Sample records for systemic microvascular nitric

  1. Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak. (United States)

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


    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.

  2. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

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    Erickson Michelle A


    LRP-1 were upregulated by LPS. Conclusions Our results show that cultured mouse brain microvascular pericytes secrete cytokines, chemokines, and nitric oxide and respond to the innate immune system stimulator LPS. These immune properties of pericytes are likely important in their communication within the neurovascular unit and provide a mechanism by which they participate in neuroinflammatory processes in brain infections and neurodegenerative diseases.

  3. Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling

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    John eHarrell


    Full Text Available Data indicate endothelium-dependent dilation (EDD may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS and cyclooxygenase (COX toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh in younger (27±1 yr obese (n=29 and lean (n=46 humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC. Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS. ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05. There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.

  4. Modeling of pulsatile flow-dependent nitric oxide regulation in a realistic microvascular network. (United States)

    Wang, Ruofan; Pan, Qing; Kuebler, Wolfgang M; Li, John K-J; Pries, Axel R; Ning, Gangmin


    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.

  5. 21 CFR 862.3080 - Breath nitric oxide test system. (United States)


    ... Systems § 862.3080 Breath nitric oxide test system. (a) Identification. A breath nitric oxide test system... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath nitric oxide test system. 862.3080 Section... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to...

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

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    Saeed Yadranji Aghdam


    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.

  7. Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity. (United States)

    Woodside, John D S; Gutowski, Mariusz; Fall, Lewis; James, Philip E; McEneny, Jane; Young, Ian S; Ogoh, Shigehiko; Bailey, Damian M


    Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  8. 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.

  9. Microvascular system forming in skeletal muscle near trichinella larvae

    International Nuclear Information System (INIS)

    Berzentsev, Y.A.; Oksov, I.V.


    The fine structure and dynamics of formation of the microcirculatory system about the larvae of the two Trichinella species, providing for the rapid entry of nutrient substances to the larvae, were investigated in the muscles of white mice. Hitological, hitochemical, autoradiographic, and electron-microscopic methods were used in the investigation. At a certain period of the experiment, the greatest quantity of RNA was found in the endotheliocyte cytoplasm, tritium-thymidine label was incorporated into the nuclei, and mitoses were visible. The transition to tissue parasitism was accompanied by a complication of the relationships with the host and the formation of a more complex independent microcirculatory system, which ensures a more intensive influx of blood

  10. Data set characterizing the systemic alterations of microvascular reactivity and capillary density, in patients presenting with infective endocarditis. (United States)

    Tibirica, Eduardo; Barcelos, Amanda; Lamas, Cristiane


    This article represents data associated with a prior publication from our research group, under the title: Evaluation of microvascular endothelial function and capillary density in patients with infective endocarditis using laser speckle contrast imaging and video-capillaroscopy [1]. Patients with definite infective endocarditis, under stable clinical conditions, were prospectively included. The clinical and laboratory features are presented for each of them in raw form. Microvascular reactivity was evaluated using a laser speckle contrast imaging (LSCI) system with a laser wavelength of 785 nm. LSCI was used in combination with the iontophoresis of acetylcholine (ACh) or sodium nitroprusside (SNP) for the noninvasive, continuous measurement of cutaneous microvascular perfusion changes in arbitrary perfusion units (APU). The images were analyzed using the manufacturer's software. One skin site on the ventral surface of the forearm was chosen for the experiment. Microvascular reactivity was also evaluated using post-occlusive reactive hyperemia, whereby arterial occlusion was achieved with supra-systolic pressure (50 mmHg above the systolic arterial pressure) using a sphygmomanometer for three minutes. Following the release of pressure, maximum flux was measured. Data on cutaneous microvascular density were obtained using intravital video-capillaroscopy. The data obtained may be helpful by showing the usefulness of laser-based noninvasive techniques in systemic infectious diseases other than sepsis, in different clinical settings and countries.

  11. Nailfold Capillaroscopy - Its Role in Diagnosis and Differential Diagnosis of Microvascular Damage in Systemic Sclerosis. (United States)

    Lambova, Sevdalina; Hermann, W; Muller-Ladner, Ulf


    In the nailfold area, specific diagnostic microvascular abnormalities are easily recognized via capillaroscopic examination in systemic sclerosis (SSc). They are termed "scleroderma" type capillaroscopic pattern, which includes presence of dilated, giant capillaries, haemorrhages, avascular areas, and neoangiogenic capillaries and are observed in the majority of SSc patients (in more than 90%). LeRoy and Medsger (2001) proposed criteria for early diagnosis of SSc with inclusion of the abnormal capillaroscopic changes and suggested to prediagnose SSc prior to the development of other manifestations of the disease. It is a new era in the diagnosis of SSc. At present, an international multicenter project is performed. It aims validation of criteria for very early diagnosis of SSc (project VEDOSS (Very Early Diagnosis of Systemic Sclerosis) and is organized by European League Against Rheumatism (EULAR) Scleroderma Trials and Reasearch. Very recently the first results of the VEDOSS project were processed and new EULAR/ACR (American College of Rheumatology) classification criteria have been validated and published (2013), in which the characteristic capillaroscopic changes have been included. Our observations confirm the high frequency of the specific capillaroscopic changes of the fingers in SSc, which have been found in 97.2% of the cases from the studied patient population. We have performed for the first time capillaroscopic examinations of the toes in SSc. Interestingly,"scleroderma type" capillaroscopic pattern was also found at the toes in a high proportion of patients - 66.7%, but it is significantly less frequent as compared with fingers (97.2%, p<0.05). In our opinion, the examination of the toes of SSc patients should be considered as it suggests an additional opportunity for evaluation of the microvascular changes in these patients although the observed changes are in a lower proportion of cases. Thus, capillaroscopic examination is a cornerstone for the very

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

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    C. Pizzorni


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

  13. [Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results]. (United States)

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


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

  14. Microvascular Cranial Nerve Palsy (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 ...

  15. Interfacial tension in systems involving TBP in dodecane, nitric acid, uranyl nitrate and water

    International Nuclear Information System (INIS)

    Kolarik, Z.; Pipkin, N.


    The interfacial tension was measured at 25 0 C in the systems TBP - n-dodecane/nitric acid - water and TBP - n-dodecane/nitric acid - uranyl nitrate - water. Empirical equations describing the interfacial tension as a function of the concentration of TBP in the starting organic phase and of uranium-(VI) and nitric acid in the equilibrium aqueous phase were suggested. In the absence of uranium (VI), the interfacial tension can also be correlated with the concentration of water in the equilibrium organic phase. Free TBP, hydrated or nonhydrated, and hydrated TBP solvates of nitric acid are interfacially active. Anhydrous TBP solvates of nitric acid and the TBP solvate of uranyl nitrate, which neither is hydrated, do not exhibit any visible interfacial activity. (orig.) [de

  16. Critical evaluation of pressurized microwave-assisted digestion efficiency using nitric acid oxidizing systems (M7)

    International Nuclear Information System (INIS)

    Matusiewicz, H.


    Full text: The possibilities of enhancement of a medium-pressure microwave-assisted digestion system for sample preparation in trace element analysis of biological material was investigated. Based on optimal digestion conditions for oxidizing systems with nitric acid, different digestion procedures were examined to minimize residual carbon. The substitution of nitric acid and the addition of hydrogen peroxide and ozone to nitric acid was evaluated. The residual carbon content of the digestate was determined coulometrically. Addition of hydrogen peroxide during organic oxidation reactions does not lower the resolved carbon in the solution. Ozone was tested as an additional, potentially non-contaminating, digestion/oxidation system to the nitric acid used in the sample preparation method. (author)

  17. A study on electrochemical redox behavior of nitric acid by using a glassy carbon fiber column electrode system

    International Nuclear Information System (INIS)

    Kim, K. W.; Song, K. C.; Lee, I. H.; Choi, I. K.; You, J. H.


    Electrochemical redox behaviors of nitric acid were studied by using a glassy carbon fiber column electrode system, and its reaction mechanism was analyzed in several ways. The electrochemical reaction in less than 2.0 M nitric acid was not observed, but in more than 2.0 M nitric acid, the reduction rate of nitric acid to produce nitrous acid was slow so that the nitric acid solution had to be contacted with electrode enough in order for a apparent reduction current of nitric acid to nitrous acid be to observed. The nitrous acid generated in more than 2.0 M nitric acid was rapidly and easily reduced to NOx through an autocatalytic reaction. Sulfamic acid was confirmed to be effective to destroy the nitrous acid. The sulfamic acid of at least 0.05M was necessary to remove the nitrous acid generated in 3.5 M nitric acid

  18. Nitric oxide in health and disease of the respiratory system

    NARCIS (Netherlands)

    Ricciardolo, Fabio L. M.; Sterk, Peter J.; Gaston, Benjamin; Folkerts, Gert


    During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO

  19. 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.


    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

  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. Requirement of argininosuccinate lyase for systemic nitric oxide production. (United States)

    Erez, Ayelet; Nagamani, Sandesh C S; Shchelochkov, Oleg A; Premkumar, Muralidhar H; Campeau, Philippe M; Chen, Yuqing; Garg, Harsha K; Li, Li; Mian, Asad; Bertin, Terry K; Black, Jennifer O; Zeng, Heng; Tang, Yaoping; Reddy, Anilkumar K; Summar, Marshall; O'Brien, William E; Harrison, David G; Mitch, William E; Marini, Juan C; Aschner, Judy L; Bryan, Nathan S; Lee, Brendan


    Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases.

  2. Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries. (United States)

    Fricchione, Gregory; Stefano, George B


    Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

  3. Nitric Acid Revamp and Upgrading of the Alarm & Protection Safety System at Petrokemija, Croatia

    Directory of Open Access Journals (Sweden)

    Hoško, I.


    Full Text Available Every industrial production, particularly chemical processing, demands special attention in conducting the technological process with regard to the security requirements. For this reason, production processes should be continuously monitored by means of control and alarm safety instrumented systems. In the production of nitric acid at Petrokemija d. d., the original alarm safety system was designed as a combination of an electrical relay safety system and transistorized alarm module system. In order to increase safety requirements and modernize the technological process of nitric acid production, revamping and upgrading of the existing alarm safety system was initiated with a new microprocessor system. The newly derived alarm safety system, Simatic PCS 7, links the function of "classically" distributed control (DCS and logical systems in a common hardware and software platform with integrated engineering tools and operator interface to meet the minimum safety standards with safety integrity level 2 (SIL2 up to level 3 (SIL3, according to IEC 61508 and IEC 61511. This professional paper demonstrates the methodology of upgrading the logic of the alarm safety system in the production of nitric acid in the form of a logical diagram, which was the basis for a further step in its design and construction. Based on the mentioned logical diagram and defined security requirements, the project was implemented in three phases: analysis and testing, installation of the safety equipment and system, and commissioning. Developed also was a verification system of all safety conditions, which could be applied to other facilities for production of nitric acid. With the revamped and upgraded interlock alarm safety system, a new and improved safety boundary in the production of nitric acid was set, which created the foundation for further improvement of the production process in terms of improved analysis.

  4. Component activities in the system thorium nitrate-nitric acid-water at 25oC

    International Nuclear Information System (INIS)

    Lemire, R.J.; Brown, C.P.


    The equilibrium composition of the vapor above thorium nitrate-nitric acid-water mixtures has been studied as a function of the concentrations of thorium nitrate and nitric acid using a transpiration technique. At 25 o C, the thorium nitrate concentrations m T ranged from 0.1 to 2.5 molal and the nitric acid concentrations m N from 0.3 to 25 molal. The vapor pressure of the nitric acid was found to increase with increasing thorium nitrate concentration for a constant molality of nitric acid in aqueous solution. At constant m T , the nitric acid vapor pressure was particularly enhanced at low nitric acid concentrations. The water vapor pressures decreased regularly with increasing concentrations of both nitric acid and thorium nitrate. The experimental data were fitted to Scatchard's ion-component model, and to empirical multiparameter functions. From the fitting parameters, and available literature data for the nitric acid-water and thorium nitrate-water systems at 25 o C, expressions were calculated for the variation of water and thorium nitrate activities, as functions of the nitric acid and thorium nitrate concentrations, using the Gibbs-Duhem equation. Calculated values for the thorium nitrate activities were strongly dependent on the form of the function originally used to fit the vapor pressure data. (author)

  5. Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients. (United States)

    Ciołkiewicz, Mariusz; Kuryliszyn-Moskal, Anna; Klimiuk, Piotr Adrian


    The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p nailfold capillaroscopy (r = 0.458, p nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.

  6. Novel Insights into the Electrochemical Detection of Nitric Oxide in Biological Systems

    Czech Academy of Sciences Publication Activity Database

    Pekarová, Michaela; Lojek, Antonín; Hrbáč, J.; Kuchta, R.; Kadlec, J.; Kubala, Lukáš


    Roč. 60, č. 1 (2014), s. 8-12 ISSN 0015-5500 R&D Projects: GA MŠk(CZ) EE2.3.30.0030; GA ČR(CZ) GP13-40882P Institutional support: RVO:68081707 Keywords : nitric oxide * electrochemical detector * biological systems Subject RIV: BO - Biophysics Impact factor: 1.000, year: 2014

  7. Influence of zirconium ion concentration in model extraction systems TBP - diluents - Zr+4 - nitric acid

    International Nuclear Information System (INIS)

    Rogoz, F.; Tlalka, M.


    In systems containing TBP, MBP, DBP and 1-butanol stable emulsions and precipitates are formed which separation is difficult in certain domain of concentration in zirconium ions. MPB and DBP increase stability of primary emulsion in kerosen and carbon tetrachloride but for different concentrations of nitric acid. Addition of 1-butanol decreases slightly the stability of primary emulsion [fr

  8. Suture-free technique for canine ureteral resection-anastomosis using a microvascular anastomotic system: a cadaveric study. (United States)

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


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

  9. A Simple, Visually Oriented Communication System to Improve Postoperative Care Following Microvascular Free Tissue Transfer: Development, Results, and Implications. (United States)

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


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

  10. Thermodynamics and kinetics of thermal decomposition of dibutylalkyl and dipentylalkyl phosphonate-nitric acid systems

    International Nuclear Information System (INIS)

    Chandran, K.; Brahmananda, C.V.S.; Anthonysamy, S.; Srinivasan, T.G.; Ganesan, V.


    Tributyl phosphate (TBP) is used in the reprocessing industry for the separation of uranium and plutonium from the spent nuclear fuels by PUREX process. A variety of dialkylalky/phosphonates were synthesised and their extraction behaviour on actinides was studied in this laboratory. The superior extraction characteristics of phosphonates make them useful for several metal recovery applications in the nuclear fuel cycle. However, higher solubility of phosphonates in aqueous phase as compared to TBP, introduces higher chances of the formation of thermally active 'red oil' like substances during the evaporation of aqueous streams. Thermal stability of neat and nitric acid solvated homologues of four dibutylalkyl phosphonates namely, dibutylpropyl phosphonate (DBPrP), dibutylbutyl phosphonate (DBBP), dibutylpentyl phosphonate (DBPP), dibutylhexyl phosphonate (DBHeP), and two dipentylalkyl phosphonates viz. dipentylbutyl phosphonate (DPBP), dipentylhexyl phosphonate (DPHeP) were studied. Experiments were conducted using an adiabatic calorimeter in heat-wait-search mode. Various stoichiometry of nitric acid-solvated DBalP and DPalP were prepared by equilibrating the respective organic with 4-15.6 M nitric acid followed by separation. Neat DBalP and DPalP are stable up to the temperature of ∼ 555 K while their acid-solvates decomposed in the temperature range 380-403 K. The results also indicated that the presence of nitric acid accelerated the decomposition of phosphonates. Decomposition of these acid solvated phosphonates is found to be exothermic and follows first order kinetics. The onset temperature, adiabatic temperature rise, pressure rise, decomposition enthalpy and activation energy were found to strongly depend on the nitric acid content of the acid-solvates. The studies also indicate that dibutylalkyl and dipentylalkyl phosphonates are also prone to form 'red oil' like substances under extreme conditions and can lead to run-away reactions

  11. Extraction of antimony from nitric acid solutions using tributyl phosphate. II. Tributyl phosphate-antimony(V)-nitric acid system

    International Nuclear Information System (INIS)

    Lakaev, V.S.; Smelov, V.S.


    The extraction of pentavalent antimony from nitric acid solutions using tributyl phosphate has been investigated. A possible mechanism for the extraction of antimony(V) has been determined and the (pre)concentration constant for the process has been calculated. The composition of the extracted antimony(V) complex has been deduced. A negative effect of temperature on the distribution coefficient for antimony(V) has also been demonstrated

  12. Systemic and Microvascular Effects of Resuscitation with Blood Products After Severe Hemorrhage in Rats (United States)


    ArmyMedical Research andMateriel Command. I.T.F. is employed by Universidade do Estado do Rio de Janeiro and Premier Consulting & Management Services, Inc...Accreditation of Laboratory Animal Care, International. Systemic Measurements Male Sprague-Dawley rats (Charles River Laboratories, Wilmington, MA; body...this article is prohibited. 23. Sondeen JL, Prince MD, Kheirabadi BS, Wade CE, Polykratis IA, de Guzman R, Dubick MA. Initial resuscitation with plasma

  13. Microvascular anastomoses in irradiated vessels: A comparison between the Unilink system and sutures

    International Nuclear Information System (INIS)

    Ragnarsson, R.; Berggren, A.; Klintenberg, C.; Ostrup, L.


    A new mechanical device (the Unilink system) was compared to conventional suture anastomoses in irradiated microvessels. Twenty rabbits received a single radiation dose of 20 Gy from a 7-MeV electron source through an anterior neck field. One and 6 months following irradiation, the carotid arteries and facial veins were divided and anastomosed on one side with the Unilink system and on the other side with suture technique. At sacrifice 4 weeks postoperatively, all vessels were evaluated for patency and histologic changes associated with radiation and anastomotic trauma. Histology disclosed severe radiation changes. Also, intimal hyperplasia was consistently found at the anastomotic sites in the arteries, while it was totally absent in the venous anastomoses. Occlusive thrombosis was found in two arteries, one anastomosed with the Unilink system and one sutured. Two other arteries, one from each group, had subtotal occlusions at the anastomotic site. No occlusions occurred in any of the venous anastomoses. The overall patency in this study was 97.5 percent, with no difference between the two techniques

  14. Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran. (United States)

    Abutarboush, Rania; Saha, Biswajit K; Mullah, Saad H; Arnaud, Francoise G; Haque, Ashraful; Aligbe, Chioma; Pappas, Georgina; Auker, Charles R; McCarron, Richard M; Moon-Massat, Paula F; Scultetus, Anke H


    Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50-100 μm) showed minor (~8-9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend.

  15. Liquid-Phase Heat-Release Rates of the Systems Hydrazine-Nitric Acid and Unsymmetrical Dimethylhydrazine-Nitric Acid (United States)

    Somogyi, Dezso; Feiler, Charles E.


    The initial rates of heat release produced by the reactions of hydrazine and unsymmetrical dimethylhydrazine with nitric acid were determined in a bomb calorimeter under conditions of forced mixing. Fuel-oxidant weight ratio and injection velocity were varied. The rate of heat release apparently depended on the interfacial area between the propellants. Above a narrow range of injection velocities representing a critical amount of interfacial area, the rates reached a maximum and were almost constant with injection velocity. The maximum rate for hydrazine was about 70 percent greater than that for unsymmetrical dimethylhydrazine. The total heat released did not vary with mixture ratio over the range studied.

  16. Periodontal disease, periodontal treatment and systemic nitric oxide in dogs. (United States)

    Nemec, A; Verstraete, F J M; Jerin, A; Šentjurc, M; Kass, P H; Petelin, M; Pavlica, Z


    Thirty-two client-owned dogs treated for periodontal disease were divided in group 1 if no periodontitis, group 2 if ≤25%, and group 3 if >25% of the teeth present were affected with periodontitis. Blood was tested before and 2 weeks after periodontal therapy for nitrosyl hemoglobin (HbNO), plasma nitrite/nitrate (NOx) and 3-nitrotyrosine (NT) levels. No HbNO was detected in any of the animals tested. There was no significant difference in the NOx plasma levels within each group or across the groups before and after the treatment, but a noticeable increase in NOx plasma levels was observed in group 3 after the treatment. Plasma NT was detected in only one third of the animals. NO levels varied greatly across individual dogs. The data are suggestive of an overall increase in systemic NO response 2 weeks after periodontal treatment in dogs with advanced periodontal disease, but the response is greatly individually-dependent. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Scioli

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

  18. Impaired systemic tetrahydrobiopterin bioavailability and increased dihydrobiopterin in adult falciparum malaria: association with disease severity, impaired microvascular function and increased endothelial activation.

    Directory of Open Access Journals (Sweden)

    Tsin W Yeo


    Full Text Available Tetrahydrobiopterin (BH₄ is a co-factor required for catalytic activity of nitric oxide synthase (NOS and amino acid-monooxygenases, including phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydrobiopterin (BH₂, which inhibits NOS. Depending on BH₄ availability, NOS oscillates between NO synthase and NADPH oxidase: as the BH₄/BH₂ ratio decreases, NO production falls and is replaced by superoxide. In African children and Asian adults with severe malaria, NO bioavailability decreases and plasma phenylalanine increases, together suggesting possible BH₄ deficiency. The primary three biopterin metabolites (BH₄, BH₂ and B₀ [biopterin] and their association with disease severity have not been assessed in falciparum malaria. We measured pterin metabolites in urine of adults with severe falciparum malaria (SM; n=12, moderately-severe malaria (MSM, n=17, severe sepsis (SS; n=5 and healthy subjects (HC; n=20 as controls. In SM, urinary BH₄ was decreased (median 0.16 ¼mol/mmol creatinine compared to MSM (median 0.27, SS (median 0.54, and HC (median 0.34]; p<0.001. Conversely, BH₂ was increased in SM (median 0.91 ¼mol/mmol creatinine, compared to MSM (median 0.67, SS (median 0.39, and HC (median 0.52; p<0.001, suggesting increased oxidative stress and insufficient recycling of BH2 back to BH4 in severe malaria. Overall, the median BH₄/BH₂ ratio was lowest in SM [0.18 (IQR: 0.04-0.32] compared to MSM (0.45, IQR 0.27-61, SS (1.03; IQR 0.54-2.38 and controls (0.66; IQR 0.43-1.07; p<0.001. In malaria, a lower BH₄/BH₂ ratio correlated with decreased microvascular reactivity (r=0.41; p=0.03 and increased ICAM-1 (r=-0.52; p=0.005. Decreased BH4 and increased BH₂ in severe malaria (but not in severe sepsis uncouples NOS, leading to impaired NO bioavailability and potentially increased oxidative stress. Adjunctive therapy to regenerate BH4 may have a role in improving NO

  19. Chromatography of 49 metal ions on stannic antimonate papers in dimethylsulfoxide: nitric acid systems and aqueous nitric acid systems

    International Nuclear Information System (INIS)

    Qureshi, M.; Varshney, K.G.; Rajput, R.P.S.


    Chromatographic separations of 49 metal ions on stannic antimonate papers have been performed using mixed solvent systems containing DMSO. Aqueous HNO 3 systems have also been used. The utility of the papers has been demonstrated by achieving various difficult separations. Some of the important separations (R/sub f/ values given in parentheses) are: Cs + (0.20)-K + (0.30) and Sm 3+ (0.00)-Pr 3+ (0.72) in pure DMSO; Nb 5+ (0.14)-VO 2+ (0.95) in DMSO-6M HNO 3 (1:1); Ti 4+ (0.00)-VO 2 (0.97) in DMSO-0.5M HNO 3 (1:1); and Ba 2+ (0.06)-K + (0.52)-Sr 2+ (0.95), Ba 2+ (0.04)-Cs + (0.41)-Mg 2+ (0.93), and Ca 2+ (0.10)-Sr 2+ (0.94) in DMSO-0.1M HNO 3 (1:1). The time of development in each case is two hours. A discussion is presented on the dependence of Ri, log R/sub f/, and R/sub M/ on pH of the solvent to understand the mechanism of the movement of metal ions on papers impregnated with inorganic materials. (U.S.)

  20. The role of nitric oxide in regulation of the cardiovascular system in reptiles. (United States)

    Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias


    The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

  1. Thermal decomposition studies on tri-iso-amyl phosphate in n-dodecane-nitric acid system

    International Nuclear Information System (INIS)

    Chandran, K.; Sreenivasalu, B.; Suresh, A.; Sivaraman, N.; Anthonysamy, S.


    Tri-iso-amyl Phosphate (TiAP) is a promising alternative solvent to TBP, with near similar extraction behaviour and physical properties but lower aqueous phase solubility and does not form third phase during the extraction of Pu(IV). In addition to the solubilised extractant, inadvertent entrainment of the extractant into the aqueous stream is a concern during the evaporation operation as the extractant comes into contact with higher nitric acid concentrations and metal nitrates. Hence the thermal decomposition behaviour of TiAP-HNO 3 systems has been studied using an adiabatic calorimeter in closed air ambience, under heat-wait-search mode (H-W-S)

  2. Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

    Directory of Open Access Journals (Sweden)

    Anne Abot


    Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

  3. Neuronal nitric oxide synthase in the olfactory system of an adult teleost fish Oreochromis mossambicus. (United States)

    Singru, Praful S; Sakharkar, Amul J; Subhedar, Nishikant


    The aim of the present study is to explore the distribution of nitric oxide synthase in the olfactory system of an adult teleost, Oreochromis mossambicus using neuronal nitric oxide synthase (nNOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry methods. Intense nNOS immunoreactivity was noticed in several olfactory receptor neurons (ORNs), in their axonal extensions over the olfactory nerve and in some basal cells of the olfactory epithelium. nNOS containing fascicles of the ORNs enter the bulb from its rostral pole, spread in the olfactory nerve layer in the periphery of the bulb and display massive innervation of the olfactory glomeruli. Unilateral ablation of the olfactory organ resulted in dramatic loss of nNOS immunoreactivity in the olfactory nerve layer of the ipsilateral bulb. In the olfactory bulb of intact fish, some granule cells showed intense immunoreactivity; dendrites arising from the granule cells could be traced to the glomerular layer. Of particular interest is the occurrence of nNOS immunoreactivity in the ganglion cells of the nervus terminalis. nNOS containing fibers were also encountered in the medial olfactory tracts as they extend to the telencephalon. The NADPHd staining generally coincides with that of nNOS suggesting that it may serve as a marker for nNOS in the olfactory system of this fish. However, mismatch was encountered in the case of mitral cells, while all are nNOS-negative, few were NADPHd positive. The present study for the first time revealed the occurrence of nNOS immunoreactivity in the ORNs of an adult vertebrate and suggests a role for nitric oxide in the transduction of odor stimuli, regeneration of olfactory epithelium and processing of olfactory signals.

  4. Development of a chromatographic micro-system for radionuclides analysis in nitric acid media

    International Nuclear Information System (INIS)

    Losno, Marion


    Radionuclides analysis is a key point for nuclear waste management and nuclear material control. Several steps of sample modification have to be carried out before measurements in order to avoid any interferences and improve measurement precision. However those different steps are long, irradiating and difficult to achieve in gloveboxes. Moreover they produce liquid and solid waste. The goal of the study is to offer a new alternative to the use of solid phase extraction column for radionuclides separation in hard nitric acid medium. The system will decrease the amount of nuclear waste due to the analysis and automatize the different steps of the analysis. A plastic device made of COC containing a micro solid phase extraction column is first designed. Stationary phase is a poly(AMA-co-EDMA) monolith synthesized in situ. Its structure is adjustable and its functionalization versatile with a high resistance to nitric acid medium. Exchange capacity is 150 mg/g of monolith for TBP and TBP/CMPO column and up to 280 mg/g of monolith in case of DAAP. Exchange coefficients are determined for U(VI), Th(IV), Eu(III) and Nd(III) for 3 different extractants (and Pu(IV) in case of TBP column). Monolith synthesis is transferred in centrifugal device and hydrodynamic behavior studied. U,Th/Eu separation was finally carried out in both classic and centrifugal micro-system on TBP column. (author) [fr

  5. 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:


    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

  6. Nitric Oxide PLIF Measurements in the Hypersonic Materials Environmental Test System (HYMETS) (United States)

    Inman, Jennifer A.; Bathel, Brett F.; Johansen, Craig T.; Danehy, Paul M.; Jones, Stephen B.; Gragg, Jeffrey G.; Splinter, Scott C.; McRae, Colin D.


    Planar laser-induced fluorescence (PLIF) of naturally occurring nitric oxide (NO) has been used to obtain instantaneous flow visualization images, and to make both radial and axial velocity measurements in the HYMETS (Hypersonic Materials Environmental Test System) 400 kW arc-heated wind tunnel at NASA Langley Research Center. This represents the first application of NO PLIF flow visualization in HYMETS. Results are presented at selected facility run conditions, including some in a simulated Earth atmosphere (75% nitrogen, 20% oxygen, 5% argon) and others in a simulated Martian atmosphere (71% carbon dioxide, 24% nitrogen, 5% argon), for specific bulk enthalpies ranging from 6.5 MJ/kg to 18.4 MJ/kg. Flow visualization images reveal the presence of large scale unsteady flow structures, and indicate nitric oxide fluorescence signal over more than 70% of the core flow for specific bulk enthalpies below about 11 MJ/kg, but over less than 10% of the core flow for specific bulk enthalpies above about 16 MJ/kg. Axial velocimetry was performed using molecular tagging velocimetry (MTV). Axial velocities of about 3 km/s were measured along the centerline. Radial velocimetry was performed by scanning the wavelength of the narrowband laser and analyzing the resulting Doppler shift. Radial velocities of +/- 0.5 km/s were measured.

  7. Nitric oxide: a physiologic messenger. (United States)

    Lowenstein, C J; Dinerman, J L; Snyder, S H


    To review the physiologic role of nitric oxide, an unusual messenger molecule that mediates blood vessel relaxation, neurotransmission, and pathogen suppression. A MEDLINE search of articles published from 1987 to 1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide synthase. Animal and human studies were selected from 3044 articles to analyze the clinical importance of nitric oxide. Descriptions of the structure and function of nitric oxide synthase were selected to show how nitric oxide acts as a biological messenger molecule. Biochemical and physiologic studies were analyzed if the same results were found by three or more independent observers. Two major classes of nitric oxide synthase enzymes produce nitric oxide. The constitutive isoforms found in endothelial cells and neurons release small amounts of nitric oxide for brief periods to signal adjacent cells, whereas the inducible isoform found in macrophages releases large amounts of nitric oxide continuously to eliminate bacteria and parasites. By diffusing into adjacent cells and binding to enzymes that contain iron, nitric oxide plays many important physiologic roles. It regulates blood pressure, transmits signals between neurons, and suppresses pathogens. Excess amounts, however, can damage host cells, causing neurotoxicity during strokes and causing the hypotension associated with sepsis. Nitric oxide is a simple molecule with many physiologic roles in the cardiovascular, neurologic, and immune systems. Although the general principles of nitric oxide synthesis are known, further research is necessary to determine what role it plays in causing disease.

  8. Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

    Directory of Open Access Journals (Sweden)

    Audrey Dooley


    Full Text Available Systemic sclerosis (scleroderma: SSc is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO, a key mediator of oxidative stress, can profoundly influence the early microvasculopathy, and possibly the ensuing fibrogenic response. Animal models and human studies have also identified dietary antioxidants, such as epigallocatechin-3-gallate (EGCG, to function as a protective system against oxidative stress and fibrosis. Hence, targeting EGCG may prove a possible candidate for therapeutic treatment aimed at reducing both oxidant stress and the fibrotic effects associated with SSc.

  9. Study on Purification Diatomite with nitric acid by Thermal Closed System

    Directory of Open Access Journals (Sweden)

    Kuang Meng


    Full Text Available In this research, a purification approach using nitric acid leaching at thermal closed system was developed to improve the porous structure of raw diatomite by removal of impurities from its surface and clogged pores. The feasibility and efficiency of this approach were determined by XRF for chemical constitution of diatomite, SEM for morphology and BET for specific surface area of purified diatomite. The investigations indicated that the content of SiO2 was in order of 85.14% for raw diatomite and 98% for purified diatomite, the content of Fe2O3 decreases after purified; the integrity of the porous structure was confirmed by SEM, and increase in specific surface area from 18m2·g-1 to 36m2·g-1.

  10. Microvascular Anastomosis Training in Neurosurgery: A Review

    Directory of Open Access Journals (Sweden)

    Vadim A. Byvaltsev


    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.

  11. Nitric oxide in the nervous system: biochemical, developmental, and neurobiological aspects. (United States)

    Cossenza, Marcelo; Socodato, Renato; Portugal, Camila C; Domith, Ivan C L; Gladulich, Luis F H; Encarnação, Thaísa G; Calaza, Karin C; Mendonça, Henrique R; Campello-Costa, Paula; Paes-de-Carvalho, Roberto


    Nitric oxide (NO) is a very reactive molecule, and its short half-life would make it virtually invisible until its discovery. NO activates soluble guanylyl cyclase (sGC), increasing 3',5'-cyclic guanosine monophosphate levels to activate PKGs. Although NO triggers several phosphorylation cascades due to its ability to react with Fe II in heme-containing proteins such as sGC, it also promotes a selective posttranslational modification in cysteine residues by S-nitrosylation, impacting on protein function, stability, and allocation. In the central nervous system (CNS), NO synthesis usually requires a functional coupling of nitric oxide synthase I (NOS I) and proteins such as NMDA receptors or carboxyl-terminal PDZ ligand of NOS (CAPON), which is critical for specificity and triggering of selected pathways. NO also modulates CREB (cAMP-responsive element-binding protein), ERK, AKT, and Src, with important implications for nerve cell survival and differentiation. Differences in the regulation of neuronal death or survival by NO may be explained by several mechanisms involving localization of NOS isoforms, amount of NO being produced or protein sets being modulated. A number of studies show that NO regulates neurotransmitter release and different aspects of synaptic dynamics, such as differentiation of synaptic specializations, microtubule dynamics, architecture of synaptic protein organization, and modulation of synaptic efficacy. NO has also been associated with synaptogenesis or synapse elimination, and it is required for long-term synaptic modifications taking place in axons or dendrites. In spite of tremendous advances in the knowledge of NO biological effects, a full description of its role in the CNS is far from being completely elucidated. © 2014 Elsevier Inc. All rights reserved.

  12. Nitric oxide synthase gene G298 allele

    International Nuclear Information System (INIS)

    Nagib El-Kilany, Galal E.; Nayel, Ehab; Hazzaa, Sahar


    Background: Nitric oxide (NO) has an important effect on blood pressure, arterial wall, and the basal release of endothelial NO in hypertension (HPN) may be reduced. Until now, there is no solid data revealing the potential role of the polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and microvascular angina. Aim: The aim of the present study is to investigate the gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this gene may be a putative candidate for HPN and initiate the process of atherosclerosis. Methods: Sixty participants were recruited for this study; 50 were hypertensive patients complaining of chest pain [30 of them have electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy volunteers served as control. All patients underwent stress myocardial perfusion imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and controls was performed. The linkages between HPN, microvascular angina and eNOS gene polymorphism were investigated. Results: MPI and coronary angiography revealed that 15 patients had chest pain with true ischemia and reversible myocardial perfusion defects (multiple and mild) but normal epicardial coronary arteries (microvascular angina), while 15 patients had significant coronary artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan and coronary angiography. The prevalence of the NOS G 298 allele was higher in the hypertensive group with microvascular angina (documented by MPI) than it was among the control participants (P<.005). The eNOS allele was significantly higher in the hypertensive group than in the control participants, but there was no significant difference in homozygote mutants among hypertensive participants, x-syndrome and patients with CAD. Conclusion: eNOS gene polymorphism is proved to be an important etiology in microvascular angina (x-syndrome) among hypertensive patients. In addition, the eNOS mutant

  13. High pressure Raman spectroscopic study of the effects of n-ethylamines and water on the 2-nitropropane/Nitric acid system

    Energy Technology Data Exchange (ETDEWEB)

    Gobin, Cedric; Petitet, Jean Pierre [Laboratoire d' Ingenierie des Materiaux et des Hautes Pressions, CNRS, Institut Galilee, Universite Paris XIII, 99 av. J-B Clement, 93430 Villetaneuse (France)


    High pressure Raman spectroscopy measurements in a diamond anvil cell (0-10 GPa) on 2-nitropropane/nitric acid/X (X=triethylamine, diethylamine, and water) ternary systems and 2-nitropropane/nitric acid/water/Y (Y=triethylamine and diethylamine) quaternary systems are reported. The modifications of the chemical behavior of the 2-nitropropane/nitric acid model system, induced by the presence of triethylamine, diethylamine, and/or water, were studied at ambient and high pressure. At ambient pressure, the ionization of the nitric acid has been observed with each of the additives. Moreover, in the case of ethylamines, new peaks have been observed and the hypothesis of a 2-nitropropane/ethylamine complex is advanced. At high pressure, the decomposition of the 2-nitropropane/nitric acid system, with an oxygen balance near zero, has been observed only in presence of triethylamine. The role of each additive to the 2-nitropropane/nitric acid system in the modification of the respective reducing and oxidizing character of the components, and in the reactivity of the system, is discussed. Several hypotheses are advanced concerning the sensitizing effect of the additives on the 2-nitropropane/nitric acid system. (Abstract Copyright [2005], Wiley Periodicals, Inc.)

  14. Microvascular inflammation in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Laura Vitiello


    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.

  15. The radiolytic formation of nitric acid in argon/air/water systems

    International Nuclear Information System (INIS)

    May, R.; Stinchcombe, D.; White, H.P.


    The extent of nitric acid formation in the γ-radiolysis of argon/air/water mixtures has been assessed. The yields of nitric acid are found to increase as water vapour pressure is increased but are lower in the presence of a discrete water phase. G values for the formation of nitric acid from argon/air mixtures based on energy absorbed in the air are increased in the presence of argon but the yields in an atmosphere of argon containing small amounts of moist air are smaller than from an atmosphere of moist air alone. The G value for nitric acid formation from pure air in the presence of a distinct water phase is 2, based on energy absorbed in the air. (author)

  16. Studies on the hydrodynamic properties of the sieve plate pulsed column for 30% TRPO-kerosene/nitric acid system

    International Nuclear Information System (INIS)

    Ma Ronglin; Chen Jing; Xu Shiping; Wu Qiulin; Tai Derong; Song Chongli


    The hydrodynamic properties of the sieve plate pulsed column for 30% TRPO-kerosene/nitric acid system is studied. With the organic phase or aqueous phase as the continuous one, the dispersed phase behaves mainly as coalescing or dispersing, respectively. The sieve plate pulsed column has a fairish flooding throughput for this system. Under the same pulsation intensity, the flooding throughput for the organic phase as the continuous one is more than that for the aqueous phase as the continuous one

  17. A stress surveillance system based on calcium and nitric oxide in marine diatoms.

    Directory of Open Access Journals (Sweden)

    Assaf Vardi


    Full Text Available Diatoms are an important group of eukaryotic phytoplankton, responsible for about 20% of global primary productivity. Study of the functional role of chemical signaling within phytoplankton assemblages is still in its infancy although recent reports in diatoms suggest the existence of chemical-based defense strategies. Here, we demonstrate how the accurate perception of diatom-derived reactive aldehydes can determine cell fate in diatoms. In particular, the aldehyde (2E,4E/Z-decadienal (DD can trigger intracellular calcium transients and the generation of nitric oxide (NO by a calcium-dependent NO synthase-like activity, which results in cell death. However, pretreatment of cells with sublethal doses of aldehyde can induce resistance to subsequent lethal doses, which is reflected in an altered calcium signature and kinetics of NO production. We also present evidence for a DD-derived NO-based intercellular signaling system for the perception of stressed bystander cells. Based on these findings, we propose the existence of a sophisticated stress surveillance system in diatoms, which has important implications for understanding the cellular mechanisms responsible for acclimation versus death during phytoplankton bloom successions.

  18. Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis. (United States)

    Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing


    There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

  19. Investigations of foam formation and its stabilization in the extraction systems: TBP in kerosene-nitric acid solutions

    International Nuclear Information System (INIS)

    Zielinski, A.


    The paper is devoted to studies of foam formation and its stabilization in TBP - kerosene - nitric acid solutions extracting systems. It was experimentally found, that TBP acts as a stabilizator of thin, liquid foam films as well as an emulgator in forming dispersions. The stabilizing effect of fine emulsions w/o on formed foams column was observed. Relevant references on the subject are also reviewed. (author)

  20. Reactive oxygen species and nitric oxide in plant mitochondria: origin and redundant regulatory systems. (United States)

    Blokhina, Olga; Fagerstedt, Kurt V


    Plant mitochondria differ from their mammalian counterparts in many respects, which are due to the unique and variable surroundings of plant mitochondria. In green leaves, plant mitochondria are surrounded by ample respiratory substrates and abundant molecular oxygen, both resulting from active photosynthesis, while in roots and bulky rhizomes and fruit carbohydrates may be plenty, whereas oxygen levels are falling. Several enzymatic complexes in mitochondrial electron transport chain (ETC) are capable of reactive oxygen species (ROS) formation under physiological and pathological conditions. Inherently connected parameters such as the redox state of electron carriers in the ETC, ATP synthase activity and inner mitochondrial membrane potential, when affected by external stimuli, can give rise to ROS formation via complexes I and III, and by reverse electron transport (RET) from complex II. Superoxide radicals produced are quickly scavenged by superoxide dismutase (MnSOD), and the resulting H(2)O(2) is detoxified by peroxiredoxin-thioredoxin system or by the enzymes of ascorbate-glutathione cycle, found in the mitochondrial matrix. Arginine-dependent nitric oxide (NO)-releasing activity of enzymatic origin has been detected in plant mitochondria. The molecular identity of the enzyme is not clear but the involvement of mitochondria-localized enzymes responsible for arginine catabolism, arginase and ornithine aminotransferase has been shown in the regulation of NO efflux. Besides direct control by antioxidants, mitochondrial ROS production is tightly controlled by multiple redundant systems affecting inner membrane potential: NAD(P)H-dependent dehydrogenases, alternative oxidase (AOX), uncoupling proteins, ATP-sensitive K(+) channel and a number of matrix and intermembrane enzymes capable of direct electron donation to ETC. NO removal, on the other hand, takes place either by reactions with molecular oxygen or superoxide resulting in peroxynitrite, nitrite or nitrate

  1. TBP 20% diluent/H N O3/H2 O liquid-liquid extraction system: equilibrium data normalization of nitric acid, ruthenium and zirconium

    International Nuclear Information System (INIS)

    Oliveira, C.A.L.G. de; Araujo, B.F. de.


    The extraction behavior of nitric acid, nitrosyl ruthenium nitrate and zirconium hydroxide nitrate in the system tri-n-butyl phosphate (TBP) 20% -diluent was studied. The main purpose was to obtain enough data to elaborate process flowsheets for the treatment of irradiated uranium fuels. During the runs, the equilibrium diagrams of nitric acid, ruthenium and zirconium were settled. From the achieved data, the influence of nitric acid, ruthenium, zirconium and nitrate ions concentration in the aqueous phase was checked. Furthermore, the density and the surface tension of the aqueous and organic phases were determined, gathering the interfacial tension after the contact between the phases. (author)

  2. SU-E-J-197: A Novel Optical Interstitial Fiber Spectroscopic System for Real-Time Tissue Micro-Vascular Hemodynamics Monitoring. (United States)

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


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

  3. Postnatal changes in the nitric oxide system of the rat cerebral cortex after hypoxia during delivery. (United States)

    Fernández, Ana Patricia; Alonso, David; Lisazoaín, Ignacio; Serrano, Julia; Leza, Juan Carlos; Bentura, María Luisa; López, Juan Carlos; Manuel Encinas, Juan; Fernández-Vizarra, Paula; Castro-Blanco, Susana; Martínez, Alfredo; Martinez-Murillo, Ricardo; Lorenzo, Pedro; Pedrosa, Juan Angel; Peinado, María Angeles; Rodrigo, José


    The impact of hypoxia in utero during delivery was correlated with the immunocytochemistry, expression and activity of the neuronal (nNOS) and inducible (iNOS) isoforms of the nitric oxide synthase enzyme as well as with the reactivity and expression of nitrotyrosine as a marker of protein nitration during early postnatal development of the cortex. The expression of nNOS in both normal and hypoxic animals increased during the first few postnatal days, reaching a peak at day P5, but a higher expression was consistently found in hypoxic brain. This expression decreased progressively from P7 to P20, but was more prominent in the hypoxic group. Immunoreactivity for iNOS was also higher in the cortex of the hypoxic rats and was more evident between days P0 and P5, decreasing dramatically between P10 and P20 in both groups of rats. Two nitrated proteins of 52 and 38 kDa, were also identified. Nitration of the 52-kDa protein was more intense in the hypoxic animals than in the controls, increasing from P0 to P7 and then decreasing progressively to P20. The 38-kDa nitrated protein was seen only from P10 to P20, and its expression was more intense in control than in the hypoxic group. These results suggest that the NO system may be involved in neuronal maturation and cortical plasticity over postnatal development. Overproduction of NO in the brain of hypoxic animals may constitute an effort to re-establish normal blood flow and may also trigger a cascade of free-radical reactions, leading to modifications in the cortical plasticity.

  4. Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes? (United States)

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


    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.

  5. 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.

  6. Nitric oxide signaling and the cross talk with prostanoids pathways in vascular system. (United States)

    Silva, Bruno R; Paula, Tiago D; Paulo, Michele; Bendhack, Lusiane M


    This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP). The second messenger (cGMP) activates protein kinase G and the signaling cascade, including K+ channels. Activation of K+ channels leads to cell membrane hyperpolarization and Ca2+ channels blockade, which induce vascular relaxation. Moreover, the enzyme cyclooxygenase (COX) is also an important regulator of the vascular function by prostanoids production such as thromboxane A2 (TXA2) and prostacyclin (PGI2), which classically induce contraction and relaxation, respectively. Additionaly, studies indicate that the activity of both enzymes can be modulated by their products and reactive oxygen species (ROS) in cardiovascular diseases such as hypertension. The interaction of NO with cellular molecules, particularly the reaction of NO with ROS, determines the biological mechanisms of action and short half-life of NO. We have been working on the vascular effects of ruthenium-derived complexes that release NO. Our research group has published works on the vasodilating effects of ruthenium-derived NO donors and the mechanisms of vascular cells involved in the relaxation of the vascular smooth muscle in health and hypertensive rats. In our previous studies, we have compared the new NO donors synthesized by our group to SNP. It shows the cellular signaling of NO

  7. Upcyte® Microvascular Endothelial Cells Repopulate Decellularized Scaffold (United States)

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


    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

  8. Alzheimer's disease: a gas model. The NADPH oxidase-Nitric Oxide system as an antibubble biomachinery. (United States)

    Denis, Pierre A


    Alzheimer's disease (AD) is a neurodegenerative disease of unknown origin. The pathological lesions that define AD would be linked to the insidious accumulation of nitrogen, having invaded the brain interstitial fluid (ISF) from the blood via the physiological cycling pool of vascular glucose transporters (GLUT-1). According to this hypothesis, the nitrogen nanobubbles, being chemically inert and actually indestructible for human beings, can not escape from the ISF anymore. They would exert a huge and deleterious pressure against cellular components, especially in microglia and in astrocytes. They could enhance the existing cell oxygen anisotropy, which might enhance the natural bubble nucleation of O2-2O2 in cells or in mitochondria. Indeed, with the help of a new symbolic representation for gas nuclei in chemical reactions, the NADPH oxidase-NO system is identified for the first time, as an antibubble biomachinery, able to break O2-2O2 bubbles up as it releases superoxide O2-. Superoxide is considered as a quantum bubble, which collapses through the reactivity of the gaseous NO radical. Their combination in soluble peroxinitrite provides the change from one state of matter to another, avoiding any risk of a bubble enlargement, and finally avoiding the risk of enzyme crowding or of a bulk pressure variation. However, a bubble is expected to entrap Nitric Oxide (NO), which leads theoretically to a decrease in its bioavailability, and is expected to trigger a guanylyl-cyclase-mediated inflammatory cascade, that could explain the inflammation in AD. In vitro, any increase in the hydrostatic pressure has already been linked to the microtubule disorganization. The amyloid deposits, also known as senile plaques, would behave as a sponge toward ISF nitrogen; Aβ is considered as a foam-stabilizing agent. By taking the shape of cerebral amyloid angiopathy, the amyloid could confine the nitrogen leak from the blood, and progressively insulate the Blood-Brain Barrier

  9. Reduced nasal nitric oxide production in cystic fibrosis patients with elevated systemic inflammation markers.

    Directory of Open Access Journals (Sweden)

    Ruth K Michl

    Full Text Available BACKGROUND: Nitric oxide (NO is produced within the respiratory tract and can be detected in exhaled bronchial and nasal air. The concentration varies in specific diseases, being elevated in patients with asthma and bronchiectasis, but decreased in primary ciliary dyskinesia. In cystic fibrosis (CF, conflicting data exist on NO levels, which are reported unexplained as either decreased or normal. Functionally, NO production in the paranasal sinuses is considered as a location-specific first-line defence mechanism. The aim of this study was to investigate the correlation between upper and lower airway NO levels and blood inflammatory parameters, CF-pathogen colonisation, and clinical data. METHODS AND FINDINGS: Nasal and bronchial NO concentrations from 57 CF patients were determined using an electrochemical analyser and correlated to pathogen colonisation of the upper and lower airways which were microbiologically assessed from nasal lavage and sputum samples. Statistical analyses were performed with respect to clinical parameters (lung function, BMI, laboratory findings (CRP, leucocytes, total-IgG, fibrinogen, and anti-inflammatory and antibiotic therapy. There were significant correlations between nasal and bronchial NO levels (rho = 0.48, p<0.001, but no correlation between NO levels and specific pathogen colonisation. In patients receiving azithromycin, significantly reduced bronchial NO and a tendency to reduced nasal NO could be found. Interestingly, a significant inverse correlation of nasal NO to CRP (rho = -0.28, p = 0.04 and to leucocytes (rho = -0.41, p = 0.003 was observed. In contrast, bronchial NO levels showed no correlation to clinical or inflammatory parameters. CONCLUSION: Given that NO in the paranasal sinuses is part of the first-line defence mechanism against pathogens, our finding of reduced nasal NO in CF patients with elevated systemic inflammatory markers indicates impaired upper airway defence. This

  10. The complex reaction kinetics of neptunium including redox and extraction process in 30% TBP-nitric acid system

    International Nuclear Information System (INIS)

    Hu Zhang; Zhan-yuan Liu; Xian-ming Zhou; Li Li


    In order to understand the complex and dynamic neptunium process chemistry in the TBP-HNO_3 system, the kinetics involved reversible redox reaction and extraction mass transfer was investigated. The results indicates that the mass transfer rate of Np(VI) is much faster than the redox reaction in aqueous solution. The concentrations of nitric acid and nitrous acid not only can change the Np(V) oxidation reaction and Np(VI) reduction reaction rate, but also can ultimately determine the distribution of neptunium extraction equilibrium. The variety of temperature can only influence the extraction equilibrium time, but cannot alter the equilibrium state of neptunium. (author)

  11. Contribution to the modelization of liquid-liquid extraction systems. Application to metallic nitrate extraction by TBP in nitric medium

    International Nuclear Information System (INIS)

    Ly, J.


    The validity of theoretical expression for activity coefficients, in concentrated aqueous solution, proposed by Mikulin-Stokes-Robinson and Ryazanov-Vdovenko is confirmed by numerous tests. This allows a better control of the reactivity of chemicals in the extraction system: nitric aqueous solution-TBP organic solution used in nuclear hydrometallurgy. A reliable methodology is proposed for the study of metal extraction mechanism. Application to palladium (II) evidences extracted species in the organic phase. Influence of degradation product from extractant radiolysis on the behavior of this metallic element is effected. 187 refs [fr

  12. Acute and chronic role of nitric oxide, renin-angiotensin system and sympathetic nervous system in the modulation of calcium sensitization in Wistar Rats

    Czech Academy of Sciences Publication Activity Database

    Brunová, Aneta; Bencze, Michal; Behuliak, Michal; Zicha, Josef


    Roč. 64, č. 4 (2015), s. 447-457 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : blood pressure * kalcium sensitization * Rho kinase * nitric oxide * renin-angiotensin system * sympathetic nervous system * fasudil Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

  13. Active cooling of microvascular composites for battery packaging (United States)

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


    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.

  14. The antidiabetic effect of L-carnitine in rats: the role of nitric oxide system

    Directory of Open Access Journals (Sweden)

    Shaghayegh Hajian-Shahri


    Full Text Available Background: Nowadays, the use of L-carnitine in the treatment of diabetes is increasing. This study was conducted to investigate the effect of co-administration of L-arginine (precursor for the synthesis of nitric oxide and nitro-L-arginine (nitric oxide synthesis inhibitor on antidiabetic activity of L-carnitine in diabetic rats. Materials and Methods: In this study, 50 male rats weighing 180-201g were divided into five groups: (1 non diabetic control rats; (2 untreated diabetic rats; (3 diabetic rats treated with L-carnitine 300 mg/kg (4; diabetic rats treated with L-carnitine 300 mg/kg + L-arginine 300 mg/kg; and (5 diabetic rats treated with L-carnitine (300 mg/kg + nitro-L-arginine (1mg/kg. Type 1 diabetes was induced by a single intraperitoneal injection of 110 mg/kg body weight alloxan. After 30 days, liver malondialdehyde levels, lipid profile, serum glucose, and glycated hemoglobin serum levels were measured. Results: Blood glucose, liver enzymes, glycated hemoglobin, and liver malondialdehyde levels significantly decreased in diabetic rats treated with L-carnitine compared to the untreated diabetic group (P<0.05. The co-administration of L-arginine and L-carnitine led to a significant decrease in glycated hemoglobin levels and serum glucose, in a manner similar to the group received only L-carnitine. Also, L-arginine and nitro-l-arginine had similar effects on liver lipid peroxidation and serum biochemical parameters. Conclusion: The results suggest that the hypoglycemic effect of L-carnitine is mediated independently from nitric oxide pathways. The interaction between L-carnitine and L-arginine may not be synergistic. So, their combined administration is not recommended for the diabetic patients.

  15. Vasoactive systems in L-NAME hypertension: the role of inducible nitric oxide synthase

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Dobešová, Zdenka; Čejka, Jakub; Kuneš, Jaroslav; Zicha, Josef


    Roč. 22, č. 1 (2004), s. 167-173 ISSN 0263-6352 R&D Projects: GA ČR GA305/03/0769; GA MŠk LN00A069 Grant - others:VEGA(SK) 2/3185/23; SAV(SK) APVT51-017902 Institutional research plan: CEZ:AV0Z5011922 Keywords : nitric oxide synthase * L-NAME hypertension * aminoguanidine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.871, year: 2004

  16. Effect of systemic nitric oxide synthase inhibition on optic disc oxygen partial pressure in normoxia and in hypercapnia. (United States)

    Petropoulos, Ioannis K; Pournaras, Jean-Antoine C; Stangos, Alexandros N; Pournaras, Constantin J


    To investigate the effect of systemic nitric oxide synthase (NOS) inhibition on optic disc oxygen partial pressure (PO(2)) in normoxia and hypercapnia. Intervascular optic disc PO(2) was measured in 12 anesthetized minipigs by using oxygen-sensitive microelectrodes placed 0.1), despite a 21% increase of mean arterial pressure. Optic disc PO(2) increase under hypercapnia was blunted after L-NAME injection (DeltaPO(2) = 0.6 +/- 1.1 mm Hg; 3%; P > 0.1), and this effect was reversible by L-arginine. Moreover, L-NAME reduced the response to carbogen by 29% (DeltaPO(2) = 9.1 +/- 4.4 mm Hg; 49%; P = 0.01 versus before L-NAME). The response to hyperoxia was not affected. Whereas systemic NOS inhibition did not affect optic disc PO(2) in normoxia, a blunting effect was noted on the CO(2)-induced optic disc PO(2) increase. Nitric oxide appears to mediate the hypercapnic optic disc PO(2) increase.

  17. Vapor pressures of nitric acid and water in the systems HNO3-H2O and HNO3-Th(NO3)4-H2O at 50oC

    International Nuclear Information System (INIS)

    Lemire, R.J.; Brown, C.P.; Campbell, A.B.


    The equilibrium compositions of the vapor above nitric acid-water, thorium nitrate-water, and nitric acid-thorium nitrate-water mixtures at 50 o C have been studied as a function of solution concentration by using a transpiration technique. Nitric acid concentrations were varied from 0 to 20 m and thorium nitrate concentrations from 0 to 2.5 m. Our data for the nitric acid-water system have been combined with literature data to obtain parameters for Scatchard's ion-component model, and these parameters provide a satisfactory description of the system at 50 o C over a wide concentration range. The enhancement, at 50 o C, of the nitric acid vapor pressure by added thorium nitrate was found to be less than that previously determined at 25 o C. The data for the nitric acid-thorium nitrate-water system at 50 o C were fitted to a single multiparameter function. (author)

  18. Changes in the nitric oxide system in the shore crab Hemigrapsus sanguineus (Crustacea, Decapoda) CNS induced by a nociceptive stimulus. (United States)

    Dyuizen, Inessa V; Kotsyuba, Elena P; Lamash, Nina E


    Using NADPH-diaphorase (NADPH-d) histochemistry, inducible nitric oxide synthase (iNOS)-immunohistochemistry and immunoblotting, we characterized the nitric oxide (NO)-producing neurons in the brain and thoracic ganglion of a shore crab subjected to a nociceptive chemical stimulus. Formalin injection into the cheliped evoked specific nociceptive behavior and neurochemical responses in the brain and thoracic ganglion of experimental animals. Within 5-10 min of injury, the NADPH-d activity increased mainly in the neuropils of the olfactory lobes and the lateral antenna I neuropil on the side of injury. Later, the noxious-induced expression of NADPH-d and iNOS was detected in neurons of the brain, as well as in segmental motoneurons and interneurons of the thoracic ganglion. Western blotting analysis showed that an iNOS antiserum recognized a band at 120 kDa, in agreement with the expected molecular mass of the protein. The increase in nitrergic activity induced by nociceptive stimulation suggests that the NO signaling system may modulate nociceptive behavior in crabs.

  19. Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling*# (United States)

    Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan


    Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H2O2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato’s response to chilling stress. PMID:27921397

  20. Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling. (United States)

    Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

    Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H 2 O 2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato's response to chilling stress.

  1. Inhibition of nitric oxide synthesis by systemic N(G)-monomethyl-L-arginine administration in humans

    DEFF Research Database (Denmark)

    Frandsen, U; Bangsbo, J; Langberg, Henning


    (controls) and with prior N(G)-nitro-L-arginine methyl ester (L-NAME) infusion (4 mg/kg, intravenously). Samples from the interstitial fluid were obtained at rest, during exercise and after exercise with the microdialysis technique. Interstitial adenosine in controls increased (p0.05) to controls. The 6......-keto-prostaglandin F1alpha concentration in controls was 1.17+/-0.20 ng/ml at rest and increased (p0.05) in L-NAME. The interstitial K(+) concentration in controls increased (p......We examined whether the formation or the release of the vasodilators adenosine, prostacyclin (PGI(2)) and potassium (K(+)) increase in skeletal muscle interstitium in response to nitric oxide synthase (NOS) inhibition. Five subjects performed one-legged knee extensor exercise at 30 W without...

  2. Antioxidant systems are regulated by nitric oxide-mediated post-translational modifications (NO-PTMs

    Directory of Open Access Journals (Sweden)

    Juan Carlos Begara-Morales


    Full Text Available Nitric oxide (NO is a biological messenger that orchestrates a plethora of plant functions, mainly through post-translational modifications (PTMs such as S-nitrosylation or tyrosine nitration. In plants, hundreds of proteins have been identified as potential targets of these NO-PTMs under physiological and stress conditions indicating the relevance of NO in plant-signaling mechanisms. Among these NO protein targets, there are different antioxidant enzymes involved in the control of reactive oxygen species (ROS, such as H2O2, which is also a signal molecule. This highlights the close relationship between ROS/NO signaling pathways. The major plant antioxidant enzymes, including catalase, superoxide dismutases (SODs peroxiredoxins (Prx and all the enzymatic components of the ascorbate-glutathione (Asa-GSH cycle, have been shown to be modulated to different degrees by NO-PTMs. This mini-review will update the recent knowledge concerning the interaction of NO with these antioxidant enzymes, with a special focus on the components of the Asa-GSH cycle and their physiological relevance.

  3. Nitric oxide-mediated intersegmental modulation of cycle frequency in the crayfish swimmeret system. (United States)

    Yoshida, Misaki; Nagayama, Toshiki; Newland, Philip


    Crayfish swimmerets are paired appendages located on the ventral side of each abdominal segment that show rhythmic beating during forward swimming produced by central pattern generators in most abdominal segments. For animals with multiple body segments and limbs, intersegmental coordination of central pattern generators in each segment is crucial for the production of effective movements. Here we develop a novel pharmacological approach to analyse intersegmental modulation of swimmeret rhythm by selectively elevating nitric oxide levels and reducing them with pharmacological agents, in specific ganglia. Bath application of L-arginine, the substrate NO synthesis, increased the cyclical spike responses of the power-stroke motor neurons. By contrast the NOS inhibitor, L-NAME decreased them. To determine the role of the different local centres in producing and controlling the swimmeret rhythm, these two drugs were applied locally to two separate ganglia following bath application of carbachol. Results revealed that there was both ascending and descending intersegmental modulation of cycle frequency of the swimmeret rhythm in the abdominal ganglia and that synchrony of cyclical activity between segments of segments was maintained. We also found that there were gradients in the strength effectiveness in modulation, that ascending modulation of the swimmeret rhythm was stronger than descending modulation. © 2018. Published by The Company of Biologists Ltd.

  4. Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

    International Nuclear Information System (INIS)

    Nakao, Atsunori; Kaczorowski, David J.; Zuckerbraun, Brian S.; Lei Jing; Faleo, Gaetano; Deguchi, Kentaro; McCurry, Kenneth R.; Billiar, Timothy R.; Kanno, Shinichi


    Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H 2 O 2 -induced cell death of mvECs in association with HO-1 induction. These protective effects were completely reversed by nuclear factor-κB (NF-κB) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-κB activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease

  5. Microvascularization on collared peccary placenta

    DEFF Research Database (Denmark)

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


    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...

  6. Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2.

    Directory of Open Access Journals (Sweden)

    María C Ortiz

    Full Text Available The aim of this study was to evaluate whether L-Arginine (L-Arg supplementation modifies nitric oxide (NO system and consequently aquaporin-2 (AQP2 expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.

  7. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses (United States)

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


    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

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

    LENUS (Irish Health Repository)

    Ewers, Michael


    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. Calculation of HNO2 concentration from redox potential in HNO3-H2O system as an aid to understanding the cathodic reaction of nitric acid corrosion

    International Nuclear Information System (INIS)

    Takeuchi, Masayuki; Whillock, G.O.H.


    Nitrous acid affects the corrosion of metals such as stainless steels in nitric acid. However nitrous acid is not particularly stable in nitric acid and the analytical methods available are quite involved. Accordingly, the calculation of nitrous acid concentration from redox potential was tested in the HNO 3 -H 2 O system as a convenient in situ analysis method. The calculation process is based on Nernst's equation and the required thermodynamic data were obtained from published values. The available thermodynamic data allow calculation of nitrous acid concentration from 273K to 373K for 0%-100% HNO 3 . The redox potential was 8 kmol·m -3 HNO 3 under NO bubbling and the nitrous acid concentration was determined by a Colourimetric method. The calculated data were compared with the measured data and a good agreement was found. It was found that the corrosion potential of stainless steel is influenced by nitrous acid concentration in nitric acid solution. The calculation process is useful for in-situ analysis of nitrous acid species in HNO 3 -H 2 O system and understanding the behavior of the cathodic reaction associated with nitric acid corrosion. (author)

  10. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity (United States)

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


    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

  11. TBP 20% - diluent/HNO3/H2O liquid-liquid extraction system: equilibrium normalization data of nitric acid, ruthenium and zirconium

    International Nuclear Information System (INIS)

    Oliveira, C.A.L.G. de.


    The extraction behaviour of nitric acid, nitrosyl-ruthenium nitrate and zirconium hydroxide nitrate in the system tri-n-butyl phosphate (TBP) 20% - diluent was studied. The main purpose was to obtain enough data to elaborate process flowsheets for the treatment of irradiated uranium fuels. During the runs, the equilibrium diagrams of nitric acid, ruthenium and zirconium were settled. From the achieved data, the influence of nitric acid, ruthenium, zirconium and nitrate ions concentration in the aqueous phase was checked. Furthermore, the density and the surface tension of the aqueous and organic phases were determined, gathering the interfacial tension after the contact between the phases. A comparison among the obtained equilibrium data and the existing one from literature allowed the elaboration of mathematical models to express the distribution behaviour of nitric acid, ruthenium and zirconium as a function of nitrate ions concentration in the aqueous phase. The reduction of TBP concentration from 30% v/v (normally used) to 20% v/v, has shown no influence in the extraction behaviour of the elements. A decreasing in the distribution values was observed and that means an important factor during the decontamination of uranium from its contaminants, ruthenium and zirconium. (Author) [pt

  12. Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Das, Amitava; Singla, Sumit K; Shah, Vijay H [Gastroenterology Research Unit, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905 (United States); Mukherjee, Priyabrata; Mukhopadhyay, Debabrata; Patra, Chitta Ranjan [Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905 (United States); Guturu, Praveen [Department of Internal Medicine, UTMB, Galveston, TX 77555 (United States); Frost, Megan C, E-mail:, E-mail: [Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 (United States)


    Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 deg. C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

  13. Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

    International Nuclear Information System (INIS)

    Das, Amitava; Singla, Sumit K; Shah, Vijay H; Mukherjee, Priyabrata; Mukhopadhyay, Debabrata; Patra, Chitta Ranjan; Guturu, Praveen; Frost, Megan C


    Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 deg. C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

  14. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. (United States)

    Salmon, Andrew H J; Satchell, Simon C


    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

  15. Fluorescence of the gamma, epsilon, and delta systems of nitric oxide - Polarization and use of calculated intensities for spectrometer calibration. (United States)

    Poland, H. M.; Broida, H. P.


    Results of a study in which fluorescence of the gamma system of nitric oxide was obtained by excitation from both the 2144 A line of ionized cadmium and a continuum source. Individual rotational lines of the 2144 A excited fluorescence spectrum were found to be partially polarized and to have polarizations of differ ing sign. Measured relative vibrational band intensities from line and continuum excitation were compared to calculated Franck-Condon factors. Those Franck-Condon factors based on a single potential for the two spin states of the X super pi state agreed better with measured values than those based on separate potentials for the two spin states. Calculated intensities of the v prime = 3 progression were used to calibrate the instrument response in the wavelength region from 2000 to 2500 A and were checked with measured intensities of the v prime = 0.1, and 2 progressions. Fluorescence of the epsilon and delta bands obtained with continuum lamp excitation also were compared to calculated intensities.

  16. Prenatal irradiation: nitric oxide and oxidative stress roles in radiation-induced apoptosis of the developing central nervous system

    International Nuclear Information System (INIS)

    Sanjurjo, Julieta


    Full text: The effects of prenatal irradiation on developing brain should be considered at cellular, structural and functional levels, integrating the information obtained from different sources in an appropriated model to explain the mechanisms involved in neuronal damage. That would permit to make risk estimations and improve radiological protection. Human brain is especially sensitive to ionizing radiation during certain stages of prenatal development. At doses such as those received by Hiroshima and Nagasaki's atomic bomb explosions survivors that were prenatally exposed, the maximum risk was to those exposed between the 8th and 15th weeks of gestation, in coincidence with the highest rate of neuron production and its migration to the brain cortex. The major effect produced on both, brain growth and development, was the augmentation of the Severe Mental Retardation (SMR) incidence. Radiation-induced apoptosis of neuronal progenitors should be considered as one of the factors associated with this pathology, apart from those of migration and synaptogenesis. Apoptosis is an innate and evolutionally conserved process by which the cells provoke the inactivation, disorganisation and degradation of their structural and functional components in a systematic fashion, with the aim of producing its own death. It is also the main cell death mechanism induced by low linear energy transfer (LET) ionizing radiation in developing Central Nervous System (CNS). Radioinduced apoptosis characterization during the different developmental stages, its kinetics and the possible implicated mechanisms (like oxidative injury and nitric oxide) was done using an 'in vitro' system of cortical micro masses (primary cultures of brain cortex cells) from rat embryo brains. Cell cultures were exposed to a single dose of gamma radiation, between 0,2 and 2 Gy, supplied by a Co 60 source (Picker C4M60) at a 70 cm distance with a field area size of 25 cm x 25 cm and at a 0,34 Gy/minute dose rate

  17. Simultaneous Laser-induced Fluorescence of Nitric Oxide and Atomic Oxygen in the Hypersonic Materials Environment Test System Arcjet Facility (United States)

    Johansen, Craig; Lincoln, Daniel; Bathel, Brett; Inman, Jennifer; Danehy, Paul


    Simultaneous nitric oxide (NO) and atomic oxygen (O) laser induced fluorescence (LIF) experiments were performed in the Hypersonic Materials Environmental Test System (HYMETS) facility at the NASA Langley Research Center. The data serves as an experimental database for validation for chemical and thermal nonequilibrium models used in hypersonic flows. Measurements were taken over a wide range of stagnation enthalpies (6.7 - 18.5 MJ/kg) using an Earth atmosphere simulant with a composition of 75% N2, 20% O2, and 5% Ar (by volume). These are the first simultaneous measurements of NO and O LIF to be reported in literature for the HYMETS facility. The maximum O LIF mean signal intensity was observed at a stagnation enthalpy of approximately 12 MJ/kg while the maximum NO LIF mean signal intensity was observed at a stagnation enthalpy of 6.7 MJ/kg. Experimental results were compared to simple fluorescence model that assumes equilibrium conditions in the plenum and frozen chemistry in the isentropic nozzle expansion (Mach 5). The equilibrium calculations were performed using CANTERA v2.1.1 with 16 species. The fluorescence model captured the correlation in mean O and NO LIF signal intensities over the entire range of stagnation enthalpies tested. Very weak correlations between single-shot O and NO LIF intensities were observed in the experiments at all of the stagnation enthalpy conditions.

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


    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. Experimental diode laser-assisted microvascular anastomosis. (United States)

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


    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.

  20. Ghrelin-related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries. (United States)

    Ku, Jacqueline M; Sleeman, Mark W; Sobey, Christopher G; Andrews, Zane B; Miller, Alyson A


    The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des-acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries. © 2016 John Wiley & Sons Australia, Ltd.

  1. GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing. (United States)

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


    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

  2. Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System (United States)

    Gomes, Felipe V.; Silva, Andréia L.; Uliana, Daniela L.; Camargo, Laura H. A.; Guimarães, Francisco S.; Cunha, Fernando Q.; Joca, Sâmia R. L.; Resstel, Leonardo B. M.


    Background: Inducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses. Methods: We evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated. Results: Contextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning. Conclusion: These data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in

  3. Solar fuels and chemicals system design study (ammonia/nitric acid production process). Volume 2. Conceptual design. Final report

    Energy Technology Data Exchange (ETDEWEB)


    As part of the Solar Central Receiver Fuels and Chemicals Program, Foster Wheeler Solar Development Corporation (FWSDC), under contract to Sandia National Laboratories-Livermore (SNLL), developed a conceptual design of a facility to produce ammonia and nitric acid using solar energy as the principal external source of process heat. In the selected process, ammonia is produced in an endothermic reaction within a steam methane (natural gas) reformer. The heat of reaction is provided by molten carbonate salt heated by both a solar central receiver and an exothermic ammonia-fired heater. After absorption by water, the product of the latter reaction is nitric acid.

  4. Electrochemistry and Spectroelectrochemistry of the Pu (III/IV) and (IV/VI) Couples in Nitric Acid Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lines, Amanda M. [Nuclear Chemistry and Engineering, Pacific Northwest National Laboratory, Richland WA 99352; Adami, Susan R. [Nuclear Chemistry and Engineering, Pacific Northwest National Laboratory, Richland WA 99352; Casella, Amanda J. [Nuclear Chemistry and Engineering, Pacific Northwest National Laboratory, Richland WA 99352; Sinkov, Sergey I. [Nuclear Chemistry and Engineering, Pacific Northwest National Laboratory, Richland WA 99352; Lumetta, Gregg J. [Nuclear Chemistry and Engineering, Pacific Northwest National Laboratory, Richland WA 99352; Bryan, Samuel A. [Nuclear Chemistry and Engineering, Pacific Northwest National Laboratory, Richland WA 99352


    The solution chemistry of Pu in nitric acid is explored via electrochemistry and spectroelectrochemistry. By utilizing and comparing these techniques, an improved understanding of Pu behavior and its dependence on nitric acid concentration can be achieved. Here the Pu (III/IV) couple is characterized using cyclic voltammetry, square wave voltammetry, and a spectroelectrochemical Nernst step. Results indicate the formal reduction potential of the couple shifts negative with increasing acid concentration and reversible electrochemistry is no longer attainable above 6 M HNO3. Spectroelectrochemistry is also used to explore the irreversible oxidation of Pu(IV) to Pu(VI) and shine light on the mechanism and acid dependence of the redox reaction.

  5. 21 CFR 868.5165 - Nitric oxide administration apparatus. (United States)


    ... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be used in conjunction with a ventilator or other breathing gas administration system. (b) Classification...

  6. Microvascular transplantation and replantation of the dog submandibular gland. (United States)

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


    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.

  7. Theorical and experimental analysis of nitrogen-15 isotope enrichment by nitrogen monoxide and nitric acid system

    International Nuclear Information System (INIS)

    Ducatti, C.


    Nitrogen-15 isotope enrichment by chemical exchange in NO/HNO 3 system was studied using two different theories. The isotope fractionation factors obtained by the countercurrent theory was compared to those estimated by the isotope equipartition theory were confronted through a model. A column in countercurrent was built at laboratory scale and parameters such as: number of theoretical plates, height equivalent to a theoretical plate, type of packing, total height of column, production of H 15 NO 3 /week, obtained under isotope dynamic equilibrium conditions, were studied in comparison to those in the literature. (Author) [pt

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

    Directory of Open Access Journals (Sweden)

    E.R. Parra


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

  9. Mass transfer studies in miniature Rotating Disc Contactor (RDC) with 30% TBP/nitric acid biphasic system

    International Nuclear Information System (INIS)

    Balasubramonian, S.; Sivakumar, D.; Kumar, Shekhar; Kamachi Mudali, U.


    The rotating disc contactor is the widely used liquid-liquid extraction equipment for its high throughput and efficiency. In this work mass transfer performance of the miniature RDC column for the 30% TBP/nitric acid biphasic system was studied in terms of the operating variables such as rotor speed and flow rate of the aqueous and organic phase. The RDC column used in the experiments was shown. The column shell is made up of thick glass having diameter of 10.5 cm and height 100 cm. The rotor diameter is 5.3 cm and stator opening diameter is 6.3 cm. Totally 25 number of rotor discs were welded in the rotating shaft. This shaft was aligned in such a way that each rotor was placed in the centre of the compartment formed in between the two stator rings. The experiments were carried out to study the effect of rotor speed and superficial velocity of the dispersed and continuous phase on mass transfer efficiency. The organic solvent was made as the continuous phase and O/A ratio was set as 4 in both the continuous to dispersed phase(c-d) and dispersed to continuous phase (d-c) mass transfer experiments. The Number of Transfer Units (NTU) was estimated based on the solvent phase. The graphical representation of NTU was shown. The NTU value was observed as 4 and 3 respectively for extraction and stripping at the combined through put of 60 L/h and the rotor speed of 1000 rpm. This corresponds to the Height of Transfer Unit (HTU) value of 15 cm and 20 cm respectively for d-c and c-d mass transfer. The estimated overall mass transfer coefficient was increasing with rotor speed and superficial velocity of the liquid phases. The overall mass transfer coefficient also increases with increase in hold up

  10. Distribution of zirconium in the nitric acid-water-TPB-diluent system

    International Nuclear Information System (INIS)

    Shu, J.; Floh de Araujo, B.


    This paper deals with the extraction behaviour of zirconium in TBP/diluent-HNO 3 -H 2 O systems. The main purpose is to increase the uranium decontamination factor by adjusting the extraction conditions so that zirconium extraction is kept at a mininum. Equilibrium diagram, TBP concentration, aqueous: organic phases ratio, salting-out effects and uranium loading in the organic phase were the main factors studied. All the experiments have been carried out with zirconium in the 10 -2 - 10 -3 M concentration range. The extractant degradation products influence upon ziconium behaviour was also verified. With the data obtained it was possible to introduce some modification in the standard Purex flow-sheet with the increase of the decontamination of uranium from zirconium. 5 refs., 9 figs

  11. Microvascular pericytes in healthy and diseased kidneys (United States)

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


    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

  12. Photoactive Nitric Oxide Delivery Systems based on Metal Nitrosyl-Biomaterial Composites (United States)

    Heilman, Brandon James

    Gaseous NO has been recognized as a potent antibiotic even against highly drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) in both animal and human studies. However, difficulties in the delivery of the toxic (and reactive) gas demands innovative techniques to deliver NO in a controlled manner to malignant sites throughout the body. Metal nitrosyls reported by our group have demonstrated rapid NO release under the complete control of visible and NIR light. Careful incorporation of these photoactive nitrosyls into polymer matrices has afforded a set of nitrosyl-polymer composites in order to localize the NO-donors at a targeted site, ensure reliable NO release kinetics in vivo, and prevent potentially cytotoxic interactions of the metal nitrosyl or its reaction-products with the treatment site. The work presented in this thesis was pursued to derive clinically relevant NO-delivery systems and demonstrate their utility for the treatment of infection. In chapter 2, an NO-releasing polyurethane film (PUX-NO) is described with dispersed xerogel particles containing up to 3 mol% of [Mn(PaPy 3)(NO)](ClO4) entrapped in a silica matrix and swelled with excess moisture. The polyurethane based xerogel-nitrosyl (PUX-NO) films demonstrated rapid NO photorelease upon illumination with low-power visible light which was sufficient to eradicate clinically relevant loads (105 CFU mL-1 ) of several gram-positive and gram-negative pathogenic bacteria, including a strain of methicillin-resistant of S. aureus. The results of this study suggest that PUX-NO films are suitable for use as a NO-releasing occlusive film for the treatment of skin and soft-tissue infections or chronic, non-healing wounds. Since the NO-release rate from the films can be modulated by simple adjustment of the intensity of the light source, the films could be used to first clear the microbial burden from the wound site using high fluxes of NO, and then, provide a moderate

  13. Phase coherence of 0.1 Hz microvascular tone oscillations during the local heating (United States)

    Mizeva, I. A.


    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.

  14. Graft microvascular disease in solid organ transplantation. (United States)

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


    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.

  15. Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig. (United States)

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


    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.

  16. 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.


    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

  17. Re-investigation of the (3, 0) band in the b4Σ- - a4Π system for nitric oxide by laser absorption spectroscopy (United States)

    Li, Chuanliang; Shao, Ligang; Wang, Hailing; Zhou, Qinghong; Qiu, Xuanbing; Wei, Jilin; Deng, Lunhua; Chen, Yangqin


    Nitric oxide (NO) radicals in the a4Π state were produced by discharging the mixture of NO gas and helium at the audio frequency. In the near infrared region, the spectra of the b4Σ- - a4Π system of the NO radical were studied by optical heterodyne - concentration modulation laser absorption spectroscopy. More than one hundred and thirty lines and eleven branches were recorded for the first time and assigned to the (3, 0) band. A global fitting was carried out to extract the molecular constants. In particular, the parameters D, p, γ and AD were precisely determined.

  18. Study of immiscibilities in the trilaurylamine - dodecane - nitric acid - plutonium system; Etude des immiscibilites dans le systeme trilaurylamine - dodecane - acide nitrique - plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Saey, J C [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires


    Phase equilibrium in systems made up of trilaurylamine, dodecane, nitric acid tetravalent plutonium is shown by drawing the triangular diagrams. the study of these diagrams provides informations concerning the causes of immiscibility. Heterogeneity of the organic mixtures can be related to some characteristics of the components- dipole moment, molecular polarizability and hydrogen bond exchanging ability-Depending on these, some rules may be established which can be used to make a proper choice of an additive in order to improve the miscibility. As an application a study on the partial substitution of dodecane with decalin, in plutonium extraction experiments, has been done showing a possible improvement of the extraction process. (author) [French] L equilibre des phases dans les systemes formes a partir de trilaurylamine, de dodecane, d'acide nitrique et de plutonium tetravalent est represente en tracant les diagrammes triangulaires. L'examen de ces diagrammes permet d'apporter certaines precisions en ce qui concerne l'origine des immiscibilites. Celles ci sont ensuite reliees a certaines caracteristiques des constituants: le moment dipolaire, la polarisabilite moleculaire et la tendance a former des liaisons hydrogene. Sur les memes bases, il est possible d'etablir un certain nombre de regles pouvant servir a guider le choix d'un additif ameliorant la miscibilite. En application, une etude sur le remplacement partiel du dodecane par la decaline montre l'interet de l'emploi de ce compose dans le procede de purification du plutonium. (auteur)

  19. Impact of hemoglobin nitrite to nitric oxide reductase on blood transfusion for resuscitation from hemorrhagic shock

    Directory of Open Access Journals (Sweden)

    Chad Brouse


    Full Text Available Background: Transfusion of blood remains the gold standard for fluid resuscitation from hemorrhagic shock. Hemoglobin (Hb within the red blood cell transports oxygen and modulates nitric oxide (NO through NO scavenging and nitrite reductase. Aims: This study was designed to examine the effects of incorporating a novel NO modulator, RRx-001, on systemic and microvascular hemodynamic response after blood transfusion for resuscitation from hemorrhagic shock in a hamster window chamber model. In addition, to RRx-001 the role of low dose of nitrite (1 × 10−9 moles per animal supplementation after resuscitation was studied. Materials and Methods: Severe hemorrhage was induced by arterial controlled bleeding of 50% of the blood volume (BV and the hypovolemic state was maintained for 1 h. The animals received volume resuscitation by an infusion of 25% of BV using fresh blood alone or with added nitrite, or fresh blood treated with RRx-001 (140 mg/kg or RRx-001 (140 mg/kg with added nitrite. Systemic and microvascular hemodynamics were followed at baseline and at different time points during the entire study. Tissue apoptosis and necrosis were measured 8 h after resuscitation to correlate hemodynamic changes with tissue viability. Results: Compared to resuscitation with blood alone, blood treated with RRx-001 decreased vascular resistance, increased blood flow and functional capillary density immediately after resuscitation and preserved tissue viability. Furthermore, in RRx-001 treated animals, both mean arterial pressure (MAP and met Hb were maintained within normal levels after resuscitation (MAP >90 mmHg and metHb <2%. The addition of nitrite to RRx-001 did not significantly improve the effects of RRx-001, as it increased methemoglobinemia and lower MAP. Conclusion: RRx-001 alone enhanced perfusion and reduced tissue damage as compared to blood; it may serve as an adjunct therapy to the current gold standard treatment for resuscitation from

  20. Nitric oxide in the rat cerebellum after hypoxia/ischemia. (United States)

    Rodrigo, José; Fernández, Ana Patricia; Alonso, David; Serrano, Julia; Fernández-Vizarra, Paula; Martínez-Murillo, Ricardo; Bentura, María Luisa; Martinez, Alfredo


    Nitric oxide is a regulatory biological substance and an important intracellular messenger that acts as a specific mediator of various neuropathological disorders. In mammals and invertebrates, nitric oxide is synthesized from L-arginine in the central and peripheral neural structures by the endothelial, neuronal and inducible enzymatic isoforms of nitric oxide synthase. Nitric oxide may affect the function of various neurotransmitter-specific systems, and is involved in neuromodulation, reproductive function, immune response, and regulation of the cerebral blood circulation. This makes nitric oxide the main candidate in brain responses to brain ischemia/hypoxia. The cerebellum has been reported to be the area of the brain that has the highest nitric oxide synthase activity and the highest concentration of glutamate and aspartate. By glutamate receptors and physiological action of nitric oxide, cyclic guanisine-5'-monophosphate may be rapidly increased. The cerebellum significantly differs with respect to ischemia and hypoxia, this response being directly related to the duration and intensity of the injury. The cerebellum could cover the eventual need for nitric oxide during the hypoxia, boosting the nitric oxide synthase activity, but overall ischemia would require de novo protein synthesis, activating the inducible nitric oxide synthase to cope with the new situation. The specific inhibitors of nitric oxide synthesis show neuroprotective effects.

  1. Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice

    Directory of Open Access Journals (Sweden)

    Viglietti-Panzica Carla


    Full Text Available Abstract Background Nitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle. Results Changes were observed in the medial preoptic area (MPA (significantly higher number in estrus and in the arcuate nucleus (Arc (significantly higher number in proestrus. In the ventrolateral part of the ventromedial nucleus (VMHvl and in the bed nucleus of the stria terminalis (BST no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle in the VMHvl and in the BST (when considering only the less intensely stained elements. In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle. Conclusion These data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle.

  2. The type III secretion system is involved in the invasion and intracellular survival of Escherichia coli K1 in human brain microvascular endothelial cells


    Yao, Yufeng; Xie, Yi; Perace, Donna; Zhong, Yi; Lu, Jie; Tao, Jing; Guo, Xiaokui; Kim, Kwang Sik


    Type III secretion systems have been documented in many Gram-negative bacteria, including enterohemorrhagic Escherichia coli. We have previously shown the existence of a putative type III secretion system in meningitis-causing E. coli K1 strains, referred to as E. coli type III secretion 2 (ETT2). The sequence of ETT2 in meningitis-causing E. coli K1 strain EC10 (O7:K1) revealed that ETT2 comprises the epr, epa and eiv genes, but bears mutations, deletions and insertions. We constructed the E...

  3. Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Fomenko Iryna


    Full Text Available The use of nonsteroidal anti-inflammatory drugs (NSAIDs in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS, arginase, cyclooxygenase (COX and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX inhibitor, darbufelone were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS. WRS brought about an increase of inducible NOS (iNOS activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

  4. 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


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

    Energy Technology Data Exchange (ETDEWEB)

    Gutiérrez-Barrios, Alejandro, E-mail: [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)


    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.

  6. Comparative kinetic and equilibrium investigations on the extraction of U(IV) in nitric acid/Tbp or TLA-Kerosene systems

    Energy Technology Data Exchange (ETDEWEB)

    Daoud, J A; Khalifa, S M; Abdel Rahman, N; Aly, H F [Hot laboratories center, Atomic energy authority post code 13758, (Egypt)


    The extraction equilibrium of U(IV) by tributyl-phosphate (Tbp) or trilaurylamine (TLA) in kerosene from nitric acid media was investigated. The effect of the different parameters affecting the extraction was separately studied and compared. The kinetics of extraction of U(IV) by Tbp or TLA was also investigated using a stirred lewis cell. The data showed that the rate of extraction of U(IV) by Tbp is controlled by chemical reactions at the interface. In the TLA system, the extraction of U(IV) is controlled by chemical reactions at the interface and bulk phase. Rate equations show that the extraction of U(IV) is first order dependent on Tbp concentration while it is of fractional negative order with respect to TLA. The effect of temperature on the rate of extraction was also studied and the thermodynamic functions were evaluated for the two systems. 5 figs.

  7. Microvascular lesions of the true vocal fold. (United States)

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


    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.

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

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


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

  9. Neuroprotective properties of nitric oxide and S-nitrosoglutathione

    International Nuclear Information System (INIS)

    Rauhala, Pekka; Andoh, Tsugunobu; Chiueh, C.C.


    Oxidative stress and apoptosis may play an important role in the neurodegeneration. The present paper outlines antioxidative and antiapototic mechanisms of nitric oxide and S-nitrosothiols, which could mediate neuroprotection. Nitric oxide generated by nitric oxide synthase or released from an endogenous S-nitrosothiol, S-nitrosoglutathione may up-regulate antioxidative thioredoxin system and antiapototic Bcl-2 protein through a cGMP-dependent mechanism. Moreover, nitric oxide radicals have been shown to have direct antioxidant effect through their reaction with free radicals and iron-oxygen complexes. In addition to serving as a stabilizer and carrier of nitric oxide, S-nitrosoglutathione may have protective effect through transnitrosylation reactions. Based on these new findings, a hypothesis arises that the homeostasis of nitric oxide, S-nitrosothiols, glutathione, and thioredoxin systems is important for protection against oxidative stress, apoptosis, and related neurodegenerative disorders

  10. Microvascular Anastomosis: Proposition of a Learning Curve. (United States)

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


    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.

  11. 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)


    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.

  12. The pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies.

    Directory of Open Access Journals (Sweden)

    Reinhold J Medina

    Full Text Available BACKGROUND: Current guidelines encourage the use of statins to reduce the risk of cardiovascular disease in diabetic patients; however the impact of these drugs on diabetic retinopathy is not well defined. Moreover, pleiotropic effects of statins on the highly specialised retinal microvascular endothelium remain largely unknown. The objective of this study was to investigate the effects of clinically relevant concentrations of simvastatin on retinal endothelium in vitro and in vivo. METHODS AND FINDINGS: Retinal microvascular endothelial cells (RMECs were treated with 0.01-10 microM simvastatin and a biphasic dose-related response was observed. Low concentrations enhanced microvascular repair with 0.1 microM simvastatin significantly increasing proliferation (p<0.05, and 0.01 microM simvastatin significantly promoting migration (p<0.05, sprouting (p<0.001, and tubulogenesis (p<0.001. High concentration of simvastatin (10 microM had the opposite effect, significantly inhibiting proliferation (p<0.01, migration (p<0.01, sprouting (p<0.001, and tubulogenesis (p<0.05. Furthermore, simvastatin concentrations higher than 1 microM induced cell death. The mouse model of oxygen-induced retinopathy was used to investigate the possible effects of simvastatin treatment on ischaemic retinopathy. Low dose simvastatin (0.2 mg/Kg promoted retinal microvascular repair in response to ischaemia by promoting intra-retinal re-vascularisation (p<0.01. By contrast, high dose simvastatin(20 mg/Kg significantly prevented re-vascularisation (p<0.01 and concomitantly increased pathological neovascularisation (p<0.01. We also demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF stimulation, Akt phosphorylation, and nitric oxide production; and the anti-vascular repair mechanism is driven by marked intracellular cholesterol depletion and related disorganisation of key intracellular structures. CONCLUSIONS: A beneficial effect of low

  13. Nitric oxide nanoparticles (United States)

    Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.


    Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections. PMID:22286699

  14. Influence of the diluent on the radiolytic degradation of TBP in TBP systems, 30% (V/V) - diluent-nitric acid

    International Nuclear Information System (INIS)

    Rubenich, M.N.


    The influence of the diluent on the degradation of TBP was studied by a gas chromatographic technique. The results obtained have shown that the aromatic diluents decrease markedly the HDBP production in the radiolysis of TBP, while n-dodecane, which is being used as diluent, promotes this radiolysis. However, the influence of the diluent become not too significant on the total (radiolysis + hydrolysis) solutions containing nitric acid. In view of foreseeing applications of aromatic diluents or their mixtures with aliphatic diluents on nuclear fuel reprocessing, it would be advisable to carry out more research on the system TBP/diluent, particularly on the kinetics of the hydrolysis of TBP and the influence of the diluent on the TBP degradation under conditions similar to those verified in the Purex Process [pt

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

    Directory of Open Access Journals (Sweden)

    Joseph Harvey


    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.

  16. Rat Pial Microvascular Changes During Cerebral Blood Flow Decrease and Recovery: Effects of Cyanidin Administration

    Directory of Open Access Journals (Sweden)

    Teresa Mastantuono


    Full Text Available The reactive oxygen species (ROS are known to play a major role in many pathophysiological conditions, such as ischemia and reperfusion injury. The present study was aimed to evaluate the in vivo cyanidin (anthocyanin effects on damages induced by rat pial microvascular hypoperfusion-reperfusion injury by cerebral blood flow decrease (CBFD and subsequent cerebral blood flow recovery (CBFR. In particular, the main purpose was to detect changes in ROS production after cyanidin administration. Rat pial microvasculature was investigated using fluorescence microscopy through a cranial window (closed; Strahler's method was utilized to define the geometric features of pial vessels. ROS production was investigated in vivo by 2′-7′-dichlorofluorescein-diacetate assay and neuronal damage was measured on isolated brain sections by 2,3,5-triphenyltetrazolium chloride staining. After 30 min of CBFD, induced by bilateral common carotid artery occlusion, and 60 min of CBFR, rats showed decrease of arteriolar diameter and capillary perfusion; furthermore, increase in microvascular leakage and leukocyte adhesion was observed. Conversely, cyanidin administration induced dose-related arteriolar dilation, reduction in microvascular permeability as well as leukocyte adhesion when compared to animals subjected to restriction of cerebral blood flow; moreover, capillary perfusion was protected. ROS generation increase and marked neuronal damage were detected in animals subjected to CBFD and CBFR. On the other hand, cyanidin was able to reduce ROS generation and neuronal damage. In conclusion, cyanidin treatment showed dose-related protective effects on rat pial microcirculation during CBFD and subsequent CBFR, inducing arteriolar dilation by nitric oxide release and inhibiting ROS formation, consequently preserving the blood brain barrier integrity.

  17. Pathways for insulin access to the brain: the role of the microvascular endothelial cell. (United States)

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


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

  18. Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Kadir Gisi


    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.

  20. Treatment of Angina and Microvascular Coronary Dysfunction (United States)

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


    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

  1. Design, manufacture and in-vitro evaluation of a new microvascular anastomotic device. (United States)

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


    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.

  2. 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 ...

  3. Impaired coronary microvascular function in diabetics

    International Nuclear Information System (INIS)

    Tsujimoto, Go


    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)

  4. Techno-Economic Feasibility Study of Renewable Power Systems for a Small-Scale Plasma-Assisted Nitric Acid Plant in Africa

    Directory of Open Access Journals (Sweden)

    Aikaterini Anastasopoulou


    Full Text Available The expected world population growth by 2050 is likely to pose great challenges in the global food demand and, in turn, in the fertilizer consumption. The Food and Agricultural Organization of the United Nations has forecasted that 46% of this projected growth will be attributed to Africa. This, in turn, raises further concerns about the sustainability of Africa’s contemporary fertilizer production, considering also its high dependence on fertilizer imports. Based on these facts, a novel “green” route for the synthesis of fertilizers has been considered in the context of the African agriculture by means of plasma technology. More precisely, a techno-economic feasibility study has been conducted for a small-scale plasma-assisted nitric acid plant located in Kenya and South Africa with respect to the electricity provision by renewable energy sources. In this study, standalone solar and wind power systems, as well as a hybrid system, have been assessed for two different electricity loads against certain economic criteria. The relevant simulations have been carried out in HOMER software and the optimized configurations of each examined renewable power system are presented in this study.


    Energy Technology Data Exchange (ETDEWEB)

    Williamson, B.


    As nitric acid molarity is increased, there are two competing phenomena affecting the reactivity of the system. First, there is interaction between each of the 10 wells in the basket-like insert. As the molarity of the nitric acid solution is increased (it moves from 100% water to 100% HNO{sub 3}), the hydrogen atom density decreases by about 80%. However, it remains a relatively efficient moderator. The moderating ratio of nitric acid is about 90% that of water. As the media between the wells is changed from 100% water to 100% nitric acid, the density of the media increases by 50%. A higher density typically leads to a better reflector. However, when the macroscopic scattering cross sections are considered, nitric acid is a much worse reflector than water. The effectiveness of nitric acid as a reflector is about 40% that of water. Since the media between the wells become a worse reflector and still remains an effective moderator, interaction between the wells increases. This phenomenon will cause reactivity to increase as nitric acid molarity increases. The seond phenomenon is due to the moderating ratio changing in the high concentration fissile-nitric acid solution in the 10 wells. Since the wells contain relatively small volumes of high concentration solutions, a small decrease in moderating power has a large effect on reactivity. This is due to the fact that neutrons are more likely to escape the high concentration fissile solution before causing another fission event. The result of this phenomenon is that as nitric acid molarity increases, reactivity decreases. Recent studies have shown that the second phenomenon is indeed the dominating force in determining reactivity changes in relation to nitric acid molarity changes. When considering the system as a whole, as nitric acid molarity increases, reactivity decreases.

  6. Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Afzelius, Pia; Bazeghi, Nassim; Bie, Peter


    Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this ...

  7. Effect of biliary cirrhosis on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum: Role of nitric oxide pathway and endocannabinoid system

    Directory of Open Access Journals (Sweden)

    Dehpour A.R.


    Full Text Available Background: Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide (NO is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic (NANC nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic (NANC-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems.Methods: Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 µM and atropine (1 µM to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride (7.5 µM and electrical field stimulation was applied at different frequencies (2, 5, 10, 15 Hz to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside (10 nM-1mM, as an NO donor, were assessed.  Results: The NANC-mediated relaxation was significantly enhanced in cirrhotic animals (P<0.01. Anandamide potentiated the relaxations in both groups (P<0.05. The cannabinoid CB1 receptor antagonist AM251 (10 µM and the vanilloid receptor antagonist capsazepine (10 µM each significantly prevented the enhanced relaxations in cirrhotic rats (P<0.01. The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME (30-1000 nM inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside (10 nM-1 mM was similar in the two groups.Conclusions: Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and

  8. The Role of Vasodilator Receptors of Renin-angiotensin System on Nitric Oxide Formation and Kidney Circulation after Angiotensin II Infusion in Renal Ischemia/Reperfusion Rats. (United States)

    Maleki, Maryam; Hasanshahi, Jalal; Moslemi, Fatemeh


    Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Sixty-three Wistar male and female rats were used. Animals from each gender were divided into four groups received saline, Ang II, PD123319 + Ang II, and A779 + Ang II after renal IRI. Renal IRI induced with an adjustable hook. Blood pressure and renal blood flow (RBF) measured continuously. The nitrite levels were measured in serum, kidney, and urine samples. In female rats, the serum and kidney nitrite levels increased significantly by Ang II ( P < 0.05) and decreased significantly ( P < 0.05) when PD123319 was accompanied with Ang II. Such observation was not seen in male. Ang II decreased RBF significantly in all groups ( P < 0.05), while PD + Ang II group showed significant decrease in RBF in comparison with the other groups in female rats ( P < 0.05). Males show more sensibility to Ang II infusion; in fact, it is suggested that there is gender dimorphism in the Ang II and NO production associated with vasodilator receptors.

  9. Study on the effect of gamma radiolysis on the chromatographic composition profile of tri-isoAmyl-phosphate-n-dodecane-nitric acid system

    International Nuclear Information System (INIS)

    Chaudhary, S.D.; Lokhande, Manisha; Bindu, M.; Tripathi, S.C.; Gandhi, P.M.


    Tri-Iso-Amyl phosphate (TiAP), a higher homologue of tri-butyl phosphate (TBP) is the solvent proposed for the reprocessing of the spent nuclear fuel of Fast Breeder Reactors (FBR) origin. TiAP-n-dodecane has extraction behavior comparable to that of TBP-n-dodecane system, without third phase formation and an aqueous solubility ∼ 19mg/L, that is far too less in case as compared to that with TBP(∼400gm/L). We have initiated our study to examine the radiolytic degradation behavior of TiAP-n-dodecane in comparison to that of TBP and explore its full potential for reprocessing of spent nuclear fuels. A 30% mixture of TiAP with n-dodecane equilibrated with nitric acid of concentrations 2M has been subjected to steady state gamma radiolysis using 60 Co source. The samples were irradiated for increasing absorbed dose of 6,12 and 18M rad. Each of these samples were subjected to gas chromatographic analysis under optimised condition using thermal conductivity detector. Separately, these samples were also methylated using diazomethane for the determination of acidic phosphate species as their volatile methyl ester

  10. On the effect of minocycline on the depressive-like behavior of mice repeatedly exposed to malathion: interaction between nitric oxide and cholinergic system. (United States)

    Saeedi Saravi, Seyed Soheil; Amirkhanloo, Roya; Arefidoust, Alireza; Yaftian, Rahele; Saeedi Saravi, Seyed Sobhan; Shokrzadeh, Mohammad; Dehpour, Ahmad Reza


    This study was performed to investigate the antidepressant-like effect of minocycline in mice exposed to organophosphate pesticide malathion and possible involvement of nitric oxide/cGMP pathway in this paradigm. Mice were administered specific doses of malathion once daily for 7 consecutive days. After induction of depression, different doses of minocycline were daily injected alone or combined with non-specific NOS inhibitor, L-NAME, specific inducible NOS inhibitor, AG, NO precursor, L-arginine, and PDE5I, sildenafil. After locomotion assessment in open-field test, immobility times were recorded in the FST and TST. Moreover, hippocampal nitrite concentrations and acetylcholinesterase activity were measured. The results showed that repeated exposure to malathion induces depressive-like behavior at dose of 250 mg/kg. Minocycline (160 mg/kg) significantly reduced immobility times in FST and TST (P minocycline (80 mg/kg) with either L-NAME (3 mg/kg) or AG (25 mg/kg) significantly exerted a robust antidepressant-like effect in FST and TST (P minocycline at the same dose which has antidepressant-like effect, significantly reduced hippocampal nitrite concentration. The investigation indicates the essential role for NO/cGMP pathway in malathion-induced depressive-like behavior and antidepressant-like effect of minocycline. Moreover, the interaction between nitrergic and cholinergic systems are suggested to be involved in malathion-induced depression.

  11. Mandibular reconstruction with composite microvascular tissue transfer

    International Nuclear Information System (INIS)

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


    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

  12. 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))


    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.



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


    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...

  14. Zirconium for nitric acid solutions

    International Nuclear Information System (INIS)

    Yau, T.L.


    The excellent corrosion resistance of zirconium in nitric acid has been known for over 30 years. Recently, there is an increasing interest in using zirconium for nitric acid services. Therefore, an extensive research effort has been carried out to achieve a better understanding of the corrosion properties of zirconium in nitric acid. Particular attention is paid to the effect of concentration, temperature, structure, solution impurities, and stress. Immersion, autoclave, U-bend, and constant strain-rate tests were used in this study. Results of this study indicate that the corrosion resistance of zirconium in nitric acid is little affected by changes in temperature and concentration, and the presence of common impurities such as seawater, sodium chloride, ferric chloride, iron, and stainless steel. Moreover, the presence of seawater, sodium chloride, ferric chloride, and stainless steel has little effect on the stress corrosion craking (SCC) susceptibility of zirconium in 70% nitric acid at room temperatures. However, zirconium could be attacked by fluoride-containing nitric acid and the vapors of chloride-containing nitric acid. Also, high sustained tensile stresses should be avoided when zirconium is used to handle 70% nitric acid at elevated temperatures or > 70% nitric acid

  15. Renal microvascular disease in an aging population: a reversible process? (United States)

    Futrakul, Narisa; Futrakul, Prasit


    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.

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


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


    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. ...

  17. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

    Directory of Open Access Journals (Sweden)

    Ingmar Lundquist

    Full Text Available Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided.

  18. Alternative wavelengths for sutureless laser microvascular anastomosis: a preliminary study on acute samples. (United States)

    Bass, L S; Oz, M C; Libutti, S K; Treat, M R


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  20. Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Langberg, Henning; Gemmer, Carsten


    The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow......, respectively (P exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction....... was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release...

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

    Directory of Open Access Journals (Sweden)

    Valentina Ticcinelli


    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

  2. Nanocarriers for Nitric Oxide Delivery

    Directory of Open Access Journals (Sweden)

    Juliana Saraiva


    Full Text Available Nitric oxide (NO is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

  3. Nitric oxide in the psychobiology of mental disorders

    Directory of Open Access Journals (Sweden)

    Altan Eşsizoğlu


    Full Text Available Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory functions, and on various neuronal mechanisms. Many studies have been conducted to investigate the location of nitric oxide in the central nervous system, its effect on anxiety and depression, its relationship with other neurotransmitters, and also about its role on neurotoxicity. There are clinical studies concerning the level of nitrate, a product of nitric oxide metabolism, and also experimental studies concerning its rewarding effect of alcohol and substance use, in patients with depression and schizophrenia. However, limited studies have been conducted to investigate its relationship with stress, which is an important factor in the etiology of psychiatric disorders. These studies demonstrate that nitric oxide is closely related with stress physiology.Nitric oxide is a neuromodulator, which is frequently being mentioned about nowadays in psychiatry. Clinical and experimental studies play an important role in the psychobiology of psychiatric disorders.

  4. Nitric oxide synthase (NOS) in the trigeminal vascular system and other brain structures related to pain in rats

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Ploug, Kenneth Beri; Hay-Schmidt, Anders


    to measure the respective levels of mRNA and protein for nNOS and eNOS in peripheral and central tissues involved in migraine pain: dura mater, pial arteries, trigeminal ganglion (TG) trigeminal nucleus caudalis (TNC), periaqueductal grey (PAG), thalamus, hypothalamus, cortex, pituitary gland, hippocampus...... and cerebellum. iNOS was excluded from the present study because it was not induced. In the trigeminal vascular system we found the highest expression of nNOS mRNA in pial arteries. However, protein expression of nNOS was maximum in TNC. Among other brain structures, nNOS mRNA and protein expression...... was remarkably higher in the cerebellum than in any other tissues. Regarding eNOS in the trigeminovascular system, the highest mRNA expression was found in pial arteries. In the other brain structures, eNOS mRNA expression was similar but with lowest mRNA concentration in the pituitary gland and the highest...

  5. Prognostic Role of Exhaled Breath Condensate pH and Fraction Exhaled Nitric Oxide in Systemic Sclerosis Related Interstitial Lung Disease. (United States)

    Guillen-Del Castillo, Alfredo; Sánchez-Vidaurre, Sara; Simeón-Aznar, Carmen P; Cruz, María J; Fonollosa-Pla, Vicente; Muñoz, Xavier


    Interstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. No differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (Log Rank P=.03 and P<.01, respectively). EB and EBC could help to detect patients likely to present a deterioration on lung function during follow up. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis. (United States)

    Degano, Bruno; Soumagne, Thibaud; Delaye, Thomas; Berger, Patrick; Perez, Thierry; Guillien, Alicia; Pellegrin, Jean-Luc; Launay, David; Magy-Bertrand, Nadine; Agard, Christian; Tiev, Kiet Phong; Hua-Huy, Thông; Tardiff, Catherine; Diaz, Véronique; Chambellan, Arnaud; Dinh-Xuan, Anh Tuan


    Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide ( T LCO ) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning T LCO into membrane conductance (diffusing capacity) for carbon monoxide ( D MCO ) and alveolar capillary blood volume ( V C ) through combined measurement of T LCO and transfer factor of the lung for nitric oxide ( T LNO ) is more effective to identify pulmonary hypertension in SSc patients compared with T LCO alone. Here, the objective was to determine whether combined T LCO - T LNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than T LCO alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. T LCO , T LNO and V C were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for T LCO (0.82, 95% CI 0.79-0.85) and T LNO (0.80, 95% CI 0.76-0.83), but lower for V C (0.75, 95% CI 0.71-0.78) and D MCO (0.66, 95% CI 0.62-0.70).Compared with T LCO alone, combined T LCO - T LNO does not add capability to detect pulmonary hypertension in unselected SSc patients. Copyright ©ERS 2017.

  7. Effect of acute alloxan diabetes on ischemic and reperfusion arrhythmias in rats with different activity of nitric oxide system. (United States)

    Belkina, L M; Terekhina, O L; Smirnova, E A; Usacheva, M A; Kruglov, S V; Saltykova, V A


    Similar degree of glycemia (28-31 mmol/liter) and similar mortality (37-42%) were revealed in August rats exhibiting enhanced activity of NO system and in Wistar rats 3 weeks after alloxan treatment. Under conditions of myocardial ischemia caused by 10-min coronary artery ligation, the intensity of arrhythmias did not differ from the control in Wistar rats with diabetes mellitus and increased in August rats. Under conditions of reperfusion, diabetes produced an antiarrhythmic effect in Wistar rats and did not affect arrhythmia in August rats. Plasma concentrations of nitrates and nitrites in Wistar and August rats increased by 82 and 143%, respectively, compared to the control. The level of hemoxygenase-1 (hsp32) in the myocardium remained unchanged in Wistar rats and decreased by 26% in August rats. Thus, the absence of antiarrhythmic effect of acute diabetes in August rats is probably related to elevated NO content and reduced antioxidant activity.

  8. Thermal decomposition studies of aqueous and nitric solutions of hydroxyurea

    International Nuclear Information System (INIS)

    Shekhar Kumar; Pranay Kumar Sinha; Kamachi Mudali, U.; Natarajan, R.


    Hydroxyurea and its derivatives are important nonsalt forming reductants in partitioning of uranium and plutonium in the nuclear fuel reprocessing operations. There is no experimental data available in open literature describing pressurization due to the thermal decomposition of aqueous and nitric solutions of hydroxyurea at elevated temperatures. Authors studied thermal decomposition of hydroxyurea-nitric acid system and resultant pressurization at various concentrations of nitric acid in an adiabatic calorimeter in closed-vent conditions. During these experiments, pressurization was observed. In this paper, results of these experiments have been discussed. (author)

  9. Zeolites as catalyzer to environmental control. Nitric oxide removal

    International Nuclear Information System (INIS)

    Montes, C.; Zapata N, M; Villa H, A.L.


    Zeolites and the microporous materials related to them are a class of environmental catalysts, it which are used to remove the produced gases in combustion process (as mobile sources). In this work the importance that has catalysis for environment improvement is emphasized. A review of recent progress in the use of certain zeolitic material as catalysts for nitric oxide elimination of combustion systems is presented. More used nitric oxide removal methods are presented, as well as its advantages and disadvantages. Furthermore, it is emphasized on the need of accomplishing more investigation projects on the development of an active catalyst for the decomposition of the nitric oxide in its elements (N and O)

  10. [Cost effectiveness and budget impact analysis of inhaled nitric oxide in a neonatal unit from the perspective of the public health system]. (United States)

    Kilchemmann Fuentes, Carlos; Vallejos Vallejos, Carlos; Román Navarro, Andrés

    Inhaled nitric oxide (iNO) is currently the first-line therapy in severe hypoxaemic respiratory failure of the newborn. Most of regional neonatal centres in Chile do not have this therapeutic alternative. To determine the cost effectiveness of inhaled nitric oxide in the treatment of respiratory failure associated with pulmonary hypertension of the newborn compared to the usual care, including the transfer to a more complex unit. A clinical decision tree was designed from the perspective of Chilean Public Health Service. Incremental cost effectiveness rates (ICER) were calculated, deterministic sensitivity analysis was performed, and probabilistic budget impact was estimated using: TreeAge Pro Healthcare 2014 software. The iNO option leads to an increase in mean cost of $ 11.7 million Chilean pesos (€15,000) per patient treated, with an ICER compared with the usual care of $23 million pesos (€30,000) in case of death or ECMO avoided. By sensitising the results by incidence, it was found that from 7 cases and upwards treated annually, inhaled nitric oxide is less costly than the transfer to a more complex unit. From the perspective of a Chilean regional hospital, incorporating inhaled nitric oxide into the management of neonatal respiratory failure is the optimal alternative in most scenarios. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Removal of fluoride from aqueous nitric acid

    International Nuclear Information System (INIS)

    Pruett, D.J.; Howerton, W.B.; Mailen, J.C.


    Several methods for removing fluoride from aqueous nitric acid were investigated and compared with the frequently used aluminum nitrate-calcium nitrate (Ca 2+ -Al 3+ ) chemical trap-distillation system. Zirconium oxynitrate solutions were found to be superior in preventing volatilization of fluoride during distillation of the nitric acid, producing decontamination factors (DFs) on the order of 2 x 10 3 (vs approx. 500 for the Ca 2+ -Al 3+ system). Several other metal nitrate systems were tested, but they were less effective. Alumina and zirconia columns proved highly effective in removing HF from HF-HNO 3 vapors distilled through the columns; fluoride DFs on the order of 10 6 and 10 4 , respectively, were obtained. A silica gel column was very effective in adsorbing HF from HF-HNO 3 solutions, producing a fluoride DF of approx. 10 4

  12. Cannula sensor for nitric oxide detection

    Energy Technology Data Exchange (ETDEWEB)

    Glazier, S.A. [National Institute of Standard and Technology, Gaithersburg, MD (United States)


    Nitric oxide (NO) has received much attention because of its numerous roles in mammalian systems. It has been found in the brain and nervous system to act as a neurotransmitter, in blood vessels as a blood pressure regulator, in the immune system to act as a bactericide and tumorcide, and in other postulated roles as well. Nitric oxide is produced in mammalian cells by the enzyme nitric oxide synthetase. Once produced, NO is oxidized or reacts rapidly with components in living systems and hence has a short half-life. Only a few sensors have been constructed which can detect NO at nanomolar to micromolar levels found in these systems. We are currently examining the use of a cannula sensor employing oxyhemoglobin for NO detection. This sensor continuously draws in liquid sample at a low rate and immediately reacts it with oxyhemoglobin. The absorbance changes which accompany the reaction are monitored. The sensor has a linear response range from approximately 50 to 1000 nM of NO in aqueous solution. Its utility in monitoring NO produced by stimulated murine macrophage cells (RAW 264.7) in culture is currently being examined. The sensor design is generic in that it can also employ fluorescence and chemiluminescence detection chemistries which may allow lower detection limits to be achieved. Details of the sensor`s performance will be given.

  13. Comparison of tissue processing methods for microvascular visualization in axolotls. (United States)

    Montoro, Rodrigo; Dickie, Renee


    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.

  14. In vitro analysis of human periodontal microvascular endothelial cells. (United States)

    Tsubokawa, Mizuki; Sato, Soh


    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

  15. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain. (United States)

    Ragavendran, J Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J; Padi, Satyanarayana S V; Zhang, Ji; Coderre, Terence J


    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected

  16. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.


    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  17. Pilot study on microvascular anastomosis: performance and future educational prospects. (United States)

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


    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.

  18. Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction. (United States)

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


    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. 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.


    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

  20. Studies on the reaction of nitric acid and sugar

    International Nuclear Information System (INIS)

    MacDougall, C.S.; Bayne, C.K.; Roberson, R.B.


    The design of vessels and off-gas systems for denitrating acidic radioactive process solutions by reacting nitric acid with sugar requires a fairly accurate determination of the rate of the controlling step. Therefore, the reaction of sugar with concentrated nitric acid was closely examined at temperatures of 100 and 110 0 C and in the presence of low levels of iron )0 to 0.2 M Fe(III)). Efficiencies of the sugar destruction by nitric acid ranged from 2.56 to 2.93 mol of acid consumed per mole of carbon added. Product off-gases were examined throughout the reaction. Release of CO was fairly constant throughout the reaction, but amounts of CO 2 increased as the nitric acid began to attack the terminal carboxylic acids produced from the consumption of sucrose. Voluminous quantities of NO 2 were released at the beginning of the reaction, but larger relative concentrations of NO were observed toward the end

  1. Gap filling of 3-D microvascular networks by tensor voting. (United States)

    Risser, L; Plouraboue, F; Descombes, X


    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.

  2. 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.


    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

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

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Moran


    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.

  4. Experimental study on thermal hazard of tributyl phosphate-nitric acid mixtures using micro calorimeter technique

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Qi; Jiang, Lin; Gong, Liang; Sun, Jin-Hua, E-mail:


    Highlights: • Heat flows after mixing TBP with nitric acid are of different orders of magnitude. • Thermodynamics and kinetics of tributyl phosphate-nitric acid mixtures are derived. • Tributyl phosphate directly reacts with nitric acid and form organic red oil. • Thermal runaway could occur at 79 °C with a high nitric acid concentration. - Abstract: During PUREX spent nuclear fuel reprocessing, mixture of tributyl phosphate (TBP) and hydrocarbon solvent are employed as organic solvent to extract uranium in consideration of radiation contaminated safety and resource recycling, meanwhile nitric acid is utilized to dissolve the spent fuel into small pieces. However, once TBP contacts with nitric acid or nitrates above 130 °C, a heavy “red oil” layer would occur accompanied by thermal runaway reactions, even caused several nuclear safety accident. Considering nitric acid volatility and weak exothermic detection, C80 micro calorimeter technique was used in this study to investigate thermal decomposition of TBP mixed with nitric acid. Results show that the concentration of nitric acid greatly influences thermal hazard of the system by direct reactions. Even with a low heating rate, if the concentration of nitric acid increases due to evaporation of water or improper operations, thermal runaway in the closed system could start at a low temperature.

  5. Some features of formation and dissolution of a series of Pu(IV) and Zr alkyl and butyl alkyl phosphates in the system TBP -n-dodecane - nitric acid - water

    International Nuclear Information System (INIS)

    Markov, G.S.; Moshkov, M.M.; Kokina, S.A.


    The formation and composition of salts produced on interaction of a series of alkyl- and butylalkylphosphoric acids having alkyl radical chain lengths from C 4 to C 1 0 with Pu(IV) and Zr in organic and aqueous phases of the system TBP - n-dodecane -nitric acid - water were studied. The composition of compounds was found to depend on the conditions of their formation, defined first of all by the HNO 3 concentration in aqueous and organic phases. (author) 12 refs.; 4 figs.; 1 tab

  6. The determination of molar volumes of uranous nitrate and nitric acid in systems of U(NO3)4-HNO3-H2O and U(NO3)4-HNO3-30% TBP kerosene

    International Nuclear Information System (INIS)

    Tao Chengying


    The data of molar volumes of uranous nitrate and nitric acid are necessary for the calculation of the changes in phase volume during the extraction in U(NO 3 ) 4 -HNO 3 /30%TBP-kerosene system. However, the data of the partial molar volume of U(NO 3 ) 4 are not available in literature. In the present work, the molar volumes of U(NO 3 ) 4 and HNO 3 are calculated by linear fitting of the experimental data. The result of the molar volume of HNO 3 is consistent with those in literature

  7. Nitric acid adduct formation during crystallization of barium and strontium nitrates and their co-precipitation from nitric acid media

    International Nuclear Information System (INIS)

    Mishina, N.E.; Zilberman, B.Ya.; Lumpov, A.A.; Koltsova, T.I.; Puzikov, E.A.; Ryabkov, D.V.


    The molar solubilities of Ba, Sr and Pb nitrates in nitric acid as a function of total nitrate concentration is presented and described by the mass action law, indicating on formation of the adducts with nitric acid. Precipitates of Ba(NO 3 ) 2 and Sr(NO 3 ) 2 crystallized from nitric acid were studied by ISP OES and IR spectroscopy. The data obtained confirmed formation of metastable adducts with nitric acid. IR and X-ray diffraction studies of the mixed salt systems indicated conversion of the mixed salts into (Ba,Sr)(NO 3 ) 2 solid solution of discrete structure in range of total nitrate ion concentration ∼6 mol/L. (author)

  8. Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Mary N. Rizk


    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.

  10. 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)


    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.

  11. 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.


    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

  12. Presence of diabetic microvascular complications does not incrementally increase risk of ischemic stroke in diabetic patients with atrial fibrillation (United States)

    Chou, Annie Y.; Liu, Chia-Jen; Chao, Tze-Fan; Wang, Kang-Ling; Tuan, Ta-Chuan; Chen, Tzeng-Ji; Chen, Shih-Ann


    Abstract Conventional stroke risk prediction tools used in atrial fibrillation (AF) incorporate the presence of diabetes mellitus (DM) as a risk factor. However, it is unknown whether this risk is homogenous or dependent on the presence of diabetic microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy. The present study examined the risk of ischemic stroke in diabetic patients with and without microvascular complications. The present study used the National Health Insurance Research Database in Taiwan with detailed healthcare data on all-comers to the Taiwanese medical system from January 1, 1996 to December 31, 2011. AF and DM were identified when listed as discharge diagnoses or confirmed more than twice in the outpatient department. Patients on antithrombotic agents were excluded. The clinical endpoint was ischemic stroke. Among the 50,180 AF patients with DM, the majority had no microvascular complications (72.7%), while 2.6% had diabetic retinopathy, 8.4% had diabetic nephropathy, and 16.1% had diabetic neuropathy. Ischemic stroke occurred in 6003 patients, with a 4.74% annual risk of ischemic stroke. When compared with DM patients without microvascular complications, those with diabetic retinopathy, nephropathy, or neuropathy had higher incidences of ischemic stroke (4.65 vs 5.07, 4.77, or 5.20 per 100 person-years, respectively). However, after adjusting for confounding factors, the differences were no longer significant. In a large nationwide AF cohort with DM, risk of ischemic stroke was similar between patients with and without microvascular complications, suggesting that risk stratification of these patients does not require inclusion of diabetic retinopathy, nephropathy, and neuropathy. PMID:27399075

  13. The effects of nitric oxide cooling and the photodissociation of molecular oxygen on the thermosphere/ionosphere system over the Argentine Islands

    Directory of Open Access Journals (Sweden)

    G. D. Wells


    Full Text Available In the past the global, fully coupled, time-dependent mathematical model of the Earth's thermosphere/ionosphere/plasmasphere (CTIP has been unable to reproduce accurately observed values of the maximum plasma frequency, foF2, at extreme geophysical locations such as the Argentine Islands during the summer solstice where the ionosphere remains in sunlight throughout the day. This is probably because the seasonal dependence of thermospheric cooling by 5.3 µm nitric oxide has been neglected and the photodissociation of O2 and heating rate calculations have been over-simplified. Now we have included an up-to-date calculation of the solar EUV and UV thermospheric heating rate, coupled with a new calculation of a diurnally varying O2 photodissociation rate, in the model. Seasonally dependent 5.3 µm nitric oxide cooling is also included. With these important improvements, it is found that model values of foF2 are in substantially better agreement with observation. The height of the F2-peak is reduced throughout the day, but remains within acceptable limits of values derived from observation, except at around 0600 h LT. We also carry out two studies of the sensitivity of the upper atmosphere to changes in the magnitude of nitric oxide cooling and photodissociation rates. We find that hmF2 increases with increased heating, whilst foF2 falls. The converse is true for an increase in the cooling rate. Similarly increasing the photodissociation rate increases both hmF2 and foF2. These changes are explained in terms of changes in the neutral temperature, composition and neutral wind.

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

    International Nuclear Information System (INIS)

    Allen, John; Howell, Kevin


    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)

  15. Extraction of Eu(III) and Th(IV) with TBP in n-dodecane in the presence of nitric acid and the thermodynamic activity of the TBP in the system

    International Nuclear Information System (INIS)

    Santos, F.S.M. dos.


    A qualitative description of the behavior of distribution coefficients of nitric acid, Th(IV) and Eu(III) separately in the system HNO 3 -H 2 O-TBP-n-dodecane and the effect of the temperature in the distribution coefficient of Th(IV) are presented. The distribution coefficient of Eu(III) between aqueous solutions nitric acid and solutions of TBP in n-dodecane are measured. Since the composition of the extracted Eu(III) complex is known, the theoretical course of the dependency of the distribution coefficient on the TBP concentration can be predicted. Deviations of experimental dependencies from theoretical ones give them information about the thermodynamic activity of TBP in the organic phase. A mathematical description for the distribution coefficients of Eu(III) and HNO 3 in the mentioned system was sugested. This description will make possible an avaliation of the behavior of the activity coefficients of TBP in the organic phase. (A.R.H.) [pt

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


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


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

  17. Nitrogen isotope exchange between nitric oxide and nitric acid

    International Nuclear Information System (INIS)

    Axente, D.; Abrudean, M.; Baldea, A.


    The rate of nitrogen isotope exchange between NO and HNO 3 has been measured as a function of nitric acid concentration of 1.5-4M x 1 -1 . The exchange rate law is shown to be R=k[HNO 3 ] 2 [N 2 O 3 ] and the measured activation energy is E=67.78 kJ x M -1 (16.2 kcal x M -1 ). It is concluded that N 2 O 3 participates in 15 N/ 14 N exchange between NO and HNO 3 at nitric acid concentrations higher than 1.5M x 1 -1 . (author). 7 refs., 3 figs., 4 tabs

  18. Verocytotoxin-induced apoptosis of human microvascular endothelial cells. (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


    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.

  19. Method of improving the decontaminating efficiency of ruthenium in evaporating treatment of nitric acid

    International Nuclear Information System (INIS)

    Kubota, Kanya; Yamana, Hajime; Takeda, Seiichiro.


    Purpose: To significantly improve the ruthenium removing efficiency in a nitric acid solution in an acid recovery system for the recovery of nitric acid from nitric acid liquid wastes through evaporating condensation. Method: Upon evaporating treatment of nitric acid solution containing ruthenium by supplying and heating the solution to a nitric acid evaporating device, hydrazine is previously added to the nitric acid solution. Hydrazine and intermediate reaction product of hydrazine such as azide causes a reduction reaction with intermediate reaction product of ruthenium tetraoxide to suppress the oxidation of ruthenium and thereby improve the decontaminating efficiency of ruthenium. The amount of hydrazine to be added is preferably between 20 - 500 mg/l and most suitably between 200 - 2000 mg/l per one liter of the liquid in the evaporating device. (Seki, T.)

  20. Evaluation of Microvascular Perfusion and Resuscitation after Severe Injury. (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


    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.

  1. Nitric Acid Poisoning: Case Report

    International Nuclear Information System (INIS)

    Quintero Giraldo, Maria Paulina; Quiceno Calderon, William de Jesus; Melo Arango Catalina


    Nitric acid (HNO 3 ) is a corrosive fluid that, when in contact with reducing agents, generates nitrogen oxides that are responsible for inhalation poisoning. We present two cases of poisoning from nitric acid gas inhalation resulting from occupational exposure. Imaging findings were similar in both cases, consistent with adult respiratory distress syndrome (ARDS): bilaterally diffuse alveolar opacities on the chest X-ray and a cobblestone pattern on computed tomography (CT).one of the patients died while the other evolved satisfactorily after treatment with n-acetyl cysteine and mechanical ventilation. The diagnosis of nitric acid poisoning was made on the basis of the history of exposure and the way in which the radiological findings evolved.

  2. Corrosion resistance of zirconium in nitric acid

    International Nuclear Information System (INIS)

    Kajimura, H.; Morikawa, H.; Nagano, H.


    Slow strain rate tests are effected on zirconium in boiling nitric acid to study the influence of nitric acid concentration, of oxidizing ions (Cr and Ce) and of electric potential. Corrosion resistance is excellent and stress corrosion cracking occurs only for severe conditions: 350 mV over electric potential for corrosion with nitric acid concentration of 40 % [fr

  3. Determination of regional flow by use of intravascular PET tracers: microvascular theory and experimental validation for pig livers

    DEFF Research Database (Denmark)

    Munk, O L; Bass, L; Feng, H


    Today, the standard approach for the kinetic analysis of dynamic PET studies is compartment models, in which the tracer and its metabolites are confined to a few well-mixed compartments. We examine whether the standard model is suitable for modern PET data or whether theories including more...... physiologic realism can advance the interpretation of dynamic PET data. A more detailed microvascular theory is developed for intravascular tracers in single-capillary and multiple-capillary systems. The microvascular models, which account for concentration gradients in capillaries, are validated and compared...... with the standard model in a pig liver study. METHODS: Eight pigs underwent a 5-min dynamic PET study after (15)O-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual...

  4. Treatment Of Sunitinib-Induced Hypertension In Solid Tumors By Nitric Oxid Donors

    Directory of Open Access Journals (Sweden)

    Luís A. Leon


    Hypertension (HT is one of the most common adverse effects of angiogenesis inhibitors. Hypertension observed in clinical trials appears to correlate with the potency of VEGF kinase inhibitor against VEGFR-2: agents with higher potency are associated with a higher incidence of hypertension. Although the exact mechanism by TKIs induce hypertension has not yet been completely clarified, two key hypotheses have been postulated. First, some studies have pointed to a VEGF inhibitors-induced decrease in nitric oxide synthase (NOS and nitric oxide (NO production, that can result in vasoconstriction and increased blood pressure. VEGF, mediated by PI3K/Akt and MAPK pathway, upregulates the endothelial nitric oxide synthase enzyme leading to up-regulation of NO production. So inhibition of signaling through the VEGF pathway would lead to a decrease in NO production, resulting in an increase in vascular resistance and blood pressure. Secondly a decrease in the number of microvascular endothelial cells and subsequent depletion of normal microvessel density (rarefaction occurs upon VEGF signaling inhibition.

  5. Evaluation of microvascular endothelial function and capillary density in patients with infective endocarditis using laser speckle contrast imaging and video-capillaroscopy. (United States)

    Barcelos, Amanda; Tibirica, Eduardo; Lamas, Cristiane


    To evaluate the systemic microcirculation of patients with infective endocarditis (IE). This is a comparative study of patients with definite IE by the modified Duke criteria admitted to our center for treatment. A reference group of sex- and age-matched healthy volunteers was included. Microvascular flow was evaluated in the forearm using a laser speckle contrast imaging system, for noninvasive measurement of cutaneous microvascular perfusion, in combination with skin iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to test microvascular reactivity. Microvascular density was evaluated using skin video-capillaroscopy. We studied 22 patients with IE; 15 were male and seven female. The mean age and standard deviation (SD) were 45.5 ± 17.3 years. Basal skin microvascular conductance was significantly increased in patients with IE, compared with healthy individuals (0.36 ± 0.13 versus 0.21 ± 0.08 APU/mmHg; P < 0.0001). The increase in microvascular conductance induced by ACh in patients was 0.21 ± 0.17 and in the reference group, it was 0.37 ± 0.14 APU/mmHg (P = 0.0012). The increase in microvascular conductance induced by SNP in patients was 0.18 ± 0.14 and it was 0.29 ± 0.15 APU/mmHg (P = 0.0140) in the reference group. The basal mean skin capillary density of patients (135 ± 24 capillaries/mm 2 ) was significantly higher, compared with controls (97 ± 21 capillaries/mm 2 ; P < 0.0001). The main findings in the microcirculation of patients with IE were greater basal vasodilation and a reduction of the endothelium-dependent and -independent microvascular reactivity, as well as greater functional skin capillary density compared to healthy individuals. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. In-vivo assessment of microvascular functional dynamics by combination of cmOCT and wavelet transform (United States)

    Smirni, Salvatore; MacDonald, Michael P.; Robertson, Catherine P.; McNamara, Paul M.; O'Gorman, Sean; Leahy, Martin J.; Khan, Faisel


    The cutaneous microcirculation represents an index of the health status of the cardiovascular system. Conventional methods to evaluate skin microvascular function are based on measuring blood flow by laser Doppler in combination with reactive tests such as post-occlusive reactive hyperaemia (PORH). Moreover, the spectral analysis of blood flow signals by continuous wavelet transform (CWT) reveals nonlinear oscillations reflecting the functionality of microvascular biological factors, e.g. endothelial cells (ECs). Correlation mapping optical coherence tomography (cmOCT) has been previously described as an efficient methodology for the morphological visualisation of cutaneous micro-vessels. Here, we show that cmOCT flow maps can also provide information on the functional components of the microcirculation. A spectral domain optical coherence tomography (SD-OCT) imaging system was used to acquire 90 sequential 3D OCT volumes from the forearm of a volunteer, while challenging the micro-vessels with a PORH test. The volumes were sampled in a temporal window of 25 minutes, and were processed by cmOCT to obtain flow maps at different tissue depths. The images clearly show changes of flow in response to the applied stimulus. Furthermore, a blood flow signal was reconstructed from cmOCT maps intensities to investigate the microvascular nonlinear dynamics by CWT. The analysis revealed oscillations changing in response to PORH, associated with the activity of ECs and the sympathetic innervation. The results demonstrate that cmOCT may be potentially used as diagnostic tool for the assessment of microvascular function, with the advantage of also providing spatial resolution and structural information compared to the traditional laser Doppler techniques.

  7. Preventing microvascular complications in type 1 diabetes mellitus


    Viswanathan, Vijay


    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...

  8. Microvascular Remodeling and Wound Healing: A Role for Pericytes (United States)

    Dulmovits, Brian M.; Herman, Ira M.


    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

  9. Preventing microvascular complications in type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Vijay Viswanathan


    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.

  10. [Microvascular decompression for hemifacial spasm. Ten years of experience]. (United States)

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


    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.

  11. Microvascular Architecture of Hepatic Metastases in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Darshini Kuruppu


    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.

  12. Preventing microvascular complications in type 1 diabetes mellitus (United States)

    Viswanathan, Vijay


    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

  13. Cell proliferation along vascular islands during microvascular network growth

    Directory of Open Access Journals (Sweden)

    Kelly-Goss Molly R


    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.

  14. Study of microvascular non-Newtonian blood flow modulated by electroosmosis. (United States)

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


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

  15. Ghrelin stimulates angiogenesis in human microvascular endothelial cells: Implications beyond GH release

    International Nuclear Information System (INIS)

    Li Aihua; Cheng Guangli; Zhu Genghui; Tarnawski, Andrzej S.


    Ghrelin, a peptide hormone isolated from the stomach, releases growth hormone and stimulates appetite. Ghrelin is also expressed in pancreas, kidneys, cardiovascular system and in endothelial cells. The precise role of ghrelin in endothelial cell functions remains unknown. We examined the expression of ghrelin and its receptor (GHSR1) mRNAs and proteins in human microvascular endothelial cells (HMVEC) and determined whether ghrelin affects in these cells proliferation, migration and in vitro angiogenesis; and whether MAPK/ERK2 signaling is important for the latter action. We found that ghrelin and GHSR1 are constitutively expressed in HMVEC. Treatment of HMVEC with exogenous ghrelin significantly increased in these cells proliferation, migration, in vitro angiogenesis and ERK2 phosphorylation. MEK/ERK2 inhibitor, PD 98059 abolished ghrelin-induced in vitro angiogenesis. This is First demonstration that ghrelin and its receptor are expressed in human microvascular endothelial cells and that ghrelin stimulates HMVEC proliferation, migration, and angiogenesis through activation of ERK2 signaling

  16. Pain modulation by nitric oxide in the spinal cord.

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire


    Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

  17. Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway. (United States)

    Achike, Francis I; Kwan, Chiu-Yin


    1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or

  18. Fabrication of a reticular poly(lactide-co-glycolide) cylindrical scaffold for the in vitro development of microvascular networks (United States)

    Tung, Yen-Ting; Chang, Cheng-Chung; Ju, Jyh-Cherng; Wang, Gou-Jen


    The microvascular network is a simple but critical system that is responsible for a range of important biological mechanisms in the bodies of all animals. The ability to generate a functional microvessel not only makes it possible to engineer vital tissue of considerable size but also serves as a platform for biomedical studies. However, most of the current methods for generating microvessel networks in vitro use rectangular channels which cannot represent real vessels in vivo and have dead zones at their corners, hence hindering the circulation of culture medium. We propose a scaffold-wrapping method which enables fabrication of a customized microvascular network in vitro in a more biomimetic way. By integrating microelectromechanical techniques with thermal reflow, we designed and fabricated a microscale hemi-cylindrical photoresist template. A replica mold of polydimethylsiloxane, produced by casting, was then used to generate cylindrical scaffolds with biodegradable poly(lactide-co-glycolide) (PLGA). Human umbilical vein endothelial cells were seeded on both sides of the PLGA scaffold and cultured using a traditional approach. The expression of endothelial cell marker CD31 and intercellular junction vascular endothelial cadherin on the cultured cell demonstrated the potential of generating a microvascular network with a degradable cylindrical scaffold. Our method allows cells to be cultured on a scaffold using a conventional culture approach and monitors cell conditions continuously. We hope our cell-covered scaffold can serve as a framework for building large tissues or can be used as the core of a vascular chip for in vitro circulation studies.

  19. Antioxidant N-acetylcysteine restores systemic nitric oxide availability and corrects depressions in arterial blood pressure and heart rate in diabetic rats. (United States)

    Xia, Zhengyuan; Nagareddy, Prabhakara R; Guo, Zhixin; Zhang, Wei; McNeill, John H


    Increased oxidative stress and reduced nitric oxide (NO) bioactivity are key features of diabetes mellitus that eventually result in cardiovascular abnormalities. We assessed whether N-acetylcysteine (NAC), an antioxidant and glutathione precursor, could prevent the hyperglycaemia induced increase in oxidative stress, restore NO availability and prevent depression of arterial blood pressure and heart rate in vivo in experimental diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were treated or not treated with NAC in drinking water for 8 weeks, initiated 1 week after induction of diabetes. At termination, plasma levels of free 15-F2t-isoprostane, a specific marker of oxygen free radical induced lipid peroxidation, was increased while the plasma total antioxidant concentration was decreased in untreated diabetic rats as compared to control rats (P<0.05). This was accompanied by a significant reduction of plasma levels of nitrate and nitrite, stable metabolites of NO, (P<0.05, D vs. C) and a reduced endothelial NO synthase protein expression in the heart and in aortic and mesenteric artery tissues. Systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP) and heart rate (HR) were reduced in diabetic rats (P<0.05 vs. C) and NAC normalised the changes that occurred in the diabetic rats. The protective effects may be attributable to restoration of NO bioavailability in the circulation.

  20. Radiation induced microvascular damage in the rat spinal cord: cellular and secretory factors

    International Nuclear Information System (INIS)

    Pfeffer, M. Raphael; Siegal, Tali; Meltzer, A; Shezen, E; Ovadia, Haim


    Purpose/Objective: To investigate the short and long-term effect of radiation on micro vessel permeability, endothelin and nitric oxide production, and cellular profile in the spinal cord of rats and to evaluate the influence of recombinant human manganese superoxide dismutase (r-hMnSOD) on these effects. Materials and Methods: The thoracolumbar spinal cord of Fischer rats was irradiated to a dose of 15 Gy. At various times afterwards the rats were killed and the spinal cord was excised. Endothelin and nitric oxide synthase (NOS) activity and microvascular permeability were assayed quantitatively. Astrocytes, microglia, vascular basal membrane and neuro filaments were immunohistochemically evaluated. Results: None of the rats developed signs of neurological dysfunction. Endothelin concentrations in the spinal cord were significantly reduced 18 hours after irradiation and continued to decrease until after 10 days (p=<0.007). After 56 days endothelin concentration returned to normal and then rose to markedly elevated levels at 120 and 180 days (p=<0.002). NOS activity was reduced soon after irradiation and remained very low throughout the period of observation despite the changes in endothelin. Vascular permeability was markedly increased after 18 hours and again after 120 and 180 days. Treatment with r-hMnSOD had no effect on normal vascular permeability but abolished the increase in vascular permeability seen after irradiation. Standard microscopic examination revealed no changes in the irradiated spinal cord. Immunohistochemical stains showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p=<0.0003). An increase in astrocytic cells was seen after 180 days with an earlier short lasting peak after 14 days. No abnormalities were found in blood vessel configuration, density and diameter. Vascular basal membrane and neuro filaments were unchanged throughout the study. Conclusions: Following radiation to the spinal cord there

  1. Variation of nitric oxide levels in imported Plasmodium falciparum ...

    African Journals Online (AJOL)



    Mar 18, 2008 ... Nitric oxide (NO) has been recognized during the past two decades as one of the most versatile players in the immune system. Even though the molecular mechanisms responsible by the naturally acquired immunity against malaria are still to be clarified, the production of NO seems to play an important role.

  2. Alternative to Nitric Acid Passivation (United States)

    Kessel, Kurt R.


    Corrosion is an extensive problem that affects the National Aeronautics and Space Administration (NASA) and European Space Agency (ESA). The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys.

  3. Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion (United States)

    Reid, Ian A.


    Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

  4. α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells.

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chung

    Full Text Available Endothelial cells (ECs express fibroblast growth factor (FGF receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot. Primary cultures of human aortic endothelial cells (HAECs and human brain microvascular endothelial cells (HBMECs were used to generate in vitro cell models. We found endogenous α-Klotho expression in ECs from various organs except in microvascular ECs from human brain. Furthermore, FGF-23 stimulated endothelial nitric oxide synthase (eNOS expression, nitric oxide (NO production, and cell proliferation in HAECs. Interestingly, these effects were not observed in our HBMEC model in vitro. High phosphate treatment and endothelial α-Klotho knockdown mitigated FGF-23 mediated eNOS induction, NO production, and cell proliferation in HAECs. Rescue treatment with soluble α-Klotho did not reverse endothelial FGF-23 resistance caused by reduced or absent α-Klotho expression in HAECs. These novel observations provide evidence for differential α-Klotho functional expression in the human endothelium and its presence may play a role in determining the response to FGF-23 in the vascular tree. α-Klotho was not detected in cerebral microvascular ECs and its absence may render these cells nonresponsive to FGF-23.

  5. Ratiometric Time-Gated Luminescence Probe for Nitric Oxide Based on an Apoferritin-Assembled Lanthanide Complex-Rhodamine Luminescence Resonance Energy Transfer System. (United States)

    Tian, Lu; Dai, Zhichao; Liu, Xiangli; Song, Bo; Ye, Zhiqiang; Yuan, Jingli


    Using apoferritin (AFt) as a carrier, a novel ratiometric luminescence probe based on luminescence resonance energy transfer (LRET) between a Tb(3+) complex (PTTA-Tb(3+)) and a rhodamine derivative (Rh-NO), PTTA-Tb(3+)@AFt-Rh-NO, has been designed and prepared for the specific recognition and time-gated luminescence detection of nitric oxide (NO) in living samples. In this LRET probe, PTTA-Tb(3+) encapsulated in the core of AFt is the energy donor, and Rh-NO, a NO-responsive rhodamine derivative, bound on the surface of AFt is the energy acceptor. The probe only emits strong Tb(3+) luminescence because the emission of rhodamine is switched off in the absence of NO. Upon reaction with NO, accompanied by the turn-on of rhodamine emission, the LRET from Tb(3+) complex to rhodamine occurs, which results in the remarkable increase and decrease of the long-lived emissions of rhodamine and PTTA-Tb(3+), respectively. After the reaction, the intensity ratio of rhodamine emission to Tb(3+) emission, I565/I539, is ∼24.5-fold increased, and the dose-dependent enhancement of I565/I539 shows a good linearity in a wide concentration range of NO. This unique luminescence response allowed PTTA-Tb(3+)@AFt-Rh-NO to be conveniently used as a ratiometric probe for the time-gated luminescence detection of NO with I565/I539 as a signal. Taking advantages of high specificity and sensitivity of the probe as well as its good water-solubility, biocompatibility, and cell membrane permeability, PTTA-Tb(3+)@AFt-Rh-NO was successfully used for the luminescent imaging of NO in living cells and Daphnia magna. The results demonstrated the efficacy of the probe and highlighted it's advantages for the ratiometric time-gated luminescence bioimaging application.

  6. Resolving the contributions of the membrane-bound and periplasmic nitrate reductase systems to nitric oxide and nitrous oxide production in Salmonella enterica serovar Typhimurium. (United States)

    Rowley, Gary; Hensen, Daniela; Felgate, Heather; Arkenberg, Anke; Appia-Ayme, Corinne; Prior, Karen; Harrington, Carl; Field, Sarah J; Butt, Julea N; Baggs, Elizabeth; Richardson, David J


    The production of cytotoxic nitric oxide (NO) and conversion into the neuropharmacological agent and potent greenhouse gas nitrous oxide (N₂O) is linked with anoxic nitrate catabolism by Salmonella enterica serovar Typhimurium. Salmonella can synthesize two types of nitrate reductase: a membrane-bound form (Nar) and a periplasmic form (Nap). Nitrate catabolism was studied under nitrate-rich and nitrate-limited conditions in chemostat cultures following transition from oxic to anoxic conditions. Intracellular NO production was reported qualitatively by assessing transcription of the NO-regulated genes encoding flavohaemoglobin (Hmp), flavorubredoxin (NorV) and hybrid cluster protein (Hcp). A more quantitative analysis of the extent of NO formation was gained by measuring production of N₂O, the end-product of anoxic NO-detoxification. Under nitrate-rich conditions, the nar, nap, hmp, norV and hcp genes were all induced following transition from the oxic to anoxic state, and 20% of nitrate consumed in steady-state was released as N₂O when nitrite had accumulated to millimolar levels. The kinetics of nitrate consumption, nitrite accumulation and N₂O production were similar to those of wild-type in nitrate-sufficient cultures of a nap mutant. In contrast, in a narG mutant, the steady-state rate of N₂O production was ~30-fold lower than that of the wild-type. Under nitrate-limited conditions, nap, but not nar, was up-regulated following transition from oxic to anoxic metabolism and very little N₂O production was observed. Thus a combination of nitrate-sufficiency, nitrite accumulation and an active Nar-type nitrate reductase leads to NO and thence N₂O production, and this can account for up to 20% of the nitrate catabolized.

  7. Effect of exogenous nitric oxide on antioxidative system and S-nitrosylation in leaves of Boehmeria nivea (L.) Gaud under cadmium stress. (United States)

    Wang, Dafei; Liu, Yunguo; Tan, Xiaofei; Liu, Hongyu; Zeng, Guangming; Hu, Xinjiang; Jian, Hao; Gu, Yanling


    Cadmium (Cd)-induced growth inhibition is one of the primary factors limiting phytoremediation effect of Boehmeria nivea (L.) Gaud in contaminated soil. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been evidenced to alleviate Cd toxicity in many plants. However, as an important mechanism of NO in orchestrating cellular functions, S-nitrosylation is still poorly understood in its relation with Cd tolerance of plants. In this study, higher exogenous NO levels were found to coincide with higher S-nitrosylation level expressed as content of S-nitrosothiols (SNO). The addition of low concentration (100 μM) SNP increased the SNO content, and it simultaneously induced an alleviating effect against Cd toxicity by enhancing the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) and reduced the accumulation of H2O2 as compared with Cd alone. Application of S-nitrosoglutathione reductase (GSNOR) inhibitors dodecanoic acid (DA) in 100 μM SNP group brought in an extra elevation in S-nitrosylation level and further reinforced the effect of SNP. While the additions of 400 μM SNP and 400 μM SNP + 50 μM DA further elevated the S-nitrosylation level, it markedly weakened the alleviating effect against Cd toxicity as compared with the addition of 100 μM SNP. This phenomenon could be owing to excess consumption of glutathione (GSH) to form SNO under high S-nitrosylation level. Therefore, the present study indicates that S-nitrosylation is involved in the ameliorating effect of SNP against Cd toxicity. This involvement exhibited a concentration-dependent property.

  8. Microvascular injury and the kidney in hypertension. (United States)

    Ruiz-Hurtado, G; Ruilope, L M

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

  9. Inter-arm Blood Pressure Difference and its Relationship with Retinal Microvascular Calibres in Young Individuals: The African-PREDICT Study. (United States)

    Strauss, Michél; Smith, Wayne; Schutte, Aletta E


    Bilateral systolic blood pressure (SBP) differences > 10mmHg is a common finding in clinical practice. Such BP differences in older individuals are associated with peripheral vascular disease, linked to microvascular dysfunction. Investigating retinal vessel calibres could provide insight into systemic microvascular function and may predict cardiovascular outcomes. Therefore we investigated the link between inter-arm systolic blood pressure differences (IASBPD) and the retinal microvasculature to determine the usefulness of IASBPD as an early marker of microvascular changes. In this cross-sectional study, we used data from 403 apparently healthy participants (20-30 years) (42% men; 49% black) taking part in the African-PREDICT study. Participants underwent retinal vessel imaging, anthropometric measurements and blood sampling. Brachial BP was measured sequentially in both arms to determine the mean IASBPD. Participants were stratified into two groups with an IASBPD difference in characteristics being a higher right arm SBP in the latter group (p=0.005). We found no association between IASBPD and retinal vessel calibres in any group. Less than 2% of the variance in IASBPD was explained by potential risk factors, with only SBP associating independently with IASBPD (β=115; p=0.039). In a young population an increased IASBPD is not related to retinal vessel diameters suggesting that it does not reflect early microvascular alterations. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sarita Bajaj


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

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

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


    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

  12. Catestatin Gly364Ser Variant Alters Systemic Blood Pressure and the Risk for Hypertension in Human Populations via Endothelial Nitric Oxide Pathway. (United States)

    Kiranmayi, Malapaka; Chirasani, Venkat R; Allu, Prasanna K R; Subramanian, Lakshmi; Martelli, Elizabeth E; Sahu, Bhavani S; Vishnuprabu, Durairajpandian; Kumaragurubaran, Rathnakumar; Sharma, Saurabh; Bodhini, Dhanasekaran; Dixit, Madhulika; Munirajan, Arasambattu K; Khullar, Madhu; Radha, Venkatesan; Mohan, Viswanathan; Mullasari, Ajit S; Naga Prasad, Sathyamangla V; Senapati, Sanjib; Mahapatra, Nitish R


    Catestatin (CST), an endogenous antihypertensive/antiadrenergic peptide, is a novel regulator of cardiovascular physiology. Here, we report case-control studies in 2 geographically/ethnically distinct Indian populations (n≈4000) that showed association of the naturally-occurring human CST-Gly364Ser variant with increased risk for hypertension (age-adjusted odds ratios: 1.483; P=0.009 and 2.951; P=0.005). Consistently, 364Ser allele carriers displayed elevated systolic (up to ≈8 mm Hg; P=0.004) and diastolic (up to ≈6 mm Hg; P=0.001) blood pressure. The variant allele was also found to be in linkage disequilibrium with other functional single-nucleotide polymorphisms in the CHGA promoter and nearby coding region. Functional characterization of the Gly364Ser variant was performed using cellular/molecular biological experiments (viz peptide-receptor binding assays, nitric oxide [NO], phosphorylated extracellular regulated kinase, and phosphorylated endothelial NO synthase estimations) and computational approaches (molecular dynamics simulations for structural analysis of wild-type [CST-WT] and variant [CST-364Ser] peptides and docking of peptide/ligand with β-adrenergic receptors [ADRB1/2]). CST-WT and CST-364Ser peptides differed profoundly in their secondary structures and showed differential interactions with ADRB2; although CST-WT displaced the ligand bound to ADRB2, CST-364Ser failed to do the same. Furthermore, CST-WT significantly inhibited ADRB2-stimulated extracellular regulated kinase activation, suggesting an antagonistic role towards ADRB2 unlike CST-364Ser. Consequently, CST-WT was more potent in NO production in human umbilical vein endothelial cells as compared with CST-364Ser. This NO-producing ability of CST-WT was abrogated by ADRB2 antagonist ICI 118551. In conclusion, CST-364Ser allele enhanced the risk for hypertension in human populations, possibly via diminished endothelial NO production because of altered interactions of CST-364Ser

  13. 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.


    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

  14. 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.


    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

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

    NARCIS (Netherlands)

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


    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

  16. 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 ...

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

    DEFF Research Database (Denmark)

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


    scanners, little use is made of earlier microvascular research in the compartmental models, which have become the standard model by which the vast majority of dynamic PET data are analysed. However, modern PET scanners provide data with a sufficient temporal resolution and good counting statistics to allow...... 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......Measurement of exchange of substances between blood and tissue has been a long-lasting challenge to physiologists, and considerable theoretical and experimental accomplishments were achieved before the development of the positron emission tomography (PET). Today, when modeling data from modern PET...

  18. Citric Acid Alternative to Nitric Acid Passivation (United States)

    Lewis, Pattie L. (Compiler)


    The Ground Systems Development and Operations GSDO) Program at NASA John F. Kennedy Space Center (KSC) has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of the GSDO Program, the purpose of this project is to demonstratevalidate citric acid as a passivation agent for stainless steel. Successful completion of this project will result in citric acid being qualified for use as an environmentally preferable alternative to nitric acid for passivation of stainless steel alloys in NASA and DoD applications.

  19. 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.

  20. Nitric acid flowsheet with late wash PHA testing

    International Nuclear Information System (INIS)

    Zamecnik, J.R.


    This Task Technical Plan outlines the activities to be conducted in the Integrated DWPF Melter System (IDMS) in ongoing support of the Defense Waste Processing Facility (DWPF) Chemical Process Cell (CPC) utilizing the Nitric Acid Flowsheet in the Sludge Receipt and Adjustment Tank (SRAT) and Precipitate Hydrolysis Aqueous (PHA) produced by the Late Wash Flowsheet. The IDMS facility is to be operated over a series of runs (2 to 4) using the Nitric Acid Flowsheet. The PHA will be produced with the Late Wash Flowsheet in the Precipitate Hydrolysis Experimental Facility (PHEF). All operating conditions shall simulate the expected DWPF operating conditions as closely as possible. The task objectives are to perform at least two IDMS runs with as many operating conditions as possible at nominal DWPF conditions. The major purposes of these runs are twofold: verify that the combined Late Wash and Nitric Acid flowsheets produce glass of acceptable quality without additional changes to process equipment, and determine the reproducibility of data from run to run. These runs at nominal conditions will be compared to previous runs made with PHA produced from the Late Wash flowsheet and with the Nitric Acid flowsheet in the SRAT (Purex 4 and Purex 5)

  1. Omega-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption Enhances Microvascular Reactivity in Young Healthy Individuals. (United States)

    Stupin, Ana; Rasic, Lidija; Matic, Anita; Stupin, Marko; Kralik, Zlata; Kralik, Gordana; Grcevic, Manuela; Drenjancevic, Ines


    Whilst the beneficial effect of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on cardiovascular (CV) system is well supported in CV patients, the effect of consumption of omega-3 PUFAs enriched functional food in healthy individuals is still not fully elucidated. This study aimed to determine the effect of consumption of omega-3 PUFAs enriched hen eggs on microvascular reactivity (primary outcome), blood pressure (BP) and serum lipid profile in young healthy individuals. Control group (N=16) ate three ordinary hen eggs (277 mg omega-3 PUFAs/day), and OMEGA-3 group (N=20) ate three omega-3 PUFAs enriched eggs containing 259 mg of omega-3 PUFAs/egg daily (ALA 167 mg/egg, EPA 7 mg/egg, DHA 84 mg/egg) for 3 weeks (777 mg omega-3 PUFAs/day). Post-occlusive reactive hyperemia (PORH) in skin microcirculation assessed by laser Doppler flowmetry, serum lipid profile, fasting blood glucose, high-sensitivity C-reactive protein (hsCRP) and arterial BP were measured in all subjects before and after the protocol. PORH was significantly enhanced, and triglycerides, hsCRP and BP were significantly decreased in OMEGA-3 group compared to baseline measurement, while there was no significant difference in Control group after the protocol compared to baseline. This is the first study to demonstrate that consumption of a mixture of omega-3 PUFAs (ALA+EPA+DHA), provided via enriched hen eggs, elicits changes in microvascular reactivity, BP and triglycerides level in healthy subjects that are associated with CV benefits, thus suggesting that daily consumption of omega-3 PUFAs enriched eggs in healthy individuals may potentially contribute to CV risk factors attenuation and disease prevention.

  2. Reduced toxicity polyester resins and microvascular pre-preg tapes for advanced composites manufacturing (United States)

    Poillucci, Richard

    Advanced composites manufacturing broadly encapsulates topics ranging from matrix chemistries to automated machines that lay-up fiber-reinforced materials. Environmental regulations are stimulating research to reduce matrix resin formulation toxicity. At present, composites fabricated with polyester resins expose workers to the risk of contact with and inhalation of styrene monomer, which is a potential carcinogen, neurotoxin, and respiratory irritant. The first primary goal of this thesis is to reduce the toxicity associated with polyester resins by: (1) identification of potential monomers to replace styrene, (2) determination of monomer solubility within the polyester, and (3) investigation of approaches to rapidly screen a large resin composition parameter space. Monomers are identified based on their ability to react with polyester and their toxicity as determined by the Globally Harmonized System (GHS) and a green screen method. Solubilities were determined by the Hoftyzer -- Van Krevelen method, Hansen solubility parameter database, and experimental mixing of monomers. A combinatorial microfluidic mixing device is designed and tested to obtain distinct resin compositions from two input chemistries. The push for safer materials is complemented by a thrust for multifunctional composites. The second primary goal of this thesis is to design and implement the manufacture of sacrificial fiber materials suitable for use in automated fiber placement of microvascaular multifunctional composites. Two key advancements are required to achieve this goal: (1) development of a roll-to-roll method to place sacrificial fibers onto carbon fiber pre-preg tape; and (2) demonstration of feasible manufacture of microvascular carbon fiber plates with automated fiber placement. An automated method for placing sacrificial fibers onto carbon fiber tapes is designed and a prototype implemented. Carbon fiber tows with manual placement of sacrificial fibers is implemented within an

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

    Directory of Open Access Journals (Sweden)

    Kislukhin Victor V


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

  4. Calculation of concentration profiles and their experimental verification with a pulsed sieve-plate column and the reactive material system of uranyl nitrate, nitric acid/tributyl phosphate, kerosine

    International Nuclear Information System (INIS)

    Ihle, E.


    The present study is concerned with the calculation of stationary and non-stationary concentration profiles as well as with the starting and disturbance behaviour of a pulsed sieve-plate extraction column. It investigates into the material system HNO 3 /uranyl nitrate in water with 30 per cent by volume of tributyl phosphate in kerosine. During the measurements of the concentration profiles for HNO 3 transition, which were effected in the direction of extraction and reextraction, it was shown that the concentration profiles measured in the mixer-settler range, in spite of a sixfold enlargement of the specific heat transfer area, do not differ essentially from those measured in the dispersion range. During the measurements of concentration profiles for HNO 3 /uranium transition, which were effected in the direction of coextraction and co-reextraction only for mixer-settler range, it was discovered that with increasing phase ratios, there is a depletion of the uranium concentration in the aqueous phase. If the phase ratio is further raised, it is the nitric acid, and not the uranium, that is depleted. (orig./PW) [de

  5. Role of nitrous acid during the dissolution of UO2 in nitric acid

    International Nuclear Information System (INIS)

    Deigan, N.; Pandey, N.K.; Kamachi Mudali, U.; Joshi, J.B.


    Understanding the dissolution behaviour of sintered UO 2 pellet in nitric acid is very important in designing an industrial scale dissolution system for the plutonium rich fast reactor MOX fuel. In the current article we have established the role of nitrous acid on the dissolution kinetics of UO 2 pellets in nitric acid. Under the chemical conditions that prevail in a typical Purex process, NO and NO 2 gases gets generated in the process streams. These gases produce nitrous acid in nitric acid medium. In addition, during the dissolution of UO 2 in nitric acid medium, nitrous acid is further produced in-situ at the pellet solution interface. As uranium dissolves oxidatively in nitric acid medium wherein it goes from U(IV) in solid to U(VI) in liquid, presence of nitrous acid (a good oxidizing agent) accelerates the reaction rate. Hence for determining the reaction mechanism of UO 2 dissolution in nitric acid medium, knowing the nitrous acid concentration profile during the course of dissolution is important. The current work involves the measurement of nitrous acid concentration during the course of dissolution of sintered UO 2 pellets in 8M starting nitric acid concentration as a function of mixing intensity from unstirred condition to 1500 RPM

  6. [Recent advances on pericytes in microvascular dysfunction and traditional Chinese medicine prevention]. (United States)

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


    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.

  7. Wide-area mapping of resting state hemodynamic correlations at microvascular resolution with multi-contrast optical imaging (Conference Presentation) (United States)

    Senarathna, Janaka; Hadjiabadi, Darian; Gil, Stacy; Thakor, Nitish V.; Pathak, Arvind P.


    Different brain regions exhibit complex information processing even at rest. Therefore, assessing temporal correlations between regions permits task-free visualization of their `resting state connectivity'. Although functional MRI (fMRI) is widely used for mapping resting state connectivity in the human brain, it is not well suited for `microvascular scale' imaging in rodents because of its limited spatial resolution. Moreover, co-registered cerebral blood flow (CBF) and total hemoglobin (HbT) data are often unavailable in conventional fMRI experiments. Therefore, we built a customized system that combines laser speckle contrast imaging (LSCI), intrinsic optical signal (IOS) imaging and fluorescence imaging (FI) to generate multi-contrast functional connectivity maps at a spatial resolution of 10 μm. This system comprised of three illumination sources: a 632 nm HeNe laser (for LSCI), a 570 nm ± 5 nm filtered white light source (for IOS), and a 473 nm blue laser (for FI), as well as a sensitive CCD camera operating at 10 frames per second for image acquisition. The acquired data enabled visualization of changes in resting state neurophysiology at microvascular spatial scales. Moreover, concurrent mapping of CBF and HbT-based temporal correlations enabled in vivo mapping of how resting brain regions were linked in terms of their hemodynamics. Additionally, we complemented this approach by exploiting the transit times of a fluorescent tracer (Dextran-FITC) to distinguish arterial from venous perfusion. Overall, we demonstrated the feasibility of wide area mapping of resting state connectivity at microvascular resolution and created a new toolbox for interrogating neurovascular function.

  8. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia


    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  9. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham


    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  10. Regulation and control of nitric oxide (NO) in macrophages

    DEFF Research Database (Denmark)

    Kovacevic, Zaklina; Sahni, Sumit; Lok, K.H.


    We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transp......We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores...... be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets....


    Directory of Open Access Journals (Sweden)

    I. V. Panova


    Full Text Available The important part in the group of biological compounds, participating in the regulation of the functions of the gastro-intestinal tract, is assigned to endothelial factors because of their impact on the majority of physiological and pathophysiological processes of the digestive system. The article provides information about physiological role of nitric oxide and endothelin-1 and presents a review of scientific data on the participation of nitric oxide and endothelin-1 in the pathogenesis of many digestive system diseases, emphasizing chronic inflammatory disorders of the upper gastrointestinal tract. The authors accentuate the importance of endothelium endocrine function research in children with esophagogastroduodenal disorders at the beginning of puberty, which is the critical period of ontogenesis.

  12. Oscillations and Multiple Equilibria in Microvascular Blood Flow. (United States)

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


    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.

  13. ABCD1 dysfunction alters white matter microvascular perfusion

    DEFF Research Database (Denmark)

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


    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...

  14. CMR of microvascular obstruction and hemorrhage in myocardial infarction

    Directory of Open Access Journals (Sweden)

    Wu Katherine C


    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.

  15. Clustering of microvascular complications in Type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Bjerg, Lasse; Hulman, Adam; Charles, Morten


    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...

  16. Statin use before diabetes diagnosis and risk of microvascular disease

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G


    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

  17. 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.


    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)

  18. A bibliographical review on the radiolysis of uranyl nitrate solutions in nitric acid medium

    International Nuclear Information System (INIS)

    Siri, Sandra; Mondino, Angel V.


    A bibliographical study on the effects of ionizing radiation on uranyl nitrate solutions in nitric acid medium was performed, and the state of knowledge on this subject is presented. The main experimental and theoretical results on water, nitric acid and uranium solutions radiolysis are reviewed and critically evaluated. This paper provides a collection of references as an aid to the development of practical applications, and to stimulate new research on fundamental processes in these systems. (author) [es

  19. Thermodynamics of uranium and nitric acid extraction from aqueous solution of TBP/diluent

    International Nuclear Information System (INIS)

    Souza Freitas, R.F. de.


    A thermodynamically consistent procedure for predicting distribution equilibria for uranyl nitrate and nitric acid between an aqueous solution and 30 vol % tributyl phosphate (TBP) in a hydrocarbon diluent is studied. Experimental work is developed in order to obtain equilibrium data for the system uranyl nitrate, nitric acid, water and 30 vol % TBP in n-dodecane, at 25 0 C and 40 0 C. The theoretical equilibrium data, obtained with the aid of a computer, are compared with the experimental results. (Author) [pt

  20. Effects of intragastric fructose and dextrose on mesenteric microvascular inflammation and postprandial hyperemia in the rat. (United States)

    Mattioli, Leone F; Thomas, James H; Holloway, Naomi B; Schropp, Kurt P; Wood, John G


    Fructose superfused on the mesenteric venules of rats induces microvascular inflammation via oxidative stress. It is unknown whether intragastric fructose exerts a similar effect and whether fructose impairs postprandial hyperemia (PPH). The goals were to determine whether intragastric fructose administration promotes leukocyte adherence and whether fructose, owing to its oxidative properties, may also impair nitric oxide-dependent PPH in the mesenteric microcirculation of rats. Leukocyte adherence to mesenteric venules, arteriolar velocity, and diameter were measured in Sprague-Dawley rats before and 30 minutes after intragastric (1 mL 0.5 M, ~0.3 g/kg) dextrose (n = 5), fructose (n = 6), and fructose after intravenous injection of the antioxidant α-lipoic acid (ALA, n = 6). Only fructose increased leukocyte adherence: control 2.3 ± 0.3 per 100 µm; fructose 9.7 ± 1.4 per 100 µm (P .05, r(2) = 0.083 for shear rate vs leukocyte adherence). Dextrose had no effect on leukocyte adherence: control 1.52 ± 0.13 per 100 µm; dextrose 2.0 ± 0.7 per 100 µm (P > .05). ALA prevented fructose-induced leukocyte adherence: control 1.9 ± 0.2 per 100 µm; fructose + ALA 1.8 ± 0.3 per 100 µm (P > .05). Neither fructose nor dextrose induced PPH: arteriolar velocity: control 3.3 ± 0.49 cm/s, fructose 3.06 ± 0.34 cm/s (P > .05); control 3.3 ± 1.0 cm/s, dextrose 3.15 ± 1.1 cm/s (P > .05); arteriolar diameter: control 19.9 ± 1.10 µm, fructose 19.7 ± 1.0 µm (P > .05); control 21.5 ± 2.6, dextrose 20.0 ± 2.7 µm (P > .05). Intragastric fructose induced leukocyte adherence via oxidative stress. Neither dextrose nor fructose induced PPH, likely because of the inhibitory effect of anesthesia on splanchnic vasomotor tone.

  1. Nitric oxide-induced interstrand cross-links in DNA. (United States)

    Caulfield, Jennifer L; Wishnok, John S; Tannenbaum, Steven R


    The DNA damaging effects of nitrous acid have been extensively studied, and the formation of interstrand cross-links have been observed. The potential for this cross-linking to occur through a common nitrosating intermediate derived from nitric oxide is investigated here. Using a HPLC laser-induced fluorescence (LIF) system, the amount of interstrand cross-link formed on nitric oxide treatment of the 5'-fluorescein-labeled oligomer ATATCGATCGATAT was determined. This self-complimentary sequence contains two 5'-CG sequences, which is the preferred site for nitrous acid-induced cross-linking. Nitric oxide was delivered to an 0.5 mM oligomer solution at 15 nmol/mL/min to give a final nitrite concentration of 652 microM. The resulting concentration of the deamination product, xanthine, in this sample was found to be 211 +/- 39 nM, using GC/MS, and the amount of interstrand cross-link was determined to be 13 +/- 2.5 nM. Therefore, upon nitric oxide treatment, the cross-link is found at approximately 6% of the amount of the deamination product. Using this system, detection of the cross-link is also possible for significantly lower doses of nitric oxide, as demonstrated by treatment of the same oligomer with NO at a rate of 18 nmol/mL/min resulting in a final nitrite concentration of 126 microM. The concentration of interstrand cross-link was determined to be 3.6 +/- 0.1 nM in this sample. Therefore, using the same dose rate, when the total nitric oxide concentration delivered drops by a factor of approximately 5, the concentration of cross-link drops by a factor of about 4-indicating a qausi-linear response. It may now be possible to predict the number of cross-links in a small genome based on the number of CpG sequences and the yield of xanthine derived from nitrosative deamination.

  2. 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


    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

  3. 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.


    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

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

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R


    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 FFM-1.min-1, P

  5. [Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer]. (United States)

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


    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.

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

    African Journals Online (AJOL)

    Bassma M. El Sabaa


    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.

  7. The altered balance between sympathetic nervous system and nitric oxide in salt hypertensive Dahl rats: ontogenetic and F2 hybrid studies

    Czech Academy of Sciences Publication Activity Database

    Dobešová, Zdenka; Kuneš, Jaroslav; Zicha, Josef


    Roč. 20, č. 5 (2002), s. 945-955 ISSN 0263-6352 R&D Projects: GA AV ČR IAA7011805; GA AV ČR IAA7011711; GA MŠk LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : salt hypertension * sympathetic nervous system * Dahl rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.534, year: 2002

  8. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M


    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  9. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)



    May 24, 2010 ... chronic periodontitis (CP), 31 with gingivitis (G) and 50 healthy controls. Probing depth ..... Periodontal disease in pregnancy I. Prevalence and severity. ... endothelial nitric oxide synthase gene in premenopausal women with.

  10. Flavonoids as scavengers of nitric oxide radical.

    NARCIS (Netherlands)

    van Acker, S.A.B.E.; Tromp, M.N.J.L.; Haenen, G.R.M.M.; van der Vijgh, W.J.F.; Bast, A.


    Flavonoids are a group of naturally occurring compounds used, e.g., in the treatment of vascular endothelial damage. They are known to be excellent scavengers of oxygen free radicals. Since the nitric oxide radical (

  11. Fate of aliphatic compounds in nitric acid processing solutions

    International Nuclear Information System (INIS)

    Clark, W.E.; Howerton, W.B.


    The reaction of hyperazeotropic iodic acid-saturated nitric acid with short chain aliphatic iodides, nitrates, and acids was studied in order to determine the conditions for complete removal of organic materials from nitric acid systems. The aliphatic iodides are converted to the nitrates and the nitrates in strong HNO 3 are extensively converted into CO 2 and acids. The aliphatic acids are rather stable; acetic acid was unattacked by boiling in 20M HNO 3 and n-butyric acid was 80 percent unattacked. The dibasic acids oxalic and malonic are extensively attacked, but succinic acid is relatively stable. A wet oxidation method is successful in destroying acetic acid in 5 to 8M HNO 3 . (U.S.)

  12. Microvascular dysfunction in the immediate aftermath of chronic total coronary occlusion recanalization. (United States)

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


    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.

  13. Improved myocardial perfusion after transmyocardial laser revascularization in a patient with microvascular coronary artery disease

    Directory of Open Access Journals (Sweden)

    Peyman Mesbah Oskui


    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.

  14. Nitric oxide in the stress axis


    Lopez-Figueroa, M.O.; Day, H.E.W.; Akil, H.; Watson, S.J.


    In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbichypothalamic- ...

  15. Striated muscle microvascular response to silver implants: A comparative in vivo study with titanium and stainless steel. (United States)

    Kraft, C N; Hansis, M; Arens, S; Menger, M D; Vollmar, B


    Local microvascular perfusion is the primary line of defense of tissue against microorganisms and plays a considerable role in reparative processes. The impairment of the microcirculation by a biomaterial may therefore have profound consequences. Silver is known to have excellent antimicrobial activity and, although regional and systemic toxic effects have been described, silver is regularly discussed as an implant material in bone surgery. Because little is known about the influence of silver implants on the adjacent host tissue microvasculature, we studied in vivo nutritive perfusion and leukocytic response, and compared these results with those of the conventionally used materials titanium and stainless steel. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, the implantation of a commercially pure silver sample led to a distinct and persistent activation of leukocytes combined with a marked disruption of the microvascular endothelial integrity, massive leukocyte extravasation, and considerable venular dilation. Whereas animals with stainless-steel implants showed a moderate increase in these parameters with a tendency to recuperate, titanium implants caused only a transient increase of leukocyte-endothelial cell interaction within the first 120 min and no significant change in macromolecular leakage, leukocyte extravasation and venular diameter. After 3 days, five of six preparations with silver samples showed severe inflammation and massive edema. Thus, the use of silver as an implant material should be critically judged despite its bactericidal properties. The implant material titanium seems to be well tolerated by the local vascular system and currently represents the golden standard. Copyright 2000 John Wiley & Sons, Inc.

  16. Dinitrosyl iron complexes and S-nitrosothiols are two possible forms for stabilization and transport of nitric oxide in biological systems. (United States)

    Vanin, A F


    The physicochemical properties, mechanisms of synthesis and decomposition of dinitrosyl iron complexes (DNICs) with thiol-containing ligands and of S-nitrosothiols (RS-NO), and the potential role of these compounds in storage and transport of NO in biological systems are reviewed. Special attention is given to the phenomenon of mutual transformation of DNIC and RS-NO catalyzed by Fe2+. Each Fe2+ binds two neutral NO molecules in the DNICs, catalyzes their mutual oxidation--reduction with formation of nitrous oxide and nitrosonium ions appearing in the DNICs. These ions S-nitrosate thiol-compounds with RS-NO formation. Fe2+ binds two RS-NO molecules and catalyzes their mutual oxidation--reduction followed by decomposition of the resulting molecules. Mutual conversion of DNICs and RS-NO regulated by iron, thiol, and NO levels is suggested to provide NO transport in cells and tissues.

  17. Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and L-arginine metabolism in mice. (United States)

    Ito, Tatsuo; Kubo, Masayuki; Nagaoka, Kenjiro; Funakubo, Narumi; Setiawan, Heri; Takemoto, Kei; Eguchi, Eri; Fujikura, Yoshihisa; Ogino, Keiki


    Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO 2 - were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO 2 - levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO 2 - levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

  18. Evaluation of microvascular endothelial function in patients with infective endocarditis using laser speckle contrast imaging and skin video-capillaroscopy: research proposal of a case control prospective study. (United States)

    Barcelos, Amanda; Lamas, Cristiane; Tibiriça, Eduardo


    Infective endocarditis is a severe condition with high in-hospital and 5-year mortality. There is increasing incidence of infective endocarditis, which may be related to healthcare and changes in prophylaxis recommendations regarding oral procedures. Few studies have evaluated the microcirculation in patients with infective endocarditis, and so far, none have utilized laser-based technology or evaluated functional capillary density. The aim of the study is to evaluate the changes in the systemic microvascular bed of patients with both acute and subacute endocarditis. This is a cohort study that will include adult patients with confirmed active infective endocarditis according to the modified Duke criteria who were admitted to our center for treatment. A control group of sex- and age-matched healthy volunteers will be included. Functional capillary density, which is defined as the number of spontaneously perfused capillaries per square millimeter of skin, will be assessed by video-microscopy with an epi-illuminated fiber optic microscope. Capillary recruitment will be evaluated using post-occlusive reactive hyperemia. Microvascular flow will be evaluated in the forearm using a laser speckle contrast imaging system for the noninvasive and continuous measurement of cutaneous microvascular perfusion changes. Laser speckle contrast imaging will be used in combination with skin iontophoresis of acetylcholine, an endothelium-dependent vasodilator, or sodium nitroprusside (endothelium independent) to test microvascular reactivity. The present study will contribute to the investigation of microcirculatory changes in infective endocarditis and possibly lead to an earlier diagnosis of the condition and/or determination of its severity and complications. Trial registration ID: NCT02940340.

  19. Glufosinate ammonium stimulates nitric oxide production through N-methyl D-aspartate receptors in rat cerebellum. (United States)

    Nakaki, T; Mishima, A; Suzuki, E; Shintani, F; Fujii, T


    Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal ingredient. The neuronal activities of this compound were investigated by use of a microdialysis system that allowed us to measure nitric oxide production in the rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10 microliter), which were administered through the microdialysis probe at a rate of 1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate ammonium-elicited increase in nitric oxide production was suppressed by an inhibitor of nitric oxide synthase and was antagonized by NMDA receptor antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist. These results suggest that glufosinate ammonium stimulates nitric oxide production through NMDA receptors.

  20. Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and pulmonary hypertension. (United States)

    Ruisi, Phillip; Ruisi, Michael


    Carbon monoxide (CO) has been widely recognized as an exogenous poison, although endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms, more specifically HO-1, in the setting of oxidative stress such as acute respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO) therapy is used to selectively vasodilate the pulmonary vasculature and improve ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic dissemination. Several experimental design studies involving lab rats have demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of nitric oxide HO-1 induction.

  1. Localization and expression of molt-inhibiting hormone and nitric oxide synthase in the central nervous system of the green shore crab, Carcinus maenas, and the blackback land crab, Gecarcinus lateralis. (United States)

    Pitts, Natalie L; Mykles, Donald L


    In decapod crustaceans, molting is controlled by the pulsatile release of molt-inhibiting hormone (MIH) from neurosecretory cells in the X-organ/sinus gland (XO/SG) complex in the eyestalk ganglia (ESG). A drop in MIH release triggers molting by activating the molting gland or Y-organ (YO). Post-transcriptional mechanisms ultimately control MIH levels in the hemolymph. Neurotransmitter-mediated electrical activity controls Ca 2+ -dependent vesicular release of MIH from the SG axon terminals, which may be modulated by nitric oxide (NO). In green shore crab, Carcinus maenas, nitric oxide synthase (NOS) protein and NO are present in the SG. Moreover, C. maenas are refractory to eyestalk ablation (ESA), suggesting other regions of the nervous system secrete sufficient amounts of MIH to prevent molting. By contrast, ESA induces molting in the blackback land crab, Gecarcinus lateralis. Double-label immunofluorescence microscopy and quantitative polymerase chain reaction were used to localize and quantify MIH and NOS proteins and transcripts, respectively, in the ESG, brain, and thoracic ganglion (TG) of C. maenas and G. lateralis. In ESG, MIH- and NOS-immunopositive cells were closely associated in the SG of both species; confocal microscopy showed that NOS was localized in cells adjacent to MIH-positive axon terminals. In brain, MIH-positive cells were located in a small number of cells in the olfactory lobe; no NOS immunofluorescence was detected. In TG, MIH and NOS were localized in cell clusters between the segmental nerves. In G. lateralis, Gl-MIH and Gl-crustacean hyperglycemic hormone (CHH) mRNA levels were ~10 5 -fold higher in ESG than in brain or TG of intermolt animals, indicating that the ESG is the primary source of these neuropeptides. Gl-NOS and Gl-elongation factor (EF2) mRNA levels were also higher in the ESG. Molt stage had little or no effect on CHH, NOS, NOS-interacting protein (NOS-IP), membrane Guanylyl Cyclase-II (GC-II), and NO-independent GC

  2. The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Talman W.T.


    Full Text Available Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO, S-nitrosoacetylpenicillamine (SNAP, and S-nitroso-D-cysteine (D-SNC produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1 the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2 L- and D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an

  3. Effective plasmid DNA and small interfering RNA delivery to diseased human brain microvascular endothelial cells. (United States)

    Slanina, H; Schmutzler, M; Christodoulides, M; Kim, K S; Schubert-Unkmeir, A


    Expression of exogenous DNA or small interfering RNA (siRNA) in vitro is significantly affected by the particular delivery system utilized. In this study, we evaluated the transfection efficiency of plasmid DNA and siRNA into human brain microvascular endothelial cells (HBMEC) and meningioma cells, which constitute the blood-cerebrospinal fluid barrier, a target of meningitis-causing pathogens. Chemical transfection methods and various lipofection reagents including Lipofectamin™, FuGene™, or jetPRIME®, as well as physical transfection methods and electroporation techniques were applied. To monitor the transfection efficiencies, HBMEC and meningioma cells were transfected with the reporter plasmid pTagGFP2-actin vector, and efficiency of transfection was estimated by fluorescence microscopy and flow cytometry. We established protocols based on electroporation using Cell Line Nucleofector® Kit V with the Amaxa® Nucleofector® II system from Lonza and the Neon® Transfection system from Invitrogen resulting in up to 41 and 82% green fluorescent protein-positive HBMEC, respectively. Optimal transfection solutions, pulse programs and length were evaluated. We furthermore demonstrated that lipofection is an efficient method to transfect meningioma cells with a transfection efficiency of about 81%. Finally, we applied the successful electroporation protocols to deliver synthetic siRNA to HBMEC and analyzed the role of the actin-binding protein cortactin in Neisseria meningitidis pathogenesis. Copyright © 2012 S. Karger AG, Basel.

  4. Exercise promotes collateral artery growth mediated by monocytic nitric oxide. (United States)

    Schirmer, Stephan H; Millenaar, Dominic N; Werner, Christian; Schuh, Lisa; Degen, Achim; Bettink, Stephanie I; Lipp, Peter; van Rooijen, Nico; Meyer, Tim; Böhm, Michael; Laufs, Ulrich


    Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion. It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOS-deficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth. © 2015 American Heart Association, Inc.

  5. Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.

    Directory of Open Access Journals (Sweden)

    Vivekanandhan Aravindhan

    Full Text Available Lipopolysaccharide (LPS/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM and its complications. Endotoxin core antibodies (EndoCAb, LPS binding protein (LBP and soluble CD14 (sCD14 act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF.A total of 197 subjects (64 normal glucose tolerance (NGT subjects, 97 T1DM subjects without MVC and 36 with MVC were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays.Compared to NGT, T1DM subjects (both with and without MVC had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p<0.05. No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC.Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications.

  6. Americium removal from nitric acid waste streams

    International Nuclear Information System (INIS)

    Muscatello, A.C.; Navratil, J.D.


    Separations research at the Rocky Flats Plant (RFP) has found ways to significantly improve americium removal from nitric acid (7M) waste streams generated by plutonium purification operations. Partial neutralization of the acid waste followed by solid supported liquid membranes (SLM) are useful in transferring and concentrating americium from nitrate solutions. Specifically, DHDECMP (dihexyl-N,N-diethylcarbamoylmethylphosphonate) supported on Accurel polypropylene hollow fibers assembled in modular form transfers >95% of the americium from high nitrate (6.9M), low acid (0.1M) feeds into 0.25M oxalic acid stripping solution. Maximum permeabilities were observed to be 0.001 cm/sec, consistent with typical values for other systems. The feed:strip volume ratio shows an inverse relationship to the fraction of metal ion transferred. Cation exchangers may be used to concentrate americium from the strip solution. Furthermore, O0D (iB)CMPO (or CMPO) (octylphenyl-N-N-diisobutylcarbamoylmethylphosphine oxide) has been tested in an extraction chromatography mode. Preliminary results show CMPO to be effective in removing americium if the feed is neutralized to 1.0M acidity and iron(III) is complexed with 0.20M oxalic acid. 3 figs

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


    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.

  8. Quantitative and qualitative retinal microvascular characteristics and blood pressure. (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


    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.

  9. Biomarker for early renal microvascular and diabetic kidney diseases. (United States)

    Futrakul, Narisa; Futrakul, Prasit


    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.

  10. CNN-SVM for Microvascular Morphological Type Recognition with Data Augmentation. (United States)

    Xue, Di-Xiu; Zhang, Rong; Feng, Hui; Wang, Ya-Lei


    This paper focuses on the problem of feature extraction and the classification of microvascular morphological types to aid esophageal cancer detection. We present a patch-based system with a hybrid SVM model with data augmentation for intraepithelial papillary capillary loop recognition. A greedy patch-generating algorithm and a specialized CNN named NBI-Net are designed to extract hierarchical features from patches. We investigate a series of data augmentation techniques to progressively improve the prediction invariance of image scaling and rotation. For classifier boosting, SVM is used as an alternative to softmax to enhance generalization ability. The effectiveness of CNN feature representation ability is discussed for a set of widely used CNN models, including AlexNet, VGG-16, and GoogLeNet. Experiments are conducted on the NBI-ME dataset. The recognition rate is up to 92.74% on the patch level with data augmentation and classifier boosting. The results show that the combined CNN-SVM model beats models of traditional features with SVM as well as the original CNN with softmax. The synthesis results indicate that our system is able to assist clinical diagnosis to a certain extent.

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


    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

  12. Microvascular versus macrovascular cerebral vasomotor reactivity in patients with severe internal carotid artery stenosis or occlusion. (United States)

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


    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.

  13. Transfer of Learning from Practicing Microvascular Anastomosis on Silastic Tubes to Rat Abdominal Aorta. (United States)

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


    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.

  14. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    Directory of Open Access Journals (Sweden)

    Almeida A


    Full Text Available Laurinda Lemos1,2, Carlos Alegria3, Joana Oliveira3, Ana Machado2, Pedro Oliveira4, Armando Almeida11Life and Health Sciences Research Institute (ICVS, School of Health Sciences, Campus de Gualtar, University of Minho, Braga, Portugal; 2Hospital Center of Alto Ave, Unit of Fafe, Fafe, Portugal; 3Department of Neurosurgery, Hospital São Marcos; 4Products and Systems Engineering, Campus de Azurém, University of Minho, Guimarães, PortugalAbstract: In idiopathic trigeminal neuralgia (TN the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1 a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol], (2 the association of gabapentin (GBP and analgesic block of trigger-points with ropivacaine (ROP (GBP+ROP protocol, and (3 a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol. Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols from cases of idiopathic TN, or selected for MVD surgery (n = 22 due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug

  15. Evaporation and NARS Nitric Acid Mass Balance Summary: 2000--2005

    International Nuclear Information System (INIS)

    Kreutzberg, B.D.; Ames, R.L.; Hansel, K.M.


    A compilation of the historical nitric acid processing data for the evaporation and nitric acid recycle system (NARS) in TA-55 has provided general acid mass balance trends, as well as the location of missing information in both the evaporation system and NARS data logs. The data were accumulated during the calendar years 2000 to 2005. After making a number of processing assumptions, the empirical system information was used to create an interactive spreadsheet that predicts, with moderate accuracy, some of the various stream variables for the combined evaporation and acid recycle processes. Empirical data and interactive calculations were compared to an Aspen Plus(trademark) simulation of the process

  16. The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function. (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


    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.

  17. Plasmalemmal V-H+-ATPases regulate intracellular pH in human lung microvascular endothelial cells

    International Nuclear Information System (INIS)

    Rojas, Jose D.; Sennoune, Souad R.; Maiti, Debasish; Martinez, Gloria M.; Bakunts, Karina; Wesson, Donald E.; Martinez-Zaguilan, Raul


    The lung endothelium layer is exposed to continuous CO 2 transit which exposes the endothelium to a substantial acid load that could be detrimental to cell function. The Na + /H + exchanger and HCO 3 - -dependent H + -transporting mechanisms regulate intracellular pH (pH cyt ) in most cells. Cells that cope with high acid loads might require additional primary energy-dependent mechanisms. V-H + -ATPases localized at the plasma membranes (pmV-ATPases) have emerged as a novel pH regulatory system. We hypothesized that human lung microvascular endothelial (HLMVE) cells use pmV-ATPases, in addition to Na + /H + exchanger and HCO 3 - -based H + -transporting mechanisms, to maintain pH cyt homeostasis. Immunocytochemical studies revealed V-H + -ATPase at the plasma membrane, in addition to the predicted distribution in vacuolar compartments. Acid-loaded HLMVE cells exhibited proton fluxes in the absence of Na + and HCO 3 - that were similar to those observed in the presence of either Na + , or Na + and HCO 3 - . The Na + - and HCO 3 - -independent pH cyt recovery was inhibited by bafilomycin A 1 , a V-H + -ATPase inhibitor. These studies show a Na + - and HCO 3 - -independent pH cyt regulatory mechanism in HLMVE cells that is mediated by pmV-ATPases

  18. Physical exercise restores microvascular function in obese rats with metabolic syndrome. (United States)

    Machado, Marcus Vinicius; Vieira, Aline Bomfim; Nascimento, Alessandro Rodrigues; Martins, Rômulo Lanza; Daleprane, Julio Beltrame; Lessa, Marcos Adriano; Tibiriçá, Eduardo


    Obesity and metabolic syndrome are related to systemic functional microvascular alterations, including a significant reduction in microvessel density. The aim of this study was to investigate the effects of exercise training on functional capillary density in the skeletal muscle and skin of obese rats with metabolic syndrome. We used male Wistar-Kyoto rats that had been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks. Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and anthropometric parameters; and functional capillary density were assessed. In addition, a maximal exercise test was performed. Exercise training increased the VO2max (69 ± 3 mL/kg per min) and exercise tolerance (30 ± 1 min) compared with the HFD+SED (41 ± 6 mL/kg per min, P Exercise training also increased the number of spontaneously perfused capillaries in the skeletal muscle (252 ± 9 vs. 207 ± 9 capillaries/mm(2)) of the training group compared with that in the sedentary animals (260 ± 15 capillaries/mm(2)). These results demonstrate that exercise training reverses capillary rarefaction in our experimental model of metabolic syndrome and obesity.

  19. Zika Virus Infects, Activates, and Crosses Brain Microvascular Endothelial Cells, without Barrier Disruption (United States)

    Papa, Michelle P.; Meuren, Lana M.; Coelho, Sharton V. A.; Lucas, Carolina G. de Oliveira; Mustafá, Yasmin M.; Lemos Matassoli, Flavio; Silveira, Paola P.; Frost, Paula S.; Pezzuto, Paula; Ribeiro, Milene R.; Tanuri, Amilcar; Nogueira, Mauricio L.; Campanati, Loraine; Bozza, Marcelo T.; Paula Neto, Heitor A.; Pimentel-Coelho, Pedro M.; Figueiredo, Claudia P.; de Aguiar, Renato S.; de Arruda, Luciana B.


    Zika virus (ZIKV) has been associated to central nervous system (CNS) harm, and virus was detected in the brain and cerebrospinal fluids of microcephaly and meningoencephalitis cases. However, the mechanism by which the virus reaches the CNS is unclear. Here, we addressed the effects of ZIKV replication in human brain microvascular endothelial cells (HBMECs), as an in vitro model of blood brain barrier (BBB), and evaluated virus extravasation and BBB integrity in an in vivo mouse experimental model. HBMECs were productively infected by African and Brazilian ZIKV strains (ZIKVMR766 and ZIKVPE243), which induce increased production of type I and type III IFN, inflammatory cytokines and chemokines. Infection with ZIKVMR766 promoted earlier cellular death, in comparison to ZIKVPE243, but infection with either strain did not result in enhanced endothelial permeability. Despite the maintenance of endothelial integrity, infectious virus particles crossed the monolayer by endocytosis/exocytosis-dependent replication pathway or by transcytosis. Remarkably, both viruses' strains infected IFNAR deficient mice, with high viral load being detected in the brains, without BBB disruption, which was only detected at later time points after infection. These data suggest that ZIKV infects and activates endothelial cells, and might reach the CNS through basolateral release, transcytosis or transinfection processes. These findings further improve the current knowledge regarding ZIKV dissemination pathways. PMID:29312238

  20. Interactive virtual simulation using a 3D computer graphics model for microvascular decompression surgery. (United States)

    Oishi, Makoto; Fukuda, Masafumi; Hiraishi, Tetsuya; Yajima, Naoki; Sato, Yosuke; Fujii, Yukihiko


    The purpose of this paper is to report on the authors' advanced presurgical interactive virtual simulation technique using a 3D computer graphics model for microvascular decompression (MVD) surgery. The authors performed interactive virtual simulation prior to surgery in 26 patients with trigeminal neuralgia or hemifacial spasm. The 3D computer graphics models for interactive virtual simulation were composed of the brainstem, cerebellum, cranial nerves, vessels, and skull individually created by the image analysis, including segmentation, surface rendering, and data fusion for data collected by 3-T MRI and 64-row multidetector CT systems. Interactive virtual simulation was performed by employing novel computer-aided design software with manipulation of a haptic device to imitate the surgical procedures of bone drilling and retraction of the cerebellum. The findings were compared with intraoperative findings. In all patients, interactive virtual simulation provided detailed and realistic surgical perspectives, of sufficient quality, representing the lateral suboccipital route. The causes of trigeminal neuralgia or hemifacial spasm determined by observing 3D computer graphics models were concordant with those identified intraoperatively in 25 (96%) of 26 patients, which was a significantly higher rate than the 73% concordance rate (concordance in 19 of 26 patients) obtained by review of 2D images only (p computer graphics model provided a realistic environment for performing virtual simulations prior to MVD surgery and enabled us to ascertain complex microsurgical anatomy.

  1. Teflon granulomas mimicking cerebellopontine angle tumors following microvascular decompression. (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


    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.

  2. [Macrovascular and microvascular complications in type 2 diabetes patients]. (United States)

    Rosolová, H; Petrlová, B; Simon, J; Sifalda, P; Sípová, I; Sefrna, F


    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.

  3. Persistent hemifacial spasm after microvascular decompression: a risk assessment model. (United States)

    Shah, Aalap; Horowitz, Michael


    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.

  4. 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.

  5. Reduction Rates for Higher Americium Oxidation States in Nitric Acid

    Energy Technology Data Exchange (ETDEWEB)

    Grimes, Travis Shane [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mincher, Bruce Jay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmitt, Nicholas C [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    The stability of hexavalent americium was measured using multiple americium concentrations and nitric acid concentrations after contact with the strong oxidant sodium bismuthate. Contrary to our hypotheses Am(VI) was not reduced faster at higher americium concentrations, and the reduction was only zero-order at short time scales. Attempts to model the reduction kinetics using zero order kinetic models showed Am(VI) reduction in nitric acid is more complex than the autoreduction processes reported by others in perchloric acid. The classical zero-order reduction of Am(VI) was found here only for short times on the order of a few hours. We did show that the rate of Am(V) production was less than the rate of Am(VI) reduction, indicating that some Am(VI) undergoes two electron-reduction to Am(IV). We also monitored the Am(VI) reduction in contact with the organic diluent dodecane. A direct comparison of these results with those in the absence of the organic diluent showed the reduction rates for Am(VI) were not statistically different for both systems. Additional americium oxidations conducted in the presence of Ce(IV)/Ce(III) ions showed that Am(VI) is reduced without the typical growth of Am(V) observed in the systems sans Ce ion. This was an interesting result which suggests a potential new reduction/oxidation pathway for Am in the presence of Ce; however, these results were very preliminary, and will require additional experiments to understand the mechanism by which this occurs. Overall, these studies have shown that hexavalent americium is fundamentally stable enough in nitric acid to run a separations process. However, the complicated nature of the reduction pathways based on the system components is far from being rigorously understood.

  6. 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


    -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...

  7. 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


    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

  8. Containment of Nitric Acid Solutions of Plutonium-238

    International Nuclear Information System (INIS)

    Reimus, M.A.H.; Silver, G.L.; Pansoy-Hjelvik, L.; Ramsey, K.


    The corrosion of various metals that could be used to contain nitric acid solutions of Pu-238 has been studied. Tantalum and tantalum/2.5% tungsten resisted the test solvent better than 304L stainless steel and several INCONEL alloys. The solvent used to imitate nitric acid solutions of Pu-238 contained 70% nitric acid, hydrofluoric acid, and ammonium hexanitratocerate

  9. Myeloperoxidase potentiates nitric oxide-mediated nitrosation. (United States)

    Lakshmi, Vijaya M; Nauseef, William M; Zenser, Terry V


    Nitrosation is an important reaction elicited by nitric oxide (NO). To better understand how nitrosation occurs in biological systems, we assessed the effect of myeloperoxidase (MPO), a mediator of inflammation, on nitrosation observed during NO autoxidation. Nitrosation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; 10 mum) to 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ) was monitored by HPLC. Using the NO donor spermine NONOate at pH 7.4, MPO potentiated N-NO-IQ formation. The minimum effective quantity of necessary components was 8.5 nm MPO, 0.25 mum H(2)O(2)/min, and 0.024 mum NO/min. Autoxidation was only detected at >/=1.2 mum NO/min. MPO potentiation was not affected by a 40-fold excess flux of H(2)O(2) over NO or less than a 2.4-fold excess flux of NO over H(2)O(2). Potentiation was due to an 8.8-fold increased affinity of MPO-derived nitrosating species for IQ. Autoxidation was inhibited by azide, suggesting involvement of the nitrosonium ion, NO(+). MPO potentiation was inhibited by NADH, but not azide, suggesting oxidative nitrosylation with NO(2)(.) or an NO(2)(.)-like species. MPO nonnitrosative oxidation of IQ with 0.3 mm NO(2)(-) at pH 5.5 was inhibited by azide, but not NADH, demonstrating differences between MPO oxidation of IQ with NO compared with NO(2)(-). Using phorbol ester-stimulated human neutrophils, N-NO-IQ formation was increased with superoxide dismutase and inhibited by catalase and NADH, but not NaN(3). This is consistent with nitrosation potentiation by MPO, not peroxynitrite. Increased N-NO-IQ formation was not detected with polymorphonuclear neutrophils from two unrelated MPO-deficient patients. Results suggest that the highly diffusible stable gas NO could initiate nitrosation at sites of neutrophil infiltration.

  10. 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.


    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

  11. Microvascular endothelial function and cognitive performance: The ELSA-Brasil cohort study. (United States)

    Brant, Luisa; Bos, Daniel; Araujo, Larissa Fortunato; Ikram, M Arfan; Ribeiro, Antonio Lp; Barreto, Sandhi M


    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.

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


    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.

  13. Electroreduction of nitric acid to hydroxylamine

    International Nuclear Information System (INIS)

    Haque, I.U.; Saima, W.


    This article reviews recent studies concerned with the synthesis of hydroxylamine Hydroxylamine plays a significant role in agriculture, photographic developing, as a component in liquid propellants and as a reducing agent etc. In this regard modification of carbon electrode surface greatly increases hydrogen overpotential in nitric acid solutions and allows electrochemical generation of hydroxylamine with good current efficiency. (author)

  14. ORIGINAL ARTICLE Relationship between endothelial nitric oxide ...

    African Journals Online (AJOL)


    The haplotype analysis confirmed ... hand, no consistent association was shown between the two SNPs and SBP or. DBP. ... Endothelial nitric oxide synthase gene polymorphisms and risk of MI .... type (-786T*+894G), the haplotypes ... Tests adjusted for age, BMI, diabetes, current smoking and alcohol consumption.

  15. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

  16. Nitric oxide enhances osmoregulation of tobacco ( Nicotiana ...

    African Journals Online (AJOL)

    This study was carried out to investigate the effect of the intracellular signaling molecule nitric oxide (NO) on osmoregulation of tobacco cells under osmotic stress caused by phenylethanoid glycosides 6000 (PEG 6000). The results show that the PEG stress induced a specific pattern of endogenous NO production with two ...

  17. Assessment of macrovascular endothelial function using pulse wave analysis and its association with microvascular reactivity in healthy subjects. (United States)

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


    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.

  18. 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


    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...

  19. eNOS对糖尿病视网膜病变的研究进展%Research Progress of Endothelial Nitric Oxide Synthase on Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    汪权志; 夏媛玲


    糖尿病视网膜病变(diabetic retinopathy ,DR)是糖尿病在眼部常见并发症,微血管的病变导致相关并发症严重影响患者视觉和生活质量。而内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)作为血管内皮细胞代谢中的限速酶,在糖尿病视网膜病变(diabetic retinopathy ,DR)疾病进展中可能有一定的作用。本文对内皮型一氧化氮合酶在糖尿病视网膜病变研究进展进行综述。%Diabetic retinopathy is a common complication of diabetes in the eye, microvascular disease-related complications seriously affect the patient's visual and quality of life. Endothelial nitric oxide synthase, a rate-limiting enzyme in the metabolism of vascular endothelial cells, may play a role in the progression of diabetic retinopathy. This review summarizes the progress of endothelial nitric oxide synthase in diabetic retinopathy.

  20. Concomitant macro and microvascular complications in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Alwakeel Jamal


    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

  1. 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


    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

  2. 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)


    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

  3. Enhanced Local Skeletal Muscle Oxidative Capacity and Microvascular Blood Flow Following 7-Day Ischemic Preconditioning in Healthy Humans

    Directory of Open Access Journals (Sweden)

    Owen Jeffries


    Full Text Available Ischemic preconditioning (IPC, which involves intermittent periods of ischemia followed by reperfusion, is an effective clinical intervention that reduces the risk of myocardial injury and confers ischemic tolerance to skeletal muscle. Repeated bouts of IPC have been shown to stimulate long-term changes vascular function, however, it is unclear what metabolic adaptations may occur locally in the muscle. Therefore, we investigated 7 days of bilateral lower limb IPC (4 × 5 min above limb occlusion pressure (220 mmHg; n = 10, or sham (20 mmHg; n = 10, on local muscle oxidative capacity and microvascular blood flow. Oxidative capacity was measured using near-infrared spectroscopy (NIRS during repeated short duration arterial occlusions (300 mmHg. Microvascular blood flow was assessed during the recovery from submaximal isometric plantar flexion exercises at 40 and 60% of maximal voluntary contraction (MVC. Following the intervention period, beyond the late phase of protection (72 h, muscle oxidative recovery kinetics were speeded by 13% (rate constant pre 2.89 ± 0.47 min-1 vs. post 3.32 ± 0.69 min-1; P < 0.05 and resting muscle oxygen consumption (mO2 was reduced by 16.4% (pre 0.39 ± 0.16%.s-1 vs. post 0.33 ± 0.14%.s-1; P < 0.05. During exercise, changes in deoxygenated hemoglobin (HHb from rest to steady state were reduced at 40 and 60% MVC (16 and 12%, respectively, P < 0.05 despite similar measures of total hemoglobin (tHb. At the cessation of exercise, the time constant for recovery in oxygenated hemoglobin (O2Hb was accelerated at 40 and 60% MVC (by 33 and 43%, respectively suggesting enhanced reoxygenation in the muscle. No changes were reported for systemic measures of resting heart rate or blood pressure. In conclusion, repeated bouts of IPC over 7 consecutive days increased skeletal muscle oxidative capacity and microvascular muscle blood flow. These findings are consistent with enhanced mitochondrial and vascular function following

  4. Characteristics and mechanism of explosive reactions of Purex solvents with Nitric Acid at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Teijiro [Radiation Application Development Association, Tokai, Ibaraki (Japan); Takada, Junichi; Koike, Tadao; Tsukamoto, Michio; Watanabe, Koji [Department of Fuel Cycle Safety Research, Nuclear Safety Research Center, Tokai Research Establishment, Japan Atomic Energy Research Institute, Tokai, Ibaraki (Japan); Ida, Masaaki [JGC PLANTECH CO., LTD (Japan); Nakagiri, Naotaka [JGC Corp., Tokyo (Japan); Nishio, Gunji [Research Organization for Information Science and Technology, Tokai, Ibaraki (Japan)


    This investigation was undertaken to make clear the energetic properties and mechanism of explosive decomposition of Purex solvent systems (TBP/n-Dodecane/HNO{sub 3}) by Nitric Acid at elevated temperatures using a calorimetric technique (DSC, ARC) and a chromatographic technique (GC, GC/MS). The measurement of exothermic events of solvent-HNO{sub 3} reactions using DSC with a stainless steel sealed cell showed distinct two peaks with maxima at around 170 and 320degC, respectively. The peak at around 170degC was mainly attributed to the reactions of dealkylation products (n-butyl nitrate) of TBP and the solvent with nitric acid, and the peak at around 320degC was attributed to the exothermic decomposition of nitrated dodecanes formed in the foregoing exothermic reaction of dodecane with nitric acid. By using the data obtained in ARC experiments, activation energies of 123.2 and 152.5 kJ/mol were determined for the exothermic reaction of TBP with nitric acid and for the exothermic pyrolysis of n-butyl nitrate, respectively. Some possible pathways were considered for the explosive decomposition of TBP by nitric acid at elevated temperatures. (author)

  5. Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression. (United States)

    Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen


    The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Study of Nitric Oxide production by murine peritoneal macrophages induced by Brucella Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Kavoosi G


    Full Text Available Brueclla is a gram negative bacteria that causes Brucellosis. Lipopolysaccharide (LPS ", the pathogenic agent of Brucella is composed of O-chain, core oligosaccharide and lipid A. in addition, the structural and biological properties of different LPS extracted from different strains are not identical. The first defense system against LPS is nonspecific immunity that causes macrophage activation. Activated macrophages produce oxygen and nitrogen radicals that enhance the protection against intracellular pathogens.In this experiment LPS was extracted by hot phenol- water procedure and the effect of various LPSs on nitric oxide prodution by peritoneal mouse macrophages was examined.Our results demonstrated that the effect of LPS on nitric oxide production is concentration-dependent we observed the maximum response in concentration of 10-20 microgram per milliliter. Also our results demonstrate that LPS extracted from vaccine Brucella abortus (S 19 had a highe effect on nitric oxide production than the LPS from other strains

  7. Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells. (United States)

    McCarthy, Ryan C; Kosman, Daniel J


    We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a cell-derived barrier. We found that iron efflux from hBMVEC through the ferrous iron permease ferroportin (Fpn) was stimulated by secretion of the soluble form of the multi-copper ferroxidase, ceruloplasmin (sCp) from the co-cultured C6 cells. Reciprocally, expression of sCp mRNA in the C6 cells was increased by neighboring hBMVEC. In addition, data indicate that C6 cell-secreted hepcidin stimulates internalization of hBMVEC Fpn but only when the end-feet projections characteristic of this glia-derived cell line are proximal to the endothelial cells. This hepcidin-dependent loss of Fpn correlated with knock-down of iron efflux from the hBMVEC; this result was consistent with the mechanism by which hepcidin regulates iron efflux in mammalian cells. In summary, the data support a model of iron trafficking across the BBB in which the capillary endothelium induce the underlying astrocytes to produce the ferroxidase activity needed to support Fpn-mediated iron efflux. Reciprocally, astrocyte proximity modulates the effective concentration of hepcidin at the endothelial cell membrane and thus the surface expression of hBMVEC Fpn. These results are independent of the source of hBMVEC iron (transferrin or non-transferrin bound) indicating that the model developed here is broadly applicable to brain iron homeostasis.

  8. Use of extractive distillation to produce concentrated nitric acid

    International Nuclear Information System (INIS)

    Campbell, P.C.; Griffin, T.P.; Irwin, C.F.


    Concentrated nitric acid (> 95 wt %) is needed for the treatment of off-gases from a fuels-reprocessing plant. The production of concentrated nitric acid by means of extractive distillation in the two-pot apparatus was studied to determine the steady-state behavior of the system. Four parameters, EDP volume (V/sub EDP/) and temperature (T/sub EDP/), acid feed rate, and solvent recycle, were independently varied. The major response factors were percent recovery (CPRR) and product purity (CCP). Stage efficiencies also provided information about the system response. Correlations developed for the response parameters are: CPRR = 0.02(V/sub EDP/ - 800 cc) + 53.5; CCP = -0.87 (T/sub EDP/ - 140 0 C) + 81; eta/sub V,EDP/ = 9.1(F/sub feed/ - 11.5 cc/min) - 0.047(V/sub EDP/ - 800 cc) - 2.8(F/sub Mg(NO 3 ) 2 / - 50 cc/min) + 390; and eta/sub L,EDP/ = 1.9(T/sub EDP/ - 140 0 C) + 79. A computer simulation of the process capable of predicting steady-state conditions was developed, but it requires further work

  9. Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

    Directory of Open Access Journals (Sweden)

    A.C. Pereira


    Full Text Available During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP production, which in turn leads to protein kinase G (PKG activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.

  10. 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: [Eye Institute of Xuzhou, Jiangsu (China); Liu, Ban, E-mail: [Department of Cardiology, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai (China)


    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.

  11. 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


    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.

  12. Hemifacial spasm : Intraoperative electromyographic monitoring as a guide for microvascular decompression

    NARCIS (Netherlands)

    Mooij, JJA; Mustafa, MK; van Weerden, TW


    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

  13. 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


    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.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    MW Laschke


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  17. 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


    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


    NARCIS (Netherlands)



    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

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


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


    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.

  20. 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


    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

  1. 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.


    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


    NARCIS (Netherlands)

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


    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

  3. 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.


    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).


    de Carlo, Talisa E; Chin, Adam T; Bonini Filho, Marco A; Adhi, Mehreen; Branchini, Lauren; Salz, David A; Baumal, Caroline R; Crawford, Courtney; Reichel, Elias; Witkin, Andre J; Duker, Jay S; Waheed, Nadia K


    To evaluate the ability of optical coherence tomography angiography to detect early microvascular changes in eyes of diabetic individuals without clinical retinopathy. Prospective observational study of 61 eyes of 39 patients with diabetes mellitus and 28 control eyes of 22 age-matched healthy subjects that received imaging using optical coherence tomography angiography between August 2014 and March 2015. Eyes with concomitant retinal, optic nerve, and vitreoretinal interface diseases and/or poor-quality images were excluded. Foveal avascular zone size and irregularity, vessel beading and tortuosity, capillary nonperfusion, and microaneurysm were evaluated. Foveal avascular zone size measured 0.348 mm² (0.1085-0.671) in diabetic eyes and 0.288 mm² (0.07-0.434) in control eyes (P = 0.04). Foveal avascular zone remodeling was seen more often in diabetic than control eyes (36% and 11%, respectively; P = 0.01). Capillary nonperfusion was noted in 21% of diabetic eyes and 4% of control eyes (P = 0.03). Microaneurysms and venous beading were noted in less than 10% of both diabetic and control eyes. Both diabetic and healthy control eyes demonstrated tortuous vessels in 21% and 25% of eyes, respectively. Optical coherence tomography angiography was able to image foveal microvascular changes that were not detected by clinical examination in diabetic eyes. Changes to the foveal avascular zone and capillary nonperfusion were more prevalent in diabetic eyes, whereas vessel tortuosity was observed with a similar frequency in normal and diabetic eyes. Optical coherence tomography angiography may be able to detect diabetic eyes at risk of developing retinopathy and to screen for diabetes quickly and noninvasively before the systemic diagnosis is made.

  5. Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy. (United States)

    Timpani, Cara A; Hayes, Alan; Rybalka, Emma


    Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

  6. Studies on the solvent extraction behaviour of Pu(IV) from nitric acid, nitric-perchloric acid and hydrochloric acids, by di,2-ethylhexyl phosphoric acid (HDEHP)

    International Nuclear Information System (INIS)

    Phal, D.G.; Kannan, S.K.; Ramakrishna, V.V.


    Extraction of plutonium (IV) from aqueous nitric acid, nitric-perchloric acid and hydrochloric acids by di,2-ethylhexyl phosphoric acid, the dimeric form of which is represented as H 2 Y 2 , in different diluents (dodecane, toluene and chloroform) was investigated. The composition of the extracted Pu(IV) species were found to be Pu(NO 3 ) 2 (HY) 2 , Pu(NO 3 )(ClO 4 )(HY 2 ) 2 , PuClY(HY 2 ) 2 and PuCl 2 (HY 2 ) 2 from nitric, nitric-perchloric and hydrochloric acids respectively, the last one being pre-dominant at high aqueous acidities (i.e. 5M HCl). Synergic enhancement in the extraction of Pu(IV) from different aqueous media, by the addition of thenoyltrifluoroacetone (HTTA) to HDEHP was also investigated and was attributed to the formation and extraction of the species PuX(TTA)(HY 2 ) 2 , and Pu(TTA) 2 (HY 2 ) 2 where X=Cl - or NO 3 - . The addition of the neutral extractant TOPO to H 2 Y 2 also resulted in synergism. The possible equilibria in these systems were inferred and the corresponding equilibrium constants determined. (author). 24 refs., 10 figs., 10 tabs

  7. A plasma needle generates nitric oxide

    International Nuclear Information System (INIS)

    Stoffels, E; Gonzalvo, Y Aranda; Whitmore, T D; Seymour, D L; Rees, J A


    Generation of nitric oxide (NO) by a plasma needle is studied by means of mass spectrometry. The plasma needle is an atmospheric glow generated by a radio-frequency excitation in a mixture of helium and air. This source is used for the treatment of living tissues, and nitric oxide may be one of the most important active agents in plasma therapy. Efficient NO generation is of particular importance in the treatment of cardiovascular diseases. Mass spectrometric measurements have been performed under various plasma conditions; gas composition in the plasma and conversion of feed gases (nitrogen and oxygen) into other species has been studied. Up to 30% of the N 2 and O 2 input is consumed in the discharge, and NO has been identified as the main conversion product

  8. Interactions between cytokines and nitric oxide. (United States)

    Liew, F Y


    There is now an impressive range of evidence supporting the important role of cytokines in sleep regulation (see Krueger et al., 1995; De Simoni et al., 1995). It has also been reported that inhibition of nitric oxide (NO) synthesis suppresses sleep in rabbits (Kapás et al., 1994). This is not surprising, since NO is closely involved in neurotransmission (Garthwaite, 1991; Schuman and Madison, 1994) and cytokines are the major inducers of NO synthesis (Hibbs et al., 1990). Further, it is now clear that NO plays an important role in modulating immune responses, possibly through the differential regulation of cytokine synthesis (Taylor-Robinson et al., 1994). In this article, I will provide evidence for the interactions between cytokines and nitric oxide, and discuss their implications in the regulation of immune responses. I shall illustrate these mainly with results from my coworkers and I, from our laboratory rather than attempting an exhaustive review of the subject.

  9. Alternative to Nitric Acid Passivation Project Overview (United States)

    Lewis, Pattie L.


    The standard practice for protection of stainless steel is a process called passivation. This procedure results in the formation of a metal oxide layer to prevent corrosion. Typical passivation procedures call for the use of nitric acid which exhibits excellent corrosion performance; however, there are a number of environmental, worker safety, and operational issues associated with its use. The longtime military specification for the passivation of stainless steel was cancelled in favor of newer specifications which allow for the use of citric acid in place of nitric acid. Citric acid offers a variety of benefits that include increased safety for personnel, reduced environmental impact, and reduced operational costs. There have been few studies, however, to determine whether citric acid is an acceptable alternative for NASA and DoD. This paper details activities to date including development of the joint test plan, on-going and planned testing, and preliminary results.

  10. On hydrazine oxidation in nitric acid media

    International Nuclear Information System (INIS)

    Zil'berman, B.Ya.; Lelyuk, G.A.; Mashkin, A.N.; Yasnovitskaya, A.L.


    Yield of products of radiolytic ( 60 Co gamma radiation) and chemical hydrazine (HZ) oxidation in nitric acid media is studied. Under radiolyte HZ oxidation by nitric acid hydrazoic acid, ammonia and nitrogen appear to be the reaction products. HN 3 yield maximum under HZN oxidation makes up ∼ 0.35 mol per a mol of oxiduzed HZN. Under chemical oxidation HZN is oxidized by HNO 3 according to reaction catalysed by technetium HN 3 yield makes up ∼ 0.35 mol per a mol of oxidized HZN. Radiation-chemical oxidation of HN 3 proceeds up to its complete decomposition, decomposition rate is comparable with HZ oxidation rate. Under the chemical oxidation HN 3 is more stable, it is slowly decomposed after complete HZ decomposition

  11. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults

    DEFF Research Database (Denmark)

    Gebistorf, Fabienne; Karam, Oliver; Wetterslev, Jørn


    BACKGROUND: Acute hypoxaemic respiratory failure (AHRF) and mostly acute respiratory distress syndrome (ARDS) are critical conditions. AHRF results from several systemic conditions and is associated with high mortality and morbidity in individuals of all ages. Inhaled nitric oxide (INO) has been...

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

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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.)

  13. Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans. (United States)

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


    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.

  14. Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training (United States)

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


    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

  15. Oxygen, nitric oxide and articular cartilage

    Directory of Open Access Journals (Sweden)

    B Fermor


    Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

  16. 2-Chlorohexadecanoic acid induces ER stress and mitochondrial dysfunction in brain microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Eva Bernhart


    Full Text Available Peripheral leukocytes induce blood-brain barrier (BBB dysfunction through the release of cytotoxic mediators. These include hypochlorous acid (HOCl that is formed via the myeloperoxidase-H2O2-chloride system of activated phagocytes. HOCl targets the endogenous pool of ether phospholipids (plasmalogens generating chlorinated inflammatory mediators like e.g. 2-chlorohexadecanal and its conversion product 2-chlorohexadecanoic acid (2-ClHA. In the cerebrovasculature these compounds inflict damage to brain microvascular endothelial cells (BMVEC that form the morphological basis of the BBB. To follow subcellular trafficking of 2-ClHA we synthesized a ‘clickable’ alkyne derivative (2-ClHyA that phenocopied the biological activity of the parent compound. Confocal and superresolution structured illumination microscopy revealed accumulation of 2-ClHyA in the endoplasmic reticulum (ER and mitochondria of human BMVEC (hCMEC/D3 cell line. 2-ClHA and its alkyne analogue interfered with protein palmitoylation, induced ER-stress markers, reduced the ER ATP content, and activated transcription and secretion of interleukin (IL−6 as well as IL-8. 2-ClHA disrupted the mitochondrial membrane potential and induced procaspase-3 and PARP cleavage. The protein kinase R-like ER kinase (PERK inhibitor GSK2606414 suppressed 2-ClHA-mediated activating transcription factor 4 synthesis and IL-6/8 secretion, but showed no effect on endothelial barrier dysfunction and cleavage of procaspase-3. Our data indicate that 2-ClHA induces potent lipotoxic responses in brain endothelial cells and could have implications in inflammation-induced BBB dysfunction.

  17. Implications of glial nitric oxyde in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Jose Enrique eYuste


    Full Text Available Nitric oxide (NO is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases.

  18. Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

    Directory of Open Access Journals (Sweden)

    Sophie A. Bradley


    Full Text Available Nitric oxide (NO is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS, new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

  19. Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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

  20. Image analysis of epicuticular damage to foliage caused by dry deposition of the air pollutant nitric acid. (United States)

    Padgett, Pamela E; Parry, Sally D; Bytnerowicz, Andrzej; Heath, Robert L


    Nitric acid vapor is produced by the same photochemical processes that produce ozone. In the laboratory, concentrated nitric acid is a strong acid and a powerful oxidant. In the environment, where the concentrations are much lower, it is an innocuous source of plant nitrogen. As an air pollutant, which mode of action does dry deposition of nitric acid follow? We investigated the effects of dry deposition of nitric acid on the foliage of four tree species native to the western United States. A novel controlled environment, fumigation system enabled a four-week exposure at concentrations consistent with ambient diurnal patterns. Scanning electron microscopy and automated image analysis revealed changes in the epicuticular wax layer during fumigation. Exposure to nitric acid resulted in a reproducible suite of damage symptoms that increased with increasing dose. Each tree species tested exhibited a unique set of damage features, including cracks, lesions, and conformation changes to epicuticular crystallite structures. Dry deposition of atmospheric nitric acid caused substantial perturbation to the epicuticular surface of all four tree species investigated, consistent with the chemical oxidation of epicuticular waxes. Automated image analysis eliminated many biases that can trouble microscopy studies. Trade names and commercial enterprises or products are mentioned solely for information. No endorsements by the U.S. Department of Agriculture are implied.

  1. Intracellular acidification reduces l-arginine transport via system y+L but not via system y+/CATs and nitric oxide synthase activity in human umbilical vein endothelial cells. (United States)

    Ramírez, Marco A; Morales, Jorge; Cornejo, Marcelo; Blanco, Elias H; Mancilla-Sierpe, Edgardo; Toledo, Fernando; Beltrán, Ana R; Sobrevia, Luis


    l-Arginine is taken up via the cationic amino acid transporters (system y + /CATs) and system y + L in human umbilical vein endothelial cells (HUVECs). l-Arginine is the substrate for endothelial NO synthase (eNOS) which is activated by intracellular alkalization, but nothing is known regarding modulation of system y + /CATs and system y + L activity, and eNOS activity by the pHi in HUVECs. We studied whether an acidic pHi modulates l-arginine transport and eNOS activity in HUVECs. Cells loaded with a pH-sensitive probe were subjected to 0.1-20 mmol/L NH 4 Cl pulse assay to generate pHi 7.13-6.55. Before pHi started to recover, l-arginine transport (0-20 or 0-1000 μmol/L, 10 s, 37 °C) in the absence or presence of 200 μmol/L N-ethylmaleimide (NEM) (system y + /CATs inhibitor) or 2 mmol/L l-leucine (systemy + L substrate) was measured. Protein abundance for eNOS and serine 1177 or threonine 495 phosphorylated eNOS was determined. The results show that intracellular acidification reduced system y + L but not system y + /CATs mediated l-arginine maximal transport capacity due to reduced maximal velocity. Acidic pHi reduced NO synthesis and eNOS serine 1177 phosphorylation. Thus, system y + L activity is downregulated by an acidic pHi, a phenomenon that may result in reduced NO synthesis in HUVECs. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach. (United States)

    Panazzolo, Diogo G; Sicuro, Fernando L; Clapauch, Ruth; Maranhão, Priscila A; Bouskela, Eliete; Kraemer-Aguiar, Luiz G


    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

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

    Directory of Open Access Journals (Sweden)

    Panazzolo Diogo G


    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

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


    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

  5. 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.


    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

  6. Preoperative evaluation of neurovascular relationships for microvascular decompression in the cerebellopontine angle in a virtual reality environment. (United States)

    Du, Zhuo-Ying; Gao, Xiang; Zhang, Xiao-Luo; Wang, Zhi-Qiu; Tang, Wei-Jun


    In this paper the authors' goal was to evaluate the feasibility and efficacy of a virtual reality (VR) system in preoperative planning for microvascular decompression (MVD) procedures treating idiopathic trigeminal neuralgia and hemifacial spasm. The system's role in surgical simulation and training was also assessed. Between May 2008 and April 2009, the authors used the Dextroscope system to visualize the neurovascular complex and simulate MVD in the cerebellopontine angle in a VR environment in 16 patients (6 patients had trigeminal neuralgia and 10 had hemifacial spasm). Reconstructions were carried out 2-3 days before MVD. Images were printed in a red-blue stereoscopic format for teaching and discussion and were brought into the operating room to be compared with real-time intraoperative findings. The VR environment was a powerful aid for spatial understanding of the neurovascular relationship in MVD for operating surgeons and trainees. Through an initial series of comparison/confirmation experiences, the senior neurosurgeon became accustomed to the system. He could predict intraoperative problems and simulate surgical maneuvering, which increased his confidence in performing the procedure. The Dextroscope system is an easy and rapid method to create a stereoscopic neurovascular model for MVD that is highly concordant with intraoperative findings. It effectively shortens the learning curve and adds to the surgeon's confidence.

  7. Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress. (United States)

    Zhang, Yin Hua


    Nitric oxide (NO) is an imperative regulator of the cardiovascular system and is a critical mechanism in preventing the pathogenesis and progression of the diseased heart. The scenario of bioavailable NO in the myocardium is complex: 1) NO is derived from both endogenous NO synthases (endothelial, neuronal, and/or inducible NOSs [eNOS, nNOS, and/or iNOS]) and exogenous sources (entero-salivary NO pathway) and the amount of NO from exogenous sources varies significantly; 2) NOSs are located at discrete compartments of cardiac myocytes and are regulated by distinctive mechanisms under stress; 3) NO regulates diverse target proteins through different modes of post-transcriptional modification (soluble guanylate cyclase [sGC]/cyclic guanosine monophosphate [cGMP]/protein kinase G [PKG]-dependent phosphorylation, S -nitrosylation, and transnitrosylation); 4) the downstream effectors of NO are multidimensional and vary from ion channels in the plasma membrane to signalling proteins and enzymes in the mitochondria, cytosol, nucleus, and myofilament; 5) NOS produces several radicals in addition to NO (e.g. superoxide, hydrogen peroxide, peroxynitrite, and different NO-related derivatives) and triggers redox-dependent responses. However, nNOS inhibits cardiac oxidases to reduce the sources of oxidative stress in diseased hearts. Recent consensus indicates the importance of nNOS protein in cardiac protection under pathological stress. In addition, a dietary regime with high nitrate intake from fruit and vegetables together with unsaturated fatty acids is strongly associated with reduced cardiovascular events. Collectively, NO-dependent mechanisms in healthy and diseased hearts are better understood and shed light on the therapeutic prospects for NO and NOSs in clinical applications for fatal human heart diseases.

  8. Microvascular function in pre-eclampsia is influenced by insulin resistance and an imbalance of angiogenic mediators. (United States)

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


    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.

  9. Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling. (United States)

    Sorokin, Andrey


    The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

  10. Nitric oxide synthase inhibition and cerebrovascular regulation

    DEFF Research Database (Denmark)

    Iadecola, C; Pelligrino, D A; Moskowitz, M A


    tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large......There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

  11. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M


    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed......-nitroso-N-acetylpenicillamine (SNAP) (1) confirmed denitrification as the main NO consumption pathway, with N2O as its major product, (2) showed that denitrification combines one free NO molecule with one NO molecule formed from nitrite to produce N2O, and (3) suggested that NO inhibits N2O reduction....

  12. Processes regulating nitric oxide emissions from soils

    DEFF Research Database (Denmark)

    Pilegaard, Kim


    , the net result is complex and dependent on several factors such as nitrogen availability, organic matter content, oxygen status, soil moisture, pH and temperature. This paper reviews recent knowledge on processes forming NO in soils and the factors controlling its emission to the atmosphere. Schemes......Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources...

  13. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

    Directory of Open Access Journals (Sweden)

    Nevzat Selim Gokay


    Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

  14. Remedial Investigation Report on the Abandoned Nitric Acid Pipeline at the Oak Ridge Y-12 Plant, Oak Ridge, Tennessee. Energy Systems Environmental Restoration Program; Y-12 Environmental Restoration Program

    Energy Technology Data Exchange (ETDEWEB)


    Upper East Fork Poplar Creek Operable Unit 2 consists of the Abandoned Nitric Acid pipeline (ANAP). This pipeline was installed in 1951 to transport liquid wastes {approximately}4800 ft from Buildings 9212, 9215, and 9206 to the S-3 Ponds. Materials known to have been discharged through the pipeline include nitric acid, depleted and enriched uranium, various metal nitrates, salts, and lead skimmings. During the mid-1980s, sections of the pipeline were removed during various construction projects. A total of 19 locations were chosen to be investigated along the pipeline for the first phase of this Remedial Investigation. Sampling consisted of drilling down to obtain a soil sample at a depth immediately below the pipeline. Additional samples were obtained deeper in the subsurface depending upon the depth of the pipeline, the depth of the water table, and the point of auger refusal. The 19 samples collected below the pipeline were analyzed by the Oak Ridge Y-12 Plant`s laboratory for metals, nitrate/nitrite, and isotopic uranium. Samples collected from three boreholes were also analyzed for volatile organic compounds because these samples produced a response with organic vapor monitoring equipment. Uranium activities in the soil samples ranged from 0.53 to 13.0 pCi/g for {sup 238}U, from 0.075 to 0.75 pCi/g for {sup 235}U, and from 0.71 to 5.0 pCi/g for {sup 238}U. Maximum total values for lead, chromium, and nickel were 75.1 mg/kg, 56.3 mg/kg, and 53.0 mg/kg, respectively. The maximum nitrate/nitrite value detected was 32.0 mg-N/kg. One sample obtained adjacent to a sewer line contained various organic compounds, at least some of which were tentatively identified as fragrance chemicals commonly associated with soaps and cleaning solutions. The results of the baseline human health risk assessment for the ANAP contaminants of potential concern show no unacceptable risks to human health.

  15. Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange. (United States)

    Bert, J; Gyenge, C; Bowen, B; Reed, R; Lund, T


    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.

  16. [Successful microvascular decompression of the medulla oblongata for a case with respiratory failure: case report]. (United States)

    Koguchi, Motofumi; Nakahara, Yukiko; Kawashima, Masatou; Takase, Yukinori; Matsushima, Toshio


    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.

  17. 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.


    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....

  18. Zebrafish as a Model for the Study of Microvascular Complications of Diabetes and Their Mechanisms

    Directory of Open Access Journals (Sweden)

    Karl Heckler


    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.

  19. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications. (United States)

    Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano


    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.

  20. 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


    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....

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

    DEFF Research Database (Denmark)

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


    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...

  2. The role of nitric oxide in the object recognition memory. (United States)

    Pitsikas, Nikolaos


    The novel object recognition task (NORT) assesses recognition memory in animals. It is a non-rewarded paradigm that it is based on spontaneous exploratory behavior in rodents. This procedure is widely used for testing the effects of compounds on recognition memory. Recognition memory is a type of memory severely compromised in schizophrenic and Alzheimer's disease patients. Nitric oxide (NO) is sought to be an intra- and inter-cellular messenger in the central nervous system and its implication in learning and memory is well documented. Here I intended to critically review the role of NO-related compounds on different aspects of recognition memory. Current analysis shows that both NO donors and NO synthase (NOS) inhibitors are involved in object recognition memory and suggests that NO might be a promising target for cognition impairments. However, the potential neurotoxicity of NO would add a note of caution in this context. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Time-Dependent Behavior of Microvascular Blood Flow and Oxygenation: A Predictor of Functional Outcomes. (United States)

    Kuliga, Katarzyna Z; Gush, Rodney; Clough, Geraldine F; Chipperfield, Andrew John


    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.

  4. Restrictive use of perioperative blood transfusion does not increase complication rates in microvascular breast reconstruction. (United States)

    O'Neill, Anne C; Barandun, Marina; Cha, Jieun; Zhong, Toni; Hofer, Stefan O P


    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.

  5. Microvascular anastomosis simulation using a chicken thigh model: Interval versus massed training. (United States)

    Schoeff, Stephen; Hernandez, Brian; Robinson, Derek J; Jameson, Mark J; Shonka, David C


    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.

  6. Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia. (United States)

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


    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

  7. Effect of Antimicrobial Compounds on Balamuthia mandrillaris Encystment and Human Brain Microvascular Endothelial Cell Cytopathogenicity▿ (United States)

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


    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

  8. Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase. (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


    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.

  9. Induction of complement proteins in a mouse model for cerebral microvascular Aβ deposition

    Directory of Open Access Journals (Sweden)

    DeFilippis Kelly


    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

  10. 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


    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....

  11. Photocoagulation of microvascular and hemorrhagic lesions of the vocal fold with the KTP laser. (United States)

    Hirano, Shigeru; Yamashita, Masaru; Kitamura, Morimasa; Takagita, Shin-ichi


    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.

  12. Barotrauma and microvascular injury in lungs of nonadult rabbits: effect of ventilation pattern. (United States)

    Peevy, K J; Hernandez, L A; Moise, A A; Parker, J C


    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.

  13. Involvement of the nitric oxide in melatonin-mediated protection against injury. (United States)

    Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen


    Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Argon Shrouded Plasma Spraying of Tantalum over Titanium for Corrosion Protection in Fluorinated Nitric Acid Media (United States)

    Vetrivendan, E.; Jayaraj, J.; Ningshen, S.; Mallika, C.; Kamachi Mudali, U.


    Argon shrouded plasma spraying (ASPS) was used to deposit a Ta coating on commercially pure Ti (CP-Ti) under inert argon, for dissolver vessel application in the aqueous spent fuels reprocessing plant with high plutonium content. Oxidation during plasma spraying was minimized by shrouding argon system. Porosity and oxide content were controlled by optimizing the spraying parameters, to obtain a uniform and dense Ta coating. The Ta particle temperature and velocity were optimized by judiciously controlling the spray parameters, using a spray diagnostic charge-coupled device camera. The corrosion resistance of the Ta coatings developed by ASPS was investigated by electrochemical studies in 11.5 M HNO3 and 11.5 M HNO3 + 0.05 M NaF. Similarly, the durability of the ASPS Ta coating/substrate was evaluated as per ASTM A262 Practice-C test in boiling nitric acid and fluorinated nitric acid for 240 h. The ASPS Ta coating exhibited higher corrosion resistance than the CP-Ti substrate, as evident from electrochemical studies, and low corrosion rate with excellent coating stability in boiling nitric, and fluorinated nitric acid. The results of the present study revealed that tantalum coating by ASPS is a promising strategy for improving the corrosion resistance in the highly corrosive reprocessing environment.

  15. MEMS-based handheld fourier domain Doppler optical coherence tomography for intraoperative microvascular anastomosis imaging.

    Directory of Open Access Journals (Sweden)

    Yong Huang

    Full Text Available To demonstrate the feasibility of a miniature handheld optical coherence tomography (OCT imager for real time intraoperative vascular patency evaluation in the setting of super-microsurgical vessel anastomosis.A novel handheld imager Fourier domain Doppler optical coherence tomography based on a 1.3-µm central wavelength swept source for extravascular imaging was developed. The imager was minimized through the adoption of a 2.4-mm diameter microelectromechanical systems (MEMS scanning mirror, additionally a 12.7-mm diameter lens system was designed and combined with the MEMS mirror to achieve a small form factor that optimize functionality as a handheld extravascular OCT imager. To evaluate in-vivo applicability, super-microsurgical vessel anastomosis was performed in a mouse femoral vessel cut and repair model employing conventional interrupted suture technique as well as a novel non-suture cuff technique. Vascular anastomosis patency after clinically successful repair was evaluated using the novel handheld OCT imager.With an adjustable lateral image field of view up to 1.5 mm by 1.5 mm, high-resolution simultaneous structural and flow imaging of the blood vessels were successfully acquired for BALB/C mouse after orthotopic hind limb transplantation using a non-suture cuff technique and BALB/C mouse after femoral artery anastomosis using a suture technique. We experimentally quantify the axial and lateral resolution of the OCT to be 12.6 µm in air and 17.5 µm respectively. The OCT has a sensitivity of 84 dB and sensitivity roll-off of 5.7 dB/mm over an imaging range of 5 mm. Imaging with a frame rate of 36 Hz for an image size of 1000(lateral×512(axial pixels using a 50,000 A-lines per second swept source was achieved. Quantitative vessel lumen patency, lumen narrowing and thrombosis analysis were performed based on acquired structure and Doppler images.A miniature handheld OCT imager that can be used for intraoperative evaluation of

  16. Microvascular oxygen partial pressure during hyperbaric oxygen in diabetic rat skeletal muscle. (United States)

    Yamakoshi, Kohei; Yagishita, Kazuyoshi; Tsuchimochi, Hirotsugu; Inagaki, Tadakatsu; Shirai, Mikiyasu; Poole, David C; Kano, Yutaka


    Hyperbaric oxygen (HBO) is a major therapeutic treatment for ischemic ulcerations that perforate skin and underlying muscle in diabetic patients. These lesions do not heal effectively, in part, because of the hypoxic microvascular O2 partial pressures (PmvO2 ) resulting from diabetes-induced cardiovascular dysfunction, which alters the dynamic balance between O2 delivery (Q̇o2) and utilization (V̇o2) rates. We tested the hypothesis that HBO in diabetic muscle would exacerbate the hyperoxic PmvO2 dynamics due, in part, to a reduction or slowing of the cardiovascular, sympathetic nervous, and respiratory system responses to acute HBO exposure. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (control) groups. A small animal hyperbaric chamber was pressurized with oxygen (100% O2) to 3.0 atmospheres absolute (ATA) at 0.2 ATA/min. Phosphorescence quenching techniques were used to measure PmvO2 in tibialis anterior muscle of anesthetized rats during HBO. Lumbar sympathetic nerve activity (LSNA), heart rate (HR), and respiratory rate (RR) were measured electrophysiologically. During the normobaric hyperoxia and HBO, DIA tibialis anterior PmvO2 increased faster (mean response time, CONT 78 ± 8, DIA 55 ± 8 s, P < 0.05) than CONT. Subsequently, PmvO2 remained elevated at similar levels in CONT and DIA muscles until normobaric normoxic recovery where the DIA PmvO2 retained its hyperoxic level longer than CONT. Sympathetic nervous system and cardiac and respiratory responses to HBO were slower in DIA vs. CONT. Specifically the mean response times for RR (CONT: 6 ± 1 s, DIA: 29 ± 4 s, P < 0.05), HR (CONT: 16 ± 1 s, DIA: 45 ± 5 s, P < 0.05), and LSNA (CONT: 140 ± 16 s, DIA: 247 ± 34 s, P < 0.05) were greater following HBO onset in DIA than CONT. HBO treatment increases tibialis anterior muscle PmvO2 more rapidly and for a longer duration in DIA than CONT, but not to a greater level. Whereas respiratory, cardiovascular

  17. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. (United States)

    Stamler, J S; Jaraki, O; Osborne, J; Simon, D I; Keaney, J; Vita, J; Singel, D; Valeri, C R; Loscalzo, J


    We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be

  18. Long-term effects of bariatric surgery on peripheral endothelial function and coronary microvascular function. (United States)

    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.

  19. Acute effects of coffee on skin blood flow and microvascular function. (United States)

    Tesselaar, Erik; Nezirevic Dernroth, Dzeneta; Farnebo, Simon


    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.

  20. Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Uma Shankar Mishra


    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

  2. Transmural Variation and Anisotropy of Microvascular Flow Conductivity in the Rat Myocardium

    KAUST Repository

    Smith, Amy F.


    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.

  3. Quantitative evaluation of capillaroscopic microvascular changes in patients with established coronary heart disease. (United States)

    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


    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.

  4. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone. (United States)

    Prisby, Rhonda D


    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.

  5. Clinical reference value of retinal microvascular changes in patients with cerebral microbleeds

    Directory of Open Access Journals (Sweden)

    Ji-Yuan Guo


    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.

  6. The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction. (United States)

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


    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.

  7. Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice. (United States)

    Gawali, Nitin B; Chowdhury, Amrita A; Kothavade, Pankaj S; Bulani, Vipin D; Nagmoti, Dnyaneshwar M; Juvekar, Archana R


    In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder (OCD), patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD influence nitric oxide. Agmatine is a polyamine and widely distributed in mammalian brain which interacts with nitrergic systems. Hence, the present study was carried out to understand the involvement of nitrergic systems in the anticompulsive-like effect of agmatine. We used marble-burying behaviour (MBB) of mice as the animal model of OCD, and nitric oxide levels in hippocampus (HC) and cortex homogenate were measured. Results revealed that, agmatine (20 and 40mg/kg, i.p) significantly inhibited the MBB. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor - l-arginine (l-ARG) (400mg/kg and 800mg/kg) increased MBB as well as brain nitrites levels, whereas treatment with N(G)-nitro-l-arginine methyl ester (l-NAME) neuronal nitric oxide synthase inhibitor (30mg/kg and 50mg/kg, i.p.) and 7-nitroindazole (7-NI) (20mg/kg and 40mg/kg) attenuated MBB and nitrites levels in brain. Further, in combination studies, the anticompulsive-like effect of agmatine (20mg/kg, ip) was exacerbated by prior administration of l-ARG (400mg/kg) and conversely l-NAME (15mg/kg) or 7-NI (10.0mg/kg) attenuated OCD-like behaviour with HC and cortex changes in the levels of NO. None of the above treatment had any significant influence on locomotor activity. In conclusion, Agmatine is effective in ameliorating the compulsive-like behaviour in mice which appears to be related to nitric oxide in brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Study of the oxidation-reduction kinetics involved in the Np(V) + Fe(II) in equilibrium Np(IV) + Fe(III) system in nitric acid solutions

    International Nuclear Information System (INIS)

    Jao, Y.


    Ferrous nitrate-hydrazine is one of the more attractive alternate reactants to the currently used reagent, ferrous sulfamate, for partitioning plutonium from neptunium and uranium. An understanding of the kinetics of the reduction of Np(VI) to Np(IV) by ferrous nitrate-hydrazine is needed before a satisfactory evaluation of the feasibility of this reductant in actinide element separations can be made. The purpose of this work was to study the kinetics and mechanisms of the reduction of Np(V) by Fe(II) and the oxidation of Np(IV) by Fe(III) in 1-2 M nitric acid solutions. The acid concentration range was chosen to include that typically used in the separation of plutonium from neptunium and uranium by solvent extraction with tributylphosphate. The forward and reverse rate constants, hydrogen ion dependence, temperature dependence, ionic strength effects and nitrate ion influence were determined. The proposed reaction mechanisms involve protonation of the NpO 2 + ions and hydroxyoxygenation of Np 4 + ions. (LK)

  9. Nitric oxide in the stress axis. (United States)

    López-Figueroa, M O; Day, H E; Akil, H; Watson, S J


    In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

  10. Vascular nitric oxide: Beyond eNOS

    Directory of Open Access Journals (Sweden)

    Yingzi Zhao


    Full Text Available As the first discovered gaseous signaling molecule, nitric oxide (NO affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC to produce cyclic guanosine monophosphate (cGMP, although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA or production of cyclic inosine monophosphate (cIMP] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

  11. Catalytic abatement of nitrous oxide from nitric and production

    NARCIS (Netherlands)

    Oonk, J.


    Nitric acid production is identified as a main source of nitrous oxide. Options for emission reduction however are not available. TNO and Hydro Agri studied the technological and economic feasibility of catalytic decomposition of nitrous oxide in nitric acid tail-gases. Although in literature

  12. Influence of nitric oxide on histamine and carbachol – induced ...

    African Journals Online (AJOL)

    The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad – Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase ...

  13. The correlation between total antioxidant capacity and nitric oxide ...

    African Journals Online (AJOL)

    DNA damage was measured by comet assay and nitric oxide concentration was evaluated by Griess assay. TAC was measured in seminal plasma based on the generation of peroxyl radicals from 2,2-azinobis (2-amidino propane) dihydrochlorid (AAPH). Our results show that the means of DNA damage and nitric oxide ...

  14. Successful Treatment with Microvascular Decompression Surgery of a Patient with Hemiparesis Caused by Vertebral Artery Compression of the Medulla Oblongata: Case Report and Review of the Literature. (United States)

    Ren, Jibin; Sun, Hongtao; Diao, Yunfeng; Niu, Xuegang; Wang, Hang; Wei, Zhengjun; Yuan, Fei


    There are few reports on hemiparesis caused by vascular medullary compression, which can occur because of dolichoectasia of the vertebrobasilar arterial system. In this article, we report a case of vertebral artery compression of the medulla oblongata in a 67-year-old woman. The patient was hypertensive, and she developed hemiparesis and intermittent spasms over 5 years. These spasms had worsened during the last year. Cranial nerve magnetic resonance imaging showed compression of the medulla oblongata by the left vertebral artery. A motor evoked potential (MEP) examination showed abnormal conduction of MEPs of bilateral toe abductors. The patient underwent microvascular decompression surgery under general anesthesia through a retrosigmoid keyhole approach. This operation led to relief of vascular compression and symptomatic improvement. Our case suggests that detailed history, imaging studies, and electrophysiologic studies help lead to a correct and early diagnosis of hemiparesis caused by vascular compression of the rostral ventrolateral medulla. Microvascular decompression surgery improves patient symptoms, and intraoperative electrophysiologic monitoring helps to avoid injury to important adjacent nerves. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

    Directory of Open Access Journals (Sweden)

    Orlando A


    Full Text Available Antonina Orlando,1 Francesca Re,1 Silvia Sesana,1 Ilaria Rivolta,1 Alice Panariti,1 Davide Brambilla,2 Julien Nicolas,2 Patrick Couvreur,2 Karine Andrieux,2 Massimo Masserini,1 Emanuela Cazzaniga1 1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; 2Institut Galien Paris Sud, University Paris-Sud, Châtenay-Malabry, France Background: As part of a project designing nanoparticles for the treatment of Alzheimer’s disease, we have synthesized and characterized a small library of nanoparticles binding with high affinity to the β-amyloid peptide and showing features of biocompatibility in vitro, which are important properties for administration in vivo. In this study, we focused on biocompatibility issues, evaluating production of nitric oxide by cultured human umbilical vein endothelial cells and macrophages, used as models of cells which would be exposed to nanoparticles after systemic administration. Methods: The nanoparticles tested were liposomes and solid lipid nanoparticles carrying phosphatidic acid or cardiolipin, and PEGylated poly(alkyl cyanoacrylate nanoparticles (PEG-PACA. We measured nitric oxide production using the Griess method as well as phosphorylation of endothelial nitric oxide synthase and intracellular free calcium, which are biochemically related to nitric oxide production. MTT viability tests and caspase-3 detection were also undertaken. Results: Exposure to liposomes did not affect the viability of endothelial cells at any concentration tested. Increased production of nitric oxide was detected only with liposomes carrying phosphatidic acid or cardiolipin at the highest concentration (120 µg/mL, together with increased synthase phosphorylation and intracellular calcium levels. Macrophages exposed to liposomes showed a slightly dose-dependent decrease in viability, with no increase in production of nitric oxide. Exposure to solid lipid nanoparticles carrying phosphatidic acid decreased viability in

  16. The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Ji Hyun Kim


    Full Text Available Dangkwisoo-San (DS is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO production in human brain microvascular endothelial cells (HBMECs. DS (10–300 μg/mL produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF, although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS inhibitor, N5-(1-iminoethyl-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.

  17. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis.

    Directory of Open Access Journals (Sweden)

    Carlos Salomon

    Full Text Available Vasculogenesis and angiogenesis are critical processes in fetal circulation and placental vasculature development. Placental mesenchymal stem cells (pMSC are known to release paracrine factors (some of which are contained within exosomes that promote angiogenesis and cell migration. The aims of this study were: to determine the effects of oxygen tension on the release of exosomes from pMSC; and to establish the effects of pMSC-derived exosomes on the migration and angiogenic tube formation of placental microvascular endothelial cells (hPMEC. pMSC were isolated from placental villi (8-12 weeks of gestation, n = 6 and cultured under an atmosphere of 1%, 3% or 8% O2. Cell-conditioned media were collected and exosomes (exo-pMSC isolated by differential and buoyant density centrifugation. The dose effect (5-20 µg exosomal protein/ml of pMSC-derived exosomes on hPMEC migration and tube formation were established using a real-time, live-cell imaging system (Incucyte™. The exosome pellet was resuspended in PBS and protein content was established by mass spectrometry (MS. Protein function and canonical pathways were identified using the PANTHER program and Ingenuity Pathway Analysis, respectively. Exo-pMSC were identified, by electron microscopy, as spherical vesicles, with a typical cup-shape and diameters around of 100 nm and positive for exosome markers: CD63, CD9 and CD81. Under hypoxic conditions (1% and 3% O2 exo-pMSC released increased by 3.3 and 6.7 folds, respectively, when compared to the controls (8% O2; p<0.01. Exo-pMSC increased hPMEC migration by 1.6 fold compared to the control (p<0.05 and increased hPMEC tube formation by 7.2 fold (p<0.05. MS analysis identified 390 different proteins involved in cytoskeleton organization, development, immunomodulatory, and cell-to-cell communication. The data obtained support the hypothesis that pMSC-derived exosomes may contribute to placental vascular adaptation to low oxygen tension under both

  18. Nitric Oxide Metabolites and Asymmetric Dimethylarginine Concentrations in Breast Milk

    Directory of Open Access Journals (Sweden)

    Hakan Öztürk


    Full Text Available Objective: Nitric oxide plays a preventive role in the development of necrotizing enterocolitis. Oral nitrite and nitrate intake has gained importance with the discovery of the conversion of nitrite to nitric oxide in acidic medium out of the synthesis of nitric oxide from L-arginine. Objective of this study was to examine the breast milk concentrations of nitric oxide and asymmetric dimethylarginine which is a competitive inhibitor of nitric oxide and to compare these concentrations in terms of gestational age and maturity of breast milk. Study Design: Forty-one women were included in the study. Milk samples were collected from 3 groups of mothers as term, late preterm and preterm on the postpartum days 3, 7 and 28. Results: When breast milk concentrations of nitric oxide were compared according to the postnatal day of the milk independently from gestational age; nitric oxide concentration was higher in the colostrum than in the transition milk and mature milk (p=0,035; p=0,001; respectively. For the comparison of asymmetric dimethylarginine concentrations among these groups and days; no statistically significant difference was observed in terms of gestational age and maturity of the milk (p=0.865, p=0.115; respectively. Conclusion: The highest nitric oxide concentration was found in the colostrum, suggesting that colostrum is a valuable food for newborns. Plasma concentrations of asymmetric dimethylarginine were negatively correlated with nitric oxide and did not show a correlation with breast milk, suggesting that asymmetric dimethylargininedoesn’t make nitric oxide inhibition in breast milk.

  19. Study of precipitation behaviour of Mo and Zr in nitric acid solution

    International Nuclear Information System (INIS)

    Lin Cansheng; Wang Xiaoying; Zhang Chonghai


    The precipitation behaviour of Mo and Zr which depends on the concentrations of Mo, Zr, nitric acid and temperature is studied. Precipitation, post-precipitation and ultracentrifugation experiments are made at 100 deg C, 80 deg C, 60 deg C, 40 deg C and room temperatures in the range of 0.6-6.0 mol/1 nitric acid. The experimental feeds are made up of molybdenum labelled with 99 Mo, zirconium labelled with 95 Zr and nitric acid solution. The feed is allowed to stand at constant temperature for some time for the observation of precipitation behaviour. The filtered precipitate and ultracentrifuged liquid is to be measured with HP (Ge)-multichannel analyser in order to determine the content of Mo, Zr and their mole ration in the precipitate and to find out whether there is colloid in the liquid. The results show that the mixed solution of Mo and Zr can produce precipitate and post-precipitate in nitric acid. If the filtrated liquid is allowed to stand for some time, precipitate can be produced again, until the concentration of Mo and Zr in the feed is too low to form precipitate, such as 2.5 x 10 -3 mol/1. If the concentration of nitric acid is less than 4.0 mol/1, the precipitation is produced easily and more precipitate is formed. Precipitation is slower in solutions which are more than 4.0 mol/1 in HNO 3 . The mole-ratio of Mo to Zr in the precipitate is 2 to 1 and it is not dependent on that ratio in the system

  20. Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis. (United States)

    Hyde, Embriette R; Andrade, Fernando; Vaksman, Zalman; Parthasarathy, Kavitha; Jiang, Hong; Parthasarathy, Deepa K; Torregrossa, Ashley C; Tribble, Gena; Kaplan, Heidi B; Petrosino, Joseph F; Bryan, Nathan S


    The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

  1. Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

    Directory of Open Access Journals (Sweden)

    Embriette R Hyde

    Full Text Available The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

  2. Experience with inhaled nitric oxide therapy in hypoxic respiratory failure of the newborn. (United States)

    Sehgal, Arvind; Callander, Ian; Stack, Jacqueline; Momsen, Tracey; Sterling-Levis, Katy


    Respiratory diseases are the commonest cause of morbidity and mortality in newborns. Inhaled nitric oxide (iNO) has been shown to be effective in the management of persistent pulmonory hypertension of newborn (PPHN). To retrospectively analyse data to determine the effectiveness of inhaled nitric oxide (iNO) in the management of newborns with PPHN in terms of survival and changes in oxygenation status. Neo-natal data since inception of iNO therapy at the unit (past six years) was reviewed. Pertinent demographic and clinical information was collected from medical records of newborns that received inhaled nitric oxide therapy during their stay. Details of underlying illnesses, other therapeutic modalities, arterial blood gas, ventilatory and nitric oxide parameters were assessed and analysed to ascertain efficacy of iNO. A total of 36 babies (gestational age ranging from 24-41 weeks) received iNO during this period; two were excluded from final analysis. Overall survival rate was 80 percent. There was a statistically significant increase in systemic oxygenation (PaO2) from 41.1 +/- 2.1 mmHg to 128.5 +/- 13.2 mmHg and a decline in oxygenation index (OI) from 49.4 +/- 5.9 to 17.3 +/- 2.5, when assessed after four hours (P < 0.001). Mean duration of iNO therapy was 63 +/- 7.3 hours and the maximum methaemoglobin levels were noted to be 2.1 percent. Inhaled nitric oxide appears to be an effective rescue therapy for the management of PPHN associated with hypoxic respiratory failure. It is safe and well tolerated with no evidence of clinical or biochemical side effects.

  3. The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone. (United States)

    Arnold, Robyn E; Weigent, Douglas A


    Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

  4. Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway. (United States)

    Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin


    Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

  5. Conflicting interactions of apolipoprotein A and high density lipoprotein cholesterol with microvascular complications of type 2 diabetes. (United States)

    Aryan, Zahra; Afarideh, Mohsen; Ghajar, Alireza; Esteghamati, Sadaf; Esteghamati, Alireza; Nakhjavani, Manouchehr


    This study is amid at investigating the associations, and interactions of serum lipid biomarkers with microvascular complications of type 2 diabetes (T2D). A nested case-control study was conducted within an ongoing prospective study on patients with T2D. Microvascular complications of T2D including diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were investigated. A total of 444 cases with at least one of the microvascular complications of T2D and 439 age- and gender-matched controls free of any of the chronic microvascular complications of T2D were included. The associations and interactions of a panel of serum lipid biomarkers with the microvascular complications of T2D were investigated. Serum triglyceride had the strongest association with microvascular complications of T2D (crude model: β=0.632, P value=0.045). Each standard deviation increment in serum TG was associated with 3.7 times increased frequency of microvascular complications. Despite high density lipoprotein cholesterol (HDL-C), serum apolipoprotein A1 (Apo A1) was positively associated with the presence of diabetic neuropathy. Each standard deviation increment in serum ApoA1 was associated with increased frequency of diabetic neuropathy (OR, 1.2, 95% CI, (1.1-1.3), P value=0.006). The frequency of diabetic neuropathy was higher in 2nd and 3rd quartiles of serum Lp(a) compared to diabetic patients in the first quartile (OR, 5.52, 95% (1.17-25.8), P value=0.047). ApoA1 but not HDL-C is straightly associated with diabetic neuropathy. Even Slight rise in serum Lp(a) is associated with increased frequency of diabetic retinopathLipid variables could serve as specific predictors of vascular complications in diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents. (United States)

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


    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.

  7. Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity


    Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.


    Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respo...

  8. Oxygen binding to nitric oxide marked hemoglobin

    International Nuclear Information System (INIS)

    Louro, S.R.W.; Ribeiro, P.C.; Bemski, G.


    Electron spin resonance spectra of organic phosphate free human hemoglobin marked with nitric oxide at the sixth coordination position of one of the four hemes allow to observe the transition from the tense (T) to the relaxed (R) conformation, as a function of parcial oxygen pressure. The spectra are composites of contributions from α sub(T), α sub(R) and β chains spectra, showing the presence of only two conformations: T and R. In the absence of organic phosphates NO binds to α and β chains with the same probability, but in the presence of phosphates NO combines preferentially with α chains. The dissociation of NO proceeds at least an order of magnitude faster in T than in R configuration. (author) [pt

  9. Nitric oxide: cancer target or anticancer agent? (United States)

    Mocellin, Simone


    Despite the improved understanding of nitric oxide (NO) biology and the large amount of preclinical experiments testing its role in cancer development and progression, it is still debated whether NO should be considered a potential anticancer agent or instead a carcinogen. The complexity of NO effects within a cell and the variability of the final biological outcome depending upon NO levels makes it highly challenging to determine the therapeutic value of interfering with the activity of this intriguing gaseous messenger. This uncertainty has so far halted the clinical implementation of NO-based therapeutics in the field of oncology. Accordingly, only an in depth knowledge of the mechanisms leading to experimental tumor regression or progression in response to NO will allow us to exploit this molecule to fight cancer.

  10. Nitric oxide and mitochondria in metabolic syndrome (United States)

    Litvinova, Larisa; Atochin, Dmitriy N.; Fattakhov, Nikolai; Vasilenko, Mariia; Zatolokin, Pavel; Kirienkova, Elena


    Metabolic syndrome (MS) is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO) plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of metabolic disorders and therefore are highlighted here. Reduced endothelial NOS activity and NO bioavailability, as the main factors underlying the endothelial dysfunction that occurs in MS, are discussed in this review in relation to mitochondrial dysfunction. We also focus on potential therapeutic strategies involving NO signaling pathways that can be used to treat patients with metabolic disorders associated with mitochondrial dysfunction. The article may help researchers develop new approaches for the diagnosis, prevention and treatment of MS. PMID:25741283

  11. Radiolysis of concentrated nitric acid solutions

    International Nuclear Information System (INIS)

    Nagaishi, R.; Jiang, P.Y.; Katsumura, Y.; Domae, M.; Ishigure, K.


    A study on electron pulse- and 60 Co γ-radiolysis of concentrated nitric acid and nitrate solutions has been carried out to elucidate the radiation induced reactions taking place in the solutions. Dissociation into NO 2 - and O( 3 P) was proposed as a direct action of the radiation on nitrate and gave the G-values were dependent on the chemical forms of nitrate: g s2 (-NO 3 - )=1.6 and g s2 (-HNO 3 )=2.2 (molecules/100eV). Based on the experimental yields of HNO 2 and reduced Ce IV , the primary yields of radiolysis products of water, g w , were evaluated to clarify the effects of nitrate on spur reactions of water in various nitrate solutions. (author)

  12. The role of nitric oxide in reproduction

    Directory of Open Access Journals (Sweden)

    McCann S.M.


    Full Text Available Nitric oxide (NO plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH. The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP. NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG.

  13. Auroral nitric oxide concentration and infrared emission (United States)

    Reidy, W. P.; Degges, T. C.; Hurd, A. G.; Stair, A. T., Jr.; Ulwick, J. C.


    Rocket-borne measurements of infrared auroral emission by nitric oxide are analyzed. Four rocket flights provided opportunities to measure 5.3- and 2.7-micron NO emission by means of infrared fixed band radiometers and CVF spectrometers, narrow band photometers, and incident energy spectra on various occasions. Analysis of infrared emission profiles and electron flux data indicates the NO density to be significantly enhanced with respect to midlatitude values. NO emission in the fundamental 5.3-micron band is attributed to resonance excitation by warm earth radiation, collisional excitation primarily by O atoms and chemiluminescence from the reaction of N with O2; with an energy efficiency of 0.015. The overtone band emission at 2.7 microns is accounted for by chemiluminescence produced with an energy efficiency of 0.0054. Total photon yield for the chemiluminescence reaction is estimated to range from 1.2 to 2.4 vibrational quanta per NO molecule.

  14. Studies of molybdenite interaction with nitric acid

    International Nuclear Information System (INIS)

    Potashnikov, Yu.M.; Lutsik, V.I.; Chursanov, Yu.V.


    Product composition and their effect on the reaction rate of molybdenite with nitric acid are specified. It is shown that alongside with NO NO 2 is included in the composition of the products of MoS 2 and HNO 3 interaction and it produces catalytic effect on the process considered. Under the conditions studied MoS 2 dissolution proceeds in the mixed regime, conditioned by similar values of molybdenite oxidation rate and reaction product diffusion into solution volume (Esub(act.=28.9 kJ/mol, K 298 =6.3x10 -7 , cmxs -1 ), at that due to catalytic effect of NO 2 the dependence V approximately αsup(-g.37) is observed

  15. Nitric oxide and plant iron homeostasis. (United States)

    Buet, Agustina; Simontacchi, Marcela


    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. © 2015 New York Academy of Sciences.

  16. Nitric oxide-induced calcium release: activation of type 1 ryanodine receptor by endogenous nitric oxide. (United States)

    Kakizawa, Sho; Yamazawa, Toshiko; Iino, Masamitsu


    Ryanodine receptors (RyRs), located in the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane, are required for intracellular Ca2+ release that is involved in a wide range of cellular functions. In addition to Ca2+-induced Ca2+ release in cardiac cells and voltage-induced Ca2+ release in skeletal muscle cells, we recently identified another mode of intracellular Ca2+ mobilization mediated by RyR, i.e., nitric oxide-induced Ca2+ release (NICR), in cerebellar Purkinje cells. NICR is evoked by neuronal activity, is dependent on S-nitrosylation of type 1 RyR (RyR1) and is involved in the induction of long-term potentiation (LTP) of cerebellar synapses. In this addendum, we examined whether peroxynitrite, which is produced by the reaction of nitric oxide with superoxide, may also have an effect on the Ca2+ release via RyR1 and the cerebellar LTP. We found that scavengers of peroxynitrite have no significant effect either on the Ca2+ release via RyR1 or on the cerebellar LTP. We also found that an application of a high concentration of peroxynitrite does not reproduce neuronal activity-dependent Ca2+ release in Purkinje cells. These results support that NICR is induced by endogenous nitric oxide produced by neuronal activity through S-nitrosylation of RyR1.

  17. Extractive distillation of nitric acid using the two-pot concept

    International Nuclear Information System (INIS)

    Counce, R.M.; Groenier, W.S.; Holland, W.D.; Jubin, R.T.; North, E.D.; Thompson, L.E. Jr.; Hebble, T.L.


    Experiments have confirmed the validity of a novel design for a nitric acid concentration system for use in shielded nuclear fuel reprocessing plants. Current plans for producing the scrub solution for the IODOX process require the concentration and recycle of low strength ( 3 ) 2 as the solvent and features two pots: an extractive distillation pot in which a concentrated acid product is obtained by contacting the acid feed with the solvent and a solvent recovery pot in which the solvent is dehydrated and recovered for recycle. In these experiments, a concentrated product of 89 wt % nitric acid was produced from azeotropic feed. The available vapor-liquid equilibria data for the Mg(NO 3 ) 2 -HNO 3 -H 2 O system has been empirically correlated, and a design methodology has been developed for the two-pot extractive distillation process

  18. Regenerable Photovoltaic Devices with a Hydrogel-Embedded Microvascular Network (United States)

    Koo, Hyung-Jun; Velev, Orlin D.


    Light-driven degradation of photoactive molecules could be one of the major obstacles to stable long term operation of organic dye-based solar light harvesting devices. One solution to this problem may be mimicking the regeneration functionality of a plant leaf. We report an organic dye photovoltaic system that has been endowed with such microfluidic regeneration functionality. A hydrogel medium with embedded channels allows rapid and uniform supply of photoactive reagents by a convection-diffusion mechanism. A washing-activation cycle enables reliable replacement of the organic component in a dye-sensitized photovoltaic system. Repetitive restoration of photovoltaic performance after intensive device degradation is demonstrated. PMID:23912814

  19. Nitric Oxide - Its Importance in Swallowing, Inflammatory Bowel Disease and Cirrhotic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    ABR Thomson


    Full Text Available Nitric oxide is a neurotransmitter found in the central and peripheral nervous systems. Nitric oxide synthase (NOS is localized in the central nervous system, including the nucleus of the solitary tract, nucleus ambiguus and dorsal motor nucleus of the vagus. These are regions that are implicated in the central control of swallowing and esophageal motility. In rats and rabbits, NOS has been shown to be present in the nucleus subcentralis of the nucleus of the solitary tract, and is thought to be responsible for the central programming of the striated muscle component of esophageal peristalsis. Beyak and co-workers from the University of Toronto, Toronto, Ontario provided evidence that the L-arginine-nitric oxide pathway is implicated in the central control of swallowing and esophageal motility. They studied oropharyngeal swallowing as well as esophageal peristalsis, and determined the functional role of brain stem nitric oxide by examining the effects of blockade of central nervous system NOS on swallowing, and on primary and secondary peristalsis. Administering NOS inhibitors intravenously or intracerebroventricularly into the fourth ventricle produced a number of oropharyngeal swallows and induced primary peristalsis in the smooth muscle portion of the esophageal body. NOS reduced the number of oropharyngeal swallows and the incidence of primary peristalsis in both smooth and striated muscle, and reduced the amplitude of peristalsis and smooth muscle contraction. This suggests that nitric oxide is a functional neurotransmitter in the central pattern generator responsible for swallowing and the central control of esophageal peristalsis. Peripherally administered NOS inhibitor can access structures within the blood-brain barrier to affect neuronal activity and physiological function. The central pattern generated for swallowing and esophageal peristalsis is suggested to be a serial network of linked neurons within the nucleus of the solitary

  20. Change in reimbursement and costs in German oncological head and neck surgery over the last decade: ablative tongue cancer surgery and reconstruction with split-thickness skin graft vs. microvascular radial forearm flap. (United States)

    Hoefert, Sebastian; Lotter, Oliver


    Defects after ablative tongue cancer surgery can be reconstructed by split-thickness skin grafts or free microvascular flaps. The different surgical options may influence costs, reimbursement, and therefore possible profits. Our goal was to analyze the development of these parameters for different procedures in head and neck reconstruction in Germany over the last decade. After tumor resection and neck dissection of tongue cancer, three different scenarios were chosen to calculate costs, reimbursement, length of stay (LoS), and profits. Two options considered were reconstruction by split-thickness skin graft with (option Ia) and without (option Ib) tracheotomy. In addition, we analyzed microvascular reconstruction with radial forearm flap (option II). Furthermore, unsatisfactory results after options Ia and Ib may make secondary tongue plastic with split-thickness skin grafting necessary (option I+). The calculations were performed considering the German Diagnosis Related Group (DRG) system and compared to the specific DRG cost data of 250 German reference hospitals. The overall average length of stay (aLoS) declined from 16.7 to 12.8 days with a reduction in every option. Until 2011, all options showed similar accumulated DRG reimbursement. From 2012 onwards, earnings almost doubled for option II due to changes in the DRG allocation. As was expected, the highest costs were observed in option II. Profits (reimbursement minus costs) were also highest for option II (mean 2052 €, maximum 3630 Euros in 2015) followed by options Ia (765 €) and Ib/I+ (681 €). Average profits over time would be 17 to 19% higher if adjusted for inflation. We showed the development of the DRG allocation of two commonly used methods of reconstruction after ablative tongue cancer surgery and the associated LoS, reimbursement, costs, and profits. As expected, the highest values were found for microvascular reconstruction. Microvascular reconstruction may also be the primary choice of

  1. Fast and Simultaneous Determination of Pu(Ⅳ) and Nitric Acid in Spent Nuclear Fuel Reprocessing Sample by Near Infrared Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    LI; Ding-ming; ZHANG; Li-hua; WANG; Ling; GONG; Yan-ping; FAN; De-jun; YI; Bao-shan; CHEN; Qiang; JI; Yong-chao; WU; Ji-zong


    Determination of Pu(Ⅳ)and nitric acid plays significant role in nuclear fuel reprocessing plant to control process accurately and timely.Coupling C-T fixed-type grating with InGaAs detector,a new novel analytical system for simultaneous measurement of nitric acid and Pu(Ⅳ)was developed by our working group.After obtaining near infrared absorptive spectra by the spectroscopic instrument,the spectra data

  2. Nitric oxide nanoparticles: Pre-clinical utility as a therapeutic for intramuscular abscesses


    Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.


    Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine absce...

  3. Computational and experimental studies of microvascular void features for passive-adaptation of structural panel dynamic properties (United States)

    Sears, Nicholas C.; Harne, Ryan L.


    The performance, integrity, and safety of built-up structural systems are critical to their effective employment in diverse engineering applications. In conflict with these goals, harmonic or random excitations of structural panels may promote large amplitude oscillations that are particularly harmful when excitation energies are concentrated around natural frequencies. This contributes to fatigue concerns, performance degradation, and failure. While studies have considered active or passive damping treatments that adapt material characteristics and configurations for structural control, it remains to be understood how vibration properties of structural panels may be tailored via internal material transitions. Motivated to fill this knowledge gap, this research explores an idea of adapting the static and dynamic material distribution of panels through embedded microvascular channels and strategically placed voids that permit the internal movement of fluids within the panels for structural dynamic control. Finite element model and experimental investigations probe how redistributing material in the form of microscale voids influences the global vibration modes and natural frequencies of structural panels. Through parameter studies, the relationships among void shape, number, size, and location are quantified towards their contribution to the changing structural dynamics. For the panel composition and boundary conditions considered in this report, the findings reveal that transferring material between strategically placed voids may result in eigenfrequency changes as great as 10.0, 5.0, and 7.4% for the first, second, and third modes, respectively.

  4. Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability.

    Directory of Open Access Journals (Sweden)

    Hongxiu Wen

    Full Text Available Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV-infected patients, is known to accelerate neuroinflammation associated with HIV-1 infection. Detailed molecular mechanisms of morphine action however, remain poorly understood. Platelet-derived growth factor (PDGF has been implicated in a number of pathological conditions, primarily due to its potent mitogenic and permeability effects. Whether morphine exposure results in enhanced vascular permeability in brain endothelial cells, likely via induction of PDGF, remains to be established. In the present study, we demonstrated morphine-mediated induction of PDGF-BB in human brain microvascular endothelial cells, an effect that was abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade (cell signaling and loss-of-function (Egr-1 approaches demonstrated the role of mitogen-activated protein kinases (MAPKs, PI3K/Akt and the downstream transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF-BB. Functional significance of increased PDGF-BB manifested as increased breach of the endothelial barrier as evidenced by decreased expression of the tight junction protein ZO-1 in an in vitro model system. Understanding the regulation of PDGF expression may provide insights into the development of potential therapeutic targets for intervention of morphine-mediated neuroinflammation.

  5. Stimulated mast cells promote maturation of myocardial microvascular endothelial cell neovessels by modulating the angiopoietin-Tie-2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Division of Cardiology, Shanghai Sixth People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, Division of Cardiology, Shanghai Sixth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Yancheng People' s First Hospital, Division of Cardiology, Yancheng, Jiangsu, China, Division of Cardiology, Yancheng People’s First Hospital, Yancheng, Jiangsu (China); Zhu, W.; Tao, J.P.; Zhang, Q.Y.; Wei, M. [Division of Cardiology, Shanghai Sixth People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, Division of Cardiology, Shanghai Sixth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)


    Angiopoietin (Ang)-1 and Ang-2 interact in angiogenesis to activate the Tie-2 receptor, which may be involved in new vessel maturation and regression. Mast cells (MCs) are also involved in formation of new blood vessels and angiogenesis. The present study was designed to test whether MCs can mediate angiogenesis in myocardial microvascular endothelial cells (MMVECs). Using a rat MMVEC and MC co-culture system, we observed that Ang-1 protein levels were very low even though its mRNA levels were increased by MCs. Interestingly, MCs were able to enhance migration, proliferation, and capillary-like tube formation, which were associated with suppressed Ang-2 protein expression, but not Tie-2 expression levels. These MCs induced effects that could be reversed by either tryptase inhibitor [N-tosyl-L-lysine chloromethyl ketone (TLCK)] or chymase inhibitor (N-tosyl-L-phenylalanyl chloromethyl ketone), with TLCK showing greater effects. In conclusion, our data indicated that MCs can interrupt neovessel maturation via suppression of the Ang-2/Tie-2 signaling pathway.

  6. Dissolution behavior of PFBR MOX fuel in nitric acid

    International Nuclear Information System (INIS)

    Kelkar, Anoop; Kapoor, Y.S.; Singh, Mamta; Meena, D.L.; Pandey, Ashish; Bhatt, R.B.; Behere, P.G.


    Present paper describes the dissolution characteristics of PFBR MOX fuel (U,Pu)O 2 in nitric acid. An overview of batch dissolution experiments, studying the percentage dissolution of uranium and plutonium in (U, Pu)O 2 MOX sintered pellets with different percentage of PuO 2 with reference to time and nitric acid concentration are described. 90% of uranium and plutonium of PFBR MOX gets dissolves in 2 hrs and amount of residue increases with the decrease in nitric acid concentration. Overall variation in percentage residue in PFBR MOX fuel after dissolution test also described. (author)

  7. Leaching of sodium carbonate cakes by nitric acid

    International Nuclear Information System (INIS)

    Troyanker, L.S.; Nikonov, V.N.


    The interaction has been studied of soda cakes of fluorite-rare-earth concentrate with nitric acid. The effect of a number of factors on extraction of REE into a nitric solution has been considered: the final acidity of the pulp, the duration of leaching, and the ratio between solid and liquid phases. The effect of adding aluminium nitrate into the pulp has also been studied. It has been shown that three-stage counterflow leaching of soda cakes with nitric acid increases REE extraction approximately by 10%

  8. Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study. (United States)

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


    Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia. In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease. Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46

  9. 76 FR 63878 - New Source Performance Standards Review for Nitric Acid Plants (United States)


    ... technologies. Nitric acid production is also one of the industrial sectors for which ``white papers'' were... standards (NSPS) for nitric acid plants. Nitric acid plants include one or more nitric acid production units. These proposed revisions include a change to the nitrogen oxides (NO X ) emission limit, which applies...

  10. Determination of americium and curium using ion-exchange in the nitric-acid-methanol medium for environmental analysis

    International Nuclear Information System (INIS)

    Holm, E.; Fukai, R.


    While transplutonic elements are only slightly sorbed to anion exchangers from hydrochloric or nitric acid media, the presence of alcohol enhances the anionic exchange of these elements, especially in nitric and sulfuric solutions. In the present work a method has been developed for determining americium and curium in environmental samples, on the basis of the difference between the sorption characteristics to anion exchangers in the acid-methanol system of these transplutonic elements and those of plutonium, polonium and thorium. The method also permits us to perform sequential determination of plutonium, when necessary

  11. Behavior of zirconium in nitric medium in the extraction with TBP 30% V/V in dodecane

    International Nuclear Information System (INIS)

    Azevedo, H.L.P. de.


    The extraction of 10 -2 M zirconium by TBP 30% V/V in dodecane from nitric acid solutions is studied as a function of the following parameters : nitric acid concentration, temperature and the presence of radiolytic degradation products of the organic phase. For this study natural zirconium is irradiated in order to obtain Zr-95, used as a tracer. The experimental results are discussed considering the displacement of the equilibrium in the systems studied as a function of different experimental variables. (Author) [pt

  12. Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms (United States)

    Dongare, Shirish; Mathur, Rajani; Saxena, Rohit; Mathur, Sandeep; Agarwal, Renu; Nag, Tapas C.; Srivastava, Sushma; Kumar, Pankaj


    Purpose Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes. Methods Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels. Results Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract–treated group compared to the vehicle-treated group. Conclusions The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation. PMID:27293376

  13. The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network. (United States)

    Sosa, Jose M; Nielsen, Nathan D; Vignes, Seth M; Chen, Tanya G; Shevkoplyas, Sergey S


    The ability of red blood cells (RBC) to undergo a wide range of deformations while traversing the microvasculature is crucial for adequate perfusion. Interpretation of RBC deformability measurements performed in vitro in the context of microvascular perfusion has been notoriously difficult. This study compares the measurements of RBC deformability performed using micropore filtration and ektacytometry with the RBC ability to perfuse an artificial microvascular network (AMVN). Human RBCs were collected from healthy consenting volunteers, leukoreduced, washed and exposed to graded concentrations (0-0.08%) of glutaraldehyde (a non-specific protein cross-linker) and diamide (a spectrin-specific protein cross-linker) to impair the deformability of RBCs. Samples comprising cells with two different levels of deformability were created by adding non-deformable RBCs (hardened by exposure to 0.08% glutaraldehyde) to the sample of normal healthy RBCs. Ektacytometry indicated a nearly linear decline in RBC deformability with increasing glutaraldehyde concentration. Micropore filtration showed a significant reduction only for concentrations of glutaraldehyde higher than 0.04%. Neither micropore filtration nor ektacytometry measurements could accurately predict the AMVN perfusion. Treatment with diamide reduced RBC deformability as indicated by ektacytometry, but had no significant effect on either micropore filtration or the AMVN perfusion. Both micropore filtration and ektacytometry showed a linear decline in effective RBC deformability with increasing fraction of non-deformable RBCs in the sample. The corresponding decline in the AMVN perfusion plateaued above 50%, reflecting the innate ability of blood flow in the microvasculature to bypass occluded capillaries. Our results suggest that in vitro measurements of RBC deformability performed using either micropore filtration or ektacytometry may not represent the ability of same RBCs to perfuse microvascular networks. Further

  14. Spectroscopic microvascular blood detection from the endoscopically normal colonic mucosa: biomarker for neoplasia risk. (United States)

    Roy, Hemant K; Gomes, Andrew; Turzhitsky, Vladimir; Goldberg, Michael J; Rogers, Jeremy; Ruderman, Sarah; Young, Kim L; Kromine, Alex; Brand, Randall E; Jameel, Mohammed; Vakil, Parmede; Hasabou, Nahla; Backman, Vadim


    We previously used a novel biomedical optics technology, 4-dimensional elastically scattered light fingerprinting, to show that in experimental colon carcinogenesis the predysplastic epithelial microvascular blood content is increased markedly. To assess the potential clinical translatability of this putative field effect marker, we characterized the early increase in blood supply (EIBS) in human beings in vivo. We developed a novel, endoscopically compatible, polarization-gated, spectroscopic probe that was capable of measuring oxygenated and deoxygenated (Dhb) hemoglobin specifically in the mucosal microcirculation through polarization gating. Microvascular blood content was measured in 222 patients from the endoscopically normal cecum, midtransverse colon, and rectum. If a polyp was present, readings were taken from the polyp tissue along with the normal mucosa 10-cm and 30-cm proximal and distal to the lesion. Tissue phantom studies showed that the probe had outstanding accuracy for hemoglobin determination (r(2) = 0.99). Augmentation of microvasculature blood content was most pronounced within the most superficial ( approximately 100 microm) layer and dissipated in deeper layers (ie, submucosa). EIBS was detectable within 30 cm from the lesion and the magnitude mirrored adenoma proximity. This occurred for both oxygenated hemoglobin and DHb, with the effect size being slightly greater for DHb. EIBS correlated with adenoma size and was not engendered by nonneoplastic (hyperplastic) polyps. We show, herein, that in vivo microvascular blood content can be measured and provides an accurate marker of field carcinogenesis. This technological/biological advance has numerous potential applications in colorectal cancer screening such as improved polyp detection and risk stratification.

  15. Uric acid is associated with inflammation, coronary microvascular dysfunction, and adverse outcomes in postmenopausal women (United States)

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


    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. The reliability of a single protocol to determine endothelial, microvascular and autonomic functions in adolescents. (United States)

    Bond, Bert; Williams, Craig A; Barker, Alan R


    Impairments in macrovascular, microvascular and autonomic function are present in asymptomatic youths with clustered cardiovascular disease risk factors. This study determines the within-day reliability and between-day reliability of a single protocol to non-invasively assess these outcomes in adolescents. Forty 12- to 15-year-old adolescents (20 boys) visited the laboratory in a fasted state on two occasions, approximately 1 week apart. One hour after a standardized cereal breakfast, macrovascular function was determined via flow-mediated dilation (FMD). Heart rate variability (root mean square of successive R-R intervals; RMSSD) was determined from the ECG-gated ultrasound images acquired during the FMD protocol prior to cuff occlusion. Microvascular function was simultaneously quantified as the peak (PRH) and total (TRH) hyperaemic response to occlusion in the cutaneous circulation of the forearm via laser Doppler imaging. To address within-day reliability, a subset of twenty adolescents (10 boys) repeated these measures 90 min afterwards on one occasion. The within-day typical error and between-day typical error expressed as a coefficient of variation of these outcomes are as follows: ratio-scaled FMD, 5·1% and 10·6%; allometrically scaled FMD, 4·4% and 9·4%; PRH, 11% and 13·3%; TRH, 29·9% and 23·1%; and RMSSD, 17·6% and 17·6%. The within- and between-day test-retest correlation coefficients for these outcomes were all significant (r > 0·54 for all). Macrovascular, microvascular and autonomic functions can be simultaneously and non-invasively determined in adolescents using a single protocol with an appropriate degree of reproducibility. Determining these outcomes may provide greater understanding of the progression of cardiovascular disease and aid early intervention. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  17. Associations between diabetes self-management and microvascular complications in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Fatemeh Mehravar


    Full Text Available OBJECTIVES: Diabetes is a major public health problem that is approaching epidemic proportions globally. Diabetes self-management can reduce complications and mortality in type 2 diabetic patients. The purpose of this study was to examine associations between diabetes self-management and microvascular complications in patients with type 2 diabetes. METHODS: In this cross-sectional study, 562 Iranian patients older than 30 years of age with type 2 diabetes who received treatment at the Diabetes Research Center of the Endocrinology and Metabolism Research Institute of the Tehran University of Medical Sciences were identified. The participants were enrolled and completed questionnaires between January and April 2014. Patients’ diabetes self-management was assessed as an independent variable by using the Diabetes Self-Management Questionnaire translated into Persian. The outcomes were the microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy, identified from the clinical records of each patient. A multiple logistic regression model was used to estimate odds ratios (ORs and 95% confidence intervals (CIs between diabetes self-management and the microvascular complications of type 2 diabetes, adjusting for potential confounders. RESULTS: After adjusting for potential confounders, a significant association was found between the diabetes self-management sum scale and neuropathy (adjusted OR, 0.64; 95% CI, 0.45 to 0.92, p=0.01. Additionally, weak evidence was found of an association between the sum scale score of diabetes self-management and nephropathy (adjusted OR, 0.71; 95% CI, 0.47 to 1.05, p=0.09. CONCLUSIONS: Among patients with type 2 diabetes, a lower diabetes self-management score was associated with higher rates of nephropathy and neuropathy.

  18. Depth-dependent flow and pressure characteristics in cortical microvascular networks.

    Directory of Open Access Journals (Sweden)

    Franca Schmid


    Full Text Available A better knowledge of the flow and pressure distribution in realistic microvascular networks is needed for improving our understanding of neurovascular coupling mechanisms and the related measurement techniques. Here, numerical simulations with discrete tracking of red blood cells (RBCs are performed in three realistic microvascular networks from the mouse cerebral cortex. Our analysis is based on trajectories of individual RBCs and focuses on layer-specific flow phenomena until a cortical depth of 1 mm. The individual RBC trajectories reveal that in the capillary bed RBCs preferentially move in plane. Hence, the capillary flow field shows laminar patterns and a layer-specific analysis is valid. We demonstrate that for RBCs entering the capillary bed close to the cortical surface (< 400 μm the largest pressure drop takes place in the capillaries (37%, while for deeper regions arterioles are responsible for 61% of the total pressure drop. Further flow characteristics, such as capillary transit time or RBC velocity, also vary significantly over cortical depth. Comparison of purely topological characteristics with flow-based ones shows that a combined interpretation of topology and flow is indispensable. Our results provide evidence that it is crucial to consider layer-specific differences for all investigations related to the flow and pressure distribution in the cortical vasculature. These findings support the hypothesis that for an efficient oxygen up-regulation at least two regulation mechanisms must be playing hand in hand, namely cerebral blood flow increase and microvascular flow homogenization. However, the contribution of both regulation mechanisms to oxygen up-regulation likely varies over depth.

  19. Microvascular volume in symptomatic Achilles tendons is associated with VISA-A score. (United States)

    Praet, S F E; Ong, J H; Purdam, C; Welvaert, M; Lovell, G; Dixon, L; Gaida, J E; Anglim, J; Manzanero, S; Vlahovich, N; Hughes, D; Waddington, G


    The role of neovascularisation in tendinopathy is still poorly understood, potentially due to technical limitations of conventional power Doppler ultrasound. This study aimed to investigate the association between contrast-enhanced ultrasound (CEUS) microvascular volume (MV), Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and intrinsic Achilles tendon tenderness, as well as two different Power Doppler modes. Cross-sectional study. 20 individuals with uni- or bilateral Achilles tendinopathy completed a VISA-A questionnaire, and underwent microvascular volume measurements of the Achilles tendon mid-portion using both conventional, ultrasensitive (SMI™) power Doppler ultrasound and CEUS. Intrinsic tendon tenderness was assessed with sensation detection threshold to extracorporeal shock waves (ESW). Linear Mixed Model analysis was used to determine the association between microvascular volume (MV), VISA-A, and ESW-detection threshold for both symptomatic and asymptomatic Achilles tendons. There was a significant association between VISA-A and MV (B=-5.3, 95%CI=[-8.5; -2.0], P=0.0004), and between MV and symptom duration (B=-1.7, 95%CI=[-3.2; -5.0], P=0.023). No significant associations were found between power Doppler ultrasound and CEUS-based MV or between CEUS-based MV and ESW-detection threshold. In comparison with conventional power Doppler ultrasound, SMI™ showed on average similar detection capacity for neovessels in the mid-portion of the Achilles tendon, whilst being superior for detecting neovessels within Kager's fat pad (t=3.46, 95%CI=[0.27; 1.03], P<0.005). Our results indicate that CEUS-based MV of the Achilles tendon is moderately associated with Achilles tendon symptoms. In accordance, CEUS-detected MV could be a novel target for treatment as it seems to be more sensitive than PDU and is correlated with symptoms. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. [Reconstruction of oral mucosa with a micro-vascularized fascia-cutaneous flap from the forearm]. (United States)

    Burgueño García, Miguel; Cebrián Carretero, José Luis; Muñoz Caro, Jesús Manuel; Arias Gallo, Javier


    Epidermoid carcinoma of jugal mucosa is an aggressive tumor. Its treatment is based on broad excision and reconstruction in order to avoid fibrosis and restriction of mouth opening. Neck dissection and radiotherapy are indicated in selected cases. We display our experience with microvascularized flaps with the aim of preventing the flaws. We reconsider 8 patients (representing 10 flaps) handle in our Department. Besides we discuss other therapeutic alternatives after the growth's removal. The conclusion reached is that the mucovascularized forearm flaps give a great quantity of thin tissue and therefore so results to be the best option for the reconstruction of the jugal mucosa.

  1. Autologous Latissimus Dorsi Breast Reconstruction Flap Salvage: Microvascular Anastomosis with Serratus Branch

    Directory of Open Access Journals (Sweden)

    Victoria Kuta, BScH


    Full Text Available Summary:. Autologous breast reconstruction has become a standard option during the recovery of breast cancer survivors. Although pedicle damage is a rare complication of this procedure, extensive torsion or tension can lead to partial or total flap failure. We report a case of partial flap salvage after accidental transection of the pedicled blood supply within the intramuscular course of a latissimus dorsi musculocutaneous flap. This salvage technique involved microvascular anastomosis between the remaining vasculature of the latissimus dorsi pedicle and the serratus branch of the thoracodorsal artery and vein.

  2. Magnetic alginate microfibers as scaffolding elements for the fabrication of microvascular-like structures. (United States)

    Sun, Tao; Shi, Qing; Huang, Qiang; Wang, Huaping; Xiong, Xiaolu; Hu, Chengzhi; Fukuda, Toshio


    Traditional cell-encapsulating scaffolds may elicit adverse host responses and inhomogeneity in cellular distribution. Thus, fabrication techniques for cellular self-assembly with micro-scaffold incorporation have been used recently to generate toroidal cellular modules for the bottom-up construction of vascular-like structures. The micro-scaffolds show advantage in promoting tissue formation. However, owing to the lack of annular cell micro-scaffolds, it remains a challenge to engineer micro-scale toroidal cellular modules (micro-TCMs) to fabricate microvascular-like structures. Here, magnetic alginate microfibers (MAMs) are used as scaffolding elements, where a winding strategy enables them to be formed into micro-rings as annular cell micro-scaffolds. These micro-rings were investigated for NIH/3T3 fibroblast growth as a function of surface chemistry and MAM size. Afterwards, micro-TCMs were successfully fabricated with the formation of NIH/3T3 fibroblasts and extracellular matrix layers on the three-dimensional micro-ring surfaces. Simple non-contact magnetic assembly was used to stack the micro-TCMs along a micro-pillar, after which cell fusion rapidly connected the assembled micro-TCMs into a microvascular-like structure. Endothelial cells or drugs encapsulated in the MAMs could be included in the microvascular-like structures as in vitro cellular models for vascular tissue engineering, or as miniaturization platforms for pharmaceutical drug testing in the future. Magnetic alginate microfibers functioned as scaffolding elements for guiding cell growth in micro-scale toroidal cellular modules (micro-TCMs) and provided a magnetic functionality to the micro-TCMs for non-contact 3D assembly in external magnetic fields. By using the liquid/air interface, the non-contact spatial manipulation of the micro-TCMs in the liquid environment was performed with a cost-effective motorized electromagnetic needle. A new biofabrication paradigm of construct of microvascular

  3. Optical measurements of microvascular circulatory function in the foot for detection of peripheral neuropathy (United States)

    Zamora, G.; Chekh, V.; Burge, M.; Barriga, E. S.; Luan, S.; Heintz, P.; Edwards, A.; McGrew, E.; Soliz, P.


    The purpose of this research is to quantify functional signals in the microvascular circulation of the plantar. Our device is based on thermal and spectral technologies that can be easily adopted in clinical and tele-screening settings. Eightytwo thousand amputations are performed annually on diabetics in the US. The cost of foot disorder diagnosis and management are estimated at $10.9 billion dollars annually. Our experiments on normal controls and diabetics assess the temperature recovery time characteristics due to cold provocation to the bottom of the foot (plantar). A difference in the nature of the recovery time between normal controls and diabetics was observed.

  4. The nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit

    International Nuclear Information System (INIS)

    Kurbonov, A.S.; Mamatov, E.D.; Suleymani, M.; Borudzherdi, A.; Mirsaidov, U.M.


    Present article is devoted to nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit of Tajikistan. The obtaining of boric acid from pre backed danburite concentrate by decomposition of nitric acid was studied. The chemical composition of danburite concentrate was determined. The laboratory study of danburite leaching by nitric acid was conducted. The influence of temperature, process duration, nitric acid concentration on nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit was studied as well. The optimal conditions of nitric acid decomposition of calcined danburite concentrate of Ak-Arkhar Deposit, including temperature, process duration, nitric acid concentration and particle size were proposed.

  5. Longitudinal study of microvascular involvement by nailfold capillaroscopy in children with Henoch-Schönlein purpura. (United States)

    Zampetti, Anna; Rigante, Donato; Bersani, Giulia; Rendeli, Claudia; Feliciani, Claudio; Stabile, Achille


    The aim of this study is to describe by video-nailfold capillaroscopy the microvascular involvement and capillary changes in children with Henoch-Schönlein purpura (HSp) and to establish a possible correlation with clinical outcome. Thirty-one patients underwent capillaroscopic evaluation through a videomicroscope during the acute phase and after 6 months. Twenty sex/age-matched controls were also examined. All capillaroscopic variables were statistically examined in combination with laboratoristic/clinical data. Architectural and morphological changes recorded during the acute phase were statistically significant in comparison to the controls (p capillaroscopy changes, laboratoristic/clinical data, and outcome. Video-nailfold capillaroscopy can be a simple tool to evaluate microvascular abnormalities in the acute phase of HSp, and the persistence of oedema could suggest an incomplete disease resolution at a microvascular level.

  6. Acute Respiratory Distress Syndrome (ARDS After Nitric Acid Inhalation

    Directory of Open Access Journals (Sweden)

    Gülay Kır


    Full Text Available Lung injury resulting from inhalation of chemical products continues to be associated with high morbidity and mortality. Concentrated nitric acids are also extremely corrosive fuming chemical liquids. Fumes of nitric acid (HNO3 and various oxides of nitrogen such as nitric oxide (NO and nitrogen dioxide (NO2 may cause fatal illnesses such as severe pulmonary edema and acute respiratory distress syndrome (ARDS when inhaled. Intensive respiratory management including mechanical ventilation with positive end expiratory pressure (PEEP, inverse ratio ventilation, replacement of surfactant and extracorporeal membrane oxygenation (ECMO, steroids and n-acetylcysteine (NAC may improve survival. In this case report we present the diagnosis and successful treatment of a 57 years old male patient who developed ARDS following pulmonary edema due to nitric acid fumes inhalation.

  7. Modulation of glucose uptake in adipose tissue by nitric oxide ...

    Indian Academy of Sciences (India)


    ion-dependent breakdown and trans-nitrosation reactions are ... [McGrowder D, Ragoobirsingh D and Brown P 2006 Modulation of glucose uptake in adipose tissue by nitric oxide-generating ... Briefly, nicotinamide (Sigma Chemical Co.,.

  8. Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

    African Journals Online (AJOL)

    Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

  9. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

    NARCIS (Netherlands)

    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.


    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric

  10. Nitric oxide inhibits glycogen synthesis in isolated rat hepatocytes

    NARCIS (Netherlands)

    Sprangers, F.; Sauerwein, H. P.; Romijn, J. A.; van Woerkom, G. M.; Meijer, A. J.


    There is increasing evidence for the existence of intrahepatic regulation of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase and phosphoenolpyruvate carboxykinase. However, NO may also influence glucose metabolism at

  11. Passive Sampler for Measurements of Atmospheric Nitric Acid Vapor (HNO3 Concentrations

    Directory of Open Access Journals (Sweden)

    Andrzej Bytnerowicz


    Full Text Available Nitric acid (HNO3 vapor is an important nitrogenous air pollutant responsible for increasing saturation of forests with nitrogen and direct injury to plants. The USDA Forest Service and University of California researchers have developed a simple and inexpensive passive sampler for monitoring air concentrations of HNO3. Nitric acid is selectively absorbed on 47-mm Nylasorb nylon filters with no interference from particulate NO3-. Concentrations determined with the passive samplers closely corresponded with those measured with the co-located honeycomb annular denuder systems. The PVC protective caps of standardized dimensions protect nylon filters from rain and wind and allow for reliable measurements of ambient HNO3 concentrations. The described samplers have been successfully used in Sequoia National Park, the San Bernardino Mountains, and on Mammoth Mountain in California.

  12. Control of instability in nitric acid evaporators for plutonium processing

    International Nuclear Information System (INIS)


    Improved control of the nitric acid process evaporators requires the detection of spontaneously unstable operating conditions. This process reduces the volume of contaminated liquid by evaporating nitric acid and concentrating salt residues. If a instability is identified quickly, prompt response can avert distillate contamination. An algorithm applied to the runtime data was evaluated to detect this situation. A snapshot of data from a histogram in the old process control software was captured during the unstable conditions and modeled

  13. Acute chemical pneumonitis caused by nitric acid inhalation: case report

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Hyung Shim; Lee, In Jae; Ko, Eun Young; Lee, Jae Young; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)


    Chemical pneumonitis induced by nitric acid inhalation is a rare clinical condition. The previously reported radiologic findings of this disease include acute permeability pulmonary edema, delayed bronchiolitis obliterans, and bronchiectasis. In very few published rare radiologic reports has this disease manifested as acute alveolar injury; we report a case of acute chemical pneumonitis induced by nitric acid inhalation which at radiography manifested as bilateral perihilar consolidation and ground-glass attenuation, suggesting acute alveolar injury.

  14. Formation of nitric acid hydrates - A chemical equilibrium approach (United States)

    Smith, Roland H.


    Published data are used to calculate equilibrium constants for reactions of the formation of nitric acid hydrates over the temperature range 190 to 205 K. Standard enthalpies of formation and standard entropies are calculated for the tri- and mono-hydrates. These are shown to be in reasonable agreement with earlier calorimetric measurements. The formation of nitric acid trihydrate in the polar stratosphere is discussed in terms of these equilibrium constants.

  15. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann


    Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has...

  16. Initiation Temperature for Runaway Tri-n-Butyl Phosphate/Nitric Acid Reaction

    Energy Technology Data Exchange (ETDEWEB)

    Rudisill, T.S.


    During a review of the H-Canyon authorization basis, Defense Nuclear Facility Safety Board (DNFSB) staff members questioned the margin of safety associated with a postulated tri-n-butyl phosphate (TBP)/nitric acid runaway reaction due to the inadvertent heating of a canyon tank containing greater than 3000 lbs (1362 kg) of TBP. The margin of safety was partially based on experiments and calculations performed by the Actinide Technology Section (ATS) to support deletion of indication of tank agitation as a Safety Class System. In the technical basis for deletion of this system, ATS personnel conservatively calculated the equilibrium temperature distribution of a canyon tank containing TBP and nitric acid layers which were inadvertently heated by a steam jet left on following a transfer. The maximum calculated temperature (128 degrees C) was compared to the minimum initiation temperature for a runaway reaction (greater than 130 degrees C) documented by experimental work in the mid 195 0s. In this work, the initiation temperature as a function of nitric acid concentration was measured for 0 and 20 wt percent dissolved solids. The DNFSB staff members were concerned that data for 0 wt percent dissolved solids were not conservative given the facts that data for 20 wt percent dissolved solids show initiation temperatures at or below 130 degrees C and H-Canyon solutions normally contained a small amount of dissolved solids.

  17. 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


    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...

  18. Evaluation of applicability and efficacy of the reconstructive microvascular surgery of advanced cancer of the lower face with mandible infiltration

    International Nuclear Information System (INIS)

    Maciejewski, A.


    The aim of this study is to evaluate applicability and efficacy of reconstructive and microvascular surgery for patients with locally advanced cancer of the lower face with mandible infiltration, regarding to various technique of mandible and tongue reconstruction using flaps and to own modifications. Complex quality of life including functional, aesthetic, social and effect has also been evaluated. For patients with advanced cancer of the region infiltrating mandible reconstructive and microvascular surgery as a sole modality or combined with postoperative radiotherapy, is effective method of radical treatment, providing 80% of chance of 3-year disease-free survival and reduces the risk of recurrence by 60%. (author)

  19. Optical measurements of lung microvascular filtration coefficient using polysulfone fibers. (United States)

    Klaesner, J W; Roselli, R J; Evans, S; Pou, N A; Parker, R E; Tack, G; Parham, M


    Lung fluid balance, which is governed by the product of net transvascular pressure difference and lung filtration coefficient, can be altered in pulmonary diseases. A simple measurement of the lung filtration coefficient (Kfc) would be clinically useful and has been examined by several researchers. Current methods of determining Kfc include gravimetric measurement in isolated lungs and lymph node cannulation, neither of which can be extended to human use. Optical measurements of protein concentration changes in venous blood can be combined with pressure measurements to calculate Kfc. Blood, though, contains red corpuscles, which tend to absorb and scatter light, obscuring these optical measurements. In this study, an optical system was developed in which a polysulfone filter cartridge was used to remove red blood cells before the filtrate was passed through a spectrophotometer. Absorbance changes caused by changes in concentration of albumin labeled with Evans Blue were monitored at 620 nm after venous pressure was elevated by about 13 cm H2O. Optical measurements of Kfc averaged 0.401 +/- 0.074 (ml/min cm H2O 100 g DLW) for an isolated canine lung. Optical measurements of Kfc (0.363 +/- 0.120 ml/min cm H2O 100 g DLW) were made for the first time in an intact, closed chest sheep in which pulmonary pressure was altered by inflating a Foley balloon in the left atrium. We conclude that absorbance and scattering artifacts introduced by red blood cells can be eliminated by first filtering the blood through polysulfone fibers. Kfc measurements using the optical method are similar to values obtained by others using gravimetric methods. Finally, we have demonstrated that the technique can be used to estimate Kfc in an intact animal.

  20. Role of nitric oxide in pheromone-mediated intraspecific communication in mice. (United States)

    Agustín-Pavón, Carmen; Martínez-Ricós, Joana; Martínez-García, Fernando; Lanuza, Enrique


    Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-NAME, 100mg/kg) blocks the innate preference displayed by female mice for sexual pheromones contained in male-soiled bedding, with a lower dose of the drug (50mg/kg) having no effect. Animals treated with the high dose of L-NAME show no reduction of olfactory discrimination of male urine in a habituation-dishabituation test, thus suggesting that the effect of the drug on the preference for male pheromones is not due to an inability to detect male urine. Alternatively, it may result from an alteration in processing the reinforcing value of pheromones as sexual signals. These results add a new piece of evidence to our understanding of the neurochemistry of intraspecific chemical communication in rodents, and suggest that the role of nitric oxide in socio-sexual behaviours should be re-evaluated taking into account the involvement of this neuromodulator in the processing of chemical signals.

  1. Nitric acid recycling and copper nitrate recovery from effluent. (United States)

    Jô, L F; Marcus, R; Marcelin, O


    The recycling of nitric acid and copper nitrate contained in an industrial effluent was studied. The experiments conducted on such a medium showed that the presence of copper nitrate significantly improves nitric acid-water separation during distillation in an azeotropic medium. At the temperature of the azeotrope, however, this metal salt starts to precipitate, making the medium pasty, thus inhibiting the nitric acid extraction process. The optimisation of parameters such as column efficiency and adding water to the boiler at the azeotrope temperature are recommended in this protocol in order to collect the various components while avoiding the formation of by-products: NOx compounds. Thus, the absence of column, along with the addition of a small volume of water at a temperature of 118 °C, significantly increases the yield, allowing 94 % nitric acid to be recovered at the end of the process, along with the residual copper nitrate. The resulting distillate, however, is sufficiently dilute to not be used as is. Rectification is required to obtain concentrated nitric acid at 15 mol·l(-1), along with a weakly acidic distillate from the distillation front. This latter is quenched using potassium hydroxide and is used as a fertiliser solution for horticulture or sheltered market gardening. This process thus allows complete recycling of all the medium's components, including that of the distillate resulting from the nitric acid rectification operation.

  2. Cellular signaling with nitric oxide and cyclic GMP

    Directory of Open Access Journals (Sweden)

    F. Murad


    Full Text Available During the past two decades, nitric oxide signaling has been one of the most rapidly growing areas in biology. This simple free radical gas can regulate an ever growing list of biological processes. In most instances nitric oxide mediates its biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis. However, the identification of effects of nitric oxide that are independent of cyclic GMP is also growing at a rapid rate. The effects of nitric oxide can mediate important physiological regulatory events in cell regulation, cell-cell communication and signaling. Nitric oxide can function as an intracellular messenger, neurotransmitter and hormone. However, as with any messenger molecule, there can be too much or too little of the substance and pathological events ensue. Methods to regulate either nitric oxide formation, metabolism or function have been used therapeutically for more than a century as with nitroglycerin therapy. Current and future research should permit the development of an expanded therapeutic armamentarium for the physician to manage effectively a number of important disorders. These expectations have undoubtedly fueled the vast research interests in this simple molecule.

  3. Nitric oxide bioavailability dysfunction involves in atherosclerosis. (United States)

    Chen, Jing-Yi; Ye, Zi-Xin; Wang, Xiu-Fen; Chang, Jian; Yang, Mei-Wen; Zhong, Hua-Hua; Hong, Fen-Fang; Yang, Shu-Long


    The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures. Copyright © 2017. Published by Elsevier Masson SAS.

  4. Nasal nitric oxide in unilateral sinus disease.

    Directory of Open Access Journals (Sweden)

    Chia-Hsiang Fu

    Full Text Available Unilateral sinus disease (USD can sometimes be difficult to accurately diagnose before surgery. The application of nasal nitric oxide (nNO for USD diagnosis and its surgical outcome in USD has not been reported in the literature. We prospectively enrolled sixty-six USD patients who underwent endoscopic sinus surgery for fungal rhinosinusitis (n = 19, chronic rhinosinusitis (CRS without nasal polyps (n = 13, CRS with nasal polyps (n = 12 and sinonasal mass lesions (n = 22. nNO levels were measured preoperatively and at three and six months postoperatively. Correlations between nNO levels and potential clinical parameters, type of disease, disease severity, and disease-related quality of life (QOL were assessed. Unlike bilateral CRS, in USD, nNO levels did not correlate with disease severity or postoperative QOL improvements. Except for fungus group, there were no differences in nNO levels between lesion and non-lesion sides in all the other groups. nNO levels on both sides were significantly elevated six months postoperatively in all groups. Fungal rhinosinusitis patients had the lowest preoperative nNO levels, and a cutoff of 239.3 ppb had the best sensitivity (79.0% and specificity (87.2% for preoperative diagnosis. While preoperative nNO levels cannot serve as an alternative marker for disease severity of USD, they were lower in fungal rhinosinusitis patients than in other USD patients and may be useful for more accurate diagnosis prior to surgery.

  5. Nitric oxide and cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Livio Dai Cas


    Full Text Available The endothelium is a dynamic organ with many properties that takes part in the regulation of the principal mechanisms of vascular physiology. Its principal functions include the control of blood-tissue exchange and permeability, the vascular tonus, and the modulation of inflammatory or coagulatory mechanisms. Many vasoactive molecules, produced by the endothelium, are involved in the control of these functions. The most important is nitric oxide (NO, a gaseous molecule electrically neutral with an odd number of electrons that gives the molecule chemically reactive radical properties. Already known in the twentieth century, NO, sometimes considered as a dangerous molecule, recently valued as an important endogenous vasodilator factor. Recently, it was discovered that it is involved in several physiological mechanisms of endothelial protection (Tab. I. In 1992, Science elected it as “molecule of the year”; 6 yrs later three American researchers (Louis Ignarro, Robert Furchgott and Fried Murad obtained a Nobel Prize for Medicine and Physiology “for their discoveries about NO as signal in the cardiovascular system”.

  6. Isothermal heat measurements of TBP-nitric acid solutions

    International Nuclear Information System (INIS)

    Smith, J.R.; Cavin, W.S.


    Net heats of reaction were measured in an isothermal calorimeter for both single phase (organic) and two phase (organic and aqueous) TBP/HNO 3 reacting solutions at temperatures above 100 C. The oxidation rate constant was determined to be 5.4E-4 min -1 at 110 C for an open ''vented'' system as compared to 1.33 E-3 min -1 in the closed system. The heat released per unit material oxidized was also reduced. The oxidation in both phases was found to be first order in nitric acid and pseudo-zero order in butylnitrate and water. The hydrolysis (esterification) rate constant determined by Nichols' (1.33E-3 min -1 ) fit the experimental data from this work well. Forced evaporation of the volatile components by the product gases from oxidation resulted in a cooling mechanism which more than balanced the heat from the oxidation reaction in the two-phased systems. Rate expressions were derived and rate constants determined for both the single and two phase systems. An approximating mathematical model was developed to fit the experimental data and to extrapolate beyond the experimental conditions. This model shows that one foot of ''reacting'' 14.3M HNO 3 aqueous phase solution at 121 C will transport sufficient water to the organic phase to replace evaporative losses, maintaining endothermicity, for organic layers up to 12.2 + 6.0 feet deep. If the pressure in a reacting system is allowed to increase due to insufficient venting the temperature of the organic phase would increase in temperature to reach a new equilibrium. The rate of oxidation would increase not only due to the increase in temperature but also from the increased concentration of dissolved HNO 3 reduction products. Another important factor is that the cooling system described in this work becomes less effective as the total pressure increases. These factors probably contributed to the explosion at Tomsk

  7. Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress (United States)

    Greaney, Jody L; DuPont, Jennifer J; Lennon-Edwards, Shannon L; Sanders, Paul W; Edwards, David G; Farquhar, William B


    Animal studies have reported dietary salt-induced reductions in vascular function independent of increases in blood pressure (BP). The purpose of this study was to determine if short-term dietary sodium loading impairs cutaneous microvascular function in normotensive adults with salt resistance. Following a control run-in diet, 12 normotensive adults (31 ± 2 years) were randomized to a 7 day low-sodium (LS; 20 mmol day−1) and 7 day high-sodium (HS; 350 mmol day−1) diet (controlled feeding study). Salt resistance, defined as a ≤5 mmHg change in 24 h mean BP determined while on the LS and HS diets, was confirmed in all subjects undergoing study (LS: 84 ± 1 mmHg vs. HS: 85 ± 2 mmHg; P > 0.05). On the last day of each diet, subjects were instrumented with two microdialysis fibres for the local delivery of Ringer solution and 20 mm ascorbic acid (AA). Laser Doppler flowmetry was used to measure red blood cell flux during local heating-induced vasodilatation (42°C). After the established plateau, 10 mm l-NAME was perfused to quantify NO-dependent vasodilatation. All data were expressed as a percentage of maximal cutaneous vascular conductance (CVC) at each site (28 mm sodium nitroprusside; 43°C). Sodium excretion increased during the HS diet (P sodium loading impairs cutaneous microvascular function independent of BP in normotensive adults and suggest a role for oxidative stress. PMID:22907057

  8. Role of aldose reductase C-106T polymorphism among diabetic Egyptian patients with different microvascular complications

    Directory of Open Access Journals (Sweden)

    Nermine Hossam Zakaria


    Full Text Available The aldose reductase pathway proves that elevated blood glucose promotes cellular dysfunction. The polyol pathway converts excess intracellular glucose into alcohols via activity of the aldose reductase. This enzyme catalyzes the conversion of glucose to sorbitol which triggers variety of intracellular changes in the tissues. Among diabetes, activity is drastically increased in association with three main co