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Find video protocols related to scientific articles indexed in Pubmed.
Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents.
N. Engl. J. Med.
PUBLISHED: 11-18-2014
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Background Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain. Methods Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding. Results A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. Conclusions Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938 .).
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Distinguishing isobaric phosphated and sulfated carbohydrates by coupling of mass spectrometry with gas phase vibrational spectroscopy.
Phys Chem Chem Phys
PUBLISHED: 09-12-2014
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An original application of the coupling of mass spectrometry with vibrational spectroscopy, used for the first time to discriminate isobaric bioactive saccharides with sulfate and phosphate functional modifications, is presented. Whereas their nominal masses and fragmentation patterns are undifferentiated by sole mass spectrometry, their distinctive OH stretching modes at 3595 cm(-1) and 3666 cm(-1), respectively, provide a reliable spectroscopic diagnostic for distinguishing their sulfate or phosphate functionalization. A detailed analysis of the 6-sulfated and 6-phosphated d-glucosamine conformations is presented, together with theoretical scaled harmonic spectra and anharmonic spectra (VPT2 and DFT-based molecular dynamics simulations). Strong anharmonic effects are observed in the case of the phosphated species, resulting in a dramatic enhancement of its phosphate diagnostic mode.
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Elevated cell-free plasma DNA level as an independent predictor of mortality in patients with severe traumatic brain injury.
J. Neurotrauma
PUBLISHED: 08-04-2014
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Trauma is the leading cause of death in individuals less than 45 years old worldwide, and up to 50% of trauma fatalities are because of brain injury. Prediction of outcome is one of the major problems associated with severe traumatic brain injury (TBI), and research efforts have focused on the investigation of biomarkers with prognostic value after TBI. Therefore, our aim was to investigate whether cell-free DNA concentrations correlated to short-term primary outcome (survival or death) and Glasgow Coma Scale (GCS) scores after severe TBI. A total of 188 patients with severe TBI were enrolled in this prospective study; outcome variables comprised survival and neurological assessment using the GCS at intensive care unit (ICU) discharge. Control blood samples were obtained from 25 healthy volunteers. Peripheral venous blood was collected at admission to the ICU. Plasma DNA was measured using a real-time quantitative polymerase chain reaction (PCR) assay for the ?-globin gene. There was correlation between higher DNA levels and both fatal outcome and lower hospital admission GCS scores. Plasma DNA concentrations at the chosen cutoff point (?171,381 kilogenomes-equivalents/L) predicted mortality with a specificity of 90% and a sensitivity of 43%. Logistic regression analysis showed that elevated plasma DNA levels were independently associated with death (p<0.001). In conclusion, high cell-free DNA concentration was a predictor of short-term mortality after severe TBI.
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Short communication: Prevalence and risk factors for human T cell lymphotropic virus infection in Southern Brazilian HIV-positive patients.
AIDS Res. Hum. Retroviruses
PUBLISHED: 06-26-2014
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HIV/human T cell lymphotropic virus (HTLV) coinfection has a large range of prevalence in the different risk groups and geographic regions of the world. Most of the HTLV-infected people live in geographic areas where the virus is endemic, as it happens in Brazil. The aim of this study was to identify HTLV prevalence and risk factors in HIV-positive patients. A cross-sectional study was conducted with 580 HIV-positive patients (mean age of 40.6 years and 45.0% men) from a specialized HIV/AIDS diagnosis and treatment center in Southern Brazil. Sociodemographic data, HIV risk factors, and HTLV-1/2 antibodies were collected. HTLV proviral DNA was detected by polymerase chain reaction (PCR). A multivariate analysis was performed to identify risk factors for HTLV infection. HTLV antibodies were detected in 29 (5.0%) and HTLV provirus in 17 (2.9%) patients. HTLV-1 was identified in 11 (64.7%) patients and HTLV-2 in 6 (35.3%) patients. No significant differences were observed between mono and coinfected patients in clinical characteristics regarding HIV/AIDS (time since HIV diagnosis, HIV viral load, lymphocytes CD4(+) count, and use of highly active antiretroviral therapy). Blood transfusion history was significantly associated with HIV/HTLV coinfection (p=0.039). Alcohol abuse was more prevalent in HTLV-positive (47.1%) than in HIV mono-infected patients (20.4%; p=0.008). Tattooing was the only risk factor independently associated with HIV/HTLV coinfection (p=0.035). This information contributes to an understanding of the epidemiology of HIV/HTLV coinfection in Brazil.
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Facial feminization surgery: the forehead. Surgical techniques and analysis of results.
Plast. Reconstr. Surg.
PUBLISHED: 06-20-2014
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Facial feminization surgery encompasses a series of surgical techniques derived from plastic and craniomaxillofacial surgery to soften facial features that are generally perceived as being more masculine, mainly in patients diagnosed with gender dysphoria. This article describes the main surgical techniques used in feminization of the forehead complex, sequences the different steps in forehead reconstruction, evaluates results obtained using cephalometric analysis, and includes the level of patient satisfaction.
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Increased levels of interleukin-6, -8 and -10 are associated with fatal outcome following severe traumatic brain injury.
Brain Inj
PUBLISHED: 05-15-2014
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Despite the involvement of cytokine production in neurotrauma, there is still controversy regarding cytokines levels and clinical outcome following severe traumatic brain injury (TBI).
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Optimized imaging of the postoperative spine.
Neuroimaging Clin. N. Am.
PUBLISHED: 05-06-2014
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Few tasks in imaging are more challenging than that of optimizing evaluations of the instrumented spine. The authors describe how applying fundamental and more advanced principles to postoperative spine computed tomography and magnetic resonance examinations mitigates the challenges associated with metal implants and significantly improves image quality and consistency. Newer and soon-to-be-available enhancements should provide improved visualization of tissues and hardware as multispectral imaging sequences continue to develop.
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Detection of glutamate and acetylcholine with organic electrochemical transistors based on conducting polymer/platinum nanoparticle composites.
Adv. Mater. Weinheim
PUBLISHED: 04-09-2014
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The aim of the study is to open a new scope for organic electrochemical transistors based on PEDOT:PSS, a material blend known for its stability and reliability. These devices can leverage molecular electrocatalysis by incorporating small amounts of nano-catalyst during the transistor manufacturing (spin coating). This methodology is very simple to implement using the know-how of nanochemistry and results in efficient enzymatic activity transduction, in this case utilizing choline oxidase and glutamate oxidase.
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A four-diode full-wave ionic current rectifier based on bipolar membranes: overcoming the limit of electrode capacity.
Adv. Mater. Weinheim
PUBLISHED: 03-20-2014
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Full-wave rectification of ionic currents is obtained by constructing the typical four-diode bridge out of ion conducting bipolar membranes. Together with conjugated polymer electrodes addressed with alternating current, the bridge allows for generation of a controlled ionic direct current for extended periods of time without the production of toxic species or gas typically arising from electrode side-reactions.
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A complete molecular biology assay for hepatitis C virus detection, quantification and genotyping.
Rev. Soc. Bras. Med. Trop.
PUBLISHED: 02-26-2014
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Molecular biology procedures to detect, genotype and quantify hepatitis C virus (HCV) RNA in clinical samples have been extensively described. Routine commercial methods for each specific purpose (detection, quantification and genotyping) are also available, all of which are typically based on polymerase chain reaction (PCR) targeting the HCV 5' untranslated region (5'UTR). This study was performed to develop and validate a complete serial laboratory assay that combines real-time nested reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) techniques for the complete molecular analysis of HCV (detection, genotyping and viral load) in clinical samples.
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Agents of earthy-musty taste and odor in water: evaluation of cytotoxicity, genotoxicity and toxicogenomics.
Sci. Total Environ.
PUBLISHED: 02-20-2014
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Considering the limited number of studies on the biological effects on human health of cyanobacterial compounds that cause taste and odor, the present study assessed the cytotoxic and genotoxic potentials of 2-methylisoborneol (2-MIB) and geosmin (GEO) using the MTT assay and the in vitro comet and cytokinesis-block micronucleus (CBMN-Cyt) assays in human HepG2 cells. The toxicogenomics of genes responsive to DNA damage and metabolization by the exposure of cells to 2-MIB and GEO were also investigated. The results showed that concentrations of 2-MIB and GEO above 100 and 75 ?g/mL, respectively, were cytotoxic to HepG2 cells. Doses of 2-MIB (12.5, 25, 50, 75 and 100 ?g/mL) and GEO (12.5, 25, 50, and 75 ?g/mL) were unable to induce neither DNA damage nor events associated with chromosomal instability. Similarly, no concentration of each compound induced increments in the expression of CDKN1A, GADD45?, MDM2 and TP53 DNA damage responsive genes as well as in CYP1A1 and CYP1A2 metabolizing genes. Although cytotoxicity was observed, concentrations that caused it are much higher than those expected to occur in aquatic environments. Thus, environmentally relevant concentrations of both compounds are not expected to exhibit cytotoxicity or genotoxicity to humans.
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Platelet-derived S100 family member myeloid-related protein-14 regulates thrombosis.
J. Clin. Invest.
PUBLISHED: 01-30-2014
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Expression of the gene encoding the S100 calcium-modulated protein family member MRP-14 (also known as S100A9) is elevated in platelets from patients presenting with acute myocardial infarction (MI) compared with those from patients with stable coronary artery disease; however, a causal role for MRP-14 in acute coronary syndromes has not been established. Here, using multiple models of vascular injury, we found that time to arterial thrombotic occlusion was markedly prolonged in Mrp14?/? mice. We observed that MRP-14 and MRP-8/MRP-14 heterodimers (S100A8/A9) are expressed in and secreted by platelets from WT mice and that thrombus formation was reduced in whole blood from Mrp14?/? mice. Infusion of WT platelets, purified MRP-14, or purified MRP-8/MRP-14 heterodimers into Mrp14?/? mice decreased the time to carotid artery occlusion after injury, indicating that platelet-derived MRP-14 directly regulates thrombosis. In contrast, infusion of purified MRP-14 into mice deficient for both MRP-14 and CD36 failed to reduce carotid occlusion times, indicating that CD36 is required for MRP-14-dependent thrombosis. Our data identify a molecular pathway of thrombosis that involves platelet MRP-14 and CD36 and suggest that targeting MRP-14 has potential for treating atherothrombotic disorders, including MI and stroke.
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Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization.
J. Biol. Chem.
PUBLISHED: 01-02-2014
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Accumulating evidence supports the importance of macrophage plasticity in a broad spectrum of biological processes operative in health and disease. A major locus of control regulating macrophage polarization is at the transcriptional level, and several major pathways have been elucidated in recent years. In this study, we identify the Kruppel-like transcription factor 6 (KLF6) as a molecular toggle controlling macrophage speciation. KLF6 expression was robustly induced by pro-inflammatory M1 stimuli (e.g. LPS and IFN-?) and strongly suppressed by M2 stimuli (e.g. IL4 and IL-13) in human and murine macrophages. Gain- and loss-of-function studies suggest that KLF6 is required for optimal LPS-induced pro-inflammatory gene expression, acting cooperatively with NF-?B. Furthermore, KLF6 inhibits anti-inflammatory gene expression by negatively regulating peroxisome proliferator-activated receptor ? expression in macrophages. Collectively, these observations identify KLF6 as a novel transcriptional regulator of macrophage polarization.
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Soluble mediators regulating immunity in early life.
Front Immunol
PUBLISHED: 01-01-2014
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Soluble factors in blood plasma have a substantial impact on both the innate and adaptive immune responses. The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, protecting against systemic infection. Levels of these innate effector proteins are generally lower in neonatal circulation at term delivery than in adults, and lower still at preterm delivery. The extracellular environment also has a critical influence on immune cell maturation, activation, and effector functions, and many of the factors in plasma, including hormones, vitamins, and purines, have been shown to influence these processes for leukocytes of both the innate and adaptive immune systems. The ontogeny of plasma factors can be viewed in the context of a lower effectiveness of immune responses to infection and immunization in early life, which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of the anti-inflammatory cytokine IL-10, among other ontogenic differences. Accordingly, we survey here a number of soluble mediators in plasma for which age-dependent differences in abundance may influence the ontogeny of immune function, particularly direct innate interaction and skewing of adaptive lymphocyte activity in response to infectious microorganisms and adjuvanted vaccines.
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Terror attacks increase the risk of vascular injuries.
Front Public Health
PUBLISHED: 01-01-2014
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Extensive literature exists about military trauma as opposed to the very limited literature regarding terror-related civilian trauma. However, terror-related vascular trauma (VT), as a unique type of injury, is yet to be addressed.
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A rapid test for soy aeroallergens exposure assessment.
PLoS ONE
PUBLISHED: 01-01-2014
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Determining soy aeroallergens levels is extremely important in the assessment of health risks due to these airborne substances. Currently, soy aeroallergens exposure in the environment is monitored using enzyme immunoassays (EIA) which must be evaluated in a specialized laboratory by skilled personnel.
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Transanal endoscopic microsurgery: also for the treatment of retrorectal tumors.
Minim Invasive Ther Allied Technol
PUBLISHED: 12-13-2013
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Abstract Retrorectal tumors are an uncommon pathological entity. Their clinical importance arises from their occasional malignant nature or malignant transformation. The treatment of choice for most presacral tumors is surgical excision. The approach depends upon the upper limit of the lesion and the presumptive pathology. We reviewed the main features of these tumors with emphasis on transanal endoscopic microsurgery (TEM) as a viable surgical approach for the treatment of the lesions, undertaken in our institution. We present our small case series, consisting of six patients with retrorectal lesions who underwent local excision via TEM. Early and late postoperative outcomes are presented. TEM for retrorectal lesions appears to be a feasible and safe approach. A remarkably low morbidity favors TEM in selected patients.
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Reconsidering Policy of Casualty Evacuation in a Remote Mass-Casualty Incident.
Prehosp Disaster Med
PUBLISHED: 11-15-2013
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Inappropriate distribution of casualties in mass-casualty incidents (MCIs) may overwhelm hospitals. This study aimed to review the consequences of evacuating casualties from a bus accident to a single peripheral hospital and lessons learned regarding policy of casualty evacuation.
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Kruppel-like factor 15 is critical for vascular inflammation.
J. Clin. Invest.
PUBLISHED: 06-28-2013
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Activation of cells intrinsic to the vessel wall is central to the initiation and progression of vascular inflammation. As the dominant cellular constituent of the vessel wall, vascular smooth muscle cells (VSMCs) and their functions are critical determinants of vascular disease. While factors that regulate VSMC proliferation and migration have been identified, the endogenous regulators of VSMC proinflammatory activation remain incompletely defined. The Kruppel-like family of transcription factors (KLFs) are important regulators of inflammation. In this study, we identified Kruppel-like factor 15 (KLF15) as an essential regulator of VSMC proinflammatory activation. KLF15 levels were markedly reduced in human atherosclerotic tissues. Mice with systemic and smooth muscle-specific deficiency of KLF15 exhibited an aggressive inflammatory vasculopathy in two distinct models of vascular disease: orthotopic carotid artery transplantation and diet-induced atherosclerosis. We demonstrated that KLF15 alters the acetylation status and activity of the proinflammatory factor NF-?B through direct interaction with the histone acetyltransferase p300. These studies identify a previously unrecognized KLF15-dependent pathway that regulates VSMC proinflammatory activation.
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Prolylcarboxypeptidase promotes angiogenesis and vascular repair.
Blood
PUBLISHED: 06-06-2013
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Prolylcarboxypeptidase (PRCP) is associated with leanness, hypertension, and thrombosis. PRCP-depleted mice have injured vessels with reduced Kruppel-like factor (KLF)2, KLF4, endothelial nitric oxide synthase (eNOS), and thrombomodulin. Does PRCP influence vessel growth, angiogenesis, and injury repair? PRCP depletion reduced endothelial cell growth, whereas transfection of hPRCP cDNA enhanced cell proliferation. Transfection of hPRCP cDNA, or an active site mutant (hPRCPmut) rescued reduced cell growth after PRCP siRNA knockdown. PRCP-depleted cells migrated less on scratch assay and murine PRCP(gt/gt) aortic segments had reduced sprouting. Matrigel plugs in PRCP(gt/gt) mice had reduced hemoglobin content and angiogenic capillaries by platelet endothelial cell adhesion molecule (PECAM) and NG2 immunohistochemistry. Skin wounds on PRCP(gt/gt) mice had delayed closure and reepithelialization with reduced PECAM staining, but increased macrophage infiltration. After limb ischemia, PRCP(gt/gt) mice also had reduced reperfusion of the femoral artery and angiogenesis. On femoral artery wire injury, PRCP(gt/gt) mice had increased neointimal formation, CD45 staining, and Ki-67 expression. Alternatively, combined PRCP(gt/gt) and MRP-14(-/-) mice were protected from wire injury with less neointimal thickening, leukocyte infiltration, and cellular proliferation. PRCP regulates cell growth, angiogenesis, and the response to vascular injury. Combined with its known roles in blood pressure and thrombosis control, PRCP is positioned as a key regulator of vascular homeostasis.
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Repeated transanal endoscopic microsurgery is feasible and safe.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 03-08-2013
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The benefits of transanal endoscopic microsurgery (TEM) for the excision of benign and low-grade malignant lesions in the low and middle rectum are well recognized. This study examined the feasibility and safety of a repeated TEM procedure.
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Transanal endoscopic microsurgery for the resection of submucosal and retrorectal tumors.
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 02-07-2013
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Transanal endoscopic microsurgery (TEM) was originally designed for local endoscopic excision of benign and low-grade mucosal rectal lesions through an endoscopic system. The procedure is particularly challenging for submucosal and retrorectal lesions, as the tumor margins are not well defined.
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Training in trauma management: the role of simulation-based medical education.
Anesthesiol Clin
PUBLISHED: 01-29-2013
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Simulation-based medical education (SBME) offers a safe and "mistake-forgiving" environment to teach and train medical professionals. The diverse range of medical-simulation modalities enables trainees to acquire and practice an array of tasks and skills. SBME offers the field of trauma training multiple opportunities to enhance the effectiveness of the education provided in this challenging domain. Further research is needed to better learn the role of simulation-based learning in trauma management and education.
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Incidence, predictors, morphological characteristics, and clinical outcomes of stent edge dissections detected by optical coherence tomography.
JACC Cardiovasc Interv
PUBLISHED: 01-16-2013
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This study sought to investigate the frequency, predictors, and detailed qualitative and quantitative assessment of optical coherence tomography (OCT)-detected stent edge dissections. Its impact on subsequent management and clinical outcomes were also investigated.
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Applying independent component analysis to clinical FMRI at 7?t.
Front Hum Neurosci
PUBLISHED: 01-01-2013
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Increased BOLD sensitivity at 7?T offers the possibility to increase the reliability of fMRI, but ultra-high field is also associated with an increase in artifacts related to head motion, Nyquist ghosting, and parallel imaging reconstruction errors. In this study, the ability of independent component analysis (ICA) to separate activation from these artifacts was assessed in a 7?T study of neurological patients performing chin and hand motor tasks. ICA was able to isolate primary motor activation with negligible contamination by motion effects. The results of General Linear Model (GLM) analysis of these data were, in contrast, heavily contaminated by motion. Secondary motor areas, basal ganglia, and thalamus involvement were apparent in ICA results, but there was low capability to isolate activation in the same brain regions in the GLM analysis, indicating that ICA was more sensitive as well as more specific. A method was developed to simplify the assessment of the large number of independent components. Task-related activation components could be automatically identified via these intuitive and effective features. These findings demonstrate that ICA is a practical and sensitive analysis approach in high field fMRI studies, particularly where motion is evoked. Promising applications of ICA in clinical fMRI include presurgical planning and the study of pathologies affecting subcortical brain areas.
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Comparing the Microvascular Specificity of the 3- and 7-T BOLD Response Using ICA and Susceptibility-Weighted Imaging.
Front Hum Neurosci
PUBLISHED: 01-01-2013
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In functional MRI it is desirable for the blood-oxygenation level dependent (BOLD) signal to be localized to the tissue containing activated neurons rather than the veins draining that tissue. This study addresses the dependence of the specificity of the BOLD signal - the relative contribution of the BOLD signal arising from tissue compared to venous vessels - on magnetic field strength. To date, studies of specificity have been based on models or indirect measures of BOLD sensitivity such as signal to noise ratio and relaxation rates, and assessment has been made in isolated vein and tissue voxels. The consensus has been that ultra-high field systems not only significantly increase BOLD sensitivity but also specificity, that is, there is a proportionately reduced signal contribution from draining veins. Specificity was not quantified in prior studies, however, due to the difficulty of establishing a reliable network of veins in the activated volume. In this study we use a map of venous vessel networks extracted from 7?T high resolution Susceptibility-Weighted Images to quantify the relative contributions of micro- and macro-vasculature to functional MRI results obtained at 3 and 7?T. High resolution measurements made here minimize the contribution of physiological noise and Independent Component Analysis (ICA) is used to separate activation from technical, physiological, and motion artifacts. ICA also avoids the possibility of timing-dependent bias from different micro- and macro-vasculature responses. We find a significant increase in the number of activated voxels at 7?T in both the veins and the microvasculature - a BOLD sensitivity increase - with the increase in the microvasculature being higher. However, the small increase in sensitivity at 7?T was not significant. For the experimental conditions of this study, our findings do not support the hypothesis of an increased specificity of the BOLD response at ultra-high field.
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Effect of antihypertensive therapy on incident stroke in cohorts with prehypertensive blood pressure levels: a meta-analysis of randomized controlled trials.
Stroke
PUBLISHED: 12-08-2011
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Compared with normotensive individuals, there is a higher incidence of stroke in patients with hypertensive, as well as prehypertensive, blood pressure levels (ie, 120-139/80-89 mm Hg). Although several studies have shown that blood pressure reduction in hypertensive patients reduces the incidence of cardiovascular events, including stroke, it is still unknown whether treatment of prehypertensive blood pressure levels has a similar effect. We sought to determine whether reduction in blood pressure in the prehypertensive range reduces the incidence of stroke by performing a meta-analysis of randomized trials comparing an antihypertensive drug against placebo in cohorts with prehypertensive baseline blood pressure levels.
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Loss of myeloid related protein-8/14 exacerbates cardiac allograft rejection.
Circulation
PUBLISHED: 12-05-2011
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The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a proinflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14(-/-) mice that lack MRP-8/14 complexes.
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Optimizing antiplatelet therapy following percutaneous coronary intervention: clinical pathways for platelet function testing.
Rev Cardiovasc Med
PUBLISHED: 11-15-2011
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Current guidelines recommend dual antiplatelet therapy (DAPT), which includes aspirin and a platelet P2Y(12) adenosine diphosphate (ADP) receptor antagonist, for treatment of patients with acute coronary syndrome and following percutaneous coronary intervention (PCI). Although DAPT significantly reduces stent thrombosis and major adverse cardiovascular events (MACE), there is considerable interindividual variability in the degree of platelet inhibition achieved with the most widely used ADP receptor antagonist, clopidogrel, and high on-treatment platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with increased adverse cardiovascular events following PCI. Personalized tailoring of antiplatelet therapy guided by patient management algorithms and/or platelet function testing has the potential to reduce MACE and stent thrombosis. This article outlines specific algorithms for using potent new antiplatelet agents, such as prasugrel and ticagrelor, and platelet function "test and treat-to-target" strategies to reduce adverse cardiovascular events following PCI.
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Critical role for Syk in responses to vascular injury.
Blood
PUBLISHED: 08-31-2011
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Although current antiplatelet therapies provide potent antithrombotic effects, their efficacy is limited by a heightened risk of bleeding and failure to affect vascular remodeling after injury. New lines of research suggest that thrombosis and hemorrhage may be uncoupled at the interface of pathways controlling thrombosis and inflammation. Here, as one remarkable example, studies using a novel and highly selective pharmacologic inhibitor of the spleen tyrosine kinase Syk [PRT060318; 2-((1R,2S)-2-aminocyclohexylamino)-4-(m-tolylamino)pyrimidine-5-carboxamide] coupled with genetic experiments, demonstrate that Syk inhibition ameliorates both the acute and chronic responses to vascular injury without affecting hemostasis. Specifically, lack of Syk (murine radiation chimeras) attenuated shear-induced thrombus formation ex vivo, and PRT060318 strongly inhibited arterial thrombosis in vivo in multiple animal species while having minimal impact on bleeding. Furthermore, leukocyte-platelet-dependent responses to vascular injury, including inflammatory cell recruitment and neointima formation, were markedly inhibited by PRT060318. Thus, Syk controls acute and long-term responses to arterial vascular injury. The therapeutic potential of Syk may be exemplary of a new class of antiatherothrombotic agents that target the interface between thrombosis and inflammation.
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IL28B polymorphism associated with spontaneous clearance of hepatitis C infection in a Southern Brazilian HIV type 1 population.
AIDS Res. Hum. Retroviruses
PUBLISHED: 07-26-2011
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About one-third of people infected with human immunodeficiency virus-1 (HIV-1) are coinfected with hepatitis C virus (HCV) because of shared transmission routes. Studies report that HIV-1 complicates hepatitis C infection by increasing HCV viral load and reducing spontaneous clearance. Single nucleotide polymorphisms (SNPs) upstream of the IL28B gene have been associated with spontaneous and treatment-induced clearance of HCV infection. The aim of this study was to evaluate the association between the SNP rs12979860 of the IL28B gene and spontaneous clearance of HCV infection in a Brazilian HIV-1 population. The SNP was analyzed by polymerase chain reaction (PCR) followed by restriction digestion in 138 anti-HCV-positive patients. Spontaneous clearance was observed in 34 subjects (24.6%). Genotype distribution was significantly different between spontaneous clearance and HCV chronic patients. The CT/TT genotypes conferred a nearly 3-fold increased odds to chronic HCV infection relative to the CC genotype (odds ratio, 2.78; 95% confidence interval, 1.16-6.64; p=0.011). In conclusion, the rs12979860 polymorphism is associated with spontaneous clearance of HCV in HIV-1 Brazilian infected patients.
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Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis.
JACC Cardiovasc Interv
PUBLISHED: 02-22-2011
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The cellular and molecular processes that control vascular injury responses after percutaneous coronary intervention involve a complex interplay among vascular cells and progenitor cells that control arterial remodeling, neointimal proliferation, and re-endothelialization. Drug-eluting stents (DES) improve the efficacy of percutaneous coronary intervention by modulating vascular inflammation and preventing neointimal proliferation and restenosis. Although positive effects of DES reduce inflammation and restenosis, negative effects delay re-endothelialization and impair endothelial function. Delayed re-endothelialization and impaired endothelial function are linked to stent thrombosis and adverse clinical outcomes after DES use. Compared with bare-metal stents, DES also differentially modulate mobilization, homing, and differentiation of vascular progenitor cells involved in re-endothelialization and neointimal proliferation. The effects of DES on vascular inflammation and repair directly impact clinical outcomes with these devices and dictate requirements for extended-duration dual antiplatelet therapy.
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Vascular access in transcatheter aortic valve implantation.
Int J Cardiovasc Imaging
PUBLISHED: 02-21-2011
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The positive early experiences with TAVI however, revealed that vascular access remains a hindrance to broader application and success of the procedure. This article will review the most common vascular routes used to deliver transcatheter aortic valves, and describe a new technique via the right axillary/subclavian artery approach.
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The impact of an eccentric intravascular ImageWire during coronary optical coherence tomography imaging.
EuroIntervention
PUBLISHED: 02-19-2011
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Optical coherence tomography (OCT) provides high-resolution imaging which enables characterisation of atherosclerosis and vascular response to injury, but to ensure optimal analysis, one must realise potential sources of image distortion. We designed a series of analyses, using coronary stents as a model, to investigate the influence of wire position on OCT-derived vascular images.
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IL-6 polymorphism associated with fatal outcome in patients with severe traumatic brain injury.
Brain Inj
PUBLISHED: 02-11-2011
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The aim of this study was to test whether a functional polymorphism (-174C/G) located in the promoter region of the interleukin-6 (IL-6) gene is associated with primary short-term outcome (death or Intensive Care Unit discharge) in patients with severe traumatic brain injury (TBI).
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Meta-analysis of randomized controlled trials on effect of angiotensin-converting enzyme inhibitors on cancer risk.
Am. J. Cardiol.
PUBLISHED: 01-31-2011
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The renin-angiotensin system is an important mediator of tumor progression and metastasis. A recent meta-analysis of randomized controlled trials reported an increased risk of cancer with angiotensin receptor blockers. It is unknown whether angiotensin-converting enzyme (ACE) inhibitors may have a similar effect. Our primary objective was to determine the effect of ACE inhibitors on cancer occurrence and cancer death. Our secondary objective was to determine the effect of ACE inhibitors on occurrence of gastrointestinal (GI) cancers given previous concerns of increased risk. Systematic searches of SCOPUS (covering MEDLINE, EMBASE, and other databases) and the Food and Drug Administration official web site were conducted for all randomized controlled trials of ACE inhibitors. Trials with ?1 year of follow-up and enrolling a minimum of 100 patients were included. Fourteen trials reported cancer data in 61,774 patients. This included 10 trials of 59,004 patients providing information on cancer occurrence, 7 trials of 37,515 patients for cancer death, and 5 trials including 23,291 patients for GI cancer. ACE inhibitor therapy did not have an effect on occurrence of cancer (I(2) 0%, risk ratio [RR] 1.01, 95% confidence interval [CI] 0.95 to 1.07, p = 0.78), cancer death (I(2) 0%, RR 1.00, 95% CI 0.88 to 1.13, p = 0.95), or GI cancer (RR 1.09, 95% CI 0.88 to 1.35, p = 0.43). In conclusion, ACE inhibitors did not significantly increase or decrease occurrence of cancer or cancer death. There was also no significant difference in risk of GI cancer.
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Cell therapy and satellite centers: the Cardiovascular Cell Therapy Research Network experience.
Contemp Clin Trials
PUBLISHED: 01-12-2011
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Due to the changing population in patients with myocardial infarction, recruiting patients in clinical trials continues to challenge clinical investigators. The Cardiovascular Cell Therapy Research Network (CCTRN) chose to expand the reach and power of its recruitment effort by incorporating both referral and treatment satellite centers. Eight treatment satellites were successfully identified and they screened patients over a two year period. The result of this effort was an increase in recruitment, with these treatment satellites contributing 30% of the patients to two of the three Network studies. The hurdles that these satellite treatment centers faced and how they surmounted them provide instruction to clinical research groups eager to expand to satellite systems and to health care practitioners who are interested in taking part in multicenter clinical trials.
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Genetic regulation of platelet receptor expression and function: application in clinical practice and drug development.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 11-19-2010
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Understanding genetic contributions to platelet function could have profound clinical ramifications for personalizing platelet-directed pharmacotherapy, by providing insight into the risks and possible benefits associated with specific genotypes. This article represents an integrated summary of presentations related to genetic regulation of platelet receptor expression and function given at the Fifth Annual Platelet Colloquium in January 2010. It is supplemented with additional highlights from the literature covering (1) approaches to determining and evidence for the associations of genetic variants with platelet hypo- and hyperresponsive phenotypes, (2) the ramifications of these polymorphisms with regard to clinical responses to antiplatelet therapies, and (3) the role of platelet function/genetic testing in guiding antiplatelet therapy.
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Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials.
Lancet Oncol.
PUBLISHED: 06-11-2010
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Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs.
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[Prevalence of HIV-1 subtypes in patients of an urban center in Southern Brazil].
Rev Saude Publica
PUBLISHED: 06-06-2010
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To estimate the prevalence of HIV-1 subtypes and analyze factors associated.
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Kruppel-like factor 15 regulates smooth muscle response to vascular injury--brief report.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 05-27-2010
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To determine the role of Kruppel-like factor (KLF) 15, a zinc finger transcriptional factor that is expressed in vascular smooth muscle cells (VSMCs) in vascular biology. VSMCs respond to mechanical injury via a tightly orchestrated series of gene regulatory events. KLF15 is broadly expressed in both arterial and venous vascular beds in a VSMC restricted fashion. KLF15 expression is markedly reduced by both pharmacological and mechanical stimuli. To examine the specific role of KLF15 in the vascular response to injury, we performed femoral artery wire injury in KLF15(-/-) and wild-type mice. KLF15(-/-) mice develop exaggerated neointimal growth, with evidence of increased SMC proliferation and migration within the neointima. In concordance, gain and loss of function studies in isolated VSMCs demonstrate that KLF15 can directly inhibit SMC proliferation and migration. To our knowledge, these data are the first to identify KLF15 as a novel inhibitor of VSMC proliferation and migration and to implicate this factor as a critical regulator of the vascular response to injury.
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Morphological transitions in partially gas-fluidized granular mixtures.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 05-10-2010
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Experiments were conducted to investigate pattern formation during the defluidization of a partially fluidized bimodal granular mixture. Partial fluidization occurs when the system is driven at gas velocities that are insufficient to fluidize all of the constituent particles. Over time, the granular mixture evolves into a variety of patterns depending on the concentrations of large and small particles and the gas velocity. We show how vertically oriented pipes, containing large particles, grow at the interface between the fluidized and static zones. The heterogeneities in the permeability field focus the flow, causing localized fluidization, which in turn localizes the sedimentation of the large particles segregating the system. We discuss how the interplay between heterogeneities in material properties, fluid flow and fluid induced deformation may be relevant to a variety of geological processes.
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Structural, electronic, magnetic and optical properties of icosahedral silver-nickel nanoclusters.
Phys Chem Chem Phys
PUBLISHED: 03-23-2010
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We present a systematic study of the structural, electronic, magnetic and optical properties of icosahedral bimetallic Ag((13-p))Ni(p) (p < or = 6) clusters in the gas phase investigated in the framework of density functional theory (DFT and TDDFT). In the most-stable structures, the central position is found to be occupied by a nickel atom. The evolution of spin-multiplicities and local atomic spin densities with Ag/Ni composition are discussed. The evolution of the optical properties with the Ag/Ni composition and the spatial positions of Ni atoms are analysed. An interpretation of spectroscopic patterns in terms of contribution from s- and d-type excitations is also given. In particular the d-electrons of nickel atoms are found to play a crucial role in the optical transitions of Ni-rich systems. Finally, our theoretical spectra are compared to the experimental ones for large Ni-core/Ag-shell clusters (about 2-5 nm in size).
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The intrinsic complement regulator decay-accelerating factor modulates the biological response to vascular injury.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 03-18-2010
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To investigate whether the presence of decay-accelerating factor (or CD55), an intrinsic complement regulator, protects against the development of vascular disease, given that complement activation can affect leukocytes and platelets.
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Management of patients with traumatic intracranial injury in hospitals without neurosurgical service.
J Trauma
PUBLISHED: 03-18-2010
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Many patients with intracranial bleeding (ICB) are being evaluated in hospitals with no neurosurgical service. Some of the patients may be safely managed in the primary hospital without transferring them to a designated neurosurgical center. In Israel, there are three approaches to alert patients with ICB: mandatory transfer, remote telemedicine neurosurgical consultation, and clinical-radiologic guidelines. We evaluated the outcome of alert patients with low-risk ICB who were managed in centers without neurosurgical service.
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Mac-1 (CD11b/CD18) links inflammation and thrombosis after glomerular injury.
Circulation
PUBLISHED: 09-14-2009
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Inflammation and thrombosis coexist in several disorders. Although it is recognized that leukocytes may induce a procoagulant state at sites of inflammation, the critical molecular determinants of this process remain largely unknown.
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Myeloid-related protein-8/14 is critical for the biological response to vascular injury.
Circulation
PUBLISHED: 07-20-2009
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Myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) are members of the S100 family of calcium-modulated proteins that regulate myeloid cell function and control inflammation, in part, through activation of Toll-like receptor-4 and the receptor for advanced glycation end products. A transcriptional profiling approach in patients with acute coronary syndromes identified MRP-14 as a novel predictor of myocardial infarction. Further studies demonstrated that elevated plasma levels of MRP-8/14 heterodimer predict increased risk of first and recurrent cardiovascular events. Beyond its serving as a risk marker, whether MRP-8/14 participates directly in vascular inflammation and disease remains unclear.
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Histology of tissue adherent to OptEase inferior vena cava filters regarding indwelling time.
Cardiovasc Intervent Radiol
PUBLISHED: 06-06-2009
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The purpose of this paper is to report on the histology of tissues found on retrieved filters with regard to indwelling time. Between February 2006 and January 2007, 28 Optease inferior vena cava filters (Cordis Europa, Roden, The Netherlands) were retrieved from 27 patients. Twenty-two filters were inserted prophylactically for trauma patients and six for patients with venous thromboembolism. Cavography was performed both before and after filter removal to evaluate the presence of thrombi or wall damage. Filters were retrieved with the snare and sheath method. All material adherents to the filters were examined histologically.The mean indwelling time of the filters was 24.9 days (range, 6-69 days). Red tissue fragments were seen on all the filters, consistent microscopically with clots and fibrin. On five filters (18%; mean indwelling time, 45.4 days) white tissue consistent with vascular intima was found. All postprocedure cavographies were normal. We conclude that most material adherent to the retrieved filters is thrombi, while vascular intima can be found in the minority of filters with a longer indwelling time.
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Matrix metalloproteinase gene polymorphisms in patients with rheumatoid arthritis.
Rheumatol. Int.
PUBLISHED: 05-20-2009
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Several genetic factors seem to be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to analyze whether functional polymorphisms in the promoter region of the MMP-1, -3 and -9 genes were associated with RA. The study population comprises 110 RA patients and 100 healthy controls. The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, and -1562 C/T MMP-9 polymorphisms were analyzed. The frequency of the 5A allele of MMP-3 gene was significantly higher in the controls when compared with the RA patients (0.45 vs. 0.32, P < 0.01). No significant differences were observed in the allele frequencies for the MMP-1 and -9 polymorphisms between RA patients and controls. Individuals carrying MMP-3 5A allele have significant higher frequency of extra-articular manifestations and rheumatoid nodules than individuals homozygous for 6A allele (P < 0.05). The results presented in this study provide evidence of an association between the MMP-3 gene polymorphism and RA.
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Intracoronary optical coherence tomography: a comprehensive review clinical and research applications.
JACC Cardiovasc Interv
PUBLISHED: 05-15-2009
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Cardiovascular optical coherence tomography (OCT) is a catheter-based invasive imaging system. Using light rather than ultrasound, OCT produces high-resolution in vivo images of coronary arteries and deployed stents. This comprehensive review will assist practicing interventional cardiologists in understanding the technical aspects of OCT based upon the physics of light and will also highlight the emerging research and clinical applications of OCT. Semi-automated imaging analyses of OCT systems permit accurate measurements of luminal architecture and provide insights regarding stent apposition, overlap, neointimal thickening, and, in the case of bioabsorbable stents, information regarding the time course of stent dissolution. The advantages and limitations of this new imaging modality will be discussed with emphasis on key physical and technical aspects of intracoronary image acquisition, current applications, definitions, pitfalls, and future directions.
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Human directed aggression in Brazilian domestic cats: owner reported prevalence, contexts and risk factors.
J. Feline Med. Surg.
PUBLISHED: 04-12-2009
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Aggression by cats towards humans is a serious behavioural, welfare and public health problem, although owners may believe it is an inevitable part of cat ownership. There has been little scientific investigation of the risk factors associated with this problem. One hundred and seven owners in the Sao Paulo region of Brazil, took part in a survey aimed at investigating the perceived prevalence of the problem, defining the most common contexts of human directed aggression and identifying associated potential risk factors. Human directed aggression occurred in 49.5% of cats and was most commonly associated with situations involving petting and play, followed by protection of a resource, when startled, when observing an unfamiliar animal and least commonly when unfamiliar people were present. Pedigree status, neuter status, a history of early trauma, sensitivity to being stroked, the absence of other cats in the home, relationship with other animals, level of background activity at home, access to the outside and tendency to be alone (meaning tendency to staying far from the family members) were all associated with an increased risk in one or more context. However, sex, age, age when acquired, source of pet, attachment to a specific household member, type of domestic accommodation, relationship with another cat if present and contact with other animals did not appear to increase the risk. The results suggest sensitivity to being stroked and background levels of stress in the home are the most pervasive risk factors, and future research should aim to investigate these factors further. These data are of relevance when advising owners about the risk and development of this problem.
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Glutamate promotes cell growth by EGFR signaling on U-87MG human glioblastoma cell line.
Pathol. Oncol. Res.
PUBLISHED: 03-12-2009
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Accumulating evidences suggest that glutamate plays a key role in the proliferation and invasion of malignant glioblastoma (GBM) tumors. It has been shown that GBM cells release and exploit glutamate for proliferation and invasion through AMPA glutamate receptors. Additionally, amplification of the epidermal growth factor receptor (EGFR) gene occurs in 40-50% of GBM. Since, PI3K/Akt is considered one of the main intracellular pathways involved in EGFR activation, AKT functions could trigger EGFR signaling. Thus, we investigated whether EGFR-phospho-Akt pathway is involved on the glutamate inducing U-87MG human GBM cell line proliferation. For these purpose, we treated the U-87MG cell line with 5 to 200 mM of glutamate and assessed the number of viable cells by trypan blue dye exclusion test. An increase in cell number (50%) was found at 5 mM glutamate, while the addition of DNQX (500 microM), an antagonist of AMPA receptor, inhibited the effect of glutamate on the U87-MG cells proliferation. Also, at 5 mM glutamate we observed an increase on the EGFR and phospho-Akt contents evaluated by immunohistochemistry. Moreover, U-87MG cells treated with glutamate exhibited an increase about 2 times in the EGFR mRNA expression. While, in the presence of the anti-EGFR gefitinib (50 muM) or the PI3K inhibitor wortmannin (5 muM), the U-87MG proliferation was restored to control levels. Together, our data suggest that glutamate signaling mediated by AMPA receptor induces U-87MG human GBM cell line proliferation via EGFR-phospho-Akt pathway.
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Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function.
Nat Mater
PUBLISHED: 02-24-2009
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Significant advances have been made in the understanding of the pathophysiology, molecular targets and therapies for the treatment of a variety of nervous-system disorders. Particular therapies involve electrical sensing and stimulation of neural activity, and significant effort has therefore been devoted to the refinement of neural electrodes. However, direct electrical interfacing suffers from some inherent problems, such as the inability to discriminate amongst cell types. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmitters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmitters, the device mimics the nerve synapse. Using the peripheral auditory system, we show that out of a diverse population of cells, the device can selectively stimulate nerve cells responding to a specific neurotransmitter. This is achieved by precise electronic control of electrophoretic migration through a polymer film. This mechanism provides several sought-after features for regulation of cell signalling: exact dosage determination through electrochemical relationships, minimally disruptive delivery due to lack of fluid flow, and on-off switching. This technology has great potential as a therapeutic platform and could help accelerate the development of therapeutic strategies for nervous-system disorders.
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Stent parameters predict major adverse clinical events and the response to platelet glycoprotein IIb/IIIa blockade: findings of the ESPRIT trial.
Circ Cardiovasc Interv
PUBLISHED: 01-23-2009
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Only limited data describe relationships between stent parameters (length and diameter), adverse events after percutaneous coronary intervention, and effects of platelet glycoprotein IIb/IIIa blockade by stent parameters.
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Clinical update on the management of adrenal hemorrhage.
Curr Urol Rep
PUBLISHED: 01-01-2009
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Adrenal hemorrhage is a rare yet potentially life-threatening event that occurs both in traumatic conditions and in a variety of nontraumatic conditions. Clinical manifestations of adrenal hemorrhage can vary widely depending on the degree and rate of hemorrhage, as well as the amount of adrenal cortex compromised by hemorrhage. Although an isolated focal unilateral adrenal hemorrhage may present subclinically, massive bilateral adrenal hemorrhage may lead to rapid cardiovascular collapse and ultimately death if not diagnosed appropriately and treated quickly. Diagnosis of adrenal hemorrhage is often complicated by its nonspecific presentation and tendency to occur in the setting of acute illness and other complicating medical conditions. This article outlines the variety of clinical situations in which adrenal hemorrhage can occur, summarizes the appropriate diagnostic tests available, and reviews the appropriate management of adrenal hemorrhage.
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Clinical results of topography-based customized ablations for myopia and myopic astigmatism.
J Refract Surg
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To evaluate clinical outcomes after primary treatments for myopia and myopic astigmatism with topography-based ablation profiles on the Allegretto Wave Eye-Q platform (Alcon Laboratories Inc).
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Platelet I?B kinase-? deficiency increases mouse arterial neointima formation via delayed glycoprotein Ib? shedding.
Arterioscler. Thromb. Vasc. Biol.
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On the luminal surface of injured arteries, platelet activation and leukocyte-platelet interactions are critical for the initiation and progression of arterial restenosis. The transcription factor nuclear factor-?B is a critical molecule in platelet activation. Here, we investigated the role of the platelet nuclear factor-?B pathway in forming arterial neointima after arterial injury.
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Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice.
J. Clin. Invest.
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The endothelium regulates vascular homeostasis, and endothelial dysfunction is a proximate event in the pathogenesis of atherothrombosis. Stimulation of the endothelium with proinflammatory cytokines or exposure to hemodynamic-induced disturbed flow leads to a proadhesive and prothrombotic phenotype that promotes atherothrombosis. In contrast, exposure to arterial laminar flow induces a gene program that confers a largely antiadhesive, antithrombotic effect. The molecular basis for this differential effect on endothelial function remains poorly understood. While recent insights implicate Kruppel-like factors (KLFs) as important regulators of vascular homeostasis, the in vivo role of these factors in endothelial biology remains unproven. Here, we show that endothelial KLF4 is an essential determinant of atherogenesis and thrombosis. Using in vivo EC-specific KLF4 overexpression and knockdown murine models, we found that KLF4 induced an antiadhesive, antithrombotic state. Mechanistically, we demonstrated that KLF4 differentially regulated pertinent endothelial targets via competition for the coactivator p300. These observations provide cogent evidence implicating endothelial KLFs as essential in vivo regulators of vascular function in the adult animal.
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Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome.
Blood
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The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.
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Unrestricted utilization of frequency domain optical coherence tomography in coronary interventions.
Int J Cardiovasc Imaging
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Frequency domain optical coherence tomography (FD-OCT) has shown promise to evaluate coronary devices in clinical trials, however, little is known about its application in clinical practice. This prospective, single center initiative planned for 100 % FD-OCT utilization in all patients undergoing coronary interventions during a 60-day period. Operators pre-specified the planned intervention based on angiography alone. FD-OCT success was defined as acquisition of good quality images enabling adequate quantification of vessel dimensions and lesion/percutaneous coronary intervention (PCI) assessment. Impact on management occurred when angiography-based planning was altered based on FD-OCT data. There were 297 FD-OCT acquisitions performed in 155 vessels from 150 patients. There were no FD-OCT procedural related cardiac adverse events and success was obtained in 85.7 % of all target vessels (pre-PCI = 76.8 % vs. post-PCI = 90.1 %, p = 0.004). Success on the first pullback occurred in 80.3 % overall (61.9 % in the initial operator experience and 85.5 % after the third procedure). FD-OCT impact on management was 81.8 % pre-PCI and 54.8 % post-PCI. Stent malapposition was detected in 39.2 % (89.4 % underwent further intervention) and edge dissection in 32.5 % (21.1 % treated with stent). FD-OCT success and management impact were similar in ACS and non-ACS patients (82.1 vs. 81.1 %, p = 1.000, and 62.5 vs. 65.1 %, p = 0.854, respectively). FD-OCT is safe, can successfully be incorporated into routine practice, and alters procedural strategy in a high proportion of patients undergoing PCI.
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Effectiveness of glycyrrhizinic Acid (glizigen) and an immunostimulant (viusid) to treat anogenital warts.
ISRN Dermatol
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Genital warts are benign proliferations of skin and mucosa caused by the human papillomavirus infection (hereinafter referred to as HPV). It is one of the most common sexually transmitted diseases in the world, whose incidence rate has increased in the last three decades. Current treatment involves the physical destruction of the infected cells. The fact that there are many different types of treatment goes to show that none of them are uniformly effective or directly antiviral. Objective. Demonstrate the efficacy of Glizigen in the III-phase clinical trial combined with a food supplement (VIUSID) formulated to boost the immune system when treating external anogenital warts. Design. 100 patients clinically diagnosed with anogenital lesions were included in the trial and assigned to two groups of 50 individuals. Those from one group where treated with Glizigen and Viusid and those from the other group with 25% podophyllin in alcohol, the results from each were then compared. Results. The combined Glizigen-Viusid treatment was seen to have an 87.5% efficacy rate, which was slightly more than that of the treatment with podophyllin, and there were hardly any adverse reactions reported during the treatment. Conclusions. the combined Glizigen-Viusid treatment was effective in treating genital warts.
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Inflammation and vascular injury: basic discovery to drug development.
Circ. J.
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The invited special lecture at the 76(th) Annual Scientific Meeting of the Japanese Circulation Society focused on the central role of inflammation in vascular injury and repair. Early studies pioneered the concept that mechanical injury, such as balloon angioplasty and endovascular stent deployment, elicits an inflammatory response from the vessel wall. This hypothesis was developed and substantiated at a time when the prevailing dogma viewed restenosis following angioplasty as a primarily proliferative smooth muscle cell disease. Antibody targeting of Mac-1 reduced leukocyte accumulation and limited neointimal formation following balloon injury or stent implantation. Genetic absence of Mac-1 resulted in diminished leukocyte accumulation and neointimal thickening after carotid artery injury in mice. In the course of those studies, our laboratory made fundamental discoveries regarding the mechanism of leukocyte recruitment at sites of vascular injury and identified platelet glycoprotein (GP) Ib?, a component of the GPIb-IX-V complex, as the previously unknown platelet counter-receptor for Mac-1. Follow-on studies have focused extensively on the structure, function, and signaling of the leukocyte integrin Mac-1. The binding site for GPIb? in Mac-1 has been mapped and subsequently showed that leukocyte engagement of platelet GPIb? via Mac-1 is critical not only for the biological response to vascular injury, but also for thrombosis, vasculitis, glomerulonephritis, and multiple sclerosis, thereby advancing the hypothesis that virtually all inflammation is platelet-dependent. Furthermore, ligand engagement of Mac-1 initiates a novel gene program that promotes inflammation by activating NF?B and downregulating the expression of the forkhead transcription factor Foxp1 that controls monocyte differentiation. Small molecule inhibitors of Mac-1 function have been pursued, including targeting of Mac-1-GPIb? binding or the downstream tyrosine kinase spleen tyrosine kinase. Drs Teruo Inoue, Koichi Node, Tatsuya Fukotomi, Masashi Sakuma, Toshifumi Morooka, and Kohsuke Nakajima, valued Japanese collaborators and post-doctoral fellows, have contributed enormously to these discoveries.
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Human gingival keratinocyte response to substances eluted from silorane composite material reveal impact on cell behavior reflected by RNA levels and induction of apoptosis.
Dent Mater
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The aim of this study was the characterization of siloran-derived composite eluates in conjunction with their putative impact on human gingival keratinocytes (HGK), i.e. levels of total RNA and induction of apoptosis compared to a methacrylate-based material.
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Chronic skin-specific inflammation promotes vascular inflammation and thrombosis.
J. Invest. Dermatol.
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Patients with psoriasis have systemic and vascular inflammation and are at increased risk for myocardial infarction, stroke, and cardiovascular death. However, the underlying mechanism(s) mediating the link between psoriasis and vascular disease is incompletely defined. This study sought to determine whether chronic skin-specific inflammation has the capacity to promote vascular inflammation and thrombosis. Using the KC-Tie2 doxycycline-repressible (Dox-off) murine model of psoriasiform skin disease, spontaneous aortic root inflammation was observed in 33% of KC-Tie2 compared with 0% of control mice by 12 months of age (P=0.04) and was characterized by the accumulation of macrophages, T lymphocytes, and B lymphocytes, as well as by reduced collagen content and increased elastin breaks. Importantly, aortic inflammation was preceded by increases in serum tumor necrosis factor-?, IL-17A, vascular endothelial growth factor, IL-12, monocyte chemotactic protein-1, and S100A8/A9, as well as splenic and circulating CD11b(+)Ly-6C(hi) pro-inflammatory monocytes. Doxycycline treatment of old mice with severe skin disease eliminated skin inflammation and the presence of aortic root lesion in 1-year-old KC-Tie2 animals. Given the bidirectional link between inflammation and thrombosis, arterial thrombosis was assessed in KC-Tie2 and control mice; mean time to occlusive thrombus formation was shortened by 64% (P=0.002) in KC-Tie2 animals; and doxycycline treatment returned thrombosis clotting times to that of control mice (P=0.69). These findings demonstrate that sustained skin-specific inflammation promotes aortic root inflammation and thrombosis and suggest that aggressive treatment of skin inflammation may attenuate pro-inflammatory and pro-thrombotic pathways that produce cardiovascular disease in psoriasis patients.
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Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells.
J. Clin. Invest.
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Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs.
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Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis.
Circ. Res.
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Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined.
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Diagnostic evaluation of the MRP-8/14 for the emergency assessment of chest pain.
J. Thromb. Thrombolysis
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Elevated levels of myeloid-related protein (MRP)-8/14 (S100A8/A9) are associated with first cardiovascular events in healthy individuals and worse prognosis in patients with acute coronary syndrome (ACS). The diagnostic utility of MRP-8/14 in patients presenting to the emergency room with symptoms concerning for ACS is uncertain. MRP-8/14 was measured in serial serum and plasma samples in a single center prospective cohort-study of patients presenting to the emergency room with non-traumatic chest pain concerning for ACS. Final diagnosis was adjudicated by an endpoint committee. Of patients with baseline MRP-8/14 results (n = 411), the median concentration in serum was 1.57 ?g/ml (25th, 75th: 0.87, 2.68) and in plasma was 0.41 ?g/ml (<0.4, 1.15) with only moderate correlation between serum and plasma (? = 0.40). A final diagnosis of MI was made in 106 (26%). Peak serum MRP-8/14 was higher in patients presenting with MI (p < 0.001). However, the overall diagnostic performance of MRP-8/14 was poor: sensitivity 28% (95% CI 20-38), specificity 82% (78-86), positive predictive value 36% (26-47), and negative predictive value 77% (72-81). The area under the ROC curve for diagnosis of MI with MRP-8/14 was 0.55 (95% CI 0.51-0.60) compared with 0.95 for cTnI. The diagnostic performance was not improved in early-presenters, patients with negative initial cTnI, or using later MRP-8/14 samples. Patients presenting with MI had elevated levels of serum MRP-8/14 compared to patients with non-cardiac chest pain. However, overall diagnostic performance of MRP-8/14 was poor and neither plasma nor serum MRP-8/14 offered diagnostic utility comparable to cardiac troponin.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.