve (FFR) during coronary angiography is the most established...

  7. Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Yii Michael

    2011-09-01

    Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the

  8. Rationality and emotionality: serotonin transporter genotype influences reasoning bias.

    Science.gov (United States)

    Stollstorff, Melanie; Bean, Stephanie E; Anderson, Lindsay M; Devaney, Joseph M; Vaidya, Chandan J

    2013-04-01

    Reasoning often occurs under emotionally charged, opinion-laden circumstances. The belief-bias effect indexes the extent to which reasoning is based upon beliefs rather than logical structure. We examined whether emotional content increases this effect, particularly for adults genetically predisposed to be more emotionally reactive. SS/SL(G) carriers of the serotonin transporter genotype (5-HTTLPR) were less accurate selectively for evaluating emotional relational reasoning problems with belief-logic conflict relative to L(A)L(A) carriers. Trait anxiety was positively associated with emotional belief-bias, and the 5-HTTLPR genotype significantly accounted for the variance in this association. Thus, deductive reasoning, a higher cognitive ability, is sensitive to differences in emotionality rooted in serotonin neurotransmitter function.

  9. Unifying concept of serotonin transporter-associated currents.

    Science.gov (United States)

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

    2012-01-02

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

  10. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Ning-Ning Song

    2017-06-01

    Full Text Available The central serotonin (5-HT system is the main target of selective serotonin reuptake inhibitors (SSRIs, the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis. We focus on data obtained from three categories of genetically engineered mouse models: (1 mice with altered central 5-HT levels from embryonic stages, (2 mice with deletion of 5-HT receptors from embryonic stages, and (3 mice with altered central 5-HT system exclusively in adulthood. These recent findings provide unique insights to interpret the multifaceted roles of central 5-HT on adult hippocampal neurogenesis and its associated effects on depression.

  11. Expression analysis for inverted effects of serotonin transporter inactivation

    International Nuclear Information System (INIS)

    Ichikawa, Manabu; Okamura-Oho, Yuko; Shimokawa, Kazuro; Kondo, Shinji; Nakamura, Sakiko; Yokota, Hideo; Himeno, Ryutaro; Lesch, Klaus-Peter; Hayashizaki, Yoshihide

    2008-01-01

    Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain

  12. Serotonin syndrome associated with sertraline use: case report

    OpenAIRE

    Bárbara Werner Griciunas; Norton Yoshiaki Kitanishi; Renata Carvalho de Souza; Daniel Azevedo Cavalcante; Leonardo Mattiolli Marini

    2017-01-01

    Case report of serotonin syndrome in patient who initiated the use of sertraline at a dose greater than twice the recommended for the treatment of psychotic depression. The patient presented contracture of the limbs, puzzled look, mutism and blood pressure 230x110 mmHg. The syndrome is increasingly common, although it is not well recognized. Many medications can cause it and this possibility should be considered in patients taking serotonergic drugs presenting autonomic or mental disorders an...

  13. Modulation of rat blood phagocyte activity by serotonin

    Czech Academy of Sciences Publication Activity Database

    Okénková, Kateřina; Lojek, Antonín; Kubala, Lukáš; Číž, Milan

    2007-01-01

    Roč. 101, č. 14 (2007), s245-s246 E-ISSN 1213-7103. [Mezioborová česko-slovenská toxikologická konference /12./. Praha, 11.06.2007-13.06.2007] R&D Projects: GA ČR(CZ) GA524/04/0897 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : phagocytes * serotonin * reactive oxygen species Subject RIV: BO - Biophysics

  14. APRESS: apical regulatory super system, serotonin, and dopamine interaction

    Directory of Open Access Journals (Sweden)

    Hinz M

    2011-08-01

    Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USABackground: The monoamines serotonin and dopamine are known to exist in two separate states: the endogenous state and the competitive inhibition state. The presence of the competitive inhibition state has been known to science for many years, but from a functional standpoint it has been noted in the literature as being "meaningless."Methods: A large database of monoamine transporter response to amino acid precursor administration variations with clinical outcomes was accumulated. In the process, a new organic cation transporter (OCT model has been published, and OCT functional status determination along with amino acid precursor manipulation methods have been invented and refined.Results: Methodology was developed whereby manipulation of the OCT, in the competitive inhibition state, is carried out in a predictable manner. This, in turn, has disproved the long-held assertion that the monoamine competitive inhibition state is functionally meaningless.Conclusion: The most significant aspect of this paper is the documentation of newly recognized relationships between serotonin and dopamine. When transport of serotonin and dopamine are both in the competitive inhibition state, manipulation of the concentrations of one will lead to predictable changes in concentrations of the other. From a functional standpoint, processes regulated and controlled by changes to only serotonin can now be controlled by changes to dopamine, and vice versa, in a predictable manner.Keywords: catecholamine, monoamine, competitive inhibition state

  15. Serotonin Signal Transduction in Two Groups of Autistic Patients

    Science.gov (United States)

    2013-12-01

    behavioral, and now molecular genetic evidence implicate dysfunction of the serotonin system in autism spectrum disorders (ASD), and specifically in...validationin individuals with autism spectrum disorders . 2007 J Autism Dev Disord . 37:855-66. Lord, C.L., Cook, E.H., Leventhal, B.L., Amaral, D.G...2000 Minireview: Autism spectrum disorders . Neuron.,28:355-363. Shao Y, Cuccaro ML, Hauser ER, Raiford KL, Menold MM, Wolpert CM, Ravan SA

  16. Rationality and emotionality: serotonin transporter genotype influences reasoning bias

    OpenAIRE

    Stollstorff, Melanie; Bean, Stephanie E.; Anderson, Lindsay M.; Devaney, Joseph M.; Vaidya, Chandan J.

    2012-01-01

    Reasoning often occurs under emotionally charged, opinion-laden circumstances. The belief-bias effect indexes the extent to which reasoning is based upon beliefs rather than logical structure. We examined whether emotional content increases this effect, particularly for adults genetically predisposed to be more emotionally reactive. SS/SLG carriers of the serotonin transporter genotype (5-HTTLPR) were less accurate selectively for evaluating emotional relational reasoning problems with belief...

  17. Molecular cloning, expression and characterization of a bovine serotonin transporter

    DEFF Research Database (Denmark)

    Mortensen, O V; Kristensen, A S; Rudnick, G

    1999-01-01

    The serotonin transporter (SERT) is a member of a highly homologous family of sodium/chloride dependent neurotransmitter transporters responsible for reuptake of biogenic amines from the extracellular fluid. SERT constitutes the pharmacological target of several clinically important antidepressan......-methylenedioxymethamphetamine (MDMA) was mainly unchanged. RT-PCR amplification of RNA from different tissues demonstrated expression of SERT in placenta, brain stem, bone marrow, kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid gland, small intestine and pancreas....

  18. Serotonin Transporter Genotype (5-HTTLPR) Predicts Utilitarian Moral Judgments

    OpenAIRE

    Marsh, Abigail A.; Crowe, Samantha L.; Yu, Henry H.; Gorodetsky, Elena K.; Goldman, David; Blair, R. J. R.

    2011-01-01

    Background The psychological and neurobiological processes underlying moral judgment have been the focus of extensive recent research. Here we show that serotonin transporter (5-HTTLPR) genotype predicts responses to moral dilemmas featuring foreseen harm to an innocent. Methodology/Principal Findings Participants in this study judged the acceptability of actions that would unintentionally or intentionally harm an innocent victim in order to save others' lives. An analysis of variance reveale...

  19. Serotonin as a Biomarker: Stress Resilience among Battlefield Airmen Trainees

    Science.gov (United States)

    2016-05-21

    anxiety, anger, impulsivity, lethargy, sleepiness, and mood disorders [2-5,11,12]. Studies have also shown that prolonged exercise increases...are likely to abandon training on their own. These data may improve the design of biomarker performance prediction models for stress, cognitive...findings demonstrate potential for using serotonin data to identify trainees who are likely to abandon training on their own. These data may improve

  20. 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

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

    Science.gov (United States)

    Panazzolo, Diogo G; Sicuro, Fernando L; Clapauch, Ruth; Maranhão, Priscila A; Bouskela, Eliete; Kraemer-Aguiar, Luiz G

    2012-11-13

    We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. 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 (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max)). 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 TRBCV(max) varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way. Principal component 3 was associated only with microvascular

  2. 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

  3. Alcohol consumption and risk of microvascular complications in type 1 diabetes patients; the EURODIAB Prospective Complications study

    NARCIS (Netherlands)

    Beulens, J.W.J.; Kruidhof, J.S.; Grobbee, D.E.; Chaturvedi, N.; Fuller, J.H.; Soedamah-Muthu, S.S.

    2008-01-01

    AIMS/HYPOTHESIS: The aim of this study was to investigate the association between alcohol consumption and risk of microvascular complications (retinopathy, neuropathy, nephropathy) in type 1 diabetes mellitus patients in the EURODIAB Prospective Complications Study. METHODS: The EURODIAB Prospective

  4. Crystal Structure of an LSD-Bound Human Serotonin Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D.; Betz, Robin M.; Venkatakrishnan, A.J.; Levit, Anat; Lansu, Katherine; Schools, Zachary L.; Che, Tao; Nichols, David E.; Shoichet, Brian K.; Dror, Ron O.; Roth, Bryan L. (UNCSM); (UNC); (Stanford); (Stanford-MED); (UCSF)

    2017-01-01

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.

  5. Crystal Structure of an LSD-Bound Human Serotonin Receptor.

    Science.gov (United States)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D; Betz, Robin M; Venkatakrishnan, A J; Levit, Anat; Lansu, Katherine; Schools, Zachary L; Che, Tao; Nichols, David E; Shoichet, Brian K; Dror, Ron O; Roth, Bryan L

    2017-01-26

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT 2B . The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT 2B R and 5-HT 2A R-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Regional distribution of serotonin transporter protein in postmortem human brain

    Energy Technology Data Exchange (ETDEWEB)

    Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2005-02-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

  7. Regional distribution of serotonin transporter protein in postmortem human brain

    International Nuclear Information System (INIS)

    Kish, Stephen J.; Furukawa, Yoshiaki; Chang Lijan; Tong Junchao; Ginovart, Nathalie; Wilson, Alan; Houle, Sylvain; Meyer, Jeffrey H.

    2005-01-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

  8. Serotonin 6 receptor controls Alzheimer's disease and depression.

    Science.gov (United States)

    Yun, Hyung-Mun; Park, Kyung-Ran; Kim, Eun-Cheol; Kim, Sanghyeon; Hong, Jin Tae

    2015-09-29

    Alzheimer's disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of Aβ via the inhibition of γ-secretase activity and the inactivation of astrocytes and microglia in the AD mouse model. It was found that the reduction of serotonin level was significantly recovered by SB271036, which was mediated by an indirect regulation of serotonergic neurons via GABA. Selective serotonin reuptake inhibitor (SSRI), fluoxetine significantly improved cognitive impairment and behavioral changes. In human brain of depression patients, we then identified the potential genes, amyloid beta (A4) precursor protein-binding, family A, member 2 (APBA2), well known AD modulators by integrating datasets from neuropathology, microarray, and RNA seq. studies with correlation analysis tools. And also, it was demonstrated in mouse models and patients of AD. These data indicate functional network of 5-HT6R between AD and depression.

  9. Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo.

    Science.gov (United States)

    Malizia, A L; Melichar, J M; Brown, D J; Gunn, R N; Reynolds, A; Jones, T; Nutt, D J

    1997-01-01

    We describe the use of 11CRTI-55 and the Multiple Objects Coincidences Counter (MOCC) to detect in-vivo binding to peripheral serotonin reuptake sites (left chest comprising platelet and lung serotonin reuptake sites) in man. Displacement and preloading experiments with clomipramine and venlafaxine in two healthy volunteers demonstrated that 11CRTI-55 binding is decreased in a dose-dependent fashion by both these drugs which bind to the serotonin transporter. In addition parallel data from the total head curve (representing 11CRTI-55 binding to central serotonin and dopamine (DA) reuptake sites) suggest that prior blockade of the serotonin transporter may be a useful strategy to maximize radioactive counts in the head when measuring the DA transporter. The MOCC is likely to be useful to determine sequential indices of relative serotonin reuptake blockade in patients on treatment.

  10. Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

    Directory of Open Access Journals (Sweden)

    Ali Tahir

    2015-01-01

    Full Text Available Patients with diabetes mellitus (DM develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC. Serotonin was observed to elevate reactive oxygen species (ROS and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT, superoxide dismutase (SOD, B-type natriuretic peptide (BNP expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

  11. Photomimetic effect of serotonin on yeast cells irradiated by far-UV radiation

    International Nuclear Information System (INIS)

    Fraikin, G.Y.; Strakhovskaya, M.G.; Rubin, L.B.

    1982-01-01

    The effect of serotonin on the survival of far-UV irradiated cells of the yeast Candida guilliermondii was studied. Serotonin was found to have a photomimetic property. Preincubation of cells with serotonin results in protection against far-UV inactivation, whereas the post-radiation treatment with serotonin causes a potentiation of far-UV lethality. Both effects are similar to those produced by near-UV (334 nm) radiation. The observations provide support to the previously proposed idea that photosynthesized serotonin is the underlying cause of the two effects of near-UV radiation, photoprotection and potentiation of far-UV lethality. Experiments with an excision-deficient strain of the yeast Saccharomyces cerevisiae suggest that the effect of serotonin is by its binding to DNA. (author)

  12. Coronary artery anomalies in Turner Syndrome.

    Science.gov (United States)

    Viuff, Mette H; Trolle, Christian; Wen, Jan; Jensen, Jesper M; Nørgaard, Bjarne L; Gutmark, Ephraim J; Gutmark-Little, Iris; Mortensen, Kristian H; Gravholt, Claus Højbjerg; Andersen, Niels H

    Congenital heart disease, primarily involving the left-sided structures, is often seen in patients with Turner Syndrome. Moreover, a few case reports have indicated that coronary anomalies may be more prevalent in Turner Syndrome than in the normal population. We therefore set out to systematically investigate coronary arterial anatomy by computed tomographic coronary angiography (coronary CTA) in Turner Syndrome patients. Fifty consecutive women with Turner Syndrome (mean age 47 years [17-71]) underwent coronary CTA. Patients were compared with 25 gender-matched controls. Coronary anomaly was more frequent in patients with Turner Syndrome than in healthy controls [20% vs. 4% (p = 0.043)]. Nine out of ten abnormal cases had an anomalous left coronary artery anatomy (absent left main trunk, n = 7; circumflex artery originating from the right aortic sinus, n = 2). One case had a tubular origin of the right coronary artery above the aortic sinus. There was no correlation between the presence of coronary arterial anomalies and karyotype, bicuspid aortic valve, or other congenital heart defects. Coronary anomalies are highly prevalent in Turner Syndrome. The left coronary artery is predominantly affected, with an absent left main coronary artery being the most common anomaly. No hemodynamically relevant coronary anomalies were found. Copyright © 2016 Society of Cardiovascular Computed Tomography. All rights reserved.

  13. 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.

  14. 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.

  15. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.

    Science.gov (United States)

    Ripken, Dina; van der Wielen, Nikkie; Wortelboer, Heleen M; Meijerink, Jocelijn; Witkamp, Renger F; Hendriks, Henk F J

    2016-06-01

    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Conundrums in neurology: diagnosing serotonin syndrome - a meta-analysis of cases.

    Science.gov (United States)

    Werneke, Ursula; Jamshidi, Fariba; Taylor, David M; Ott, Michael

    2016-07-12

    Serotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. Serotonin syndrome's main feature is neuro-muscular hyperexcitability, which in many cases is mild but in some cases can become life-threatening. The diagnosis of serotonin syndrome remains challenging since it can only be made on clinical grounds. Three diagnostic criteria systems, Sternbach, Radomski and Hunter classifications, are available. Here we test the validity of four assumptions that have become widely accepted: (1) The Hunter classification performs clinically better than the Sternbach and Radomski criteria; (2) in contrast to neuroleptic malignant syndrome, the onset of serotonin syndrome is usually rapid; (3) hyperthermia is a hallmark of severe serotonin syndrome; and (4) serotonin syndrome can readily be distinguished from neuroleptic malignant syndrome on clinical grounds and on the basis of medication history. Systematic review and meta-analysis of all cases of serotonin syndrome and toxicity published between 2004 and 2014, using PubMed and Web of Science. Two of the four assumptions (1 and 2) are based on only one published study each and have not been independently validated. There is little agreement between current criteria systems for the diagnosis of serotonin syndrome. Although frequently thought to be the gold standard for the diagnosis of the serotonin syndrome, the Hunter criteria did not perform better than the Sternbach and Radomski criteria. Not all cases seem to be of rapid onset and only relatively few cases may present with hyperthermia. The 0 differential diagnosis between serotonin syndrome and neuroleptic malignant syndrome is not always clear-cut. Our findings challenge four commonly made assumptions about serotonin syndrome. We propose our meta-analysis of cases (MAC) method as a new way to systematically pool and interpret anecdotal but important clinical information concerning uncommon or emergent phenomena that cannot be

  17. The serotonin system in autism spectrum disorder: from biomarker to animal models

    OpenAIRE

    Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

    2015-01-01

    Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophy...

  18. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    OpenAIRE

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen...

  19. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder

    DEFF Research Database (Denmark)

    Mc Mahon, Brenda; Andersen, Sofie B.; Madsen, Martin K.

    2016-01-01

    controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding...... between summer and winter (Psex-(P = 0.02) and genotype-(P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom...

  20. Characterization and regulation of [3H]-serotonin uptake and release in rodent spinal

    International Nuclear Information System (INIS)

    Stauderman, K.A.

    1986-01-01

    The uptake and release of [ 3 H]-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent [ 3 H]-serotonin accumulation processes were found. Sodium-dependent [ 3 H]-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC 50 75 nM), followed by desipramine (IC 50 430 nM) and nomifensine (IC 50 950 nM). The sodium-independent [ 3 H]-serotonin accumulation process was insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent [ 3 H]-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K + -induced release of previously accumulated [ 3 H]-serotonin was Ca 2+ -dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited [ 3 H]-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca 2+ -sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord

  1. Early results of coronary artery bypass grafting with coronary endarterectomy for severe coronary artery disease

    Directory of Open Access Journals (Sweden)

    Toischer Karl

    2009-09-01

    Full Text Available Abstract Background Despite the existence of controversial debates on the efficiency of coronary endarterectomy (CE, it is still used as an adjunct to coronary artery bypass grafting (CABG. This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed. Methods Patient demographic information, operative details and outcome data of 104 patients with diffuse calcified coronary artery disease were retrospectively analyzed with respect to functional capacity (NYHA, angina pectoris (CCS and mortality. Actuarial survival was reported using a Kaplan-Meyer analysis. Results Between August 2001 and March 2005, 104 patients underwent coronary artery bypass grafting (CABG with adjunctive coronary endarterectomy (CE in the Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen. Four patients were lost during follow-up. Data were gained from 88 male and 12 female patients; mean age was 65.5 ± 9 years. A total of 396 vessels were bypassed (4 ± 0.9 vessels per patient. In 98% left internal thoracic artery (LITA was used as arterial bypass graft and a total of 114 vessels were endarterectomized. CE was performed on right coronary artery (RCA (n = 55, on left anterior descending artery (LAD (n = 52 and circumflex artery (RCX (n = 7. Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2 from 1-vessel-disease. Closed technique was used in 18%, open technique in 79% and in 3% a combination of both. The most frequent endarterectomized localization was right coronary artery (RCA = 55%. Despite the severity of endstage atherosclerosis, hospital mortality was only 5% (n = 5. During follow-up (24.5 ± 13.4 months, which is 96% complete (4 patients were lost caused by unknown address 8 patients died (cardiac

  2. Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange.

    Science.gov (United States)

    Bert, J; Gyenge, C; Bowen, B; Reed, R; Lund, T

    1997-03-01

    A validated mathematical model of microvascular exchange in thermally injured humans has been used to predict the consequences of different forms of resuscitation and potential modes of action of pharmaceuticals on the distribution and transport of fluid and macromolecules in the body. Specially, for 10 and/or 50 per cent burn surface area injuries, predictions are presented for no resuscitation, resuscitation with the Parkland formula (a high fluid and low protein formulation) and resuscitation with the Evans formula (a low fluid and high protein formulation). As expected, Parkland formula resuscitation leads to interstitial accumulation of excess fluid, while use of the Evans formula leads to interstitial accumulation of excessive amounts of proteins. The hypothetical effects of pharmaceuticals on the transport barrier properties of the microvascular barrier and on the highly negative tissue pressure generated postburn in the injured tissue were also investigated. Simulations predict a relatively greater amelioration of the acute postburn edema through modulation of the postburn tissue pressure effects.

  3. Alternative wavelengths for sutureless laser microvascular anastomosis: a preliminary study on acute samples.

    Science.gov (United States)

    Bass, L S; Oz, M C; Libutti, S K; Treat, M R

    1992-06-01

    Attempts to improve the speed and patency of microvascular anastomosis with laser-assisted techniques have provided a modest reduction in operative time and comparable success rates. Using sutureless microvascular anastomoses, 30 end-to-end anastomoses were created in the rat carotid artery using the gallium-aluminum-arsenide diode laser (808 nm). Indocyanine green and fibrinogen were applied to enhance tissue absorption of the laser energy and strengthen the bond created. These were compared with previously reported welds using the THC:YAG laser (2150 nm). Mean welding times were 140 and 288 s, and mean bursting pressures immediately after welding were 515 and 400 mmHg for the diode and THC:YAG laser groups, respectively. Histologically, both lateral and vertical spread of thermal damage was limited. Since both lasers create welds of adequate initial strength without stay sutures and are faster and easier to use than existing systems, evaluation of long-term patency would be worthwhile.

  4. [Successful microvascular decompression of the medulla oblongata for a case with respiratory failure: case report].

    Science.gov (United States)

    Koguchi, Motofumi; Nakahara, Yukiko; Kawashima, Masatou; Takase, Yukinori; Matsushima, Toshio

    2011-11-01

    We report a case of the medulla oblongata syndrome successfully treated by microvascular decompression surgery. The patient was a 75-year-old woman and had been suffering from gradual progressive dyspnea since July, 2009. Two month later, intubation and medial ventilator treatments were began because of severe respiratory problems. The central respiratory problems were considered in extensive testing by the physician. The head MR imaging showed that the left vertebral artery had markedly compressed the medulla oblongata. We thought that her respiratory problems were associated with this vertebral artery compression of the medulla oblongata. We performed the microvascular decompression surgery by left trans-condylar fossa approach. Her hypoventilation graduately improved after the surgery and she needed neither ventilator nor oxygen in several months. She is able to perform daily activities by herself. We report the case, and discuss the cause of respiratory problems especially by compression of the medulla oblongata.

  5. A model of physical factors in the structural adaptation of microvascular networks in normotension and hypertension

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Gustafsson, Finn; Holstein-Rathlou, N.-H.

    2003-01-01

    Adequate function of the microcirculation is vital to any tissue. To maintain an optimal function, microvascular networks must be able to adapt structurally to changes in the physical environment. Here we present a mathematical network model based on vessel wall mechanics. We assume based...... diameter, until equilibrium is restored. The model explains several of the key features observed experimentally in the microcirculation in normotension and hypertension. Most importantly, it suggests a scenario where overall network structure and network hemodynamics depend on adaptation to local...... hemodynamic stimuli in the individual vessel. Simulated results show emanating microvascular networks with properties similar to those observed in vivo. The model points to an altered endothelial function as a key factor in the development of vascular changes characteristic of hypertension....

  6. 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...

  7. Zebrafish as a Model for the Study of Microvascular Complications of Diabetes and Their Mechanisms

    Directory of Open Access Journals (Sweden)

    Karl Heckler

    2017-09-01

    Full Text Available Diabetes mellitus (DM is a crucial metabolic disease that leads to severe disorders. These include macrovascular complications such as myocardial infarction, stroke, and peripheral artery disease and microvascular complications including diabetic nephropathy, neuropathy, and retinopathy. Diabetes mellitus, along with its associated organ pathologies, is one of the key problems in today’s medicine. Zebrafish is an upcoming disease model organism in diabetes research. Its glucose metabolism and the pathways of reactive metabolite formation are very similar to those of humans. Moreover, several physiological and pathophysiological pathways that also exist in humans and other mammals have been identified in this species or are currently under intense investigation. Zebrafish offer sophisticated imaging techniques and allow simple and fast genetic and pharmacological approaches with a high throughput. In this review, we highlight achievements and mechanisms concerning microvascular complications discovered in zebrafish, and we discuss the advantages and disadvantages of zebrafish as a model for studying diabetic complications.

  8. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.

    Science.gov (United States)

    Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano

    2016-05-04

    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs.

  9. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram Vinod; Hansen, Stinus; Nielsen, Morten Frost Munk

    2016-01-01

    OBJECTIVE AND DESIGN: Patients with type 2 diabetes mellitus (T2D) have an increased fracture risk despite a normal or elevated bone mineral density (BMD). The aim of this cross-sectional in vivo study was to assess parameters of peripheral bone microarchitecture, estimated bone strength and bone...... remodeling in T2D patients with and without diabetic microvascular disease (MVD+ and MVD- respectively) and to compare them with healthy controls. METHODS: Fifty-one T2D patients (MVD+ group: n=25) were recruited from Funen Diabetic Database and matched for age, sex and height with 51 healthy subjects. High...... deficits are not a characteristic of all T2D patients but of a subgroup characterized by the presence of microvascular complications. Whether this influences fracture rates in these patients needs further investigation....

  10. Coronary ostium occlusion by coronary cusp displacement in Williams syndrome.

    Science.gov (United States)

    Shiohama, Tadashi; Fujii, Katsunori; Ebata, Ryota; Funabashi, Nobusada; Matsumiya, Goro; Saito, Yuko Kazato; Takechi, Fumie; Yonemori, Yoko; Nakatani, Yukio; Shimojo, Naoki

    2016-06-01

    Williams syndrome is a contiguous gene deletion syndrome resulting from a heterozygous deletion on chromosome 7q11.23, and is characterized by distinctive facial features and supravalvular aortic stenosis (SVAS). This syndrome rarely presents unpredictable cardiac death, and yet, as illustrated in the present case, it is still not possible to predict it, even on close monitoring. We herein describe the case of a 6-year-old Japanese girl with Williams syndrome, who had sudden cardiac collapse due to cardiac infarction after pharyngitis. Cardiac failure followed a critical course that did not respond to catecholamine support or heart rest with extracardiac mechanical support. Although marked coronary stenosis was not present, the left coronary cusp abnormally adhered to the aortic wall, which may synergistically cause coronary ostium occlusion with SVAS. Altered hemodynamic state, even that caused by the common cold, may lead to critical myocardial events in Williams syndrome with SVAS. © 2015 Japan Pediatric Society.

  11. NEUROTICISM PROFILE IN CORONARY HEART DISEASE

    OpenAIRE

    Bhargava, S. C.; Sharma, S. N.; Agarwal, B. V.

    1980-01-01

    SUMMARY Thirty seven cases of coronary heart disease and 30 normal healthy controls were administered Hindi version of MHQ. The coronary heart disease patients scored significantly higher on total neuroticism, free-floating anxiety and somatic anxiety subscales of MHQ.

  12. Coronary artery with aberrant origin malignant right

    International Nuclear Information System (INIS)

    Ozcan, E.; Bozlar, U.; Demirkol, S.; Saglam, M.

    2012-01-01

    Full text: Introduction: Congenital anomalies of the coronary arteries is a major cause of sudden death, especially in young patients. Objectives and tasks: In this study we aim to present a young patient with chest pain who had malignant right coronary artery (RCA) with aberrant origin. Materials and methods: 24-year-old man who applied cardiology clinic for chest pain and palpitations especially after exercise, was referred to our clinic for coronary computed tomography (CT) angiography to evaluate coronary artery anomalies. Results: In CT angiography; we detected aberrant RCA with origin of tubularly part of ascendant aorta with a malignant course between aorta and pulmonary artery. Left main coronary artery, left anterior descending and circumflex artery had normal origin and course. Conclusion: Coronary artery with malignant course may cause sudden death especially after exercise. Coronary CT angiography has an important role in diagnosis of congenital coronary artery anomalies, with high resolution multiplanner reformatted images

  13. Serotonin receptors influencing cell proliferation in the jejunal crypt epithelium and in colonic adenocarcinomas.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1986-01-01

    Serotonin has previously been shown to stimulate cell proliferation in the jejunal crypt epithelium and in colonic tumours. The original classification of serotonin receptors into D and M groups was not conductive to the understanding of these observations. The more recent classification of serotonin receptors into 5HT1 and 5HT2 groups is considered in this report. On the balance of evidence it appears that similar receptors mediate the response to serotonin in the two tissues under consideration and that these receptors resemble those of the 5HT1 group. Such receptors are usually positively linked to adenylate cyclase.

  14. [The effect of mineral water on serotonin and insulin production (an experimental study)].

    Science.gov (United States)

    Polushina, N D

    1998-01-01

    Radioimmunoassay (DRG kits) and orthotoluidine test were conducted to measure blood serotonin, insulin and glucose in 70 intact Wistar rat males before and after a course of drinking mineral water Essentuki 17 (MW). After the MW drinking course, a single dose of mineral water increases basal levels of serotonin and insulin, sensitivity of endocrine cells to MW. Serotonin and insulin rose maximally on minute 5 after the drink while in contrast to minute 15 and 30 before initiation of the MW drinking course. A direct correlation was found between blood concentrations of serotonin and insulin.

  15. Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata.

    Science.gov (United States)

    Girish, B P; Swetha, C H; Reddy, P Sreenivasula

    2017-09-02

    In the current study, we have examined the role of serotonin in regulating the levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata and validated that serotonin indeed is a reproductive hormone. Administration of serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor (RXR) and ecdysteroid receptor (EcR) respectively and these receptors are involved in the regulation of reproduction in crustaceans, we have determined the mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of serotonin injected crabs when compared to the controls. In vitro organ culture studies revealed that incubation of Y-orgas and mandibular organ explants in the presence of serotonin resulted in a significant increase in the secretion of ecdysteroids by Y-organs, but without alterations in MF synthesis in mandibular organs. From the above studies it is evident that serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though the circulatory levels methyl farnesoate elevated after serotonin administration, organ culture studies revealed serotonin mediated methyl farnesaote synthesis is indirect probably by inhibiting release of mandibular organ inhibiting hormone from eyestalks. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Radioenzymatic microassay for picogram quantities of serotonin or acetylserotonin in biological fluids and tissues

    International Nuclear Information System (INIS)

    Hussain, M.N.; Benedict, C.R.

    1987-01-01

    This paper describes several modifications of the original radioenzymatic assay for serotonin which increase the sensitivity of the assay 20-fold as well as enhance its reliability. Using this method serotonin concentrations can be directly measured in biological examples without precleaning the sample. When compared to currently available methods this assay is specific and sensitive to approximately 1 pg of serotonin and can be used to measure serotonin levels in individual brain nuclei or microliter quantities of biological fluids. This assay can be easily adapted for the direct measurement of N-acetylserotonin. A large number of samples can be assayed in a single working day

  17. Coronary spasm induced by dipyridamole

    International Nuclear Information System (INIS)

    Wartski, M.; Caussin, C.; Lancelin, B.

    2001-01-01

    A 59 years old man was admitted at hospital for recurrent instable angina 1 month after coronary artery bypass surgery. Coronary artery disease started with a transmural antero-septo-apical myocardial infarction without thrombolysis and a percutaneous angioplasty with endo-prothesis on proximal left anterior descendant artery (LAD) is performed Because of recurrent rest angina and subacute stent thrombosis, a coronary artery bypass surgery (CABG) is performed with anastomosis of the left internal thoracic artery on LAD. The patient is admitted for recurrent rest angina one month after CABG. On ECG performed during chest pain, a ST-T segment elevation occurred on inferior leads. Coronary angiography showed no significant stenosis on endo-prothesis and no bypass graft dysfunction. Dipyridamole scintigraphy was realized. 2 minutes after the beginning of Dipyridamole infusion, a ST-T elevation occurred on inferior leads and two marked antero-septal and inferior defects were noticed on myocardial scintigraphy. Images at rest showed a clear improvement in the anterior wall and the inferior wall became normally perfused Patient was treated with anti-spastic drugs and a new coronarography with methyl-ergotamine test was performed inducing chest pain, ST-T elevation on inferior leads and tri-truncular coronary spasm. Patient's treatment was then modified with introduction of Nifedipine. The patient did not experienced new recurrent chest pain and remained totally asymptomatic few months later. (authors)

  18. Time-Dependent Behavior of Microvascular Blood Flow and Oxygenation: A Predictor of Functional Outcomes.

    Science.gov (United States)

    Kuliga, Katarzyna Z; Gush, Rodney; Clough, Geraldine F; Chipperfield, Andrew John

    2018-05-01

    This study investigates the time-dependent behaviour and algorithmic complexity of low-frequency periodic oscillations in blood flux (BF) and oxygenation signals from the microvasculature. Microvascular BF and oxygenation (OXY: oxyHb, deoxyHb, totalHb, and SO 2 %) was recorded from 15 healthy young adult males using combined laser Doppler fluximetry and white light spectroscopy with local skin temperature clamped to 33  °C and during local thermal hyperaemia (LTH) at 43 °C. Power spectral density of the BF and OXY signals was evaluated within the frequency range (0.0095-1.6 Hz). Signal complexity was determined using the Lempel-Ziv (LZ) algorithm. Fold increase in BF during LTH was 15.6 (10.3, 22.8) and in OxyHb 4.8 (3.5, 5.9) (median, range). All BF and OXY signals exhibited multiple oscillatory components with clear differences in signal power distribution across frequency bands at 33 and 43 °C. Significant reduction in the intrinsic variability and complexity of the microvascular signals during LTH was found, with mean LZ complexity of BF and OxyHb falling by 25% and 49%, respectively ( ). These results provide corroboration that in human skin microvascular blood flow and oxygenation are influenced by multiple time-varying oscillators that adapt to local influences and become more predictable during increased haemodynamic flow. Recent evidence strongly suggests that the inability of microvascular networks to adapt to an imposed stressor is symptomatic of disease risk which might be assessed via BF and OXY via the combination signal analysis techniques described here.

  19. Restrictive use of perioperative blood transfusion does not increase complication rates in microvascular breast reconstruction.

    Science.gov (United States)

    O'Neill, Anne C; Barandun, Marina; Cha, Jieun; Zhong, Toni; Hofer, Stefan O P

    2016-08-01

    With increasing appreciation of the possible adverse effects of peri-operative blood transfusion, restrictive policies regarding use of blood products have been adopted in many surgical specialties. Although microvascular breast reconstruction has become a routine procedure, high peri-operative transfusion rates continue to be reported in the literature. In this study we examine the impact of our restrictive approach on blood transfusion rates and postoperative complications in patients undergoing microvascular blood transfusion. A retrospective review of patients undergoing microvascular breast reconstruction with abdominal flaps at a single institution was performed. Patient age and body mass index as well as type, timing and laterality of reconstruction was recorded. Pre-operative and post-operative hemoglobin and hematocrit were recorded. Peri-operative blood transfusion rates were calculated. Post-operative complication rates were compared between patients with higher and lower post-operative hemoglobin levels. Five hundred and twelve patients were included in this study. The peri-operative transfusion rate was 0.98% in this series. There was no significant difference between transfusion rates in unilateral and bilateral reconstructions (0.68 vs 1.36% p = 0.08) or immediate and delayed reconstructions (1.02 vs 0.51% p = 0.72 and 1.01 vs 1.60% p = 0.09 for unilateral and bilateral respectively). Lower post-operative hemoglobin levels were not associated with increased flap related, surgical or medical complications rates. A restrictive approach to peri-operative blood transfusion can be safely adopted in microvascular breast reconstruction without compromising flap viability or overall complication rates. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. Microvascular anastomosis simulation using a chicken thigh model: Interval versus massed training.

    Science.gov (United States)

    Schoeff, Stephen; Hernandez, Brian; Robinson, Derek J; Jameson, Mark J; Shonka, David C

    2017-11-01

    To compare the effectiveness of massed versus interval training when teaching otolaryngology residents microvascular suturing on a validated microsurgical model. Otolaryngology residents were placed into interval (n = 7) or massed (n = 7) training groups. The interval group performed three separate 30-minute practice sessions separated by at least 1 week, and the massed group performed a single 90-minute practice session. Both groups viewed a video demonstration and recorded a pretest prior to the first training session. A post-test was administered following the last practice session. At an academic medical center, 14 otolaryngology residents were assigned using stratified randomization to interval or massed training. Blinded evaluators graded performance using a validated microvascular Objective Structured Assessment of Technical Skill tool. The tool is comprised of two major components: task-specific score (TSS) and global rating scale (GRS). Participants also received pre- and poststudy surveys to compare subjective confidence in multiple aspects of microvascular skill acquisition. Overall, all residents showed increased TSS and GRS on post- versus pretest. After completion of training, the interval group had a statistically significant increase in both TSS and GRS, whereas the massed group's increase was not significant. Residents in both groups reported significantly increased levels of confidence after completion of the study. Self-directed learning using a chicken thigh artery model may benefit microsurgical skills, competence, and confidence for resident surgeons. Interval training results in significant improvement in early development of microvascular anastomosis skills, whereas massed training does not. NA. Laryngoscope, 127:2490-2494, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

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

    Science.gov (United States)

    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. 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...

  3. Effect of Antimicrobial Compounds on Balamuthia mandrillaris Encystment and Human Brain Microvascular Endothelial Cell Cytopathogenicity▿

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Matin, Abdul; Warhurst, David; Stins, Monique; Khan, Naveed Ahmed

    2007-01-01

    Cycloheximide, ketoconazole, or preexposure of organisms to cytochalasin D prevented Balamuthia mandrillaris-associated cytopathogenicity in human brain microvascular endothelial cells, which constitute the blood-brain barrier. In an assay for inhibition of cyst production, these three agents prevented the production of cysts, suggesting that the biosynthesis of proteins and ergosterol and the polymerization of actin are important in cytopathogenicity and encystment. PMID:17875991

  4. Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase.

    Science.gov (United States)

    Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

    2016-04-15

    Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. Copyright © 2016 the American Physiological Society.

  5. Induction of complement proteins in a mouse model for cerebral microvascular Aβ deposition

    Directory of Open Access Journals (Sweden)

    DeFilippis Kelly

    2007-09-01

    Full Text Available Abstract The deposition of amyloid β-protein (Aβ in cerebral vasculature, known as cerebral amyloid angiopathy (CAA, is a common pathological feature of Alzheimer's disease and related disorders. In familial forms of CAA single mutations in the Aβ peptide have been linked to the increase of vascular Aβ deposits accompanied by a strong localized activation of glial cells and elevated expression of neuroinflammatory mediators including complement proteins. We have developed human amyloid-β precursor protein transgenic mice harboring two CAA Aβ mutations (Dutch E693Q and Iowa D694N that mimic the prevalent cerebral microvascular Aβ deposition observed in those patients, and the Swedish mutations (K670N/M671L to increase Aβ production. In these Tg-SwDI mice, we have reported predominant fibrillar Aβ along microvessels in the thalamic region and diffuse plaques in cortical region. Concurrently, activated microglia and reactive astrocytes have been detected primarily in association with fibrillar cerebral microvascular Aβ in this model. Here we show that three native complement components in classical and alternative complement pathways, C1q, C3, and C4, are elevated in Tg-SwDI mice in regions rich in fibrillar microvascular Aβ. Immunohistochemical staining of all three proteins was increased in thalamus, hippocampus, and subiculum, but not frontal cortex. Western blot analysis showed significant increases of all three proteins in the thalamic region (with hippocampus as well as the cortical region, except C3 that was below detection level in cortex. Also, in the thalamic region (with hippocampus, C1q and C3 mRNAs were significantly up-regulated. These complement proteins appeared to be expressed largely by activated microglial cells associated with the fibrillar microvascular Aβ deposits. Our findings demonstrate that Tg-SwDI mice exhibit elevated complement protein expression in response to fibrillar vascular Aβ deposition that is

  6. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

    2017-01-01

    and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand....

  7. Photocoagulation of microvascular and hemorrhagic lesions of the vocal fold with the KTP laser.

    Science.gov (United States)

    Hirano, Shigeru; Yamashita, Masaru; Kitamura, Morimasa; Takagita, Shin-ichi

    2006-04-01

    Ectasias and varices of the vocal fold are microvascular lesions that are often due to chronic abuse of the voice, and are occasionally encountered in association with other disorders such as polyps, Reinke's edema, and hematoma. The KTP laser can be used for photocoagulation of small vascular lesions, because the laser beam is well absorbed by hemoglobin, and damage to the epithelium is minimal. The present pilot study examined how the KTP laser could be used for microvascular lesions and their associated lesions. Twelve patients who had undergone phonomicrosurgery were enrolled in the present study. The microvascular lesions were treated by photocoagulation with the laser set at a low power of 1.5 W in the continuous mode, while preserving the epithelium, and associated lesions were then treated by microdissection with cold instruments. The postoperative phonatory function was assessed by maximum phonation time, a perceptual test rating (GRBAS scale), and stroboscopy. The procedures were completed successfully in all cases. An exceptional case of a small hemorrhagic polyp allowed treatment with the laser only. The postoperative stroboscopic findings, maximum phonation time, and perceptual test rating all showed significant improvement compared with the preoperative state. No adverse effects, such as scarring or reduction of the mucosal wave, were observed in the current series. KTP laser photocoagulation is a relatively simple and safe procedure for treating microvascular lesions of the vocal fold. It is not recommended for photocoagulation of hemorrhagic polyps or hematomas, because such lesions have little blood flow inside and thus photocoagulation is usually impossible or requires too much laser energy. However, photocoagulation of perimeter or feeding vessels of such disorders may facilitate the following procedure by avoiding unnecessary bleeding, as well as preventing recurrence of hemorrhagic lesions.

  8. Barotrauma and microvascular injury in lungs of nonadult rabbits: effect of ventilation pattern.

    Science.gov (United States)

    Peevy, K J; Hernandez, L A; Moise, A A; Parker, J C

    1990-06-01

    To study the pulmonary microvascular injury produced by ventilation barotrauma, the isolated perfused lungs of 4 to 6-wk-old New Zealand white rabbits were ventilated by one of the following methods: peak inspiratory pressure (PIP) 23 cm H2O, gas flow rate 1.1 L/min (group 1); PIP 27 cm H2O, gas flow rate 6.9 L/min (group 2); PIP 50 cm H2O, gas flow rate 1.9 L/min (group 3); or PIP 53 cm H2O, gas flow rate 8.3 L/min (group 4). Microvascular permeability was assessed using the capillary filtration coefficient (Kfc) before and 5, 30, and 60 min after a 15-min period of ventilation. Baseline Kfc was not significantly different between groups. A significant increase over the baseline Kfc was noted at 60 min in group 2 and in all postventilation Kfc values in groups 3 and 4 (p less than .05). Group 1 Kfc values did not change significantly after ventilation. At all post-ventilation times, values for Kfc were significantly greater in groups 3 and 4 than in group 1 (p less than .05). Group 4 Kfc values were significantly greater than those in group 2 at 5 and 30 min postventilation. These data indicate that high PIP, and to a lesser extent, high gas flow rates cause microvascular injury in the compliant nonadult lung and suggest that the combination of high PIP and high gas flow rates are the most threatening to microvascular integrity.

  9. Acute effects of coffee on skin blood flow and microvascular function.

    Science.gov (United States)

    Tesselaar, Erik; Nezirevic Dernroth, Dzeneta; Farnebo, Simon

    2017-11-01

    Studies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin. We measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee. Vasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, Pcoffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (-1.36PU/mmHg vs. -0.52PU/mmHg, P=0.002). Caffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Modeling of pulsatile flow-dependent nitric oxide regulation in a realistic microvascular network.

    Science.gov (United States)

    Wang, Ruofan; Pan, Qing; Kuebler, Wolfgang M; Li, John K-J; Pries, Axel R; Ning, Gangmin

    2017-09-01

    Hemodynamic pulsatility has been reported to regulate microcirculatory function. To quantitatively assess the impact of flow pulsatility on the microvasculature, a mathematical model was first developed to simulate the regulation of NO production by pulsatile flow in the microcirculation. Shear stress and pressure pulsatility were selected as regulators of endothelial NO production and NO-dependent vessel dilation as feedback to control microvascular hemodynamics. The model was then applied to a real microvascular network of the rat mesentery consisting of 546 microvessels. As compared to steady flow conditions, pulsatile flow increased the average NO concentration in arterioles from 256.8±93.1nM to 274.8±101.1nM (Pflow as compared to steady flow conditions. Network perfusion and flow heterogeneity were improved under pulsatile flow conditions, and vasodilation within the network was more sensitive to heart rate changes than pulse pressure amplitude. The proposed model simulates the role of flow pulsatility in the regulation of a complex microvascular network in terms of NO concentration and hemodynamics under varied physiological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Phase coherence of 0.1 Hz microvascular tone oscillations during the local heating

    Science.gov (United States)

    Mizeva, I. A.

    2017-06-01

    The origin of the mechanisms of blood flow oscillations at low frequencies is discussed. It is known that even isolated arteriole demonstrates oscillations with the frequency close to 0.1 Hz, which is caused by the synchronous activity of myocyte cells. On the other hand, oscillations with close frequency are found in the heart rate, which are associated with quite different mechanism. The main purpose of this work is to study phase coherence of the blood flow oscillations in the peripheral vessels under basal and perturbed conditions. Local heating which locally influences the microvascular tone, as one of currently elucidated in sufficient detail physiological test, was chosen. During such provocation blood flow though the small vessels significantly increases because of vasodilation induced by the local synthesis of nitric oxide. In the first part of the paper microvascular response to the local test is quantified in healthy and pathological conditions of diabetes mellitus type 1. It is obtained that regardless of the pathology, subjects with high basal perfusion had lower reserve for vasodilation, which can be caused by the low elasticity of microvascular structure. Further synchronization of pulsations of the heated and undisturbed skin was evaluated on the base of wavelet phase coherency analysis. Being highly synchronised in basal conditions 0.1 Hz pulsations became more independent during heating, especially during NO-mediated vasodilation.

  12. Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

    Science.gov (United States)

    Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut

    2014-01-01

    The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

  13. COAGULATION PROFILE IN DIABETES MELLITUS AND ITS ASSOCIATION WITH MICROVASCULAR COMPLICATIONS

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    Uma Shankar Mishra

    2017-12-01

    Full Text Available BACKGROUND This study intends to assess the changes in the simple routine coagulation parameters in diabetes mellitus and to investigate whether any relationship exists among changes in these coagulation parameters and development of microvascular complication in diabetes mellitus. MATERIALS AND METHODS Period of study was from 2010-2012. It was done in M.K.C.G. Medical College with the approval from Berhampur University. It is a case control study. 50 diabetic patients and 50 age and sex matched non-diabetic patients were randomly selected. Simple coagulation parameters like Activated Partial Thromboplastin Time (aPTT, Prothrombin Time (PT, serum fibrinogen, platelet count and Plasminogen Activator Inhibitor-1 (PAI-1 were measured. Statistical study was done using unpaired t-test and analysis and calculations were done using GraphPad software. RESULTS Serum fibrinogen was found to be increased in diabetic patients when compared to non-diabetic patients (mean 278 ± 26.9 v/s 232.52 ± 16.5, P value - 0.009, significant. PAI-1 levels was found to be higher among the diabetics when compared to nondiabetics (47.64 ± 8.82 v/s 31.06 ± 7.12, the two-tailed P value is <0.0001, considered extremely significant. Platelet count through within normal limits. It was found to be decreased in diabetic patient when compared to non-diabetic (2.25 ± 0.18 v/s 2.33 ± 0.03, P value - 0.022. Prothrombin Time (PT (13.15 ± 0.52 v/s 13.04 ± 0.49, P value - 0.28 and PTT (33.04 ± 1.31 v/s 32.99 ± 1.29, P value 0.85, found to be statistically insignificant. Among 50 diabetic patients, 24 had neuropathy, 20 had nephropathy, 10 had retinopathy and 21 had none of these complications. On comparing diabetic patients with microvascular complications and without microvascular complications, significant age difference was observed (59.55 ± 5.06 v/s 51.00 ± 3.31, P=0.003. This probably was a reflection of increase in microvascular complications with increasing duration

  14. Transmural Variation and Anisotropy of Microvascular Flow Conductivity in the Rat Myocardium

    KAUST Repository

    Smith, Amy F.

    2014-05-28

    Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the "longitudinal" direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

  15. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    Science.gov (United States)

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (pnecrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Clinical reference value of retinal microvascular changes in patients with cerebral microbleeds

    Directory of Open Access Journals (Sweden)

    Ji-Yuan Guo

    2014-12-01

    Full Text Available AIM: To study clinical reference value of retinal microvascular changes in patients with cerebral microbleeds(CMBsand discuss its clinical significance. METHODS:From January 2012 to December 2013, 125 hospitalized patients were collected, including 81 cases were male, 44 cases were female, mean age 76.3±11.2 years old. For all patients, functions of liver and kidney, blood-lipoids, blood sugar and blood biochemical examination were tested, and fundus photography and cerebral MR was done. According to the fundus camera eyes, retinal arteriolar equivalent(RAE, retinal venular equivalent(RVE, retinal vein diameter ratio(AVRand arteriovenous crossing sign(AVNwere identified, CMBs were classified with cerebral MRI. All the data were processed by SPSS statistical software. RESULTS: The central retinal arteriolar equivalent(CRAE, central retinal venular equivalent(CRVEand AVR values in the eyes were found no statistical difference(PPCOCLUSION: The results show that retinal microvascular changes, especially small retinal vein arteriovenous cross width, and arteriovenous crossing phenomenon, in which CMBs will happen more likely. After sex, age, hypertension and hyperglycemia in patients with traditional cardiovascular risk factors being ruled out, the retinal microvascular changes are still relatively factors of CMB's occurrence.

  17. The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction.

    Science.gov (United States)

    Buise, Marc P; Ince, Can; Tilanus, Hugo W; Klein, Jan; Gommers, Diederik; van Bommel, Jasper

    2005-04-01

    Esophagectomy followed by gastric tube reconstruction is the surgical treatment of choice for patients with esophageal cancer. Complications of the cervical anastomosis are associated with impaired microvascular blood flow (MBF) and ischemia in the gastric fundus. The aim of the present study was to differentiate whether the decrease in MBF is a result of arterial insufficiency or of venous congestion. To do this we assessed MBF, microvascular hemoglobin oxygen saturation (muHbSo(2)), and microvascular hemoglobin concentration (muHbcon) simultaneously during different stages of gastric tube reconstruction. In 14 patients, MBF was determined with laser Doppler flowmetry, and muHbSo(2) and muHbcon were determined with reflectance spectro- photometry. After completion of the anastomosis, nitroglycerin was applied at the fundus. Although MBF did not change significantly in the pylorus, MBF decreased progressively during surgery in the fundus from 210 +/- 18 Arbitrary Units at baseline (normal stomach) to 52 +/- 9 Arbitrary Units after completion of reconstruction (mean +/- sem; P tube reconstruction but that muHbSo(2) and muHbcon do not. This decrease might be the result of venous congestion, which can partly be counteracted by application of nitroglycerin.

  18. Microvascular obstruction on delayed enhancement cardiac magnetic resonance imaging after acute myocardial infarction, compared with myocardial {sup 201}Tl and {sup 123}I-BMIPP dual SPECT findings

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Hiroaki [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Department of Cardiology, Kainan Hospital, Yatomi (Japan); Isobe, Satoshi, E-mail: sisobe@med.nagoya-u.ac.jp [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Sakai, Shinichi [Department of Cardiology, Kainan Hospital, Yatomi (Japan); Yamada, Takashi [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Watanabe, Naoki; Miura, Manabu [Department of Cardiology, Kainan Hospital, Yatomi (Japan); Uchida, Yasuhiro; Kanashiro, Masaaki; Ichimiya, Satoshi [Department of Cardiology, Yokkaichi Municipal Hospital, Yokkaichi (Japan); Okumura, Takahiro; Murohara, Toyoaki [Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya (Japan)

    2015-08-15

    Highlights: • The percentage infarct size (%IS) was significantly greater in the microvascular obstruction (MO) group than in the non-MO group. • The percentage mismatch score (%MMS) on dual scintigraphy significantly correlated with the %IS and the percentage MO. • The %MMS was significantly greater in the non-MO group than in the MO group, and was an independent predictor for MO. - Abstract: Background: The hypo-enhanced regions within the hyper-enhanced infarct areas detected by cardiac magnetic resonance (CMR) imaging reflect microvascular obstruction (MO) after acute myocardial infarction (AMI). The combined myocardial thallium-201 ({sup 201}Tl)/iodine-123-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ({sup 123}I-BMIPP) dual single-photon emission computed tomography (SPECT) is a useful tool for detecting myocardial reversibility after AMI. We evaluated whether MO could be an early predictor of irreversible myocardial damage in comparison with {sup 201}Tl and {sup 123}I-BMIPP dual SPECT findings in AMI patients. Methods: Sixty-two patients with initial AMI who successfully underwent coronary revascularization were enrolled. MO was defined by CMR imaging. Patients were divided into 2 groups as follows: MO group (n = 32) and non-MO group (n = 30). Scintigraphic defect scores were calculated using a 17-segment model with a 5-point scoring system. The mismatch score (MMS) was calculated as follows: the total sum of (Σ) {sup 123}I-BMIPP defect score minus Σ{sup 201}Tl defect score. The percentage mismatch score (%MMS) was calculated as follows: MMS/(Σ{sup 123}I-BMIPP score) × 100 (%). Results: The percentage infarct size (%IS) was significantly greater in the MO group than in the non-MO group (32.2 ± 13.8% vs. 18.3 ± 12.1%, p < 0.001). The %MMS significantly correlated with the %IS and the percentage MO (r = −0.26, p = 0.03; r = −0.45, p < 0.001, respectively). The %MMS was significantly greater in the non-MO group than in the MO group (45.4

  19. Detection of coronary calcification in ultrafast CT compared to coronary angiography

    International Nuclear Information System (INIS)

    Koesling, S.; Hoffmann, U.; Rother, T.; Lieberenz, S.; Heywang-Koebrunner, S.H.; Schulz, H.G.

    1994-01-01

    The angiographical findings of 24 patients with coronary artery disease were compared with qualitative and quantitative detection of coronary calcification by ultrafast CT. Doubts concerning the capabilities of the ultrafast CT for a screening of coronary artery disease arise when the results of one third false positive and fase negative findings are considered. Variations in the quantification of coronary calcification were too great to allow a realistic assessment of the degree of stenosis of the coronary arteries. (orig.) [de

  20. HUMAN CORONARY ARTERIES- A STUDY BASED ON GROSS ANATOMY AND CORONARY CAST

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    Vijayamma K. N

    2018-01-01

    Full Text Available BACKGROUND Present study is an attempt to throw light upon the coronary arterial pattern, variations in arterial distribution and extent of intercoronary anastomosis and arterial preponderance in different age groups. MATERIALS AND METHODS Total of 115 hearts were made use for this study. Ninety hearts were dissected for the gross anatomical study of coronary arteries and 25 hearts including three fetal hearts were used for the coronary cast study. The right and left coronary arteries were traced from aortic sinus along the atrioventricular groove to the area of its termination. The atrial ventricular and septal branches were traced and looked for anastomosis. Coronary casts were prepared by injecting coloured liquid latex through the coronary ostia and the branching pattern and anastomosis were studied. The coronary arterial pattern, extent of distribution of its branches, arterial preponderance and variations were observed. RESULTS It was found that 73 % cases of SA nodal branch arise from right coronary artery and 27 % from circumflex branch of left coronary artery. SA node has dual blood supply from both coronary arteries in 4% cases. Right coronary preponderance was observed in 83% of cases and left coronary preponderance in 11 % cases, and balanced supply in 6% cases. Coronary cast was helpful to understand the branching pattern of vessels, and the anastomosis of small capillaries. It was also seen that all 11 % of left preponderance were seen in male hearts and all of the 31 female hearts dissected were right preponderant. CONCLUSION Coronary arteries are called end arteries functionally. Right coronary artery originates from anterior aortic sinus in all cases except one which takes origin from posterior left aortic sinus along with left coronary artery. Right coronary preponderance is observed in 83% cases. Left coronary artery branching pattern shows variability. Left coronary preponderance was observed in 11% and all cases are male