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Sample records for acute microvascular plasticity

  1. Retinal microvascular plasticity in a premature neonate.

    PubMed

    Kandasamy, Y; Hartley, L; Smith, R

    2017-01-31

    Dilation and abnormal tortuosity of retinal vessels are the hallmarks of severe retinopathy of prematurity (ROP) in premature infants. The stages of ROP are defined by vessel appearance at the interface between the vascular and avascular retinal areas. Deregulated signaling pathways involving hypoxia-inducible factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of ROP. VEGF-antagonists are increasingly being used as 'off-label medication' to treat this condition, with some success. We present Baby SM (female), who was born prematurely at 24 weeks gestation in a tertiary neonatal intensive care unit, and with a birth weight of 640 g. On screening at 35 weeks postmenstrual age (PMA), she was noted to have ROP, which became severe by 37 weeks PMA. She received one dose of intravitreal VEGF antagonist (Bevacizumab), resulting in a decrease in vessel tortuosity and dilation. However, repeat imaging at 4 weeks showed a re-emergence of vessel tortuosity. We believe the observed changes demonstrate an inherent retinal microvascular plasticity in premature neonates. With improved survival of extremely premature neonates and the availability of retinal imaging technology, we are now able to observe this plasticity.

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

    PubMed

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

    2017-01-01

    Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P < 0.01). Taken together, these data suggest that acute lower limb heating improves both macro- and microvascular dilator function in an age dependent manner.

  3. Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

    NASA Technical Reports Server (NTRS)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.

    1993-01-01

    The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous microcirculation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, O deg, -6 deg (HDT), -12 deg, -6 deg, O deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P less than 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

  4. Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

    NASA Technical Reports Server (NTRS)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.

    1993-01-01

    The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous micro- circulation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, 0 deg, -6 deg (HDT), -12 deg, -6 deg, 0 deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P < 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar-X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

  5. Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb necrosis?

    PubMed

    Warkentin, T E; Pai, M

    2016-02-01

    For unknown reasons, a small minority of critically ill patients with septic or cardiogenic shock, multiorgan failure, and disseminated intravascular coagulation develop symmetrical acral (distal extremity) limb loss due to microvascular thrombosis ('limb gangrene with pulses'). Case reports have described preceding 'shock liver' in some critically ill patients who developed such a picture of ischemic limb necrosis. This suggests that profoundly disturbed procoagulant-anticoagulant balance featuring uncontrolled generation of thrombin-resulting from failure of the protein C and antithrombin natural anticoagulant systems due to insufficient hepatic synthesis of these crucial proteins-could explain the microvascular thrombosis and associated limb loss. We hypothesize that shock liver is the key predisposing risk factor underlying ischemic limb necrosis in the majority of patients who develop this complication in the setting of acute disseminated intravascular coagulation complicating septic or cardiogenic shock. As shock liver precedes onset of limb ischemia by several days, therapeutic intervention may be possible.

  6. Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men.

    PubMed

    Phillips, Bethan E; Atherton, Philip J; Varadhan, Krishna; Limb, Marie C; Williams, John P; Smith, Kenneth

    2016-05-01

    The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

  7. Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane.

    PubMed

    Eldridge, Brittany N; Xing, Fei; Fahrenholtz, Cale D; Singh, Ravi N

    2017-03-09

    There is a growing interest in the use of multiwalled carbon nanotubes (MWCNTs) to treat diseases of the brain. Little is known about the effects of MWCNTs on human brain microvascular endothelial cells (HBMECs), which make up the blood vessels in the brain. In our studies, we evaluate the cytotoxicity of MWCNTs and acid oxidized MWNCTs, with or without a phospholipid-polyethylene glycol coating. We determined the cytotoxic effects of MWCNTs on both tissue-mimicking cultures of HBMECs grown on basement membrane and on monolayer cultures of HBMECs grown on plastic. We also evaluated the effects of MWCNT exposure on the capacity of HBMECs to form rings after plating on basement membrane, a commonly used assay to evaluate angiogenesis. We show that tissue-mimicking cultures of HBMECs are less sensitive to all types of MWCNTs than monolayer cultures of HBMECs. Furthermore, we found that MWCNTs have little impact on the capacity of HBMECs to form rings. Our results indicate that relative cytotoxicity of MWCNTs is significantly affected by the type of cell culture model used for testing, and supports further research into the use of tissue-mimicking endothelial cell culture models to help bridge the gap between in vitro and in vivo toxicology.

  8. Impact of microvascular obstruction on semiautomated techniques for quantifying acute and chronic myocardial infarction by cardiovascular magnetic resonance

    PubMed Central

    Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; Bhuva, Anish N; Treibel, Thomas A; Fontana, Marianna; Weinmann, Shane; Sirker, Alex; Herrey, Anna S; Manisty, Charlotte; Moon, James C; Hausenloy, Derek J

    2016-01-01

    Aims The four most promising semiautomated techniques (5-SD, 6-SD, Otsu and the full width half maximum (FWHM)) were compared in paired acute and follow-up cardiovascular magnetic resonance (CMR), taking into account the impact of microvascular obstruction (MVO) and using automated extracellular volume fraction (ECV) maps for reference. Furthermore, their performances on the acute scan were compared against manual myocardial infarct (MI) size to predict adverse left ventricular (LV) remodelling (≥20% increase in end-diastolic volume). Methods 40 patients with reperfused ST segment elevation myocardial infarction (STEMI) with a paired acute (4±2 days) and follow-up CMR scan (5±2 months) were recruited prospectively. All CMR analysis was performed on CVI42. Results Using manual MI size as the reference standard, 6-SD accurately quantified acute (24.9±14.0%LV, p=0.81, no bias) and chronic MI size (17.2±9.7%LV, p=0.88, no bias). The performance of FWHM for acute MI size was affected by the acquisition sequence used. Furthermore, FWHM underestimated chronic MI size in those with previous MVO due to the significantly higher ECV in the MI core on the follow-up scans previously occupied by MVO (82 (75–88)% vs 62 (51–68)%, p<0.001). 5-SD and Otsu were precise but overestimated acute and chronic MI size. All techniques were performed with high diagnostic accuracy and equally well to predict adverse LV remodelling. Conclusions 6-SD was the most accurate for acute and chronic MI size and should be the preferred semiautomatic technique in randomised controlled trials. However, 5-SD, FWHM and Otsu could also be used when precise MI size quantification may be adequate (eg, observational studies). PMID:28008358

  9. Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

    PubMed Central

    LeBlanc, Amanda J.; Touroo, Jeremy S.; Hoying, James B.

    2012-01-01

    A three-dimensional tissue construct was created using adipose-derived stromal vascular fraction (SVF) cells and evaluated as a microvascular protection treatment in a myocardial infarction (MI) model. This study evaluated coronary blood flow (BF) and global left ventricular function after MI with and without the SVF construct. Fischer-344 rats were separated into four groups: sham operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF). SVF cells were labeled with green fluorescent protein (GFP). Immediately postinfarct, constructs were implanted onto the epicardium at the site of ischemia. Four weeks postsurgery, the coronary BF reserve was significantly decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the sham group. The coronary BF reserve of the sham and MI SVF groups in the area at risk was not significantly different (sham group: 83 ± 22% and MI SVF group: 57 ± 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed engrafted SVF cells around microvessels in the infarct region 4 wk postimplant. Overall heart function, specifically ejection fraction, was significantly greater in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 ± 4%, MI: 37 ± 8%, and MI Vicryl: 29 ± 6%). In conclusion, adipose-derived SVF cells can be used to construct a novel therapeutic modality for treating microvascular instability and ischemia through implantation on the epicardial surface of the heart. The SVF construct implanted immediately after MI not only maintains heart function but also sustains microvascular perfusion and function in the infarct area by sustaining the coronary BF reserve. PMID:22140045

  10. [Using prostaglandin E1 in microvascular reconstruction of the upper extremity after acute trauma].

    PubMed

    Slodicka, R; Lautenbach, M; Eisenschenk, A

    2002-01-01

    The operative treatment of hand and upper extremity trauma with injury of main vessels becomes a daily standard work in trauma and microsurgical replantation centers. The techniques of vessel and soft tissue reconstruction are well known. The outcome of the replantation depends on various factors. Main influences are the intraoperative status of the vessel wall and the unobstructed flow in the vessel after the operation. Another factor for successful replantation is the homeostasis of the patient. It can be influenced by many drugs which are applied according to a replantation schema. Aim of this therapy is the correction of the rheologic properties of a patient. In a patient group of 25 treated with Prostaglandin E1 (Prostavasin) we observed better wound healing with a 80% rate of successful replantation and microvascular vessel reconstruction.

  11. Microvascular obstruction assessed by 3-tesla magnetic resonance imaging in acute myocardial infarction is correlated with plasma troponin I levels

    PubMed Central

    2014-01-01

    Background Microvascular obstruction (MVO) at the acute phase of myocardial infarction (MI) is associated with poor prognosis. We aimed to evaluate the correlation between plasma cardiac troponin I (cTnI) at the acute phase of MI and extent of no-reflow, as assessed by 3-T cardiac magnetic resonance imaging (MRI). Secondly, we defined a cut-off value for cTnI predictive of no-reflow. Methods 51 consecutive patients with no previous history of cardiovascular disease, presenting ST elevation MI within <12 h. Infarct size and extent of no-reflow were evaluated by 3-T MRI at day 5. Extent of no-reflow at 15 minutes (MVO) was correlated with cTnI at admission, 6, 12, 24, 48 and 72 hours. At 6 months, MRI was performed to evaluate the impact of MVO on LV remodeling. Results MVO was diagnosed in 29 patients (57%). Extent of MVO was significantly correlated to peak troponin, cTnI (except admission values) and area under the curve. Using Receiver-operating characteristic (ROC) curve analysis, a cut-off cTnI value >89 ng/mL at 12 h seemed to best predict presence of early MVO (sensitivity 63%, specificity 88%). At 6 months, MVO was associated with left ventricular (LV) remodeling, resulting in higher LV volumes. Conclusion There is a relationship between cTnI at the acute phase of AMI and extent of MVO as assessed by 3-T cardiac MRI. A cut-off cTnI value of 89 ng/mL at 12 h seems to best predict presence of MVO, which contributes to LV remodeling. PMID:24886208

  12. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal

    PubMed Central

    Harvey, Jennifer C.; Roseguini, Bruno T.; Goerger, Benjamin M.; Fallon, Elizabeth A.

    2016-01-01

    We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT. PMID:27595112

  13. Role of endothelin in microvascular dysfunction following percutaneous coronary intervention for non-ST elevation acute coronary syndromes: a single-centre randomised controlled trial

    PubMed Central

    Guddeti, Raviteja R; Prasad, Abhiram; Matsuzawa, Yasushi; Aoki, Tatsuo; Rihal, Charanjit; Holmes, David; Best, Patricia; Lennon, Ryan J; Lerman, Lilach O; Lerman, Amir

    2016-01-01

    Objectives Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1 (ET-1) is a potent vasoconstrictor, and its expression is increased in atherosclerosis and after PCI. In this study, we aim to define the role of endothelin in regulating coronary microvascular blood flow and myocardial perfusion following PCI in patients with non-ST elevation acute coronary syndromes (NSTACS), by assessing whether adjunctive therapy with a selective endothelin A (ETA) receptor antagonist acutely improves postprocedural coronary microvascular blood flow. Methods In a randomised, double-blinded, placebo-controlled trial, 23 NSTACS patients were enrolled to receive an intracoronary infusion of placebo (n=11) or BQ-123 (n=12) immediately before PCI. Post-PCI coronary microvascular blood flow and myocardial perfusion were assessed by measuring Doppler-derived average peak velocity (APV), and cardiac biomarker levels were quantified. Results Compared with the placebo group, APV was significantly higher in the drug group immediately after PCI (30 (20, 37) vs 19 (9, 26) cm/s; p=0.03). Hyperaemic APV, measured post-adenosine administration, was higher in the BQ-123 group, but the difference did not achieve statistical significance (56 (48, 72) vs 46 (34, 64) cm/s; p=0.090). Maximum coronary flow reserve postprocedure was not different between the two groups (2.1 (1.6, 2.3) vs 2.5 (1.8, 3.0)). Per cent change in creatine kinase isoenzyme MB from the time of PCI to 8 and 16 hours post-PCI was significantly lower in the drug group compared with the placebo group (−17 (−26, −10) vs 26 (−15, 134); p=0.02 and −17 (−38, 14) vs 107 (2, 446); p=0.007, respectively). Conclusions Endothelin is a mediator of microvascular dysfunction during PCI in NSTACS, and adjunctive selective ETA antagonist may augment myocardial perfusion during PCI. Trial registration number

  14. Acute synthesis of CPEB is required for plasticity of visual avoidance behavior in Xenopus

    PubMed Central

    Shen, Wanhua; Liu, Han-Hsuan; Schiapparelli, Lucio; McClatchy, Daniel; He, Hai-yan; Yates, John R.; Cline, Hollis T.

    2014-01-01

    Summary Neural plasticity requires protein synthesis, however the identity of newly synthesized proteins generated in response to plasticity-inducing stimuli remains unclear. We used in vivo bio-orthogonal non-canonical amino acid tagging (BONCAT) with the methionine analog, azidohomoalanine (AHA) combined with multidimensional protein identification technique (MudPIT) to identify proteins that are synthesized in tadpole brain over 24 h. We induced conditioning-dependent plasticity of visual avoidance behavior. Induction of behavioral plasticity required NMDA and Ca2+-permeable AMPA receptors, αCaMKII and rapid protein synthesis. Combining BONCAT with Western blots revealed that proteins including αCaMKII, MEK1, CPEB, and GAD65 are synthesized during conditioning. Acute synthesis of CPEB during conditioning is required for behavioral plasticity as well as conditioning-induced synaptic and structural plasticity in the tectal circuit. We outline a signaling pathway regulating protein synthesis-dependent behavioral plasticity in intact animals, identify newly synthesized proteins induced by visual experience and demonstrate a requirement for acute synthesis of CPEB in plasticity. PMID:24529705

  15. Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

    PubMed Central

    Lee, Bong-Ki; Nam, Chang-Wook; Doh, Joon-Hyung; Chung, Woo-Young; Cho, Byung-Ryul; Fearon, William F.

    2016-01-01

    Background and Objectives There is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI. Subjects and Methods Seventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinase-myocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI. Results The baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001). Conclusion Pre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS. PMID:27482255

  16. Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment–Elevation Myocardial Infarction

    PubMed Central

    Carrick, David; Haig, Caroline; Ahmed, Nadeem; Carberry, Jaclyn; Yue May, Vannesa Teng; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Lindsay, Mitchell; Hood, Stuart; Watkins, Stuart; Davie, Andrew; Mahrous, Ahmed; Mordi, Ify; Ford, Ian; Radjenovic, Aleksandra; Oldroyd, Keith G.

    2016-01-01

    Background: Primary percutaneous coronary intervention is frequently successful at restoring coronary artery blood flow in patients with acute ST-segment–elevation myocardial infarction; however, failed myocardial reperfusion commonly passes undetected in up to half of these patients. The index of microvascular resistance (IMR) is a novel invasive measure of coronary microvascular function. We aimed to investigate the pathological and prognostic significance of an IMR>40, alone or in combination with a coronary flow reserve (CFR≤2.0), in the culprit artery after emergency percutaneous coronary intervention for acute ST-segment–elevation myocardial infarction. Methods: Patients with acute ST-segment–elevation myocardial infarction were prospectively enrolled during emergency percutaneous coronary intervention and categorized according to IMR (≤40 or >40) and CFR (≤2.0 or >2.0). Cardiac magnetic resonance imaging was acquired 2 days and 6 months after myocardial infarction. All-cause death or first heart failure hospitalization was a prespecified outcome (median follow-up, 845 days). Results: IMR and CFR were measured in the culprit artery at the end of percutaneous coronary intervention in 283 patients with ST-segment–elevation myocardial infarction (mean±SD age, 60±12 years; 73% male). The median IMR and CFR were 25 (interquartile range, 15–48) and 1.6 (interquartile range, 1.1–2.1), respectively. An IMR>40 was a multivariable associate of myocardial hemorrhage (odds ratio, 2.10; 95% confidence interval, 1.03–4.27; P=0.042). An IMR>40 was closely associated with microvascular obstruction. Symptom-to-reperfusion time, TIMI (Thrombolysis in Myocardial Infarction) blush grade, and no (≤30%) ST-segment resolution were not associated with these pathologies. An IMR>40 was a multivariable associate of the changes in left ventricular ejection fraction (coefficient, −2.12; 95% confidence interval, −4.02 to −0.23; P=0.028) and left ventricular

  17. Serial transthoracic coronary Doppler shows complete reversibility of microvascular obstruction pattern at one month after reperfused acute myocardial infarction.

    PubMed

    Ober, Camelia Diana; Ober, Mihai Claudiu; Iancu, Adrian Corneliu

    2017-01-31

    "No reflow" phenomenon is a common complication with significant prognostic repercussions after reperfused acute myocardial infarction. Previous studies have shown the feasibility and prognostic significance of coronary microcirculation assessment by transthoracic Doppler of left anterior descending artery (LAD). The aim of the study was to evaluate the time course of the coronary microcirculation status after acute anterior myocardial infarction reperfused by primary angioplasty with stent on LAD.

  18. Inhibition of gustatory plasticity due to acute nicotine exposure in the nematode Caenorhabditis elegans.

    PubMed

    Matsuura, Tetsuya; Miura, Hitoshi; Nishino, Asuka

    2013-11-01

    The present study investigated the effect of nicotine exposure on gustatory plasticity in the nematode Caenorhabditis elegans. The chemotactic response of wild-type N2 nematodes pre-exposed to 100mM NaCl with 3.0mM nicotine was almost the same as that of mock-conditioned nematodes unexposed to NaCl; however, the response of N2 nematodes pre-exposed to NaCl without nicotine was significantly lower than that of mock-conditioned nematodes. These results indicate that gustatory plasticity is inhibited by acute nicotine exposure. Inhibition of gustatory plasticity was observed when cat-2 mutants with a defect in dopamine biosynthesis were pre-exposed to NaCl with 3.0mM nicotine. Acute nicotine exposure did not cause inhibition of gustatory plasticity in bas-1 mutants, which had defects in both serotonin and dopamine secretion, and tph-1 mutants, which had a defect in serotonin secretion only. However, inhibition of gustatory plasticity was observed when bas-1 and tph-1 mutants were maintained on a growth plate that included serotonin. These results suggest that serotonin signaling plays an essential role in the modulation of the acute effects of nicotine.

  19. Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits.

    PubMed

    Mang, Cameron S; Brown, Katlyn E; Neva, Jason L; Snow, Nicholas J; Campbell, Kristin L; Boyd, Lara A

    2016-01-01

    Acute aerobic exercise facilitated long-term potentiation-like plasticity in the human primary motor cortex (M1). Here, we investigated the effect of acute aerobic exercise on cerebellar circuits, and their potential contribution to altered M1 plasticity in healthy individuals (age: 24.8 ± 4.1 years). In Experiment   1, acute aerobic exercise reduced cerebellar inhibition (CBI) (n = 10, p = 0.01), elicited by dual-coil paired-pulse transcranial magnetic stimulation. In Experiment   2, we evaluated the facilitatory effects of aerobic exercise on responses to paired associative stimulation, delivered with a 25 ms (PAS25) or 21 ms (PAS21) interstimulus interval (n = 16 per group). Increased M1 excitability evoked by PAS25, but not PAS21, relies on trans-cerebellar sensory pathways. The magnitude of the aerobic exercise effect on PAS response was not significantly different between PAS protocols (interaction effect: p = 0.30); however, planned comparisons indicated that, relative to a period of rest, acute aerobic exercise enhanced the excitatory response to PAS25 (p = 0.02), but not PAS21 (p = 0.30). Thus, the results of these planned comparisons indirectly provide modest evidence that modulation of cerebellar circuits may contribute to exercise-induced increases in M1 plasticity. The findings have implications for developing aerobic exercise strategies to "prime" M1 plasticity for enhanced motor skill learning in applied settings.

  20. Promoting Motor Cortical Plasticity with Acute Aerobic Exercise: A Role for Cerebellar Circuits

    PubMed Central

    Mang, Cameron S.; Brown, Katlyn E.; Neva, Jason L.; Snow, Nicholas J.; Campbell, Kristin L.; Boyd, Lara A.

    2016-01-01

    Acute aerobic exercise facilitated long-term potentiation-like plasticity in the human primary motor cortex (M1). Here, we investigated the effect of acute aerobic exercise on cerebellar circuits, and their potential contribution to altered M1 plasticity in healthy individuals (age: 24.8 ± 4.1 years). In Experiment   1, acute aerobic exercise reduced cerebellar inhibition (CBI) (n = 10, p = 0.01), elicited by dual-coil paired-pulse transcranial magnetic stimulation. In Experiment   2, we evaluated the facilitatory effects of aerobic exercise on responses to paired associative stimulation, delivered with a 25 ms (PAS25) or 21 ms (PAS21) interstimulus interval (n = 16 per group). Increased M1 excitability evoked by PAS25, but not PAS21, relies on trans-cerebellar sensory pathways. The magnitude of the aerobic exercise effect on PAS response was not significantly different between PAS protocols (interaction effect: p = 0.30); however, planned comparisons indicated that, relative to a period of rest, acute aerobic exercise enhanced the excitatory response to PAS25 (p = 0.02), but not PAS21 (p = 0.30). Thus, the results of these planned comparisons indirectly provide modest evidence that modulation of cerebellar circuits may contribute to exercise-induced increases in M1 plasticity. The findings have implications for developing aerobic exercise strategies to “prime” M1 plasticity for enhanced motor skill learning in applied settings. PMID:27127659

  1. Microvascular Angina

    MedlinePlus

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  2. Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome

    PubMed Central

    McMahon, Dallan; Bendayan, Reina; Hynynen, Kullervo

    2017-01-01

    Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Expression changes in individual genes and bioinformatic analysis suggests that FUS may induce a transient inflammatory response in microvessels. Increased transcription of proinflammatory cytokine genes appears to be short-lived, largely returning to baseline by 24 hrs. This observation may help to explain some previously observed bioeffects of FUS and may also be a driving force for the angiogenic processes and reduced drug efflux suggested by this work. While further studies are necessary, these results open up intriguing possibilities for novel FUS applications and suggest possible routes for pharmacologically modifying the technique. PMID:28374753

  3. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization.

  4. Acute and Chronic Effects of Ethanol on Learning-Related Synaptic Plasticity

    PubMed Central

    Zorumski, Charles F.; Mennerick, Steven; Izumi, Yukitoshi

    2014-01-01

    Alcoholism is associated with acute and long-term cognitive dysfunction including memory impairment, resulting in substantial disability and cost to society. Thus, understanding how ethanol impairs cognition is essential for developing treatment strategies to dampen its adverse impact. Memory processing is thought to involve persistent, use-dependent changes in synaptic transmission, and ethanol alters the activity of multiple signaling molecules involved in synaptic processing, including modulation of the glutamate and gamma-aminobutyric acid (GABA) transmitter systems that mediate most fast excitatory and inhibitory transmission in the brain. Effects on glutamate and GABA receptors contribute to ethanol-induced changes in long-term potentiation (LTP) and long-term depression (LTD), forms of synaptic plasticity thought to underlie memory acquisition. In this paper, we review the effects of ethanol on learning-related forms of synaptic plasticity with emphasis on changes observed in the hippocampus, a brain region that is critical for encoding contextual and episodic memories. We also include studies in other brain regions as they pertain to altered cognitive and mental function. Comparison of effects in the hippocampus to other brain regions is instructive for understanding the complexities of ethanol’s acute and long-term pharmacological consequences. PMID:24447472

  5. Plastic isolators for treatment of acute leukaemia patients under "germ-free" conditions.

    PubMed Central

    Trexler, P C; Spiers, A S; Gaya, H

    1975-01-01

    A gnotobiotic isolation system based on those developed in veterinary research has been constructed for hospital use. Fifteen patients with leukaemia and neutropenia spent a total of 110 weeks in plastic isolators, and none acquired any infection. Endogenous flora was effectively suppressed by topical antiseptics and gastrointestinal decontamination effected with nonabsorbable antibiotics. The isolator system was acceptable to patients and staff and much cheaper than the use of sterile rooms. Other advantages of the system are portability, easy storage, and use on ordinary open wards without prejudice to the microbiological protection afforded. It is as yet uncertain whether protective environments of this type will substantially improve the outcome of treatment for the acute leukaemias. PMID:1203666

  6. T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin

    PubMed Central

    Baranovski, Boris M.; Freixo-Lima, Gabriella S.; Lewis, Eli C.; Rider, Peleg

    2015-01-01

    The traditional model of T helper differentiation describes the naïve T cell as choosing one of several subsets upon stimulation and an added reciprocal inhibition aimed at maintaining the chosen subset. However, to date, evidence is mounting to support the presence of subset plasticity. This is, presumably, aimed at fine-tuning adaptive immune responses according to local signals. Reprograming of cell phenotype is made possible by changes in activation of master transcription factors, employing epigenetic modifications that preserve a flexible mode, permitting a shift between activation and silencing of genes. The acute phase response represents an example of peripheral changes that are critical in modulating T cell responses. α1-antitrypsin (AAT) belongs to the acute phase responses and has recently surfaced as a tolerogenic agent in the context of adaptive immune responses. Nonetheless, AAT does not inhibit T cell responses, nor does it shutdown inflammation per se; rather, it appears that AAT targets non-T cell immunocytes towards changing the cytokine environment of T cells, thus promoting a regulatory T cell profile. The present review focuses on this intriguing two-way communication between innate and adaptive entities, a crosstalk that holds important implications on potential therapies for a multitude of immune disorders. PMID:26583093

  7. What Causes Coronary Microvascular Disease?

    MedlinePlus

    ... Living With Clinical Trials Links Related Topics Angina Atherosclerosis Coronary Heart Disease Coronary Heart Disease Risk Factors ... Microvascular Disease? The same risk factors that cause atherosclerosis may cause coronary microvascular disease. Atherosclerosis is a ...

  8. Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke

    PubMed Central

    Stein, Efrat Shavit; Itsekson-Hayosh, Zeev; Aronovich, Anna; Reisner, Yair; Bushi, Doron; Pick, Chaim G.; Tanne, David; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D-aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects synaptic plasticity in an NMDAR dependent manner. Since its activity and concentration is increased in brain tissue upon acute stroke, we sought to clarify whether thrombin could mediate iLTP through the activation of its receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal slices, while OGD-induced changes in prothrombin mRNA levels were assessed by (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust potentiation of excitatory synaptic strength was detected, which occluded the ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1 blocked iLTP and restored the physiological, stimulus induced LTP. Our study provides important insights on the early changes occurring at excitatory synapses after ischemia and indicates the thrombin/PAR1 pathway as a novel target for developing therapeutic strategies to restore synaptic function in the acute phase of ischemic stroke. PMID:25604482

  9. Microvascular Autonomic Composites

    DTIC Science & Technology

    2012-01-06

    characterization of carbon nanotube yarns, 3-D braids, and their composites. SAMPE Journal 43: 6-19. Bogdanovich A and Mohamed MH. 2009. Three-Dimensional... carbon in red and bromine in yellow. The fracture surfaces were analyzed by SEM to show film was indistinguishable from the matrix, but by using the...nature, the mother of composite materials, applying microvascular technology to create skin, cartilages, tendons, bones and teeth. Cellulose fiber

  10. Cortical Synaptic Transmission and Plasticity in Acute Liver Failure Are Decreased by Presynaptic Events.

    PubMed

    Popek, Mariusz; Bobula, Bartosz; Sowa, Joanna; Hess, Grzegorz; Polowy, Rafał; Filipkowski, Robert Kuba; Frontczak-Baniewicz, Małgorzata; Zabłocka, Barbara; Albrecht, Jan; Zielińska, Magdalena

    2017-01-23

    Neurological symptoms of acute liver failure (ALF) reflect decreased excitatory transmission, but the status of ALF-affected excitatory synapse has not been characterized in detail. We studied the effects of ALF in mouse on synaptic transmission and plasticity ex vivo and its relation to distribution of (i) synaptic vesicles (sv) and (ii) functional synaptic proteins within the synapse. ALF-competent neurological and biochemical changes were induced in mice with azoxymethane (AOM). Electrophysiological characteristics (long-term potentiation, whole-cell recording) as well as synapse ultrastructure were evaluated in the cerebral cortex. Also, sv were quantified in the presynaptic zone by electron microscopy. Finally, presynaptic proteins in the membrane-enriched (P2) and cytosolic (S2) fractions of cortical homogenates were quantitated by Western blot. Slices derived from symptomatic AOM mice presented a set of electrophysiological correlates of impaired transmitter release including decreased field potentials (FPs), increased paired-pulse facilitation (PPF), and decreased frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) accompanied by reduction of the spontaneous transmitter release-driving protein, vti1A. Additionally, an increased number of sv per synapse and a decrease of P2 content and/or P2/S2 ratio for sv-associated proteins, i.e. synaptophysin, synaptotagmin, and Munc18-1, were found, in spite of decreased content of the sv-docking protein, syntaxin-1. Slices from AOM-treated asymptomatic mice showed impaired long-term potentiation (LTP) and increased PPF but no changes in transmitter release or presynaptic protein composition. Our findings demonstrate that a decrease of synaptic transmission in symptomatic ALF is associated with inefficient recruitment of sv proteins and/or impaired sv trafficking to transmitter release sites.

  11. Impact of Initial Culprit Vessel Flow on Infarct Size, Microvascular Obstruction, and Myocardial Salvage in Acute Reperfused ST-Elevation Myocardial Infarction.

    PubMed

    Joost, Alexander; Stiermaier, Thomas; Eitel, Charlotte; Fuernau, Georg; de Waha, Suzanne; Desch, Steffen; Thiele, Holger; Eitel, Ingo

    2016-11-01

    Data on the impact of initial Thrombolysis In Myocardial Infarction (TIMI) flow in the culprit coronary artery on myocardial damage after ST-elevation myocardial infarction (STEMI) are limited. Aim of this multicenter study was, therefore, to elucidate the impact of TIMI flow grade before percutaneous coronary intervention (PCI) on infarct size (IS), myocardial salvage index (MSI), and microvascular obstruction (MVO) assessed by cardiac magnetic resonance (CMR) imaging in patients with STEMI. We enrolled 738 patients with STEMI reperfused by primary PCI within 12 hours after symptom onset at 8 centers. Impaired coronary flow was defined as an initial coronary TIMI flow grade ≤1, whereas preserved coronary flow was defined as an initial coronary TIMI flow grade ≥2. CMR was performed in median 3 days (interquartile range 2 to 4 days) after infarction using a standardized infarction protocol. IS, MVO, and MSI were determined in central core laboratory-masked analyses. The primary clinical end point of the study was the time to major adverse cardiac events defined as death, reinfarction, and new onset of heart failure within 12 months after infarction. TIMI flow ≤1 before PCI was present in 507 patients (68.7%) and was significantly associated with larger IS (19% left ventricular [LV] vs 9% LV; p <0.001), less MSI (0.46 vs 0.65; p <0.001), reduced left ventricular ejection fraction (49% vs 55%; p <0.001), and a higher extent of MVO (0.6% LV vs 0.0% LV; p <0.001). Moreover, TIMI flow before PCI was identified as an independent predictor of IS, MVO, and MSI. However, there were no significant differences in major adverse cardiac event rates between groups (6.1% vs 7.5%; p = 0.48). In conclusion, TIMI flow pre-PCI is reversely associated with myocardial injury and is an independent predictor of myocardial damage assessed by CMR.

  12. Monitoring in microvascular surgery.

    PubMed

    Furnas, H; Rosen, J M

    1991-03-01

    The importance of monitoring in microvascular surgery is underscored by the high reported salvage rates of failing free flaps and replants. In this overview, we begin by defining the physiology of ischemic tissue with emphasis given to the no-reflow phenomenon and the secondary critical ischemia times. Based on the physiological changes accompanying ischemia, several variables are defined that can be monitored to reflect the vascular state of a free flap or replant. Multifarious monitoring systems are then reviewed, including clinical observation, temperature, isotope clearance, ultrasonic Doppler, laser Doppler, transcutaneous oxygen tension, reflection plethysmography, dermofluorometry, pH, electromagnetic flowmetry, serial hematocrits, interstitial fluid pressure, and magnetic resonance imaging.

  13. Intracranial microvascular free flaps.

    PubMed

    Levine, Steven; Garfein, Evan S; Weiner, Howard; Yaremchuk, Michael J; Saadeh, Pierre B; Gurtner, Geoffrey; Levine, Jamie P; Warren, Stephen M

    2009-02-01

    Large acquired intracranial defects can result from trauma or surgery. When reoperation is required because of infection or tumor recurrence, management of the intracranial dead space can be challenging. By providing well-vascularized bulky tissue, intracranial microvascular free flaps offer potential solutions to these life-threatening complications. A multi-institutional retrospective chart and radiographic review was performed of all patients who underwent microvascular free-flap surgery for salvage treatment of postoperative intracranial infections between 1998 and 2006. A total of six patients were identified with large intracranial defects and postoperative intracranial infections. Four patients had parenchymal resections for tumor or seizure and two patients had posttraumatic encephalomalacia. All patients underwent operative debridement and intracranial free-flap reconstruction using the latissimus dorsi muscle (N=2), rectus abdominis muscle (N=2), or omentum (N=2). All patients had titanium (N=4) or Medpor (N=2) cranioplasties. We concluded that surgery or trauma can result in significant intracranial dead space. Treatment of postoperative intracranial infection can be challenging. Vascularized free tissue transfer not only fills the void, but also provides a delivery system for immune cells, antibodies, and systemically administered antibiotics. The early use of this technique when intracranial dead space and infection coexist is beneficial.

  14. Neuroligin 2 regulates spinal GABAergic plasticity in hyperalgesic priming, a model of the transition from acute to chronic pain.

    PubMed

    Kim, Ji-Young V; Megat, Salim; Moy, Jamie K; Asiedu, Marina N; Mejia, Galo L; Vagner, Josef; Price, Theodore J

    2016-06-01

    Plasticity in inhibitory receptors, neurotransmission, and networks is an important mechanism for nociceptive signal amplification in the spinal dorsal horn. We studied potential changes in GABAergic pharmacology and its underlying mechanisms in hyperalgesic priming, a model of the transition from acute to chronic pain. We find that while GABAA agonists and positive allosteric modulators reduce mechanical hypersensitivity to an acute insult, they fail to do so during the maintenance phase of hyperalgesic priming. In contrast, GABAA antagonism promotes antinociception and a reduction in facial grimacing after the transition to a chronic pain state. During the maintenance phase of hyperalgesic priming, we observed increased neuroligin (nlgn) 2 expression in the spinal dorsal horn. This protein increase was associated with an increase in nlgn2A splice variant mRNA, which promotes inhibitory synaptogenesis. Disruption of nlgn2 function with the peptide inhibitor, neurolide 2, produced mechanical hypersensitivity in naive mice but reversed hyperalgesic priming in mice previously exposed to brain-derived neurotrophic factor. Neurolide 2 treatment also reverses the change in polarity in GABAergic pharmacology observed in the maintenance of hyperalgesic priming. We propose that increased nlgn2 expression is associated with hyperalgesic priming where it promotes dysregulation of inhibitory networks. Our observations reveal new mechanisms involved in the spinal maintenance of a pain plasticity and further suggest that disinhibitory mechanisms are central features of neuroplasticity in the spinal dorsal horn.

  15. Neuroligin 2 regulates spinal GABAergic plasticity in hyperalgesic priming, a model of the transition from acute to chronic pain

    PubMed Central

    Kim, Ji-Young V.; Megat, Salim; Moy, Jamie K.; Asiedu, Marina N.; Mejia, Galo L.; Vagner, Josef; Price, Theodore J.

    2016-01-01

    Plasticity in inhibitory receptors, neurotransmission, and networks is an important mechanism for nociceptive signal amplification in the spinal dorsal horn. We studied potential changes in GABAergic pharmacology and its underlying mechanisms in hyperalgesic priming, a model of the transition from acute to chronic pain. We find that while GABAA agonists and positive allosteric modulators reduce mechanical hypersensitivity to an acute insult, they fail to do so during the maintenance phase of hyperalgesic priming. In contrast, GABAA antagonism promotes antinociception and a reduction in facial grimacing after the transition to a chronic pain state. During the maintenance phase of hyperalgesic priming, we observed increased neuroligin (nlgn) 2 expression in the spinal dorsal horn. This protein increase was associated with an increase in nlgn2A splice variant mRNA, which promotes inhibitory synaptogenesis. Disruption of nlgn2 function with the peptide inhibitor, neurolide 2, produced mechanical hypersensitivity in naive mice but reversed hyperalgesic priming in mice previously exposed to brain-derived neurotrophic factor. Neurolide 2 treatment also reverses the change in polarity in GABAergic pharmacology observed in the maintenance of hyperalgesic priming. We propose that increased nlgn2 expression is associated with hyperalgesic priming where it promotes dysregulation of inhibitory networks. Our observations reveal new mechanisms involved in the spinal maintenance of a pain plasticity and further suggest that disinhibitory mechanisms are central features of neuroplasticity in the spinal dorsal horn. PMID:26859820

  16. Microvascular Cranial Nerve Palsy

    MedlinePlus

    ... Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center Global Ophthalmology Guide Academy Publications EyeNet Ophthalmology Information for: International Ophthalmologists Media Medical Students Patients and Public Technicians and Nurses ...

  17. The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex.

    PubMed

    Nava, Nicoletta; Treccani, Giulia; Müller, Heidi Kaastrup; Popoli, Maurizio; Wegener, Gregers; Elfving, Betina

    2017-01-01

    It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI). In the present study we evaluated the effects of acute Foot-shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on the gene expression of key regulators of synaptic plasticity and structure. Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI specifically increases the short-term expression of Spinophilin, as well as Homer and Shank family genes, and that both acute stress and DMI exert significant long-term effects on mRNA levels of genes involved in spine plasticity. These findings support the knowledge that acute FS stress and antidepressant treatment induce both rapid and sustained time-dependent alterations in structural components of synaptic plasticity in rodent medial PFC.

  18. Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

    PubMed Central

    Ahmed, Nadeem; Layland, Jamie; Carrick, David; Petrie, Mark C.; McEntegart, Margaret; Eteiba, Hany; Hood, Stuart; Lindsay, Mitchell; Watkins, Stuart; Davie, Andrew; Mahrous, Ahmed; Carberry, Jaclyn; Teng, Vannesa; McConnachie, Alex; Curzen, Nick; Oldroyd, Keith G.; Berry, Colin

    2016-01-01

    Aims Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.3% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon. PMID:26418191

  19. Aspects of cerebral plasticity related to clinical features in acute vestibular neuritis: a "starting point" review from neuroimaging studies.

    PubMed

    Micarelli, A; Chiaravalloti, A; Schillaci, O; Ottaviani, F; Alessandrini, M

    2016-04-01

    Vestibular neuritis (VN) is one of the most common causes of vertigo and is characterised by a sudden unilateral vestibular failure (UVF). Many neuroimaging studies in the last 10 years have focused on brain changes related to sudden vestibular deafferentation as in VN. However, most of these studies, also due to different possibilities across diverse centres, were based on different times of first acquisition from the onset of VN symptoms, neuroimaging techniques, statistical analysis and correlation with otoneurological and psychological findings. In the present review, the authors aim to merge together the similarities and discrepancies across various investigations that have employed neuroimaging techniques and group analysis with the purpose of better understanding about how the brain changes and what characteristic clinical features may relate to each other in the acute phase of VN. Six studies that strictly met inclusion criteria were analysed to assess cortical-subcortical correlates of acute clinical features related to VN. The present review clearly reveals that sudden UVF may induce a wide variety of cortical and subcortical responses - with changes in different sensory modules - as a result of acute plasticity in the central nervous system.

  20. Regulation of postsynaptic plasticity genes' expression and topography by sustained dopamine perturbation and modulation by acute memantine: relevance to schizophrenia.

    PubMed

    Iasevoli, Felice; Buonaguro, Elisabetta F; Sarappa, Chiara; Marmo, Federica; Latte, Gianmarco; Rossi, Rodolfo; Eramo, Anna; Tomasetti, Carmine; de Bartolomeis, Andrea

    2014-10-03

    A relevant role for dopamine-glutamate interaction has been reported in the pathophysiology and treatment of psychoses. Dopamine and glutamate may interact at multiple levels, including the glutamatergic postsynaptic density (PSD), an electron-dense thickening that has gained recent attention as a switchboard of dopamine-glutamate interactions and for its role in synaptic plasticity. Recently, glutamate-based strategies, such as memantine add-on to antipsychotics, have been proposed for refractory symptoms of schizophrenia, e.g. cognitive impairment. Both antipsychotics and memantine regulate PSD transcripts but sparse information is available on memantine's effects under dopamine perturbation. We tested gene expression changes of the Homer1 and PSD-95 PSD proteins in models of sustained dopamine perturbation, i.e. subchronic treatment by: a) GBR-12909, a dopamine receptor indirect agonist; b) haloperidol, a D2R antagonist; c) SCH-23390, a dopamine D1 receptor (D1R) antagonist; and d) SCH-23390+haloperidol. On the last day of treatment, rats were acutely treated with vehicle or memantine. The Homer1a immediate-early gene was significantly induced by haloperidol and by haloperidol+SCH-23390. The gene was not induced by SCH-23390 per se or by GBR-12909. Expression of the constitutive genes Homer1b/c and PSD-95 was less affected by these dopaminergic paradigms. Acute memantine administration significantly increased Homer1a expression by the dopaminergic compounds used herein. Both haloperidol and haloperidol+SCH-23390 shifted Homer1a/Homer1b/c ratio of expression toward Homer1a. This pattern was sharpened by acute memantine. Dopaminergic compounds and acute memantine also differentially affected topographic distribution of gene expression and coordinated expression of Homer1a among cortical-subcortical regions. These results indicate that dopaminergic perturbations may affect glutamatergic signaling in different directions. Memantine may help partially revert dopamine

  1. Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

    PubMed Central

    Guo, Xiaoli; He, Yongzhi; Lu, Hongyang; Li, Yao; Su, Xin; Jiang, Ying; Tong, Shanbao

    2016-01-01

    The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input. PMID:27144032

  2. Diverse impact of acute and long-term extracellular proteolytic activity on plasticity of neuronal excitability

    PubMed Central

    Wójtowicz, Tomasz; Brzdąk, Patrycja; Mozrzymas, Jerzy W.

    2015-01-01

    Learning and memory require alteration in number and strength of existing synaptic connections. Extracellular proteolysis within the synapses has been shown to play a pivotal role in synaptic plasticity by determining synapse structure, function, and number. Although synaptic plasticity of excitatory synapses is generally acknowledged to play a crucial role in formation of memory traces, some components of neural plasticity are reflected by nonsynaptic changes. Since information in neural networks is ultimately conveyed with action potentials, scaling of neuronal excitability could significantly enhance or dampen the outcome of dendritic integration, boost neuronal information storage capacity and ultimately learning. However, the underlying mechanism is poorly understood. With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses. Here, we review the most recent studies addressing the impact of extracellular proteolysis on plasticity of neuronal excitability and discuss how enzymatic activity may alter input-output/transfer function of neurons, supporting cognitive processes. Interestingly, extracellular proteolysis may alter intrinsic neuronal excitability and excitation/inhibition balance both rapidly (time of minutes to hours) and in long-term window. Moreover, it appears that by cleavage of extracellular matrix (ECM) constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments (AISs) in adjusting neuronal input/output function. Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic

  3. Genome-wide alterations in hippocampal 5-hydroxymethylcytosine links plasticity genes to acute stress

    PubMed Central

    Li, Sisi; Papale, Ligia A.; Zhang, Qi; Madrid, Andy; Chen, Li; Chopra, Pankaj; Keleş, Sündüz; Jin, Peng; Alisch, Reid S.

    2015-01-01

    Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders, including anxiety and post-traumatic stress disorder. While even acute stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive DNA modification that is highly enriched in post-mitotic neurons and is associated with active transcription of neuronal genes. Recently, we found a hippocampal increase of 5hmC in the glucocorticoid receptor gene (Nr3c1) following acute stress, warranting a deeper investigation of stress-related 5hmC levels. Here, we used an established chemical labeling and affinity purification method coupled with high-throughput sequencing technology to generate the first genome-wide profile of hippocampal 5hmC following exposure to acute restraint stress and a one-hour recovery. This approach found a genome-wide disruption in 5hmC associated with acute stress response, primarily in genic regions, and identified known and potentially novel stress-related targets that have a significant enrichment for neuronal ontological functions. Integration of these data with hippocampal gene expression data from these same mice found stress-related hydroxymethylation correlated to altered transcript levels and sequence motif predictions indicated that 5hmC may function by mediating transcription factor binding to these transcripts. Together, these data reveal an environmental impact on this newly discovered epigenetic mark in the brain and represent a critical step toward understanding stress-related epigenetic mechanisms that alter gene expression and can lead to the development of psychiatric disorders. PMID:26598390

  4. A New Era in Diagnostic Ultrasound, Superb Microvascular Imaging: Preliminary Results in Pediatric Hepato-Gastrointestinal Disorders.

    PubMed

    Ohno, Yasuharu; Fujimoto, Tamotsu; Shibata, Yukari

    2017-02-01

    Introduction Superb microvascular imaging is a new ultrasound image processing technique that uses advanced clutter suppression to extract flow signals from vessels and which helps us visualize very small vascular structures that were not previously visible without the use of a contrast agent. We herein analyzed the usefulness of superb microvascular imaging in the diagnosis of hepato-gastrointestinal disorders in pediatric patients. Materials and Methods Fifty-six pediatric patients who underwent a total of 81 superb microvascular imaging examinations with an Aplio 300 ultrasound system (Toshiba Medical Systems, Tokyo, Japan) were enrolled in this study. The subjects underwent conventional ultrasound examinations, including Doppler imaging followed by superb microvascular imaging. The superb microvascular imaging findings and standard imaging were compared. All of the examinations were performed without sedation. Results The average age of the patients (male, n = 38; female, n = 18) was 4 years. The clinical diagnoses included hepatobiliary disorders (n = 29), acute appendicitis (n = 10), and other intestinal disorders (n = 17). The target organs for superb microvascular imaging were the liver, appendix, rectum, intestine, gallbladder, and lymph node. In most of the patients, superb microvascular imaging achieved the excellent visualization of microvascular structures, revealing abnormal vasculature in 21 out of 46 (45.7%) examinations of the liver, 9/9 (100%) examinations of the appendix, 0/11 (0%) examinations of the rectum, 9/11 (81.8%) examinations of the intestine, 0/1 (0%) examinations of the gallbladder, and 3/3 (100%) examinations of the lymph nodes. Superb microvascular imaging was superior to Doppler imaging for depicting the microvascular structures. Conclusions Superb microvascular imaging is especially useful for depicting the microvascular flow and can aid in the diagnosis and treatment planning for pediatric patients with

  5. Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity.

    PubMed

    Jonas, Elizabeth A

    2014-08-01

    Mitochondria manufacture and release metabolites and manage calcium during neuronal activity and synaptic transmission, but whether long term alterations in mitochondrial function contribute to the neuronal plasticity underlying changes in organism behavior patterns is still poorly understood. Although normal neuronal plasticity may determine learning, in contrast a persistent decline in synaptic strength or neuronal excitability may portend neurite retraction and eventual somatic death. Anti-death proteins such as Bcl-xL not only provide neuroprotection at the neuronal soma during cell death stimuli, but also appear to enhance neurotransmitter release and synaptic growth and development. It is proposed that Bcl-xL performs these functions through its ability to regulate mitochondrial release of bioenergetic metabolites and calcium, and through its ability to rapidly alter mitochondrial positioning and morphology. Bcl-xL also interacts with proteins that directly alter synaptic vesicle recycling. Bcl-xL translocates acutely to sub-cellular membranes during neuronal activity to achieve changes in synaptic efficacy. After stressful stimuli, pro-apoptotic cleaved delta N Bcl-xL (ΔN Bcl-xL) induces mitochondrial ion channel activity leading to synaptic depression and this is regulated by caspase activation. During physiological states of decreased synaptic stimulation, loss of mitochondrial Bcl-xL and low level caspase activation occur prior to the onset of long term decline in synaptic efficacy. The degree to which Bcl-xL changes mitochondrial membrane permeability may control the direction of change in synaptic strength. The small molecule Bcl-xL inhibitor ABT-737 has been useful in defining the role of Bcl-xL in synaptic processes. Bcl-xL is crucial to the normal health of neurons and synapses and its malfunction may contribute to neurodegenerative disease.

  6. Plasticity of the histamine H3 receptors after acute vestibular lesion in the adult cat

    PubMed Central

    Tighilet, Brahim; Mourre, Christiane; Lacour, Michel

    2014-01-01

    After unilateral vestibular neurectomy (UVN) many molecular and neurochemical mechanisms underlie the neurophysiological reorganizations occurring in the vestibular nuclei (VN) complex, as well as the behavioral recovery process. As a key regulator, the histaminergic system appears to be a likely candidate because drugs interfering with histamine (HA) neurotransmission facilitate behavioral recovery after vestibular lesion. This study aimed at analyzing the post-lesion changes of the histaminergic system by quantifying binding to histamine H3 receptors (H3R; mediating namely histamine autoinhibition) using a histamine H3 receptor agonist ([3H]N-α-methylhistamine). Experiments were done in brain sections of control cats (N = 6) and cats submitted to UVN and killed 1 (N = 6) or 3 (N = 6) weeks after the lesion. UVN induced a bilateral decrease in binding density of the agonist [3H]N-α-methylhistamine to H3R in the tuberomammillary nuclei (TMN) at 1 week post-lesion, with a predominant down-regulation in the ipsilateral TMN. The bilateral decrease remained at the 3 weeks survival time and became symmetric. Concerning brainstem structures, binding density in the VN, the prepositus hypoglossi, the subdivisions of the inferior olive decreased unilaterally on the ipsilateral side at 1 week and bilaterally 3 weeks after UVN. Similar changes were observed in the subdivisions of the solitary nucleus only 1 week after the lesion. These findings indicate vestibular lesion induces plasticity of the histamine H3R, which could contribute to vestibular function recovery. PMID:24427120

  7. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity

    PubMed Central

    Jacoby, Elad; Nguyen, Sang M.; Fountaine, Thomas J.; Welp, Kathryn; Gryder, Berkley; Qin, Haiying; Yang, Yinmeng; Chien, Christopher D.; Seif, Alix E.; Lei, Haiyan; Song, Young K.; Khan, Javed; Lee, Daniel W.; Mackall, Crystal L.; Gardner, Rebecca A.; Jensen, Michael C.; Shern, Jack F.; Fry, Terry J.

    2016-01-01

    Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL. PMID:27460500

  8. Osmoregulation and branchial plasticity after acute freshwater transfer in red drum, Sciaenops ocellatus.

    PubMed

    Watson, Caroline J; Nordi, Wiolene M; Esbaugh, Andrew J

    2014-12-01

    Red drum, Sciaenops ocellatus, is an estuarine-dependent fish species commonly found in the Gulf of Mexico and along the coast of the southeastern United States. This economically important species has demonstrated freshwater tolerance; however, the physiological mechanisms and costs related to freshwater exposure remain poorly understood. The current study therefore investigated the physiological response of red drum using an acute freshwater transfer protocol. Plasma osmolality, Cl⁻, Mg²⁺ and Ca²⁺ were all significantly reduced by 24h post-transfer; Cl⁻ and Mg²⁺ recovered to control levels by 7days post-transfer. No effect of transfer was observed on muscle water content; however, muscle Cl⁻ was significantly reduced. Interestingly, plasma and muscle Na⁺ content was unaffected by freshwater transfer. Intestinal fluid was absent by 24h post-transfer indicating cessation of drinking. Branchial gene expression analysis showed that both CFTR and NKCC1 exhibited significant down-regulation at 8 and 24h post-transfer, respectively, although transfer had no impact on NHE2, NHE3 or Na⁺, K⁺ ATPase (NKA) activity. These general findings are supported by immunohistochemical analysis, which revealed no apparent NKCC containing cells in the gills at 7days post transfer while NKA cells localization was unaffected. The results of the current study suggest that red drum can effectively regulate Na⁺ balance upon freshwater exposure using already present Na⁺ uptake pathways while also down-regulating ion excretion mechanisms.

  9. Integrating metabolic performance, thermal tolerance, and plasticity enables for more accurate predictions on species vulnerability to acute and chronic effects of global warming.

    PubMed

    Magozzi, Sarah; Calosi, Piero

    2015-01-01

    Predicting species vulnerability to global warming requires a comprehensive, mechanistic understanding of sublethal and lethal thermal tolerances. To date, however, most studies investigating species physiological responses to increasing temperature have focused on the underlying physiological traits of either acute or chronic tolerance in isolation. Here we propose an integrative, synthetic approach including the investigation of multiple physiological traits (metabolic performance and thermal tolerance), and their plasticity, to provide more accurate and balanced predictions on species and assemblage vulnerability to both acute and chronic effects of global warming. We applied this approach to more accurately elucidate relative species vulnerability to warming within an assemblage of six caridean prawns occurring in the same geographic, hence macroclimatic, region, but living in different thermal habitats. Prawns were exposed to four incubation temperatures (10, 15, 20 and 25 °C) for 7 days, their metabolic rates and upper thermal limits were measured, and plasticity was calculated according to the concept of Reaction Norms, as well as Q10 for metabolism. Compared to species occupying narrower/more stable thermal niches, species inhabiting broader/more variable thermal environments (including the invasive Palaemon macrodactylus) are likely to be less vulnerable to extreme acute thermal events as a result of their higher upper thermal limits. Nevertheless, they may be at greater risk from chronic exposure to warming due to the greater metabolic costs they incur. Indeed, a trade-off between acute and chronic tolerance was apparent in the assemblage investigated. However, the invasive species P. macrodactylus represents an exception to this pattern, showing elevated thermal limits and plasticity of these limits, as well as a high metabolic control. In general, integrating multiple proxies for species physiological acute and chronic responses to increasing

  10. Using Multiple Whole-Cell Recordings to Study Spike-Timing-Dependent Plasticity in Acute Neocortical Slices

    PubMed Central

    Lalanne, Txomin; Abrahamsson, Therese; Sjöström, P. Jesper

    2017-01-01

    This protocol provides a method for quadruple whole-cell recording to study synaptic plasticity of neocortical connections, with a special focus on spike-timing-dependent plasticity (STDP). It also describes how to morphologically identify recorded cells from two-photon laser-scanning microscopy (2PLSM) stacks. PMID:27250948

  11. No difference in acute effects of supplemental v. dietary calcium on blood pressure and microvascular function in obese women challenged with a high-fat meal: a cross-over randomised study.

    PubMed

    Ferreira, Thaís da Silva; Leal, Priscila Mansur; Antunes, Vanessa Parada; Sanjuliani, Antonio Felipe; Klein, Márcia Regina Simas Torres

    2016-11-01

    Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

  12. Host defenses to Rickettsia rickettsii infection contribute to increased microvascular permeability in human cerebral endothelial cells.

    PubMed

    Woods, Michael E; Olano, Juan P

    2008-03-01

    Rickettsiae are arthropod-borne intracellular bacterial pathogens that primarily infect the microvascular endothelium leading to systemic spread of the organisms and the major pathophysiological effect, increased microvascular permeability, and edema in vital organs such as the lung and brain. Much work has been done on mechanisms of immunity to rickettsiae, as well as the responses of endothelial cells to rickettsial invasion. However, to date, no one has described the mechanisms of increased microvascular permeability during acute rickettsiosis. We sought to establish an in vitro model of human endothelial-target rickettsial infection using the etiological agent of Rocky Mountain spotted fever, Rickettsia rickettsii, and human cerebral microvascular endothelial cells. Endothelial cells infected with R. rickettsii exhibited a dose-dependent decrease in trans-endothelial electrical resistance, which translates into increased monolayer permeability. Additionally, we showed that the addition of pro-inflammatory stimuli essential to rickettsial immunity dramatically enhanced this effect. This increase in permeability correlates with dissociation of adherens junctions between endothelial cells and is not dependent on the presence of nitric oxide. Taken together, these results demonstrate for the first time that increased microvascular permeability associated with rickettsial infection is partly attributable to intracellular rickettsiae and partly attributable to the immune defenses that have evolved to protect the host from rickettsial spread.

  13. Morphologic Plasticity and Periodicity: Porcine Cerebral Microvascular Cells in Culture

    DTIC Science & Technology

    1990-02-01

    The cells were subcultured no Bandeiraea Simplicifolia (BSA-1), Ulex europaeus ( UEA -1), earlier than 7 d by treatment with trypsin-EDTA. The Triticum...EP013, DdCUMENTATION ,AG,.) I FILE COPY! * lb. RESTRICTIVE MARKINGS 2 AA 967 -- 3. DISTRIBUTIONIAVAILAaITY OFROT _2 967 Approved for public release...ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Naval Medical ResearchI (if applicable) I INaval Medical Command 6-. ADDRESS (Cty

  14. Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

    PubMed

    Amin, Shaimaa Nasr; El-Aidi, Ahmed Amro; Ali, Mohamed Mostafa; Attia, Yasser Mahmoud; Rashed, Laila Ahmed

    2015-06-01

    Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

  15. Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices

    PubMed Central

    Edelmann, Elke; Lessmann, Volkmar

    2011-01-01

    Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons. PMID:22065958

  16. Effect of high altitude and exercise on microvascular parameters in acclimatized subjects.

    PubMed

    Bauer, Andreas; Demetz, Florian; Bruegger, Dirk; Schmoelz, Martin; Schroepfer, Sebastian; Martignoni, André; Baschnegger, Heiko; Hoelzl, Josef; Thiel, Manfred; Choukér, Alexander; Peter, Klaus; Gamble, John; Christ, Frank

    2006-02-01

    The role of microvascular fluid shifts in the adaptation to hypobaric hypoxia and its contribution to the pathophysiology of AMS (acute mountain sickness) is unresolved. In a systematic prospective study, we investigated the effects of hypobaric hypoxia and physical exercise alone, and in combination, on microvascular fluid exchange and related factors. We used computer-assisted VCP (venous congestion plethysmography) on the calves of ten altitude-acclimatized volunteers. We investigated the effects of: (i) actively climbing to an altitude of 3196 m, (ii) airlifting these subjects to the same altitude, and (iii) exercise at low altitude. CFC (capillary filtration capacity), Pvi (isovolumetric venous pressure) and Qa (calf blood flow) were assessed before and after each procedure and then repeated after an overnight rest. Measurements of CFC showed no evidence of increased microvascular permeability after any of the procedures. Pvi was significantly decreased (P<0.001) from 20.3+/-4.4 to 8.9+/-4.3 mmHg after active ascent, and was still significantly lower (P=0.009) after overnight rest at high altitude (13.6+/-5.9 mmHg). No such changes were observed after the passive ascent (16.7+/-4.0 mmHg at baseline; 17.3+/-4.5 mmHg after passive ascent; and 19.9+/-5.3 mmHg after overnight rest) or after exercise at low altitude. After the active ascent, Qa was significantly increased. We also found a significant correlation between Qa, Pvi and the number of circulating white blood cells. In conclusion, we found evidence to support the hypothesis that increased microvascular permeability associated with AMS does not occur in acclimatized subjects. We also observed that the microvascular equilibrium pressure (Pvi) fell in inverse relation to the increase in Qa, especially in hypoxic exercise. We hypothesize that this inverse relationship reflects the haemodynamic changes at the microvascular interface, possibly attributable to the flow-induced increases in endothelial surface

  17. Microvascular protection is essential for successful neuroprotection in stroke.

    PubMed

    Gursoy-Ozdemir, Yasemin; Yemisci, Muge; Dalkara, Turgay

    2012-11-01

    Currently, the best way of neuroprotection for acute ischemic stroke appears to be restoration of blood flow to the ischemic area by thrombolysis. Unfortunately, a short therapeutic time window as well as thrombolysis-induced bleeding and edema limit the use of recanalization therapies. Here, we review the evidence suggesting that ischemia/reperfusion-induced microvascular injury plays a critical role in determining tissue survival after recanalization in focal cerebral ischemia by disrupting the blood-brain barrier integrity and promoting microcirculatory clogging. Among many complex mechanisms of the ischemia-reperfusion injury, overproduction of oxygen and nitrogen radicals on the microvascular wall appears to significantly contribute to these pathological processes. These developments bring about the exciting possibility that effective suppression of oxidative/nitrative stress during pharmacological or interventional re-opening of the occluded artery may significantly improve the outcome of recanalization therapies in stroke patients by improving microcirculatory reflow as well as by preventing hemorrhagic conversion and vasogenic edema. They also point to the critical (but partly neglected) importance of the microcirculation in neuroprotection.

  18. Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II.

    PubMed

    Wu, Zhiyong; Wang, Zhiwei; Dai, Feifeng; Liu, Huagang; Ren, Wei; Chang, Jinxing; Li, Bowen

    2016-01-01

    Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement.

  19. Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II

    PubMed Central

    Wang, Zhiwei; Dai, Feifeng; Liu, Huagang; Ren, Wei; Chang, Jinxing; Li, Bowen

    2016-01-01

    Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement. PMID:28119542

  20. Predicting plasticity: acute context-dependent changes to vocal performance predict long-term age-dependent changes

    PubMed Central

    James, Logan S.

    2015-01-01

    Understanding the factors that predict and guide variation in behavioral change can lend insight into mechanisms of motor plasticity and individual differences in behavior. The performance of adult birdsong changes with age in a manner that is similar to rapid context-dependent changes to song. To reveal mechanisms of vocal plasticity, we analyzed the degree to which variation in the direction and magnitude of age-dependent changes to Bengalese finch song could be predicted by variation in context-dependent changes. Using a repeated-measures design, we found that variation in age-dependent changes to the timing, sequencing, and structure of vocal elements (“syllables”) was significantly predicted by variation in context-dependent changes. In particular, the degree to which the duration of intersyllable gaps, syllable sequencing at branch points, and fundamental frequency of syllables within spontaneous [undirected (UD)] songs changed over time was correlated with the degree to which these features changed from UD song to female-directed (FD) song in young-adult finches (FDyoung). As such, the structure of some temporal features of UD songs converged over time onto the structure of FDyoung songs. This convergence suggested that the FDyoung song could serve as a stable target for vocal motor plasticity. Consequently, we analyzed the stability of FD song and found that the temporal structure of FD song changed significantly over time in a manner similar to UD song. Because FD song is considered a state of heightened performance, these data suggest that age-dependent changes could reflect practice-related improvements in vocal motor performance. PMID:26311186

  1. Transplantation and Perfusion of Microvascular Fragments in a Rodent Model of Volumetric Muscle Loss Injury

    DTIC Science & Technology

    2014-07-01

    Microvascular transplantation after acute myocardial infarction . Tissue Eng 13: 2871-2879. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ...when grafts were implanted after murine myocardial infarction (Shepherd, 2007, text reference). However, caution should be made when extrapolating...these findings to the current study due to the differences between the models ( myocardial infarction vs. VML) and the time allowed for microvessel

  2. Roles of LOX-1 in microvascular dysfunction.

    PubMed

    Lubrano, Valter; Balzan, Silvana

    2016-05-01

    Studies from human and animal models with metabolic disease and hypertension highlight atrophic remodeling, reduced lumen size and thinner vascular walls of microvessels with profound density reduction. This impaired vascular response limits the perfusion of peripheral tissues inducing organ damage. These conditions are strongly associated with oxidative stress and in particular with the up-regulation of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Several factors such as cytokines, shear stress, and advanced glycation end-products, especially oxLDL, can up-regulate LOX-1. The activation of this receptor induces the production of adhesion molecules, cytokines and the release of reactive oxygen species via NADPH oxidase. LOX-1 is considered a potent mediator of endothelial dysfunction and it is significantly associated with reduced microvascular endothelium NO-dependent vasodilation in hypercholesterolemia and hypertension. Microvascular endothelial cells increased the expression of IL-6 in association with the increased concentration of LDL and its degree of oxidation. Moreover, increased IL-6 levels are associated with up-regulation of LOX-1 in a dose-dependent manner. Another consequence of microvascular inflammation is the generation of small amounts of ROS, similar to those induced by low concentration of oxLDL (<5 μg/mL) which induces capillary tube formation of endothelial cells, through LOX-1 up-regulation. In light of its central role, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases and microvascular disorders.

  3. Plastic Surgery

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Plastic Surgery KidsHealth > For Teens > Plastic Surgery Print A ... her forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word " ...

  4. Transfer of free vascular cutaneous flaps by microvascular anastomosis. Results in six dogs.

    PubMed

    Fowler, J D; Miller, C W; Bowen, V; Johnston, G H

    1987-01-01

    Skin defects on the distal extremities of six dogs were reconstructed with free vascular cutaneous transfers by microvascular anastomosis. The donor flaps were based on the superficial cervical artery and vein. In five of the dogs, bone was exposed and skin was lost from half of the circumference of the limb. Two had infected fractures with sequestra and three had acute shearing injuries. The sixth dog had sensory denervation of the left antebrachium and a carpal acral lick granuloma. Before surgery, the patency of potential recipient vessels was confirmed with arteriography in five dogs and an ultrasonic doppler in one dog. Microvascular technique was used to reestablish circulation to the flaps after they were transferred to the recipient site. Total ischemic time of the flaps averaged 100 minutes. All flaps survived. Successful reconstruction of the cutaneous defects was achieved in these six cases.

  5. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation.

    PubMed

    Wang, Ling; Mohan, Chandra

    2016-09-01

    This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease.

  6. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation

    PubMed Central

    2016-01-01

    Abstract This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease. PMID:28191530

  7. Modulation of platelet-derived growth factor receptor expression in microvascular endothelial cells during in vitro angiogenesis.

    PubMed Central

    Marx, M; Perlmutter, R A; Madri, J A

    1994-01-01

    Microvascular endothelial cells in vivo exhibit a plastic phenotype, forming a nonproliferative, differentiated capillary network, while retaining their ability to respond to injury by proliferation, migration and neovascularization. The presence of PDGF receptors and PDGF responsiveness in microvascular endothelial cells and the significance of PDGF isoforms in the control of endothelial cell growth and differentiation remain controversial. Since culture of microvascular endothelial cells in a three-dimensional (3D) system induced cell differentiation and angiogenesis and inhibited proliferation, the present study investigates the role of different extracellular matrix environments in inducing different microvascular endothelial cell phenotypes on microvascular endothelial cell PDGF receptor expression and PDGF responsiveness. In conventional two-dimensional (2D) culture, microvascular endothelial cells expressed both PDGF receptor alpha and beta chains. Suramin treatment demonstrated continuous downregulation of the alpha receptor surface expression. PDGF BB and, to a lesser extent, PDGF AB were mitogenic in 2D-culture, PDGF AA failed to induce any proliferative response despite inducing receptor autophosphorylation. During in vitro angiogenesis induced by 3D-culture, both PDGF receptors were rapidly downregulated. Assessment of cell proliferation showed quiescent cells and PDGF unresponsiveness. We conclude that the induction of a differentiated phenotype during in vitro angiogenesis (tube formation) driven in part by the spatial organization of the surrounding matrix is associated with a downregulation of PDGF receptors. Identification of the molecular cell-matrix interactions involved in this receptor regulation may allow for targeted manipulation of cell growth in vivo and lead to novel therapeutic applications for PDGF. Images PMID:7506710

  8. Treatment of hemimasticatory spasm with microvascular decompression.

    PubMed

    Wang, Yong-Nan; Dou, Ning-Ning; Zhou, Qiu-Meng; Jiao, Wei; Zhu, Jin; Zhong, Jun; Li, Shi-Ting

    2013-01-01

    Hemimasticatory spasm is a rare disorder characterized by paroxysmal involuntary contraction of the jaw-closing muscles. As the ideology and pathogenesis of the disease are still unclear, there has been no treatment that could give rise to a good outcome so far. Herein, we tried to use surgical management to cure the disease. Six patients with the disease were included in this study. These patients underwent microvascular decompression of the motor fibers of the trigeminal root. After the operation, all faces of the patients felt relaxed at varied degrees, except for 1 patient. Our study showed that microvascular decompression of the trigeminal nerve could lead to a better outcome. However, a control study with a large sample is needed before this technique is widely used.

  9. Microvascular Targets for Anti-Fibrotic Therapeutics

    PubMed Central

    Pu, Kai-Ming T.; Sava, Parid; Gonzalez, Anjelica L.

    2013-01-01

    Fibrosis is characterized by excessive extracellular matrix deposition and is the pathological outcome of repetitive tissue injury in many disorders. The accumulation of matrix disrupts the structure and function of the native tissue and can affect multiple organs including the lungs, heart, liver, and skin. Unfortunately, current therapies against the deadliest and most common fibrosis are ineffective. The pathogenesis of fibrosis is the result of aberrant wound healing, therefore, the microvasculature plays an important role, contributing through regulation of leukocyte recruitment, inflammation, and angiogenesis. Further exacerbating the condition, microvascular endothelial cells and pericytes can transdifferentiate into matrix depositing myofibroblasts. The contribution of the microvasculature to fibrotic progression makes its cellular components and acellular products attractive therapeutic targets. In this review, we examine many of the cytokine, matrix, and cellular microvascular components involved in fibrosis and discuss their potential as targets for fibrotic therapies with a particular focus on developing nanotechnologies. PMID:24348218

  10. Sex-Specific Factors in Microvascular Angina

    PubMed Central

    Humphries, Karin H.; Bairey Merz, C. Noel

    2014-01-01

    Among women presenting for evaluation of suspected ischemic symptoms, a diagnosis of normal coronary arteries is five times more common, as compared to men. These women are often labeled as cardiac syndrome X (CSX), a subset of which have microvascular angina (MA) due to microvascular coronary dysfunction (MCD). MCD is not benign and is associated with an annual 2.5% cardiac event rate. Non-invasive testing for MCD remains insensitive although newer imaging modalities such as adenosine cardiac magnetic resonance imaging (CMRI) appear promising. The gold standard for diagnosis of MCD is coronary reactivity testing (CRT), an invasive technique which is not available in many countries. With regard to treatment, large scale trials are lacking. While research is ongoing, the current platform of therapy consists of anti-anginal, anti-platelet and endothelial modifying agents (primarily angiotensin converting enzyme inhibitors and statins). PMID:24582724

  11. Vitamin D and retinal microvascular damage

    PubMed Central

    Mutlu, Unal; Ikram, M Arfan; Hofman, Albert; de Jong, Paulus T V M; Uitterlinden, Andre G; Klaver, Caroline C W; Ikram, M Kamran

    2016-01-01

    Abstract Vitamin D has been linked to various cardiovascular risk factors including indices of large-vessel disease. However, it remains unclear whether vitamin D is also associated with microvascular damage. In a community-dwelling population, we studied associations between vitamin D serum levels and retinal microvascular damage defined as retinopathy signs, narrower arterioles, and wider venules. From the population-based Rotterdam Study, we included 5675 participants (age ≥45 years) with vitamin D data and gradable retinal photographs. Serum levels of vitamin D were measured using an antibody-based assay. Retinal exudates, microaneurysms, cotton wool spots, and dot/blot hemorrhages were graded on fundus photographs by experienced graders in the whole sample; retinal vascular calibers, that is, arteriolar and venular diameters, were semiautomatically measured in a subsample (n = 2973). We examined the cross-sectional association between vitamin D and retinal microvascular damage using logistic and linear regression models, adjusting for age, sex, and cardiovascular risk factors. We found that persons with lower vitamin D levels were more likely to have retinopathy (adjusted odds ratio per standard deviation (SD) decrease of vitamin D = 1.30; 95% confidence interval (CI): = 1.12–1.49). Furthermore, lower vitamin D levels were associated with wider venular calibers (adjusted mean difference per SD decrease in vitamin D = 1.35; 95% CI = 0.64–2.06). This association was strongest among men (P for interaction = 0.023). Lower levels of vitamin D are associated with retinal microvascular damage, suggesting that the link with cardiovascular risk may partly run through changes in the microvasculature. PMID:27930528

  12. Fabrication, characterization, and modeling of microvascular composites

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas J.

    Composite laminates of glass fiber and epoxy pre-preg were fabricated with microvascular channels. The channels were created using polylactic acid (PLA) filament that evaporates at a temperature of 392 °F (200 °C) above the resin cure temperature of 250 °F (121 °C). After the composite is cured, the panel was removed from the oven and allowed to cool to room temperature. The panel is then reheated to 392 °F to vaporize the filament, leaving a cylindrical channel. A microvascular channel can be used for withdrawing heat, damage detection and self-healing. However, increasing the temperatures of the laminate above the cure temperature of the resin causes excess cross linking, potentially decreasing the mechanical properties. Tensile and flexural mechanical tests were performed on composite specimens and tensile tests were performed on neat resin specimens. A three-dimensional finite element model (FEM) was developed to study the progressive deformation and damage mechanics under tensile loading. The load carrying capacity of the microvascular composite was shown to decrease by 40% from a standard composite material. This paper will present the details of the fabrication, characterization and modeling techniques that were used in this study.

  13. Antidepressant-like cognitive and behavioral effects of acute ketamine administration associated with plasticity in the ventral hippocampus to medial prefrontal cortex pathway

    PubMed Central

    Jett, Julianne D.; Boley, Angela M.; Girotti, Milena; Shah, Amiksha; Lodge, Daniel J.; Morilak, David A.

    2015-01-01

    Rationale Acute low-dose administration of the NMDA receptor antagonist, ketamine, produces rapid and sustained antidepressant-like effects in humans and rodents. Recently, we found that the long-lasting effect of ketamine on the forced swim test requires ventral hippocampal (vHipp) activity at the time of drug administration. The medial prefrontal cortex (mPFC), a target of the vHipp dysregulated in depression, is important for cognitive flexibility and response strategy selection. Deficits in cognitive flexibility, the ability to modify thoughts and behaviors in response to changes in the environment, are associated with depression. We have shown that chronic stress impairs cognitive flexibility on the attentional set-shifting test (AST), and induces a shift from active to passive response strategies on the shock-probe defensive burying test (SPDB). Objective In this study, we tested the effects of ketamine on chronic stress-induced changes in cognitive flexibility and coping behavior on the AST and SPDB, respectively. Subsequently, we investigated vHipp-mPFC plasticity as a potential mechanism of ketamine’s therapeutic action. Results Ketamine reversed deficits in cognitive flexibility and restored active coping behavior in chronically stressed rats. Further, high frequency stimulation in the vHipp replicated ketamine’s antidepressant-like effects on the forced swim test and AST, but not on the SPDB. Conclusion These results show that ketamine restores cognitive flexibility and coping response strategy compromised by stress. Activity in the vHipp-mPFC pathway may represent a neural substrate for some of the antidepressant-like behavioral effects of ketamine, including cognitive flexibility, but other circuits may mediate the effects of ketamine on coping response strategy. PMID:25986748

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

    PubMed Central

    2013-01-01

    Background: Microvascular reconstruction for oncologic defects is a challenging and rewarding endeavor, and successful outcomes are dependent on a multitude of factors. This study represents lessons learned from a personal prospective experience with 100 consecutive free flaps. Methods: All patients’ medical records were reviewed for demographics, operative notes, and complications. Results: Overall 100 flaps were performed in 84 consecutive patients for reconstruction of breast, head and neck, trunk, and extremity defects. Nineteen patients underwent free flap breast reconstruction with 10 patients undergoing bilateral reconstruction and 2 patients receiving a bipedicle flap for reconstruction of a unilateral breast defect. Sixty-five free flaps were performed in 61 patients with 3 patients receiving 2 free flaps for reconstruction of extensive head and neck defects and 1 patient who required a second flap for partial flap loss. Trunk and extremity reconstruction was less common with 2 free flaps performed in each group. Overall, 19 patients (22.6%) developed complications and 14 required a return to the operating room. There were no flap losses in this cohort. Thorough preoperative evaluation and workup, meticulous surgical technique and intraoperative planning, and diligent postoperative monitoring and prompt intervention are critical for flap success. 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. PMID:25289221

  15. Direct ink writing of microvascular networks

    NASA Astrophysics Data System (ADS)

    Wu, Willie

    Nature is replete with examples of embedded microvascular systems that enable efficient fluid flow and distribution for autonomic healing, cooling, and energy harvesting. The ability to incorporate microvascular networks in functional materials systems is therefore both scientifically and technologically important. In this PhD thesis, the direct-write assembly of planar and 3D biomimetic microvascular networks within polymer and hydrogel matrices is demonstrated. In addition, the influence of network design of fluid transport efficiency is characterized. Planar microvascular networks composed of periodic lattices of uniformal microchannels and hierarchical, branching architectures are constructed by direct-write assembly of a fugitive organic ink. Several advancements are required to facilitate their patterning, including pressure valving, dual ink printing, and dynamic pressure variation to allow tunable control of ink deposition. The hydraulic conductance is measured using a high pressure flow meter as a function of network design. For a constant vascular volume and areal coverage, 2- and 4-generation branched architectures that obey Murray's Law exhibited the highest hydraulic conductivity. These experimental observations are in good agreement with predictions made by analytic models. 3D microvascular networks are fabricated by omnidirectional printing a fugitive organic ink into a photopolymerizable hydrogel matrix that is capped with fluid filler of nearly identical composition. Using this approach, 3D networks of arbitrary design can be patterned. After ink deposition is complete, the matrix and fluid filler are chemically cross-linked via UV irradiation, and the ink is removed by liquefication. Aqueous solutions composed of a triblock copolymer of polyethylene oxide (PEO)-polypropylene oxide (PPO)-PEO constitute the materials system of choice due to their thermal- and concentration-dependent phase behavior. Specifically, the fugitive ink consists of a 23 w

  16. Skin microvascular reactivity in trained adolescents.

    PubMed

    Roche, Denise M; Rowland, T W; Garrard, M; Marwood, S; Unnithan, V B

    2010-04-01

    Whilst endothelial dysfunction is associated with a sedentary lifestyle, enhanced endothelial function has been documented in the skin of trained individuals. The purpose of this study was to investigate whether highly trained adolescent males possess enhanced skin microvascular endothelial function compared to their untrained peers. Seventeen highly and predominantly soccer trained boys (V(O)(2)(peak): 55 +/- 6 mL kg(-1) min(-1)) and nine age- and maturation-matched untrained controls (V(O)(2)(peak): 43 +/- 5 mL kg(-1) min(-1)) aged 13-15 years had skin microvascular endothelial function assessed using laser Doppler flowmetry. Baseline and maximal thermally stimulated skin blood flow (SkBF) responses were higher in forearms of trained subjects compared to untrained participants [baseline SkBF: 11 +/- 4 vs. 9 +/- 3 perfusion units (PU), p < 0.05; SkBF(max): 282 +/- 120 vs. 204 +/- 68 PU, p < 0.05]. Similarly, cutaneous vascular conductance (CVC) during local heating was superior in the forearm skin of trained versus untrained individuals (CVC(max): 3 +/- 1 vs. 2 +/- 1 PU mmHg(-1), p < 0.05). Peak hyperaemia following arterial occlusion and area under the reactive hyperaemia curve were also greater in forearm skin of the trained group (peak hyperaemia: 51 +/- 21 vs. 35 +/- 15 PU, p < 0.05; area under curve: 1596 +/- 739 vs. 962 +/- 796 PUs, p < 0.05). These results suggest that chronic exercise training in adolescents is associated with enhanced microvascular endothelial vasodilation in non-glabrous skin.

  17. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Rapid homogeneous endothelialization of high aspect ratio microvascular networks.

    PubMed

    Naik, Nisarga; Hanjaya-Putra, Donny; Haller, Carolyn A; Allen, Mark G; Chaikof, Elliot L

    2015-08-01

    Microvascularization of an engineered tissue construct is necessary to ensure the nourishment and viability of the hosted cells. Microvascular constructs can be created by seeding the luminal surfaces of microfluidic channel arrays with endothelial cells. However, in a conventional flow-based system, the uniformity of endothelialization of such an engineered microvascular network is constrained by mass transfer of the cells through high length-to-diameter (L/D) aspect ratio microchannels. Moreover, given the inherent limitations of the initial seeding process to generate a uniform cell coating, the large surface-area-to-volume ratio of microfluidic systems demands long culture periods for the formation of confluent cellular microconduits. In this report, we describe the design of polydimethylsiloxane (PDMS) and poly(glycerol sebacate) (PGS) microvascular constructs with reentrant microchannels that facilitates rapid, spatially homogeneous endothelial cell seeding of a high L/D (2 cm/35 μm; > 550:1) aspect ratio microchannels. MEMS technology was employed for the fabrication of a monolithic, elastomeric, reentrant microvascular construct. Isotropic etching and PDMS micromolding yielded a near-cylindrical microvascular channel array. A 'stretch - seed - seal' operation was implemented for uniform incorporation of endothelial cells along the entire microvascular area of the construct yielding endothelialized microvascular networks in less than 24 h. The feasibility of this endothelialization strategy and the uniformity of cellularization were established using confocal microscope imaging.

  19. Plastic Jellyfish.

    ERIC Educational Resources Information Center

    Moseley, Christine

    2000-01-01

    Presents an environmental science activity designed to enhance students' awareness of the hazards of plastic waste for wildlife in aquatic environments. Discusses how students can take steps to reduce the effects of plastic waste. (WRM)

  20. Evidence of Microvascular Changes in the Retina following Kawasaki Disease

    PubMed Central

    Chen, Katherine Y. H.; Burgner, David P.; Wong, Tien Y.; Saw, Seang Mei; Quek, Swee Chye; Pang, Audrey Y. C.; Leo, Seo Wei; Wong, Inez B.; Zannino, Diana; Curtis, Nigel; Cheung, Michael; Cheung, Carol Y.; Lim, Terence C. W.

    2017-01-01

    It is unclear whether all children with Kawasaki disease (KD) have increased later cardiovascular risk. The retinal microvasculature reflects changes in the microcirculation and is associated with traditional cardiovascular risk factors and events. The aim of this study was to investigate retinal microvascular parameters in two populations of patients with previous KD and control participants. We performed case-control studies of 116 (57 patients and 59 control participants) Australian and 156 (78 patients and 78 control participants) Singaporean individuals, at least two years since their acute illness. Standardised retinal photographs were graded by trained technicians using a semi-automated software, which quantifies the retinal microvasculature (calibre, branching angle, fractal dimensions, and tortuosity). Retinal venules of Singaporean KD patients were 9.67 μm (95% CI 4.87 to 14.51, p < 0.001) larger than control participants following correction for traditional cardiovascular risk factors. An incremental increase in the size of retinal venules in those with coronary artery abnormalities was observed. There was limited evidence that retinal venules were larger in Australian KD patients with coronary artery abnormalities compared to control participants (7.34 μm, 95% CI 1.30 to 15.99, p = 0.10). Differences in retinal microvasculature were particularly evident in Singaporean KD patients. Larger retinal venules may reflect chronic inflammation and endothelial dysfunction, and are associated with coronary artery disease in adults. PMID:28094311

  1. Skin microvascular reactivity in patients with hypothyroidism.

    PubMed

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

    2016-11-04

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

  2. Myocardial perfusion echocardiography and coronary microvascular dysfunction

    PubMed Central

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-01-01

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  3. Heterogeneous ageing of skeletal muscle microvascular function.

    PubMed

    Muller-Delp, Judy M

    2016-04-15

    The distribution of blood flow to skeletal muscle during exercise is altered with advancing age. Changes in arteriolar function that are muscle specific underlie age-induced changes in blood flow distribution. With advancing age, functional adaptations that occur in resistance arterioles from oxidative muscles differ from those that occur in glycolytic muscles. Age-related adaptations of morphology, as well as changes in both endothelial and vascular smooth muscle signalling, differ in muscle of diverse fibre type. Age-induced endothelial dysfunction has been reported in most skeletal muscle arterioles; however, unique alterations in signalling contribute to the dysfunction in arterioles from oxidative muscles as compared with those from glycolytic muscles. In resistance arterioles from oxidative muscle, loss of nitric oxide signalling contributes significantly to endothelial dysfunction, whereas in resistance arterioles from glycolytic muscle, alterations in both nitric oxide and prostanoid signalling underlie endothelial dysfunction. Similarly, adaptations of the vascular smooth muscle that occur with advancing age are heterogeneous between arterioles from oxidative and glycolytic muscles. In both oxidative and glycolytic muscle, late-life exercise training reverses age-related microvascular dysfunction, and exercise training appears to be particularly effective in reversing endothelial dysfunction. Patterns of microvascular ageing that develop among muscles of diverse fibre type and function may be attributable to changing patterns of physical activity with ageing. Importantly, aerobic exercise training, initiated even at an advanced age, restores muscle blood flow distribution patterns and vascular function in old animals to those seen in their young counterparts.

  4. Fractal analysis of microvascular networks in malignant brain tumors.

    PubMed

    Di Ieva, Antonio

    2012-01-01

    Brain tumors are characterized by a microvascular network which differs from normal brain vascularity. Different tumors show individual angiogenic patterns. Microvascular heterogeneity can also be observed within a neoplastic histotype. It has been shown that quantification of neoplastic microvascular patterns could be used in combination with the histological grade for tumor characterization and to refine clinical prognoses, even if no objective parameters have yet been validated. To overcome the limits of the Euclidean approach, we employ fractal geometry to analyze the geometric complexity underlying the microangioarchitectural networks in brain tumors. We have developed a computer-aided fractal-based analysis for the quantification of the microvascular patterns in histological specimens and ultra-high-field (7-Tesla) magnetic resonance images. We demonstrate that the fractal parameters are valid estimators of microvascular geometrical complexity. Furthermore, our analysis allows us to demonstrate the high geometrical variability underlying the angioarchitecture of glioblastoma multiforme and to differentiate low-grade from malignant tumors in histological specimens and radiological images. Based on the results of this study, we speculate the existence of a gradient in the geometrical complexity of microvascular networks from those in the normal brain to those in malignant brain tumors. Here, we summarize a new methodology for the application of fractal analysis to the study of the microangioarchitecture of brain tumors; we further suggest this approach as a tool for quantifying and categorizing different neoplastic microvascular patterns and as a potential morphometric biomarker for use in clinical practice.

  5. Consumer hazards of plastics.

    PubMed Central

    Wiberg, G S

    1976-01-01

    The modern consumer is exposed to a wide variety of plastic and rubber products in his day to day life: at home, work, school, shopping, recreation and play, and transport. A large variety of toxic sequellae have resulted from untoward exposures by many different routes: oral, dermal, inhalation, and parenteral. Toxic change may result from the plastic itself, migration of unbound components and additives, chemical decomposition or toxic pyrolysis products. The type of damage may involve acute poisoning, chronic organ damage, reproductive disorders, and carcinogenic, mutagenic and teratogenic episodes. Typical examples for all routes are cited along with the activites of Canadian regulatory agencies to reduce both the incidence and severity of plastic-induced disease. PMID:1026409

  6. Differentiation state determines neural effects on microvascular endothelial cells

    SciTech Connect

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

    2012-10-01

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

  7. Phase transition of the microvascular network architecture in human pathologies.

    PubMed

    Bianciardi, Giorgio; Traversi, Claudio; Cattaneo, Ruggero; De Felice, Claudia; Monaco, Annalisa; Tosi, Gianmarco; Parrini, Stefano; Latini, Giuseppe

    2012-01-01

    We have investigated the microvascular pattern in acquired or genetic diseases in humans. The lower gingival and vestibular oral mucosa, as well as the optic nerve head, was chosen to characterize the vascular pattern complexity due to the simple accessibility and visibility Local fractal dimensions, fractal dimension of the minimum path and Lempel-Ziv complexity have been used as operational numerical tools to characterize the microvascular networks. In the normal healthy subjects microvascular networks show nonlinear values corresponding to the complexity of a diffusion limited aggregation (DLA) model, while in several acquired or genetic diseases they are approaching the ones of an invasion percolation model.

  8. Microvascular free flaps in skull base reconstruction.

    PubMed

    Herr, Marc W; Lin, Derrick T

    2013-01-01

    The anatomical challenges of skull base surgery are well known. Furthermore, ablative and traumatic defects in this region produce complex reconstructive problems with a high risk of significant postoperative morbidity and mortality. Over the past two decades, microvascular free tissue reconstruction following open resection has been shown to improve outcomes and reduce complication rates when compared to the traditional use of pedicled flaps. The increasing use of free tissue transfer has been further strengthened by improved technical expertise and high flap success rates. Since the size and type of free tissue to be utilized must be individualized to each defect, the accomplished reconstructive surgeon should be extremely versatile and, by extension, facile with a several types of free flaps. Thus, four of the most commonly used flaps--the rectus abdominis, radial forearm, latissimus dorsi and anterolateral thigh flaps--are discussed.

  9. Mandibular reconstruction with composite microvascular tissue transfer

    SciTech Connect

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

    1990-10-01

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

  10. Microvascular and interstitial oxygen tension in the renal cortex and medulla studied in a 4-h rat model of LPS-induced endotoxemia.

    PubMed

    Dyson, Alex; Bezemer, Rick; Legrand, Matthieu; Balestra, Gianmarco; Singer, Mervyn; Ince, Can

    2011-07-01

    The pathophysiology of sepsis-induced acute kidney injury remains poorly understood. As changes in renal perfusion and oxygenation have been shown, we aimed to study the short-term effects of endotoxemia on microvascular and interstitial oxygenation in the cortex and medulla, in conjunction with global and renal hemodynamics. In a 4-h rat model of endotoxemia, we simultaneously assessed renal artery blood flow and microvascular and interstitial oxygen tensions in the renal cortex and medulla using ultrasonic flowmetry, dual wavelength phosphorimetry, and tissue oxygen tension monitoring, respectively. Whereas medullary microvascular and interstitial oxygen tensions decreased promptly in line with macrovascular blood flow, changes in cortical oxygenation were only seen later on. During the entire experimental protocol, the gradient between microvascular PO₂ and tissue oxygen tension remained unchanged in both cortex and outer medulla. At study end, urine output was significantly decreased despite a maintained oxygen consumption rate. In this 4-h rat model of endotoxemia, total renal oxygen consumption and the gradient between microvascular PO₂ and tissue oxygen tension remained unaltered, despite falls in renal perfusion and oxygen delivery and urine output. Taken in conjunction with the decrease in urine output, our results could represent either a functional renal impairment or an adaptive response.

  11. Impact of hetastarch on the intestinal microvascular barrier during ECLS.

    PubMed

    Cox, C S; Brennan, M; Allen, S J

    2000-04-01

    The effects of hetastarch on microvascular fluid flux were determined in anesthetized dogs undergoing extracorporeal life support (ECLS) with a roller pump and membrane oxygenator. ECLS with a lactated Ringer priming solution resulted in a decrease in microvascular protein reflection coefficient and an increase in transvascular protein clearance. Use of a 6% hetastarch priming solution attenuated the decrease in microvascular protein reflection coefficient and blunted the increase in transvascular protein clearance. Ileal tissue water increased in the group treated with the lactated Ringer priming solution compared with the group treated with 6% hetastarch. The effective plasma-to-interstitial colloid osmotic pressure gradient was greater in the group treated with hetastarch than in the group treated with lactated Ringer solution. Hetastarch decreases the edema associated with ECLS. The reduction in edema is due to the maintenance of the plasma-to-interstitial colloid osmotic pressure gradient and the reduction in the microvascular permeability to protein.

  12. Plastics Technology.

    ERIC Educational Resources Information Center

    Barker, Tommy G.

    This curriculum guide is designed to assist junior high schools industrial arts teachers in planning new courses and revising existing courses in plastics technology. Addressed in the individual units of the guide are the following topics: introduction to production technology; history and development of plastics; safety; youth leadership,…

  13. SDF-1/CXCR4 signaling preserves microvascular integrity and renal function in chronic kidney disease.

    PubMed

    Chen, Li-Hao; Advani, Suzanne L; Thai, Kerri; Kabir, M Golam; Sood, Manish M; Gibson, Ian W; Yuen, Darren A; Connelly, Kim A; Marsden, Philip A; Kelly, Darren J; Gilbert, Richard E; Advani, Andrew

    2014-01-01

    The progressive decline of renal function in chronic kidney disease (CKD) is characterized by both disruption of the microvascular architecture and the accumulation of fibrotic matrix. One angiogenic pathway recently identified as playing an essential role in renal vascular development is the stromal cell-derived factor-1α (SDF-1)/CXCR4 pathway. Because similar developmental processes may be recapitulated in the disease setting, we hypothesized that the SDF-1/CXCR4 system would regulate microvascular health in CKD. Expression of CXCR4 was observed to be increased in the kidneys of subtotally nephrectomized (SNx) rats and in biopsies from patients with secondary focal segmental glomerulosclerosis (FSGS), a rodent model and human correlate both characterized by aberration of the renal microvessels. A reno-protective role for local SDF-1/CXCR4 signaling was indicated by i) CXCR4-dependent glomerular eNOS activation following acute SDF-1 administration; and ii) acceleration of renal function decline, capillary loss and fibrosis in SNx rats treated with chronic CXCR4 blockade. In contrast to the upregulation of CXCR4, SDF-1 transcript levels were decreased in SNx rat kidneys as well as in renal fibroblasts exposed to the pro-fibrotic cytokine transforming growth factor β (TGF-β), the latter effect being attenuated by histone deacetylase inhibition. Increased renal SDF-1 expression was, however, observed following the treatment of SNx rats with the ACE inhibitor, perindopril. Collectively, these observations indicate that local SDF-1/CXCR4 signaling functions to preserve microvascular integrity and prevent renal fibrosis. Augmentation of this pathway, either purposefully or serendipitously with either novel or existing therapies, may attenuate renal decline in CKD.

  14. Hydrogen peroxide-induced calcium influx in lung microvascular endothelial cells involves TRPV4

    PubMed Central

    Suresh, Karthik; Servinsky, Laura; Reyes, Jose; Baksh, Syeda; Undem, Clark; Caterina, Michael; Pearse, David B.

    2015-01-01

    In acute respiratory distress syndrome, both reactive oxygen species (ROS) and increased intracellular calcium ([Ca2+]i) are thought to play important roles in promoting endothelial paracellular permeability, but the mechanisms linking ROS and [Ca2+]i in microvascular endothelial cells are not known. In this study, we assessed the effect of hydrogen peroxide (H2O2) on [Ca2+]i in mouse and human lung microvascular endothelial cells (MLMVEC and HLMVEC, respectively). We found that in both MLMVECs and HLMVECs, exogenously applied H2O2 increased [Ca2+]i through Ca2+ influx and that pharmacologic inhibition of the calcium channel transient receptor potential vanilloid 4 (TRPV4) attenuated the H2O2-induced Ca2+ influx. Additionally, knockdown of TRPV4 in HLMVEC also attenuated calcium influx following H2O2 challenge. Administration of H2O2 or TRPV4 agonists decreased transmembrane electrical resistance (TER), suggesting increased barrier permeability. To explore the regulatory mechanisms underlying TRPV4 activation by ROS, we examined H2O2-induced Ca2+ influx in MLMVECs and HLMVECs with either genetic deletion, silencing, or pharmacologic inhibition of Fyn, a Src family kinase. In both MLMVECs derived from mice deficient for Fyn and HLMVECs treated with either siRNA targeted to Fyn or the Src family kinase inhibitor SU-6656 for 24 or 48 h, the H2O2-induced Ca2+ influx was attenuated. Treatment with SU-6656 decreased the levels of phosphorylated, but not total, TRPV4 protein and had no effect on TRPV4 response to the external agonist, GSK1016790A. In conclusion, our data suggest that application of exogenous H2O2 increases [Ca2+]i and decreases TER in microvascular endothelial cells via activation of TRPV4 through a mechanism that requires the Src kinase Fyn. PMID:26453519

  15. Plastic bronchitis: a management challenge.

    PubMed

    Eberlein, Michael H; Drummond, Michael B; Haponik, Edward F

    2008-02-01

    Plastic bronchitis is an uncommon and underdiagnosed entity, characterized by recurrent expectoration of large, branching bronchial casts. We describe a 39-year-woman with no prior lung disease who had episodic wheezing, severe dyspnea with expectoration of large and thick secretions, branching in appearance, which she described as resembling squid. A comprehensive evaluation revealed no specific cause and a diagnosis of idiopathic plastic bronchitis was made. In plastic bronchitis the bronchial casts may vary in size from small segmental casts of a bronchus to casts filling the airways of an entire lung. Plastic bronchitis can therefore present as an acute life-threatening emergency if mechanical obstruction of major airways occurs. The casts are differentiated into type I, inflammatory casts, or type II, acellular casts. The type I inflammatory casts are often associated with bronchial disease and often have an acute presentation. The acellular type of cast production is often chronic or recurrent. Numerous systemic illnesses are associated with plastic bronchitis, but often, as in our patient, no underlying cause can be identified. The treatment of plastic bronchitis includes acute therapy to aid the removal and expectoration of casts, and specific short- or long-term treatments attempting to address the underlying hypersecretory process. The therapeutic options are supported only by anecdotal evidence based on case reports as the rarity and heterogeneity of plastic bronchitis confounds systematic investigations of its treatment. Improved understanding of the regulation of mucus production may allow for new treatment options in plastic bronchitis and other chronic lung diseases characterized by hypersecretion of mucus.

  16. Fifty Years of Innovation in Plastic Surgery

    PubMed Central

    Hughes-Hallett, Archie; Marcus, Hani J; Yang, Guang-Zhong; Darzi, Ara; Hettiaratchy, Shehan

    2016-01-01

    Background Innovation has molded the current landscape of plastic surgery. However, documentation of this process only exists scattered throughout the literature as individual articles. The few attempts made to profile innovation in plastic surgery have been narrative, and therefore qualitative and inherently biased. Through the implementation of a novel innovation metric, this work aims to identify and characterise the most prevalent innovations in plastic surgery over the last 50 years. Methods Patents and publications related to plastic surgery (1960 to 2010) were retrieved from patent and MEDLINE databases, respectively. The most active patent codes were identified and grouped into technology areas, which were subsequently plotted graphically against publication data. Expert-derived technologies outside of the top performing patents areas were additionally explored. Results Between 1960 and 2010, 4,651 patents and 43,118 publications related to plastic surgery were identified. The most active patent codes were grouped under reconstructive prostheses, implants, instruments, non-invasive techniques, and tissue engineering. Of these areas and other expert-derived technologies, those currently undergoing growth include surgical instruments, implants, non-invasive practices, transplantation and breast surgery. Innovations related to microvascular surgery, liposuction, tissue engineering, lasers and prostheses have all plateaued. Conclusions The application of a novel metric for evaluating innovation quantitatively outlines the natural history of technologies fundamental to the evolution of plastic surgery. Analysis of current innovation trends provides some insight into which technology domains are the most active. PMID:27019807

  17. Scalp reconstruction by microvascular free tissue transfer

    SciTech Connect

    Furnas, H.; Lineaweaver, W.C.; Alpert, B.S. )

    1990-05-01

    We report on a series of patients with scalp defects who have been treated with a variety of free flaps, spanning the era of microvascular free tissue transfer from its incipient stages to the present. Between 1971 and 1987, 18 patients underwent scalp reconstruction with 21 free flaps: 11 latissimus dorsi, 3 scalp transfers between identical twins, 3 groin, one combined latissimus dorsi and serratus anterior, two serratus anterior, and one omentum. These flaps were used to cover scalp defects resulting from burns, trauma, radiation, and tumors in patients ranging from 7 to 79 years of age. Follow-up has ranged from 3 weeks to 7 years. All of our flaps survived and covered complex defects, many of which had failed more conservative attempts at cover. One patient received radiation therapy to his flap without unfavorable sequelae. This experience began with a pioneering omental flap and includes cutaneous and muscle flaps. The latissimus dorsi is our first choice for free flap reconstruction of extensive, complicated scalp wounds because of its large size, predictable blood supply, ease of harvesting, and provision of excellent vascularity to compromised beds.

  18. [Microvascular anastomoses in cervical esophageal reconstruction].

    PubMed

    Takushima, A; Harii, K; Asato, H

    2001-09-01

    Ischemia or hemostasis in the gastric, jejunal, and colonic pedicle after esophagectomy is believed to contribute significantly to postoperative complications. With the advent of microvascular anastomoses, many surgeons have adopted vascular augmentation (supercharge) as a means of avoiding these difficulties. Microsurgical free tissue transfer represented by the free jejunum and forearm flap also plays an important role in esophageal reconstruction. In this paper, the authors introduce the technical points important for successful revascularization including the choice of recipient vessels, setting up of the reconstructive materials, and postoperative monitoring. In cases of gastric pull-up elevated via posterior mediastinum, the left gastroduodenal vessels are anastomosed to the cervical transverse or superior thyroidal vessels. In cases of duodenal or colonic pull-up elevated via the anterosternal route, the vascular pedicles are anastomosed to the internal mammary vessels which are dissected by resecting the costal cartilage. When the free jejunum flap is used, the cervical transverse or superior thyroidal vessels are most frequently used as recipients. Postoperative monitoring of free flaps is performed using Doppler ultrasound or through a small skin incision made above the transferred tissue. Although gastric or colonic pull-up is difficult to monitor, color Doppler sonography permits quantitative analysis of blood flow and may be a useful option.

  19. Polysialic Acid Acute Depletion Induces Structural Plasticity in Interneurons and Impairs the Excitation/Inhibition Balance in Medial Prefrontal Cortex Organotypic Cultures

    PubMed Central

    Castillo-Gómez, Esther; Pérez-Rando, Marta; Vidueira, Sandra; Nacher, Juan

    2016-01-01

    The structure and function of the medial prefrontal cortex (mPFC) is affected in several neuropsychiatric disorders, including schizophrenia and major depression. Recent studies suggest that imbalances between excitatory and inhibitory activity (E/I) may be responsible for this cortical dysfunction and therefore, may underlie the core symptoms of these diseases. This E/I imbalance seems to be correlated with alterations in the plasticity of interneurons but there is still scarce information on the mechanisms that may link these phenomena. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate, because it modulates the neuronal plasticity of interneurons and its expression is altered in schizophrenia and major depression. To address this question, we have developed an in vitro model using mPFC organotypic cultures of transgenic mice displaying fluorescent spiny interneurons. After enzymatic depletion of PSA, the spine density of interneurons, the number of synaptic puncta surrounding pyramidal neuron somata and the E/I ratio were strongly affected. These results point to the polysialylation of NCAM as an important factor in the maintenance of E/I balance and the structural plasticity of interneurons. This may be particularly relevant for better understanding the etiology of schizophrenia and major depression. PMID:27445697

  20. Lipopolysaccharide Induces Human Pulmonary Micro-Vascular Endothelial Apoptosis via the YAP Signaling Pathway

    PubMed Central

    Yi, Lei; Huang, Xiaoqin; Guo, Feng; Zhou, Zengding; Chang, Mengling; Tang, Jiajun; Huan, Jingning

    2016-01-01

    Gram-negative bacterial lipopolysaccharide (LPS) induces a pathologic increase in lung vascular leakage under septic conditions. LPS-induced human pulmonary micro-vascular endothelial cell (HPMEC) apoptosis launches and aggravates micro-vascular hyper-permeability and acute lung injury (ALI). Previous studies show that the activation of intrinsic apoptotic pathway is vital for LPS-induced EC apoptosis. Yes-associated protein (YAP) has been reported to positively regulate intrinsic apoptotic pathway in tumor cells apoptosis. However, the potential role of YAP protein in LPS-induced HPMEC apoptosis has not been determined. In this study, we found that LPS-induced activation and nuclear accumulation of YAP accelerated HPMECs apoptosis. LPS-induced YAP translocation from cytoplasm to nucleus by the increased phosphorylation on Y357 resulted in the interaction between YAP and transcription factor P73. Furthermore, inhibition of YAP by small interfering RNA (siRNA) not only suppressed the LPS-induced HPMEC apoptosis but also regulated P73-mediated up-regulation of BAX and down-regulation of BCL-2. Taken together, our results demonstrated that activation of the YAP/P73/(BAX and BCL-2)/caspase-3 signaling pathway played a critical role in LPS-induced HPMEC apoptosis. Inhibition of the YAP might be a potential therapeutic strategy for lung injury under sepsis. PMID:27807512

  1. Non-invasive evaluation of vasomotor and metabolic functions of microvascular endothelium in human skin.

    PubMed

    Fedorovich, Andrey A

    2012-07-01

    Correlation between metabolic and microhemodynamic processes in skin was assessed through acute pharmacological test with metabolically active Actovegin in 28 healthy volunteers. Laser Doppler flowmetry in combination with wavelet analysis of blood flow oscillations was used to identify functional state of arteriolar-venular areas of microvascular bed in the right forearm skin; capillary blood flow parameters were assessed through computer capillaroscopy in the nail bed of the right hand on the 4th finger. The metabolic effect (improved oxygen uptake and glucose disposal by tissues) was accompanied by significant increase in endothelial rhythm amplitude by 98% (p<0.00006), neurogenic rhythm amplitude by 50% (p<0.003) and myogenic rhythm amplitude by 54% (p<0.03), with capillary blood flow rate increasing by 90μm/s (p<0.04), pericapillary zone reducing by 15μm (p<0.0001) and diastolic blood pressure dropping by 4mm Hg (p<0.02). These results show close correlation between metabolic and microhemodynamic processes, which suggests that the amplitude activity within the range of endothelial rhythm (0.0095-0.021Hz) during laser Doppler flowmetry reflects not only solely vasomotor function but also metabolic function of microvascular endothelium.

  2. Inhibition of Murine Pulmonary Microvascular Endothelial Cell Apoptosis Promotes Recovery of Barrier Function under Septic Conditions

    PubMed Central

    Wang, Lefeng; Mehta, Sanjay; Brock, Michael

    2017-01-01

    Sepsis is characterized by injury of the pulmonary microvasculature and the pulmonary microvascular endothelial cells (PMVEC), leading to barrier dysfunction and acute respiratory distress syndrome (ARDS). Our recent work identified a strong correlation between PMVEC apoptosis and microvascular leak in septic mice in vivo, but the specific role of apoptosis in septic PMVEC barrier dysfunction remains unclear. Thus, we hypothesize that PMVEC apoptosis is likely required for PMVEC barrier dysfunction under septic conditions in vitro. Septic stimulation (mixture of tumour necrosis factor α, interleukin 1β, and interferon γ [cytomix]) of isolated murine PMVEC resulted in a significant loss of barrier function as early as 4 h after stimulation, which persisted until 24 h. PMVEC apoptosis, as reflected by caspase activation, DNA fragmentation, and loss of membrane polarity, was first apparent at 8 h after cytomix. Pretreatment of PMVEC with the pan-caspase inhibitor Q-VD significantly decreased septic PMVEC apoptosis and was associated with reestablishment of PMVEC barrier function at 16 and 24 h after stimulation but had no effect on septic PMVEC barrier dysfunction over the first 8 h. Collectively, our data suggest that early septic murine PMVEC barrier dysfunction driven by proinflammatory cytokines is not mediated through apoptosis, but PMVEC apoptosis contributes to late septic PMVEC barrier dysfunction. PMID:28250575

  3. Plastic Surgery Statistics

    MedlinePlus

    ... PRS GO PSN PSEN GRAFT Contact Us News Plastic Surgery Statistics Plastic surgery procedural statistics from the ... Plastic Surgery Statistics 2005 Plastic Surgery Statistics 2016 Plastic Surgery Statistics Stats Report 2016 National Clearinghouse of ...

  4. Cutaneous tactile allodynia associated with microvascular dysfunction in muscle

    PubMed Central

    Laferrière, Andre; Millecamps, Magali; Xanthos, Dimitris N; Xiao, Wen Hua; Siau, Chiang; de Mos, Marissa; Sachot, Christelle; Ragavendran, J Vaigunda; Huygen, Frank JPM; Bennett, Gary J; Coderre, Terence J

    2008-01-01

    Background Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia. Results Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist. Conclusion Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia. PMID:18957097

  5. Brain microvascular function during cardiopulmonary bypass

    SciTech Connect

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

    1987-11-01

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

  6. Effects of short-term walnut consumption on human microvascular function and its relationship to plasma epoxide content.

    PubMed

    Holt, Roberta R; Yim, Sun J; Shearer, Gregory C; Hackman, Robert M; Djurica, Dragana; Newman, John W; Shindel, Alan W; Keen, Carl L

    2015-12-01

    Improved vascular function after the incorporation of walnuts into controlled or high-fat diets has been reported; however, the mechanism(s) underlying this effect of walnuts is(are) poorly defined. The objective of the current study was to evaluate the acute and short-term effects of walnut intake on changes in microvascular function and the relationship of these effects to plasma epoxides, the cytochrome-P450-derived metabolites of fatty acids. Thirty-eight hypercholesterolemic postmenopausal women were randomized to 4 weeks of 5 g or 40 g of daily walnut intake. All outcomes were measured after an overnight fast and 4 h after walnut intake. Microvascular function, assessed as the reactive hyperemia index (RHI), was the primary outcome measure, with serum lipids and plasma epoxides as secondary measures. Compared to 5 g of daily walnut intake, consuming 40 g/d of walnuts for 4 weeks increased the RHI and Framingham RHI. Total cholesterol and low- and high-density cholesterol did not significantly change after walnut intake. The change in RHI after 4 weeks of walnut intake was associated with the change in the sum of plasma epoxides (r=0.65, P=.002) but not with the change in the sum of plasma hydroxyeicosatetraenoic acids. Of the individual plasma epoxides, arachidonic-acid-derived 14(15)-epoxyeicosatrienoic acid was most strongly associated with the change in microvascular function (r=0.72, P<.001). These data support the concept that the intake of walnut-derived fatty acids can favorably affect plasma epoxide production, resulting in improved microvascular function.

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

    PubMed Central

    Moran, Elizabeth P.; Ma, Jian-xing

    2015-01-01

    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. PMID:25705219

  8. Vascular grafts in microvascular surgery. An experimental study

    SciTech Connect

    Marrangoni, A.G.; Marcelli, G.; Culig, M.; Simone, S.T.

    1988-02-01

    The patency of microvascular grafts depends on the luminal diameter, which is determined by the amount of fibrin and platelets deposited on the intraluminal surface and the anastomotic site, and the extent of pseudointimal formation. An experimental microvascular model in rats has been developed in our laboratory using Indium-111-labeled platelets to measure the amount of deposition on grafts inserted into the infrarenal aorta. This study was designed to assess the patency rates in these grafts and the pathologic maturation as determined by light and electron microscopy. Our study suggests that substantial patency rates can be achieved in aspirin-treated rats, although there was little influence on the pathologic maturation. Indium-111 oxine-labeled platelets can be used to document platelet aggregation, and the technique can be a valuable adjunct in the study of microvascular grafts.

  9. Regional cutaneous microvascular flow responses during gravitational and LBNP stresses

    NASA Technical Reports Server (NTRS)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Murthy, Gita; Hargens, Alan R.

    1993-01-01

    Due to the regional variability of local hydrostatic pressures, microvascular flow responses to gravitational stress probably vary along the length of the body. Although these differences in local autoregulation have been observed previously during whole-body tilting, they have not been investigated during application of artificial gravitational stresses, such as lower body negative pressure or high gravity centrifugation. Although these stresses can create equivalent G-levels at the feet, they result in distinct distributions of vascular transmural pressure along the length of the body, and should consequently elicit different magnitudes and distributions of microvascular response. In the present study, the effects of whole-body tilting and lower body negative pressure on the level and distribution of microvascular flows within skin along the length of the body were compared.

  10. Microvascular permeability changes might explain cardiac tamponade after alcohol septal ablation for hypertrophic cardiomyopathy.

    PubMed

    Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Jung-Jung; Chung, Chang-Min; Chang, Shih-Tai; Pan, Kuo-Li

    2014-04-01

    Various sequelae of alcohol septal ablation for hypertrophic obstructive cardiomyopathy have been reported. Of note, some cases of cardiac tamponade after alcohol septal ablation cannot be well explained. We describe the case of a 78-year-old woman with hypertrophic obstructive cardiomyopathy in whom cardiac tamponade developed one hour after alcohol septal ablation, probably unrelated to mechanical trauma. At that time, we noted a substantial difference in the red blood cell-to-white blood cell ratio between the pericardial effusion (1,957.4) and the peripheral blood (728.3). In addition to presenting the patient's case, we speculate that a possible mechanism for acute tamponade--alcohol-induced changes in microvascular permeability--is a reasonable explanation for cases of alcohol septal ablation that are complicated by otherwise-unexplainable massive pericardial effusions.

  11. Plastic Bronchitis.

    PubMed

    Rubin, Bruce K

    2016-09-01

    Plastic bronchitis is an uncommon and probably underrecognized disorder, diagnosed by the expectoration or bronchoscopic removal of firm, cohesive, branching casts. It should not be confused with purulent mucous plugging of the airway as seen in patients with cystic fibrosis or bronchiectasis. Few medications have been shown to be effective and some are now recognized as potentially harmful. Current research directions in plastic bronchitis research include understanding the genetics of lymphatic development and maldevelopment, determining how abnormal lymphatic malformations contribute to cast formation, and developing new treatments.

  12. Diabetes augments in vivo microvascular blood flow dynamics after stroke.

    PubMed

    Tennant, Kelly A; Brown, Craig E

    2013-12-04

    Stroke usually affects people with underlying medical conditions. In particular, diabetics are significantly more likely to have a stroke and the prognosis for recovery is poor. Because diabetes is associated with degenerative changes in the vasculature of many organs, we sought to determine how hyperglycemia affects blood flow dynamics after an ischemic stroke. Longitudinal in vivo two-photon imaging was used to track microvessels before and after photothrombotic stroke in a diabetic mouse model. Chronic hyperglycemia exacerbated acute (3-7 d) ischemia-induced increases in blood flow velocity, vessel lumen diameter, and red blood cell flux in peri-infarct regions. These changes in blood flow dynamics were most evident in superficial blood vessels within 500 μm from the infarct, rather than deeper or more distant cortical regions. Long-term imaging of diabetic mice not subjected to stroke indicated that these acute stroke-related changes in vascular function could not be attributed to complications from hyperglycemia alone. Treating diabetic mice with insulin immediately after stroke resulted in less severe alterations in blood flow within the first 7 d of recovery, but had more variable results at later time points. Analysis of microvessel branching patterns revealed that stroke led to a pruning of microvessels in peri-infarct cortex, with very few instances of sprouting. These results indicate that chronic hyperglycemia significantly affects the vascular response to ischemic stroke and that insulin only partially mitigates these changes. The combination of these acute and chronic alterations in blood flow dynamics could underlie diabetes-related deficits in cortical plasticity and stroke recovery.

  13. Plastics Technician.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document contains 16 units to consider for use in a tech prep competency profile for the occupation of plastics technician. All the units listed will not necessarily apply to every situation or tech prep consortium, nor will all the competencies within each unit be appropriate. Several units appear within each specific occupation and would…

  14. Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke

    PubMed Central

    Yu, Qi-jin; Tao, Hong; Wang, Xin; Li, Ming-chang

    2015-01-01

    Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions. PMID:26807131

  15. Thermal provocation to evaluate microvascular reactivity in human skin

    PubMed Central

    2010-01-01

    With increased interest in predictive medicine, development of a relatively noninvasive technique that can improve prediction of major clinical outcomes has gained considerable attention. Current tests that are the target of critical evaluation, such as flow-mediated vasodilation of the brachial artery and pulse-wave velocity, are specific to the larger conduit vessels. However, evidence is mounting that functional changes in the microcirculation may be an early sign of globalized microvascular dysfunction. Thus development of a test of microvascular reactivity that could be used to evaluate cardiovascular risk or response to treatment is an exciting area of innovation. This mini-review is focused on tests of microvascular reactivity to thermal stimuli in the cutaneous circulation. The skin may prove to be an ideal site for evaluation of microvascular dysfunction due to its ease of access and growing evidence that changes in skin vascular reactivity may precede overt clinical signs of disease. Evaluation of the skin blood flow response to locally applied heat has already demonstrated prognostic utility, and the response to local cooling holds promise in patients in whom cutaneous disorders are present. Whether either of these tests can be used to predict cardiovascular morbidity or mortality in a clinical setting requires further evaluation. PMID:20507974

  16. Thermal provocation to evaluate microvascular reactivity in human skin.

    PubMed

    Minson, Christopher T

    2010-10-01

    With increased interest in predictive medicine, development of a relatively noninvasive technique that can improve prediction of major clinical outcomes has gained considerable attention. Current tests that are the target of critical evaluation, such as flow-mediated vasodilation of the brachial artery and pulse-wave velocity, are specific to the larger conduit vessels. However, evidence is mounting that functional changes in the microcirculation may be an early sign of globalized microvascular dysfunction. Thus development of a test of microvascular reactivity that could be used to evaluate cardiovascular risk or response to treatment is an exciting area of innovation. This mini-review is focused on tests of microvascular reactivity to thermal stimuli in the cutaneous circulation. The skin may prove to be an ideal site for evaluation of microvascular dysfunction due to its ease of access and growing evidence that changes in skin vascular reactivity may precede overt clinical signs of disease. Evaluation of the skin blood flow response to locally applied heat has already demonstrated prognostic utility, and the response to local cooling holds promise in patients in whom cutaneous disorders are present. Whether either of these tests can be used to predict cardiovascular morbidity or mortality in a clinical setting requires further evaluation.

  17. Methods to investigate coronary microvascular function in clinical practice.

    PubMed

    Lanza, Gaetano A; Camici, Paolo G; Galiuto, Leonarda; Niccoli, Giampaolo; Pizzi, Carmine; Di Monaco, Antonio; Sestito, Alfonso; Novo, Salvatore; Piscione, Federico; Tritto, Isabella; Ambrosio, Giuseppe; Bugiardini, Raffaele; Crea, Filippo; Marzilli, Mario

    2013-01-01

    A growing amount of data is increasingly showing the relevance of coronary microvascular dysfunction (CMVD) in several clinical contexts. This article reviews techniques and clinical investigations of the main noninvasive and invasive methods proposed to study coronary microcirculation and to identify CMVD in the presence of normal coronary arteries, also trying to provide indications for their application in clinical practice.

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

    PubMed

    Allen, John; Howell, Kevin

    2014-07-01

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

  19. Xenobiotic Particle Exposure and Microvascular Endpoints: A Call to Arms

    PubMed Central

    Stapleton, Phoebe A.; Minarchick, Valerie C.; McCawley, Michael; Knuckles, Travis L.; Nurkiewicz, Timothy R.

    2011-01-01

    Xenobiotic particles can be considered in two genres: air pollution particulate matter and engineered nanoparticles. Particle exposures can occur in the greater environment, the workplace, and our homes. The majority of research in this field has, justifiably, focused on pulmonary reactions and outcomes. More recent investigations indicate that cardiovascular effects are capable of correlating with established mortality and morbidity epidemiological data following particle exposures. While the preliminary and general cardiovascular toxicology has been defined, the mechanisms behind these effects, specifically within the microcirculation, are largely unexplored. Therefore, the purpose of this review is several fold: first, a historical background on toxicological aspects of particle research is presented. Second, essential definitions, terminology, and techniques that may be unfamiliar to the microvascular scientist will be discussed. Third, the most current concepts and hypotheses driving cardiovascular research in this field will be reviewed. Lastly, potential future directions for the microvascular scientist will be suggested. Collectively speaking, microvascular research in the particle exposure field represents far more than a “niche”. The immediate demand for basic, translational, and clinical studies is high and diverse. Microvascular scientists at all career stages are strongly encouraged to expand their research interests to include investigations associated with particle exposures. PMID:21951337

  20. Real-time 3D Fourier-domain optical coherence tomography guided microvascular anastomosis

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Ibrahim, Zuhaib; Lee, W. P. A.; Brandacher, Gerald; Kang, Jin U.

    2013-03-01

    Vascular and microvascular anastomosis is considered to be the foundation of plastic and reconstructive surgery, hand surgery, transplant surgery, vascular surgery and cardiac surgery. In the last two decades innovative techniques, such as vascular coupling devices, thermo-reversible poloxamers and suture-less cuff have been introduced. Intra-operative surgical guidance using a surgical imaging modality that provides in-depth view and 3D imaging can improve outcome following both conventional and innovative anastomosis techniques. Optical coherence tomography (OCT) is a noninvasive high-resolution (micron level), high-speed, 3D imaging modality that has been adopted widely in biomedical and clinical applications. In this work we performed a proof-of-concept evaluation study of OCT as an assisted intraoperative and post-operative imaging modality for microvascular anastomosis of rodent femoral vessels. The OCT imaging modality provided lateral resolution of 12 μm and 3.0 μm axial resolution in air and 0.27 volume/s imaging speed, which could provide the surgeon with clearly visualized vessel lumen wall and suture needle position relative to the vessel during intraoperative imaging. Graphics processing unit (GPU) accelerated phase-resolved Doppler OCT (PRDOCT) imaging of the surgical site was performed as a post-operative evaluation of the anastomosed vessels and to visualize the blood flow and thrombus formation. This information could help surgeons improve surgical precision in this highly challenging anastomosis of rodent vessels with diameter less than 0.5 mm. Our imaging modality could not only detect accidental suture through the back wall of lumen but also promptly diagnose and predict thrombosis immediately after reperfusion. Hence, real-time OCT can assist in decision-making process intra-operatively and avoid post-operative complications.

  1. Pericyte abundance affects sucrose permeability in cultures of rat brain microvascular endothelial cells.

    PubMed

    Parkinson, Fiona E; Hacking, Cindy

    2005-07-05

    The blood-brain barrier is a physical and metabolic barrier that restricts diffusion of blood-borne substances into brain. In vitro models of the blood-brain barrier are used to characterize this structure, examine mechanisms of damage and repair and measure permeability of test substances. The core component of in vitro models of the blood-brain barrier is brain microvascular endothelial cells. We cultured rat brain microvascular endothelial cells (RBMEC) from isolated rat cortex microvessels. After 2-14 days in vitro (DIV), immunohistochemistry of these cells showed strong labeling for zona occludens 1 (ZO-1), a tight junction protein expressed in endothelial cells. Pericytes were also present in these cultures, as determined by expression of alpha-actin. The present study was performed to test different cell isolation methods and to compare the resulting cell cultures for abundance of pericytes and for blood-brain barrier function, as assessed by 14C-sucrose flux. Two purification strategies were used. First, microvessels were preabsorbed onto uncoated plastic for 4 h, then unattached microvessels were transferred to coated culture ware. Second, microvessels were incubated with an antibody to platelet-endothelial cell adhesion molecule 1 (PECAM-1; CD31) precoupled to magnetic beads, and a magnetic separation procedure was performed. Our results indicate that immunopurification, but not preadsorption, was an effective method to purify microvessels and reduce pericyte abundance in the resulting cultures. This purification significantly reduced 14C-sucrose fluxes across cell monolayers. These data indicate that pericytes can interfere with the development of blood-brain barrier properties in in vitro models that utilize primary cultures of RBMECs.

  2. GLASS FIBER REINFORCED PLASTICS,

    DTIC Science & Technology

    Contents: Fibrous glass fillers Binders used in the glass plastic industry Method of manufacturing glass plastics and glass plastic articles Properties of fiberglass Primary areas for use of glass fibre reinforced plastics

  3. Plastic bronchitis

    PubMed Central

    Singhi, Anil Kumar; Vinoth, Bharathi; Kuruvilla, Sarah; Sivakumar, Kothandam

    2015-01-01

    Plastic bronchitis, a rare but serious clinical condition, commonly seen after Fontan surgeries in children, may be a manifestation of suboptimal adaptation to the cavopulmonary circulation with unfavorable hemodynamics. They are ominous with poor prognosis. Sometimes, infection or airway reactivity may provoke cast bronchitis as a two-step insult on a vulnerable vascular bed. In such instances, aggressive management leads to longer survival. This report of cast bronchitis discusses its current understanding. PMID:26556975

  4. Coronary Microvascular Dysfunction and Microvascular Angina: A Systematic Review of Therapies

    PubMed Central

    Marinescu, Mark A; Löffler, Adrián I.; Ouellette, Michelle; Smith, Lavone; Kramer, Christopher M.; Bourque, Jamieson

    2015-01-01

    Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10–30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50–65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve (CFR) or myocardial perfusion reserve (MPR) <2.5 by positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 articles met strict inclusion criteria. The articles were heterogeneous, using different treatments, end-points, and definitions of CMD. Small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating, sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation (TENS) application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded literature. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD. PMID:25677893

  5. The effect of acute swim stress and training in the water maze on hippocampal synaptic activity as well as plasticity in the dentate gyrus of freely moving rats: revisiting swim-induced LTP reinforcement.

    PubMed

    Tabassum, Heena; Frey, Julietta U

    2013-12-01

    Hippocampal long-term potentiation (LTP) is a cellular model of learning and memory. An early form of LTP (E-LTP) can be reinforced into its late form (L-LTP) by various behavioral interactions within a specific time window ("behavioral LTP-reinforcement"). Depending on the type and procedure used, various studies have shown that stress differentially affects synaptic plasticity. Under low stress, such as novelty detection or mild foot shocks, E-LTP can be transformed into L-LTP in the rat dentate gyrus (DG). A reinforcing effect of a 2-min swim, however, has only been shown in (Korz and Frey (2003) J Neurosci 23:7281-7287; Korz and Frey (2005) J Neurosci 25:7393-7400; Ahmed et al. (2006) J Neurosci 26:3951-3958; Sajikumar et al., (2007) J Physiol 584.2:389-400) so far. We have reinvestigated these studies using the same as well as an improved recording technique which allowed the recording of field excitatory postsynaptic potentials (fEPSP) and the population spike amplitude (PSA) at their places of generation in freely moving rats. We show that acute swim stress led to a long-term depression (LTD) in baseline values of PSA and partially fEPSP. In contrast to earlier studies a LTP-reinforcement by swimming could never be reproduced. Our results indicate that 2-min swim stress influenced synaptic potentials as well as E-LTP negatively.

  6. TREATMENT OF MICROVASCULAR MICRO-EMBOLIZATION USING MICROBUBBLES AND LONG-TONE-BURST ULTRASOUND: AN IN VIVO STUDY

    PubMed Central

    Pacella, John J.; Brands, Judith; Schnatz, Frederick G.; Black, John J.; Chen, Xucai; Villanueva, Flordeliza S.

    2015-01-01

    Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 5 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction

  7. Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies.

    PubMed

    Gupta, Anjali; Broin, Pilib Ó; Bao, Yi; Pullman, James; Kamal, Layla; Ajaimy, Maria; Lubetzky, Michelle; Colovai, Adriana; Schwartz, Daniel; de Boccardo, Graciela; Golden, Aaron; Akalin, Enver

    2016-01-01

    The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1-3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell-associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA-selective gene transcripts may be used as molecular markers for AMR, especially in C4d- biopsies.

  8. Temporal course of microvascular obstruction after myocardial infarction assessed by MRI

    PubMed Central

    Abanador-Kamper, Nadine; Karamani, Vasiliki; Kamper, Lars; Brinkmann, Hilmar; Haage, Patrick; Seyfarth, Melchior

    2016-01-01

    PURPOSE We aimed to analyze the extent of microvascular obstruction (MO) after the index event compared with the follow-up at a median of three months. METHODS We identified 31 patients with MO after primary percutaneous coronary intervention of acute myocardial infarction by cardiac magnetic resonance imaging. The initial examination was performed after the index event, and 27 patients had the follow-up exam after a median of three months (interquartile range, 2–4 months). In addition, we examined 10 patients without MO after transmural myocardial infarction, as a control group. RESULTS MO disappeared in 23 of 27 patients (85%) in the follow-up and transformed into transmural late gadolinium enhancement. In patients with persistent MO, mean MO size decreased from 2.25% to 1.25%. In patients with MO, mean infarct size decreased significantly from 20.8% to 14.7% (P < 0.001). In the control group, mean infarct size decreased from 12.7% to 10.5% in the follow-up scan (P = 0.137). CONCLUSION MO is significantly reduced during the follow-up after acute myocardial infarction. PMID:26714055

  9. Photoacoustic microscopy of microvascular responses to cortical electrical stimulation

    NASA Astrophysics Data System (ADS)

    Tsytsarev, Vassiliy; Hu, Song; Yao, Junjie; Maslov, Konstantin; Barbour, Dennis L.; Wang, Lihong V.

    2011-07-01

    Advances in the functional imaging of cortical hemodynamics have greatly facilitated the understanding of neurovascular coupling. In this study, label-free optical-resolution photoacoustic microscopy (OR-PAM) was used to monitor microvascular responses to direct electrical stimulations of the mouse somatosensory cortex through a cranial opening. The responses appeared in two forms: vasoconstriction and vasodilatation. The transition between these two forms of response was observed in single vessels by varying the stimulation intensity. Marked correlation was found between the current-dependent responses of two daughter vessels bifurcating from the same parent vessel. Statistical analysis of twenty-seven vessels from three different animals further characterized the spatial-temporal features and the current dependence of the microvascular response. Our results demonstrate that OR-PAM is a valuable tool to study neurovascular coupling at the microscopic level.

  10. Treatment of Angina Pectoris Associated with Coronary Microvascular Dysfunction.

    PubMed

    Ong, Peter; Athanasiadis, Anastasios; Sechtem, Udo

    2016-08-01

    Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (i.e. absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors and thus receive statins and ACE-inhibitors in most cases. Antianginal medication consists of ß-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individually titrated combinations of these drugs up to 30 % of patients have refractory angina. Rho-kinase inhibitors and endothelin-receptor antagonists represent potential drugs that may prove useful in these patients in the future.

  11. Cerebral microvascular architecture in the common tree shrew (Tupaia glis) revealed by plastic corrosion casts.

    PubMed

    Poonkhum, R; Pongmayteegul, S; Meeratana, W; Pradidarcheep, W; Thongpila, S; Mingsakul, T; Somana, R

    2000-09-01

    The vascularization of the cerebrum (cerebral cortex and basal ganglia) in the common tree shrew (Tupaia glis) has been studied in detail using vinyl injection and vascular corrosion cast/SEM techniques. It is found that the arterial supply of the cerebral cortex are from cortical branches of the middle cerebral artery (MCA) and of the anterior cerebral artery (ACA). These arteries are in turn branches of the internal carotid artery (ICA). In addition, the cerebral cortex receives the blood from the cortical branches of the posterior cerebral artery (PCA) that originates from the basilar artery (BA). These cortical arteries gives rise to rectilinear orientated intracortical arteries that are divided into dense capillary networks to supply the cerebral cortex. The capillary networks drain the blood into intracortical veins and then into the tributaries of major superficial cerebral veins. The basal ganglia (caudate and lentiform nuclei) are supplied by central or perforating branches of the ACA and MCA. These central or medullary arteries give rise to arterioles that ramify into dense capillary plexuses. The venous blood from both nuclei drains into venules and finally into the tributaries of internal cerebral veins. It is obvious that on the ventral aspect, the diameter of the lateral striate artery (LSA) and of the penetrating arterioles from the MCA are much smaller than that of the MCA. These arterioles have few side branches while the peripheral branches of the superficial cerebral arteries exhibit several series of branches that are gradually reduced in diameter before branching into intracortical arteries. This could be one of the reasons why the rupture of cerebral arteries in man mostly occurs in the those originating from the ventral surface rather than from the dorsolateral surface.

  12. A microvascular system for chemical reactions using surface waste heat.

    PubMed

    Nguyen, Du Thai; Esser-Kahn, Aaron P

    2013-12-16

    Coffee-powered chemistry: Low-grade waste heat on surfaces can be used to drive chemical reactions, including the regeneration of a CO2 capture solution. Flowing two-phase heat transfer has been implemented within microvascular systems. This stripping system can be adapted to pre-fabricated surfaces, as demonstrated by a coffee mug containing a 1.2 m long microchannel. MEA=monoethanolamine.

  13. Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization

    PubMed Central

    Johnson, Carmen Gacchina; Sharma, Karun V.; Levy, Elliot B.; Woods, David L.; Morris, Aaron H.; Bacher, John D.; Lewis, Andrew L.; Wood, Bradford J.; Dreher, Matthew R.

    2015-01-01

    Purpose To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Materials and Methods Rabbit Vx2 liver tumors were embolized with 100–300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3–5 per group; 18 total). Results Mean microvascular density was 70 vessels/mm2 ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31+ structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Conclusions Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy. PMID:26321051

  14. Patterns and Variations in Microvascular Decompression for Trigeminal Neuralgia

    PubMed Central

    TODA, Hiroki; GOTO, Masanori; IWASAKI, Koichi

    2015-01-01

    Microvascular decompression (MVD) is a highly effective surgical treatment for trigeminal neuralgia (TN). Although there is little prospective clinical evidence, accumulated observational studies have demonstrated the benefits of MVD for refractory TN. In the current surgical practice of MVD for TN, there have been recognized patterns and variations in surgical anatomy and various decompression techniques. Here we provide a stepwise description of surgical procedures and relevant anatomical characteristics, as well as procedural options. PMID:25925756

  15. Hemimasticatory spasm treated with microvascular decompression of the trigeminal nerve.

    PubMed

    Chon, Kyu-Hyon; Lee, Jong-Myong; Koh, Eun-Jeong; Choi, Ha-Young

    2012-09-01

    Hemimasticatory spasm is a very rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contraction of the jaw-closing muscles. The mechanisms leading to hemimasticatory spasm are still unclear. Recently, injection of botulinum toxin has become the treatment of choice due to its excellent results. We report a case of a successful treatment of hemimasticatory spasm via microvascular decompression of the motor branch of the trigeminal nerve.

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

    PubMed

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

    2011-06-01

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

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

    PubMed Central

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

    2016-01-01

    Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics. PMID:27313624

  18. Pulmonary microvascular cytology in the diagnosis of lymphangitic carcinomatosis.

    PubMed

    Masson, R G; Krikorian, J; Lukl, P; Evans, G L; McGrath, J

    1989-07-13

    The diagnosis of lymphangitic spread of carcinoma in the lungs is sometimes difficult. We studied the cytologic characteristics of blood drawn through a wedged pulmonary-artery catheter from eight patients in whom lymphangitic carcinomatosis was confirmed by subsequent autopsy, lung biopsy, or clinical evaluation. The sites of the primary tumors were the prostate, breast, esophagus, and lung. Malignant cells were found in seven of the eight patients. Cytologic findings were normal in 16 of 17 patients with cancer but without pulmonary metastases and in 22 of 23 patients with nonmalignant pulmonary disorders. In a patient with cancer with tumor embolism to the lungs, the findings were positive, probably because of extensive intravascular tumor in large hepatic veins. One false positive finding occurred in a patient with extensive pulmonary infarction. Megakaryocytes, which are present in large numbers in the pulmonary capillary bed, are the hallmark of a satisfactory pulmonary vascular blood sample for pulmonary microvascular cytologic study. Familiarity with the cytologic characteristics of these cells in Papanicolaou preparations is essential to avoid mistakenly identifying them as malignant. Although transbronchial lung biopsy remains the diagnostic procedure of choice in this disorder, our findings suggest that the presence of malignant cells in pulmonary microvascular-cytology preparations in patients with cancer and unexplained dyspnea constitutes presumptive evidence of lymphangitic carcinomatosis. Pulmonary microvascular cytology may be particularly valuable when lung biopsy is refused or is thought to be too hazardous.

  19. Delayed, bilateral, non-microvascular ear replantation after violent amputation.

    PubMed

    García-Murray, E; Adán-Rivas, O; Salcido-Calzadilla, H

    2009-06-01

    Amputation of any body part is undoubtedly a traumatic experience leaving a terrible deformity, especially when the part or parts involved are visible and constitute an essential component of someone's facial whole. Bilateral ear amputation and successful subsequent replantation has been reported historically, but not in the modern surgical literature. We report the case of a 27-year-old female who was abducted and suffered a bilateral ear amputation at the hands of one of her captors to speed delivery of ransom money; the severed parts were sent to the parents approximately 2 hours after the amputation had taken place, and the girl was released some 48 hours after the ears were delivered. Microvascular replantation was attempted immediately after admission to the hospital some 2 hours after her release, but failed, and so a non-microvascular replantation was performed and was successful, after approximately 54 hours of ischaemia time. We consider this the first report of a complete bilateral, delayed, non-microvascular, successful ear replantation in a human being in the modern literature.

  20. Early Experiences with Microvascular Free Tissue Transfer in Lagos, Nigeria

    PubMed Central

    Mofikoya, Bolaji O; Ugburo, Andrew O

    2014-01-01

    Objectives: Microvascular free tissue transfer within our subregion is fraught with considerable challenges. We aim to highlight our experiences gained with our first fifteen cases of microvascular free tissue transfer at the Lagos University Teaching Hospital. We believe our report will be useful to colleagues embarking on such reconstructions in similar settings. Materials and Methods: The clinical records of the first 15 cases of free flaps done at our center were reviewed. The indications for surgery, choice of flap, recipient vessels, duration of surgery and complications were noted. Results: Fifteen cases were done, 10 flaps survived, ten defects occurred following trauma while remaining five followed cancer resections. Anterolateral thigh and radial forearm flaps were the most common flap used. The mean duration of surgeries was 7.1 hours SD ± 1.10 hours. Our take back rate was 13.3%, with a salvage rate of 50%. Three flaps failed on account venous congestion while remaining two failed due to arterial occlusion. Conclusion: 66.67% free flap success rate recorded reflect our early experiences in our institution. We believe meticulous planning, careful vessel selection, close flap monitoring as well as improved infrastructural support can lead to much better success rates in microvascular reconstruction in our country. PMID:24665201

  1. [Microvascular anastomoses in reconstructive head and neck surgery].

    PubMed

    Remmert, S

    1995-04-01

    At the ENT Department of the University of Lübeck, 57 microvascular tissue transplants with 129 anastomoses (61 arterial and 68 venous) have been performed in the last three years. Arteries have always been anastomosed end to end. The venous anastomoses have primarily been performed as end-to-side unions with the jugular vein. In nine patients, great distances between the donor and recipient vessel had to be connected with venous interponates. In two cases in which veins were lacking in the neck after radical neck dissection or radiation fibrosis, we used the cephalic vein or veins of the capsule of the thyroid gland as recipient vessels. The jejunal or osteomyocutaneous transplants were first fitted into the defect before performing the anastomosis. The jejunal peristalsis and the required freedom of movement in shaping the bone necessitated this technique. Microvascular anastomosis was first performed on the transplant of the radialis flap and the neurovascular infrahyoid muscular flap, and then they were integrated into the defect. We lost two transplants postoperatively because of venous thrombosis. In this article wie describe our anastomosis technique, the frequency distribution of recipient vessels, and the rules and characteristics of microvascular anastomosis after radiation and neck dissection.

  2. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain

    PubMed Central

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

    2015-01-01

    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 α2-adrenergic (α2A) 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 anti-allodynic effects in rats with chronic post-ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5–10 fold leftward when combined with non-analgesic doses of α2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic 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 h 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 α2A 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. Perspective This article presents the synergistic anti-allodynic effects of combinations of α2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas

  3. Structural plasticity and reorganisation in chronic pain.

    PubMed

    Kuner, Rohini; Flor, Herta

    2016-12-15

    Chronic pain is not simply a temporal continuum of acute pain. Studies on functional plasticity in neural circuits of pain have provided mechanistic insights and linked various modulatory factors to a change in perception and behaviour. However, plasticity also occurs in the context of structural remodelling and reorganisation of synapses, cells and circuits, potentially contributing to the long-term nature of chronic pain. This Review discusses maladaptive structural plasticity in neural circuits of pain, spanning multiple anatomical and spatial scales in animal models and human patients, and addresses key questions on structure-function relationships.

  4. [Erythropoietin in plastic surgery].

    PubMed

    Günter, C I; Rezaeian, F; Harder, Y; Lohmeyer, J A; Egert, S; Bader, A; Schilling, A F; Machens, H-G

    2013-04-01

    EPO is an autologous hormone, which is known to regulate erythropoiesis. For 30 years it has been used for the therapy of diverse forms of anaemia, such as renal anaemia, tumour-related anaemias, etc. Meanwhile, a multitude of scientific publications were able to demonstrate its pro-regenerative effects after trauma. These include short-term effects such as the inhibition of the "primary injury response" or apoptosis, and mid- and long-term effects for example the stimulation of stem cell recruitment, growth factor production, angiogenesis and re-epithelialisation. Known adverse reactions are increases of thromboembolic events and blood pressure, as well as a higher mortality in patients with tumour anaemias treated with EPO. Scientific investigations of EPO in the field of plastic surgery included: free and local flaps, nerve regeneration, wound healing enhancement after dermal thermal injuries and in chronic wounds.Acute evidence for the clinical use of EPO in the field of plastic surgery is still not satisfactory, due to the insufficient number of Good Clinical Practice (GCP)-conform clinical trials. Thus, the initiation of more scientifically sound trials is indicated.

  5. Methodological issues in the assessment of skin microvascular endothelial function in humans.

    PubMed

    Cracowski, Jean-Luc; Minson, Christopher T; Salvat-Melis, Muriel; Halliwill, John R

    2006-09-01

    The study of microvascular function can be performed in humans using laser Doppler flowmetry of the skin. This technology lends itself to a wide range of applications for studying the endothelial function of skin blood vessels. We review the advantages and limitations of postocclusive hyperemia, local thermal hyperemia, acetylcholine iontophoresis, flowmotion and association with microdialysis as tools with which to investigate skin microvascular endothelial function in humans. Postocclusive hyperemia, thermal hyperemia and acetylcholine iontophoresis provide integrated indexes of microvascular function rather than specific endothelial markers. However, they are valuable tools and can be used as surrogate endpoints in clinical trials in which the assessment of microvascular function in humans is required.

  6. Microvascular reconstruction of complex foot defects, a new anatomo-functional classification.

    PubMed

    Santanelli di Pompeo, Fabio; Pugliese, Pierfrancesco; Sorotos, Michail; Rubino, Corrado; Paolini, Guido

    2015-08-01

    Up until recently severe foot defects have been underestimated and amputation considered the treatment of choice. Inadequate treatment of foot defects is generally responsible for impaired deambulation resulting in physical and psychological handicap to the patient and producing a negative impact on social life. Foot reconstruction represents a recent advancement but is still a great challenge to the plastic surgeon; indeed the absence of a comprehensive anatomical classification of foot defects makes sharing clinical experiences difficult, slowing down the progress in this field. We report a single surgeon experience on a consecutive series of 47 complex foot reconstructions performed on 45 patients with microvascular free flaps over a 27-year period. A retrospective review of the cases was performed, a detailed analysis of the defects is presented and possible solutions debated so as to outline the key points in the diagnosis and treatment of foot defects. In the decision making process, soft tissue defect location, dimension, and functional relevance have proven to be as important as the exact definition of the bone defect. A new anatomical classification scheme for composite defects of the foot, involving both bone and soft tissue, is proposed in order to allow for a correct evaluation of the wound and an easier identification of the ideal treatment.

  7. Expression and significance of fgl2 prothrombinase in cardiac microvascular endothelial cells of rats with type 2 diabetes.

    PubMed

    Ding, Yanping; Liu, Kun; Wang, Yan; Su, Guanhua; Deng, Heping; Zeng, Qiutang; Liao, Yuhua; Wang, Zhaohui

    2010-10-01

    Microthrombosis may be involved in the pathogenesis of cardiac microangiopathy due to diabetes. Recent studies have shown that fibrinogen-like protein 2 (fgl2) plays a pivotal role in microthrombosis in viral hepatitis, acute vascular xenograft rejection and cytokine-induced fetal loss syndrome. The current study was designed to examine the expression of fgl2 in microvascular endothelial cells and investigate the effects of microthrombi due to fgl2 on cardiac function and structure in rats with type 2 diabetes. Following induction of type 2 diabetes, 24 rats were observed dynamically. Fgl2 expression and related cardiac microthrombosis were examined. Local or circulating TNF-α was measured. Coronary flow (CF) per min was calculated as an index of cardiac microcirculation. Cardiac function and morphology were evaluated. It was found that Fgl2 was highly expressed in cardiac microvascular endothelial cells of rats with type 2 diabetes, which was promoted by local or circulating TNF-α. The Fgl2 expression was associated with cardiac hyaline microthrombosis. In parallel with the fgl2 expression, CF per min, cardiac diastolic or systolic function and cardiac morphology were aggravated to some extent. It was concluded that in rats with type 2 diabetes, microthrombosis due to fgl2 contributes to the impairment of cardiac diastolic or systolic function and morphological changes.

  8. Effects of exercise training and detraining on cutaneous microvascular function in man: the regulatory role of endothelium-dependent dilation in skin vasculature.

    PubMed

    Wang, Jong-Shyan

    2005-01-01

    This study investigated how exercise training and detraining affect the cutaneous microvascular function and the regulatory role of endothelium-dependent dilation in skin vasculature. Ten healthy sedentary subjects cycled on an ergometer at 50% of maximal oxygen uptake (VO(2max)) for 30 min daily, 5 days a week, for 8 weeks, and then detrained for 8 weeks. Plasma nitric oxide (NO) metabolites (nitrite plus nitrate) were measured by a microplate fluorometer. The cutaneous microvascular perfusion responses to six graded levels of iontophoretically applied 1% acetylcholine (ACh) and 1% sodium nitroprusside (SNP) in the forearm skin were determined by laser Doppler. After training, (1) resting heart rate and blood pressure were reduced, whereas VO(2max), skin blood flow and cutaneous vascular conductance to acute exercise were enhanced; (2) plasma NO metabolite levels and ACh-induced cutaneous perfusion were increased; (3) skin vascular responses to SNP did not change significantly. However, detraining reversed these effects on cutaneous microvascular function and plasma NO metabolite levels. The results suggest that endothelium-dependent dilation in skin vasculature is enhanced by moderate exercise training and reversed to the pretraining state with detraining.

  9. ["Plastic lung". Broncho-pulmonary pathology related to plastics (author's transl)].

    PubMed

    Anthoine, D; Martinet, Y; Zuck, P; Peiffer, G; Dangelzer, J; Lamy, P

    1980-01-01

    Plastics can induce three main groups of respiratory accidents.--Acute and subacute intoxications related to the inhalation of volatil substances from decomposing plastics (mostly during burning and pyrolysis) or on the contrary during synthesis. They are accidental chemical broncho-pneumopathies (acute tracheo-bronchitis and pulmonary edema).--Chronic broncho-pneumopathies following repeated inhalation of dusts or suspension of plastics: pneumoconioses and thesaurismoses leading to pulmonary fibrosis.--Broncho-pneumopathies related to the irritant and sensitizing action of some components of plastics: professional asthma and sensitization pneumopathies. Diagnosis of such diseases therefore imposes a careful study of working conditions. Proof rests on two arguments:--curing by risk eviction;--analysis of the products in order to reveal their toxicity.

  10. Microvascular transplantation of epiphyseal plates: studies utilizing allograft donor material.

    PubMed

    Boyer, Martin I; Bowen, C Vaughan A

    2007-01-01

    Compromised function of an epiphyseal plate caused by trauma, tumor, infection, or congenital malformation can result in significant musculoskeletal deformity. Techniques used to correct or minimize the extent of these deformities include autogenous or allogeneic cancellous bone grafts, nonvascularized cortical allografts, vascularized bone and composite tissue transfers, and distraction osteogenesis. These solutions are not ideal for children because they do not adequately address the actively growing nature of the extremity. Microvascular techniques have enabled the experimental transplantation of vascularized epiphyseal plates with high levels of postoperative viability and subsequent growth and offer a potential advantage over conventional treatments.

  11. Autonomic neurosurgery: from microvascular decompression to image guided stimulation

    PubMed Central

    Pereira, EAC; Green, AL

    2007-01-01

    The paper reviews mechanisms underlying autonomic disorders, with a focus on cardiovascular dysfunction. Neurosurgical approaches are described for medically refractory hypertension and orthostatic hypotension. After review of microvascular decompression of the rostral ventrolateral medulla, stereotactic CT and MRI guided deep brain stimulation of the periaqueductal grey matter (PAG) is evaluated. Results are presented from patient studies showing reductions in blood pressure with ventral PAG stimulation and increases in blood pressure with dorsal PAG stimulation. A rationale for the treatment of autonomic disorders by neurosurgical intervention is discussed. PMID:21614256

  12. Quantifying Therapeutic and Diagnostic Efficacy in 2D Microvascular Images

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; Vickerman, Mary B.; Keith, Patricia A.

    2009-01-01

    VESGEN is a newly automated, user-interactive program that maps and quantifies the effects of vascular therapeutics and regulators on microvascular form and function. VESGEN analyzes two-dimensional, black and white vascular images by measuring important vessel morphology parameters. This software guides the user through each required step of the analysis process via a concise graphical user interface (GUI). Primary applications of the VESGEN code are 2D vascular images acquired as clinical diagnostic images of the human retina and as experimental studies of the effects of vascular regulators and therapeutics on vessel remodeling.

  13. Antiproliferative effect of elevated glucose in human microvascular endothelial cells

    NASA Technical Reports Server (NTRS)

    Kamal, K.; Du, W.; Mills, I.; Sumpio, B. E.

    1998-01-01

    Diabetic microangiopathy has been implicated as a fundamental feature of the pathological complications of diabetes including retinopathy, neuropathy, and diabetic foot ulceration. However, previous studies devoted to examining the deleterious effects of elevated glucose on the endothelium have been performed largely in primary cultured cells of macrovessel origin. Difficulty in the harvesting and maintenance of microvascular endothelial cells in culture have hindered the study of this relevant population. Therefore, the objective of this study was to characterize the effect of elevated glucose on the proliferation and involved signaling pathways of an immortalized human dermal microvascular endothelial cell line (HMEC-1) that possess similar characteristics to their in vivo counterparts. Human dermal microvascular endothelial cells (HMEC-1) were grown in the presence of normal (5 mM) or high D-glucose (20 mM) for 14 days. The proliferative response of HMEC-1 was compared under these conditions as well as the cAMP and PKC pathways by in vitro assays. Elevated glucose significantly inhibited (P < 0.05) HMEC-1 proliferation after 7, 10, and 14 days. This effect was not mimicked by 20 mM mannitol. The antiproliferative effect was more pronounced with longer exposure (1-14 days) to elevated glucose and was irreversible 4 days after a 10-day exposure. The antiproliferative effect was partially reversed in the presence of a PKA inhibitor, Rp-cAMP (10-50 microM), and/or a PKC inhibitor, Calphostin C (10 nM). HMEC-1 exposed to elevated glucose (20 mM) for 14 days caused an increase in cyclic AMP accumulation, PKA, and PKC activity but was not associated with the activation of downstream events such as CRE and AP-1 binding activity. These data support the hypothesis that HMEC-1 is a suitable model to study the deleterious effects of elevated glucose on microvascular endothelial cells. Continued studies with HMEC-1 may prove advantageous in delineation of the molecular

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

    PubMed

    Bonsen, Thomas; Wijnstok, Nienke J; Hoekstra, Trynke; Eringa, Etto C; Serné, Erik H; Smulders, Yvo M; Twisk, Jos W R

    2015-04-01

    Sleep and sleep disorders are related to cardiovascular disease, and microvascular function is an early cardiovascular disease marker. Therefore, the relationship of sleep (measured in sleep quality and duration) with microvascular function was examined in healthy adults. Sleep quality was assessed with the validated Sleep Wake Experience List (SWEL) questionnaire. Duration of sleep was self-reported in an additional question. Microvascular function was measured using nailfold capillaroscopy. Linear regression analyses were used to examine the relationship between sleep and microvascular function. Potential confounders included physical activity, smoking, blood pressure, body mass index and several biochemical parameters. Analyses were performed in 259 participants (116 men). For women reporting insufficient (<7 h) sleep duration, microvascular function (post-ischaemic capillary recruitment) was significantly lower (b = -11.17; P = 0.04) compared to women reporting sufficient sleep duration. There was no relationship between sleep quality and microvascular function in females. In males, a trend towards lower capillary recruitment was found in those reporting a combination of poor sleep quality and insufficient duration (b = -7.54; P = 0.09), compared to those reporting good sleep quality as well as sufficient duration. This study suggests an association between sleep and microvascular function. Which aspects of sleep exactly affect microvascular function, and if indeed the association is different between males and females in other samples, needs further research.

  15. The role of intrinsic apoptotic signaling in hemorrhagic shock-induced microvascular endothelial cell barrier dysfunction.

    PubMed

    Sawant, Devendra A; Tharakan, Binu; Hunter, Felicia A; Childs, Ed W

    2014-11-01

    Hemorrhagic shock leads to endothelial cell barrier dysfunction resulting in microvascular hyperpermeability. Hemorrhagic shock-induced microvascular hyperpermeability is associated with worse clinical outcomes in patients with traumatic injuries. The results from our laboratory have illustrated a possible pathophysiological mechanism showing involvement of mitochondria-mediated "intrinsic" apoptotic signaling in regulating hemorrhagic shock-induced microvascular hyperpermeability. Hemorrhagic shock results in overexpression of Bcl-2 family of pro-apoptotic protein, BAK, in the microvascular endothelial cells. The increase in BAK initiates "intrinsic" apoptotic signaling cascade with the release of mitochondrial cytochrome c in the cytoplasm and activation of downstream effector caspase-3, leading to loss of endothelial cell barrier integrity. Thus, this review article offers a brief overview of important findings from our past and present research work along with new leads for future research. The summary of our research work will provide information leading to different avenues in developing novel strategies against microvascular hyperpermeability following hemorrhagic shock.

  16. Microvascular Obstruction Evaluation Using Cardiovascular Magnetic Resonance (CMR) in ST-Elevated Myocardial Infarction (STEMI) Patients

    PubMed Central

    Piotrowska-Kownacka, Dorota; Kownacki, Łukasz; Kochman, Janusz; Kołodzińska, Agnieszka; Kobylecka, Małgorzata; Królicki, Leszek

    2015-01-01

    Summary Backround Restoration of blood flow in epicardial coronary artery in patients with acute myocardial infarction can, but does not have to restore efficient blood flow in coronary circulation. The aim of the study was a direct comparison of microvascular obstruction (MVO) detected by rest and stress perfusion imaging and gadolinium enhancement obtained 2 min. (early MVO) and 15 min. (delayed MVO) post contrast. Material/Methods 106 patients with first anterior myocardial infarction were studied. Cardiovascular magnetic resonance (CMR) was performed 5±2 days after primary percutaneous coronary intervention (pPCI). Stress and rest perfusion imaging was performed as well as early and delayed gadolinium enhancement and systolic function assessment. Scoring of segmental function, perfusion defect, MVO and scar transmurality was performed in 16 segment left ventricular model. Results The prevalence of MVO varies significantly between imaging techniques ranging from 48.8% for delayed MVO to 94% with stress perfusion. Median sum of scores was significantly different for each technique: stress perfusion 13 (7; 18), rest perfusion 3 (0.5; 6), early MVO 3 (0; 8), delayed MVO 0 (0; 4); p<0.05. Infarct size, stress and rest perfusion defects were independent predictors of LV EF at discharge from hospital. Conclusions Imaging protocol has a significant impact on MVO results. The study is the first to describe a stress-induced MVO in STEMI patients. Further research is needed to evaluate its impact on a long term prognosis. PMID:26740825

  17. Providing plastic zone extrusion

    DOEpatents

    Manchiraju, Venkata Kiran; Feng, Zhili; David, Stan A.; Yu, Zhenzhen

    2017-04-11

    Plastic zone extrusion may be provided. First, a compressor may generate frictional heat in stock to place the stock in a plastic zone of the stock. Then, a conveyer may receive the stock in its plastic zone from the compressor and transport the stock in its plastic zone from the compressor. Next, a die may receive the stock in its plastic zone from the conveyer and extrude the stock to form a wire.

  18. Injection of WGA-Alexa 488 into the ipsilateral hemidiaphragm of acutely and chronically C2 hemisected rats reveals activity-dependent synaptic plasticity in the respiratory motor pathways.

    PubMed

    Buttry, Janelle L; Goshgarian, Harry G

    2014-11-01

    WGA-Alexa 488 is a fluorescent neuronal tracer that demonstrates transsynaptic transport in the central nervous system. The transsynaptic transport occurs over physiologically active synaptic connections rather than less active or silent connections. Immediately following C2 spinal cord hemisection (C2Hx), when WGA-Alexa 488 is injected into the ipsilateral hemidiaphragm, the tracer diffuses across the midline of the diaphragm and retrogradely labels the phrenic nuclei (PN) bilaterally in the spinal cord. Subsequently, the tracer is transsynaptically transported bilaterally to the rostral Ventral Respiratory Groups (rVRGs) in the medulla over physiologically active connections. No other neurons are labeled in the acute C2Hx model at the level of the phrenic nuclei or in the medulla. However, with a recovery period of at least 7weeks (chronic C2Hx), the pattern of WGA-Alexa 488 labeling is notably changed. In addition to the bilateral PN and rVRG labeling, the chronic C2Hx model reveals fluorescence in the ipsilateral ventral and dorsal spinocerebellar tracts, and the ipsilateral reticulospinal tract. Furthermore, interneurons are labeled bilaterally in laminae VII and VIII of the spinal cord as well as neurons in the motor nuclei bilaterally of the intercostal and forelimb muscles. Moreover, in the chronic C2Hx model, there is bilateral labeling of additional medullary centers including raphe, hypoglossal, spinal trigeminal, parvicellular reticular, gigantocellular reticular, and intermediate reticular nuclei. The selective WGA-Alexa 488 labeling of additional locations in the chronic C2Hx model is presumably due to a hyperactive state of the synaptic pathways and nuclei previously shown to connect with the respiratory centers in a non-injured model. The present study suggests that hyperactivity not only occurs in neuronal centers and pathways caudal to spinal cord injury, but in supraspinal centers as well. The significance of such injury-induced plasticity is

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

    PubMed

    Penta, R; Ambrosi, D

    2015-01-07

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

  20. Bosentan fosters microvascular de-remodelling in systemic sclerosis.

    PubMed

    Guiducci, S; Bellando Randone, S; Bruni, C; Carnesecchi, G; Maresta, A; Iannone, F; Lapadula, G; Matucci Cerinic, M

    2012-12-01

    Bosentan, a dual endothelin receptor antagonist, may reduce blood pressure by blocking the vasoconstrictor effect of endothelin-1. In systemic sclerosis (SSc) nailfold videocapillaroscopy (NVC); allows diagnostic and follow-up of microvascular damage. Distinct NVC patterns have been identified for the evaluation of severity of SSc microvascular damage. The objective of this study is to evaluate the modification of the microvasculature under Bosentan therapy in SSc patients with pulmonary arterial hypertension (PAH). Nine patients with PAH related to SSc in New York Heart Association classes III-IV were treated with Bosentan 125 mg twice a day. NVC optical probe videocapillaroscopy equipped with 100× and 200× contact lenses and connected to image analyse software was performed before and after 12 months of Bosentan therapy to evaluate the modification of microvasculature. Nine PAH SSc patients treated with Iloprost were used as controls. Before Bosentan therapy, seven patients showed at NVC severe loss of capillaries with large avascular areas and vascular architectural disorganisation which are typically "late" SSc pattern. After 12 months of Bosentan, NVC pattern changed in seven patients from "late" into "active" SSc pattern. The disappearance of avascular areas and capillary haemorrhages was the most striking result. Two patients had an "active" SSc pattern, not modified by Bosentan treatment. These data show that Bosentan may improve NVC pattern in SSC and the presence of new capillaries suggests that it may favour angiogenesis. Bosentan may improve and stabilise the microvasculature in long-term treatment modulating the structural modifications detected by NVC.

  1. Microvascular flow estimation by microbubble-assisted Nakagami imaging.

    PubMed

    Tsui, Po-Hsiang; Yeh, Chih-Kuang; Chang, Chien-Cheng

    2009-04-01

    The destruction and replenishment of microbubbles has been previously applied to estimating blood flow in the microcirculation. The rate of increase of the time-intensity curve (TIC) due to microbubbles flowing into the region-of-interest (ROI) as measured from the conventional B-mode images reflects the flow velocity. In this study, we monitored microbubble replenishment using a new proposed approach called the time-Nakagami-parameter curve (TNC) obtained from the parametric image based on the Nakagami statistical parameter for quantifying the microvascular flow velocity. The Nakagami parameter is estimated from signal envelope to reflect the backscattered statistics. The feasibility of using the TNC to estimate the microvascular flow was explored by carrying out phantom measurements and in vivo animal experiments. The rates of increase of the TIC and TNC were quantified as the rate constants beta(I) and beta(N) of monoexponential fitted curves, respectively. The experimental results showed that beta(N) behaves similarly to the conventional beta(I) in quantifying the flow velocity. Moreover, the tolerance to the effects of clutter is greater for the TNC than for the TIC, which makes it possible to use beta(N) to differentiate various flow velocities even when the ROI contains nonperfused areas. This finding suggests that the TNC-based technique can be used as a complementary tool for the conventional TIC to improve measurement of blood flow in the microcirculation.

  2. Assessment of Conjunctival Microvascular Hemodynamics in Stages of Diabetic Microvasculopathy

    PubMed Central

    Khansari, Maziyar M.; Wanek, Justin; Tan, Michael; Joslin, Charlotte E.; Kresovich, Jacob K.; Camardo, Nicole; Blair, Norman P.; Shahidi, Mahnaz

    2017-01-01

    Diabetes impairs the microcirculation and function of various vital tissues throughout the body. The conjunctival microcirculation can be non-invasively imaged and thus enables assessment of microvascular hemodynamics. In this study, alterations in conjunctival microvascular hemodynamics were quantitatively assessed at stages of increasing diabetic microvasculopathy based on diabetic retinopathy (DR). Subjects were categorized into non-diabetic control (C, N = 34), no clinically visible DR (NDR, N = 47), non-proliferative DR (NPDR, N = 45), and proliferative DR (PDR, N = 35). Conjunctival hemodynamic descriptors, namely vessel diameter (D), blood velocity (V), blood flow (Q), wall shear rate (WSR), and wall shear stress (WSS) were measured in arterioles and venules, and compared between DR and C subjects using generalized linear mixed models. In arterioles, V, WSR, and WSS were lower in NDR (P ≤ 0.01). V was lower in NDR than NPDR and PDR subjects (P ≤ 0.02). In venules, D was higher in NDR and NPDR (P ≤ 0.03), while V was lower in PDR (P = 0.04). Venular V and Q were higher in NPDR than PDR subjects (P ≤ 0.04). WSR and WSS were lower in all stages of DR (P ≤ 0.05), suggestive of the potential of WSS as a marker of diabetic microvasculopathy. Quantitative assessment of conjunctival hemodynamics can potentially be useful for evaluation of diabetic microvasculopathy. PMID:28387229

  3. Effects of hyperoxia on microvascular cells in vitro

    SciTech Connect

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

    1987-02-01

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

  4. Informational dynamics of vasomotion in microvascular networks: a review.

    PubMed

    Pradhan, R K; Chakravarthy, V S

    2011-02-01

    Vasomotion refers to spontaneous oscillation of small vessels observed in many microvascular beds. It is an intrinsic phenomenon unrelated to cardiac rhythm or neural and hormonal regulation. Vasomotion is found to be particularly prominent under conditions of metabolic stress. In spite of a significant existent literature on vasomotion, its physiological and pathophysiological roles are not clear. It is thought that modulation of vasomotion by vasoactive substances released by metabolizing tissue plays a role in ensuring optimal delivery of nutrients to the tissue. Vasomotion rhythms exhibit a great variety of temporal patterns from regular oscillations to chaos. The nature of vasomotion rhythm is believed to be significant to its function, with chaotic vasomotion offering several physiological advantages over regular, periodic vasomotion. In this article, we emphasize that vasomotion is best understood as a network phenomenon. When there is a local metabolic demand in tissue, an ideal vascular response should extend beyond local microvasculature, with coordinated changes over multiple vascular segments. Mechanisms of information transfer over a vessel network have been discussed in the literature. The microvascular system may be regarded as a network of dynamic elements, interacting, either over the vascular anatomical network via gap junctions, or physiologically by exchange of vasoactive substances. Drawing analogies with spatiotemporal patterns in neuronal networks of central nervous system, we ask if properties like synchronization/desynchronization of vasomotors have special significance to microcirculation. Thus the contemporary literature throws up a novel view of microcirculation as a network that exhibits complex, spatiotemporal and informational dynamics.

  5. Monitoring microvascular free flaps with tissue oxygen measurement and PET.

    PubMed

    Schrey, Aleksi R; Kinnunen, Ilpo A J; Grénman, Reidar A; Minn, Heikki R I; Aitasalo, Kalle M J

    2008-07-01

    Tissue oxygen measurement and positron emission tomography (PET) were evaluated as methods for predicting ischemia in microvascular free flaps of the head and neck. Ten patients with head and neck squamous cell cancer underwent resection of the tumour followed by microvascular reconstruction with a free flap. Tissue oxygenation of the flap (P(ti)O(2)) was continuously monitored for three postoperative (POP) days and the blood flow of the flap was assessed using oxygen-15 labelled water and PET. In three free flaps a perfusion problem was suspected due to a remarkable drop in P(ti)O(2)-values, due to two anastomosis problems and due to POP turgor. No flap losses occurred. During the blood flow measurements with PET [mean 8.5 mL 100 g(-1) min(-1 )(SD 2.5)], the mean P(ti)O(2) of the flaps [46.8 mmHg (SD 17.0)] appeared to correlate with each other in each patient (p<0.05, n=10). Tissue oxygenation measurement is a feasible monitoring system of free flaps. The perfusion-study with PET correlates with P(ti)O(2)-measurement.

  6. [The problem of information value in microvascular networks].

    PubMed

    Krupatkin, A I

    2011-01-01

    The methodology of quantitative estimation of information value in microvascular networks is proposed for the first time with the use of wavelet analysis of skin blood flow oscillations registrated by laser Doppler flowmetry at 30 healthy persons and 56 patients after hand injuries and diseases. It includes calculation of relative indices for the information preservation, the predomination of preserved information and the efficacy of information. The most deviation from multistable information regimen happened after formation of resonance oscillations: the general quantity of information decreased but the preservation of predominated information increased. The preservation of trophic myogenic information predominated after reduction of sympathetic influences. With the increase in the number of information channels the quantity of information increased but its preservation varied. Sensory peptidergic nerve fibres were activated during local heating to 34 degrees C at dorsal forearm skin. This information was the most effective at the beginning of heating during the growth of blood flow to the plateau level. Blood flow oscillations represented in wavelet spectrum serve as operators build on the basis of effective information. These oscillations play not only hemodynamic role but are the bearers of information in microvascular networks.

  7. Angina pectoris in women: focus on microvascular disease.

    PubMed

    Zuchi, Cinzia; Tritto, Isabella; Ambrosio, Giuseppe

    2013-02-20

    Ischemic heart disease (IHD) is the leading cause of death among women in Western countries, and it is associated with higher morbidity and mortality than in men. Nevertheless, IHD in women remains underdiagnosed and undertreated, and the misperception that females are "protected" against cardiovascular disease leads to underestimation of their cardiovascular risk; instead, women with chest pain have a high risk of cardiovascular events. Women suffering from angina pectoris tend to have different characteristics compared to men, with a high prevalence of non-significant coronary artery disease. Angina in women is more commonly microvascular in origin than in men, and therefore standard diagnostic algorithms may be suboptimal for women. This different pathophysiology impacts clinical management of IHD in women. While response to medical therapy may differ in women, they are scarcely represented in clinical trials. Therefore, solid data in terms of gender efficacy of antianginal drugs are lacking, and particularly when angina is microvascular in origin women often continue to be symptomatic despite maximal therapy with classical antianginal drugs. Recently, new molecules have shown promising results in women. In conclusion, women with angina are a group of patients in whom it seems appropriate to concentrate efforts aimed at reducing morbidity and improving quality of life.

  8. The expression of ADAMTS13 in human microvascular endothelial cells.

    PubMed

    Wang, Anyou; Duan, Qiaohong; Wu, Jingsheng; Liu, Xin; Sun, Zimin

    2016-06-01

    ADAMTS13, as a specific von Willebrand factor (VWF)-cleaving protease, prevents microvascular thrombosis of VWF/platelet thrombi. It has been reported that human vascular endothelial cells could also synthesize and secrete ADAMTS13, and these reports were focused in human umbilical vascular endothelial cells. Considering the particularity of its huge quantity and structure of human microvascular endothelial cells (HMECs) in the body, whether ADAMTS13 is expressed in HMECs also needs to be confirmed. To investigate whether ADAMTS13 is expressed in HMECs. Real-time PCR (RT-PCR) amplification detected ADAMTS13 mRNA in HMEC-1 cell line. The expression and distribution of ADAMTS13 protein and VWF were detected by fluorescence immunoassay and western blot. We observed the expression and distribution of ADAMTS13 in HMECs. We confirmed the expression of ADAMTS13 mRNA in HMEC-1, and found that there were some partly common distributions of ADAMTS13 protein and VWF. This study provides the evidence that HMECs also express ADAMTS13. HMECs might also be a primary source for human plasma ADAMTS13. The overlap region for the distribution of ADAMTS13 and VWF suggests that ADAMTS13 might have a potential regulation role for VWF inside cells.

  9. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    SciTech Connect

    Chen Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-03

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  10. Tissue viability imaging for assessment of microvascular events

    NASA Astrophysics Data System (ADS)

    O'Doherty, Jim; Nilsson, Gert E.; Henricson, Joakim; Sjoberg, Folke; Leahy, Martin J.

    2005-08-01

    A new technique for the investigation of microvascular tissue blood concentration is presented, based on the method of polarisation spectroscopy of blood in superficial skin tissue. Linearly polarised light incident on the skin is partly reflected by the surface layers, and partly backscattered from the dermal tissue. Use of orthogonal polarisation filters over both a light source and a CCD suppresses the reflections from the surface, and only the depolarised light backscattered from the dermal matrix reaches the CCD array. By separating the colour planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the amount of red blood cells (RBCs) in the underlying area of tissue can be discovered. The algorithm incorporates theory that utilises the differences in light absorption of RBCs and dermal tissue in the red and green wavelength regions. In vitro fluid models compare well to computer simulations in describing a linear relationship between output signal (called TiViindex) and RBC concentration in the physiological range of 0%-4%. In vivo evaluation of the technique via transepidermal application of acetylcholine by iontophoresis displayed a heterogeneity pattern of vasodilation, which is typical of the vasoactive agent. Extension of the technique to capture and process continuous real-time data creates a new possibility of online real-time image processing. Application of tissue viability (TiVi) imaging include skin care products and drug development, as well as investigations of microvascular angiogenesis.

  11. Hyperosmolarity attenuates TNFα–mediated pro-inflammatory activation of human pulmonary microvascular endothelial cells

    PubMed Central

    Banerjee, Anirban; Moore, Ernest E.; McLaughlin, Nathan J.; Lee, Luis; Jones, Wilbert L.; Johnson, Jeffrey L.; Nydam, Trevor L.; Silliman, Christopher C.

    2013-01-01

    Firm neutrophil (PMN)-endothelial (EC) adhesion is crucial to the PMN-mediated hyperinflammation observed in acute lung injury. Hypertonic saline (HTS) used for resuscitation of hemorrhagic shock has been associated with a decreased incidence of PMN-mediated lung injury/acute respiratory distress syndrome. We hypothesize that physiologically accessible hypertonic incubation (170mM vs. 140mM, osmolarity ranging from 360-300 mOsm/L) inhibits pro-inflammatory activation of human pulmonary microvascular endothelial cells (HMVECs). Pro-inflammatory activation of HMVECs was investigated in response to TNFα including IL-8 release, ICAM-1 surface expression, PMN adhesion, and signaling mechanisms under both isotonic (control) and hypertonic conditions. Hyperosmolarity alone had no effect on either basal IL-8 release or ICAM-1 surface expression, but did lead to concentration-dependent decreases in TNFα–induced IL-8 release, ICAM-1 surface expression, and PMN:HMVEC adhesion. Conversely, HTS activated p38 mitogen-activated protein kinase (MAPK) and enhanced TNFα activation of p38 MAPK. Despite this basal activation, hyperosmolar incubation attenuated TNFα stimulated IL-8 release and ICAM-1 surface expression and subsequent PMN adherence, while p38 MAPK inhibition did not further influence the effects of hyperosmolar conditions on ICAM-1 surface expression. In addition, TNFα induced NF-kB DNA binding, but HTS conditions attenuated this by 31% (p<0.01). In conclusion, HTS reduces PMN:HMVEC adhesion as well as TNFα-induced pro-inflammatory activation of primary HMVECs via attenuation of NF-kB signaling. PMID:23364439

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

    PubMed

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

    2016-03-01

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

  13. Retinal fractals and acute lacunar stroke.

    PubMed

    Cheung, Ning; Liew, Gerald; Lindley, Richard I; Liu, Erica Y; Wang, Jie Jin; Hand, Peter; Baker, Michelle; Mitchell, Paul; Wong, Tien Y

    2010-07-01

    This study aimed to determine whether retinal fractal dimension, a quantitative measure of microvascular branching complexity and density, is associated with lacunar stroke. A total of 392 patients presenting with acute ischemic stroke had retinal fractal dimension measured from digital photographs, and lacunar infarct ascertained from brain imaging. After adjusting for age, gender, and vascular risk factors, higher retinal fractal dimension (highest vs lowest quartile and per standard deviation increase) was independently and positively associated with lacunar stroke (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.49-12.17 and OR, 1.85; 95% CI, 1.20-2.84, respectively). Increased retinal microvascular complexity and density is associated with lacunar stroke.

  14. Directed assembly of three-dimensional microvascular networks

    NASA Astrophysics Data System (ADS)

    Therriault, Daniel

    Three-dimensional (3-D) microvascular networks with pervasive, interconnected channels less than 300 mum in diameter may find widespread application in microfluidic devices, biotechnology, sensors, and autonomic healing materials. Although microchannel arrays are readily constructed in two-dimensions by photolithographic or soft lithographic techniques, their construction in three-dimensions remains a challenging problem. The development of a microfabrication method to build 3-D microvascular networks based on direct-write assembly is described is this thesis. The method is based on the robotic deposition of a fugitive organic ink to form a free-standing scaffold structure. Secondary infiltration of a structural resin followed by setting of the matrix and removal of the scaffold yields an embedded pervasive network of smooth cylindrical channels (˜10--500 mum) with defined connectivity. Rheological and other material properties studies of fugitive organic ink were performed in order to identify the critical characteristics required for successful deposition of 3-D scaffolds by direct-write assembly. Guided by the results of these studies, several new ink formulations were screened for improved deposition performance. The most successful of these inks (40wt% microcrystalline wax, 60wt% petroleum jelly) showed excellent deposition and had an equilibrium modulus at room temperature (G 'eq ˜ 7.70 kPa 1 Hz) nearly two orders of magnitude higher than the original ink. The optimized ink was used to successfully build thick (i.e., ˜100 layers) scaffold structures at room temperature with negligible time-dependent deformation post-deposition. Secondary infiltration of the resin was accomplished at room temperature while maintaining the scaffold architecture. The optimized ink was also successfully extruded through small micronozzles (1 mum). The construction of 3-D microvascular networks enables microfluidic devices with unparallel geometric complexity. In one example, a

  15. [Changes in the microvascular pattern of the periodontal ligament in an experimental tooth extrusion].

    PubMed

    Kobayashi, K

    1989-08-01

    Forty eight adult cats were employed to investigate the serial changes of vascular patterns of the periodontal ligament on tooth extrusion. The right upper canines have been successively extruded (initial load 40 gr) with a open coil spring. The experimental periods were set on 1, 2, 3, 4 and 6 weeks respectively. On each experimental period, the microvascular casts of the periodontal ligament and alveolar bone around the experimental tooth were prepared for the scanning electron microscopy, utilizing the acrylic plastic injection method (Taniguchi and Ohta, et al. 1952 and 1955). And the serial sections of the surrounding tissues of the experimental tooth were made. In order to elucidate the mode of the tooth movement, the load of applied force and the distance of extrusion were measured. Results obtained were as follows: 1. The experimental tooth was extruded rapidly during first two weeks. The speed reduced gradually afterwards. 2. The new vascularization was seen around the apex first, then widely spread in the periodontal ligament. And the remarkable trabecula-shaped bone formation were observed around the venous networks of the root apex after two week period. 3. The tissue reactions after the tooth extrusion delayed in comparison with the movement of the tooth. 4. Although the tissue reactions of the root apex of the extruded tooth were originally similar to the one in the transverse tooth movement, slight differences were found in timing of the tissue change and shape of the capillary network. The findings of the tissue change showed that the light force was indicated in extrusion of the tooth. And the range of action of the force applied should be limited in orthodontic clinic.

  16. Surgical variation of microvascular decompression for trigeminal neuralgia: A technical note and anatomical study

    PubMed Central

    da Silva, Otávio T.; de Almeida, César C.; Iglesio, Ricardo F.; de Navarro, Jessie M.; Teixeira, Manoel J.; Duarte, Kleber P.

    2016-01-01

    Background: In this article, the authors described their experience in microvascular decompression for trigeminal neuralgia. Methods: The microvascular decompression technique used in the authors’ institution is described in a step by step manner with some illustrative cases as well as a cadaver dissection to highlight the differences with other previously described techniques. Results: Since 2013, 107 patients were operated in the Neurosurgery Division of the University of São Paulo using the described technique, with a shorter operative time and avoiding cerebellar retractor compared with classic techniques. Conclusion: Our modified microvascular decompression technique for trigeminal neuralgia can be used with safety and efficiency for treating trigeminal neuralgia. PMID:27625893

  17. Diabetic microvascular complications: possible targets for improved macrovascular outcomes

    PubMed Central

    D’Elia, John A; Bayliss, George; Roshan, Bijan; Maski, Manish; Gleason, Ray E; Weinrauch, Larry A

    2011-01-01

    The results of recent outcome trials challenge hypotheses that tight control of both glycohemoglobin and blood pressure diminishes macrovascular events and survival among type 2 diabetic patients. Relevant questions exist regarding the adequacy of glycohemoglobin alone as a measure of diabetes control. Are we ignoring mechanisms of vasculotoxicity (profibrosis, altered angiogenesis, hypertrophy, hyperplasia, and endothelial injury) inherent in current antihyperglycemic medications? Is the polypharmacy for lowering cholesterol, triglyceride, glucose, and systolic blood pressure producing drug interactions that are too complex to be clinically identified? We review angiotensin–aldosterone mechanisms of tissue injury that magnify microvascular damage caused by hyperglycemia and hypertension. Many studies describe interruption of these mechanisms, without hemodynamic consequence, in the preservation of function in type 1 diabetes. Possible interactions between the renin–angiotensin–aldosterone system and physiologic glycemic control (through pulsatile insulin release) suggest opportunities for further clinical investigation. PMID:21694944

  18. Microvascular Function in Aging Among Women Living with HIV.

    PubMed

    Monsuez, Jean-Jacques; Belin, Catherine; Bouchaud, Olivier

    2016-12-01

    Combined antiretroviral therapy (CART) has turned HIV-infection to a treatable chronic disease during which many patients survive to middle and older age. However, they prematurely develop non-AIDS comorbidities such as cardiovascular disease, metabolic syndrome, diabetes, and HIV-associated neurocognitive disorders (HAND). Microcirculatory changes and endothelial dysfunction occur early both in HIV-infected and in aging patients, in whom they usually precede cardiovascular and neurocognitive impairments. Also, mild cognitive involvement has been reported in women during the menopausal transition. Disruption of the blood-brain barrier, as well as microvascular and cerebral blood flow changes, has been reported in HIV patients with HAND, including postmenopausal women. However, most studies addressing this issue included women aged less than 50 years. Whether HIV-infected women growing older with CART would be subsequently exposed to an increased progression of cognitive impairment overtime remains unknown.

  19. Inflammation in the pathogenesis of microvascular complications in diabetes

    PubMed Central

    Nguyen, Dung V.; Shaw, Lynn C.; Grant, Maria B.

    2012-01-01

    Diabetes and hyperglycemia create a proinflammatory microenvironment that progresses to microvascular complications such as nephropathy, retinopathy, and neuropathy. Diet-induced insulin resistance is a potential initiator of this change in type 2 diabetes which can increase adipokines and generate a chronic low-grade inflammatory state. Advanced glycation end-products and its receptor, glycation end-products AGE receptor axis, reactive oxygen species, and hypoxia can also interact to worsen complications. Numerous efforts have gained way to understanding the mechanisms of these modulators and attenuation of the inflammatory response, however, effective treatments have still not emerged. The complexity of inflammatory signaling may suggest a need for multi-targeted therapy. This review presents recent findings aimed at new treatment strategies. PMID:23267348

  20. Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?

    PubMed Central

    Gupta, Akanksha

    2015-01-01

    Abstract Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine. PMID:26669709

  1. Intra-operative neurophysiology during microvascular decompression for hemifacial spasm.

    PubMed

    Fernández-Conejero, I; Ulkatan, S; Sen, C; Deletis, V

    2012-01-01

    There is evidence that primary hemifacial spasm (HFS) in the majority of patients is related to a vascular compression of the facial nerve at its root exit zone (REZ). As a consequence, the hyperexcitability of facial nerve generates spasms of the facial muscles. Microvascular decompression (MVD) of the facial nerve near its REZ has been established as an effective treatment of HFS. Intra-operative disappearance of abnormal muscle responses (lateral spread) elicited by stimulating one of the facial nerve branches has been used as a method to predict MVD effectiveness. Other neurophysiologic techniques, such as facial F-wave, blink reflex and facial corticobulbar motor evoked potentials (FCoMEP), are feasible to intra-operatively study changes in excitability of the facial nerve and its nucleus during MVDs. Intra-operative neuromonitoring with the mentioned techniques allows a better understanding of HFS pathophysiology and helps to optimise the MVD.

  2. Plastic encapsulated parts

    SciTech Connect

    Castillo, T.

    1994-10-01

    Plastic semiconductor packages were characterized as possible alternatives for canned devices, which are susceptible to internal shorts caused by conductive particles. Highly accelerated stress testing (HAST) as well as electrical and mechanical testing were conducted on plastic technology devices.

  3. Plastic casting resin poisoning

    MedlinePlus

    Epoxy poisoning; Resin poisoning ... Epoxy and resin can be poisonous if they are swallowed or their fumes are breathed in. ... Plastic casting resins are found in various plastic casting resin products.

  4. Novel Genetic Loci Associated with Retinal Microvascular Diameter

    PubMed Central

    Jensen, Richard A.; Sim, Xueling; Smith, Albert Vernon; Li, Xiaohui; Jakobsdóttir, Jóhanna; Cheng, Ching-Yu; Brody, Jennifer A.; Cotch, Mary Frances; Mcknight, Barbara; Klein, Ronald; Wang, Jie Jin; Kifley, Annette; Harris, Tamara B.; Launer, Lenore J.; Taylor, Kent D.; Klein, Barbara E.K.; Raffel, Leslie J.; Li, Xiang; Ikram, M. Arfan; Klaver, Caroline C.; van der Lee, Sven J.; Mutlu, Unal; Hofman, Albert; Uitterlinden, Andre G.; Liu, Chunyu; Kraja, Aldi T.; Mitchell, Paul; Gudnason, Vilmundur; Rotter, Jerome I.; Boerwinkle, Eric; van Duijn, Cornelia M.; Psaty, Bruce M.; Wong, Tien Y.

    2015-01-01

    Background There is increasing evidence that retinal microvascular diameters are associated with cardio- and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size. Methods and Results This study extends previous genome-wide association study results using 24,000+ multi-ethnic participants from 7 discovery and 5,000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single nucleotide polymorphisms (SNPs) and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent (CRVE) and the central retinal arteriole equivalent (CRAE). We report 4 new loci associated with CRVE, one of which is also associated with CRAE. The 4 SNPs are rs7926971 in TEAD1 (p=3.1×10−11, minor allele frequency (MAF)=0.43), rs201259422 in TSPAN10 (p=4.4×10−9, MAF=0.27), rs5442 in GNB3 (p=7.0×10−10, MAF=0.05) and rs1800407 in OCA2 (p=3.4×10−8, MAF=0.05). The latter SNP, rs1800407, was also associated with CRAE (p=6.5×10−12). Results from the gene-based burden tests were null. In phenotype look-ups, SNP rs201255422 was associated with both systolic (p=0.001) and diastolic blood pressure (p=8.3×10−04). Conclusions Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease. PMID:26567291

  5. Peroxynitrite mediates testosterone-induced vasodilation of microvascular resistance vessels.

    PubMed

    Puttabyatappa, Yashoda; Stallone, John N; Ergul, Adviye; El-Remessy, Azza B; Kumar, Sanjiv; Black, Stephen; Johnson, Maribeth; Owen, Mary P; White, Richard E

    2013-04-01

    Our knowledge of how androgens influence the cardiovascular system is far from complete, and this lack of understanding is especially true of how androgens affect resistance vessels. Our aim was to identify the signaling mechanisms stimulated by testosterone (TES) in microvascular arteries and to understand how these mechanisms mediate TES-induced vasodilation. Mesenteric microvessels were isolated from male Sprague-Dawley rats. Tension studies demonstrated a rapid, concentration-dependent, vasodilatory response to TES that did not involve protein synthesis or aromatization to 17β-estradiol. Dichlorofluorescein fluorescence and nitrotyrosine immunoblot experiments indicated that TES stimulated peroxynitrite formation in microvessels, and functional studies demonstrated that TES-induced vasodilation was inhibited by scavenging peroxynitrite. As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production. Functional and biochemical studies indicated that TES signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the androgen receptor and culminated in enhanced production of cGMP and microvascular vasodilation. These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from xanthine oxidase-generated superoxide and NO. This response was associated with activation of the PI3 kinase-Akt signaling cascade initiated by activation of the androgen receptor. We propose this mechanism could account for TES-stimulated cGMP production in microvessels and, ultimately, vasodilation.

  6. Isolation of primary murine brain microvascular endothelial cells.

    PubMed

    Ruck, Tobias; Bittner, Stefan; Epping, Lisa; Herrmann, Alexander M; Meuth, Sven G

    2014-11-14

    The blood-brain-barrier is ultrastructurally assembled by a monolayer of brain microvascular endothelial cells (BMEC) interconnected by a junctional complex of tight and adherens junctions. Together with other cell-types such as astrocytes or pericytes, they form the neurovascular unit (NVU), which specifically regulates the interchange of fluids, molecules and cells between the peripheral blood and the CNS. Through this complex and dynamic system BMECs are involved in various processes maintaining the homeostasis of the CNS. A dysfunction of the BBB is observed as an essential step in the pathogenesis of many severe CNS diseases. However, specific and targeted therapies are very limited, as the underlying mechanisms are still far from being understood. Animal and in vitro models have been extensively used to gain in-depth understanding of complex physiological and pathophysiological processes. By reduction and simplification it is possible to focus the investigation on the subject of interest and to exclude a variety of confounding factors. However, comparability and transferability are also reduced in model systems, which have to be taken into account for evaluation. The most common animal models are based on mice, among other reasons, mainly due to the constantly increasing possibilities of methodology. In vitro studies of isolated murine BMECs might enable an in-depth analysis of their properties and of the blood-brain-barrier under physiological and pathophysiological conditions. Further insights into the complex mechanisms at the BBB potentially provide the basis for new therapeutic strategies. This protocol describes a method to isolate primary murine microvascular endothelial cells by a sequence of physical and chemical purification steps. Special considerations for purity and cultivation of MBMECs as well as quality control, potential applications and limitations are discussed.

  7. Serum factors involved in human microvascular endothelial cell morphogenesis.

    PubMed

    Harvey, Kevin; Siddiqui, Rafat A; Sliva, Daniel; Garcia, Joe G N; English, Denis

    2002-09-01

    Our previous studies have demonstrated that lipid and protein angiogenic factors operate in tandem to induce optimal angiogenic responses in vivo. This study was undertaken to clarify the nature of the substances in human serum that are responsible for its remarkable ability to promote capillary morphogenesis in vitro. The ability of dilute (2%) human serum to promote the morphogenic differentiation of human dermal microvascular endothelial cells on Matrigel supports was depleted by more than 50% by treatment of the serum with activated charcoal, a procedure that effectively removes biologically active lipid growth factors. The remainder of the activity within serum was lost on heating to 60 degrees C for 60 minutes, indicating the involvement of a protein in the response. The ability of charcoal-treated serum to promote capillary morphogenesis was completely restored by the addition of sphingosine 1-phosphate (SPP, 500 nmol/L), but other lipids thought to be released into serum during clotting were ineffective. In addition, basic fibroblast growth factor (bFGF) effectively restored the ability of heat-treated serum to promote endothelial cell morphogenesis, but other protein growth factors, including vascular endothelial growth factor and platelet-derived growth factor, were ineffective. Together, SPP and bFGF were as effective as whole serum in promoting capillary morphogenesis. Responses to purified SPP were entirely sensitive to the effects of preexposure of the cells to pertussis toxin, whereas responses to bFGF were entirely pertussis toxin-resistant. Consistent with our hypothesis that two distinct factors in serum play a role in promoting capillary morphogenesis, responses induced by serum were inhibited approximately 50% by preexposure of endothelial cells to pertussis toxin. We conclude that platelet-released SPP acts in conjunction with circulating bFGF to promote capillary formation by microvascular endothelial cells. Lipid and protein growth factors

  8. Alteration of the sublingual microvascular glycocalyx in critically ill patients.

    PubMed

    Donati, Abele; Damiani, Elisa; Domizi, Roberta; Romano, Rocco; Adrario, Erica; Pelaia, Paolo; Ince, Can; Singer, Mervyn

    2013-11-01

    Glycocalyx degradation may contribute to microvascular dysfunction and tissue hypoperfusion during systemic inflammation and sepsis. In this observational study we evaluated the alteration of the sublingual microvascular glycocalyx in 16 healthy volunteers and 50 critically ill patients. Sidestream Dark Field images of the sublingual microcirculation were automatically analyzed by dedicated software. The Perfused Boundary Region (PBR) was calculated as the dimensions of the permeable part of the glycocalyx allowing the penetration of circulating red blood cells, providing an index of glycocalyx damage. The PBR was increased in ICU patients compared to healthy controls (2.7 [2.59-2.88] vs. 2.46 [2.37-2.59]μm, p<0.0001) and tended to be higher in the 32 septic patients compared to non-septics (2.77 [2.62-2.93] vs. 2.67 [2.55-2.75]μm, p=0.05), suggesting more severe glycocalyx alterations. A PBR of 2.76 showed the best discriminative ability towards the presence of sepsis (sensitivity: 50%, specificity: 83%; area under the receiver operating characteristic curve: 0.67, 95% CI 0.52-0.82, p=0.05). A weak positive correlation was found between PBR and heart rate (r=0.3, p=0.03). In 17 septic patients, a correlation was found between PBR and number of rolling leukocytes in post-capillary venules (RL/venule) (r=0.55, p=0.02), confirming that glycocalyx shedding enhances leukocyte-endothelium interaction.

  9. Comprehensive Analysis of Chicken Vessels as Microvascular Anastomosis Training Model

    PubMed Central

    Kang, Bo Young; Jeon, Byung-Joon; Lee, Kyeong-Tae

    2017-01-01

    Background Nonliving chickens are commonly used as a microvascular anastomosis training model. However, previous studies have investigated only a few types of vessel, and no study has compared the characteristics of the various vessels. The present study evaluated the anatomic characteristics of various chicken vessels as a training model. Methods Eight vessels—the brachial artery, basilic vein, radial artery, ulnar artery, ischiatic artery and vein, cranial tibial artery, and common dorsal metatarsal artery—were evaluated in 26 fresh chickens and 30 chicken feet for external diameter (ED) and thicknesses of the tunica adventitia and media. The dissection time from skin incision to application of vessel clamps was also measured. Results The EDs of the vessels varied. The ischiatic vein had the largest ED of 2.69±0.33 mm, followed by the basilic vein (1.88±0.36 mm), ischiatic artery (1.68±0.24 mm), common dorsal metatarsal artery (1.23±0.23 mm), cranial tibial artery (1.18±0.19 mm), brachial artery (1.08±0.15 mm), ulnar artery (0.82±0.13 mm), and radial artery (0.56±0.12 mm), and the order of size was consistent across all subjects. Thicknesses of the tunica adventitia and media were also diverse, ranging from 74.09±19.91 µm to 158.66±40.25 µm (adventitia) and from 31.2±7.13 µm to 154.15±46.48 µm (media), respectively. Mean dissection time was <3 minutes for all vessels. Conclusions Our results suggest that nonliving chickens can provide various vessels with different anatomic characteristics, which can allow trainees the choice of an appropriate microvascular anastomosis training model depending on their purpose and skillfulness. PMID:28194342

  10. Changes in retinal microvascular diameter in patients with diabetes

    PubMed Central

    da Silva, Andréa Vasconcellos Batista; Gouvea, Sonia Alves; da Silva, Aurélio Paulo Batista; Bortolon, Saulo; Rodrigues, Anabel Nunes; Abreu, Glaucia Rodrigues; Herkenhoff, Fernando Luiz

    2015-01-01

    Background and objectives Diabetic retinopathy is the main microvascular complication in diabetes mellitus and needs to be diagnosed early to prevent severe sight-threatening retinopathy. The purpose of this study was to quantify the retinal microvasculature pattern and analyze the influence of blood glucose level and the duration of diabetes mellitus on the retinal microvasculature. Methods Two groups were analyzed: patients with diabetes (N=26) and patients without diabetes, ie, controls (N=26). A quantitative semiautomated method analyzed retinal microvasculature. The diameters of arterioles and venules were measured. The total numbers of arterioles and venules were counted. The ratio of arteriole diameter to venule diameter was calculated. The retinal microvasculature pattern was related to clinical and biochemical parameters. Results Patients with diabetes exhibited larger venule diameters in the upper temporal quadrant of the retina compared to the lower temporal quadrant (124.85±38.03 µm vs 102.92±15.69 µm; P<0.01). Patients with diabetes for 5 or more years had larger venule diameters in the upper temporal quadrant than patients without diabetes (141.62±44.44 vs 112.58±32.11 µm; P<0.05). The degree of venodilation in the upper temporal quadrant was positively correlated with blood glucose level and the estimated duration of diabetes mellitus. Interpretation and conclusion The employed quantitative method demonstrated that patients with diabetes exhibited venule dilation in the upper temporal quadrant, and the duration of diabetes mellitus was positively correlated with blood glucose level. Therefore, the early assessment of retinal microvascular changes is possible prior to the onset of diabetic retinopathy. PMID:26345217

  11. Microvascular response to red blood cell transfusion in trauma patients.

    PubMed

    Weinberg, Jordan A; MacLennan, Paul A; Vandromme-Cusick, Marianne J; Angotti, Jonathan M; Magnotti, Louis J; Kerby, Jeffrey D; Rue, Loring W; Barnum, Scott R; Patel, Rakesh P

    2012-03-01

    Trauma patients are often transfused allogeneic red blood cells (RBCs) in an effort to augment tissue oxygen delivery. However, the effect of RBC transfusion on microvascular perfusion in this patient population is not well understood. To this end, we investigated the effect of RBC transfusion on sublingual microvascular perfusion in trauma patients. Sublingual microcirculation was imaged at bedside with a sidestream dark-field illumination microscope before and after transfusion of one RBC unit in hemodynamically stable, anemic trauma patients. The perfused proportion of capillaries (PPC) before and after transfusion was determined, and the percent change in capillary perfusion following transfusion (ΔPPC) calculated. Sublingual microcirculation was observed in 30 patients. Mean age was 47 (SD, 21) years, mean Injury Severity Score was 29 (SD, 16), and mean pretransfusion hemoglobin was 7.5 (SD, 0.9) g/dL. No patients had a mean arterial pressure of less than 65 mmHg (mean, 89 [SD, 17] mmHg) or lactate of greater than 2.5 mmol/L (mean, 1.1 [SD, 0.3] mmol/L). Following transfusion, ΔPPC ranged from +68% to -36% and was found to inversely correlate significantly with pretransfusion PPC (Spearman r = -0.63, P = 0.0002). Pretransfusion PPC may be selectively deranged in otherwise stable trauma patients. Patients with relatively altered baseline PPC tend to demonstrate improvement in perfusion following transfusion, whereas those with relatively normal perfusion at baseline tend to demonstrate either no change or, in fact, a decline in PPC. Bedside sublingual imaging may have the potential to detect subtle perfusion defects and ultimately inform clinical decision making with respect to transfusion.

  12. Microvascular Response to Red Blood Cell Transfusion in Trauma Patients

    PubMed Central

    Weinberg, Jordan A.; MacLennan, Paul A.; Vandromme–Cusick, Marianne J.; Angotti, Jonathan M.; Magnotti, Louis J.; Kerby, Jeffrey D.; Rue, Loring W.; Barnum, Scott R.; Patel, Rakesh P.

    2014-01-01

    Background Trauma patients are often transfused allogeneic red blood cells (RBCs) in an effort to augment tissue oxygen delivery. However, the effect of RBC transfusion on microvascular perfusion in this patient population is not well understood. To this end, we investigated the effect of RBC transfusion on sublingual microvascular perfusion in trauma patients. Methods Sublingual microcirculation was imaged at bedside with a sidestream dark field illumination microscope before and after transfusion of one RBC unit in hemodynamically stable, anemic trauma patients. The proportion of perfused capillaries (PPC) pre- and post-transfusion was determined, and the percent change in capillary perfusion following transfusion (ΔPPC) calculated. Results Sublingual microcirculation was observed in 30 patients. Mean age was 47 (SD=21), mean ISS was 29 (SD=16), and mean pre-transfusion hemoglobin was 7.5 g/dL (SD=0.9). No patients had MAP < 65 mm Hg (mean 89 mm Hg, SD 17) or lactate > 2.5 mmol/L (mean 1.1 mmol/L, SD 0.3). Following transfusion, ΔPPC ranged from +68% to -36% and was found to inversely correlate significantly with pre-transfusion PPC (Spearman r= -0.63, p=0.0002). Conclusions Pre-transfusion PPC may be selectively deranged in otherwise stable trauma patients. Patients with relatively altered baseline PPC tend to demonstrate improvement in perfusion following transfusion, while those with relatively normal perfusion at baseline tend to demonstrate either no change or, in fact, a decline in PPC. Bedside sublingual imaging may have the potential to detect subtle perfusion defects and ultimately inform clinical decision making with respect to transfusion. PMID:22344313

  13. Recovering automotive plastics

    SciTech Connect

    Not Available

    1993-10-01

    This article reports on the results of a study on increasing the recycling of plastics in automobiles. Plastics are being used in increasing amounts in vehicles and new methods of retrieving these plastics for recycling are needed to reduce the amount of automotive shredder residue that is currently being sent to residues. The study concentrated on increasing the ease of disassembly and contaminant removal.

  14. Plastics in Building.

    ERIC Educational Resources Information Center

    Skeist, Irving, Ed.

    The evaluation and use of plastics in the construction industry are explained. The contributors offer extensive, timely, and thoroughly researched data on the chemistry, properties, functions, engineering behavior, and specific applications of plastics to building requirements. The major subjects discussed in depth are--(1) the role of plastics in…

  15. Processing of plastics

    PubMed Central

    Spaak, Albert

    1975-01-01

    An overview is given of the processing of plastic materials from the handling of polymers in the pellet and powder form to manufacturing of a plastic fabricated product. Various types of equipment used and melt processing ranges of various polymer formulations to make the myriad of plastic products that are commercially available are discussed. PMID:1175556

  16. Tomorrow's Plastic World

    ERIC Educational Resources Information Center

    Macdonald, Averil

    2005-01-01

    Far from being just cheap packaging materials, plastics may be the materials of tomorrow. Plastic can conduct electricity, and this opens up a host of high-tech possibilities in the home and in energy generation. These possibilities are discussed here along with how plastic can be recycled and perhaps even grown.

  17. Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture

    PubMed Central

    Kuklin, Vladimir; Sovershaev, Mikhail; Andreasen, Thomas; Skogen, Vegard; Ytrehus, Kirsti; Bjertnaes, Lars

    2005-01-01

    Introduction We recently demonstrated that the non-selective endothelin-1 (ET-1) receptor blocker tezosentan antagonizes ovine acute lung injury (ALI) following infusion of endotoxin or ET-1 by reducing the enhanced lung microvascular pressure, although we could not exclude the possibility of a simultaneous decline in microvascular permeability. In the present study, our aim was to find out if tezosentan reverses the rise in microvascular filtration coefficient (Kfc) in rat lungs that have been isolated and perfused 12 h after cecum ligation and puncture (CLP) or infusion of ET-1. Methods Wistar rats (n = 42) were subjected to CLP. Postoperatively, rats were randomized to a CLP group (n = 7) and a CLP + tezosentan group (n = 7); the latter received tezosentan 30 mg/kg. A sham-operated group (n = 5) underwent laparotomy without CLP. Twelve hours postoperatively, the lungs were isolated and perfused with blood from similarly treated rats that also were used to assess plasma concentration of ET-1 and protein kinase Cα (PKCα) in lung tissue. Additionally, isolated blood perfused lungs from healthy rats were randomized to a control group (n = 8), an ET-1 group (n = 7) subjected to pulmonary arterial injection of ET-1 10 nM, and an ET-1 + tezosentan group (n = 7) that received tezosentan 30 mg/kg. All lung preparations received papaverine 0.1 μg/kg added to the perfusate for vasoplegia. Pulmonary hemodynamic variables, Kfc and lung compliance (CL) were assessed. Results After CLP, the plasma concentration of ET-1 increased. Papaverine abolished the vasoconstrictor response to ET-1 and the pulmonary vascular pressures remained close to baseline throughout the experiments. Both CLP and injection of ET-1 caused significant changes in Kfc and CL that were prevented in tezosentan-treated rats. Compared to sham-operated animals, CLP increased the content of PKCα by 50% and 70% in the cytosolic and the membrane fractions of lung tissue homogenates, respectively. Tezosentan

  18. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE

    EPA Science Inventory

    SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE.
    PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti. US EPA, ORD, NHEERL, ETD, PTB, Research Triangle Park, NC USA.
    Environmental particles (PM...

  19. The Impact of Multi-pollutant Clusters on the Association between Fine Particulate Air Pollution and Microvascular Function

    PubMed Central

    Ljungman, Petter L.; Wilker, Elissa H.; Rice, Mary B.; Austin, Elena; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Benjamin, Emelia J.; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.

    2016-01-01

    Background Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. Methods We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003-2008. Results In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction p value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% CI 4.6%; 33%) higher baseline pulse amplitude per 5 μg/m3 and days with high contributions of oil and wood combustion with 16% (95% CI 0.2%; 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. Conclusions PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil and wood combustion was associated with higher baseline pulse amplitude but not PAT ratio. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences. PMID:26562062

  20. Biodegradability of Plastics

    PubMed Central

    Tokiwa, Yutaka; Calabia, Buenaventurada P.; Ugwu, Charles U.; Aiba, Seiichi

    2009-01-01

    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed. PMID:19865515

  1. Biodegradability of plastics.

    PubMed

    Tokiwa, Yutaka; Calabia, Buenaventurada P; Ugwu, Charles U; Aiba, Seiichi

    2009-08-26

    Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

  2. Differential expression of PDGFRB and EGFR in microvascular proliferation in glioblastoma.

    PubMed

    Xu, Guiyan; Li, Jian Yi

    2016-08-01

    Glioblastoma (GBM) is the highly malignant glioma and exhibits microvascular proliferation. PCR mRNA arrays and immunohistochemical stains on tissue microarray demonstrated that the expression level of PDGFRB in GBM microvascular proliferation was significantly higher than that in GBM tumor cells while the expression level of EGFR was lower in microvascular proliferation than in GBM tumor cells. PDGFRB protein was selectively expressed in pericytes in GBM microvascular proliferation. By analyzing The Cancer Genome Atlas (TCGA) datasets for GBM, it was found that genomic DNA alterations were the main reason for the high expression of EGFR in GBM tumor cells. Our miRNA microarray data showed that microRNAs (miRNAs) (miR-193b-3p, miR-518b, miR-520f-3p, and miR-506-5p) targeting PDGFRB were downregulated in microvascular proliferation, which might be the most likely reason for the high expression of PDGFRB in GBM microvascular proliferation. The increase of several miRNAs (miR-133b, miR-30b-3p, miR-145-5p, and miR-146a-5p) targeting EGFR in GBM microvascular proliferation was one of the reasons for the lack of expression of EGFR in GBM microvascular proliferation. These findings implicated that miRNAs, such as miR-506, miR-133b, miR-145, and miR-146a, that target PDGFRB or EGFR, might be potential therapeutic agents for GBM. A new generation of targeted therapeutic agents against both EGFR and PDGFRB might be developed in the future.

  3. Added Qualifications in Microsurgery: Consideration for Subspecialty Certification in Microvascular Surgery in Europe.

    PubMed

    Heidekrueger, Paul I; Tanna, Neil; Weichman, Katie E; Szpalski, Caroline; Tos, Pierluigi; Ninkovic, Milomir; Broer, P Niclas

    2016-07-01

    Background While implementation of subspecializations may increase expertise in a certain area of treatment, there also exist downsides. Aim of this study was, across several disciplines, to find out if the technique of microsurgery warrants the introduction of a "Certificate of Added Qualifications (CAQ) in microsurgery." Methods An anonymous, web-based survey was administered to directors of microsurgical departments in Europe (n = 205). Respondents were asked, among other questions, whether they had completed a 12-month microvascular surgery fellowship and whether they believed a CAQ in microvascular surgery should be instituted. Results The response rate was 57%, and 33% of the respondents had completed a 12-month microvascular surgery fellowship.A total of 61% of all surgeons supported a CAQ in microsurgery. Answers ranged from 47% of support to 100% of support, depending on the countries surveyed. Discussion This is one of the few reports to evaluate the potential role of subspecialty certification of microvascular surgery across several European countries. The data demonstrate that the majority of directors of microsurgical departments support such a certificate. There was significantly greater support for a CAQ in microsurgery among those who have completed a formal microvascular surgery fellowship themselves. Conclusion This study supports the notion that further discussion and consideration of subspecialty certification in microvascular surgery appears necessary. There are multiple concerns surrounding this issue. Similar to the evolution of hand surgery certification, an exploratory committee of executive members of the respective medical boards and official societies may be warranted.

  4. DRAG REDUCING POLYMER ENCHANCES MICROVASCULAR PERFUSION IN THE TRAUMATIZED BRAIN WITH INTRACRANIAL HYPERTENSION

    PubMed Central

    Bragin, Denis E.; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V.; Nemoto, Edwin M.

    2016-01-01

    SUMMARY Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood soluble non-toxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and limb, but have not yet been studied in the brain. Recently, we demonstrated that that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using the in-vivo 2-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow and, as a result, reduced tissue hypoxia in both un-traumatized and traumatized rat brains at high ICP. Our study suggests that DRP could be an effective treatment for improving microvascular flow in brain ischemia caused by high ICP after TBI. PMID:27165871

  5. Deeper Penetration of Erythrocytes into the Endothelial Glycocalyx Is Associated with Impaired Microvascular Perfusion

    PubMed Central

    Lee, Dae Hyun; Dane, Martijn J. C.; van den Berg, Bernard M.; Boels, Margien G. S.; van Teeffelen, Jurgen W.; de Mutsert, Renée; den Heijer, Martin; Rosendaal, Frits R.; van der Vlag, Johan; van Zonneveld, Anton Jan; Vink, Hans; Rabelink, Ton J.

    2014-01-01

    Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43–2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: −0.034; 95% confidence interval: −0.037 to −0.031). We conclude that microvascular beds with a thick (“healthy”) glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin (“risk”) glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion. PMID:24816787

  6. Classification of microvascular patterns via cluster analysis reveals their prognostic significance in glioblastoma.

    PubMed

    Chen, Long; Lin, Zhi-Xiong; Lin, Guo-Shi; Zhou, Chang-Fu; Chen, Yu-Peng; Wang, Xing-Fu; Zheng, Zong-Qing

    2015-01-01

    There are limited researches focusing on microvascular patterns (MVPs) in human glioblastoma and their prognostic impact. We evaluated MVPs of 78 glioblastomas by CD34/periodic acid-Schiff dual staining and by cluster analysis of the percentage of microvascular area for distinct microvascular formations. The distribution of 5 types of basic microvascular formations, that is, microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), glomeruloid vascular proliferation (GVP), and vasculogenic mimicry (VM), was variable. Accordingly, cluster analysis classified MVPs into 2 types: type I MVP displayed prominent MSs and VCs, whereas type II MVP had numerous VGs, GVPs, and VMs. By analyzing the proportion of microvascular area for each type of formation, we determined that glioblastomas with few MSs and VCs had many GVPs and VMs, and vice versa. VG seemed to be a transitional type of formation. In case of type I MVP, expression of Ki-67 and p53 but not MGMT was significantly higher as compared with those of type II MVP (P < .05). Survival analysis showed that the type of MVPs presented as an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) (both P < .001). Type II MVP had a more negative influence on PFS and OS than did type I MVP. We conclude that the heterogeneous MVPs in glioblastoma can be categorized properly by certain histopathologic and statistical analyses and may influence clinical outcome.

  7. High-speed swept source optical coherence Doppler tomography for deep brain microvascular imaging

    PubMed Central

    Chen, Wei; You, Jiang; Gu, Xiaochun; Du, Congwu; Pan, Yingtian

    2016-01-01

    Noninvasive microvascular imaging using optical coherence Doppler tomography (ODT) has shown great promise in brain studies; however, high-speed microcirculatory imaging in deep brain remains an open quest. A high-speed 1.3 μm swept-source ODT (SS-ODT) system is reported which was based on a 200 kHz vertical-cavity-surface-emitting laser. Phase errors induced by sweep-trigger desynchronization were effectively reduced by spectral phase encoding and instantaneous correlation among the A-scans. Phantom studies have revealed a significant reduction in phase noise, thus an enhancement of minimally detectable flow down to 268.2 μm/s. Further in vivo validation was performed, in which 3D cerebral-blood-flow (CBF) networks in mouse brain over a large field-of-view (FOV: 8.5 × 5 × 3.2 mm3) was scanned through thinned skull. Results showed that fast flows up to 3 cm/s in pial vessels and minute flows down to 0.3 mm/s in arterioles or venules were readily detectable at depths down to 3.2 mm. Moreover, the dynamic changes of the CBF networks elicited by acute cocaine such as heterogeneous responses in various vessel compartments and at different cortical layers as well as transient ischemic events were tracked, suggesting the potential of SS-ODT for brain functional imaging that requires high flow sensitivity and dynamic range, fast frame rate and a large FOV to cover different brain regions. PMID:27934907

  8. High-speed swept source optical coherence Doppler tomography for deep brain microvascular imaging

    NASA Astrophysics Data System (ADS)

    Chen, Wei; You, Jiang; Gu, Xiaochun; Du, Congwu; Pan, Yingtian

    2016-12-01

    Noninvasive microvascular imaging using optical coherence Doppler tomography (ODT) has shown great promise in brain studies; however, high-speed microcirculatory imaging in deep brain remains an open quest. A high-speed 1.3 μm swept-source ODT (SS-ODT) system is reported which was based on a 200 kHz vertical-cavity-surface-emitting laser. Phase errors induced by sweep-trigger desynchronization were effectively reduced by spectral phase encoding and instantaneous correlation among the A-scans. Phantom studies have revealed a significant reduction in phase noise, thus an enhancement of minimally detectable flow down to 268.2 μm/s. Further in vivo validation was performed, in which 3D cerebral-blood-flow (CBF) networks in mouse brain over a large field-of-view (FOV: 8.5 × 5 × 3.2 mm3) was scanned through thinned skull. Results showed that fast flows up to 3 cm/s in pial vessels and minute flows down to 0.3 mm/s in arterioles or venules were readily detectable at depths down to 3.2 mm. Moreover, the dynamic changes of the CBF networks elicited by acute cocaine such as heterogeneous responses in various vessel compartments and at different cortical layers as well as transient ischemic events were tracked, suggesting the potential of SS-ODT for brain functional imaging that requires high flow sensitivity and dynamic range, fast frame rate and a large FOV to cover different brain regions.

  9. The human brain intracerebral microvascular system: development and structure

    PubMed Central

    Marín-Padilla, Miguel

    2012-01-01

    The capillary from the meningeal inner pial lamella play a crucial role in the development and structural organization of the cerebral cortex extrinsic and intrinsic microvascular compartments. Only pial capillaries are capable of perforating through the cortex external glial limiting membrane (EGLM) to enter into the nervous tissue, although incapable of perforating the membrane to exit the brain. Circulatory dynamics and functional demands determine which capillaries become arterial and which capillaries become venous. The perforation of the cortex EGLM by pial capillaries is a complex process characterized by three fundamental stages: (1) pial capillary contact with the EGLM with fusion of vascular and glial basal laminae at the contact site, (2) endothelial cell filopodium penetration through the fussed laminae with the formation of a funnel between them that accompanies it into the nervous tissue while remaining open to the meningeal interstitium and, (3) penetration of the whole capillary carrying the open funnel with it and establishing an extravascular Virchow-Robin Compartment (V-RC) that maintains the perforating vessel extrinsic (outside) the nervous tissue through its entire length. The V-RC is walled internally by the vascular basal lamina and externally by the basal lamina of joined glial cells endfeet. The VRC outer glial wall appear as an extension of the cortex superficial EGLM. All the perforating vessels within the V-RCs constitute the cerebral cortex extrinsic microvascular compartment. These perforating vessels are the only one capable of responding to inflammatory insults. The V-RC remains open (for life) to the meningeal interstitium permitting the exchanges of fluid and of cells between brain and meninges. The V-RC function as the brain sole drainage (prelymphatic) system in both physiological as well as pathological situations. During cortical development, capillaries emerge from the perforating vessels, by endothelial cells growing sprouts

  10. Microvascular system of anterior cruciate ligament in dogs.

    PubMed

    Kobayashi, Shigeru; Baba, Hisatoshi; Uchida, Kenzo; Negoro, Kohei; Sato, Mituhiko; Miyazaki, Tsuyoshi; Nomura, Eiki; Murakami, Kaname; Shimizubata, Matsuyuki; Meir, Adam

    2006-07-01

    This study was done to investigate the microvascular system of anterior cruciate ligament (ACL) using dogs. The objective was to study the microvascular architecture and the status of the barrier function of the capillary wall in the ACL by using microangiogram, scanning (SEM), and transmission electron microscopy (TEM). The vascular system in the ACL has been intensively studied by a number of researchers, using several microangiographic techniques in dogs, rabbits, and humans. However, most of these microangiographic studies had significant shortcomings, including the lack of three-dimensional observations and function of the blood-joint barrier in the ACL. In this study, the microstructure of the ACL was examined using microangiogram, SEM, and TEM. We investigated the vasculature of the ACL with SEM of vascular corrosion casts. In addition, we examined the status of the barrier function of the capillary wall in the ACL using the protein tracer horseradish peroxidase (HRP). Feeding vessels of the ligament were predominantly coming from the synovial-derived vessels originating from the synovium attached to the ligament near the tibial and femoral bone insertions of the ACL. The anterior cruciate ligament was surrounded by synovium, which had abundant vessels. The branches of these synovial vessels were penetrating into the ligament and making the intrinsic vascular network. It was also ascertained under SEM that the perivascular space around the intrinsic vessels were communicating through the intrinsic ligament fiber bundles and the mesh-like synovial membrane. The capillaries in the ACL were all of the continuous type under TEM. The protein tracer that was injected into the joint space passed through the synovial membrane and entered into the capillary lumen in the ACL, but the tracer that was injected intravenously did not appear in the perivascular space. The existence of a blood-ACL barrier does not necessarily imply the existence of an ACL-blood barrier. We

  11. How Plastics Work

    NASA Astrophysics Data System (ADS)

    Bloomfield, Louis

    2013-03-01

    We encounter plastics every day, but despite their widespread use, amazing range of properties, and basic scientific underpinnings, most physicists--like most people--know relatively little about plastics. In contrast to hard crystalline and amorphous solids (e.g., metals, salts, ceramics, and glasses), we take plastics for granted, select them carelessly, and examine them more closely only on a need-to-know basis. By ignoring plastics until we need them, however, we risk not knowing what we don't know and using the wrong ones. To repurpose a familiar advertisement, ``there's a plastic for that.'' This talk will review some of the basic physics and science of plastics. It will examine the roles of temperature, order, intermolecular forces, entanglements, and linkages in plastics, and how those issues affect the properties of a given plastic. We'll stop along the way to recognize a few of the more familiar plastics, natural and synthetic, and explain some of their mechanical, chemical, and optical properties. The talk will conclude by explaining the remarkable properties of a plastic that has been largely misunderstood since its discovery 70 years ago: Silly Putty.

  12. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

    PubMed

    Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

    2014-07-01

    Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

  13. Our plastic age.

    PubMed

    Thompson, Richard C; Swan, Shanna H; Moore, Charles J; vom Saal, Frederick S

    2009-07-27

    Within the last few decades, plastics have revolutionized our daily lives. Globally we use in excess of 260 million tonnes of plastic per annum, accounting for approximately 8 per cent of world oil production. In this Theme Issue of Philosophical Transactions of the Royal Society, we describe current and future trends in usage, together with the many benefits that plastics bring to society. At the same time, we examine the environmental consequences resulting from the accumulation of waste plastic, the effects of plastic debris on wildlife and concerns for human health that arise from the production, usage and disposal of plastics. Finally, we consider some possible solutions to these problems together with the research and policy priorities necessary for their implementation.

  14. Microvascular decompression for elderly patients with trigeminal neuralgia.

    PubMed

    Phan, Kevin; Rao, Prashanth J; Dexter, Mark

    2016-07-01

    Microvascular decompression (MVD) has been demonstrated to be an excellent surgical treatment approach in younger patients with trigeminal neuralgia (TN). However, it is not clear whether there are additional morbidity and mortality risks for MVD in the elderly population. We performed a systematic literature review using six electronic databases for studies that compared outcomes for MVD for TN in elderly (cut-off ⩾60, 65, 70years) versus younger populations. Outcomes examined included success rate, deaths, strokes, thromboembolism, meningitis, cranial nerve deficits and cerebrospinal fluid leaks. There were 1524 patients in the elderly cohort and 3488 patients in the younger cohort. There was no significant difference in success rates in elderly versus younger patients (87.5% versus 84.8%; P=0.47). However, recurrence rates were lower in the elderly (11.9% versus 15.6%; P=0.03). The number of deaths in the elderly cohort was higher (0.9% versus 0.1%; P=0.003). Rates of stroke (2.5% versus 1%) and thromboembolism (1.1% versus 0%) were also higher for elderly TN patients. No differences were found for rates of meningitis, cranial nerve deficits or cerebrospinal fluid leak. MVD remains an effective and reasonable strategy in the elderly population. There is evidence to suggest that rates of complications such as death, stroke, and thromboembolism may be significantly higher in the elderly population. The presented results may be useful in the decision-making process for MVD in elderly patients with TN.

  15. Specific albumin binding to microvascular endothelium in culture

    SciTech Connect

    Schnitzer, J.E.; Carley, W.W.; Palade, G.E. )

    1988-03-01

    The specific binding of rat serum albumin (RSA) to confluent microvascular endothelial cells in culture derived from the vasculature of the rat epididymal fat pad was studied at 4{degree}C by radioassay and immunocytochemistry. Radioiodinated RSA ({sup 125}I-RSA) binding to the cells reached equilibrium at {approximately} 20 min incubation. Albumin binding was a slowly saturating function over concentrations ranging from 0.01 to 50 mg/ml. Specific RSA binding with a moderate apparent affinity constant of 1.0 mg/ml and with a maximum binding concentration of 90 ng/cm{sup 2} was immunolocalized with anti-RSA antibody to the outer (free) side of the enothelium. Scatchard analysis of the binding yielded a nonlinear binding curve with a concave-upward shape. Dissociation rate analysis supports negative cooperativity of albumin binding, but multiple binding sites may also be present. Albumin binding fulfilled many requirements for ligand specificity including saturability, reversibility, competibility, and dependence on both cell type and cell number. The results are discussed in terms of past in situ investigations on the localization of albumin binding to vascular endothelium and its effect on transendothelial molecular transport.

  16. Syndecan-2 downregulation impairs angiogenesis in human microvascular endothelial cells

    SciTech Connect

    Noguer, Oriol Villena, Joan; Lorita, Jordi; Vilaro, Senen; Reina, Manuel

    2009-03-10

    The formation of new blood vessels, or angiogenesis, is a necessary process during development but also for tumour growth and other pathologies. It is promoted by different growth factors that stimulate endothelial cells to proliferate, migrate, and generate new tubular structures. Syndecans, transmembrane heparan sulphate proteoglycans, bind such growth factors through their glycosaminoglycan chains and could transduce the signal to the cytoskeleton, thus regulating cell behaviour. We demonstrated that syndecan-2, the major syndecan expressed by human microvascular endothelial cells, is regulated by growth factors and extracellular matrix proteins, in both bidimensional and tridimensional culture conditions. The role of syndecan-2 in 'in vitro' tumour angiogenesis was also examined by inhibiting its core protein expression with antisense phosphorothioate oligonucleotides. Downregulation of syndecan-2 reduces spreading and adhesion of endothelial cells, enhances their migration, but also impairs the formation of capillary-like structures. These results suggest that syndecan-2 has an important function in some of the necessary steps that make up the angiogenic process. We therefore propose a pivotal role of this heparan sulphate proteoglycan in the formation of new blood vessels.

  17. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

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

    PubMed

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

    2014-11-01

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

  19. Microvascular network topology of the human retinal vessels.

    PubMed

    Schröder, S; Brab, M; Schmid-Schönbein, G W; Reim, M; Schmid-Schönbein, H

    1990-01-01

    A quantitative analysis of blood flow in the human retinal vessels requires a detailed picture of the microvascular network topology. In order to lay the foundation for a quantitative microcirculatory network analysis of the human retina, a novel technique for tissue preparation and network characterization was developed. After injection of hydrogen peroxide into the human bulb, the microvasculature was filled with oxygen produced by endothelial catalase and visualized after embedding in a mixture of cedar oil and gum damar. The vessel topology was documented in the form of photomicrographs, which permitted complete reconstruction of the microvasculature on transparent overlays. By considering the complete capillary system it was possible to divide the retinal network into dichotomous, asymmetric arteriolar and venular trees. The Strahler ordering method, which considers both dichotomous and side branching configurations, was selected and applied to analyze the retinal vascular trees, using the capillaries as the zero order reference vessels. The number of vessel segments was found to be an approximate logarithmic function of the order number, in accordance with Horton's law. Vessel lengths within each order were found to be log-normal distributed, and median lengths for different orders could be approximated by a 2nd degree polynomial curve. Diameters within each order could be approximated by a Gaussian distribution, and the mean values for different orders could be expressed by an exponential curve. These data provide the basis for conductance, pressure and flow computations within the retinal microvessels.

  20. The photosensitizer talaporfinum caused microvascular embolization for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Li, Liming; Aizawa, Katsuo

    2005-07-01

    Photodynamic therapy (PDT) has been evolving rapidly in the recent years. A second-generation Photosensitizer mono-1-aspartyl chlorine 6 (Talaporfin / Npe6 / ME2906, Japan Meiji Seika, Ltd.) has been sanctified for the lung cancer clinical PDT by the Japan Ministry of Health, Labor and Welfare. In this paper, Talaporfin was injected to the implant cancer of a mouse a Talaporfin dose of 5mg/kg through intravenous. After 6 hours, the fluorescence images of the mouse were observed with a microscope and a 664 nm diode laser. Effects of therapy were clarified using the different irradiation energies of the laser (50, 100, 200 J/cm2). Both in plasma and in cancer, the concentrations of Talaporfin were analyzed using High Performance Liquid Chromatography (HPLC). Authors find that the higher concentrations of Talaporfin in plasma, the better PDD effect. It is experimentally verified that local microvascular embolisms in the cancer are formed for photodynamic therapy after the Talaporfin injection and the laser irradiation.

  1. Plastics and health risks.

    PubMed

    Halden, Rolf U

    2010-01-01

    By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrine-disrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs--i.e., reduce, reuse, recycle, rethink, restrain--for minimizing pre- and postnatal exposures to potentially harmful components of plastics.

  2. Additives in plastics.

    PubMed Central

    Deanin, R D

    1975-01-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products. PMID:1175566

  3. Additives in plastics.

    PubMed

    Deanin, R D

    1975-06-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products.

  4. Peripheral microvascular vasodilatory response to estradiol and genistein in women with insulin resistance

    PubMed Central

    Wenner, Megan M.; Taylor, Hugh S.; Stachenfeld, Nina S.

    2015-01-01

    Objective Estradiol enhances vasodilation in healthy women, but vascular effects of the phytoestrogen genistein are still under investigation. Insulin resistance (IR) compromises microvascular function. We therefore examined the interaction of estradiol, genistein, and IR on microvascular vasodilatory responsiveness. Methods We hypothesized that estradiol and genistein increase microvascular vasodilation in healthy women (control, n=8, 23±2 yr, BMI 25.9±2.9 kg/m2) but not in women with IR (n=7, 20±1 yr, BMI 27.3±3.0 kg/m2). We used the cutaneous circulation as a model of microvascular vasodilatory function. We determined cutaneous vascular conductance (CVC) with laser Doppler flowmetry and beat-to-beat blood pressure during local cutaneous heating (42°C) with estradiol or genistein microdialysis perfusions. Because heat induced vasodilation is primarily an NO mediated response, we examined microvascular vasodilation with and without L-NMMA. Results In control women, estradiol enhanced CVC (94.4±2.6 % vs. saline 81.6±4.2 % CVCmax, P<0.05), which was reversed with L-NMMA (80.9±7.8 % CVCmax, P<0.05), but genistein did not affect vasodilation. Neither estradiol nor genistein altered CVC in IR, although L-NMMA attenuated CVC during genistein. Conclusions Our study does not support improved microvascular responsiveness during genistein exposure in healthy young women, and demonstrates that neither estradiol nor genistein improve microvascular vasodilatory responsiveness in women with IR. PMID:25996650

  5. Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes.

    PubMed

    Olver, T Dylan; Laughlin, M Harold

    2016-02-01

    Type 2 diabetes (T2D) alters capillary hemodynamics, causes capillary rarefaction in skeletal muscle, and alters endothelial and vascular smooth muscle cell phenotype, resulting in impaired vasodilatory responses. These changes contribute to altered blood flow responses to physiological stimuli, such as exercise and insulin secretion. T2D-induced microvascular dysfunction impairs glucose and insulin delivery to skeletal muscle (and other tissues such as skin and nervous), thereby reducing glucose uptake and perpetuating hyperglycemia and hyperinsulinemia. In patients with T2D, exercise training (EX) improves microvascular vasodilator and insulin signaling and attenuates capillary rarefaction in skeletal muscle. EX-induced changes subsequently augment glucose and insulin delivery as well as glucose uptake. If these adaptions occur in a sufficient amount of tissue, and skeletal muscle in particular, chronic exposure to hyperglycemia and hyperinsulinemia and the risk of microvascular complications in all vascular beds will decrease. We postulate that EX programs that engage as much skeletal muscle mass as possible and recruit as many muscle fibers within each muscle as possible will generate the greatest improvements in microvascular function, providing that the duration of the stimulus is sufficient. Primary improvements in microvascular function occur in tissues (skeletal muscle primarily) engaged during exercise, and secondary improvements in microvascular function throughout the body may result from improved blood glucose control. We propose that the added benefit of combined resistance and aerobic EX programs and of vigorous intensity EX programs is not simply "more is better." Rather, we believe the additional benefit is the result of EX-induced adaptations in and around more muscle fibers, resulting in more muscle mass and the associated microvasculature being changed. Thus, to acquire primary and secondary improvements in microvascular function and improved

  6. Role of leukocytes in ethanol-induced microvascular injury in the rat brain in situ: potential role in alcohol brain pathology and stroke.

    PubMed

    Altura, Burton M; Gebrewold, Asefa; Zhang, Aimin; Altura, Bella T

    2002-07-12

    Effects of acute and chronic alcohol ethanol administration on in vivo microvascular-leukocyte dynamics was studied in brains of naive and leukocyte-depleted rats by direct, quantitative intravital high-resolution TV microscopy, fluorescence microscopy and myeloperoxidase staining. Administration of alcohol produced dose-dependent venular vasospasm, and rolling and adherence of leukocytes to venular walls; leukocyte velocity concomitantly decreased. Intermediate to high doses of ethanol resulted in infiltration of leukocytes and macrophages across venular walls, and concentration-dependent increases in myeloperoxidase staining in parenchyma, and rupture of postcapillary venules with focal hemorrhages. Use of phosphorus 31-nuclear magnetic resonance spectroscopy on intact animals revealed that the latter were associated with whole brain losses in intracellular levels of ATP and phosphocreatine with concomitant rises in intracellular inorganic phosphate and hydrogen ion concentration. Vinblastine-depletion of circulating leukocytes prevented or ameliorated greatly the alcohol-induced microvascular damage and proinflammatory-like reactions. These new results, when viewed in light of other recent findings, suggest that alcohol-induced cerebral vascular and brain damage is dependent, to a large extent, on recruitment of leukocytes.

  7. VE-cadherin involved in the pulmonary microvascular endothelial cell barrier injury induced by angiotensin II through modulating the cellular apoptosis and skeletal rearrangement

    PubMed Central

    Wu, Zhiyong; Liu, Huagang; Ren, Wei; Dai, Feifeng; Chang, Jinxing; Li, Bowen

    2016-01-01

    Objective: Angiotensin II (AngII) involved in the pathogenesis of pulmonary injury through impairing the integrity of pulmonary microvascular endothelial barrier, but the mechanism is still not clear. We aim to determine the roles of VE-cadherin, playing crucial roles in the adhesion of the vascular endothelial barrier and the barrier function, in the pulmonary microvascular endothelial cell (PMVEC) barrier injury mediated by AngII. Methods: Mice acute lung injury (ALI) model was induced through pumping of AngII. The infiltration of macrophages and neutrophils as well as the PMVEC permeability were determined in order to determine the barrier injury in vivo and in vitro. Knockdown of VE-cadherin was established using siRNA technique, and its roles in the apoptosis and skeletal rearrangement in the PMVECs were evaluated. Results: After AngII interference, the expression of VE-cadherin in the PMVECs and pulmonary tissues in mice was down-regulated. Upon VE-cadherin knockdown through siRNA technique, AngII induced susceptibility of PMVECs to apoptosis. Knockdown of VE-cadherin contributed to the skeletal rearrangement in the endothelial cells, together with increase of permeability. Conclusions: VE-cadherin expression is closely related to the apoptosis and skeletal rearrangement of PMVECs induced by AngII. PMID:27830014

  8. Studies of pathological dynamics after microvascular injury using nonlinear optical methods

    NASA Astrophysics Data System (ADS)

    Rosidi, Nathanael L.

    Microvascular lesions are a common feature in the aging brain and clinical evidence has correlated microvascular pathology with the development of neurodegenerative diseases such as Alzheimer's disease and dementia. Traditional animal models that replicate hemorrhagic and ischemic lesions in the brain typically affect large regions in the cortex and do not reproduce the small-scale lesions linked to neurodegeneration that likely stem from injuries to single microvessels. Due in part to this lack of small-scale injury animal models, there remains an incomplete understanding of the cellular and pathophysiological dynamics following small-scale vascular lesions, making progress on therapeutic strategies difficult. We used tightly focused femtosecond laser pulses to injure single penetrating arterioles (PA) (i.e., arterioles that plunge into the brain) in the cortex of live anesthetized rodents and used two-photon excited fluorescence (2PEF) imaging to quantify blood flow changes and to determine the time course of pathological consequences in the brain after injury. We find that after ischemic occlusion of a PA, nearby pial and penetrating arterioles do not actively compensate for the reduction of blood flow observed near the occluded blood vessel. We find that capillaries connected downstream to the clotted vessel dilate but other capillaries in the vicinity do not, suggesting that any compensatory signal that results in a physiological response travels vascularly. We ruptured individual PAs to induce microhemorrhages that resulted in extravasation of blood into the parenchyma. We find that tissue compression due to the hematoma does not collapse capillaries and cause acute ischemia. 2PEF imaging of mice expressing yellow fluorescent protein (YFP) in a subset of cortical neurons revealed no dendrite degeneration out to seven days after microhemorrhage. However, we did observe an inflammatory response by microglia/macrophages as quickly as 1.5-hrs after

  9. Network-timing-dependent plasticity.

    PubMed

    Delattre, Vincent; Keller, Daniel; Perich, Matthew; Markram, Henry; Muller, Eilif B

    2015-01-01

    Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding.

  10. Network-timing-dependent plasticity

    PubMed Central

    Delattre, Vincent; Keller, Daniel; Perich, Matthew; Markram, Henry; Muller, Eilif B.

    2015-01-01

    Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding. PMID:26106298

  11. Free flap monitoring in plastic and reconstructive surgery.

    PubMed

    Pickett, John A; Thorniley, Maureen S; Carver, Nigel; Jones, Deric P

    2003-01-01

    Free flaps are regularly used in plastic and reconstructive surgery but have a significant failure rate due to vessel thrombosis in the re-established arterial or venous circulation. A monitor of flap perfusion and oxygenation would allow the early detection of progressing flap ischaemia, hastening the required intervention and maximising the chances of salvaging the flap. A dual wavelength spectrophotometer has been designed and constructed which can monitor haemodynamic events in flaps during surgery and postoperatively. Eleven patients undergoing free flap surgery were studied. Measurements were made during surgery before division of the vessels and during and after microvascular anastomosis. Significant changes in all parameters were observed on reperfusion of the flaps after anastomosis or tourniquet ischaemia. Abnormal reperfusion in one flap and subsequent ischaemic events in two others were identified.

  12. Detecting plastics in seedcotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To increase global market share and value the US cotton industry needs to supply cotton lint that is free of contamination. Removing plastic contamination first requires developing a means to detect plastics in seedcotton. This study was conducted to validate a custom Ion Mobility Spectrometer (IM...

  13. Detecting plastics in seedcotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The US cotton industry wants to increase market share and value by supplying pure cotton. Removing contamination requires developing a means to detect plastics in seedcotton. This study was conducted to determine if Ion Mobility Spectrometry (IMS) could be used to find small amounts of plastic in ...

  14. Biodegradation of plastics.

    PubMed

    Shimao, M

    2001-06-01

    Widespread studies on the biodegradation of plastics have been carried out in order to overcome the environmental problems associated with synthetic plastic waste. Recent work has included studies of the distribution of synthetic polymer-degrading microorganisms in the environment, the isolation of new microorganisms for biodegradation, the discovery of new degradation enzymes, and the cloning of genes for synthetic polymer-degrading enzymes.

  15. Effect of acetylsalicylic acid on microvascular thrombosis in autologous breast reconstruction.

    PubMed

    Enajat, Morteza; Aziz Mohammadi, Mujzgan; Debeij, Jan; van der Hulst, Rene R W J; Mureau, Marc A M

    2014-01-01

    Although advances in microsurgery have increased success rates of autologous breast reconstruction, microvascular thrombosis still remains a major concern as a cause of flap failure. At present, no evidence-based guidelines on pharmacological prevention of microvascular thrombosis exist. This study investigates the effect of acetylsalicylic acid on the incidence of microvascular complications in patients undergoing autologous breast reconstruction. Patients undergoing deep inferior epigastric artery perforator or free transverse rectus abdominis myocutaneous flap breast reconstruction at two academic centers in the Netherlands between 2005 and 2011 were included. Patients at one center received once daily 0.6 mL of nadroparine and 40 mg acetylsalicylic acid, while patients at the other center received 0.6 mL nadroparine only. A total of 430 consecutive patients underwent 592 breast reconstructions. No statistically significant differences were found between the two groups in the incidence of flap failure (2.8 and 2.5%), microvascular thromboembolic complications (2.6 and 3.8%), venous congestion (3.4 and 2.8%), or overall complications (28.0 and 32.3%). Hematoma tended to occur more often in the group receiving acetylsalicylic acid (9.2 and 4.7%).It was found that no protective effect of acetylsalicylic acid on microvascular complications was present. Given its known risks and the somewhat increased occurrence of hematoma in the present study, we stopped to routinely administer acetylsalicylic acid after autologous breast reconstruction.

  16. Conditioned Media from Microvascular Endothelial Cells Cultured in Simulated Microgravity Inhibit Osteoblast Activity

    PubMed Central

    Cazzaniga, Alessandra; Castiglioni, Sara; Maier, Jeanette A. M.

    2014-01-01

    Background and Aims. Gravity contributes to the maintenance of bone integrity. Accordingly, weightlessness conditions during space flight accelerate bone loss and experimental models in real and simulated microgravity show decreased osteoblastic and increased osteoclastic activities. It is well known that the endothelium and bone cells cross-talk and this intercellular communication is vital to regulate bone homeostasis. Because microgravity promotes microvascular endothelial dysfunction, we anticipated that the molecular cross-talk between endothelial cells exposed to simulated microgravity and osteoblasts might be altered. Results. We cultured human microvascular endothelial cells in simulated microgravity using the rotating wall vessel device developed by NASA. Endothelial cells in microgravity show growth inhibition and release higher amounts of matrix metalloproteases type 2 and interleukin-6 than controls. Conditioned media collected from microvascular endothelial cells in simulated microgravity were used to culture human osteoblasts and were shown to retard osteoblast proliferation and inhibit their activity. Discussion. Microvascular endothelial cells in microgravity are growth retarded and release high amounts of matrix metalloproteases type 2 and interleukin-6, which might play a role in retarding the growth of osteoblasts and impairing their osteogenic activity. Conclusions. We demonstrate that since simulated microgravity modulates microvascular endothelial cell function, it indirectly impairs osteoblastic function. PMID:25210716

  17. Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction

    PubMed Central

    Lin, Jie; Zhang, Lei; Zhang, Mingming; Hu, Jianqiang; Wang, Tingting; Duan, Yu; Man, Wanrong; Wu, Bin; Feng, Jiaxu; Sun, Lei; Li, Congye; Zhang, Rongqing; Wang, Haichang; Sun, Dongdong

    2016-01-01

    Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function. Mst1 overexpression deceased CMECs autophagy as evidenced by decreased LC3 expression and enhanced protein aggregation when subjected to high glucose culture. Mst1 knockout improved cardiac microvessel integrity and enhanced cardiac functions in diabetic mice. Mst1 knockdown up-regulated autophagy as indicated by more typical autophagosomes and increased LC3 expression in CMECs subjected to high glucose cultures. Mst1 knockdown also promoted autophagic flux in the presence of bafilomycin A1. Mst1 overexpression increased CMECs apoptosis, whereas Mst1 knockout decreased CMECs apoptosis. Sirt1 knockout abolished the effects of Mst1 overexpression in cardiac microvascular injury and cardiac dysfunction. In conclusion, Mst1 knockout preserved cardiac microvessel integrity and improved cardiac functions in diabetic mice. Mst1 decreased sirt1 activity, inhibited autophagy and enhanced apoptosis in CMECs, thus participating in the pathogenesis of diabetic coronary microvascular dysfunction. PMID:27680548

  18. Methylene blue solder re-absorption in microvascular anastomoses

    NASA Astrophysics Data System (ADS)

    Birch, Jeremy F.; Hepplewhite, J.; Frier, Malcolm; Bell, Peter R. F.

    2003-06-01

    Soldered vascular anastomoses have been reported using several chromophores but little is known of the optimal conditions for microvascular anastomosis. There are some indications of the optimal protein contents of a solder, and the effects of methylene blue on anastomotic strength. The effects of varying laser power density in vivo have also been described, showing a high rate of thrombosis with laser power over 22.9Wcm-2. However no evidence exists to describe how long the solder remains at the site of the anastomosis. Oz et al reported that the fibrin used in their study had been almost completely removed by 90 days but without objective evidence of solder removal. In order to address the issue of solder re-absorption from the site of an anastomosis we used radio-labelled albumin (I-125) incorporated into methylene blue based solder. This was investigated in both the situation of the patent and thrombosed anastomosis with anastomoses formed at high and low power. Iodine-125 (half life: 60.2 days) was covalently bonded to porcine albumin and mixed with the solder solution. Radio-iodine has been used over many years to determine protein turnover using either I-125 or I-131. Iodine-125 labelled human albumin is regularly used as a radiopharmaceutical tool for the determination of plasma volume. Radio-iodine has the advantages of not affecting protein metabolism and the label is rapidly excreted after metabolic breakdown. Labelling with chromium (Cr-51) causes protein denaturation and is lost from the protein with time. Labelled albumin has been reported in human studies over a 21-day period, with similar results reported by Matthews. Most significantly McFarlane reported a different rate of catabolism of I-131 and I-125 over a 22-day period. The conclusion from this is that the rate of iodine clearance is a good indicator of protein catabolism. In parallel with the surgery a series of blank standards were prepared with a known mass of solder to correct for isotope

  19. Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

    PubMed Central

    Nguyen, Gerard K.; Monahan, John F. W.; Davis, Gabrielle B.; Lee, Yong Suk; Ragina, Neli P.; Wang, Charles; Zhou, Zhao Y.; Hong, Young Kwon; Spivak, Ryan M.; Wong, Alex K.

    2013-01-01

    both diagnose and successfully treat microvascular complications before irreversible tissue damage and flap loss occurs. PMID:23977093

  20. Microvascular Fragment Transplantation Improves Rat Dorsal Skin Flap Survival

    PubMed Central

    Rathbone, Christopher R.

    2016-01-01

    Background: The development of flap necrosis distally remains a concern during microsurgical flap transfers because, at least in part, of decreased perfusion. Microvascular fragments (MVFs) are microvessels isolated from adipose tissue that are capable of improving tissue perfusion in a variety of tissue defects. The aim of this study was to determine whether the transplantation of MVFs in a dorsal rat skin flap model can improve flap survival. Methods: A 10 × 3 cm flap was raised in a cranial to caudal fashion on the dorsal side of 16 Lewis rats, with the caudal side remaining intact. The rats were equally divided into a treatment group (MVFs) and a control group (sterile saline). At the time of surgery, sterile saline with or without MVFs was injected directly into the flap. Microvessel density was determined after harvesting flap tissue by counting vessels that positively stained for Griffonia simplicifolia lectin I-isolectin B4. Laser Doppler was used to measure blood flow before and after surgery and 7 and 14 days later. Flap survival was evaluated 7 and 14 days after surgery by evaluating the percentage of viable tissue of the flap with photodigital planimetry. Results: Despite the lack of a significant difference in microvessel density and tissue perfusion, flap survival increased 6.4% (P < 0.05) in MVF-treated animals compared with controls. Conclusions: The use of MVFs may be a means to improve flap survival. Future studies are required to delineate mechanisms whereby this occurs and to further optimize their application. PMID:28293502

  1. Track recording plastic compositions

    NASA Technical Reports Server (NTRS)

    Tarle, Gregory (Inventor)

    1983-01-01

    Improved nuclear track recording plastic compositions are provided which exhibit greatly decreased surface roughness when etched to produce visible tracks of energetic nuclear particles which have passed into and/or through said plastic. The improved compositions incorporate a small quantity of a phthalic acid ester into the major plastic component which is derived from the polymerization of monomeric di-ethylene glycol bis allyl carbonate. Di-substituted phthalic acid esters are preferred as the added component, with the further perference that the ester substituent has a chain length of 2 or more carbon atoms. The inclusion of the phthalic acid ester to an extent of from about 1-2% by weight of the plastic compositions is sufficient to drastically reduce the surface roughness ordinarily produced when the track recording plastic is contacted by etchants.

  2. Endothelial Progenitor Cells Physiology and Metabolic Plasticity in Brain Angiogenesis and Blood-Brain Barrier Modeling

    PubMed Central

    Malinovskaya, Natalia A.; Komleva, Yulia K.; Salmin, Vladimir V.; Morgun, Andrey V.; Shuvaev, Anton N.; Panina, Yulia A.; Boitsova, Elizaveta B.; Salmina, Alla B.

    2016-01-01

    Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB) development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons). Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies. PMID:27990124

  3. American Society of Plastic Surgeons

    MedlinePlus

    ... that instill confidence. Do Your Homework Patient Safety Plastic Surgery When you choose a doctor who is ... to procedure selector Why Choose A Board Certified Plastic Surgeon Choose a board-certified plastic surgeon and ...

  4. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  5. Microvascular Branching as a Determinant of Blood Flow by Intravital Particle Imaging Velocimetry

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; McKay, Terri L.; Vickerman, Mary B.; Wernet, Mark P.; Myers, Jerry G.; Radhakrishnan, Krishnan

    2007-01-01

    The effects of microvascular branching on blood flow were investigated in vivo by microscopic particle imaging velocimetry (micro-PIV). We use micro-PIV to measure blood flow by tracking red blood cells (RBC) as the moving particles. Velocity flow fields, including flow pulsatility, were analyzed for the first four branching orders of capillaries, postcapillary venules and small veins of the microvascular network within the developing avian yolksac at embryonic day 5 (E5). Increasing volumetric flowrates were obtained from parabolic laminar flow profiles as a function of increasing vessel diameter and branching order. Maximum flow velocities increased approximately twenty-fold as the function of increasing vessel diameter and branching order compared to flow velocities of 100 - 150 micron/sec in the capillaries. Results from our study will be useful for the increased understanding of blood flow within anastomotic, heterogeneous microvascular networks.

  6. Gene expression microarray data from human microvascular endothelial cells supplemented with a low concentration of niacin

    PubMed Central

    Hughes-Large, Jennifer M.; Borradaile, Nica M.

    2016-01-01

    The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors “Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity” (Hughes-Large et al. 2014). Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, NAP1L2, and OR13C8 was confirmed by real time quantitative PCR. PMID:26937468

  7. Gene expression microarray data from human microvascular endothelial cells supplemented with a low concentration of niacin.

    PubMed

    Hughes-Large, Jennifer M; Borradaile, Nica M

    2016-03-01

    The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors "Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity" (Hughes-Large et al. 2014). Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, NAP1L2, and OR13C8 was confirmed by real time quantitative PCR.

  8. POLYESTER GLASS PLASTICS FOR SHIPBUILDING,

    DTIC Science & Technology

    POLYESTER PLASTICS , SHIP HULLS), (*SHIP HULLS, POLYESTER PLASTICS ), GLASS TEXTILES, REINFORCING MATERIALS, SHIP STRUCTURAL COMPONENTS, COMPOSITE MATERIALS, PROCESSING, CHEMISTRY, HANDBOOKS, BINDERS, USSR

  9. Effect of phentolamine on the hyperemic response to adenosine in patients with microvascular disease.

    PubMed

    Aarnoudse, Wilbert; Geven, Maartje; Barbato, Emanuele; Botman, Kees-joost; De Bruyne, Bernard; Pijls, Nico H J

    2005-12-15

    For accurate measurement of the fractional flow reserve (FFR) of the myocardium, the presence of maximum hyperemia is of paramount importance. It has been suggested that the hyperemic effect of the conventionally used hyperemic stimulus, adenosine, could be submaximal in patients who have microvascular dysfunction and that adding alpha-blocking agents could augment the hyperemic response in these patients. We studied the effect of the nonselective alpha-blocking agent phentolamine, which was administered in addition to adenosine after achieving hyperemia, in patients who had microvascular disease and those who did not. Thirty patients who were referred for percutaneous coronary intervention were selected. Of these 30 patients, 15 had strong indications for microvascular disease and 15 did not. FFR was measured using intracoronary adenosine, intravenous adenosine, and intracoronary papaverine before and after intracoronary administration of the nonselective alpha blocker phentolamine. In patients who did not have microvascular disease, no differences in hyperemic response to adenosine were noted, whether or not alpha blockade was given before adenosine administration; FFR levels before and after phentolamine were 0.76 and 0.75, respectively, using intracoronary adenosine (p = 0.10) and 0.75 and 0.74, respectively, using intravenous adenosine (p = 0.20). In contrast, in patients who had microvascular disease, some increase in hyperemic response was observed after administration of phentolamine; FFR levels decreased from 0.74 to 0.70 using intracoronary adenosine (p = 0.003) and from 0.75 to 0.72 using intravenous adenosine (p = 0.04). Although statistically significant, the observed further decrease in microvascular resistance after addition of phentolamine was small and did not affect clinical decision making in any patient. In conclusion, when measuring FFR, routinely adding an alpha-blocking agent to adenosine does not affect clinical decision making.

  10. Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction.

    PubMed

    Fu, Zhuo; Wu, Jing; Nesil, Tanseli; Li, Ming D; Aylor, Kevin W; Liu, Zhenqi

    2017-02-01

    Insulin action on hippocampus improves cognitive function, and obesity and type 2 diabetes are associated with decreased cognitive function. Cerebral microvasculature plays a critical role in maintaining cerebral vitality and function by supplying nutrients, oxygen, and hormones such as insulin to cerebral parenchyma, including hippocampus. In skeletal muscle, insulin actively regulates microvascular opening and closure, and this action is impaired in the insulin-resistant states. To examine insulin's action on hippocampal microvasculature and parenchyma and the impact of diet-induced obesity, we determined cognitive function and microvascular insulin responses, parenchyma insulin responses, and capillary density in the hippocampus in 2- and 8-mo-old rats on chow diet and 8-mo-old rats on a long-term high-fat diet (6 mo). Insulin infusion increased hippocampal microvascular perfusion in rats on chow diet by ~80-90%. High-fat diet feeding completely abolished insulin-mediated microvascular responses and protein kinase B phosphorylation but did not alter the capillary density in the hippocampus. This was associated with a significantly decreased cognitive function assessed using both the two-trial spontaneous alternation behavior test and the novel object recognition test. As the microvasculature provides the needed endothelial surface area for delivery of nutrients, oxygen, and insulin to hippocampal parenchyma, we conclude that hippocampal microvascular insulin resistance may play a critical role in the development of cognitive impairment seen in obesity and diabetes. Our results suggest that improvement in hippocampal microvascular insulin sensitivity might help improve or reverse cognitive function in the insulin-resistant states.

  11. Effects of local anaesthesia on subdermal needle insertion pain and subsequent tests of microvascular function in human.

    PubMed

    Cracowski, Jean-Luc; Lorenzo, Santiago; Minson, Christopher T

    2007-03-22

    Post-occlusive and local thermal hyperemia are currently used as integrated tests to study microvascular function in microvascular diseases. However, further pathophysiological insight would require its association with microdialysis. The major limitation remains the microinvasive approach as local anaesthesia prior to fiber insertion could lead to confounding effects. The objective of our study was to determine whether EMLA cream treatment, applied for 20 min, 40 or 60 min, significantly decreases the pain related to intradermal needle insertions, while not decreasing the microvascular response to post-occlusive and thermal hyperemia 2 h after cream removal. EMLA cream, when applied during 40 min, induces a significant 75% decrease in the pain following intradermal needle insertion, while not modifying skin post-occlusive and thermal hyperemia 2 h after cream removal. Therefore, we recommend its use in such conditions before performing microdialysis coupled with laser Doppler flowmetry in cohort studies aimed at studying microvascular dysfunction in patients with microvascular diseases.

  12. Quantitative in vitro assay to measure neutrophil adhesion to activated primary human microvascular endothelial cells under static conditions.

    PubMed

    Wilhelmsen, Kevin; Farrar, Katherine; Hellman, Judith

    2013-08-23

    The vascular endothelium plays an integral part in the inflammatory response. During the acute phase of inflammation, endothelial cells (ECs) are activated by host mediators or directly by conserved microbial components or host-derived danger molecules. Activated ECs express cytokines, chemokines and adhesion molecules that mobilize, activate and retain leukocytes at the site of infection or injury. Neutrophils are the first leukocytes to arrive, and adhere to the endothelium through a variety of adhesion molecules present on the surfaces of both cells. The main functions of neutrophils are to directly eliminate microbial threats, promote the recruitment of other leukocytes through the release of additional factors, and initiate wound repair. Therefore, their recruitment and attachment to the endothelium is a critical step in the initiation of the inflammatory response. In this report, we describe an in vitro neutrophil adhesion assay using calcein AM-labeled primary human neutrophils to quantitate the extent of microvascular endothelial cell activation under static conditions. This method has the additional advantage that the same samples quantitated by fluorescence spectrophotometry can also be visualized directly using fluorescence microscopy for a more qualitative assessment of neutrophil binding.

  13. Sleep and protein synthesis-dependent synaptic plasticity: impacts of sleep loss and stress

    PubMed Central

    Grønli, Janne; Soulé, Jonathan; Bramham, Clive R.

    2014-01-01

    Sleep has been ascribed a critical role in cognitive functioning. Several lines of evidence implicate sleep in the consolidation of synaptic plasticity and long-term memory. Stress disrupts sleep while impairing synaptic plasticity and cognitive performance. Here, we discuss evidence linking sleep to mechanisms of protein synthesis-dependent synaptic plasticity and synaptic scaling. We then consider how disruption of sleep by acute and chronic stress may impair these mechanisms and degrade sleep function. PMID:24478645

  14. Effect of angiopoietin-like protein 4 on rat pulmonary microvascular endothelial cells exposed to LPS

    PubMed Central

    WANG, YUXI; CHEN, HAILONG; LI, HAILONG; ZHANG, JINGWEN; GAO, YANYAN

    2013-01-01

    Pulmonary microvascular endothelial cells (PMVECs) possess highly proliferative and angiogenic capacities and are localized at the critical interface between the blood and microvessel wall; they are the primary targets of inflammatory cytokines during lung inflammation. Angiopoietin-like protein 4 (Angptl4) is a circulating protein that has recently been implicated in the regulation of angiogenesis and metastasis. This study aimed to investigate the effect of Angptl4 on rat PMVECs (RPMVECs) exposed to lipopolysaccharide (LPS). The cell culture was stimulated with LPS. Total Angptl4 cDNA was obtained from Source BioScience. The PCR product was cloned into the pcDNA3.1-eGFP or the pcDNA3.1-eGFP-Angptl4 vector, which were then transfected into the RPMVECs using SuperFect transfection reagent. The Angptl4 mRNA levels, protein levels and cell morphology of the RPMVECs in the experimental groups were detected using real time-PCR, western blot analysis, MTT assay, ELISA and confocal microscopy methods, respectively. The Angptl4 expression vector, pcDNA3.1-eGFP-Angptl4, was successfully constructed. The Angptl4 mRNA level in the LPS-pcDNA3.1-eGFP-transfected group (blank control) was slightly increased and was significantly higher in the experimental group compared with the empty vector and blank control group with significant differences. Pro-apoptotic caspase-8, -9 and Bax protein were inhibited, while p-AKT/AKT and p-MEK1/2 protein expression was also decreased. The rosiglitazone group had significantly decreased levels of the inflammatory cytokine, tumor necrosis factor (TNF)-α (P<0.01). The overexpression of Angptl4 inhibited the LPS-induced increase in the permeability of the RPMVECs, which was associated with the depolymerization of central F-actin in the RPMVECs. In conclusion, our study demonstrates that the overexpression of Angptl4 exerts protective, anti-inflammatory and anti-angiogenic effects. It represents a novel therapeutic target gene for the treatment

  15. Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage

    PubMed Central

    Foley, James R J; Musa, Tarique Al; Ripley, David P; Swoboda, Peter P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Greenwood, John P; Plein, Sven

    2016-01-01

    Background Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography. Objective We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling. Methods 54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging. Results 44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (β=−0.655, p<0.001) and MVO (β=−0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22). Conclusions Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH. PMID:27175286

  16. Microvascular Decompression for Hemifacial Spasm Associated with Vertebrobasilar Artery

    PubMed Central

    Kim, Joo Pyung; Choi, Seok Keun; Rhee, Bong Arm; Lim, Young Jin

    2008-01-01

    Objective Hemifacial spasm (HFS) is considered as a reversible pathophysiological condition mainly induced by continuous vascular compression of the facial nerve root exit zone (REZ) at the cerebellopontine angle. As an offending vessel, vertebrobasilar artery tends to compress much more heavily than others. The authors analyzed HFS caused by vertebrobasilar artery and described the relationships between microsurgical findings and clinical courses. Methods Out of 1,798 cases treated with microvascular decompression (MVD) from Jan. 1980 to Dec. 2004, the causative vessels were either vertebral artery or basilar artery in 87 patients. Seventy-nine patients were enrolled in this study. Preoperatively, computed tomography (CT) or brain magnetic resonance (MR) imaging with 3-dimentional short range MR technique was performed and CT was checked immediately or 2-3 days after anesthetic recovery. The authors retrospectively analyzed the clinical features, the compression patterns of the vessels at the time of surgery and treatment outcomes. Results There were 47 were male and 32 female patients. HFS developed on the left side in 52 cases and on the right side in 27. The mean age of onset was 52.3 years (range 19-60) and the mean duration of symptoms was 10.7 years. Many patients (39 cases; 49.1%) had past history of hypertension. HFS caused only by the vertebral artery was 8 cases although most of the other cases were caused by vertebral artery (VA) in combination with its branching arteries. Most frequently, the VA and the posterior inferior cerebellar artery (PICA) were the simultaneous causative blood vessels comprising 32 cases (40.5%), and in 27 cases (34.2%) the VA and the anterior inferior cerebellar artery (AICA) were the offenders. Facial symptoms disappeared in 61 cases (77.2%) immediately after the operation and 68 cases (86.1%) showed good outcome after 6 months. Surgical outcome just after the operation was poor in whom the perforators arose from the offending

  17. Mechanical plasticity of cells

    NASA Astrophysics Data System (ADS)

    Bonakdar, Navid; Gerum, Richard; Kuhn, Michael; Spörrer, Marina; Lippert, Anna; Schneider, Werner; Aifantis, Katerina E.; Fabry, Ben

    2016-10-01

    Under mechanical loading, most living cells show a viscoelastic deformation that follows a power law in time. After removal of the mechanical load, the cell shape recovers only incompletely to its original undeformed configuration. Here, we show that incomplete shape recovery is due to an additive plastic deformation that displays the same power-law dynamics as the fully reversible viscoelastic deformation response. Moreover, the plastic deformation is a constant fraction of the total cell deformation and originates from bond ruptures within the cytoskeleton. A simple extension of the prevailing viscoelastic power-law response theory with a plastic element correctly predicts the cell behaviour under cyclic loading. Our findings show that plastic energy dissipation during cell deformation is tightly linked to elastic cytoskeletal stresses, which suggests the existence of an adaptive mechanism that protects the cell against mechanical damage.

  18. Shape-Shifting Plastic

    SciTech Connect

    2015-05-20

    A new plastic developed by ORNL and Washington State University transforms from its original shape through a series of temporary shapes and returns to its initial form. The shape-shifting process is controlled through changes in temperature

  19. A Plastic Menagerie

    ERIC Educational Resources Information Center

    Hadley, Mary Jane

    2010-01-01

    Bobble heads had become quite popular, depicting all sorts of sports figures, animals, and even presidents. In this article, the author describes how her fourth graders made bobble head sculptures out of empty plastic drink bottles. (Contains 1 online resource.)

  20. Strain avalanches in plasticity

    NASA Astrophysics Data System (ADS)

    Argon, A. S.

    2013-09-01

    Plastic deformation at the mechanism level in all solids occurs in the form of discrete thermally activated individual stress relaxation events. While there are clear differences in mechanisms between dislocation mediated events in crystalline solids and by individual shear transformations in amorphous metals and semiconductors, such relaxation events interact strongly to form avalanches of strain bursts. In all cases the attendant distributions of released energy as amplitudes of acoustic emissions, or in serration amplitudes in flow stress, the levels of strain bursts are of fractal character with fractal exponents in the range from -1.5 to -2.0, having the character of phenomena of self-organized criticality, SOC. Here we examine strain avalanches in single crystals of ice, hcp metals, the jerky plastic deformations of nano-pillars of fcc and bcc metals deforming in compression, those in the plastic flow of bulk metallic glasses, all demonstrating the remarkable universality of character of plastic relaxation events.

  1. Dreaming in plastic

    NASA Astrophysics Data System (ADS)

    Korzhov, Marianna; Andelman, David; Shikler, Rafi

    2008-07-01

    Plastic is one of the most versatile materials available. It is cheap, flexible and easy to process, and as a result it is all around us - from our computer keyboards to the soles of our shoes. One of its most common applications is as an insulating coating for electric wires; indeed, plastic is well known for its insulating characteristics. It came as something of a surprise, therefore, when in the late 1970s a new generation of plastics was discovered that displayed exactly the opposite behaviour - the ability to conduct electricity. In fact, plastics can be made with a whole range of conductivities - there are polymer materials that behave like semiconductors and there are those that can conduct as well as metals. This discovery sparked a revolution in the electronics community, and three decades of research effort is now yielding a range of stunning new applications for this ubiquitous material.

  2. Physics in Plastics Technology.

    ERIC Educational Resources Information Center

    Thomas, Ken

    1980-01-01

    Discusses the increasing role of the physicist in plastics technology. Relationships of molecular structure to material behavior, design which is related to the material, and the practical problems of fabricating a material into an article are included. (HM)

  3. Laser cutting plastic materials

    SciTech Connect

    Van Cleave, R.A.

    1980-08-01

    A 1000-watt CO/sub 2/ laser has been demonstrated as a reliable production machine tool for cutting of plastics, high strength reinforced composites, and other nonmetals. More than 40 different plastics have been laser cut, and the results are tabulated. Applications for laser cutting described include fiberglass-reinforced laminates, Kevlar/epoxy composites, fiberglass-reinforced phenolics, nylon/epoxy laminates, ceramics, and disposable tooling made from acrylic.

  4. The Need for Plastics Education.

    ERIC Educational Resources Information Center

    Society of Plastics Engineers, Inc., Stamford, CT.

    In view of a lack of trained personnel in the industry, the Plastics Education Foundation proposes that educators (1) add more plastics programs, (2) establish plastics engineering degrees at appropriate 4-year institutions, (3) add plastics processing technology to current engineering curricula, and (4) interest younger students in courses and/or…

  5. Diffuse reflectance spectroscopy: Systemic and microvascular oxygen saturation is linearly correlated and hypoxia leads to increased spatial heterogeneity of microvascular saturation.

    PubMed

    Awan, Z A; Häggblad, E; Wester, T; Kvernebo, M S; Halvorsen, P S; Kvernebo, K

    2011-05-01

    The microvascular oxygen saturation (SmvO(2)) in the skin and tongue (sublingual mucosa) in pigs (n=6) was characterised using diffuse reflectance spectroscopy (DRS). The correlation between arterial oxygen saturation (SaO(2)) and SmvO(2) as well as the spatial heterogeneity of SmvO(2) was examined during hypoxia. DRS uses shallow-penetrating visible light to assess microvascular oxygen saturation (SmvO(2)) in superficial tissue. Hypoxia was induced by gradual reduction in ventilation or reduction of the inspiratory oxygen fraction. The spatial heterogeneity of SmvO(2) was expressed as the coefficient of variation (CV) of repeated SmvO(2) measurements. Baseline SmvO(2) before interventions was 20.2% (10.3%-38.1%, median with range) in groin skin, 32.9% (13.0%-49.3%) in the ear and 42.2% (32.1%-51.5%) in the tongue. SmvO(2) in the groin was significantly lower than venous oxygen saturation (SvO(2)) (p<0.05) and SmvO(2) in the tongue (p=0.03). There was a significant linear correlation between SaO(2) and SmvO(2) in all measuring sites for both interventions (p<0.05). Similarly there was a significant correlation between CV of repeated SmvO(2) measurements and SmvO(2) in all measuring sites for both interventions (p<0.01). The results from baseline measurements indicate a surprisingly high oxygen extraction in the measurement volume of DRS, especially in the groin skin. A reduction of SmvO(2) with decreasing SaO(2) was found and additionally the results suggest that spatial heterogeneity of microvascular oxygen saturation increases during hypoxia. Microvascular disturbances have been demonstrated in both local vascular diseases and systemic conditions such as shock and sepsis, an assessment of microvascular oxygen saturation using DRS may be useful in the monitoring of the microcirculation in such patients. This study is a part of an ongoing characterization of the DRS technique.

  6. Demonstration of actin filament stress fibers in microvascular endothelial cells in situ.

    PubMed

    Nehls, V; Drenckhahn, D

    1991-07-01

    We have developed a method for immunostaining the microvascular tree of rat mesenteric windows in situ. The procedure consists of three steps, i.e., mild fixation with formaldehyde, controlled proteolytic digestion of the mesothelial layer, and permeabilization with acetone. Discrimination between different microvascular segments was possible by double-fluorescent staining with antibodies to the smooth muscle isoform of alpha-actin and to nonmuscle myosin from platelets. Antibodies to nonmuscle myosin labeled numerous longitudinally oriented cables in endothelial cells of all microvascular segments (arterioles, metarterioles, pre-, mid-, and postcapillaries, small venules). Occasionally, the myosin-containing cables displayed the interrupted sarcomere-like staining pattern that is diagnostic for stress fibers. In contrast, staining of actin filaments with phalloidin-rhodamin resulted in a noninterrupted, continuous fluorescence of the stress fibers. A possible functional role of microvascular endothelial stress fibers is to serve as a tensile cytoskeletal scaffold that stabilizes the tubular, three-dimensional geometry of microvessels and, in addition, to help the endothelium resist the shear forces created by blood flow and by collision with red and white blood cells.

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

    PubMed

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

    2015-12-01

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

  8. Systemic and Microvascular Effects of Resuscitation with Blood Products After Severe Hemorrhage in Rats

    DTIC Science & Technology

    2014-01-01

    thickness, blood flow, and microvascular permeability were studied using intravital microscopy. Hemodynamics and coagulation tests (rotational...Microcirculation; packed red blood cells; intravital microscopy; ROTEM; plasma proteins; rats. Current US military guidance for the resuscitation of warfighters...was used for coagulation assays (rotational thromboelast- ometry [ROTEM], TEM Innovations GmbH, Germany). Intravital Microscopy and Animal Preparation

  9. Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke

    PubMed Central

    Kampschulte, Marian; Hyvelin, Jean-Marc; Botteron, Catherine; Juenemann, Martin; Yeniguen, Mesut; Krombach, Gabriele A.; Kaps, Manfred; Spratt, Neil J.; Gerriets, Tibo; Nedelmann, Max

    2016-01-01

    Background Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model. Methods We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography. Results Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1). Conclusions Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory. PMID:27077372

  10. Human microvascular endothelial cells express receptors for platelet-derived growth factor

    SciTech Connect

    Beitz, J.G.; Kim, Insoon; Calabresi, P.; Frackelton, A.R. Jr. )

    1991-03-01

    Endothelial cells have been widely thought to be unresponsive to platelet-derived growth factor (PDGF, a major growth factor released from stimulated platelets at the sites of vascular insults) and devoid of PDGF receptors. Nevertheless, in examining the growth-factor responses of microvascular endothelial cells isolated from human omental adipose tissue, the authors were surprised to detect PDGF-induced tyrosine phosphorylation of a 180-kDa glycoprotein, subsequently identified as the cellular receptor for PDGF by specific immunoprecipitation. Scatchard analysis of {sup 125}I-labeled PDGF binding to human microvascular endothelial cells revealed 30,000 PDGF receptors per cell with a K{sub d} of 0.14 nM. Normal cellular consequences of receptor activation were also observed, including tyrosine phosphorylation of a 42-kDa protein and serine phosphorylation of ribosomal protein S6. Furthermore, PDGF was mitogenic for these cells. Microvascular endothelial cells play a central role in neovascularization required for wound healing and solid tumor growth. Thus, the discovery of functional PFDG receptors on human microvascular endothelial cells suggests a direct role for PDGF in this process.

  11. A one-dimensional mathematical model for studying the pulsatile flow in microvascular networks.

    PubMed

    Pan, Qing; Wang, Ruofan; Reglin, Bettina; Cai, Guolong; Yan, Jing; Pries, Axel R; Ning, Gangmin

    2014-01-01

    Techniques that model microvascular hemodynamics have been developed for decades. While the physiological significance of pressure pulsatility is acknowledged, most of the microcirculatory models use steady flow approaches. To theoretically study the extent and transmission of pulsatility in microcirculation, dynamic models need to be developed. In this paper, we present a one-dimensional model to describe the dynamic behavior of microvascular blood flow. The model is applied to a microvascular network from a rat mesentery. Intravital microscopy was used to record the morphology and flow velocities in individual vessel segments, and boundaries are defined according to the experimental data. The system of governing equations constituting the model is solved numerically using the discontinuous Galerkin method. An implicit integration scheme is adopted to increase computing efficiency. The model allows the simulation of the dynamic properties of blood flow in microcirculatory networks, including the pressure pulsatility (quantified by a pulsatility index) and pulse wave velocity (PWV). From the main input arteriole to the main output venule, the pulsatility index decreases by 66.7%. PWV obtained along arterioles declines with decreasing diameters, with mean values of 77.16, 25.31, and 8.30 cm/s for diameters of 26.84, 17.46, and 13.33 μm, respectively. These results suggest that the 1D model developed is able to simulate the characteristics of pressure pulsatility and wave propagation in complex microvascular networks.

  12. Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes

    PubMed Central

    Laughlin, M. Harold

    2015-01-01

    Type 2 diabetes (T2D) alters capillary hemodynamics, causes capillary rarefaction in skeletal muscle, and alters endothelial and vascular smooth muscle cell phenotype, resulting in impaired vasodilatory responses. These changes contribute to altered blood flow responses to physiological stimuli, such as exercise and insulin secretion. T2D-induced microvascular dysfunction impairs glucose and insulin delivery to skeletal muscle (and other tissues such as skin and nervous), thereby reducing glucose uptake and perpetuating hyperglycemia and hyperinsulinemia. In patients with T2D, exercise training (EX) improves microvascular vasodilator and insulin signaling and attenuates capillary rarefaction in skeletal muscle. EX-induced changes subsequently augment glucose and insulin delivery as well as glucose uptake. If these adaptions occur in a sufficient amount of tissue, and skeletal muscle in particular, chronic exposure to hyperglycemia and hyperinsulinemia and the risk of microvascular complications in all vascular beds will decrease. We postulate that EX programs that engage as much skeletal muscle mass as possible and recruit as many muscle fibers within each muscle as possible will generate the greatest improvements in microvascular function, providing that the duration of the stimulus is sufficient. Primary improvements in microvascular function occur in tissues (skeletal muscle primarily) engaged during exercise, and secondary improvements in microvascular function throughout the body may result from improved blood glucose control. We propose that the added benefit of combined resistance and aerobic EX programs and of vigorous intensity EX programs is not simply “more is better.” Rather, we believe the additional benefit is the result of EX-induced adaptations in and around more muscle fibers, resulting in more muscle mass and the associated microvasculature being changed. Thus, to acquire primary and secondary improvements in microvascular function and

  13. Early Systemic Microvascular Damage in Pigs with Atherogenic Diabetes Mellitus Coincides with Renal Angiopoietin Dysbalance

    PubMed Central

    Khairoun, Meriem; van den Heuvel, Mieke; van den Berg, Bernard M.; Sorop, Oana; de Boer, Rients; van Ditzhuijzen, Nienke S.; Bajema, Ingeborg M.; Baelde, Hans J.; Zandbergen, Malu; Duncker, Dirk J.; Rabelink, Ton J.; Reinders, Marlies E. J.; Rotmans, Joris I.

    2015-01-01

    Background Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage. Methods Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF). Results Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/ Angpt1balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05). Conclusion In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of systemic microvascular damage

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

    PubMed Central

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

    2016-01-01

    Background Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of “uremic microangiopathy”, we have measured microvascular density in biopsies of the omentum of children with CKD. Patients and Methods Omental tissue was collected from 32 healthy children (0–18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2. Results Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01). Conclusions Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished

  15. A review of the surgical management of breast cancer: plastic reconstructive techniques and timing implications.

    PubMed

    Rosson, Gedge D; Magarakis, Michael; Shridharani, Sachin M; Stapleton, Sahael M; Jacobs, Lisa K; Manahan, Michele A; Flores, Jaime I

    2010-07-01

    The oncologic management of breast cancer has evolved over the past several decades from radical mastectomy to modern-day preservation of chest and breast structures. The increased rate of mastectomies over recent years made breast reconstruction an integral part of the breast cancer management. Plastic surgery now offers patients a wide variety of reconstruction options from primary closure of the skin flaps to performance of microvascular and autologous tissue transplantation. Well-coordinated partnerships between surgical oncologists, plastic surgeons, and patients address concerns of tumor control, cosmesis, and patients' wishes. The gamut of breast reconstruction options is reviewed, particularly noting state-of-the-art techniques, as well as the advantages and disadvantages of various timing modalities.

  16. Microvascular response to transfusion in elective spine surgery

    PubMed Central

    Walz, J Matthias; Stundner, Ottokar; Girardi, Federico P; Barton, Bruce A; Koll-Desrosiers, Aimee R; Heard, Stephen O; Memtsoudis, Stavros G

    2017-01-01

    AIM To investigate the microvascular (skeletal muscle tissue oxygenation; SmO2) response to transfusion in patients undergoing elective complex spine surgery. METHODS After IRB approval and written informed consent, 20 patients aged 18 to 85 years of age undergoing > 3 level anterior and posterior spine fusion surgery were enrolled in the study. Patients were followed throughout the operative procedure, and for 12 h postoperatively. In addition to standard American Society of Anesthesiologists monitors, invasive measurements including central venous pressure, continual analysis of stroke volume (SV), cardiac output (CO), cardiac index (CI), and stroke volume variability (SVV) was performed. To measure skeletal muscle oxygen saturation (SmO2) during the study period, a non-invasive adhesive skin sensor based on Near Infrared Spectroscopy was placed over the deltoid muscle for continuous recording of optical spectra. All administration of fluids and blood products followed standard procedures at the Hospital for Special Surgery, without deviation from usual standards of care at the discretion of the Attending Anesthesiologist based on individual patient comorbidities, hemodynamic status, and laboratory data. Time stamps were collected for administration of colloids and blood products, to allow for analysis of SmO2 immediately before, during, and after administration of these fluids, and to allow for analysis of hemodynamic data around the same time points. Hemodynamic and oxygenation variables were collected continuously throughout the surgery, including heart rate, blood pressure, mean arterial pressure, SV, CO, CI, SVV, and SmO2. Bivariate analyses were conducted to examine the potential associations between the outcome of interest, SmO2, and each hemodynamic parameter measured using Pearson’s correlation coefficient, both for the overall cohort and within-patients individually. The association between receipt of packed red blood cells and SmO2 was performed by

  17. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

    SciTech Connect

    Kali, Avinash; Cokic, Ivan; Tang, Richard; Dohnalkova, Alice; Kovarik, Libor; Yang, Hsin-Jung; Kumar, Andreas; Prato, Frank S.; Wood, John C.; Underhill, David; Marbán, Eduardo; Dharmakumar, Rohan

    2016-11-01

    Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI to characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r

  18. Usefulness of retinal microvascular endothelial dysfunction as a predictor of coronary artery disease.

    PubMed

    Al-Fiadh, Ali H; Wong, Tien Y; Kawasaki, Ryo; Clark, David J; Patel, Sheila K; Freeman, Melanie; Wilson, Andrew; Burrell, Louise M; Farouque, Omar

    2015-03-01

    Endothelial dysfunction is a key feature of atherosclerosis. Retinal microvascular endothelial function can be assessed using noninvasive dynamic vessel imaging techniques. Whether it is impaired in subjects with coronary artery disease (CAD) is unknown. The aim of this study was to examine the relation of retinal microvascular endothelial function with CAD. Vascular studies were performed in 197 prospectively recruited subjects divided into 2 groups: those without CAD but ≥2 cardiovascular risk factors (non-CAD controls; n = 119) and those with stable CAD (n = 78). Retinal microvascular endothelial dysfunction was assessed by measuring retinal arteriolar and venular dilatation to flicker light, a nitric oxide-dependent phenomenon, expressed as percentage increase over baseline diameter. Fingertip pulse-volume amplitude was measured to calculate reactive hyperaemia index and brachial artery flow-mediated dilatation assessed as measures of peripheral microvascular and conduit vessel endothelial function, respectively. Mean retinal arteriolar dilatation was attenuated in patients with CAD compared with non-CAD controls (1.51 ± 1.51% vs 2.37 ± 1.95%, p = 0.001). Retinal arteriolar dilatation was independently associated with CAD after adjustment for age, gender, cardiovascular risk factors, and medication use (odds ratio 1.60, 95% confidence interval 1.14 to 2.25, p = 0.007). Reactive hyperaemia index and flow-mediated dilatation were not different. In conclusion, the capacity of retinal arterioles to dilate in response to flicker light is an independent predictor of the presence of CAD and suggests that retinal microvascular endothelial dysfunction is a marker for underlying CAD.

  19. Hyperosmolality-mediated peritoneal microvascular vasodilation is linked to aquaporin function.

    PubMed

    Zakaria, El Rasheid; Althani, Asma; Fawzi, Ashraf A; Fituri, Omar M

    2014-01-01

    Glucose-based peritoneal dialysis (PD) solutions dilate the parietal and visceral peritoneal microvasculature by endothelium-dependent mechanisms that primarily involve hyperosmolality. This PD-mediated dilation occurs by active intracellular glucose uptake and adenosine Al receptor activation, and by hyperosmolality-stimulated glibenclamide-sensitive potassium channels. Both pathways invoke NO as a second messenger for vasodilation. We hypothesized that during crystalloid-induced osmosis, the osmotic water flux through the transendothelial water-exclusive aquaporin 1 (AQP1) channels is the primary mechanism whereby the endothelium is being stimulated to instigate hyperosmolality-driven vasodilation. Four microvascular levels (diameters in the range 6 - 100 microm) were visualized by intravital videomicroscopy of the terminal ileum in anesthetized rats. Microvascular diameters and flow were measured after topical exposure to a 5% hypertonic mannitol or 2.5% glucose-based PD solution, at baseline and after brief tissue pre-treatment (with 0.1% glutaraldehyde for 10 seconds) or after combined tissue pre-treatment and pharmacologic blockade of AQP1 with HgCl2 (100 micromol/L). Vascular endothelial integrity was verified by the response to acetylcholine (10(-4) mol/L) and sodium nitroprusside (10(-4) mol/L). The hyperosmolar solutions both caused rapid and sustained vasodilation at all microvascular levels, which was not altered by tissue pre-treatment. Inhibition of AQP1 completely abolished the mannitol-induced vasodilation and markedly attenuated the PD fluid-mediated vasodilation. Neither glutaraldehyde pre-treatment nor HgCl2 affected tissue integrity or endothelial cell function. We conclude that the peritoneal microvascular vasodilation caused by hyperosmolar PD fluid is instigated by the osmotic water flux through AQP1. Clinical PD solutions have components other than hyperosmolality that can induce endothelium-dependent peritoneal microvascular vasodilation

  20. Effect of Overlapping Operations on Outcomes in Microvascular Reconstructions of the Head and Neck.

    PubMed

    Sweeny, Larissa; Rosenthal, Eben L; Light, Tyler; Grayson, Jessica; Petrisor, Daniel; Troob, Scott H; Greene, Benjamin J; Carroll, William R; Wax, Mark K

    2017-04-01

    Objective To compare outcomes after microvascular reconstructions of head and neck defects between overlapping and nonoverlapping operations. Study Design Retrospective cohort study. Setting Tertiary care center. Subjects and Methods Patients undergoing microvascular free tissue transfer operations between January 2010 and February 2015 at 2 tertiary care institutions were included (n = 1315). Patients were divided into 2 cohorts by whether the senior authors performed a single or consecutive microvascular reconstruction (nonoverlapping; n = 773, 59%) vs performing overlapping microvascular reconstructions (overlapping; n = 542, 41%). Variables reviewed were as follows: defect location, indication, T classification, surgical details, duration of the operation and hospitalization, and complications (major, minor, medical). Results Microvascular free tissue transfers performed included radial forearm (49%, n = 639), osteocutaneous radial forearm (14%, n = 182), anterior lateral thigh (12%, n = 153), fibula (10%, n = 135), rectus abdominis (7%, n = 92), latissimus dorsi (6%, n = 78), and scapula (<1%, n = 4). The mean duration of the overlapping operations was 21 minutes longer than nonoverlapping operations ( P = .003). Mean duration of hospitalization was similar for nonoverlapping (9.5 days) and overlapping (9.1 days) cohorts ( P = .39). There was no difference in complication rates when stratified by overlapping (45%, n = 241) and nonoverlapping (45%, n = 344) ( P = .99). Subset analysis yielded similar results when minor, major, and medical complications between groups were assessed. The overall survival rate of free tissue transfers was 96%, and this was same for overlapping (96%) and nonoverlapping (96%) operations ( P = .71). Conclusions Patients had similar complication rates and durations of hospitalization for overlapping and nonoverlapping operations.

  1. The plasticity of clays

    USGS Publications Warehouse

    Group, F.F.

    1905-01-01

    (1) Sand injures plasticity little at first because the grains are suspended in a plastic mass. It is only when grains are abundant enough to come in contact with their neighbors, that the effect becomes serious, and then both strength and amount of possible flow are injured. (2) Certain rare organic colloids increase the plasticity by rendering the water viscous. (3) Fineness also tends to increase plasticity. (4) Plane surfaces (plates) increase the amount of possible flow. They also give a chance for lubrication by thinner films, thus increasing the friction of film, and the strength of the whole mass. The action of plates is thus twofold ; but fineness may be carried to such an extent as to break up plate-like grains into angular fragments. The beneficial effects of plates are also decreased by the fact that each is so closely surrounded by others in the mass. (5) Molecular attraction is twofold in increasing plasticity. As the attraction increases, the coherence and strength of the mass increase, and the amount of possible deformation before crumbling also increases. Fineness increases this action by requiring more water. Colloids and crystalloids in solution may also increase the attraction. It is thus seen to be more active than any other single factor.

  2. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  3. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria.

    PubMed

    Barber, Bridget E; William, Timothy; Grigg, Matthew J; Parameswaran, Uma; Piera, Kim A; Price, Ric N; Yeo, Tsin W; Anstey, Nicholas M

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

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

    PubMed

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

    2015-09-01

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

  5. F8-SIP mediated targeted photodynamic therapy leads to microvascular dysfunction and reduced glioma growth.

    PubMed

    Acker, G; Palumbo, A; Neri, D; Vajkoczy, P; Czabanka, M

    2016-08-01

    The extra domain A (ED A) of fibronectin has been identified as a tumor vessel specific neovascular marker in glioma. Antibody based vascular targeting against ED A of fibronectin allows precise accumulation of photosensitizer in glioma microvasculature and thereby promises to overcome drawbacks of current photodynamic therapy (PDT) for glioma treatment. Our aim was to characterize microcirculatory consequences of F8-small immunoprotein (SIP) mediated PDT by intravital microscopy (IVM) and to analyze the effects on glioma growth. For IVM SF126 glioma cells were implanted into dorsal skinfold-chamber of nude mice. PDT was performed after intravenous injection of photosensitizer (PS)-coupled F8-SIP or PBS (n = 4). IVM was performed before and after PDT for 4 days. Analysis included total and functional (TVD, FVD) vessel densities, perfusion index (PI), microvascular permeability and blood flow rate (Q). To assess tumor growth SF126 glioma cells were implanted subcutaneously. PDT was performed as a single and repetitive treatment after PS-F8-SIP injection (n = 5). Subcutaneous tumors were treated after uncoupled F8-SIP injection as control group (n = 5). PDT induced microvascular stasis and thrombosis with reduced FVD (24 h: 115.98 ± 0.7 vs. 200.8 ± 61.9 cm/cm(2)) and PI (39 ± 11 vs. 70 ± 10 %), whereas TVD was not altered (298 ± 39.2 vs. 278.2 ± 51 cm/cm(2)). Microvascular dysfunction recovered 4 days after treatment. Microvascular dysfunction led to a temporary reduction of glioma growth in the first 48 h after treatment with complete recovery 5 days after treatment. Repetitive PDT resulted in sustained reduction of tumor growth. F8-SIP mediated PDT leads to microvascular dysfunction and reduced glioma growth in a preclinical glioma model with recovery of microcirculation 4 days after treatment. Repetitive application of PDT overcomes microvascular recovery and leads to prolonged antiglioma effects.

  6. Parasite Biomass-Related Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Vivax Malaria

    PubMed Central

    Barber, Bridget E.; William, Timothy; Grigg, Matthew J.; Parameswaran, Uma; Piera, Kim A.; Price, Ric N.; Yeo, Tsin W.; Anstey, Nicholas M.

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  7. Recurrent plastic bronchitis in a child with 2009 influenza A (H1N1) and influenza B virus infection.

    PubMed

    Kim, Sun; Cho, Hwa Jin; Han, Dong Kyun; Choi, Yoo Duk; Yang, Eun Seok; Cho, Young Kuk; Ma, Jae Sook

    2012-09-01

    Plastic bronchitis is an uncommon disorder characterized by the formation of bronchial casts. It is associated with congenital heart disease or pulmonary disease. In children with underlying conditions such as allergy or asthma, influenza can cause severe plastic bronchitis resulting in respiratory failure. A review of the literature showed nine cases of plastic bronchitis with H1N1 including this case. We report a case of a child with recurrent plastic bronchitis with eosinophilic cast associated with influenza B infection, who had recovered from plastic bronchitis associated with an influenza A (H1N1) virus infection 5 months previously. To the best of our knowledge, this is the first case of recurrent plastic bronchitis related to influenza viral infection. If patients with influenza virus infection manifest acute respiratory distress with total lung atelectasis, clinicians should consider plastic bronchitis and early bronchoscopy should be intervened. In addition, management for underlying disease may prevent from recurrence of plastic bronchitis.

  8. Plastics in Perspective.

    ERIC Educational Resources Information Center

    Bergandine, David R.; Holm, D. Andrew

    The materials in this curriculum supplement, developed for middle school or high school science classes, present solid waste problems related to plastics. The set of curriculum materials is divided into two units to be used together or independently. Unit I begins by comparing patterns in solid waste from 1960 to 1990 and introducing methods for…

  9. Hydrodynamic Elastic Magneto Plastic

    SciTech Connect

    Wilkins, M. L.; Levatin, J. A.

    1985-02-01

    The HEMP code solves the conservation equations of two-dimensional elastic-plastic flow, in plane x-y coordinates or in cylindrical symmetry around the x-axis. Provisions for calculation of fixed boundaries, free surfaces, pistons, and boundary slide planes have been included, along with other special conditions.

  10. Preserving in Plastic.

    ERIC Educational Resources Information Center

    Wahla, James

    1985-01-01

    Outlines steps for casting insects in permanent molds prepared from commercially available liquid plastic. Also describes dry mountings in glass, acrylic, and petri dishes. The rationale for specimen use, hints for producing quality results, purchasing information, and safety precautions are considered. (DH)

  11. Peoniflorin suppresses tumor necrosis factor-α induced chemokine production in human dermal microvascular endothelial cells by blocking nuclear factor-κB and ERK pathway.

    PubMed

    Chen, Tao; Guo, Zai-Pei; Jiao, Xiao-Yan; Jia, Rui-Zhen; Zhang, Yu-Hong; Li, Jing-Yi; Huang, Xu-Lei; Liu, Hong-Jie

    2011-07-01

    Peoniflorin (PF) extracted from the root of Paeonia lactiflora pall displays anti-inflammation and antioxidant properties in several animal models. Chemokines are vital for directing the movement of circulating leukocytes to the sites of inflammation and are involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated the effects and potential mechanisms of PF on tumor necrosis factor-α (TNF-α) induced chemokine production in human dermal microvascular endothelial cells. Human dermal microvascular endothelial cell line (HMEC-1) was treated by TNF-α with or without PF. PF markedly attenuated TNF-α-induced chemokines (including CCL2, CCL5, CCL20, CXCL8, CXCL16 and CX3CL1) mRNA expression in HMEC-1. PF also reduced the secretion of these chemokines in culture supernatants. In addition, endothelial activation in the presence of PF markedly blocked the chemotactic activities of TNF-α-stimulated HMEC-1 supernatant on promyelocytic leukemia cell line (HL-60) or the acute mature monocytic leukemia cell line (THP-1) cell migration. Furthermore, Western blot data revealed TNF-α upregulated phosphorylation of inhibitor of κB-α (IκBα) and phosphorylation of extracellular signal-regulated kinase (ERK)1/2, which was almost completely reversed by PF. Finally, PF inhibited nuclear factor-κB (NF-κB) nuclear translocation to the nucleus. Taken together, our data provide the first evidence that PF has an anti-inflammatory ability against TNF-α-induced chemokine production and leukocyte migration, which may be at least partly related to the inhibition of NF-κB and ERK pathway. PF may be a candidate medicine for the treatment of inflammatory skin diseases.

  12. Histochemical analyses and quantum dot imaging of microvascular blood flow with pulmonary edema in living mouse lungs by "in vivo cryotechnique".

    PubMed

    Saitoh, Yurika; Terada, Nobuo; Saitoh, Sei; Ohno, Nobuhiko; Jin, Takashi; Ohno, Shinichi

    2012-02-01

    Light microscopic imaging of blood vessels and distribution of serum proteins is essential to analyze hemodynamics in living animal lungs under normal respiration or respiratory diseases. In this study, to demonstrate dynamically changing morphology and immunohistochemical images of their living states, "in vivo cryotechnique" (IVCT) combined with freeze-substitution fixation was applied to anesthetized mouse lungs. By hematoxylin-eosin staining, morphological features, such as shapes of alveolar septum and sizes of alveolar lumen, reflected their respiratory conditions in vivo, and alveolar capillaries were filled with variously shaped erythrocytes. Albumin was usually immunolocalized in the capillaries, which was confirmed by double-immunostaining for aquaporin-1 of endothelium. To capture accurate time-courses of blood flow in peripheral pulmonary alveoli, glutathione-coated quantum dots (QDs) were injected into right ventricles, and then IVCT was performed at different time-points after the QD injection. QDs were localized in most arterioles and some alveolar capillaries at 1 s, and later in venules at 2 s, reflecting a typical blood flow direction in vivo. Three-dimensional QD images of microvascular networks were reconstructed by confocal laser scanning microscopy. It was also applied to lungs of acute pulmonary hypertension mouse model. Erythrocytes were crammed in blood vessels, and some serum components leaked into alveolar lumens, as confirmed by mouse albumin immunostaining. Some separated collagen fibers and connecting elastic fibers were still detected in edematous tunica adventitia near terminal bronchioles. Thus, IVCT combined with histochemical approaches enabled us to capture native images of dynamically changing structures and microvascular hemodynamics of living mouse lungs.

  13. Toxicity of leachate from weathering plastics: An exploratory screening study with Nitocra spinipes.

    PubMed

    Bejgarn, Sofia; MacLeod, Matthew; Bogdal, Christian; Breitholtz, Magnus

    2015-08-01

    Between 60% and 80% of all marine litter is plastic. Leachate from plastics has previously been shown to cause acute toxicity in the freshwater species Daphnia magna. Here, we present an initial screening of the marine environmental hazard properties of leachates from weathering plastics to the marine harpacticoid copepod [Crustacea] Nitocra spinipes. Twenty-one plastic products made of different polymeric materials were leached and irradiated with artificial sunlight. Eight of the twenty-one plastics (38%) produced leachates that caused acute toxicity. Differences in toxicity were seen for different plastic products, and depending on the duration of irradiation. There was no consistent trend in how toxicity of leachate from plastics changed as a function of irradiation time. Leachate from four plastics became significantly more toxic after irradiation, two became significantly less toxic and two did not change significantly. Analysis of leachates from polyvinyl chloride (PVC) by liquid chromatography coupled to a full-scan high-resolution mass spectrometer showed that the leachates were a mixture of substances, but did not show evidence of degradation of the polymer backbone. This screening study demonstrates that leachates from different plastics differ in toxicity to N. spinipes and that the toxicity varies under simulated weathering.

  14. Plastics (Environmental Health Student Portal)

    MedlinePlus

    ... Pollutants Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Videos Games Experiments For Teachers Home ... Pollutants Natural Disasters Drinking Water Waterborne Diseases & Illnesses Water Cycle Water Treatment Plastics The Basics Plastics play a ...

  15. Adult cortical plasticity following injury: Recapitulation of critical period mechanisms?

    PubMed Central

    Nahmani, Marc; Turrigiano, Gina G.

    2014-01-01

    A primary goal of research on developmental critical periods is the recapitulation of a juvenile-like state of malleability in the adult brain that might enable recovery from injury. These ambitions are often framed in terms of the simple reinstatement of enhanced plasticity in the growth-restricted milieu of an injured adult brain. Here, we provide an analysis of the similarities and differences between deprivation-induced and injury-induced cortical plasticity, to provide for a nuanced comparison of these remarkably similar processes. As a first step, we review the factors that drive ocular dominance plasticity in the primary visual cortex of the uninjured brain during the critical period (CP) and in adults, to highlight processes that might confer adaptive advantage. In addition, we directly compare deprivation-induced cortical plasticity during the CP and plasticity following acute injury or ischemia in mature brain. We find that these two processes display a biphasic response profile following deprivation or injury: an initial decrease in GABAergic inhibition and synapse loss transitions into a period of neurite expansion and synaptic gain. This biphasic response profile emphasizes the transition from a period of cortical healing to one of reconnection and recovery of function. Yet while injury-induced plasticity in adult shares several salient characteristics with deprivation-induced plasticity during the CP, the degree to which the adult injured brain is able to functionally rewire, and the time required to do so, present major limitations for recovery. Attempts to recapitulate a measure of CP plasticity in an adult injury context will need to carefully dissect the circuit alterations and plasticity mechanisms involved while measuring functional behavioral output to assess their ultimate success. PMID:24791715

  16. Plastics Pollution Control Technology Research

    DTIC Science & Technology

    1992-01-01

    various machines, the plastics processor, the pulper, and the compactor, being developed to address the plastics problem firsthand. The Dialogue...incinerators themselves may not be a part of the Navy’s solution to the plastics problem , the space that the incinerators occupy will be useful. It is the... plastics problem although they believe that the Navy will not be in compliance by 1993. They suggested that a change in the law which will allow them to keep

  17. Reducing Navy Marine Plastic Pollution

    DTIC Science & Technology

    1988-06-28

    pollution. Plastic debris from ships is littering beaches, and killing and debilitating fish and wildlife because they are ingesting plastic , or because...they are becoming entangled in plastic debris . While no one is purposefully causing these impacts, the effects are becoming more pronounced. In the...generate support for shipboard and service-wide activities. The recommendations in this section call for disseminating information about the plastic debris

  18. Induction of Brain Microvascular Endothelial Cell Urokinase Expression by Cryptococcus neoformans Facilitates Blood-Brain Barrier Invasion

    PubMed Central

    Stie, Jamal; Fox, Deborah

    2012-01-01

    The invasive ability of the blood-borne fungal pathogen Cryptococcus neoformans can be enhanced through interactions with host plasma components, such as plasminogen. Previously we showed by in vitro studies that plasminogen coats the surface of C. neoformans and is converted to the active serine protease, plasmin, by host plasminogen activators. Viable, but not formaldehyde- or sodium azide-killed, cryptococcal strains undergo brain microvascular endothelial cell-dependent plasminogen-to-plasmin activation, which results in enhanced, plasmin-dependent cryptococcal invasion of primary bovine brain microvascular endothelial cells and fungal ability to degrade plasmin substrates. In the present work, brain microvascular endothelial cells cultured with viable, but not killed, cryptococcal strains led to significant increases in both urokinase mRNA transcription and cell-associated urokinase protein expression. Soluble urokinase was also detected in conditioned medium from brain microvascular endothelial cells cultured with viable, but not killed, C. neoformans. Exposure of plasminogen pre-coated viable C. neoformans to conditioned medium from strain-matched brain microvascular endothelial cell-fungal co-cultures resulted in plasminogen-to-plasmin activation and plasmin-dependent cryptococcal invasion. siRNA-mediated silencing of urokinase gene expression or the use of specific inhibitors of urokinase activity abrogated both plasminogen-to-plasmin activation on C. neoformans and cryptococcal-brain microvascular endothelial cell invasion. Our results suggest that pathogen exploitation of the host urokinase-plasmin(ogen) system may contribute to C. neoformans virulence during invasive cryptococcosis. PMID:23145170

  19. Characterizing nanoscale changes in the activity of VEGFR-2 on glioma microvascular endothelial cell membranes using atomic force microscopy

    PubMed Central

    Zhou, Dexiang; Zhan, Shengquan; Zhou, Dong; Wang, Peng; Chen, Guangzhong; Qin, Kun; Lin, Xiaofeng

    2017-01-01

    The aim of the current study was to demonstrate the distribution of VEGFR-2 on glioma microvascular endothelial cells on a nanoscale and investigate changes in VEGFR-2 activity following treatment with the VEGFR-2 inhibitor and agonist sorafenib and bradykinin, respectively. Three groups were evaluated in this study: Control glioma microvascular endothelial cells, sorafenib-treated glioma microvascular endothelial cells and bradykinin-treated glioma microvascular endothelial cells. Changes in the activity of VEGFR-2 on the glioma microvascular endothelial cell membranes following treatment with sorafenib and bradykinin were characterized by atomic force microscopy (AFM). Colloidal gold-labeled immune complexes and AFM were used to visualize the distribution of VEGFR-2 on the cell membranes. In the control group, VEGFR-2, which was observed as numerous globular structures, was evenly distributed on the cell surface membranes. The majority of the receptors were active. In the sorafenib group, only a few globular structures were observed on the cell membranes, with a density significantly lower than that in the control group (P<0.01). Furthermore, compared with the control group, fewer of the receptors were active. In the bradykinin group, numerous globular structures were densely distributed on the cell membranes, with a density significantly higher than that in the control group (P<0.01). The distribution and activity of VEGFR-2 on glioma microvascular endothelial cell membranes treated with sorafenib and bradykinin suggested that the activity of VEGFR-2 could be regulated by its inhibitor or agonist. PMID:28352319

  20. Plastics for Elementary School Children

    ERIC Educational Resources Information Center

    Hanson, Jack

    1977-01-01

    Describes three plastics projects (which involve making a styrene fishing bobber, an acrylic salad fork and spoon set, and acetate shrink art) designed to provide elementary level students an opportunity to work with plastics and to learn about careers in plastics production and distribution. (TA)

  1. Venlafaxine protects methylglyoxal-induced apoptosis in the cultured human brain microvascular endothelial cells.

    PubMed

    Lv, Qinghua; Gu, Chengyao; Chen, Caijing

    2014-05-21

    It was reported that venlafaxine protects microvascular endothelial cells injury in several models. But the mechanisms of venlafaxine protects cell injury still poor understanding. Here, we shows that in the cultured human brain microvascular endothelial cells (HBMEC), we found that venlafaxine protects methylglyoxal (MGO)-induced cell injury, and the venlafaxine significant reduction in the level of reactive oxygen species, down-regulated expression of pro-apoptotic activated caspase-3 and Bax, increased BDNF release and expression of anti-apoptotic Bcl-2 in the cultured HBMEC. Furthermore, we found that venlafaxine inhibits MGO-induced phosphorylation of JNK. Moreover, venlafaxine increased AKT phosphorylation and the protective effects of venlafaxine was inhibited by PI3K/AKT inhibitor. These findings suggest that venlafaxine protects MGO-induced HBMEC injury through PI3K/AKT and JNK pathway as the potential underlying mechanisms of HBMEC injury in diabetes.

  2. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications

    PubMed Central

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

    2016-01-01

    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. PMID:27141997

  3. Emerging therapeutic strategies to prevent infection-related microvascular endothelial activation and dysfunction

    PubMed Central

    Darwish, Ilyse; Liles, W Conrad

    2013-01-01

    Recent evidence suggests that loss of endothelial barrier function and resulting microvascular leak play important mechanistic roles in the pathogenesis of infection-related end-organ dysfunction and failure. Several distinct therapeutic strategies, designed to prevent or limit infection-related microvascular endothelial activation and permeability, thereby mitigating end-organ injury/dysfunction, have recently been investigated in pre-clinical models. In this review, these potential therapeutic strategies, namely, VEGFR2/Src antagonists, sphingosine-1-phosphate agonists, fibrinopeptide Bβ15–42, slit2N, secinH3, angiopoietin-1/tie-2 agonists, angiopoietin-2 antagonists, statins, atrial natriuretic peptide, and mesenchymal stromal (stem) cells, are discussed in terms of their translational potential for the management of clinical infectious diseases. PMID:23863603

  4. The effect of moesin overexpression on ageing of human dermal microvascular endothelial cells.

    PubMed

    Lee, Ju Hee; Hong, In Ae; Oh, Sang Ho; Kwon, Yeon Sook; Cho, Soo Hyun; Lee, Kwang Hoon

    2009-11-01

    Senescence of microvascular endothelial cells is known to play an important role in the pathophysiology of vascular diseases related to ageing, but the accurate mechanism or related genes are not known. Moesin, a cytoskeletal protein and the most potent candidate as an ageing-related protein, showed obvious changes in expression when compared before and after ageing. In this study, a lentivirus was used to overexpress moesin in endothelial cells. The expression of cell cycle mediators such as p16, cyclin D1 and cdk4, which can be the markers of ageing, was compared by RNA and was shown to be suppressed in moesin overexpressed endothelial cells. In conclusion, it can be said that the expression of moesin delays senescence of human dermal microvascular endothelial cells and this fundamental discovery can be used as a basis for understanding the mechanism of ageing and age-related diseases.

  5. Capsule independent uptake of the fungal pathogen Cryptococcus neoformans into brain microvascular endothelial cells.

    PubMed

    Sabiiti, Wilber; May, Robin C

    2012-01-01

    Cryptococcosis is a life-threatening fungal disease with a high rate of mortality among HIV/AIDS patients across the world. The ability to penetrate the blood-brain barrier (BBB) is central to the pathogenesis of cryptococcosis, but the way in which this occurs remains unclear. Here we use both mouse and human brain derived endothelial cells (bEnd3 and hCMEC/D3) to accurately quantify fungal uptake and survival within brain endothelial cells. Our data indicate that the adherence and internalisation of cryptococci by brain microvascular endothelial cells is an infrequent event involving small numbers of cryptococcal yeast cells. Interestingly, this process requires neither active signalling from the fungus nor the presence of the fungal capsule. Thus entry into brain microvascular endothelial cells is most likely a passive event that occurs following 'trapping' within capillary beds of the BBB.

  6. Metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline

    PubMed Central

    Wang, Maggie; Norman, Jennifer E; Srinivasan, Vivek J; Rutledge, John C

    2016-01-01

    White Matter Disease is increasingly being recognized as an important cause of cognitive decline and dementia. Various investigations have linked chronic diet-related conditions to the development of white matter lesions, which appear as white matter hyperintensities on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Thus, it can be postulated that the metabolic, inflammatory, and microvascular changes accompanying a western diet, hyperlipidemia, hypertension, and diabetes mellitus type II (DMII) are potential mediators in the development and progression of white matter disease, which in turn contributes to the development and progression of cognitive decline. This review will examine evidence for potential metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Specifically, we will focus on the effects of altered insulin signaling in diabetes, obesity-induced oxidative stress, neuroinflammation, arterial stiffness due to hypertension, ischemia secondary to cerebral small vessel disease, and blood brain barrier disturbances. PMID:28078193

  7. Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol.

    PubMed

    Joshi, Mandar S; Williams, David; Horlock, Duncan; Samarasinghe, Thilini; Andrews, Karen L; Jefferis, Ann-Maree; Berger, Philip J; Chin-Dusting, Jaye P; Kaye, David M

    2015-05-01

    Microvascular complications are now recognized to play a major role in diabetic complications, and understanding the mechanisms is critical. Endothelial dysfunction occurs early in the course of the development of complications; the precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur in a diabetic rat heart and may act as a source of the oxidative stress. However, the role of endothelial cell-specific mitochondrial dysfunction in diabetic vascular complications is poorly studied. Here, we studied the role of diabetes-induced abnormal endothelial mitochondrial function and the resultant endothelial dysfunction. Understanding the role of endothelial mitochondrial dysfunction in diabetic vasculature is critical in order to develop new therapies. We demonstrate that hyperglycaemia leads to mitochondrial dysfunction in microvascular endothelial cells, and that mitochondrial inhibition induces endothelial dysfunction. Additionally, we show that resveratrol acts as a protective agent; resveratrol-mediated mitochondrial protection may be used to prevent long-term diabetic cardiovascular complications.

  8. Imaging Microvascular Dysfunction and Mechanisms for Female-Male Differences in CAD.

    PubMed

    Patel, Monica B; Bui, Linh P; Kirkeeide, Richard L; Gould, K Lance

    2016-04-01

    Microvascular dysfunction or disease is most commonly associated with diffuse epicardial coronary atherosclerosis and endothelial dysfunction, whereas it is less common as a distinct, separate, isolated pathophysiology. The different manifestations of coronary artery disease in women relate in part to their smaller coronary arteries, higher coronary blood flow, and higher endothelial shear stress, which have profound effects on endothelial function and development or resistance to atherosclerosis, its symptomatic presentation, outcomes, and treatment. The complex interactions of focal stenosis, diffuse epicardial atherosclerotic coronary narrowing, and microvascular dysfunction make definitive diagnosis and management difficult by use of standard noninvasive and invasive physiological and anatomic technologies. However, quantitative rest-stress myocardial perfusion, best documented by positron emission tomography, combined with clinical circumstances usually provides a definitive diagnosis to guide management, including vigorous risk factor management and revascularization for patients with physiologically severe epicardial stenosis by quantitative positron emission tomography.

  9. Speckle-correlation monitoring of the internal micro-vascular flow

    NASA Astrophysics Data System (ADS)

    Zimnyakov, D. A.; Khmara, M. B.; Vilensky, M. A.; Kozlov, V. V.; Gorfinkel, I. V.; Zdrajevsky, R. A.

    2009-10-01

    The results of experimental study of possibility to monitor the micro-vascular blood flow in superficial tissues of various organs with the use of endoscope-based full-field speckle correlometer are presented. The blood microcirculation monitoring was carried out in the course of the laparotomy of abdominal cavity of laboratory animals (rats). Transfer of laser light to the area of interest and scattered radiation from the probed zone to the detector (CMOS camera) was carried out via fiber-optic bundles of endoscopic system. Microscopic hemodynamics was analyzed for small intestine, liver, spleen, kidney, and pancreas under different conditions (normal state, provocated peritonitis and ischemia, administration of vasodilative agents such as papaverine, lidocaine). The prospects and problems of internal monitoring of microvascular flow in laboratory and clinical conditions are discussed.

  10. Compliance of laser-assisted microvascular anastomosis: a comparative study with manual anastomosis (preliminary results)

    NASA Astrophysics Data System (ADS)

    Demaria, Roland G.; Lhote, Francois-Marie; Dauzat, Michel; Juan, Jean-Marie; Oliva-Lauraire, Marie-Claire; Durrleman, Nicolas; Delacretaz, Guy P.; Albat, Bernard; Frapier, Jean-Marc; Chaptal, Paul-Andre; Godlewski, Guilhem

    1999-01-01

    The compliance of microvascular anastomosis is an important predictive factor for long term patency of graft or vascular reconstruction. This experimental study compare the compliance of manual suture and laser assisted end to end microvascular anastomosis. In nine New-Zealand white rabbits we performed manual end-to-end suture anastomosis on the left femoral artery and laser assisted anastomosis on the right femoral artery, with a diode laser (wavelength 988 nm, power output 500 mW). Compliance was obtained by echotracking (CBI 8000 sonomicrometry system with 20 MHz implantable microprobe from Crystal-Biotech, USA) on the anastomosis site as well as upstream, and downstream from the anastomosis. Vessel compliance was lower on the manual suture side compared to the laser assisted anastomosis side, especially downstream from the anastomosis.

  11. A three-dimensional microvascular gas exchange unit for carbon dioxide capture.

    PubMed

    Nguyen, Du T; Leho, Y T; Esser-Kahn, Aaron P

    2012-04-07

    For the capture of CO(2) from mixed gas streams, materials for increased gas exchange are necessary. Efficient gas exchange systems already exist in the form of vascularized lung-tissue. Herein we report a fabrication technique for the synthesis of three-dimensional microvascular gas exchange units capable of removing CO(2) from flowing gas created using the recently reported Vaporization of a Sacrificial Component (VaSC) technique. We demonstrate the spatiotemporal pattern of CO(2) reactivity in the microvascular gas exchange unit using colorimetric, pH sensitive dyes. Control over three-dimensional placement of channels is shown to increase capture efficiencies. A computational finite element model validates and explains the experimental observations.

  12. [Successful microvascular decompression of the medulla oblongata for a case with respiratory failure: case report].

    PubMed

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

    2011-11-01

    We report a case of the medulla oblongata syndrome successfully treated by microvascular decompression surgery. The patient was a 75-year-old woman and had been suffering from gradual progressive dyspnea since July, 2009. Two month later, intubation and medial ventilator treatments were began because of severe respiratory problems. The central respiratory problems were considered in extensive testing by the physician. The head MR imaging showed that the left vertebral artery had markedly compressed the medulla oblongata. We thought that her respiratory problems were associated with this vertebral artery compression of the medulla oblongata. We performed the microvascular decompression surgery by left trans-condylar fossa approach. Her hypoventilation graduately improved after the surgery and she needed neither ventilator nor oxygen in several months. She is able to perform daily activities by herself. We report the case, and discuss the cause of respiratory problems especially by compression of the medulla oblongata.

  13. Transcriptional network analysis for the regulation of left ventricular hypertrophy and microvascular remodeling.

    PubMed

    Moreno-Moral, Aida; Mancini, Massimiliano; D'Amati, Giulia; Camici, Paolo; Petretto, Enrico

    2013-12-01

    Hypertension and cardiomyopathies share maladaptive changes of cardiac morphology, eventually leading to heart failure. These include left ventricular hypertrophy (LVH), myocardial fibrosis, and structural remodeling of coronary microcirculation, which is the morphologic hallmark of coronary microvascular dysfunction. To pinpoint the complex molecular mechanisms and pathways underlying LVH-associated cardiac remodeling independent of blood pressure effects, we employed gene network approaches to the rat heart. We used the Spontaneously Hypertensive Rat model showing many features of human hypertensive cardiomyopathy, for which we collected histological and histomorphometric data of the heart and coronary vasculature, and genome-wide cardiac gene expression. Here, we provide a large catalogue of gene co-expression networks in the heart that are significantly associated with quantitative variation in LVH, microvascular remodeling, and fibrosis-related traits. Many of these networks were significantly conserved to human idiopathic and/or ischemic cardiomyopathy patients, suggesting a potential role for these co-expressed genes in human heart disease.

  14. A QSPR for the plasticization efficiency of polyvinylchloride plasticizers.

    PubMed

    Chandola, Mridula; Marathe, Sujata

    2008-01-01

    A simple quantitative structure property relationship (QSPR) for correlating the plasticization efficiency of 25 polyvinylchloride (PVC) plasticizers was obtained using molecular modeling. The plasticizers studied were-aromatic esters (phthalate, terephthalate, benzoate, trimellitate), aliphatic esters (adipate, sebacate, azelate), citrates and a phosphate. The low temperature flex point, Tf, of plasticized polyvinylchloride resins was considered as an indicator of plasticization efficiency. Initially, we attempted to predict plasticization efficiency of PVC plasticizers from physical and structural descriptors derived from the plasticizer molecule alone. However, the correlation of these descriptors with Tf was not very good with R=0.78 and r2=0.613. This implied that the selected descriptors were unable to predict all the interactions between PVC and plasticizer. Hence, to account for these interactions, a model containing two polyvinylchloride (PVC) chain segments along with a plasticizer molecule in a simulation box was constructed, using molecular mechanics. A good QSPR equation correlating physical and structural descriptors derived from the model to Tf of the plasticized resins was obtained with R=0.954 and r2=0.909.

  15. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    PubMed

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p < .001) and VEGF expression (r = .35, p < .001). For the prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  16. Intravenous and Gastric Cerium Dioxide Nanoparticle Exposure Disrupts Microvascular Smooth Muscle Signaling

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Fix, Natalie R.; Leonard, Stephen S.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    Cerium dioxide nanoparticles (CeO2 NP) hold great therapeutic potential, but the in vivo effects of non-pulmonary exposure routes are unclear. The first aim was to determine whether microvascular function is impaired after intravenous and gastric CeO2 NP exposure. The second aim was to investigate the mechanism(s) of action underlying microvascular dysfunction following CeO2 NP exposure. Rats were exposed to CeO2 NP (primary diameter: 4 ± 1 nm, surface area: 81.36 m2/g) by intratracheal instillation, intravenous injection, or gastric gavage. Mesenteric arterioles were harvested 24 h post-exposure and vascular function was assessed using an isolated arteriole preparation. Endothelium-dependent and independent function and vascular smooth muscle (VSM) signaling (soluble guanylyl cyclase [sGC] and cyclic guanosine monophosphate [cGMP]) were assessed. Reactive oxygen species (ROS) generation and nitric oxide (NO) production were analyzed. Compared with controls, endothelium-dependent and independent dilation were impaired following intravenous injection (by 61% and 45%) and gastric gavage (by 63% and 49%). However, intravenous injection resulted in greater microvascular impairment (16% and 35%) compared with gastric gavage at an identical dose (100 µg). Furthermore, sGC activation and cGMP responsiveness were impaired following pulmonary, intravenous, and gastric CeO2 NP treatment. Finally, nanoparticle exposure resulted in route-dependent, increased ROS generation and decreased NO production. These results indicate that CeO2 NP exposure route differentially impairs microvascular function, which may be mechanistically linked to decreased NO production and subsequent VSM signaling. Fully understanding the mechanisms behind CeO2 NP in vivo effects is a critical step in the continued therapeutic development of this nanoparticle. PMID:25481005

  17. Molecular and Cellular Basis of Microvascular Perfusion Deficits Induced by Clostridium perfringens and Clostridium septicum

    PubMed Central

    Hickey, Michael J.; Kwan, Rain Y. Q.; Awad, Milena M.; Kennedy, Catherine L.; Young, Lauren F.; Hall, Pam; Cordner, Leanne M.; Lyras, Dena; Emmins, John J.; Rood, Julian I.

    2008-01-01

    Reduced tissue perfusion leading to tissue ischemia is a central component of the pathogenesis of myonecrosis caused by Clostridium perfringens. The C. perfringens α-toxin has been shown capable of inducing these changes, but its potential synergy with perfringolysin O (θ-toxin) is less well understood. Similarly, Clostridium septicum is a highly virulent causative agent of spontaneous gas gangrene, but its effect on the microcirculation has not been examined. Therefore, the aim of this study was to use intravital microscopy to examine the effects of C. perfringens and C. septicum on the functional microcirculation, coupled with the use of isogenic toxin mutants to elucidate the role of particular toxins in the resultant microvascular perfusion deficits. This study represents the first time this integrated approach has been used in the analysis of the pathological response to clostridial toxins. Culture supernatants from wild-type C. perfringens induced extensive cell death within 30 min, as assessed by in vivo uptake of propidium iodide. Furthermore, significant reductions in capillary perfusion were observed within 60 min. Depletion of either platelets or neutrophils reduced the alteration in perfusion, consistent with a role for these blood-borne cells in obstructing perfusion. In addition, mutation of either the α-toxin or perfringolysin O structural genes attenuated the reduction in perfusion, a process that was reversed by genetic complementation. C. septicum also induced a marked reduction in perfusion, with the degree of microvascular compromise correlating with the level of the C. septicum α-toxin. Together, these data indicate that as a result of its ability to produce α-toxin and perfringolysin O, C. perfringens rapidly induces irreversible cellular injury and a marked reduction in microvascular perfusion. Since C. septicum induces a similar reduction in microvascular perfusion, it is postulated that this function is central to the pathogenesis of

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

    PubMed

    Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

    2016-04-15

    Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts.

  19. Anemia and Microvascular Complications in Patients With Type 2 Diabetes Mellitus

    PubMed Central

    Hosseini, Mahboobeh Sadat; Rostami, Zohreh; Saadat, Alireza; Saadatmand, Sayyed Mehdi; Naeimi, Effat

    2014-01-01

    Background: Although chronic kidney disease-induced anemia is more prevalent in patients with diabetes mellitus (DM), anemia is a common finding prior to manifestation of kidney disease. In presence of some risk factors at the time of diagnosing DM, microvascular complications must be considered. The effect of anemia as a risk factor on progression of DM complications is still unclear. Objectives: The aim of the study was to determine the prevalence of anemia and its association with microvascular complications in patients with type 2 DM. Patients and Methods: This cross-sectional study was performed in the outpatient endocrinology clinic at Baqiyatallah University of Medical Sciences Hospital, Tehran, Iran. Study was done from February 2011 to February 2012. Patients with type 2 DM without any obvious symptom or sign of anemia were included in study. Results: A total of 93 patients (30.4%) had anemia including 46 (15.1%) with normochromic normocytic, 44 (14.4%) with hyperchromic microcytic, and 3 (1%) with hyperchromic macrocytic anemias. There was a positive correlation between duration of DM and anemia. Microvascular complications were more frequent with normocytic or microcytic anemias. Glomerular filtration rate (GFR) was higher in patients without anemia; moreover, nephropathy was less frequent among them. Among patients with anemia, 43% had GFR of more than 90 mL/min and 19.4% had normoalbuminuria. Neuropathy, nephropathy, and retinopathy had strong association with anemia (odds ratio of 1.99, 1.7, and 1.5, respectively). Conclusions: Anemia is a common complication of DM and is associated with duration of disease and microvascular complications. PMID:25695026

  20. Intravenous and gastric cerium dioxide nanoparticle exposure disrupts microvascular smooth muscle signaling.

    PubMed

    Minarchick, Valerie C; Stapleton, Phoebe A; Fix, Natalie R; Leonard, Stephen S; Sabolsky, Edward M; Nurkiewicz, Timothy R

    2015-03-01

    Cerium dioxide nanoparticles (CeO2 NP) hold great therapeutic potential, but the in vivo effects of non-pulmonary exposure routes are unclear. The first aim was to determine whether microvascular function is impaired after intravenous and gastric CeO2 NP exposure. The second aim was to investigate the mechanism(s) of action underlying microvascular dysfunction following CeO2 NP exposure. Rats were exposed to CeO2 NP (primary diameter: 4 ± 1 nm, surface area: 81.36 m(2)/g) by intratracheal instillation, intravenous injection, or gastric gavage. Mesenteric arterioles were harvested 24 h post-exposure and vascular function was assessed using an isolated arteriole preparation. Endothelium-dependent and independent function and vascular smooth muscle (VSM) signaling (soluble guanylyl cyclase [sGC] and cyclic guanosine monophosphate [cGMP]) were assessed. Reactive oxygen species (ROS) generation and nitric oxide (NO) production were analyzed. Compared with controls, endothelium-dependent and independent dilation were impaired following intravenous injection (by 61% and 45%) and gastric gavage (by 63% and 49%). However, intravenous injection resulted in greater microvascular impairment (16% and 35%) compared with gastric gavage at an identical dose (100 µg). Furthermore, sGC activation and cGMP responsiveness were impaired following pulmonary, intravenous, and gastric CeO2 NP treatment. Finally, nanoparticle exposure resulted in route-dependent, increased ROS generation and decreased NO production. These results indicate that CeO2 NP exposure route differentially impairs microvascular function, which may be mechanistically linked to decreased NO production and subsequent VSM signaling. Fully understanding the mechanisms behind CeO2 NP in vivo effects is a critical step in the continued therapeutic development of this nanoparticle.

  1. Evidence that reduced nitric oxide signal contributes to cutaneous microvascular dysfunction in peripheral arterial disease.

    PubMed

    Hodges, Gary J; Nawaz, Shah; Tew, Garry A

    2015-01-01

    Peripheral arterial disease (PAD) is associated with cutaneous microvascular dysfunction and an increased risk of arterial ulceration in the affected lower-limb(s). The purpose of this study was to investigate the role of nitric oxide (NO) in cutaneous microvascular dysfunction in patients with PAD. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in 5 patients with unilateral symptomatic PAD and 10 age-matched healthy controls at baseline and during 40 min of local skin heating to 42°C at 1) untreated lower-leg sites, and 2) lower-leg sites treated with 20 mM N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase activity. SkBF was expressed as laser-Doppler flux (LDF) and normalized to maximal LDF (%LDF(max)) achieved through localized heating to 44°C and concomitant infusion of 56 mM sodium nitroprusside. Pharmacological agents and control treatments (lactated Ringer's) were administered using intradermal microdialysis. The plateau LDF response to local skin warming at the untreated skin sites was significantly (P<0.05) lower in the diseased limb of the PAD patients (70.3±13.6 %max) compared to the non-diseased contralateral limb (85.0±10.2 %max) and the response observed for the control participants (89.0±5.2 %max). The NO contribution to the plateau SkBF response tended to be lower in the diseased limb of the PAD patients (45.1±16.4% versus 56.1±10.7% [P=0.12] and 55.4±11.5% [P=0.13], respectively). The results suggest that PAD impairs downstream cutaneous microvascular vasodilatory function and that the microvascular dysfunction is probably explained, at least in part, by a reduced NO signal.

  2. Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells.

    PubMed

    Huang, Minghai; Wang, Bowen; Wan, Pengxia; Liang, Xuanwei; Wang, Xiaoran; Liu, Ying; Zhou, Qiang; Wang, Zhichong

    2015-02-01

    Knowledge of the microenvironment (niche) of stem cells is helpful for stem-cell-based regenerative medicine. In the eye, limbal epithelial stem cells (corneal epithelial stem cells) provide the self-renewal capacity of the corneal epithelium and are essential for maintaining corneal transparency and vision. Limbal epithelial stem cell deficiency results in significant visual deterioration. Successful treatment of this type of blinding disease requires studies of the limbal epithelial stem cells and their microenvironment. We investigate the function of the limbal microvascular net and the limbal stroma in the maintenace of the limbal epithelial stem cell niche in vivo and examine the regulation of limbal epithelial stem cell survival, proliferation and differentiation in vivo. We assess the temporal and spatial changes in the expression patterns of the following markers during a six-month follow-up of various rabbit limbal autograft transplantation models: vascular endothelial cell marker CD31, corneal epithelium differentiation marker K3, limbal epithelial stem-cell-associated markers P63 and ABCG2 and proliferating cell nuclear marker Ki67. Our results suggest that limbal epithelial stem cells cannot maintain their stemness or proliferation without the support of the limbal microvascular net microenvironment. Thus, both the limbal microvascular net and the limbal stroma play important roles as components of the limbal epithelial stem cell niche maintaining limbal epithelial stem cell survival and proliferation and the avoidance of differentiation. The limbal stroma constitutes the structural basis of the limbal epithelial stem cell niche and the limbal microvascular net is a requirement for this niche. These new insights should aid the eventual construction of tissue-engineered cornea for corneal blind patients in the future.

  3. EFFECTS OF DOBUTAMINE ON INTESTINAL MICROVASCULAR BLOOD FLOW HETEROGENEITY AND OXYGEN EXTRACTION DURING SEPTIC SHOCK.

    PubMed

    Ospina-Tascón, Gustavo Adolfo; García Marín, Alberto Federico; Echeverri, Gabriel J; Bermúdez, William Fernando; Madriñán Navia, Humberto José; Valencia, Juan David; Quiñones, Edgardo; Rodríguez, Fernando; Marulanda, Angela; Arango Davila, César Augusto; Bruhn, Alejandro; Hernández, Glenn; De Backer, Daniel

    2017-03-23

    Derangements of microvascular blood flow distribution might contribute to disturbing oxygen extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric oxygen extraction ratio (mes-ERO2) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa, during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to fixed-dose of dobutamine (5 µgr/kg/min) or placebo, while three sham models with identical monitoring served as controls. At the time-of-shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small-vessels (SL-PPV), paralleling an increase in mes-ERO2 in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, while mes-ERO2 exhibited a corresponding significant decrease (repeated-measures ANOVA, p=0.02 and p=0.04 for time*group-interactions and inter-group differences for villi-PPV and mes-ERO2, respectively). Variations in villi-PPV were paralleled by variations in mes-ERO2 (R(2)=0.88, p<0.001) and these, in turn, by mesenteric lactate changes (R(2)=0.86, p<0.001). There were no significant differences in cardiac output and systemic oxygen delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric oxygen extraction ratio, suggesting a crucial role for microvascular blood flow distribution on oxygen uptake during development and resuscitation from septic shock.

  4. Trigemino-cardiac reflex during microvascular trigeminal decompression in cases of trigeminal neuralgia.

    PubMed

    Schaller, Bernhard

    2005-01-01

    The trigemino-cardiac reflex (TCR) is a well-recognized phenomenon consisting of bradycardia, arterial hypotension, apnea, and gastric hypermotility during ocular surgery or other manipulations in and around the orbit. Thus far, it could bee shown that central stimulation of the trigeminal nerve during transsphenoidal surgery and surgery for tumors in the cerebellopontine angle can lead to TCR. In cases of microvascular trigeminal decompression for trigeminal neuralgia, no data of the possible occurrence of TCR are available. TCR was defined as a drop in mean arterial blood pressure (MABP) and the heart rate (HR) of more than 20% to the baseline values before the stimulus and coinciding with the manipulation of the trigeminal nerve. Electronic anesthetic recorded perioperative HR and MABP values were reviewed retrospectively in 28 patients who received microvascular trigeminal decompression in cases of trigeminal neuralgia and were divided into two subgroups on the basis of occurrence of TCR during surgery. Of the 28 patients, 5 (18%) showed evidence of TCR during manipulation at the trigeminal radix by separation from microvascular structures. Their HR fell 46% and their MABP 57% during operative procedures near the trigeminal nerve as compared with levels immediately before the stimulus. After cessation of manipulation, HR and MABP returned (spontaneously) to levels before the stimulus. Risk factors of TCR were compared with results from the literature. In conclusion, the present results give evidence of TCR during manipulation of the central part of the trigeminal nerve during microvascular trigeminal decompression in cases of trigeminal neuralgia under a standardized anesthetic protocol.

  5. Shear stress-induced Ets-1 modulates protease inhibitor expression in microvascular endothelial cells.

    PubMed

    Milkiewicz, Malgorzata; Uchida, Cassandra; Gee, Eric; Fudalewski, Tomasz; Haas, Tara L

    2008-11-01

    Elevated shear stress within the skeletal muscle microvasculature is implicated in the induction of a longitudinal splitting form of angiogenesis, which is characterized by the lack of basement membrane breakage. We investigated whether the transcriptional regulator, Ets-1, is responsive to changes in hemodynamic forces and if so, whether Ets-1 controls microvascular endothelial cell integrity by inducing the expression of inhibitors of matrix degrading proteases. Rats were treated with prazosin for 2, 4, and 7 days to increase in microvascular shear stress in hindlimb skeletal muscles. In complimentary in vitro experiments, rat microvascular skeletal muscle endothelial cells were exposed to laminar shear stress (15 dyne/cm(2)) for 0.5, 2, and 24 h. TaqMan PCR analysis of laser microdissected capillaries isolated from EDL muscles demonstrated transient (after 2 days) induction of Ets-1 gene expression. In cultured cells, a transient up-regulation of Ets-1 mRNA was observed after 2 h shear stimulation, accompanied by increased phosphorylation of Ets-1 and enhanced Ets-1 DNA binding activity. This response was modulated by ERK1/2 and p38 MAP kinases, but was not dependent on NOS or COX-2 activity. PAI-1, TIMP-1 and TIMP-3 mRNA were elevated significantly in prazosin treated EDL, and in response to shear stimulation in vitro. In cultured endothelial cells, Ets-1 RNA interference abolished the shear-induced increases in Ets-1, PAI-1, TIMP-1, and TIMP-3 mRNA expression. These results suggest that enhanced laminar shear stress may act to preserve the integrity of microvascular walls in part through Ets-1-dependent induction of protease inhibitors.

  6. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    PubMed

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. 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

  7. Modulation of perfusion and oxygenation by red blood cell oxygen affinity during acute anemia.

    PubMed

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

    2008-03-01

    Responses to exchange transfusion using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen (O(2)) affinity were studied in the hamster window chamber model during acute anemia to determine its role on microvascular perfusion and tissue oxygenation. Allosteric effectors were introduced in the RBCs by electroporation. Inositol hexaphosphate (IHP) and 5-hydroxymethyl-2-furfural (5HMF) were used to decrease and increase Hb-O(2) affinity. In vitro P50s (partial pressure of O(2) at 50% Hb saturation) were modified to 10, 25, 45, and 50 mm Hg (normal P50 is 32 mm Hg). Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kD to 18% hematocrit (Hct). Modified RBCs (at 18% Hct in 5% albumin solution) were infused by exchange transfusion of 35% of blood volume. Systemic parameters, microvascular perfusion, capillary perfusion (functional capillary density, FCD), and microvascular Po(2) levels were measured. RBcs with P50 of 45 mm Hg increased tissue Po(2) and decreased O(2) delivery (Do(2)) and extraction (Vo(2)) and RBCs with P50 of 60 mmHg reduced FCD, microvascular flow, tissue Po(2), Do(2) and Vo(2). Erythrocytes with increased Hb-O(2) affinity maintained hemodynamic conditions, Do(2) and decreased tissue Po(2). This study shows that in an anemic condition, maximal tissue Po(2) does not correspond to maximal Do(2) and Vo(2).

  8. Promotion of airway anastomotic microvascular regeneration and alleviation of airway ischemia by deferoxamine nanoparticles

    PubMed Central

    Tian, Wen; Sung, Yon K.; Sun, Wenchao; Hsu, Joe L.; Manickam, Sathish; Wagh, Dhananjay; Joubert, Lydia-Marie; Semenza, Gregg L.; Rajadas, Jayakumar; Nicolls, Mark R.

    2014-01-01

    Airway tissue ischemia and hypoxia in human lung transplantation is a consequence of the sacrifice of the bronchial circulation during the surgical procedure and is a major risk factor for the development of airway anastomotic complications. Augmented expression of hypoxia-inducible factor (HIF)-1α promotes microvascular repair and alleviates allograft ischemia and hypoxia. Deferoxamine mesylate (DFO) is an FDA-approved iron chelator which has been shown to upregulate cellular HIF-1α. Here, we developed a nanoparticle formulation of DFO that can be topically applied to airway transplants at the time of surgery. In a mouse orthotopic tracheal transplant (OTT) model, the DFO nanoparticle was highly effective in enhancing airway microvascular perfusion following transplantation through the production of the angiogenic factors, placental growth factor (PLGF) and stromal cell-derived factor (SDF)-1. The endothelial cells in DFO treated airways displayed higher levels of p-eNOS and Ki67, less apoptosis, and decreased production of perivascular reactive oxygen species (ROS) compared to vehicle-treated airways. In summary, a DFO formulation topically-applied at the time of surgery successfully augmented airway anastomotic microvascular regeneration and the repair of alloimmune-injured microvasculature. This approach may be an effective topical transplant-conditioning therapy for preventing airway complications following clinical lung transplantation. PMID:24161166

  9. Ascorbate inhibits NADPH oxidase subunit p47phox expression in microvascular endothelial cells.

    PubMed

    Wu, Feng; Schuster, David P; Tyml, Karel; Wilson, John X

    2007-01-01

    The production of reactive oxygen species (ROS) is central to the etiology of endothelial dysfunction in sepsis. Endothelial cells respond to infection by activating NADPH oxidases that are sources of intracellular ROS and potential targets for therapeutic administration of antioxidants. Ascorbate is an antioxidant that accumulates in these cells and improves capillary blood flow, vascular reactivity, arterial blood pressure, and survival in experimental sepsis. Therefore, the present study tested the hypothesis that ascorbate regulates NADPH oxidases in microvascular endothelial cells exposed to septic insult. We observed that incubation with Escherichia coli lipopolysaccharide (LPS) and interferon-gamma (IFNgamma) increased NADPH oxidase activity and expression of the enzyme subunit p47phox in mouse microvascular endothelial cells of skeletal muscle origin. Pretreatment of the cells with ascorbate prevented these increases. Polyethylene glycol-conjugated catalase and selective inhibitors of Jak2 also abrogated induction of p47phox. Exogenous hydrogen peroxide induced p47phox expression that was prevented by pretreatment of the cells with ascorbate. LPS+IFNgamma or hydrogen peroxide activated the Jak2/Stat1/IRF1 pathway and this effect was also inhibited by ascorbate. In conclusion, ascorbate blocks the stimulation by septic insult of redox-sensitive Jak2/Stat1/IRF1 signaling, p47phox expression, and NADPH oxidase activity in microvascular endothelial cells. Because endothelial NADPH oxidases produce ROS that can cause endothelial dysfunction, their inhibition by ascorbate may represent a new strategy for sepsis therapy.

  10. Air Pollution Particulate Matter Collected from an Appalachian Mountaintop Mining Site Induces Microvascular Dysfunction

    PubMed Central

    KNUCKLES, TRAVIS L.; STAPLETON, PHOEBE A.; MINARCHICK, VALERIE C.; ESCH, LAURA; MCCAWLEY, MICHAEL; HENDRYX, MICHAEL; NURKIEWICZ, TIMOTHY R.

    2016-01-01

    Objective Air pollution PM is associated with cardiovascular morbidity and mortality. In Appalachia, PM from mining may represent a health burden to this sensitive population that leads the nation in cardiovascular disease, among others. Cardiovascular consequences following inhalation of PMMTM are unclear, but must be identified to establish causal effects. Methods PM was collected within 1 mile of an active MTM site in southern WV. The PM was extracted and was primarily <10μm in diameter (PM10), consisting largely of sulfur (38%) and silica (24%). Adult male rats were IT with 300 μg PMMTM. Twenty-four hours following exposure, rats were prepared for intravital microscopy, or isolated arteriole experiments. Results PMMTM exposure blunted endothelium-dependent dilation in mesenteric and coronary arterioles by 26%, and 25%, respectively, as well as endothelium-independent dilation. In vivo, PMMTM exposure inhibited endothelium-dependent arteriolar dilation (60% reduction). α-adrenergic receptor blockade inhibited PVNS-induced vasoconstriction in exposed animals compared with sham. Conclusions These data suggest that PMMTM exposure impairs microvascular function in disparate microvascular beds, through alterations in NO-mediated dilation and sympathetic nerve influences. Microvascular dysfunction may contribute to cardiovascular disease in regions with MTM sites. PMID:22963349

  11. Clearing microvascular lesions of the true vocal fold with the KTP/532 laser.

    PubMed

    Hsiung, Ming-Wang; Kang, Bor-Hwang; Su, Wan-Fu; Pai, Lu; Wang, Hsing-Won

    2003-06-01

    Although used for treating vascular malformations, KTP (532 nm) lasers have not been used to treat microvascular lesions of the vocal fold. The efficiency of KTP laser operation in the continuous mode with a 0.4- or 0.6-mm beam (1- to 2-W aim for 3 to 7 seconds delivering a total energy of 3 to 7 J) was studied retrospectively in patients with microvascular lesions of the vocal fold (n = 14). The perceptual acoustic, phonatory function, and videolaryngostroboscopic data were evaluated before and after operation in 10 patients. At follow-up (mean, 7 months), the results were excellent in all patients. Their phonatory function (jitter, shimmer, grade, breathiness, and roughness) significantly improved (p < .01). The videolaryngostroboscopic rating showed significant improvement in the amplitude of vocal fold vibration and excursion of the mucosal wave (p < .05). No postoperative recurrence or complications were noted. The KTP laser operation is a useful, cost-effective, and time-saving procedure and can be considered as an option in management of patients with microvascular lesions of the vocal fold, particularly those with repeated hemorrhages. Because the operation is easy (compared to other surgical methods) and has no major side effects, the prospect of total patient recovery is excellent.

  12. Involvement of the cellular prion protein in the migration of brain microvascular endothelial cells.

    PubMed

    Watanabe, Takuya; Yasutaka, Yuki; Nishioku, Tsuyoshi; Kusakabe, Sae; Futagami, Koujiro; Yamauchi, Atsushi; Kataoka, Yasufumi

    2011-06-01

    The conversion of cellular prion protein (PrP(C)) to its protease-resistant isoform is involved in the pathogenesis of prion disease. Although PrP(C) is a ubiquitous glycoprotein that is present in various cell types, the physiological role of PrP(C) remains obscure. The present study aimed to determine whether PrP(C) mediates migration of brain microvascular endothelial cells. Small interfering RNAs (siRNAs) targeting PrP(C) were transfected into a mouse brain microvascular endothelial cell line (bEND.3 cells). siPrP1, selected among three siRNAs, reduced mRNA and protein levels of PrP(C) in bEND.3 cells. Cellular migration was evaluated with a scratch-wound assay. siPrP1 suppressed migration without significantly affecting cellular proliferation. This study provides the first evidence that PrP(C) may be necessary for brain microvascular endothelial cells to migrate into damaged regions in the brain. This function of PrP(C) in the brain endothelium may be a mechanism by which the neurovascular unit recovers from an injury such as an ischemic insult.

  13. Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage

    PubMed Central

    Breslin, Jerome W.; Sun, Hengrui; Xu, Wenjuan; Rodarte, Charles; Moy, Alan B.; Wu, Mack H.; Yuan, Sarah Y.

    2009-01-01

    Neutrophil-induced coronary microvascular barrier dysfunction is an important pathophysiological event in heart disease. Currently, the precise cellular and molecular mechanisms of neutrophil-induced microvascular leakage are not clear. The aim of this study was to test the hypothesis that rho kinase (ROCK) increases coronary venular permeability in association with elevated endothelial tension. We assessed permeability to albumin (Pa) in isolated porcine coronary venules and in coronary venular endothelial cell (CVEC) monolayers. Endothelial barrier function was also evaluated by measuring transendothelial electrical resistance (TER) of CVEC monolayers. In parallel, we measured isometric tension of CVECs grown on collagen gels. Transference of constitutively active (ca)-ROCK protein into isolated coronary venules or CVEC monolayers caused a significant increase in Pa and decreased TER in CVECs. The ROCK inhibitor Y-27632 blocked the ca-ROCK-induced changes. C5a-activated neutrophils (106/ml) also significantly elevated venular Pa, which was dose-dependently inhibited by Y-27632 and a structurally distinct ROCK inhibitor, H-1152. In CVEC monolayers, activated neutrophils increased permeability with a concomitant elevation in isometric tension, both of which were inhibited by Y-27632 or H-1152. Treatment with ca-ROCK also significantly increased CVEC monolayer permeability and isometric tension, coupled with actin polymerization and elevated phosphorylation of myosin regulatory light chain on Thr18/Ser19. The data suggest that during neutrophil activation, ROCK promotes microvascular leakage in association with actin-myosin-mediated tension development in endothelial cells. PMID:16172166

  14. Microvascular anastomosis using fibrin glue and venous cuff in rat carotid artery.

    PubMed

    Sacak, Bulent; Tosun, Ugur; Egemen, Onur; Sakiz, Damlanur; Ugurlu, Kemal

    2015-04-01

    Conventional anastomosis with interrupted sutures can be time-consuming, can cause vessel narrowing, and can lead to thrombosis at the site of repair. The amount of suture material inside the lumen can impair the endothelium of the vessel, triggering thrombosis. In microsurgery, fibrin sealants have the potential beneficial effects of reducing anastomosis time and promoting accurate haemostasis at the anastomotic site. However, there has been a general reluctance to use fibrin glue for microvascular anastomoses because the fibrin polymer is highly thrombogenic and may not provide adequate strength. To overcome these problems, a novel technique was defined for microvascular anastomosis with fibrin glue and a venous cuff. Sixty-four rats in two groups are included in the study. In the experimental group (n = 32), end-to-end arterial anastomosis was performed with two stay sutures, fibrin glue, and a venous cuff. In the control group (n = 32), conventional end-to-end arterial anastomosis was performed. Fibrin glue assisted anastomosis with a venous cuff took less time, caused less bleeding at the anastomotic site, and achieved a patency rate comparable to that provided by the conventional technique. Fibrin sealant assisted microvascular anastomosis with venous cuff is a rapid, easy, and reliable technique compared to the end-to-end arterial anastomosis.

  15. Microvascular and macrovascular complications of type 2 diabetic mellitus in Central, Kingdom of Saudi Arabia

    PubMed Central

    Alaboud, Aboud F.; Tourkmani, Ayla M.; Alharbi, Turki J.; Alobikan, Aljoharah H.; Abdelhay, Osama; Batal, Saad M. Al; Alkhashan, Hesham I.; Mohammed, Umar Y.

    2016-01-01

    Objectives To determine the prevalence of macrovascular and microvascular complications of type 2 diabetes mellitus and its associated determinants. Methods We evaluated the online medical records of patients with type 2 diabetes mellitus who have been seen in chronic disease unit between April and June 2014. Seven hundred and forty-eight participants satisfied the inclusion criteria. Of these, 317 (42.4%) were males with a mean age of 57.9 years, 681 (64.3%) were obese with body mass index (BMI) of greater than 30, while only 9.6% had normal BMI (<25). Results Only 158 (21.1%) had controlled hemoglobin A1c level. Retinopathy prevalence was 14.8% and neuropathy was 5.6%. Macrovascular complications accounted for 12.1%. Patients’ age and duration of diabetes were main predictors of developing complications. Patients with more than 20 years history of diabetes have 30% more odds of developing the complications when compared to patients with less than 10 years of diabetes history. Each increment in age by one year increases the odds of developing microvascular complications by 4% and macro vascular complication by 2%. Conclusion Our results showed diabetic patients with poor glycemic control, and longer duration of diabetic history had higher prevalence of both macrovascular and microvascular. PMID:27874160

  16. Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

    PubMed

    Noguchi, Katsuhiko; Matsuzaki, Toshihiro; Sakanashi, Mayuko; Hamadate, Naobumi; Uchida, Taro; Kina-Tanada, Mika; Kubota, Haruaki; Nakasone, Junko; Sakanashi, Matao; Ueda, Shinichiro; Masuzaki, Hiroaki; Ishiuchi, Shogo; Ohya, Yusuke; Tsutsui, Masato

    2015-02-01

    Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals.

  17. Determination of Optical and Microvascular Parameters of Port Wine Stains Using Diffuse Reflectance Spectroscopy.

    PubMed

    Qiu, Zhihai; Yao, Guangping; Chen, Defu; Wang, Ying; Gu, Ying; Li, Buhong

    2016-01-01

    Characterizing port wine stains (PWS) with its optical parameters [i.e. absorption coefficient (μ a) and reduced scattering coefficient (μ s')] and microvascular parameters [i.e. blood volume fraction (BVF), mean vessel diameter (MVD), and oxygen saturation (StO2)] is extremely important for elucidating the mechanisms for its light-based treatments, such as pulsed dye laser and photodynamic therapy. In this study, a customized diffuse reflectance spectroscopy (DRS) probe with an appropriate source-detector distance was used to measure the diffuse reflectance spectra of PWS lesions in clinical practice. The results demonstrate that optical parameters of different types of PWS lesions can be accurately extracted by fitting the DRS with diffusion equation. Since the sampling depth of the probe coincides with the depth distribution of abnormal vasculature in PWS, the obtained microvascular parameters of PWS lesions that changed from pink to purple are in agreement with the corresponding physiological conditions. This study suggests that DRS can be utilized to quantitatively determine the optical and microvascular parameters of PWS lesions, which have the potential for planning the protocol and predicting the efficiency for light-based PWS treatments.

  18. Hypoxia inducible factor-1: regulation by nitric oxide in posthypoxic microvascular endothelium.

    PubMed

    Natarajan, Ramesh; Jones, Drew G; Fisher, Bernard J; Wallace, Timothy J; Ghosh, Shobha; Fowler, Alpha A

    2005-10-01

    Microvascular endothelial cells provide a critical regulatory interface between blood constituents and tissue. Hypoxia inducible factor-1 (HIF-1) is a key transcription factor required for expression of hypoxia-dependent genes. We employed a model of hypoxia and reoxygenation (H/R) using the dermal microvascular endothelial cell line HMEC-1 to examine the effects of altered oxygen concentrations on microvascular HIF-1 expression and nitric oxide (NO) formation. Hypoxia increased inducible NO synthase (iNOS) mRNA in a time-dependent manner in HMEC-1. However, endothelial NO synthase mRNA progressively declined during hypoxia. H/R promoted significant increases in cellular nitrite levels that were significantly abrogated by the specific iNOS inhibitor N6-(1-iminoethyl)-L-lysine, di hy drochloride. Exogenous NO promoted stabilization of the alpha subunit of HIF-1 and produced functional DNA binding. Exposure of HMEC-1 to H/R resulted in previously unrecognized biphasic HIF-1alpha stabilization during reoxygenation. When the iNOS gene was silenced through the use of iNOS-specific small interfering RNA, HIF-1alpha stabilization and HIF-1 activation were dramatically diminished, suggesting that inducible NOS-derived NO is a key factor sustaining HIF-1 activation during both hypoxia and reoxygenation.

  19. Microvascular Reconstruction of Free Jejunal Graft in Larynx-preserving Esophagectomy for Cervical Esophageal Carcinoma

    PubMed Central

    Natori, Yuhei; Komoto, Masakazu; Matsumura, Takashi; Horiguchi, Masatoshi; Yoshizawa, Hidekazu; Iwanuma, Yoshimi; Tsurumaru, Masahioko; Kajiyama, Yoshiaki; Mizuno, Hiroshi

    2016-01-01

    Background: Losing the ability to speak severely affects the quality of life, and patients who have undergone laryngectomy tend to become depressed, which may lead to social withdrawal. Recently, with advancements in chemoradiotherapy and with alternative perspectives on postoperative quality of life, larynx preservation has been pursued; however, the selection of candidates and the optimal reconstructive procedure remain controversial. In this study, we retrospectively reviewed our experience with free jejunal graft for larynx-preserving cervical esophagectomy (LPCE), focusing on microvascular reconstruction. Methods: Seven patients underwent LPCE for cervical esophageal carcinoma, and defects were reconstructed by free jejunal transfer subsequently. We collected preoperative and postoperative data of the patients and assessed the importance of the procedure. Results: We mostly used the transverse cervical artery as the recipient, and a longer operative time was required, particularly for the regrowth cases. The operative field for microvascular anastomosis was more limited and deeper than those in the laryngectomy cases. Two graft necrosis cases were confirmed at postoperative day 9 or 15, and vessels contralateral from the graft were chosen as recipients in both patients. Conclusions: Microvascular reconstruction for free jejunal graft in LPCE differed in several ways from the procedure combined with laryngectomy. Compression from the tracheal cartilage to the pedicle was suspected as the reason of the necrosis clinically and pathologically. Therefore, we should select recipient vessels from the ipsilateral side of the graft, and careful and extended monitoring of the flap should be considered to make this procedure successful. PMID:27257562

  20. Analysis of Microvascular Free Flap Failure Focusing on the Microscopic Findings of the Anastomosed Vessels.

    PubMed

    Seo, Mi Hyun; Kim, Soung Min; Huan, Fan; Myoung, Hoon; Lee, Jong Ho; Lee, Suk Keun

    2015-10-01

    Microvascular flap reconstruction is known as successful technique, although vascular thrombosis can cause free flap failure. To analyze the histologic characteristics and causes of free flap failure, this clinical study examined failed free flaps, including the microanastomosed sites. This study included a total of 5 failed flaps, including 3 radial forearm free flaps, 1 latissimus dorsi free flap, and 1 fibular free flap, all performed with microvascular reconstruction surgery from 2009 to 2011 at Seoul National University Dental Hospital. At the resection surgeries of the failed nonviable flaps, histologic specimens including the microanastomosed vessels were acquired. For light microscope observation, the slides were stained with hematoxylin and eosin (HE), and also with Masson trichrome. Selected portions of graft tissue were also observed under transmission electron microscope (TEM). It was found that the cause of flap failure was the occlusion of vessels because of thrombi formation. During the microanastomosis, damage to the vessel endothelium occurred, followed by intimal hyperplasia and medial necrosis at the anastomosed site. In the TEM findings, some smooth muscle cells beneath endothelium were atrophied and degenerated. The formation of thrombi and the degeneration of the smooth muscle cells were coincident with vascular dysfunction of graft vessel. The damaged endothelium and the exposed connective tissue elements might initiate the extrinsic pathway of thrombosis at the microanastomotic site. Therefore, it is suggested that accurate surgical planning, adequate postoperative monitoring, and skillful technique for minimizing vascular injury are required for successful microvascular transfer.

  1. Platelets play an important role in TNF-induced microvascular endothelial cell pathology.

    PubMed Central

    Lou, J.; Donati, Y. R.; Juillard, P.; Giroud, C.; Vesin, C.; Mili, N.; Grau, G. E.

    1997-01-01

    Tumor necrosis factor-alpha (TNF) is known to be an important mediator in the pathogenesis of several inflammatory diseases. Vascular endothelial cells represent a major target of TNF effects. Platelet sequestration has been found in brain microvessels during experimental cerebral malaria and lung in experimental pulmonary fibrosis, implying that it may participate in TNF-dependent microvascular pathology. In this study, we investigated the mechanisms of platelet-endothelial interaction, using co-cultures between platelets and TNF-activated mouse brain microvascular endothelial cells (MVECs). Adhesion and fusion of platelets to MVECs was evidenced by electron microscopy, dye transfer, and flow cytometry. It was induced by TNF and interferon-gamma and depended on LFA-1 expressed on the platelet surface and ICAM-1 expressed on MVECs. The adhesion and fusion also led to the transfer of platelet markers on the MVEC surface, rendering these more adherent for leukocytes, and to an enhanced MVEC sensitivity to TNF-induced injury. These results suggest that platelets can participate in TNF-induced microvascular pathology. Images Figure 2 Figure 3 Figure 6 PMID:9358766

  2. Cutaneous microvascular response during local cold exposure - the effect of female sex hormones and cold perception.

    PubMed

    Cankar, Ksenija; Music, Mark; Finderle, Zare

    2016-11-01

    It is generally known that differences exist between males and females with regard to sensitivity to cold. Similar differences even among females in different hormonal balance might influence microvascular response during cold provocation testing. The aim of the present study was to measure sex hormone levels, cold and cold pain perception thresholds and compare them to cutaneous laser-Doppler flux response during local cooling in both the follicular and luteal phases of the menstrual cycle. In the luteal phase a more pronounced decrease in laser-Doppler flux was observed compared to follicular phase during local cooling at 15°C (significant difference by Dunnett's test, p<0.05). In addition, statistically significant correlations between progesterone level and laser-Doppler flux response to local cooling were observed during the follicular (R=-0.552, p=0.0174) and during the luteal phases (R=0.520, p=0.0271). In contrast, the correlation between estradiol level and laser-Doppler flux response was observed only in the follicular phase (R=-0.506, p=0.0324). Our results show that individual sensitivity to cold influences cutaneous microvascular response to local cooling; that microvascular reactivity is more pronounced during the luteal phase of the menstrual cycle; and that reactivity correlates with hormone levels. The effect of specific sex hormone levels is related to the cold-provocation temperature.

  3. Microvascular free-tissue transfer. The Atlanta Veterans Administration Medical Center experience.

    PubMed

    Carlson, G W; Coleman, J J

    1989-04-01

    The entire microvascular tissue transfer experience from 1977 through 1987 at the Atlanta Veterans Administration Medical Center has been reviewed. Seventy-four free flaps were done in 68 patients. Assessable records were available in 52 patients who had 58 reconstructive procedures. The most frequently used flaps were jejunum in 15 patients (25.8%), latissimus dorsi in 11 patients (18.9%), rectus abdominis in eight patients (13.8%), and gracilis in seven patients (12.1%). Major complications occurred in 43.1% of the cases. Total flap loss occurred in eight patients (13.8%); from 1977 through 1982, four (28.6%) of 14 patients had total flap loss, and from 1983 through 1987, four (9.1%) had total flap loss. Partial flap loss occurred in four cases (6.9%). Of the 52 patients, 43 had their problems resolved expeditiously by free-tissue transfer. We conclude that in a university-affiliated Veterans Administration medical center, microvascular reconstruction is an important and necessary surgical tool. Failure rates have decreased markedly with time and increasing experience. Definition of new anatomic microvascular units for transfer has increased the number of reconstructive choices.

  4. Imaging biomarkers of angiogenesis and the microvascular environment in cerebral tumours

    PubMed Central

    Thompson, G; Mills, S J; Coope, D J; O’connor, J P B; Jackson, A

    2011-01-01

    Conventional contrast-enhanced CT and MRI are now in routine clinical use for the diagnosis, treatment and monitoring of diseases in the brain. The presence of contrast enhancement is a proxy for the pathological changes that occur in the normally highly regulated brain vasculature and blood-brain barrier. With recognition of the limitations of these techniques, and a greater appreciation for the nuanced mechanisms of microvascular change in a variety of pathological processes, novel techniques are under investigation for their utility in further interrogating the microvasculature of the brain. This is particularly important in tumours, where the reliance on angiogenesis (new vessel formation) is crucial for tumour growth, and the resulting microvascular configuration and derangement has profound implications for diagnosis, treatment and monitoring. In addition, novel therapeutic approaches that seek to directly modify the microvasculature require more sensitive and specific biological markers of baseline tumour behaviour and response. The currently used imaging biomarkers of angiogenesis and brain tumour microvascular environment are reviewed. PMID:22433824

  5. 77 FR 54930 - Carlyle Plastics and Resins, Formerly Known as Fortis Plastics, A Subsidiary of Plastics...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... Employment and Training Administration Carlyle Plastics and Resins, Formerly Known as Fortis Plastics, A Subsidiary of Plastics Acquisitions Inc., Including On-Site Leased Workers From Kelly Services and Shelley... Adjustment Assistance on July 3, 2012, applicable to workers and former workers of workers of Fortis...

  6. Respiratory muscle plasticity.

    PubMed

    Rowley, Katharine L; Mantilla, Carlos B; Sieck, Gary C

    2005-07-28

    Plasticity of respiratory muscles must be considered in the context of their unique physiological demands. The continuous rhythmic activation of respiratory muscles makes them among the most active in the body. Respiratory muscles, especially the diaphragm, are non-weight-bearing, and thus, in contrast to limb muscles, are not exposed to gravitational effects. Perturbations in normal activation and load known to induce plasticity in limb muscles may not cause similar adaptations in respiratory muscles. In this review, we explore the structural and functional properties of the diaphragm muscle and their response to alterations in load and activity. Overall, relatively modest changes in diaphragm structural and functional properties occur in response to perturbations in load or activity. However, disruptions in the normal influence of phrenic innervation by frank denervation, tetrodotoxin nerve block and spinal hemisection, induce profound changes in the diaphragm, indicating the substantial trophic influence of phrenic motoneurons on diaphragm muscle.

  7. Stress-gradient plasticity

    PubMed Central

    Chakravarthy, Srinath S.; Curtin, W. A.

    2011-01-01

    A new model, stress-gradient plasticity, is presented that provides unique mechanistic insight into size-dependent phenomena in plasticity. This dislocation-based model predicts strengthening of materials when a gradient in stress acts over dislocation source–obstacle configurations. The model has a physical length scale, the spacing of dislocation obstacles, and is validated by several levels of discrete-dislocation simulations. When incorporated into a continuum viscoplastic model, predictions for bending and torsion in polycrystalline metals show excellent agreement with experiments in the initial strengthening and subsequent hardening as a function of both sample-size dependence and grain size, when the operative obstacle spacing is proportional to the grain size. PMID:21911403

  8. Compensatory plasticity: time matters

    PubMed Central

    Lazzouni, Latifa; Lepore, Franco

    2014-01-01

    Plasticity in the human and animal brain is the rule, the base for development, and the way to deal effectively with the environment for making the most efficient use of all the senses. When the brain is deprived of one sensory modality, plasticity becomes compensatory: the exception that invalidates the general loss hypothesis giving the opportunity of effective change. Sensory deprivation comes with massive alterations in brain structure and function, behavioral outcomes, and neural interactions. Blind individuals do as good as the sighted and even more, show superior abilities in auditory, tactile and olfactory processing. This behavioral enhancement is accompanied with changes in occipital cortex function, where visual areas at different levels become responsive to non-visual information. The intact senses are in general used more efficiently in the blind but are also used more exclusively. New findings are disentangling these two aspects of compensatory plasticity. What is due to visual deprivation and what is dependent on the extended use of spared modalities? The latter seems to contribute highly to compensatory changes in the congenitally blind. Short-term deprivation through the use of blindfolds shows that cortical excitability of the visual cortex is likely to show rapid modulatory changes after few minutes of light deprivation and therefore changes are possible in adulthood. However, reorganization remains more pronounced in the congenitally blind. Cortico-cortical pathways between visual areas and the areas of preserved sensory modalities are inhibited in the presence of vision, but are unmasked after loss of vision or blindfolding as a mechanism likely to drive cross-modal information to the deafferented visual cortex. The development of specialized higher order visual pathways independently from early sensory experience is likely to preserve their function and switch to the intact modalities. Plasticity in the blind is also accompanied with

  9. New perspectives in plastic biodegradation.

    PubMed

    Sivan, Alex

    2011-06-01

    During the past 50 years new plastic materials, in various applications, have gradually replaced the traditional metal, wood, leather materials. Ironically, the most preferred property of plastics--durability--exerts also the major environmental threat. Recycling has practically failed to provide a safe solution for disposal of plastic waste (only 5% out of 1 trillion plastic bags, annually produced in the US alone, are being recycled). Since the most utilized plastic is polyethylene (PE; ca. 140 million tons/year), any reduction in the accumulation of PE waste alone would have a major impact on the overall reduction of the plastic waste in the environment. Since PE is considered to be practically inert, efforts were made to isolate unique microorganisms capable of utilizing synthetic polymers. Recent data showed that biodegradation of plastic waste with selected microbial strains became a viable solution.

  10. Plastic footwear for leprosy.

    PubMed

    Antia, N H

    1990-03-01

    The anaesthetic foot in leprosy poses the most major problem in the rehabilitation of its patients. Various attempts have been made to produce protective footwear such as the microcellular rubber-car-tyre sandals. Unfortunately these attempts have had little success on a large scale because of the inability to produce them in large numbers and the stigma attached to such unusual footwear. While such footwear may be superior to the 'tennis' shoe in protecting the foot from injury by the penetration of sharp objects, it fails to distribute the weight-bearing forces which is the major cause of plantar damage and ulceration in the anaesthetic foot. This can be achieved by providing rigidity to the sole, as demonstrated by the healing of ulcers in plaster of paris casts or the rigid wooden clog. A new type of moulded plastic footwear has been evolved in conjunction with the plastic footwear industry which provides footwear that can be mass produced at a low price and which overcomes the stigma of leprosy. Controlled rigidity is provided by the incorporation of a spring steel shank between the sponge insole and the hard wearing plastic sole. Trials have demonstrated both the acceptability of the footwear and its protective effects as well as its hard wearing properties.

  11. Respiratory muscle plasticity.

    PubMed

    Gransee, Heather M; Mantilla, Carlos B; Sieck, Gary C

    2012-04-01

    Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle's plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles.

  12. Microelectronics plastic molded packaging

    SciTech Connect

    Johnson, D.R.; Palmer, D.W.; Peterson, D.W.

    1997-02-01

    The use of commercial off-the-shelf (COTS) microelectronics for nuclear weapon applications will soon be reality rather than hearsay. The use of COTS for new technologies for uniquely military applications is being driven by the so-called Perry Initiative that requires the U.S. Department of Defense (DoD) to accept and utilize commercial standards for procurement of military systems. Based on this philosophy, coupled with several practical considerations, new weapons systems as well as future upgrades will contain plastic encapsulated microelectronics. However, a conservative Department of Energy (DOE) approach requires lifetime predictive models. Thus, the focus of the current project is on accelerated testing to advance current aging models as well as on the development of the methodology to be used during WR qualification of plastic encapsulated microelectronics. An additional focal point involves achieving awareness of commercial capabilities, materials, and processes. One of the major outcomes of the project has been the definition of proper techniques for handling and evaluation of modern surface mount parts which might be used in future systems. This program is also raising the familiarity level of plastic within the weapons complex, allowing subsystem design rules accommodating COTS to evolve. A two year program plan is presented along with test results and commercial interactions during this first year.

  13. Interfacial interactions between plastic particles in plastics flotation.

    PubMed

    Wang, Chong-qing; Wang, Hui; Gu, Guo-hua; Fu, Jian-gang; Lin, Qing-quan; Liu, You-nian

    2015-12-01

    Plastics flotation used for recycling of plastic wastes receives increasing attention for its industrial application. In order to study the mechanism of plastics flotation, the interfacial interactions between plastic particles in flotation system were investigated through calculation of Lifshitz-van der Waals (LW) function, Lewis acid-base (AB) Gibbs function, and the extended Derjaguin-Landau-Verwey-Overbeek potential energy profiles. The results showed that van der Waals force between plastic particles is attraction force in flotation system. The large hydrophobic attraction, caused by the AB Gibbs function, is the dominant interparticle force. Wetting agents present significant effects on the interfacial interactions between plastic particles. It is found that adsorption of wetting agents promotes dispersion of plastic particles and decreases the floatability. Pneumatic flotation may improve the recovery and purity of separated plastics through selective adsorption of wetting agents on plastic surface. The relationships between hydrophobic attraction and surface properties were also examined. It is revealed that there exists a three-order polynomial relationship between the AB Gibbs function and Lewis base component. Our finding provides some insights into mechanism of plastics flotation.

  14. Cerium Dioxide Nanoparticle Exposure Improves Microvascular Dysfunction and Reduces Oxidative Stress in Spontaneously Hypertensive Rats

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    The elevated production of reactive oxygen species (ROS) in the vascular wall is associated with cardiovascular diseases such as hypertension. This increase in oxidative stress contributes to various mechanisms of vascular dysfunction, such as decreased nitric oxide bioavailability. Therefore, anti-oxidants are being researched to decrease the high levels of ROS, which could improve the microvascular dysfunction associated with various cardiovascular diseases. From a therapeutic perspective, cerium dioxide nanoparticles (CeO2 NP) hold great anti-oxidant potential, but their in vivo activity is unclear. Due to this potential anti-oxidant action, we hypothesize that injected CeO2 NP would decrease microvascular dysfunction and oxidative stress associated with hypertension. In order to simulate a therapeutic application, spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were intravenously injected with either saline or CeO2 NP (100 μg suspended in saline). Twenty-four hours post-exposure mesenteric arteriolar reactivity was assessed via intravital microscopy. Endothelium-dependent and –independent function was assessed via acetylcholine and sodium nitroprusside. Microvascular oxidative stress was analyzed using fluorescent staining in isolated mesenteric arterioles. Finally, systemic inflammation was examined using a multiplex analysis and venular leukocyte flux was counted. Endothelium-dependent dilation was significantly decreased in the SH rats (29.68 ± 3.28%, maximal response) and this microvascular dysfunction was significantly improved following CeO2 NP exposure (43.76 ± 4.33%, maximal response). There was also an increase in oxidative stress in the SH rats, which was abolished following CeO2 NP treatment. These results provided evidence that CeO2 NP act as an anti-oxidant in vivo. There were also changes in the inflammatory profile in the WKY and SH rats. In WKY rats, IL-10 and TNF-α were increased following CeO2 NP treatment. Finally, leukocyte

  15. Plastic surgery-myths and realities in developing countries: experience from eastern Nepal.

    PubMed

    Mishra, Brijesh; Koirala, Robin; Tripathi, Nalini; Shrestha, Kajan Raj; Adhikary, Buddhinath; Shah, Surendra

    2011-01-01

    B.P. Koirala Institute of Health Sciences, Dharan, Nepal, is the only tertiary care referral centre in the eastern region of Nepal. This paper discusses the author's experience of starting a plastic surgery unit in eastern Nepal regarding need and present status of plastic surgery care in Nepal. Methods. We analyzed the data of patients treated in Plastic surgery unit from July 2007 to February 2009. We did evaluation regarding type of patients, procedures, and their outcome. We also evaluated the limitations and their possible solutions to overcome the barriers to establish effective plastic surgical centers in developing countries. Results. Plastic surgery services were started as a unit in general surgery by single plastic surgeon and one general surgery resident on rotation. Total 848 patients were treated for different plastic-surgery-related conditions, which included 307 acute burn patients 541 general plastic surgery patients. Trauma constituted the major bulk 22%, followed by tumors 20%, while aesthetic surgery operations were only 10.1%. Conclusions. In developing countries, aesthetic procedures constitute very small part of plastic surgery interventions and plastic surgery units are primarily required for reconstructive needs for optimum management of patients.

  16. Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

    PubMed Central

    Arendt, Kristin L.; Zhang, Zhenjie; Ganesan, Subhashree; Hintze, Maik; Shin, Maggie M.; Tang, Yitai; Cho, Ahryon; Graef, Isabella A.; Chen, Lu

    2015-01-01

    Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity. PMID:26443861

  17. Acute Appendicitis Secondary to Acute Promyelocytic Leukemia

    PubMed Central

    Rodriguez, Eduardo A.; Lopez, Marvin A.; Valluri, Kartik; Wang, Danlu; Fischer, Andrew; Perdomo, Tatiana

    2015-01-01

    Patient: Female, 43 Final Diagnosis: Myeloid sarcoma appendicitis Symptoms: Abdominal pain • chills • fever Medication: — Clinical Procedure: Laparoscopic appendectomy, bone marrow biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: The gastrointestinal tract is a rare site for extramedullary involvement in acute promyelocytic leukemia (APL). Case Report: A 43-year-old female with no past medical history presented complaining of mild abdominal pain, fever, and chills for the past day. On examination, she was tachycardic and febrile, with mild tenderness of her right lower quadrant and without signs of peritoneal irritation. Laboratory examination revealed pancytopenia and DIC, with a fibrinogen level of 290 mg/dL. CT of the abdomen showed a thickened and hyperemic appendix without perforation or abscess, compatible with acute appendicitis. The patient was given IV broad-spectrum antibiotics and was transfused with packed red blood cells and platelets. She underwent uncomplicated laparoscopic appendectomy and bone marrow biopsy, which revealed neo-plastic cells of 90% of the total bone marrow cellularity. Flow cytometry indicated presence of 92.4% of immature myeloid cells with t (15: 17) and q (22: 12) mutations, and FISH analysis for PML-RARA demonstrated a long-form fusion transcript, positive for APL. Appendix pathology described leukemic infiltration with co-expression of myeloperoxidase and CD68, consistent with myeloid sarcoma of the appendix. The patient completed a course of daunorubicin, cytarabine, and all trans-retinoic acid. Repeat bone marrow biopsy demonstrated complete remission. She will follow up with her primary care physician and hematologist/oncologist. Conclusions: Myeloid sarcoma of the appendix in the setting of APL is very rare and it might play a role in the development of acute appendicitis. Urgent management, including bone marrow biopsy for definitive diagnosis and urgent surgical intervention

  18. Correlation of microvascular fractal dimension with positron emission tomography [(11)C]-methionine uptake in glioblastoma multiforme: preliminary findings.

    PubMed

    Di Ieva, Antonio; Grizzi, Fabio; Tschabitscher, Manfred; Colombo, Piergiuseppe; Casali, Massimiliano; Simonelli, Matteo; Widhalm, Georg; Muzzio, Pier Carlo; Matula, Christian; Chiti, Arturo; Rodriguez y Baena, Riccardo

    2010-09-01

    Neuroradiological and metabolic imaging is a fundamental diagnostic procedure in the assessment of patients with primary and metastatic brain tumors. The correlation between objective parameters capable of quantifying the neoplastic angioarchitecture and imaging data may improve our understanding of the underlying physiopathology and make it possible to evaluate treatment efficacy in brain tumors. Only a few studies have so far correlated the quantitative parameters measuring the neovascularity of brain tumors with the metabolic profiles measured by means of amino acid uptake in positron emission tomography (PET) scans. Fractal geometry offers new mathematical tools for the description and quantification of complex anatomical systems, including microvascularity. In this study, we evaluated the microvascular network complexity of six cases of human glioblastoma multiforme quantifying the surface fractal dimension on CD34 immunostained specimens. The microvascular fractal dimension was estimated by applying the box-counting algorithm. As the fractal dimension depends on the density, size and shape of the vessels, and their distribution pattern, we defined it as an index of the whole complexity of microvascular architecture and compared it with the uptake of (11)C-methionine (MET) assessed by PET. The different fractal dimension values observed showed that the same histological category of brain tumor had different microvascular network architectures. Fractal dimension ranged between 1.19 and 1.77 (mean: 1.415+/-0.225), and the uptake of (11)C-methionine ranged between 1.30 and 5.30. A statistically significant direct correlation between the microvascular fractal dimension and the uptake of (11)C-methionine (p=0.02) was found. Our preliminary findings indicate that that vascularity (estimated on the histologic specimens by means of the fractal dimension) and (11)C-methionine uptake (assessed by PET) closely correlate in glioblastoma multiforme and that microvascular

  19. The role of the plastic surgeon in disaster relief.

    PubMed

    Thakar, Hema J; Pepe, Paul E; Rohrich, Rod J

    2009-09-01

    Awareness of large-scale disasters among members of the medical community and the public at large has been heightened by recent events such as the 1995 Oklahoma City bombing incident, the 2001 World Trade Center attack, and the 2005 London Underground bombings. Experience with these events has highlighted the critical role of surgical specialists, including plastic surgeons. As part of their residency, plastic surgeons are trained in acute trauma management. In addition, they also are required to demonstrate expertise in the assessment and treatment of soft-tissue injuries, upper extremity trauma, facial fractures, and both operative and nonoperative burn management. Accordingly, the plastic surgeon is among the most qualified of physicians to provide specialized injury care, especially in the disaster medicine setting. In turn, training programs should include key elements of incident command and catastrophe relief.

  20. Plastics in the Marine Environment.

    PubMed

    Law, Kara Lavender

    2017-01-03

    Plastics contamination in the marine environment was first reported nearly 50 years ago, less than two decades after the rise of commercial plastics production, when less than 50 million metric tons were produced per year. In 2014, global plastics production surpassed 300 million metric tons per year. Plastic debris has been detected worldwide in all major marine habitats, in sizes from microns to meters. In response, concerns about risks to marine wildlife upon exposure to the varied forms of plastic debris have increased, stimulating new research into the extent and consequences of plastics contamination in the marine environment. Here, I present a framework to evaluate the current understanding of the sources, distribution, fate, and impacts of marine plastics. Despite remaining knowledge gaps in mass budgeting and challenges in investigating ecological impacts, the increasing evidence of the ubiquity of plastics contamination in the marine environment, the continued rapid growth in plastics production, and the evidence-albeit limited-of demonstrated impacts to marine wildlife support immediate implementation of source-reducing measures to decrease the potential risks of plastics in the marine ecosystem.

  1. Abiotic degradation of plastic films

    NASA Astrophysics Data System (ADS)

    Ángeles-López, Y. G.; Gutiérrez-Mayen, A. M.; Velasco-Pérez, M.; Beltrán-Villavicencio, M.; Vázquez-Morillas, A.; Cano-Blanco, M.

    2017-01-01

    Degradable plastics have been promoted as an option to mitigate the environmental impacts of plastic waste. However, there is no certainty about its degradability under different environmental conditions. The effect of accelerated weathering (AW), natural weathering (NW) and thermal oxidation (TO) on different plastics (high density polyethylene, HDPE; oxodegradable high density polyethylene, HDPE-oxo; compostable plastic, Ecovio ® metalized polypropylene, PP; and oxodegradable metalized polypropylene, PP-oxo) was studied. Plastics films were exposed to AW per 110 hours; to NW per 90 days; and to TO per 30 days. Plastic films exposed to AW and NW showed a general loss on mechanical properties. The highest reduction in elongation at break on AW occurred to HDPE-oxo (from 400.4% to 20.9%) and was higher than 90% for HDPE, HDPE-oxo, Ecovio ® and PP-oxo in NW. No substantial evidence of degradation was found on plastics exposed to TO. Oxo-plastics showed higher degradation rates than their conventional counterparts, and the compostable plastic was resistant to degradation in the studied abiotic conditions. This study shows that degradation of plastics in real life conditions will vary depending in both, their composition and the environment.

  2. Plastics in the Marine Environment

    NASA Astrophysics Data System (ADS)

    Law, Kara Lavender

    2017-01-01

    Plastics contamination in the marine environment was first reported nearly 50 years ago, less than two decades after the rise of commercial plastics production, when less than 50 million metric tons were produced per year. In 2014, global plastics production surpassed 300 million metric tons per year. Plastic debris has been detected worldwide in all major marine habitats, in sizes from microns to meters. In response, concerns about risks to marine wildlife upon exposure to the varied forms of plastic debris have increased, stimulating new research into the extent and consequences of plastics contamination in the marine environment. Here, I present a framework to evaluate the current understanding of the sources, distribution, fate, and impacts of marine plastics. Despite remaining knowledge gaps in mass budgeting and challenges in investigating ecological impacts, the increasing evidence of the ubiquity of plastics contamination in the marine environment, the continued rapid growth in plastics production, and the evidence—albeit limited—of demonstrated impacts to marine wildlife support immediate implementation of source-reducing measures to decrease the potential risks of plastics in the marine ecosystem.

  3. Use of recycled plastics in wood plastic composites - a review.

    PubMed

    Kazemi Najafi, Saeed

    2013-09-01

    The use of recycled and waste thermoplastics has been recently considered for producing wood plastic composites (WPCs). They have great potential for WPCs manufacturing according to results of some limited researches. This paper presents a detailed review about some essential properties of waste and recycled plastics, important for WPCs production, and of research published on the effect of recycled plastics on the physical and mechanical properties of WPCs.

  4. Evidence of myocardial scarring and microvascular obstruction on cardiac magnetic resonance imaging in a series of patients presenting with myocardial infarction without obstructed coronary arteries.

    PubMed

    Hermens, Jeannine A J M; van Es, Jan; von Birgelen, Clemens; Op den Akker, Jeroen W; Wagenaar, Lodewijk J

    2014-08-01

    Patients with acute chest pain, electrocardiographic ST-elevation and significant elevation of cardiac troponin but without obstructive coronary artery disease represent a diagnostic and therapeutic dilemma. Cardiac magnetic resonance imaging (CMR) can elucidate underlying alternative causes of troponin elevation including detection of (minor) myocardial infarction (MI) by identifying myocardial scarring as delayed enhancement. Of 77 patients, who were admitted between March 2009 and December 2012 with electrocardiographic (ECG) and biochemical evidence of acute MI without obstructive coronary artery disease, 45 patients underwent CMR that showed in 11/77 (14%) late gadolinium enhancement (LGE), compatible with myocardial scarring. We analyzed clinical, echocardiographic, and CMR data of these patients. Elevated troponin I levels were observed in all patients (median 1.3 ng/l, IQR 0.44-187) with median peak creatinine phosphokinase of 485 U/l (IQR 234-618). Echocardiographic wall motion abnormalities were detected in 8/11 (73%) patients; in 75% of these segments, ECG abnormalities were observed in corresponding leads. CMR detected LGE in the inferior (4/11), the inferolateral (5/11), the inferoseptal (2/11), the anterior (3/11), apical (3/11) and in the lateral segments (2/11). In addition, in all but two patients, these segments matched ECG abnormalities in corresponding leads. CMR identified microvascular obstruction in 4/11 (36%) patients. Patients with clinical, ECG, and biochemical signs of acute MI but unobstructed coronary arteries may have CMR-detectable myocardial scars. Information on myocardial scarring may help to make the diagnosis and draw therapeutic consequences. This case series underlines the value of contrast-enhanced CMR for myocardial tissue characterization.

  5. One plasticity model for problems of plastic metal working

    NASA Astrophysics Data System (ADS)

    Greshnov, V. M.

    2008-11-01

    Scalar and tensor models of plastic flow of metals extending plasticity theory are considered over a wide range of temperatures and strain rates. Equations are derived using the physico-phenomenological approach based on modern concepts and methods of the physics and mechanics of plastic deformation. For hardening and viscoplastic solids, a new mathematical formulation of the boundary-value plasticity problem taking into account loading history is obtained. Results of testing of the model are given. A numerical finite-element algorithm for the solution of applied problems is described.

  6. Plastic Surgery and Suicide: A Clinical Guide for Plastic Surgeons.

    PubMed

    Reddy, Vikram; Coffey, M Justin

    2016-08-01

    Several studies have identified an increased risk of suicide among patient populations which a plastic surgeon may have a high risk of encountering: women undergoing breast augmentation, cosmetic surgery patients, and breast cancer patients. No formal guidelines exist to assist a plastic surgeon when faced with such a patient, and not every plastic surgery team has mental health clinicians that are readily accessible for consultation or referral. The goal of this clinical guide is to offer plastic surgeons a set of practical approaches to manage potentially suicidal patients. In addition, the authors review a screening tool, which can assist surgeons when encountering high-risk patients.

  7. Plastic Surgery and Suicide: A Clinical Guide for Plastic Surgeons

    PubMed Central

    Coffey, M. Justin

    2016-01-01

    Summary: Several studies have identified an increased risk of suicide among patient populations which a plastic surgeon may have a high risk of encountering: women undergoing breast augmentation, cosmetic surgery patients, and breast cancer patients. No formal guidelines exist to assist a plastic surgeon when faced with such a patient, and not every plastic surgery team has mental health clinicians that are readily accessible for consultation or referral. The goal of this clinical guide is to offer plastic surgeons a set of practical approaches to manage potentially suicidal patients. In addition, the authors review a screening tool, which can assist surgeons when encountering high-risk patients. PMID:27622096

  8. Direct liquefaction of plastics and coprocessing of coal with plastics

    SciTech Connect

    Huffman, G.P.; Feng, Z.; Mahajan, V.

    1995-12-31

    The objectives of this work were to optimize reaction conditions for the direct liquefaction of waste plastics and the coprocessing of coal with waste plastics. In previous work, the direct liquefaction of medium and high density polyethylene (PE), polypropylene (PPE), poly(ethylene terephthalate) (PET), and a mixed plastic waste, and the coliquefaction of these plastics with coals of three different ranks was studied. The results established that a solid acid catalyst (HZSM-5 zeolite) was highly active for the liquefaction of the plastics alone, typically giving oil yields of 80-95% and total conversions of 90-100% at temperatures of 430-450 {degrees}C. In the coliquefaction experiments, 50:50 mixtures of plastic and coal were used with a tetralin solvent (tetralin:solid = 3:2). Using approximately 1% of the HZSM-5 catalyst and a nanoscale iron catalyst, oil yields of 50-70% and total conversion of 80-90% were typical. In the current year, further investigations were conducted of the liquefaction of PE, PPE, and a commingled waste plastic obtained from the American Plastics Council (APC), and the coprocessing of PE, PPE and the APC plastic with Black Thunder subbituminous coal. Several different catalysts were used in these studies.

  9. Processing plastics in Packerland

    SciTech Connect

    Ridgley, H.

    1998-04-01

    Located in Green Bay, Wisconsin, Catenation, Inc. is a privately held recycling company dedicated to the recovery of post-consumer plastic containers. What makes the company stand out is its ability to separate and sort material from a commingled bale. Catenation uses custom-made, high-speed, computer-driven vision equipment to scan and sort every bottle by category. The computer even can be programmed to distinguish soiled jugs from clean containers. This is a selling point for buyers of resin who are insistent on receiving high-grade material.

  10. Fabrication of plastic biochips

    SciTech Connect

    Saaem, Ishtiaq; Ma, Kuo-Sheng; Alam, S. Munir; Tian Jingdong

    2010-07-15

    A versatile surface functionalization procedure based on rf magnetron sputtering of silica was performed on poly(methylmethacrylate), polycarbonate, polypropylene, and cyclic olefin copolymers (Topas 6015). The hybrid thermoplastic surfaces were characterized by x-ray photoelectron spectrometer analysis and contact angle measurements. The authors then used these hybrid materials to perform a sandwich assay targeting an HIV-1 antibody using fluorescent detection and biotinylated peptides immobilized using the bioaffinity of biotin-neutravidin. They found a limit of detection similar to arrays on glass surfaces and believed that this plastic biochip platform may be used for the development of disposable immunosensing and diagnostic applications.

  11. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  12. A Conservative Formulation for Plasticity

    DTIC Science & Technology

    1992-01-01

    diverse. For instance, the microphysical pictures of metal plasticity and of the flow of granular materials are quite different. Furthermore, passage from...of inhomogeneous materials can be adapted to model plasticity by allowing- the local reference frames of Noll to be dynramic [6]. In this approach...gradient and the entropy. Choosing a plasticity model amounts to specifying thle evolu- tion and constitutive e-vations. 472 PLOHIR AND SHARP A general

  13. The commercialization of plastic surgery.

    PubMed

    Swanson, Eric

    2013-09-01

    The last decade has brought a major challenge to the traditional practice of plastic surgery from corporations that treat plastic surgery as a commercial product and market directly to the public. This corporate medicine model may include promotion of a trademarked procedure or device, national advertising that promises stunning results, sales consultants, and claims of innovation, superiority, and improved safety. This article explores the ethics of this business practice and whether corporate medicine is a desirable model for patients and plastic surgeons.

  14. Americium behaviour in plastic vessels.

    PubMed

    Legarda, F; Herranz, M; Idoeta, R; Abelairas, A

    2010-01-01

    The adsorption of (241)Am dissolved in water in different plastic storage vessels was determined. Three different plastics were investigated with natural and distilled waters and the retention of (241)Am by these plastics was studied. The same was done by varying vessel agitation time, vessel agitation speed, surface/volume ratio of water in the vessels and water pH. Adsorptions were measured to be between 0% and 70%. The adsorption of (241)Am is minimized with no water agitation, with PET or PVC plastics, and by water acidification.

  15. White matter plasticity in adulthood.

    PubMed

    Wang, S; Young, K M

    2014-09-12

    CNS white matter is subject to a novel form of neural plasticity which has been termed "myelin plasticity". It is well established that oligodendrocyte generation and the addition of new myelin internodes continue throughout normal adulthood. These new myelin internodes maybe required for the de novo myelination of previously unmyelinated axons, myelin sheath replacement, or even myelin remodeling. Each process could alter axonal conduction velocity, but to what end? We review the changes that occur within the white matter over the lifetime, the known regulators and mediators of white matter plasticity in the mature CNS, and the physiological role this plasticity may play in CNS function.

  16. THERMAL STABILITY OF GLASS PLASTICS.

    DTIC Science & Technology

    COMPOSITE MATERIALS, THERMAL STABILITY), (* GLASS TEXTILES, THERMAL STABILITY), (*LAMINATED PLASTICS , THERMAL STABILITY), HEATING, COOLING, MECHANICAL PROPERTIES, FATIGUE(MECHANICS), FLEXURAL STRENGTH, THERMAL STRESSES, USSR

  17. Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement

    PubMed Central

    Del Rosso, A; Distler, O; Milia, A; Emanueli, C; Ibba-Manneschi, L; Guiducci, S; Conforti, M; Generini, S; Pignone, A; Gay, S; Madeddu, P; Matucci-Cerinic, M

    2005-01-01

    Background: In systemic sclerosis (SSc) the lack of an angiogenic response to hypoxia may be due to inappropriate synthesis of angiogenic and angiostatic factors. Tissue kallikrein (t-kallikrein), regulating the kallikrein-kinin system and acting on the microcirculation, is a potent angiogenic agent, and kallistatin is its natural inhibitor. Objective: To evaluate, in patients with SSc, t-kallikrein and kallistatin levels and their correlation with clinical features and measures of microvascular involvement. Patients and methods: Serum levels of t-kallikrein and kallistatin (ELISA) and t-kallikrein skin expression (immunohistochemistry) were studied in patients with SSc, and evaluated for subset (dSSc or lSSc), clinical and immunological features, and microvascular involvement (ulcers, telangiectasias, nailfold videocapillaroscopy). Results: Circulating levels of t-kallikrein were higher in SSc than in controls (p<0.001). T-kallikrein did not differ between lSSc and dSSc, although it was higher in lSSc than in controls (p<0.001).T-kallikrein levels were higher in patients with early and active capillaroscopic pattern than in those with late pattern (p = 0.019 and 0.023). Patients with giant capillaries and capillary microhaemorrhages had higher t-kallikrein concentrations than patients with architectural derangement (p = 0.04). No differences in kallistatin levels were detected between patients with SSc and controls, or between lSSc and dSSc. In early SSc skin, the presence of t-kallikrein was found in endothelial and in perivascular inflammatory cells, while no staining in skin of advanced SSc was detected. Conclusion: T-kallikrein levels are increased in patients with SSc, particularly in lSSc, and are associated with early and active capillaroscopic patterns. T-kallikrein may play a part in SSc microvascular changes. PMID:15708892

  18. Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis

    PubMed Central

    Liu, Xiaohui; Xu, Dongzhou; Wang, Yuxin; Chen, Ting; Wang, Qi; Zhang, Jian; You, Tao; Zhu, Li

    2016-01-01

    Background The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. Material/Methods Myocardial ischemia-reperfusion in wild-type C57BL/6J mice was induced by transient ligation of the left anterior descending artery. GLA or vehicle (solvent) was administrated intraperitoneally to the mice before reperfusion started. After 24 h of myocardial reperfusion, ischemic size was revealed by Evans blue/TTC staining. Cardiac function was evaluated by echocardiography and microvascular thrombosis was assessed by immunofluorescence staining of affected heart tissue. We also measured the phosphorylation of AKT, ERK, P-GSK-3β, and cleaved caspase 3 in the myocardium. Results Compared to the solvent-treated control group, GLA administration significantly reduced infarct size (GLA 13.85±2.08% vs. Control 18.95±0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF) (GLA 53.13±1.11% vs. Control 49.99±1.25%, p<0.05) and left ventricular fractional shortening (LVFS) (28.34±0.71% vs. Control 25.11±0.74%, p<0.05) in mice subjected to myocardial ischemia-reperfusion. GLA also attenuated microvascular thrombosis (P<0.05) and increased the phosphorylation of pro-survival kinase AKT (P<0.05) and GSK-3β (P<0.05) in the myocardium upon reperfusion injury. Conclusions Administration of GLA before reperfusion ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective roles of GLA may be mediated through the attenuation of microvascular thrombosis. PMID:27716735

  19. Monitoring of microvascular free flaps following oropharyngeal reconstruction using infrared thermography: first clinical experiences.

    PubMed

    Just, Maren; Chalopin, Claire; Unger, Michael; Halama, Dirk; Neumuth, Thomas; Dietz, Andreas; Fischer, Miloš

    2016-09-01

    The aim of this study is to investigate static and dynamic infrared (IR) thermography for intra- and postoperative free-flap monitoring following oropharyngeal reconstruction. Sixteen patients with oropharyngeal reconstruction by free radial forearm flap were included in this prospective, clinical study (05/2013-08/2014). Prior ("intraop_pre") and following ("intraop_post") completion of the microvascular anastomoses, IR thermography was performed for intraoperative flap monitoring. Further IR images were acquired one day ("postop_1") and 10 days ("postop_10") after surgery for postoperative flap monitoring. Of the 16, 15 transferred free radial forearm flaps did not show any perfusion failure. A significant decreasing mean temperature difference (∆T: temperature difference between the flap surface and the surrounding tissue in Kelvin) was measured at all investigation points in comparison with the temperature difference at "intraop_pre" (mean values on all patients: ∆T intraop_pre = -2.64 K; ∆T intraop_post = -1.22 K, p < 0.0015; ∆T postop_1 = -0.54 K, p < 0.0001; ∆T postop_10 = -0.58 K, p < 0.0001). Intraoperative dynamic IR thermography showed typical pattern of non-pathological rewarming due to re-established flap perfusion after completion of the microvascular anastomoses. Static and dynamic IR thermography is a promising, objective method for intraoperative and postoperative monitoring of free-flap reconstructions in head and neck surgery and to detect perfusion failure, before macroscopic changes in the tissue surface are obvious. A lack of significant decrease of the temperature difference compared to surrounding tissue following completion of microvascular anastomoses and an atypical rewarming following a thermal challenge are suggestive of flap perfusion failure.

  20. EFFECT OF IRRADIATION ON MICROVASCULAR ENDOTHELIAL CELLS OF PAROTID GLANDS IN THE MINIATURE PIG

    PubMed Central

    Xu, Junji; Yan, Xing; Gao, Runtao; Mao, Lisha; Cotrim, Ana P.; Zheng, Changyu; Zhang, Chunmei; Baum, Bruce J.; Wang, Songlin

    2013-01-01

    Purpose To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands. Methods and Materials A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg2+-dependent SMase (ASMase and NSMase, respectively) was also assayed. Results Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics. Conclusions Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage. PMID:20832188

  1. Computer-based analysis of microvascular alterations in a mouse model for Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Heinzer, Stefan; Müller, Ralph; Stampanoni, Marco; Abela, Rafael; Meyer, Eric P.; Ulmann-Schuler, Alexandra; Krucker, Thomas

    2007-03-01

    Vascular factors associated with Alzheimer's disease (AD) have recently gained increased attention. To investigate changes in vascular, particularly microvascular architecture, we developed a hierarchical imaging framework to obtain large-volume, high-resolution 3D images from brains of transgenic mice modeling AD. In this paper, we present imaging and data analysis methods which allow compiling unique characteristics from several hundred gigabytes of image data. Image acquisition is based on desktop micro-computed tomography (µCT) and local synchrotron-radiation µCT (SRµCT) scanning with a nominal voxel size of 16 µm and 1.4 µm, respectively. Two visualization approaches were implemented: stacks of Z-buffer projections for fast data browsing, and progressive-mesh based surface rendering for detailed 3D visualization of the large datasets. In a first step, image data was assessed visually via a Java client connected to a central database. Identified characteristics of interest were subsequently quantified using global morphometry software. To obtain even deeper insight into microvascular alterations, tree analysis software was developed providing local morphometric parameters such as number of vessel segments or vessel tortuosity. In the context of ever increasing image resolution and large datasets, computer-aided analysis has proven both powerful and indispensable. The hierarchical approach maintains the context of local phenomena, while proper visualization and morphometry provide the basis for detailed analysis of the pathology related to structure. Beyond analysis of microvascular changes in AD this framework will have significant impact considering that vascular changes are involved in other neurodegenerative diseases as well as in cancer, cardiovascular disease, asthma, and arthritis.

  2. NEU1 and NEU3 Sialidase Activity Expressed in Human Lung Microvascular Endothelia

    PubMed Central

    Cross, Alan S.; Hyun, Sang Won; Miranda-Ribera, Alba; Feng, Chiguang; Liu, Anguo; Nguyen, Chinh; Zhang, Lei; Luzina, Irina G.; Atamas, Sergei P.; Twaddell, William S.; Guang, Wei; Lillehoj, Erik P.; Puché, Adam C.; Huang, Wei; Wang, Lai-Xi; Passaniti, Antonino; Goldblum, Simeon E.

    2012-01-01

    The microvascular endothelial surface expresses multiple molecules whose sialylation state regulates multiple aspects of endothelial function. To better regulate these sialoproteins, we asked whether endothelial cells (ECs) might express one or more catalytically active sialidases. Human lung microvascular EC lysates contained heat-labile sialidase activity for a fluorogenic substrate, 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (4-MU-NANA), that was dose-dependently inhibited by the competitive sialidase inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid but not its negative control. The EC lysates also contained sialidase activity for a ganglioside mixture. Using real time RT-PCR to detect mRNAs for the four known mammalian sialidases, NEU1, -2, -3, and -4, NEU1 mRNA was expressed at levels 2700-fold higher that those found for NEU2, -3, or -4. Western analyses indicated NEU1 and -3 protein expression. Using confocal microscopy and flow cytometry, NEU1 was immunolocalized to both the plasma membrane and the perinuclear region. NEU3 was detected both in the cytosol and nucleus. Prior siRNA-mediated knockdown of NEU1 and NEU3 each decreased EC sialidase activity for 4-MU-NANA by >65 and >17%, respectively, and for the ganglioside mixture by 0 and 40%, respectively. NEU1 overexpression in ECs reduced their migration into a wound by >40%, whereas NEU3 overexpression did not. Immunohistochemical studies of normal human tissues immunolocalized NEU1 and NEU3 proteins to both pulmonary and extrapulmonary vascular endothelia. These combined data indicate that human lung microvascular ECs as well as other endothelia express catalytically active NEU1 and NEU3. NEU1 restrains EC migration, whereas NEU3 does not. PMID:22403397

  3. Eccentric exercise slows in vivo microvascular reactivity during brief contractions in human skeletal muscle.

    PubMed

    Larsen, Ryan G; Hirata, Rogerio P; Madzak, Adnan; Frøkjær, Jens B; Graven-Nielsen, Thomas

    2015-12-01

    Unaccustomed exercise involving eccentric contractions results in muscle soreness and an overall decline in muscle function, however, little is known about the effects of eccentric exercise on microvascular reactivity in human skeletal muscle. Fourteen healthy men and women performed eccentric contractions of the dorsiflexor muscles in one leg, while the contralateral leg served as a control. At baseline, and 24 and 48 h after eccentric exercise, the following were acquired bilaterally in the tibialis anterior muscle: 1) transverse relaxation time (T2)-weighted magnetic resonance images to determine muscle cross-sectional area (mCSA) and T2; 2) blood oxygen level-dependent (BOLD) images during and following brief, maximal voluntary contractions (MVC) to monitor the hyperemic responses with participants positioned supine in a 3T magnet; 3) muscle strength; and 4) pain pressure threshold. Compared with the control leg, eccentric exercise resulted in soreness, decline in strength (∼20%), increased mCSA (∼7%), and prolonged T2 (∼7%) at 24 and 48 h (P < 0.05). The BOLD response to a brief MVC was altered 24 and 48 h after eccentric exercise, such that time-to-peak (∼35%, P < 0.05) and time-to-half-recovery (∼23%, P < 0.05) were prolonged. The altered contraction-induced hyperemic response suggests slowed microvascular reactivity and altered matching of O2 delivery to O2 utilization within muscle tissue showing signs of muscle damage. These changes in microvascular regulation after eccentric exercise may impede rapid adjustments in muscle blood flow at exercise onset and during activities involving brief bursts of muscle activation, which may impair O2 delivery and contribute to reduced muscle function after eccentric exercise.

  4. Effect of Irradiation on Microvascular Endothelial Cells of Parotid Glands in the Miniature Pig

    SciTech Connect

    Xu Junji; Yan Xing; Gao Runtao; Mao Lisha; Cotrim, Ana P.; Zheng Changyu; Zhang Chunmei; Baum, Bruce J.; Wang Songlin

    2010-11-01

    Purpose: To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands. Methods and Materials: A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg{sup 2+}-dependent SMase (ASMase and NSMase, respectively) was also assayed. Results: Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics. Conclusions: Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage.

  5. Nanoparticle Inhalation Impairs Coronary Microvascular Reactivity via a Local Reactive Oxygen Species-Dependent Mechanism

    PubMed Central

    LeBlanc, A. J.; Moseley, A. M.; Chen, B. T.; Frazer, D.; Castranova, V.

    2010-01-01

    We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO2 nanoparticles via inhalation to produce a pulmonary deposition of 10 µg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with NG-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO2 exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated Ach-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO2. Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO2, but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range. PMID:20033351

  6. Effects of extreme hemodilution with hemoglobin-based O2 carriers on microvascular pressure.

    PubMed

    Cabrales, Pedro; Tsai, Amy G; Winslow, Robert M; Intaglietta, Marcos

    2005-05-01

    A surface-modified polyethylene glycol-conjugated human hemoglobin (MP4) and alpha alpha-cross-linked human hemoglobin (alpha alpha Hb) were used to restore oxygen carrying capacity in conditions of extreme hemodilution (hematocrit 11%) in the hamster window model preparation. Changes in microvascular function were analyzed in terms of effects on capillary pressure and functional capillary density (FCD). MP4, at 1.0 +/- 0.2 g/dl blood concentration, significantly lowered mean arterial pressure (MAP) below baseline (99.6 +/- 7.6 mmHg) to 82.4 +/- 6.9 mmHg (P < 0.05) and decreased of FCD to 70 +/- 9%. alpha alpha Hb caused a greater recovery in MAP to 94.4 +/- 6.2 mmHg and lowered FCD to 62 +/- 8%. However, differences between alpha alpha Hb and MP4 in FCD were not statistically significant. Capillary pressures were in the ranges of 17-21 mmHg for MP4 and 15-19 mmHg for alpha alpha Hb, with both significantly lower than baseline (P < 0.05). Pressure in 80-microm-diameter arterioles was significantly increased with alpha alpha Hb relative to MP4 (P < 0.05). These results were compared with previous findings on the relation between capillary pressure and FCD; they supported the concept of a relationship between FCD and capillary pressure. Measurement of changes in arteriolar diameter, microvascular blood flow, and FCD show that there was no statistical difference between using alpha alpha Hb and MP4 in extreme hemodilution. Microvascular resistance in arterioles with a diameter range of 70-80 microm showed an increase relative to control with alpha alpha Hb, whereas MP4 caused a decrease.

  7. Depth-dependent flow and pressure characteristics in cortical microvascular networks

    PubMed Central

    Schmid, Franca; Kleinfeld, David; Jenny, Patrick; Weber, Bruno

    2017-01-01

    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. PMID:28196095

  8. Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans.

    PubMed

    Velasco, Alejandro; Solow, Elizabeth; Price, Angela; Wang, Zhongyun; Arbique, Debbie; Arbique, Gary; Adams-Huet, Beverley; Schwedhelm, Edzard; Lindner, Jonathan R; Vongpatanasin, Wanpen

    2016-07-01

    Use of β-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation β-blocker, which is thought to avoid this side effect via its vasodilating property. However, the effects of nebivolol on skeletal muscle perfusion during exercise have not been determined in hypertensive patients. Accordingly, we performed contrast-enhanced ultrasound perfusion imaging of the forearm muscles in 25 untreated stage I hypertensive patients at rest and during handgrip exercise at baseline or after 12 wk of treatment with nebivolol (5-20 mg/day) or metoprolol succinate (100-300 mg/day), with a subsequent double crossover for 12 wk. Metoprolol and nebivolol each induced a reduction in the resting blood pressure and heart rate (130.9 ± 2.6/81.7 ± 1.8 vs. 131.6 ± 2.7/80.8 ± 1.5 mmHg and 63 ± 2 vs. 64 ± 2 beats/min) compared with baseline (142.1 ± 2.0/88.7 ± 1.4 mmHg and 75 ± 2 beats/min, respectively, both P < 0.01). Metoprolol significantly attenuated the increase in microvascular blood volume (MBV) during handgrip at 12 and 20 repetitions/min by 50% compared with baseline (mixed-model P < 0.05), which was not observed with nebivolol. Neither metoprolol nor nebivolol affected microvascular flow velocity (MFV). Similarly, metoprolol and nebivolol had no effect on the increase in the conduit brachial artery flow as determined by duplex Doppler ultrasound. Thus our study demonstrated a first direct evidence for metoprolol-induced impairment in the recruitment of microvascular units during exercise in hypertensive humans, which was avoided by nebivolol. This selective reduction in MBV without alteration in MFV by metoprolol suggested impaired vasodilation at the precapillary arteriolar level.

  9. Differential effects of Bartonella henselae on human and feline macro- and micro-vascular endothelial cells.

    PubMed

    Berrich, Moez; Kieda, Claudine; Grillon, Catherine; Monteil, Martine; Lamerant, Nathalie; Gavard, Julie; Boulouis, Henri Jean; Haddad, Nadia

    2011-01-01

    Bartonella henselae, a zoonotic agent, induces tumors of endothelial cells (ECs), namely bacillary angiomatosis and peliosis in immunosuppressed humans but not in cats. In vitro studies on ECs represent to date the only way to explore the interactions between Bartonella henselae and vascular endothelium. However, no comparative study of the interactions between Bartonella henselae and human (incidental host) ECs vs feline (reservoir host) ECs has been carried out because of the absence of any available feline endothelial cell lines.To this purpose, we have developed nine feline EC lines which allowed comparing the effects of Bartonella strains on human and feline micro-vascular ECs representative of the infection development sites such as skin, versus macro-vascular ECs, such as umbilical vein.Our model revealed intrinsic differences between human (Human Skin Microvascular ECs -HSkMEC and Human Umbilical Vein ECs - iHUVEC) and feline ECs susceptibility to Bartonella henselae infection.While no effect was observed on the feline ECs upon Bartonella henselae infection, the human ones displayed accelerated angiogenesis and wound healing.Noticeable differences were demonstrated between human micro- and macro-vasculature derived ECs both in terms of pseudo-tube formation and healing. Interestingly, Bartonella henselae effects on human ECs were also elicited by soluble factors.Neither Bartonella henselae-infected Human Skin Microvascular ECs clinically involved in bacillary angiomatosis, nor feline ECs increased cAMP production, as opposed to HUVEC.Bartonella henselae could stimulate the activation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) in homologous cellular systems and trigger VEGF production by HSkMECs only, but not iHUVEC or any feline ECs tested.These results may explain the decreased pathogenic potential of Bartonella henselae infection for cats as compared to humans and strongly suggest that an autocrine secretion of VEGF by human skin

  10. Objective outcomes analysis following microvascular gracilis transfer for facial reanimation: a review of 10 years' experience.

    PubMed

    Bhama, Prabhat K; Weinberg, Julie S; Lindsay, Robin W; Hohman, Marc H; Cheney, Mack L; Hadlock, Tessa A

    2014-01-01

    IMPORTANCE Objective assessment of smile outcome after microvascular free gracilis transfer is challenging, and quantification of smile outcomes in the literature is inconsistent. OBJECTIVE To report objective excursion and symmetry outcomes from a series of free gracilis cases and investigate the predictive value of intraoperative measurements on final outcomes. DESIGN, SETTING, AND PARTICIPANTS A retrospective medical chart review was undertaken of all patients who underwent microvascular free gracilis transfer for smile at our institution over the past 10 years. MAIN OUTCOMES AND MEASURES Outcome measures included the following: smile excursion, angle of smile with respect to the vertical midline, and facial symmetry during repose and with smile. Measurements were obtained using an automated tool for assessment of facial landmarks (FACE-Gram). An exhaustive set of intraoperative parameters including degree of recoil of the gracilis muscle following harvest, the degree to which the muscle foreshortened during stimulation of the obturator nerve, final stretched length of the inset muscle, surgeon assessment of neurorrhaphy and pulse pressure, ischemia time, number of sutures used during neurorrhaphy, nerve used to innervate the flap, and surgeon assessment of oral commissure overcorrection were recorded and placed into a linear regression model to investigate correlations with smile. RESULTS From March 2003 to March 2013, 154 microvascular free gracilis transfers were performed for facial reanimation at our institution, 14 (9%) of which were deemed failures. Of the remaining 140 flaps, 127 fulfilled inclusion criteria and constituted the study cohort. Smile excursion, angle excursion, and symmetry of the oral commissure at repose and with smile all improved following gracilis free flap (P < .05). Associations between selected outcomes measures and intraoperative gracilis measurements were identified. CONCLUSIONS AND RELEVANCE Facial reanimation using free

  11. The study of synchronization of rhythms of microvascular blood flow and oxygen saturation during adaptive changes

    NASA Astrophysics Data System (ADS)

    Dunaev, Andrey V.; Sidorov, Victor V.; Krupatkin, Alexander I.; Rafailov, Ilya E.; Palmer, Scott G.; Sokolovski, Sergei G.; Stewart, Neil A.; Rafailov, Edik U.

    2014-02-01

    Multi-functional laser non-invasive diagnostic systems, such as "LAKK-M", allow the study of a number of microcirculatory parameters, including blood microcirculatory index (Im) (by laser Doppler flowmetry, LDF) and oxygen saturation (StO2) of skin tissue (by tissue reflectance oximetry, TRO). Such systems may provide significant information relevant to physiology and clinical medicine. The aim of this research was to use such a system to study the synchronization of microvascular blood flow and oxygen saturation rhythms under normal and adaptive change conditions. Studies were conducted with 8 healthy volunteers - 3 females and 5 males of 21-49 years. Each volunteer was subjected to basic 3 minute tests. The volunteers were observed for between 1-4 months each, totalling 422 basic tests. Measurements were performed on the palmar surface of the right middle finger and the forearm medial surface. Wavelet analysis was used to study rhythmic oscillations in LDF- and TRO-data. Tissue oxygen consumption (from arterial and venal blood oxygen saturation and nutritive flux volume) was calculated for all volunteers during "adaptive changes" as (617+/-123 AU) and (102+/-38 AU) with and without arteriovenous anastomoses (AVAs) respectively. This demonstrates increased consumption compared to normal (495+/-170 AU) and (69+/-40 AU) with and without AVAs respectively. Data analysis demonstrated the emergence of resonance and synchronization of rhythms of microvascular blood flow and oxygen saturation as an adaptive change in myogenic oscillation (vasomotion) resulting from exercise and potentially from psychoemotional stress. Synchronization of myogenic rhythms during adaptive changes suggest increased oxygen consumption resulting from increased microvascular blood flow velocity.

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

    PubMed Central

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

    2015-01-01

    Background 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. Methods and Results 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. Conclusion 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

  13. Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms

    PubMed Central

    Dongare, Shirish; Mathur, Rajani; Saxena, Rohit; Mathur, Sandeep; Agarwal, Renu; Nag, Tapas C.; Srivastava, Sushma; Kumar, Pankaj

    2016-01-01

    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

  14. Management of plastic bronchitis with nebulized tissue plasminogen activator: another brick in the wall.

    PubMed

    Colaneri, Massimo; Quarti, Andrea; Pozzi, Marco; Gasparini, Stefano; Carloni, Ines; de Benedictis, Fernando Maria

    2014-02-13

    Plastic bronchitis is a rare complication of a variety of respiratory diseases and congenital heart disease surgery, particularly Fontan procedure. Bronchial casts with rubber-like consistency develop acutely and may cause severe life-threatening respiratory distress. The management of plastic bronchitis is yet not well defined. Early intermittent, self-administered nebulization of tissue plasminogen activator was found to be effective in preventing deterioration of acute respiratory symptoms in a patient with primary ciliary dyskinesia and recurrent cast formation. Further investigation into new therapeutic strategies for this devastating disease is advocated.

  15. Activity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance

    PubMed Central

    Cheung, Giselle; Sibille, Jérémie; Zapata, Jonathan; Rouach, Nathalie

    2015-01-01

    Recent evidence has shown that astrocytes play essential roles in synaptic transmission and plasticity. Nevertheless, how neuronal activity alters astroglial functional properties and whether such properties also display specific forms of plasticity still remain elusive. Here, we review research findings supporting this aspect of astrocytes, focusing on their roles in the clearance of extracellular potassium and glutamate, two neuroactive substances promptly released during excitatory synaptic transmission. Their subsequent removal, which is primarily carried out by glial potassium channels and glutamate transporters, is essential for proper functioning of the brain. Similar to neurons, different forms of short- and long-term plasticity in astroglial uptake have been reported. In addition, we also present novel findings showing robust potentiation of astrocytic inward currents in response to repetitive stimulations at mild frequencies, as low as 0.75 Hz, in acute hippocampal slices. Interestingly, neurotransmission was hardly affected at this frequency range, suggesting that astrocytes may be more sensitive to low frequency stimulation and may exhibit stronger plasticity than neurons to prevent hyperexcitability. Taken together, these important findings strongly indicate that astrocytes display both short- and long-term plasticity in their clearance of excess neuroactive substances from the extracellular space, thereby regulating neuronal activity and brain homeostasis. PMID:26346563

  16. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  17. Optical measurements of microvascular circulatory function in the foot for detection of peripheral neuropathy

    NASA Astrophysics Data System (ADS)

    Zamora, G.; Chekh, V.; Burge, M.; Barriga, E. S.; Luan, S.; Heintz, P.; Edwards, A.; McGrew, E.; Soliz, P.

    2012-03-01

    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.

  18. Bilateral microvascular second toe transfer for bilateral post-traumatic thumb amputation.

    PubMed

    Nehete, Rajendra; Nehete, Anita; Singla, Sandeep; Adhav, Harshad

    2012-01-01

    In bilateral thumb amputations, the functional impairment is serious and every attempt should be made to reconstruct the thumb. We report a case of bilateral post traumatic thumb amputation, reconstructed with bilateral second toe transfer. Only two such cases have been reported in literature so far. Though there are various modalities for the reconstruction of thumb, microvascular toe transfer has its own merits. The convalescent period is minimal with excellent function. It is bilaterally symmetric and aesthetically superior to the osteoplastic reconstruction. The technical details are discussed, and the long term functional and aesthetic results are presented.

  19. Early Activation of Primary Brain Microvascular Endothelial Cells by Nipah Virus Glycoprotein-Containing Particles

    PubMed Central

    Freitag, Tanja C.

    2015-01-01

    Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes pronounced infection of brain endothelia and central nervous system (CNS) inflammation. Using primary porcine brain microvascular endothelial cells, we showed that upregulation of E-selectin precedes cytokine induction and is induced not only by infectious NiV but also by NiV-glycoprotein-containing virus-like particles. This demonstrates that very early events in NiV brain endothelial infection do not depend on NiV replication but can be triggered by the NiV glycoproteins alone. PMID:26676791

  20. Microvascular Porcine Model for the Optimization of Vascularized Composite Tissue Transplantation

    DTIC Science & Technology

    2012-04-21

    animal model Microvascular techniques Ischemia Reperfusion injury Gracilis flap a b s t r a c t Background: Devastating extremity injuries are...the neck. Flaps then undergo either immediate or delayed inset and reperfusion (1 h [n¼ 6] or 3 h [n¼ 6] of ischemia , respectively). Flaps designated...reperfusion injury [5,6]. LDH peaked for both ischemic time groups at 24 h (Fig. 10). Those flaps that were subjected to 1 h of ischemia had a mean

  1. Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo

    NASA Astrophysics Data System (ADS)

    Jung, Yeongri; Zhi, Zhongwei; Wang, Ruikang K.

    2010-09-01

    Sentinel lymph nodes (SLNs) are the first lymph nodes to drain wastes originated from cancerous tissue. There is a need for an in vivo imaging method that can image the intact SLN to further our understanding of its normal as well as abnormal functions. We report the use of ultrahigh sensitive optical microangiography (UHS-OMAG) to image functional microvascular and lymphatic vessel networks that innervate the intact lymph node in mice in vivo. The promising results show a potential role of UHS-OMAG in the future understanding and diagnosis of the SLN involvement in cancer development.

  2. [Reconstruction of oral mucosa with a micro-vascularized fascia-cutaneous flap from the forearm].

    PubMed

    Burgueño García, Miguel; Cebrián Carretero, José Luis; Muñoz Caro, Jesús Manuel; Arias Gallo, Javier

    2002-01-01

    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.

  3. Bilateral microvascular second toe transfer for bilateral post-traumatic thumb amputation

    PubMed Central

    Nehete, Rajendra; Nehete, Anita; Singla, Sandeep; Adhav, Harshad

    2012-01-01

    In bilateral thumb amputations, the functional impairment is serious and every attempt should be made to reconstruct the thumb. We report a case of bilateral post traumatic thumb amputation, reconstructed with bilateral second toe transfer. Only two such cases have been reported in literature so far. Though there are various modalities for the reconstruction of thumb, microvascular toe transfer has its own merits. The convalescent period is minimal with excellent function. It is bilaterally symmetric and aesthetically superior to the osteoplastic reconstruction. The technical details are discussed, and the long term functional and aesthetic results are presented. PMID:22754176

  4. Indications for the microvascular medial femoral condylar flap in craniomaxillofacial surgery.

    PubMed

    Thiele, Oliver Christian; Kremer, Thomas; Kneser, Ulrich; Mischkowski, Robert Andreas

    2014-07-01

    The medial femoral condylar flap makes it possible to reconstruct bone, cartilage, and skin, but elongation of the pedicle is usually required to bridge the distances to the vascular connections in the neck. The indications in the maxillofacial area include reconstruction of the temporomandibular joint (TMJ), pseudarthrosis of the jaws, osteonecrosis of the jaws and skull, and augmentation of bone in irradiated or otherwise compromised tissue. If small bony defects require safe and reliable osseous, osteochondral, or osteocutaneous reconstruction, the medial femoral condylar flap can be used to fill the gap between small avascular, and larger microvascular, bone transplants.

  5. Plastics recycling: challenges and opportunities.

    PubMed

    Hopewell, Jefferson; Dvorak, Robert; Kosior, Edward

    2009-07-27

    Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3-4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it

  6. Plastics recycling: challenges and opportunities

    PubMed Central

    Hopewell, Jefferson; Dvorak, Robert; Kosior, Edward

    2009-01-01

    Plastics are inexpensive, lightweight and durable materials, which can readily be moulded into a variety of products that find use in a wide range of applications. As a consequence, the production of plastics has increased markedly over the last 60 years. However, current levels of their usage and disposal generate several environmental problems. Around 4 per cent of world oil and gas production, a non-renewable resource, is used as feedstock for plastics and a further 3–4% is expended to provide energy for their manufacture. A major portion of plastic produced each year is used to make disposable items of packaging or other short-lived products that are discarded within a year of manufacture. These two observations alone indicate that our current use of plastics is not sustainable. In addition, because of the durability of the polymers involved, substantial quantities of discarded end-of-life plastics are accumulating as debris in landfills and in natural habitats worldwide. Recycling is one of the most important actions currently available to reduce these impacts and represents one of the most dynamic areas in the plastics industry today. Recycling provides opportunities to reduce oil usage, carbon dioxide emissions and the quantities of waste requiring disposal. Here, we briefly set recycling into context against other waste-reduction strategies, namely reduction in material use through downgauging or product reuse, the use of alternative biodegradable materials and energy recovery as fuel. While plastics have been recycled since the 1970s, the quantities that are recycled vary geographically, according to plastic type and application. Recycling of packaging materials has seen rapid expansion over the last decades in a number of countries. Advances in technologies and systems for the collection, sorting and reprocessing of recyclable plastics are creating new opportunities for recycling, and with the combined actions of the public, industry and governments it

  7. [Postoperative complications in plastic surgery].

    PubMed

    Vogt, P M

    2009-09-01

    Plastic surgery covers a broad spectrum of diseases and conditions in the areas of reconstructive surgery, hand, burn and aesthetic surgery. Besides acquired defects or malformations an increasing number of patients are being treated for surgical or multimodal complications. In a considerable number of patients plastic and reconstructive surgery remains the only therapeutic alternative after other therapy has failed. Therefore complication management in plastic surgery is of utmost importance for a successful outcome. In addition patient expectations in the results of plastic surgery as a discipline of invention and problem solving are steadily increasing. This challenge is reflected in clinical patient management by intensive research in tissue engineering and regenerative medicine. Patients in plastic surgery are recruited from all age groups of either gender, involving traumatic and oncologic as well as congenital and aesthetic disorders. The demographics of aging, multimorbidity and obesity pose new challenges to plastic surgery. Although age over 70 years is not an independent risk factor per se for complications in plastic surgery, e.g. for complex free flap transfer, medical problems are present at a higher rate, which is to be expected in this age group. Risk factors such as alcoholism and coronary heart diseases seem to be independent predictors of perioperative complications. Therefore older patients can also benefit from plastic surgery and recurrent operations by the corresponding risk and complication management. Complication management necessitates careful patient selection, estimation of operative risks and patient-adapted selection of procedures. In addition to expertise in plastic surgery a thorough knowledge of non-surgical and surgical back-up procedures for technical incidents as well as vascular circulatory and wound healing disorders is required to deal successfully with complications in plastic surgery. This article presents these specific

  8. Administration of Traditional Chinese Blood Circulation Activating Drugs for Microvascular Complications in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    He, Lisha; Wang, Han; Gu, Chengjuan; He, Xinhui

    2016-01-01

    Traditional Chinese medicine (TCM) is an important complementary strategy for treating diabetes mellitus (DM) in China. Traditional Chinese blood circulation activating drugs are intended to guide an overall approach to the prevention and treatment of microvascular complications of DM. The core mechanism is related to the protection of the vascular endothelium and the basement membrane. Here, we reviewed the scientific evidence underpinning the use of blood circulation activating drugs to prevent and treat DM-induced microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR). Furthermore, we summarized the effects and mechanism of TCM on improving blood rheology, inhibiting aggregation of platelet, forming advanced glycation end products (AGEs), regulating oxidative stress, reducing blood fat, and improving lipid metabolism. The paper provides a new theoretical basis for the clinical practice of TCM in the prevention and treatment of DM and its microvascular complications. PMID:27830156

  9. Flash Cracking Reactor for Waste Plastic Processing

    NASA Technical Reports Server (NTRS)

    Timko, Michael T.; Wong, Hsi-Wu; Gonzalez, Lino A.; Broadbelt, Linda; Raviknishan, Vinu

    2013-01-01

    Conversion of waste plastic to energy is a growing problem that is especially acute in space exploration applications. Moreover, utilization of heavy hydrocarbon resources (wastes, waxes, etc.) as fuels and chemicals will be a growing need in the future. Existing technologies require a trade-off between product selectivity and feedstock conversion. The objective of this work was to maintain high plastic-to-fuel conversion without sacrificing the liquid yield. The developed technology accomplishes this goal with a combined understanding of thermodynamics, reaction rates, and mass transport to achieve high feed conversion without sacrificing product selectivity. The innovation requires a reaction vessel, hydrocarbon feed, gas feed, and pressure and temperature control equipment. Depending on the feedstock and desired product distribution, catalyst can be added. The reactor is heated to the desired tempera ture, pressurized to the desired pressure, and subject to a sweep flow at the optimized superficial velocity. Software developed under this project can be used to determine optimal values for these parameters. Product is vaporized, transferred to a receiver, and cooled to a liquid - a form suitable for long-term storage as a fuel or chemical. An important NASA application is the use of solar energy to convert waste plastic into a form that can be utilized during periods of low solar energy flux. Unlike previous work in this field, this innovation uses thermodynamic, mass transport, and reaction parameters to tune product distribution of pyrolysis cracking. Previous work in this field has used some of these variables, but never all in conjunction for process optimization. This method is useful for municipal waste incinerator operators and gas-to-liquids companies.

  10. Stress induced neuroendocrine-immune plasticity

    PubMed Central

    Liezmann, Christiane; Stock, Daniel; Peters, Eva M. J.

    2012-01-01

    Research over the past decade has revealed close interaction between the nervous and immune systems in regulation of peripheral inflammation linking psychosocial stress with chronic somatic disease and aging. Moreover emerging data suggests that chronic inflammations lead to a pro-inflammatory status underlying premature aging called inflammaging. In this context, the spleen can be seen as a switch board monitoring peripherally derived neuroendocrine-immune mediators in the blood and keeping up a close communication with the central stress response via its mainly sympathetic innervation. The effect aims at balanced and well-timed stress axis activation and immune adaptation in acute peripheral inflammatory events. Constant adjustment to the needs generated by environmental and endogenous challenges is provided by neuroendocrine-immune plasticity. However, maladaptive plasticity induced e.g., by chronic stress-axis activation and excessive non-neuronal derived neuroendocrine mediators may be at the heart of the observed stress sensitivity promote inflammaging under chronic inflammatory conditions. We here review the role of neurotransmitters, neuropeptides and neurotrophins as stress mediators modulating the immune response in the spleen and their potential role in inflammaging. PMID:23467333

  11. Physical and Mechanical Properties of Glass--Reinforced Plastics,

    DTIC Science & Technology

    REINFORCED PLASTICS , REVIEWS), GLASS TEXTILES, MECHANICAL PROPERTIES, ELECTRICAL PROPERTIES, SILICONE PLASTICS , POLYESTER PLASTICS , PHENOLIC... PLASTICS , EPOXY RESINS, TEST METHODS, NONDESTRUCTIVE TESTING, FIRE RESISTANT MATERIALS, POLYVINYL CHLORIDE, USSR

  12. Plastics to fuel: A review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper reviews recent developments in catalytic and non-catalytic degradation of waste plastics into fuels. Thermal degradation decomposes plastic into three fractions: gas, crude oil, and solid residue. Crude oil from non-catalytic pyrolysis is usually composed of higher boiling point hydrocarb...

  13. Splicing plastic optical fibers

    NASA Astrophysics Data System (ADS)

    Carson, Susan D.; Salazar, Roberto A.

    1991-12-01

    Polymethylmethacrylate (PMMA) plastic optical fiber (500 micrometers diameter, fluoropolymer cladding) has been spliced using a fused silica sleeve and a variety of solvent/PMMA solutions as adhesives. Mechanical splicing using index matching fluid has also been investigated. To ensure good bonding and minimize scattering, fiber ends are polished prior to application of adhesive. Using an LED ((lambda) max approximately 640 nm), losses are routinely less than 1.0 dB/splice, and some adhesive formulations have exhibited losses as low as 0.2 dB/splice. Five-meter fibers with as many as ten splices/fiber have been monitored over a period of several months. No fiber has exhibited an increase in optical loss with time.

  14. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  15. Bronchitis - acute

    MedlinePlus

    ... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...

  16. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...

  17. 3-D Ultrasound Localization Microscopy for Identifying Microvascular Morphology Features of Tumor Angiogenesis at a Resolution Beyond the Diffraction Limit of Conventional Ultrasound

    PubMed Central

    Lin, Fanglue; Shelton, Sarah E.; Espíndola, David; Rojas, Juan D.; Pinton, Gianmarco; Dayton, Paul A.

    2017-01-01

    Angiogenesis has been known as a hallmark of solid tumor cancers for decades, yet ultrasound has been limited in its ability to detect the microvascular changes associated with malignancy. Here, we demonstrate the potential of 'ultrasound localization microscopy' applied volumetrically in combination with quantitative analysis of microvascular morphology, as an approach to overcome this limitation. This pilot study demonstrates our ability to image complex microvascular patterns associated with tumor angiogenesis in-vivo at a resolution of tens of microns - substantially better than the diffraction limit of traditional clinical ultrasound, yet using an 8 MHz clinical ultrasound probe. Furthermore, it is observed that data from healthy and tumor-bearing tissue exhibit significant differences in microvascular pattern and density. Results suggests that with continued development of these novel technologies, ultrasound has the potential to detect biomarkers of cancer based on the microvascular 'fingerprint' of malignant angiogenesis rather than through imaging of blood flow dynamics or the tumor mass itself. PMID:28042327

  18. Microvascular anatomy of the large intestine in adult Xenopus laevis: scanning electron microscopy of vascular corrosion casts and correlative light microscopy.

    PubMed

    Lametschwandtner, A; Bartel, H; Lametschwandtner, U; Tholo, S; Minnich, B

    2010-01-01

    The microvascular anatomy of the large intestine of the adult South African Clawed Toad, Xenopus laevis (Daudin), was studied by scanning electron microscopy (SEM) of vascular corrosion casts (VCCs) and correlative light microscopy. Observations showed the large intestine to be supplied by the haemorrhoidal artery and the posterior mesenteric artery and drain via the posterior haemorrhoidal vein into either the left or right posterior abdominal vein. Both arteries and veins showed a bipinnate supply/draining pattern with branches running circumferentially. Vessels embraced the gut wall while arteries and veins in most cases alternated along the gut length. Many short terminal arterioles arose from the circumferential arteries at almost acute angles and capillarized after a short distance. Capillary lengths were short and continued into numerous postcapillary venules which merged either in a leaf vein-like formation or in a rosette-like formation with up to four draining sites per supplying arteriole. The microvasculature was found to be well adapted 1) to sustain blood flow under different amounts of feces in the gut and 2) to provide optimal conditions for the resorption of water and salts from the gut lumen into the blood vascular system by the high number of venules and their conspiciouos rosette-like and leaf vein-like patterns.

  19. The vascular pattern and viability of microvascularized rib grafts based on periosteal circulation--an experimental study

    SciTech Connect

    Papanastasiou, V.W.; Lalonde, D.H.; Williams, H.B.

    1984-11-01

    Previous reports have stressed the importance of the nutrient blood supply in rib grafts transferred by microvascular anastomoses. In the present experimental study, we have demonstrated that a rib graft transferred by microvascular anastomoses based on periosteal vessels can survive; vascular clearing studies demonstrated that the vascularity of these grafts extends not only into the cortex but the medulla as well. The relative facility of harvesting these grafts (compared with those based on nutrient vessels) should make them the favored choice. Technetium bone scintigraphy proved accurate in the assessment of both vascular pattern and microanastomotic patency. Tetracycline labeling did not correlate well with the patency of a rib graft's pedicle blood supply.

  20. Injection molding of engineering plastics

    NASA Astrophysics Data System (ADS)

    Kalyon, Dilhan M.

    1991-03-01

    This final report summarizes the findings of a study in injection molding of engineering plastics. Two engineering plastic resins, i.e., unmodified grades of a polyetherimide and a poly (2,6-dimethyl-1,4-phenylene ether) were thoroughly characterized. The characterization included rheology, thermal properties and P-V-T behavior. The data were employed to predict various microstructural distributions including density, residual stress and birefringence distributions in compression and injection molded specimens of these two engineering plastics. The detailed microstructural distributions were also studied experimentally upon processing the two engineering plastics, employing instrumented machines and industrial practices. The experimental findings were elucidated under the light of the numerical simulation results. Overall, this study should furnish a first order understanding of the microstructure development in articles injection molded from amorphous engineering plastic resins.

  1. Microvascular responses to body tilt in cutaneous maximus muscle of conscious rats

    NASA Technical Reports Server (NTRS)

    Puri, Rohit K.; Segal, Steven S.

    1994-01-01

    We investigated microvascular responses to head-up tilt (HUT) and head-down tilt (HDT) in striated muscle of conscious male rats. To observe the microcirculation in the cutaneous maximus muscle, a transparent polycarbonate chamber was implanted aseptically into a skin fold created between the shoulders. Rats were trained to sit quietly during HUT and HDT while positioned on a horizontal microscope that rotated in the sagittal plane. At 4-5 days after surgery, arteriole and venule diameters were recorded using videomicroscopy while the rat experienced 10 min each (in random order) of HUT or HDT at 20 deg or 40 deg separated by 2-h rest periods. HUT had no affect on microvessel diameter; 20 deg HDT had little affect. In response to 40 deg HDT, 'large' arterioles constricted by 18 +/- 2% and 'small' arterioles dilated by 21 +/- 3%; this difference suggested variation in mechanisms controlling arteriolar responses. Venules exhibited a larger fluctuation in diameter during 40 deg HDT compared with other body positions, suggesting that venomotor activity may be induced with sufficient fluid shift or change in central venous pressure. These observations illustrate a viable model for studying microvascular responses to gravitational stress in conscious rats.

  2. Quality improvement of microsurgery through telecommunication--the postoperative care after microvascular transfer of intestine.

    PubMed

    Chen, Hung-Chi; Kuo, Hsin-Chih; Chung, Kuo-Piao; Chen, Shih-Heng; Tang, Yueh-Bih; Su, Syi

    2012-02-01

    The purpose of this report is to describe the use of telecommunication to improve the quality of postoperative care following microsurgery, especially following microvascular transfer of intestinal transfer for which shortening of ischemia time is of utmost importance to achieve high success rate. From 2003 to 2009 microvascular transfer of intestinal flaps had been performed in 112 patients. After surgery the patients were put in intensive care unit and the flaps were checked every 1 hour. The image for circulatory status of the flaps was sent directly to the attending surgeon for judgment. The information was sent through intranet and the surgeon can get access to the intranet through internet if necessary. Among the 112 cases, there were 9 cases of reexploration. The average duration between the time of problem detection and the time of starting reexploration was 54 min in 7 cases, and other 2 cases were delayed to enter the operating room which had been occupied by other cases of major trauma. Only two flaps were lost completely, two patients developed narrowing at the junction of cervical esophagus and thoracic esophagus. The rate of salvage for intestinal flap is apparently higher than those reported in the literature. In the postoperative management of microsurgery in ICU, telecommunication can help to reduce the ischemia time after vascular compromise in the transfer of free intestinal flap. Telecommunication is really an easy and effective tool in improving the outcome of reconstructive surgery.

  3. Differential susceptibility of equine and mouse brain microvascular endothelial cells to equine herpesvirus 1 infection.

    PubMed

    Hasebe, R; Kimura, T; Nakamura, K; Ochiai, K; Okazaki, K; Wada, R; Umemura, T

    2006-04-01

    Equine herpesvirus 1 (EHV-1) shows endotheliotropism in the central nervous system (CNS) of infected horses. However, infection of endothelial cells has not been observed in the CNS of infected mice. To explore the basis for this difference in endotheliotropism, we compared the susceptibility of equine brain microvascular endothelial cells (EBMECs) and mouse brain microvascular endothelial cells (MBMECs) to EHV-1 infection. The kinetics of viral growth in EBMECs was typical of a fully productive infection whereas viral infection in MBMECs seemed to be nonproductive. Immunofluorescence microscopy using anti-EHV-1 polyclonal antibody demonstrated viral antigen in infected EBMECs, but not infected MBMECs. EHV-1 immediate early (IE), early (ICP0), and late (gB, gD and gK) transcripts were expressed in infected EBMECs. However, none of these genes was detected in infected MBMECs by reverse transcription-polymerase chain reaction. Electron microscopic examination at the stage of viral entry showed that viral particles were present within uncoated vesicles in the cytoplasm of EBMECs, but absent from those of MBMECs. These results suggest that viral entry is an important determinant of the susceptibility of EBMECs and MBMECs to EHV-1 infection.

  4. 3D functional and perfusable microvascular networks for organotypic microfluidic models.

    PubMed

    Bersini, Simone; Moretti, Matteo

    2015-05-01

    The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases.

  5. The Association of Serum Vascular Endothelial Growth Factor and Ferritin in Diabetic Microvascular Disease

    PubMed Central

    Guo, Li; Jiang, Fang; Tang, Yue-Ting; Si, Meng-Ya

    2014-01-01

    Abstract Background: Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic microvascular disease. Most diabetes patients have higher serum levels of ferritin that may participate in diabetic vascular complications through high oxidative stress induced by iron. However, the mechanistic link between ferritin and VEGF is obscure. The study investigated the association of VEGF and ferritin in patients with diabetic microvascular disease. Patients and Methods: Sixty patients with type 2 diabetes mellitus (T2DM) and 26 healthy individuals were selected in this study. Serum ferritin, VEGF, hematological parameters, and clinical data were assessed in this cohort. The Spearman rank method was used to evaluate the associations among them. Results: Serum levels of VEGF and ferritin were significantly higher in diabetes patients compared with the controls; levels of both were elevated with development of the disease. There were positive correlations between VEGF and glucose levels and between VEGF and ferritin in diabetes groups, especially in patients with diabetic retinopathy. Positive correlations were also found between VEGF level and the parameters of age, hemoglobin, and albumin in patients with diabetes hypertension. Conclusions: Our data suggest that high ferritin levels in T2DM are closely related to the development of diabetic vascular complications through interaction with VEGF. PMID:24279470

  6. Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study

    PubMed Central

    Yacoub, Sophie; Lam, Phung Khanh; Vu, Le Hoang Mai; Le, Thi Lien; Ha, Ngo Thanh; Toan, Tran Thi; Van, Nguyen Thu; Quyen, Nguyen Than Ha; Le Duyen, Huynh Thi; Van Kinh, Nguyen; Fox, Annette; Mongkolspaya, Juthathip; Wolbers, Marcel; Simmons, Cameron Paul; Screaton, Gavin Robert; Wertheim, Heiman; Wills, Bridget

    2016-01-01

    Background. The hallmark of severe dengue is increased microvascular permeability, but alterations in the microcirculation and their evolution over the course of dengue are unknown. Methods. We conducted a prospective observational study to evaluate the sublingual microcirculation using side-stream dark-field imaging in patients presenting early (<72 hours after fever onset) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical findings, microvascular function, global hemodynamics assessed with echocardiography, and serological markers of endothelial activation were determined at 4 time points. Results. A total of 165 patients were enrolled. No difference was found between the microcirculatory parameters comparing dengue with other febrile illnesses. The proportion of perfused vessels (PPV) and the mean flow index (MFI) were lower in patients with dengue with plasma than those without leakage (PPV, 88.1% vs 90.6% [P = .01]; MFI, 2.1 vs 2.4 [P = .007]), most markedly during the critical phase. PPV and MFI were correlated with the endothelial activation markers vascular cell adhesion molecule 1 (P < .001 for both) and angiopoietin 2 (P < .001 for both), negatively correlated. Conclusions. Modest microcirculatory alterations occur in dengue, are associated with plasma leakage, and are correlate with molecules of endothelial activation, angiopoietin 2 and vascular cell adhesion molecule 1. PMID:27230099

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

    SciTech Connect

    Li Aihua; Cheng Guangli; Zhu Genghui; Tarnawski, Andrzej S. . E-mail: atarnawski@yahoo.com

    2007-02-09

    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.

  8. Epidermal devices for noninvasive, precise, and continuous mapping of macrovascular and microvascular blood flow

    PubMed Central

    Webb, R. Chad; Ma, Yinji; Krishnan, Siddharth; Li, Yuhang; Yoon, Stephen; Guo, Xiaogang; Feng, Xue; Shi, Yan; Seidel, Miles; Cho, Nam Heon; Kurniawan, Jonas; Ahad, James; Sheth, Niral; Kim, Joseph; Taylor VI, James G.; Darlington, Tom; Chang, Ken; Huang, Weizhong; Ayers, Joshua; Gruebele, Alexander; Pielak, Rafal M.; Slepian, Marvin J.; Huang, Yonggang; Gorbach, Alexander M.; Rogers, John A.

    2015-01-01

    Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macrovascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities. PMID:26601309

  9. Microvascular anastomosis in rodent model evaluated by Fourier domain Doppler optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

    2014-03-01

    Vascular and microvascular anastomosis are critical components of reconstructive microsurgery, vascular surgery and transplant surgery. Imaging modality that provides immediate, real-time in-depth view and 3D structure and flow information of the surgical site can be a great valuable tool for the surgeon to evaluate surgical outcome following both conventional and innovative anastomosis techniques, thus potentially increase the surgical success rate. Microvascular anastomosis for vessels with outer diameter smaller than 1.0 mm is extremely challenging and effective evaluation of the outcome is very difficult if not impossible using computed tomography (CT) angiograms, magnetic resonance (MR) angiograms and ultrasound Doppler. Optical coherence tomography (OCT) is a non-invasive high-resolution (micron level), high-speed, 3D imaging modality that has been adopted widely in biomedical and clinical applications. Phaseresolved Doppler OCT that explores the phase information of OCT signals has been shown to be capable of characterizing dynamic blood flow clinically. In this work, we explore the capability of Fourier domain Doppler OCT as an evaluation tool to detect commonly encountered post-operative complications that will cause surgical failure and to confirm positive result with surgeon's observation. Both suture and cuff based techniques were evaluated on the femoral artery and vein in the rodent model.

  10. Micropuncture measurement of lung microvascular pressure profile during hypoxia in cats.

    PubMed

    Nagasaka, Y; Bhattacharya, J; Nanjo, S; Gropper, M A; Staub, N C

    1984-01-01

    To determine the lung microvascular pressure profile during hypoxia, we micropunctured the subpleural microcirculation of isolated perfused cat lungs. Our procedures involved exsanguinating a cat, then cannulating its pulmonary artery, left atrium, and trachea. Using the cat's own blood, we perfused the lungs at pulmonary artery and left atrial pressures of 18 and 9 cm water, respectively, to obtain lung blood flow of 81 +/- 29 ml/(kg body weight x min), which we held constant throughout the experiment. We stabilized the lung surface with a vacuum ring and micropunctured 30- to 50-micrometers arterioles and venules to measure microvascular pressure by the servo-null method. During micropuncture, we held the lungs at constant inflation using airway pressure of 8 cm water. We varied the oxygen concentration of the inflation gas from 30% during baseline to 2% during hypoxia. We studied groups with high (more than 7.5) or normal pH. During normoxia, 27, 44, and 29% of the pressure drop occurred in the arterial, capillary and venous segments, respectively. During hypoxia, the increase in pulmonary vascular resistance, which was marked in both groups, was significantly greater in the normal pH group. All segmental pressure drops increased significantly during hypoxia. However, the predominant increase occurred in the arteries where segmental pressure drop increased by 148% and 210%, respectively, in the high and normal pH groups. We conclude that the major site of hypoxic vasoconstriction is in the pulmonary arteries.

  11. From homogeneous to fractal normal and tumorous microvascular networks in the brain.

    PubMed

    Risser, Laurent; Plouraboué, Franck; Steyer, Alexandre; Cloetens, Peter; Le Duc, Géraldine; Fonta, Caroline

    2007-02-01

    We studied normal and tumorous three-dimensional (3D) microvascular networks in primate and rat brain. Tissues were prepared following a new preparation technique intended for high-resolution synchrotron tomography of microvascular networks. The resulting 3D images with a spatial resolution of less than the minimum capillary diameter permit a complete description of the entire vascular network for volumes as large as tens of cubic millimeters. The structural properties of the vascular networks were investigated by several multiscale methods such as fractal and power-spectrum analysis. These investigations gave a new coherent picture of normal and pathological complex vascular structures. They showed that normal cortical vascular networks have scale-invariant fractal properties on a small scale from 1.4 mum up to 40 to 65 mum. Above this threshold, vascular networks can be considered as homogeneous. Tumor vascular networks show similar characteristics, but the validity range of the fractal regime extend to much larger spatial dimensions. These 3D results shed new light on previous two dimensional analyses giving for the first time a direct measurement of vascular modules associated with vessel-tissue surface exchange.

  12. Mechanisms of modulation of brain microvascular endothelial cells function by thrombin.

    PubMed

    Brailoiu, Eugen; Shipsky, Megan M; Yan, Guang; Abood, Mary E; Brailoiu, G Cristina

    2017-02-15

    Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca(2+) concentration in RBMVEC via Ca(2+) release from endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors and Ca(2+) influx from extracellular space. Thrombin increases nitric oxide production; the effect is abolished by inhibition of the nitric oxide synthase or by antagonism of PAR1 receptors. In addition, thrombin increases mitochondrial and cytosolic reactive oxygen species production via PAR1-dependent mechanisms. Immunocytochemistry studies indicate that thrombin increases F-actin stress fibers, and disrupts the tight junctions. Thrombin increased the RBMVEC permeability assessed by a fluorescent flux assay. Taken together, our results indicate multiple mechanisms by which thrombin modulates the function of RBMVEC and may contribute to the blood-brain barrier dysfunction.

  13. Hearing outcomes after loss of brainstem auditory evoked potentials during microvascular decompression.

    PubMed

    Thirumala, Parthasarathy D; Krishnaiah, Balaji; Habeych, Miguel E; Balzer, Jeffrey R; Crammond, Donald J

    2015-04-01

    The primary aim of this paper is to study the pre-operative characteristics, intra-operative changes and post-operative hearing outcomes in patients after complete loss of wave V of the brainstem auditory evoked potential. We retrospectively analyzed the brainstem auditory evoked potential data of 94 patients who underwent microvascular decompression for hemifacial spasm at our institute. Patients were divided into two groups - those with and those without loss of wave V. The differences between the two groups and outcomes were assessed using t-test and chi-squared tests. In our study 23 (24%) patients out of 94 had a complete loss of wave V, with 11 (48%) patients experiencing transient loss and 12 (52%) patients experiencing permanent loss. The incidence of hearing loss in patients with no loss of wave V was 5.7% and 26% in patients who did experience wave V loss. The incidence of hearing change in patients with no loss of wave V was 12.6% and 30.43% in patients who did experience wave V loss. Loss of wave V during the procedure or at the end of procedure significantly increases the odds of hearing loss. Hearing change is a significant under-reported clinical condition after microvascular decompression in patients who have loss of wave V.

  14. Impact of patient comorbidities on head and neck microvascular reconstruction. A report on 423 cases.

    PubMed

    Vandersteen, Clair; Dassonville, Olivier; Chamorey, Emmanuel; Poissonnet, Gilles; Nao, Eric Edi Martial; Pierre, Cédric Sandy; Leyssale, Axel; Peyrade, Frédéric; Falewee, Marie Noelle; Sudaka, Anne; Haudebourg, Juliette; Demard, François; Santini, José; Bozec, Alexandre

    2013-05-01

    The aim of this study was to assess the impact of the different subtypes of patient comorbidities on the outcomes of head and neck microvascular reconstruction. A total of 423 patients who underwent head and neck free flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. The impact of the different subtypes of patient comorbidities (as defined by the Kaplan-Feinstein Index) and other global health status-related factors on free flap success, local and general complications, postoperative mortality and length of stay was assessed in univariate and multivariate analysis. We found no correlation between patient comorbidities and free flap failure. In multivariate analysis, we demonstrated a significant correlation between tobacco consumption (p = 0.04) and local complications. Gastro-intestinal comorbidity (p = 0.005) and malnutrition (p = 0.02) were associated with a higher risk of fistula formation. Diabetes mellitus (p = 0.003), gastro-intestinal (p = 0.02), systemic (p = 0.02) and cardiac comorbidities (p = 0.03) were significant predictors of medical complications. We concluded that the different subtypes of patient comorbidities were relevant predictors of complications in head and neck microvascular reconstruction.

  15. Emerging roles for microRNAs in diabetic microvascular disease - novel targets for therapy.

    PubMed

    Zhang, Yu; Sun, Xinghui; Icli, Basak; Feinberg, Mark W

    2017-02-17

    Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs, non-coding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury. We highlight current pathophysiological paradigms of microRNAs and their targets involved in regulating the diabetic microvasculature in a range of diabetes-associated complications such as retinopathy, nephropathy, wound healing, and myocardial injury. We provide an update of the potential use of circulating miRNAs diagnostically in type I or type II diabetes. Finally, we discuss emerging delivery platforms for manipulating miRNA expression or function as the next frontier in therapeutic intervention to improve diabetes-associated microvascular dysfunction and its attendant clinical consequences.

  16. Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

    PubMed Central

    Patel, Sunni R.; Bellary, Srikanth; Karimzad, Said; Gherghel, Doina

    2016-01-01

    The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p < 0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range. PMID:27578554

  17. The role of the microvascular network structure on diffusion and consumption of anticancer drugs.

    PubMed

    Mascheroni, Pietro; Penta, Raimondo

    2016-12-06

    We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy-double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells. The coefficients are then injected into the macroscale equations, and these are solved for an isolated, vascularized spherical tumor. We consider the effect of vascular tortuosity on the transport of anticancer molecules, focusing on Vinblastine and Doxorubicin dynamics, which are considered as a tracer and as a highly interacting molecule, respectively. The computational model is able to quantify the treatment performance through the analysis of the interstitial drug concentration and the quantity of drug metabolized in the tumor. Our results show that both drug advection and diffusion are dramatically impaired by increasing geometrical complexity of the microvasculature, leading to nonoptimal absorption and delivery of therapeutic agents. However, this effect apparently has a minor role whenever the dynamics are mostly driven by metabolic reactions in the tumor interstitium, eg, for highly interacting molecules. In the latter case, anticancer therapies that aim at regularizing the microvasculature might not play a major role, and different strategies are to be developed.

  18. Clinical and pathological assessment of different suture techniques for microvascular anastomosis in rat femoral artery

    PubMed Central

    El-Shazly, Mohamed

    2007-01-01

    This study examined the clinical and pathological features after a microvascular anastomosis of a rat femoral artery using four different suture techniques. Sixty Sprage-Dawely rats were divided randomly into 4 groups. Fifteen bisected arteries (one from each animal) in Group I, II, III and IV were sutured with the simple interrupted suture, continuous suture, sleeve suture and cuff suture, respectively. The anastomosis times in Group I, II, III and IV were 28.67, 14.67, 15.47 and 15.93 min, respectively. Immediate bleeding that stopped without intervention (grade I) was observed in 67%, 73% and 60% of the anastomosed vessels in Groups II, III and IV, respectively, while 60% of the vessels in Group I showed light bleeding that was inhibited by gentile pressure (grade II). All vessels examined appeared to be patent at 5 and 15 min after the anastomosis. On the 7th day postoperatively, the vessels of Group I showed the highest patency rate (93%) compared with Groups II (67%), III (73%) and IV (87%). Moreover, there were more pronounced pathological changes in Group I than in the other groups. These changes included endothelial loss, endothelial proliferation, degeneration and necrosis of the tunica media. Suture materials surrounded by an inflammatory reaction were also observed. In conclusion, the simple interrupted suture is preferable for microvascular anastomosis due to its highest patency rate. The other techniques investigated can be good alternatives because of their short anastomotic time and moderate pathological changes. PMID:17679774

  19. The goal of blood pressure control for prevention of early diabetic microvascular complications.

    PubMed

    Williams, Mark E

    2011-08-01

    Lowering blood pressure may confer a benefit to diabetic microvascular complications comparable with glycemic control. Hypertension is causally related to kidney outcomes and is a risk factor for the development of diabetic retinopathy. The prevalence of hypertension increases as kidney disease progresses, so that it coexists with diabetes in up to 80% of those with overt nephropathy. A significant number of patients have hypertension or rising blood pressures in earlier stages, or even before microvascular complications appear. Because microalbuminuria markedly increases the risk of overt nephropathy as well as of cardiovascular complications, primary prevention (i.e., preventing or delaying the onset of microalbuminuria) continues to be explored, predominantly through use of renin-angiotensin blockade. Available data reviewed suggest that primary prevention through blood pressure reduction is more likely to benefit select groups (those with hypertension, cardiovascular risks, or old age). This review discusses the relationship between hypertension, diabetes, and kidney disease, the rationale for primary prevention, and the data that led to that conclusion.

  20. Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx

    PubMed Central

    Salmon, Andrew H.J.; Neal, Christopher R.; Sage, Leslie M.; Glass, Catherine A.; Harper, Steven J.; Bates, David O.

    2009-01-01

    Aims In this study, we wished to determine whether angiopoietin-1 (Ang1) modified the permeability coefficients of non-inflamed, intact continuous, and fenestrated microvessels in vivo and to elucidate the underlying cellular mechanisms. Methods and results Permeability coefficients were measured using the Landis–Michel technique (in frog and rat mesenteric microvessels) and an oncopressive permeability technique (in glomeruli). Ang1 decreased water permeability (LP: hydraulic conductivity) in continuous and fenestrated microvessels and increased the retention of albumin (σ: reflection coefficient) in continuous microvessels. Endothelial glycocalyx is common to these anatomically distinct microvascular beds, and contributes to the magnitude of both LP and σ. Ang1 treatment increased the depth of endothelial glycocalyx in intact microvessels and increased the content of glycosaminoglycan of cultured microvascular endothelial cell supernatant. Ang1 also prevented the pronase-induced increase in LP (attributable to selective removal of endothelial glycocalyx by pronase) by restoration of glycocalyx at the endothelial cell surface. The reduction in permeability was inhibited by a cell transport inhibitor, Brefeldin. Conclusion Ang1 modifies basal microvessel permeability coefficients, in keeping with previous reports demonstrating reduced solute flux in inflamed vessels. Anatomical, biochemical, and physiological evidence indicates that modification of endothelial glycocalyx is a novel mechanism of action of Ang1 that contributes to these effects. PMID:19297368

  1. Influence of red blood cell aggregation on perfusion of an artificial microvascular network.

    PubMed

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

    2016-09-19

    Red blood cells (RBCs) suspended in plasma form multicellular aggregates under low flow conditions, increasing apparent blood viscosity at low shear rates. It has previously been unclear, however, if RBC aggregation affects microvascular perfusion. Here we analyzed the impact of RBC aggregation on perfusion and 'capillary' hematocrit in an artificial microvascular network (AMVN) at driving pressures ranging from 5 to 60 cmH2 O to determine if aggregation could improve tissue oxygenation. RBCs were suspended at 30% hematocrit in either 46.5 g/L dextran 40 (D40, non-aggregating medium) or 35 g/L dextran 70 (D70, aggregating medium) solutions with equal viscosity. Aggregation was readily observed in the AMVN for RBCs suspended in D70 at driving pressures ≤ 40 cmH2 O. The AMVN perfusion rate was the same for RBCs suspended in aggregating and non-aggregating medium, at both 'venular' and 'capillary' level. Estimated 'capillary' hematocrit was higher for D70 suspensions than for D40 suspensions at intermediate driving pressures (5 - 40 cm H2 O). We conclude that although RBC aggregation did not affect the AMVN perfusion rate independently of the driving pressure, a higher hematocrit in the 'capillaries' of the network for D70 suspensions suggested a better oxygen transport capacity in the presence of RBC aggregation. This article is protected by copyright. All rights reserved.

  2. The Effects of Copper on Brain Microvascular Endothelial Cells and Claudin Via Apoptosis and Oxidative Stress.

    PubMed

    Wang, Jian; Chen, Junquan; Tang, Zhaoxin; Li, Ying; Hu, Lianmei; Pan, Jiaqiang

    2016-11-01

    Many neurodegenerative diseases are related to copper although the effects on brain microvascular endothelial cells (BMECs) are poorly understood. In the present study, a primary BMEC culture model was established to evaluate the effects of copper on brain microvascular endothelial cells and whether claudin-1, claudin-3, claudin-5, and claudin-12 isoforms contribute to apoptosis and intrinsic antioxidant activity. Our results showed that copper ions had dual effects on BMECs by regulating intracellular reactive oxygen species (ROS) levels. Copper levels between 30 and 120 μM could enhance viability and promote proliferation. On the other hand, copper cytotoxicity was a result of apoptosis indicating a redox-independent manner of cell death. Expression levels of claudins were also regulated by copper in a concentration-dependent manner. We identified four claudin isoforms (1, 3, 5, and 12) and showed that their expression levels were regulated as a group by copper. Antioxidant activity of BMECs was also copper regulated, and superoxide dismutase and catalase were the main contributors to BMEC antioxidant functions. Together, our results indicated that copper had dual effects on BMEC growth and intrinsic antioxidant activities played a crucial role in BMEC survival and tight junction.

  3. A Comparative Investigation on the Performance of Different Micro Mixers: Toward Cerebral Microvascular Analysis

    NASA Astrophysics Data System (ADS)

    Abdi, Mohsen; Pishbin, Esmail; Karimi, Alireza; Navidbakhsh, Mahdi

    In this study, a novel fluidic concept was presented to resemble the cerebral microvascular in four types to assess its complexity by using centrifugal platform. The setup consisted of a microstructured disk with a round mixing chamber rotating on a macroscopic drive unit. The left and right internal carotid arteries (L.ICA and R.ICA) and basilar artery (BA) are two isolated vascular system supplying circle of Willis (CoW). The left and right middle cerebral arteries (L.MCA and R.MCA), left and right anterior cerebral arteries (L.ACA and R.ACA), and finally left and right posterior cerebral arteries (L.PCA and R.PCA) constitute efferent arteries of CoW. In this study, cerebral microvascular was investigated by microfluidics approach. The results revealed that a more complex mixing chamber provides normal pixel percentage distribution with respect to the other ones. The outcomes of this study may have implications not only for perception of the intracranial vascular hemodynamic in healthy circumstance, but also for diagnosing the diseases in the blood circulatory system of the human body.

  4. The Proangiogenic Effect of Iroquois Homeobox Transcription Factor Irx3 in Human Microvascular Endothelial Cells*

    PubMed Central

    Scarlett, Kisha; Pattabiraman, Vaishnavi; Barnett, Petrina; Liu, Dong; Anderson, Leonard M.

    2015-01-01

    Angiogenesis is a dynamic process required for embryonic development. However, postnatal vascular growth is characteristic of multiple disease states. Despite insights into the multistep process in which adhesion molecules, extracellular matrix proteins, growth factors, and their receptors work in concert to form new vessels from the preexisting vasculature, there remains a lack of insight of the nuclear transcriptional mechanisms that occur within endothelial cells (ECs) in response to VEGF. Iroquois homeobox gene 3 (Irx3) is a transcription factor of the Iroquois family of homeobox genes. Irx homeodomain transcription factors are involved in the patterning and development of several tissues. Irx3 is known for its role during embryogenesis in multiple organisms. However, the expression and function of Irx3 in human postnatal vasculature remains to be investigated. Here we show that Irx3 is expressed in human microvascular endothelial cells, and expression is elevated by VEGF stimulation. Genetic Irx3 gain and loss of function studies in human microvascular endothelial cells resulted in the modulation of EC migration during wound healing, chemotaxis and invasion, and tubulogenesis. Additionally, we observed increased delta-like ligand 4 (Dll4) expression, which suggests an increase in EC tip cell population. Finally, siRNA screening studies revealed that transient knockdown of Hey1, a downstream Notch signaling mediator, resulted in increased Irx3 expression in response to VEGF treatment. Strategies to pharmacologically regulate Irx3 function in adult endothelial cells may provide new therapies for angiogenesis. PMID:25512384

  5. Changes of perfusion of microvascular free flaps in the head and neck: a prospective clinical study.

    PubMed

    Mücke, Thomas; Rau, Andrea; Merezas, Andreas; Kanatas, Anastasios; Mitchell, David A; Wagenpfeil, Stefan; Wolff, Klaus-Dietrich; Steiner, Timm

    2014-11-01

    Reconstruction with a free flap is routine in head and neck surgery. However, reliable assessment of perfusion can be difficult, so we prospectively evaluated it in 4 types of microvascular free flaps in the oral cavity (n=196) and assessed differences in blood flow by non-invasive monitoring with a laser Doppler flowmetry unit. We measured oxygen saturation, haemoglobin concentration, and velocity on the surface of the flap preoperatively at the donor site, and on the flap on the first, second, and seventh postoperative days, and after 4 weeks in 186/196 patients, mean (SD) age of 60 (13) years. We studied the radial forearm (n=76, 41%), fibular (n=45, 24%), anterolateral thigh (n=53, 28%), and soleus perforator (n=12, 7%) flaps. The values for the radial forearm flap differed significantly from the others. There were significant differences in haemoglobin concentrations between the fibular and soleus perforator flaps, and between the anterolateral thigh and soleus perforator flaps (p=0.002 each). Free flaps are unique in the way that perfusion develops after microvascular anastomoses. Knowledge of how each flap is perfused may indicate different patterns of healing that could potentially influence long term rehabilitation and detection of future deficits in perfusion.

  6. Suprameatal extension of retrosigmoid approach for microvascular decompression of trigeminal nerve: Case report

    PubMed Central

    Moreira-Holguin, Juan Carlos; Revuelta-Gutierrez, Rogelio; Monroy-Sosa, Alejandro; Almeida-Navarro, Samuel

    2015-01-01

    Introduction Trigeminal neuralgia is produced in a significant number of cases by vascular compression at the level of cisternal segment of the nerve at the entry of the pons. It is common to find superior cerebellar artery (SCA) responsible for this compression. The retrosigmoid approach (RA), with asterional craniectomy, clearly exposes the cisternal portion of the trigeminal nerve (TN). Presentation of case We describe in this case report how vessels at the trigeminal pore level known as “Meckel’s segment” can compress the TN. This situation is unusual. One of the reasons why the compression of this Meckel’s segment level could be overlooked is a suprameatal tubercle (ST) prominence that would prevent trigeminal pore visualization through retrosigmoid approach. Discussion The suprameatal extension of this approach has been described for other purposes, especially in tumors invading Meckel’s cave resection. We could not find publications for the use of the resection of the suprameatal tubercle in the retrosigmoid approach for microvascular decompression of the trigeminal neuralgia. Conclusion Microvascular decompression of the TN is an effective treatment for trigeminal neuralgia, however in some cases, in which vascular compression is not evident when exploring the cerebellopontine angle, it is important to note that association of a prominent ST can hide a vascular compression of the nerve in this region. PMID:26298243

  7. Human Pulmonary Microvascular Endothelial Cells Support Productive Replication of Highly Pathogenic Avian Influenza Viruses: Possible Involvement in the Pathogenesis of Human H5N1 Virus Infection

    PubMed Central

    Zeng, Hui; Pappas, Claudia; Belser, Jessica A.; Houser, Katherine V.; Zhong, Weiming; Wadford, Debra A.; Stevens, Troy; Balczon, Ron; Katz, Jacqueline M.

    2012-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (α2-3-linked) receptors were more abundant than human-like (α2-6-linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza virus strains. We observed that these cells support productive replication only of HPAI H5N1 viruses, which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multibasic cleavage site did not affect virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells, resulting in the potent induction of host inflammatory responses. PMID:22072765

  8. International policies to reduce plastic marine pollution from single-use plastics (plastic bags and microbeads): A review.

    PubMed

    Xanthos, Dirk; Walker, Tony R

    2017-02-18

    Marine plastic pollution has been a growing concern for decades. Single-use plastics (plastic bags and microbeads) are a significant source of this pollution. Although research outlining environmental, social, and economic impacts of marine plastic pollution is growing, few studies have examined policy and legislative tools to reduce plastic pollution, particularly single-use plastics (plastic bags and microbeads). This paper reviews current international market-based strategies and policies to reduce plastic bags and microbeads. While policies to reduce microbeads began in 2014, interventions for plastic bags began much earlier in 1991. However, few studies have documented or measured the effectiveness of these reduction strategies. Recommendations to further reduce single-use plastic marine pollution include: (i) research to evaluate effectiveness of bans and levies to ensure policies are having positive impacts on marine environments; and (ii) education and outreach to reduce consumption of plastic bags and microbeads at source.

  9. Evaluation of microvascular structure in humans: a 'state-of-the-art' document of the Working Group on Macrovascular and Microvascular Alterations of the Italian Society of Arterial Hypertension.

    PubMed

    Virdis, Agostino; Savoia, Carmine; Grassi, Guido; Lembo, Giuseppe; Vecchione, Carmine; Seravalle, Gino; Taddei, Stefano; Volpe, Massimo; Rosei, Enrico Agabiti; Rizzoni, Damiano

    2014-11-01

    The evaluation of microvascular structure is, in general, not an easy task. Among the methods that may be applied to humans, plethysmographic evaluation of small arteries and wire or pressure micromyography were extensively used in the last decades. The media-to-lumen ratio of small arteries evaluated by micromyography was demonstrated to possess a strong prognostic significance; however, its extensive evaluation is limited by the local invasiveness of the assessment. Noninvasive approaches were then proposed, including capillaroscopy, which provides information about microvascular rarefaction. Recently, the interest of investigators was focused on the retinal microvascular bed. In particular, a noninvasive measurement of the wall-to-lumen ratio of retinal arterioles using scanning laser Doppler flowmetry has been introduced.Recent data suggest a rather good agreement between this approach and micromyographic measurements, generally considered the gold standard approach. Therefore, the evaluation of microvascular structure is progressively moving from bench to bedside, and it could represent, in the immediate future, an evaluation to be performed in all hypertensive patients, in order to obtain a better stratification of cardiovascular risk.

  10. Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells.

    PubMed

    Ju, Zhihai; Ma, Jinhui; Wang, Chen; Yu, Jie; Qiao, Yeru; Hei, Feilong

    2017-04-01

    The pro-inflammatory activation of pulmonary microvascular endothelial cells resulting in continuous expression of cellular adhesion molecules, and subsequently recruiting primed neutrophils to form a firm neutrophils-endothelium (PMN-EC) adhesion, has been examined and found to play a vital role in acute lung injury (ALI). RNA interference (RNAi) is a cellular process through harnessing a natural pathway silencing target gene based on recognition and subsequent degradation of specific mRNA sequences. It opens a promising approach for precision medicine. However, this application was hampered by many obstacles, such as immunogenicity, instability, toxicity problems, and difficulty in across the biological membrane. In this study, we reprogrammed urine exfoliated renal epithelial cells into human induced pluripotent stem cells (huiPSCs) and purified the exosomes (Exo) from huiPSCs as RNAi delivery system. Through choosing the episomal system to deliver transcription factors, we obtained a non-integrating huiPSCs. Experiments in both vitro and vivo demonstrated that these huiPSCs possess the pluripotent properties. The exosomes of huiPSCs isolated by differential centrifugation were visualized by transmission electron microscopy (TEM) showing a typical exosomal appearance with an average diameter of 122 nm. Immunoblotting confirmed the presence of the typical exosomal markers, including CD63, TSG 101, and Alix. Co-cultured PKH26-labeled exosomes with human primary pulmonary microvascular endothelial cells (HMVECs) confirmed that they could be internalized by recipient cells at a time-dependent manner. Then, electroporation was used to introduce siRNA against intercellular adhesion molecule-1 (ICAM-1) into exosomes to form an Exo/siRNA compound. The Exo/siRNA compound efficiently delivered the target siRNA into HMVECs causing selective gene silencing, inhibiting the ICAM-1 protein expression, and PMN-EC adhesion induced by lipopolysaccharide (LPS). These data suggest

  11. Extruding plastic scintillator at Fermilab

    SciTech Connect

    Anna Pla-Dalmau; Alan D. Bross; Victor V. Rykalin

    2003-10-31

    An understanding of the costs involved in the production of plastic scintillators and the development of a less expensive material have become necessary with the prospects of building very large plastic scintillation detectors. Several factors contribute to the high cost of plastic scintillating sheets, but the principal reason is the labor-intensive nature of the manufacturing process. In order to significantly lower the costs, the current casting procedures had to be abandoned. Since polystyrene is widely used in the consumer industry, the logical path was to investigate the extrusion of commercial-grade polystyrene pellets with dopants to yield high quality plastic scintillator. This concept was tested and high quality extruded plastic scintillator was produced. The D0 and MINOS experiments are already using extruded scintillator strips in their detectors. An extrusion line has recently been installed at Fermilab in collaboration with NICADD (Northern Illinois Center for Accelerator and Detector Development). This new facility will serve to further develop and improve extruded plastic scintillator. This paper will discuss the characteristics of extruded plastic scintillator and its raw materials, the different manufacturing techniques and the current R&D program at Fermilab.

  12. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    PubMed

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  13. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors

    PubMed Central

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E.; O’Carroll, Simon J.; Graham, E. Scott

    2016-01-01

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors. PMID:26813587

  14. Circadian Regulation of Synaptic Plasticity.

    PubMed

    Frank, Marcos G

    2016-07-13

    Circadian rhythms refer to oscillations in biological processes with a period of approximately 24 h. In addition to the sleep/wake cycle, there are circadian rhythms in metabolism, body temperature, hormone output, organ function and gene expression. There is also evidence of circadian rhythms in synaptic plasticity, in some cases driven by a master central clock and in other cases by peripheral clocks. In this article, I review the evidence for circadian influences on synaptic plasticity. I also discuss ways to disentangle the effects of brain state and rhythms on synaptic plasticity.

  15. [Neuronal plasticity and gene expression].

    PubMed

    Sokolova, O O; Shtark, M B; Lisachev, P D

    2010-01-01

    Neuronal plasticity--a fundamental feature of brain--provides adequate interactions with dynamic environment. One of the most deeply investigated forms of the neuronal plasticity is a long-term potentiation (LTP)--a phenomenon underlying learning and memory. Signal paths activated during LTP converge into the nuclear of the neuron, giving rise to launch of the molecular-genetic programs, which mediate structural and functional remodeling of synapses. In the review data concerning involvement of multilevel gene expression into plastic change under neuronal activation are summarized.

  16. Biodegradable plastics from renewable sources.

    PubMed

    Flieger, M; Kantorová, M; Prell, A; Rezanka, T; Votruba, J

    2003-01-01

    Plastic waste disposal is a huge ecotechnological problem and one of the approaches to solving this problem is the development of biodegradable plastics. This review summarizes data on their use, biodegradability, commercial reliability and production from renewable resources. Some commercially successful biodegradable plastics are based on chemical synthesis (i.e. polyglycolic acid, polylactic acid, polycaprolactone, and polyvinyl alcohol). Others are products of microbial fermentations (i.e. polyesters and neutral polysaccharides) or are prepared from chemically modified natural products (e.g., starch, cellulose, chitin or soy protein).

  17. Circadian Regulation of Synaptic Plasticity

    PubMed Central

    Frank, Marcos G.

    2016-01-01

    Circadian rhythms refer to oscillations in biological processes with a period of approximately 24 h. In addition to the sleep/wake cycle, there are circadian rhythms in metabolism, body temperature, hormone output, organ function and gene expression. There is also evidence of circadian rhythms in synaptic plasticity, in some cases driven by a master central clock and in other cases by peripheral clocks. In this article, I review the evidence for circadian influences on synaptic plasticity. I also discuss ways to disentangle the effects of brain state and rhythms on synaptic plasticity. PMID:27420105

  18. Recycling of Reinforced Plastics

    NASA Astrophysics Data System (ADS)

    Adams, R. D.; Collins, Andrew; Cooper, Duncan; Wingfield-Digby, Mark; Watts-Farmer, Archibald; Laurence, Anna; Patel, Kayur; Stevens, Mark; Watkins, Rhodri

    2014-02-01

    This work has shown is that it is possible to recycle continuous and short fibre reinforced thermosetting resins while keeping almost the whole of the original material, both fibres and matrix, within the recyclate. By splitting, crushing hot or cold, and hot forming, it is possible to create a recyclable material, which we designate a Remat, which can then be used to remanufacture other shapes, examples of plates and tubes being demonstrated. Not only can remanufacturing be done, but it has been shown that over 50 % of the original mechanical properties, such as the E modulus, tensile strength, and interlaminar shear strength, can be retained. Four different forms of composite were investigated, a random mat Glass Fibre Reinforced Plastic (GFRP) bathroom component and boat hull, woven glass and carbon fibre cloth impregnated with an epoxy resin, and unidirectional carbon fibre pre-preg. One of the main factors found to affect composite recyclability was the type of resin matrix used in the composite. Thermoset resins tested were shown to have a temperature range around the Glass Transition Temperature (Tg) where they exhibit ductile behaviour, hence aiding reforming of the material. The high-grade carbon fibre prepreg was found to be less easy to recycle than the woven of random fibre laminates. One method of remanufacturing was by heating the Remat to above its glass transition temperature, bending it to shape, and then cooling it. However, unless precautions are taken, the geometric form may revert. This does not happen with the crushed material.

  19. [Memory and synaptic plasticity].

    PubMed

    Maitre, M

    1996-01-01

    Short term memory traces are probably induced by a sustained and specific functional activation of some sensory and/or motor circuits in brain. These modifications, which could concern a large proportion of the brain but especially the limbic areas, are constituted primarily by ionic mechanisms and second messengers cascades induced by the activation of glutamatergic receptors (namely NMDA). In the invertebrate (Drosophilia melanogaster, aplysia), the role of serotonergic receptors seems to be more important. The activated cAMP-dependent and calcium dependent protein kinases target several proteins which are reversibly phosphorylated modifying the synaptic functions which in turn induce potentiated (PLT) or depressed (DLT) post-synaptic responses. These phenomena are at the basis of specific protein neosynthesis which is initiated by several early genes or trancription factor (cfos, zif 268, jun, CREB). Specific mRNA migrate to the potentiated synapse or dendritic spine where activated polyribosomes synthesize trophic factor, adhesion molecules and synaptic constituents. The building of new synaptic contacts and/or the plastic evolution of existing synapses could explain long-term LTP and long-term memory traces.

  20. Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation.

    PubMed

    Gagnon, Louis; Smith, Amy F; Boas, David A; Devor, Anna; Secomb, Timothy W; Sakadžić, Sava

    2016-01-01

    Oxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These "bottom-up" models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans.

  1. Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation

    PubMed Central

    Gagnon, Louis; Smith, Amy F.; Boas, David A.; Devor, Anna; Secomb, Timothy W.; Sakadžić, Sava

    2016-01-01

    Oxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These “bottom-up” models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans. PMID:27630556

  2. Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

    PubMed Central

    Packard, Scott D; Mandeville, Joseph B; Ichikawa, Tomotsugu; Ikeda, Keiro; Terada, Kinya; Niloff, Stephanie; Chiocca, E Antonio; Rosen, Bruce R; Marota, John J A

    2003-01-01

    Abstract In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1% / mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/ mm Hg CO2, (P < .0001, group t-test). Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed. PMID:14511404

  3. Can C-peptide mediated anti-inflammatory effects retard the development of microvascular complications of type 1 diabetes?

    PubMed

    Luppi, Patrizia; Kallas, Åsa; Wahren, John

    2013-07-01

    Hyperglycemia is considered to be the major cause of microvascular complications of diabetes. Growing evidence highlights the importance of hyperglycemia-mediated inflammation in the initiation and progression of microvascular complications in type 1 diabetes. We hypothesize that lack of proinsulin C-peptide and lack of its anti-inflammatory properties contribute to the development of microvascular complications. Evidence gathered over the past 20 years shows that C-peptide is a biologically active peptide in its own right. It has been shown to reduce formation of reactive oxygen species and nuclear factor-κB activation induced by hyperglycemia, resulting in inhibition of cytokine, chemokine and cell adhesion molecule formation as well as reduced apoptotic activity. In addition, C-peptide stimulates and induces the expression of both Na⁺, K⁺-ATPase and endothelial nitric oxide synthase. Animal studies and small-scale clinical trials in type 1 diabetes patients suggest that C-peptide replacement combined with regular insulin therapy exerts beneficial effects on kidney and nerve dysfunction. Further clinical trials in patients with microvascular complications including measurements of inflammatory markers are warranted to explore the clinical significance of the aforementioned, previously unrecognized, C-peptide effects.

  4. Modeling the drift of plastics in the Adriatic Basin

    NASA Astrophysics Data System (ADS)

    Liubartseva, Svitlana; Coppini, Giovanni; Lecci, Rita; Creti, Sergio

    2016-04-01

    Recently, plastic pollution at sea has become widely recognized as an acute environmental problem. Distribution of plastics in the marine environment is controlled by (1) locations and time-varying intensity of inputs; (2) the dynamics of the upper mixed layer of the ocean, where the majority of plastics float; and (3) the sinks of plastics. In the present work, we calculate the plastic concentrations at the sea surface and fluxes onto the coastline (2009-2015) that originated from terrestrial and maritime inputs. We construct a Markov chain model based on coupling the MEDSLIK-II model (De Dominicis et al., 2013) with the daily Adriatic Forecasting System (AFS) ocean currents simulations (1/45° horizontal resolution) (Guarneri et al., 2010) and ECMWF surface wind analyses (0.25° horizontal and 6-h temporal resolutions). We assume that the coastline is the main sink of plastics in the Adriatic Sea (Liubartseva et al., 2015). Our calculations have shown that the mean particle half-life in the basin approximately equals 43.7 days, which allows us to define the Adriatic Sea as a highly dissipative system with respect to floating plastics. On long-term time-mean scales, the most polluted sea surface area (more than 10 g/km2 floating plastics) is represented by an elongated band shifted to the Italian coastline and narrowed from northwest to southeast. That corresponds to the spatial distributions of plastic inputs, and indicates a tight connection with patterns of the general Adriatic circulation, including the Western Adriatic Coastal Current and the South Adriatic gyre. On seasonal time-mean scales, we indicate the winter plastics' expansion into the basin's interior, spring trapping in the northern Adriatic, summer cleansing the middle and southern Adriatic and autumn spreading into the southeastern Adriatic. Distinctive coastal "hot spot" is found on the Po Delta coastline that receives a plastic flux of 70 kg/(kmṡday). Complex source-receptor relationships

  5. Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study

    PubMed Central

    2014-01-01

    Background Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. Methods CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. Results Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). Conclusions Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia. PMID:25160568

  6. The impact of early aerobic exercise on brain microvascular alterations induced by cerebral hypoperfusion.

    PubMed

    Leardini-Tristão, Marina; Borges, Juliana Pereira; Freitas, Felipe; Rangel, Raquel; Daliry, Anissa; Tibiriçá, Eduardo; Estato, Vanessa

    2017-02-15

    The therapeutic potential of early exercise training following cerebral hypoperfusion was investigated on brain perfusion and inflammation in rats with permanent bilateral occlusion of the common carotid arteries (2VO). Wistar rats were subjected to 2VO or sham surgery and each group was then subdivided randomly into sedentary or exercise groups. Early exercise training was initiated after three days of 2VO or sham surgery and consisted of seven days of treadmill training (30min/day at ∼60% of maximal exercise test), composing four groups: 1) Sham sedentary (Sham-Sed), 2) Sham exercised (Sham-Ex), 3) 2VO sedentary (2VO-Sed) and 4) 2VO exercised (2VO-Ex). Microvascular cerebral blood flow (MCBF) and NADPH oxidase and eNOS gene expression were evaluated by laser speckle contrast imaging and RT-PCR, respectively, and brain functional capillary density and endothelial-leukocyte interactions were evaluated by fluorescence intravital video-microscopy. The 2VO-Sed group presented a decrease in MCBF (Sham-Sed: 230.9±12.2 vs. 2VO-Sed: 183.6±10.6 arbitrary perfusion units, P<0.05) and in functional capillary density (Sham-Sed: 336.4±25.3 vs. 2VO-Sed: 225.5±28.1capillaries/mm(2), P<0.05). Early intervention with physical exercise was able to prevent the cerebral microvascular inflammation by decreasing endothelial-leukocyte interactions (2VO-Ex: 0.9±0.3 vs. 2VO-Sed: 5±0.6cells/min/100μm, P<0.0001) and reducing brain NADPH oxidase gene expression (2VO-Ex: 1.7±0.1 arbitrary units, P<0.05). Cerebral microcirculatory and inflammatory alterations appear to be triggered during the first days after 2VO surgery, and early intervention with physical exercise may represent a means of preventing the microvascular alterations induced by chronic cerebral hypoperfusion.

  7. WEATHERABILITY OF ENHANCED DEGRADABLE PLASTICS

    EPA Science Inventory

    The main objective of this study was to assess the performance and the asociated variability of several selected enhanced degradable plastic materials under a variety of different exposure conditions. Other objectives were to identify the major products formed during degradation ...

  8. Network Plasticity as Bayesian Inference

    PubMed Central

    Legenstein, Robert; Maass, Wolfgang

    2015-01-01

    General results from statistical learning theory suggest to understand not only brain computations, but also brain plasticity as probabilistic inference. But a model for that has been missing. We propose that inherently stochastic features of synaptic plasticity and spine motility enable cortical networks of neurons to carry out probabilistic inference by sampling from a posterior distribution of network configurations. This model provides a viable alternative to existing models that propose convergence of parameters to maximum likelihood values. It explains how priors on weight distributions and connection probabilities can be merged optimally with learned experience, how cortical networks can generalize learned information so well to novel experiences, and how they can compensate continuously for unforeseen disturbances of the network. The resulting new theory of network plasticity explains from a functional perspective a number of experimental data on stochastic aspects of synaptic plasticity that previously appeared to be quite puzzling. PMID:26545099

  9. Smartphones and the plastic surgeon.

    PubMed

    Al-Hadithy, Nada; Ghosh, Sudip

    2013-06-01

    Surgical trainees are facing limited training opportunities since the introduction of the European Working Time Directive. Smartphone sales are increasing and have usurped computer sales for the first time. In this context, smartphones are an important portable reference and educational tool, already in the possession of the majority of surgeons in training. Technology in the palm of our hands has led to a revolution of accessible information for the plastic surgery trainee and surgeon. This article reviews the uses of smartphones and applications for plastic surgeons in education, telemedicine and global health. A comprehensive guide to existing and upcoming learning materials and clinical tools for the plastic surgeon is included. E-books, podcasts, educational videos, guidelines, work-based assessment tools and online logbooks are presented. In the limited resource setting of modern clinical practice, savvy plastic surgeons can select technological tools to democratise access to education and best clinical care.

  10. THERMAL DEPOLYMERIZATION OF POSTCONSUMER PLASTICS

    EPA Science Inventory

    The University of North Dakota Energy & Environmental Research Center (EERC) performed two series of tests to evaluate process conditions for thermal depolymerization of postconsumer plastics. The objective of the first test series was to provide data for optimization of reactio...

  11. Nano-Ceramic Coated Plastics

    NASA Technical Reports Server (NTRS)

    Cho, Junghyun

    2013-01-01

    Plastic products, due to their durability, safety, and low manufacturing cost, are now rapidly replacing cookware items traditionally made of glass and ceramics. Despite this trend, some still prefer relatively expensive and more fragile ceramic/glassware because plastics can deteriorate over time after exposure to foods, which can generate odors, bad appearance, and/or color change. Nano-ceramic coatings can eliminate these drawbacks while still retaining the advantages of the plastic, since the coating only alters the surface of the plastic. The surface coating adds functionality to the plastics such as self-cleaning and disinfectant capabilities that result from a photocatalytic effect of certain ceramic systems. These ceramic coatings can also provide non-stick surfaces and higher temperature capabilities for the base plastics without resorting to ceramic or glass materials. Titanium dioxide (TiO2) and zinc oxide (ZnO) are the candidates for a nano-ceramic coating to deposit on the plastics or plastic films used in cookware and kitchenware. Both are wide-bandgap semiconductors (3.0 to 3.2 eV for TiO2 and 3.2 to 3.3 eV for ZnO), so they exhibit a photocatalytic property under ultraviolet (UV) light. This will lead to decomposition of organic compounds. Decomposed products can be easily washed off by water, so the use of detergents will be minimal. High-crystalline film with large surface area for the reaction is essential to guarantee good photocatalytic performance of these oxides. Low-temperature processing (<100 C) is also a key to generating these ceramic coatings on the plastics. One possible way of processing nanoceramic coatings at low temperatures (< 90 C) is to take advantage of in-situ precipitated nanoparticles and nanostructures grown from aqueous solution. These nanostructures can be tailored to ceramic film formation and the subsequent microstructure development. In addition, the process provides environment- friendly processing because of the

  12. Plastic Deformation of Granular Materials

    DTIC Science & Technology

    1993-01-25

    discontinuities. These result will be important in our granular flow work, when considering viscoplastic constitutive relations (i.e. relaxation systems...5 CUNDN( NUMRES Plastic Deformation of Granular Materials (U) 61102F 6. AUTHOR(S) 2304/A4 Dr. E. Bruce Pitman 7 PERFORMING ORGANIZATION NA .h • 8...lose hyperbolicity. 98 3 81 061! SUBJECT TERMS 15. NUMBER OF PAGES granular material ; plastic deformation; hyperbolic 12 equations 16. PRICE CODE 17

  13. Presence of diabetic microvascular complications does not incrementally increase risk of ischemic stroke in diabetic patients with atrial fibrillation

    PubMed Central

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

    2016-01-01

    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

  14. Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease.

    PubMed

    Fedele, Francesco; Mancone, Massimo; Chilian, William M; Severino, Paolo; Canali, Emanuele; Logan, Suzanna; De Marchis, Maria Laura; Volterrani, Maurizio; Palmirotta, Raffaele; Guadagni, Fiorella

    2013-11-01

    Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we proposed that genetic anomalies of ion channels or specific endothelial regulators may underlie coronary microvascular disease. We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for ion channels expressed in the coronary vasculature and the possible correlation with IHD resulting from microvascular dysfunction. 242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted, analyzing genetic polymorphisms relative to (1) NOS3 encoding for endothelial nitric oxide synthase (eNOS); (2) ATP2A2 encoding for the Ca²⁺/H⁺-ATPase pump (SERCA); (3) SCN5A encoding for the voltage-dependent Na⁺ channel (Nav1.5); (4) KCNJ8 and KCNJ11 encoding for the Kir6.1 and Kir6.2 subunits of K-ATP channels, respectively; and (5) KCN5A encoding for the voltage-gated K⁺ channel (Kv1.5). No significant associations between clinical IHD manifestations and polymorphisms for SERCA, Kir6.1, and Kv1.5 were observed (p > 0.05), whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with IHD and microvascular dysfunction. Interestingly, genetic polymorphisms for ion channels seem to have an important clinical impact influencing the susceptibility for microvascular dysfunction and IHD, independent of the presence of classic cardiovascular risk factors.

  15. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

    PubMed Central

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

  16. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background.

    PubMed

    Ksiazek-Winiarek, Dominika Justyna; Szpakowski, Piotr; Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets.

  17. Helene: A Plastic Model

    NASA Astrophysics Data System (ADS)

    Umurhan, O. M.; Moore, J. M.; Howard, A. D.; Schenk, P.; White, O. L.

    2014-12-01

    Helene, the Saturnian L4 Trojan satellite co-orbiting Dionne and sitting within the E-ring, possesses an unusual morphology characteristic of broad km-scale basins and depressions and a generally smooth surface patterned with streaks and grooves which are indicative of non-typical mass transport. Elevation angles do not appear to exceed 10o at most. The nature and origin of the surface materials forming these grooved patterns is unknown. Given the low surface gravity (<5mm/s2), it hard to imagine how such transport features can come about with such low grades and surface gravities. Preliminary examinations of classical linear and nonlinear mass wasting mechanisms do not appear to reproduce these curious features. A suite of hypothesis that we examine is the possibility that the fine grain material on the surface has been either (i) accreted or (ii) generated as refractory detritus resulting from sublimation of the icy bedrock, and that these materials subsequently mass-waste like a non-Newtonian highly non-linear creeping flow. Modifying the landform evolution model MARSSIM to handle two new mass-wasting mechanism, the first due to glacial-like flow via Glen's Law and the second due to plastic-like flow like a Bingham fluid, we setup and test a number of likely scenarios to explain the observations. The numerical results qualitatively indicate that treating the mass-wasting materials as a Bingham material reproduces many of the qualitative features observed. We also find that in those simulations in which accretion is concomitant with Bingham mass-wasting, the long time-evolution of the surface flow shows intermittency in the total surface activity (defined as total surface integral of the absolute magnitude of the mass-flux). Detailed analyses identify the locations where this activity is most pronounced and we will discuss these and its implications in further detail.

  18. 49 CFR 192.281 - Plastic pipe.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Plastic pipe. 192.281 Section 192.281... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion may not be disturbed until it has properly set. Plastic pipe may not be joined by a threaded joint...

  19. 49 CFR 192.281 - Plastic pipe.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Plastic pipe. 192.281 Section 192.281... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion may not be disturbed until it has properly set. Plastic pipe may not be joined by a threaded joint...

  20. 49 CFR 192.59 - Plastic pipe.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Plastic pipe. 192.59 Section 192.59 Transportation... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Materials § 192.59 Plastic pipe. (a) New plastic pipe... specification; and (2) It is resistant to chemicals with which contact may be anticipated. (b) Used plastic...

  1. 49 CFR 192.281 - Plastic pipe.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Plastic pipe. 192.281 Section 192.281... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion may not be disturbed until it has properly set. Plastic pipe may not be joined by a threaded joint...

  2. 49 CFR 192.59 - Plastic pipe.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Plastic pipe. 192.59 Section 192.59 Transportation... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Materials § 192.59 Plastic pipe. (a) New plastic pipe... specification; and (2) It is resistant to chemicals with which contact may be anticipated. (b) Used plastic...

  3. 49 CFR 192.59 - Plastic pipe.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Plastic pipe. 192.59 Section 192.59 Transportation... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Materials § 192.59 Plastic pipe. (a) New plastic pipe... specification; and (2) It is resistant to chemicals with which contact may be anticipated. (b) Used plastic...

  4. 49 CFR 192.281 - Plastic pipe.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Plastic pipe. 192.281 Section 192.281... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion may not be disturbed until it has properly set. Plastic pipe may not be joined by a threaded joint...

  5. 49 CFR 192.59 - Plastic pipe.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Plastic pipe. 192.59 Section 192.59 Transportation... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Materials § 192.59 Plastic pipe. (a) New plastic pipe... specification; and (2) It is resistant to chemicals with which contact may be anticipated. (b) Used plastic...

  6. 49 CFR 192.281 - Plastic pipe.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Plastic pipe. 192.281 Section 192.281... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion may not be disturbed until it has properly set. Plastic pipe may not be joined by a threaded joint...

  7. 49 CFR 192.59 - Plastic pipe.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Plastic pipe. 192.59 Section 192.59 Transportation... BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Materials § 192.59 Plastic pipe. (a) New plastic pipe... specification; and (2) It is resistant to chemicals with which contact may be anticipated. (b) Used plastic...

  8. The Story of the Plastics Industry.

    ERIC Educational Resources Information Center

    Masson, Don, Ed.

    This is an illustrated informative booklet, designed to serve members of the Society of the Plastics Industry, Inc., and the plastics industry as a whole. It provides basic information about the industry's history and growth, plastics raw materials, typical uses of plastics, properties, and methods of processing and fabricating. (Author/DS)

  9. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  10. Skin microvascular reactivity in children and adolescents with type 1 diabetes in relation to levels of physical activity and aerobic fitness.

    PubMed

    Roche, Denise M; Edmunds, Sarah; Cable, Tim; Didi, Mo; Stratton, Gareth

    2008-11-01

    No studies to date have evaluated the relationship between exercise and microvascular function in youth with type 1 diabetes mellitus (T1DM). Twenty-nine complication free children and adolescents with T1DM were assessed for skin microvascular reactivity, aerobic fitness (VO2peak) and physical activity. VO2peak but not physical activity was significantly and independently associated with maximal hyperemia of the skin microcirculation (p < .01). No significant associations were found between venoarteriolar reflex (VAR) vasoconstriction and VO2peak or physical activity. Aerobic fitness may be an important indicator or mediator of effective microvascular endothelial function in youth with T1DM.

  11. Vertebral artery dolicoectasia with brainstem compression: role of mi