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Find video protocols related to scientific articles indexed in Pubmed.
A correlational study of illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure.
J Nurs Res
PUBLISHED: 05-14-2014
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Patients with heart failure experience adverse physical symptoms that affect quality of life. The number of patients with heart failure in Taiwan has been growing in recent years.
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Bone marrow rejuvenation accelerates re-endothelialization and attenuates intimal hyperplasia after vascular injury in aging mice.
Circ. J.
PUBLISHED: 09-13-2013
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Background:?Aging-associated functional impairment of endothelial progenitor cells (EPCs) contributes to delayed re-endothelialization after vascular injury and exaggerated intimal hyperplasia (IH). This study tested if bone marrow (BM) rejuvenation accelerates post-injury re-endothelialization in aging mice. Methods and Results:?Using BM transplantation (BMT(Gfp?Wild)), young(Gfp) to young(Wild) (YTY), old(Gfp) to old(Wild) (OTO), young(Gfp) to old(Wild) (YTO), and old(Gfp) to young(Wild) (OTY) groups were created. After vascular injury, IH was significantly greater in the old group than the young group (P<0.001). BM rejuvenation (YTO) significantly accelerated re-endothelialization and attenuated IH. Compared with the OTO group, the YTY and YTO groups had earlier and greater EPC-derived re-endothelialization (P<0.001). The number of Sca-1(+)KDR(+) EPCs mobilized in the circulation induced by vascular injury was higher in young, YTO, and YTY mice than in old mice (P<0.05). Sca-1(+) BM cells from the young, YTO, and YTY groups had better migration and adhesion capacities than those from the old group (P<0.05). The increase in blood vascular endothelial growth factor (VEGF) levels after vascular injury was higher in young than in old mice. PI3K, Akt, and FAK pathways played a pivotal role in VEGF-associated EPC migration. Specifically, EPCs from young and YTO mice, compared with old mice, demonstrated stronger FAK phosphorylation after VEGF stimulation. Conclusions:?EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.??(Circ J?2013; 77: 3045-3053).
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Differences of left ventricular systolic deformation in hypertensive patients with and without apical hypertrophic cardiomyopathy.
Cardiovasc Ultrasound
PUBLISHED: 08-03-2013
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We tested the hypothesis that the apical myocardial mechanics differ from those of other ventricular segments in hypertensive patients with and without apical hypertrophic cardiomyopathy (ApHCM).
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Plasma P-selectin predicts long-term cardiovascular events in hospitalized patients with suspected coronary artery disease and preserved left ventricular function: a 10-year follow-up study.
Biomed J
PUBLISHED: 06-29-2013
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A variety of biomarkers have been investigated on their values to predict cardiovascular outcomes, such as high-sensitivity C-reactive protein (hs-CRP), fibrinogen, troponin-I (TnI), and soluble P-selectin (sP-sel). By a design of head-to-head comparison, this study sought to figure out the long-term prognostic values of these parameters in patients hospitalized with suspected coronary artery disease.
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Rapid identification of Mycobacterium avium clinical isolates by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
J Microbiol Immunol Infect
PUBLISHED: 02-06-2013
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Rapid and accurate discrimination of Mycobacterium avium from other mycobacteria is essential for appropriate therapeutic management and timely intervention for infection control. However, routine clinical identification methods for M. avium are both time consuming and labor intensive. In the present study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify specific cellular protein pattern for rapid identification of M. avium isolates.
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c-Src-dependent MAPKs/AP-1 activation is involved in TNF-?-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells.
Biochem. Pharmacol.
PUBLISHED: 01-16-2013
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TNF-? plays a critical mediator in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. The implication of TNF-? in inflammatory responses has been shown to be mediated through up-regulation of inflammatory genes, including matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of TNF-?-induced MMP-9 expression are largely unclear in the heart cells. Here, we demonstrated that in rat embryonic-heart derived H9c2 cells, TNF-? could induce MMP-9 mRNA expression associated with an increase in the secretion of MMP-9, determined by real-time PCR, zymography, and promoter activity assays. TNF-?-mediated responses were attenuated by pretreatment with the inhibitor of c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA) and transfection with siRNA of c-Src, EGFR, PDGFR, p110, Akt, or c-Jun. TNF-? stimulated c-Src, PDGFR, and EGFR phosphorylation, which were reduced by PP1. In addition, TNF-?-stimulated Akt phosphorylation was inhibited by PP1, AG1478, AG1296, or LY294002. We further demonstrated that TNF-? markedly stimulated p38 MAPK, p42/p44 MAPK, and JNK1/2 phosphorylation via a c-Src/EGFR, PDGFR/PI3K/Akt pathway. Finally, we showed that, in H9c2 cells, TNF-?-stimulated AP-1 promoter activity, c-Jun mRNA expression, and c-Jun phosphorylation were attenuated by PP1, AG1478, AG1296, LY294002, SB202190, SP600125, or U0126. These results suggested that TNF-?-induced MMP-9 expression is mediated through a c-Src/EGFR, PDGFR/PI3K/Akt/MAPKs/AP-1 cascade in H9c2 cells. Consequently, MMP-9 induction may contribute to cell migration and cardiovascular inflammation.
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ATP stimulates PGE(2)/cyclin D1-dependent VSMCs proliferation via STAT3 activation: role of PKCs-dependent NADPH oxidase/ROS generation.
Biochem. Pharmacol.
PUBLISHED: 01-11-2013
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Vascular smooth muscle cells (VSMCs) that function as synthetic units play important roles in cardiovascular diseases. Extracellular nucleotides, such as ATP, have been shown to act via activation of P2 purinoceptors implicated in various inflammatory diseases, we hypothesized that extracellular nucleotides contribute to vascular diseases via up-regulation of inflammatory proteins, including cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) in VSMCs. However, the mechanisms of ATP-induced cPLA2 and COX-2 expression and PGE2 synthesis remain largely unclear. We showed that pretreatment with the inhibitors of STAT3 (CBE), NADPH oxidase [diphenyleneiodonium chloride (DPI) or apocynin (APO)], ROS [N-acetyl-l-cysteine (NAC)], and PKC (Ro-318220, Gö6983, or Rottlerin) or transfection with siRNAs of STAT3 and p47(phox) markedly inhibited ATP?S-induced cPLA2 and COX-2 mRNA/protein expression and promoter activity and PGE2 secretion. ATP?S further stimulated PKC, p47(phox), and STAT3 translocation. Moreover, ATP?S-induced STAT3 phosphorylation and translocation was inhibited by pretreatment with the inhibitors of PKC, NADPH oxidase, and ROS. ATP?S enhanced NADPH oxidase activity and ROS generation in VSMCs, which were reduced by pretreatment with Ro-318220, Gö6983, or Rottlerin. Finally, we found that ATP?S significantly induced cyclin D1 expression and VSMCs proliferation, which were inhibited by pretreatment with NAC, APO, DPI, Ro-318220, Gö6983, Rottlerin, or CBE or transfection with siRNAs of COX-2 and cyclin D1. We also demonstrated that ATP?S induced cyclin D1 expression via a PGE2-dependent pathway. These results suggested that ATP?S-induced cPLA2/COX-2 expression and PGE2 secretion is mediated through a PKC/NADPH oxidase/ROS/STAT3-dependent pathway in VSMCs.
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VE-Cadherin(low)?-smooth muscle actin+ component of vascular progenitor cells correlates with the coronary artery Gensini score.
Circ. J.
PUBLISHED: 12-02-2011
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Vascular progenitor cells (VPCs) are a heterogeneous population, containing a subpopulation co-expressing both endothelial and smooth muscle phenotypes. This study sought to determine whether the level of this subpopulation correlated with the coronary Gensini score.
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Proteopolymersomes: in vitro production of a membrane protein in polymersome membranes.
Biointerphases
PUBLISHED: 11-25-2011
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Polymersomes are stable self-assembled architectures which mimic cell membranes. For characterization, membrane proteins can be incorporated into such bio-mimetic membranes by reconstitution methods, leading to so-called proteopolymersomes. In this work, we demonstrate the direct incorporation of a membrane protein into polymersome membranes by a cell-free expression system. Firstly, we demonstrate pore formation in the preformed polymersome membrane using ?-hemolysin. Secondly, we use claudin-2, a protein involved in cell-cell interactions, to demonstrate the in vitro expression of a membrane protein into these polymersomes. Surface plasmon resonance (Biacore) binding studies with the claudin-2 proteopolymersomes and claudin-2 specific antibodies are performed to show the presence of the in vitro expressed protein in polymersome membranes.
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Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury--beyond the direct renin inhibition.
Hypertens. Res.
PUBLISHED: 11-17-2011
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Chronic renal ischemia leads to renal fibrosis and atrophy. Activation of the renin-angiotensin-aldosterone system is one of the main mechanisms driving chronic renal ischemic injury. The aim of the present study was to define the effect of aliskiren in chronic ischemia of the kidney. Two-kidney, one-clip mice were used to study chronic renal ischemia. Aliskiren significantly lowered the blood pressure in mice with renal artery constriction (92.1±1.1 vs. 81.0±1.8?mm Hg, P<0.05). Renin expression was significantly increased in ischemic kidneys when treated with aliskiren. In addition, (Pro)renin receptor expression was decreased by aliskiren in ischemic kidneys. Aliskiren treatment significantly increased klotho expression and reduced the expression of fibrogenic cystokines, caspase-3 and Bax in ischemic kidneys. Histological examination revealed that aliskiren significantly reduced the nephrosclerosis score (4.5±1.9 vs. 7.3±0.4, P<0.05). Immunofluorescence staining also showed that aliskiren decreased the deposition of interstitial collagen I in ischemic kidneys. In conclusion, direct renin inhibition significantly reduced renal fibrosis and apoptosis following chronic renal ischemia.
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Aerobic interval training improves oxygen uptake efficiency by enhancing cerebral and muscular hemodynamics in patients with heart failure.
Int. J. Cardiol.
PUBLISHED: 08-16-2011
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Abnormal ventilatory/hemodynamic responses to exercise contribute to functional impairment in patients with heart failure (HF). This study investigates how interval and continuous exercise regimens influence functional capacity by modulating ventilatory efficiency and hemodynamic function in HF patients.
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The diagnostic value of computed tomographic coronary angiography in patients with acute myocardial infarction versus stable angina pectoris: a preliminary report.
Chang Gung Med J
PUBLISHED: 07-08-2011
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Computed tomographic coronary angiography (CTA) is a non-invasive alternative to conventional coronary angiography (CCA) in detecting chronic coronary artery disease (CAD). However, the value of CTA in estimating acute myocardial infarction (AMI) has not been evaluated.
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The small molecule TGF-? signaling inhibitor SM16 synergizes with agonistic OX40 antibody to suppress established mammary tumors and reduce spontaneous metastasis.
Cancer Immunol. Immunother.
PUBLISHED: 06-07-2011
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Effective tumor immunotherapy may require not only activation of anti-tumor effector cells, but also abrogation of tumor-mediated immunosuppression. The cytokine TGF-?, is frequently elevated in the tumor microenvironment and is a potent immunosuppressive agent and promoter of tumor metastasis. OX40 (CD134) is a member of the TNF-? receptor superfamily and ligation by agonistic antibody (anti-OX40) enhances effector function, expansion, and survival of activated T cells. In this study, we examined the therapeutic efficacy and anti-tumor immune response induced by the combination of a small molecule TGF-? signaling inhibitor, SM16, plus anti-OX40 in the poorly immunogenic, highly metastatic, TGF-?-secreting 4T1 mammary tumor model. Our data show that SM16 and anti-OX40 mutually enhanced each other to elicit a potent anti-tumor effect against established primary tumors, with a 79% reduction in tumor size, a 95% reduction in the number of metastatic lung nodules, and a cure rate of 38%. This positive treatment outcome was associated with a 3.2-fold increase of tumor-infiltrating, activated CD8+ T cells, an overall accumulation of CD4+ and CD8+ T cells, and an increased tumor-specific effector T cell response. Complete abrogation of the therapeutic effect in vivo following depletion of CD4+ and CD8+ T cells suggests that the anti-tumor efficacy of SM16+ anti-OX40 therapy is T cell dependent. Mice that were cured of their tumors were able to reject tumor re-challenge and manifested a significant tumor-specific peripheral memory IFN-? response. Taken together, these data suggest that combining a TGF-? signaling inhibitor with anti-OX40 is a viable approach for treating metastatic breast cancer.
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Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I).
Bioorg. Med. Chem. Lett.
PUBLISHED: 04-04-2011
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A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model.
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Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-08-2011
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We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the DFG-out conformation.
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Suppression of cerebral hemodynamics is associated with reduced functional capacity in patients with heart failure.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 01-28-2011
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This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiac-cerebral-muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe (?[THb](FC)) and vastus lateralis muscle (?[THb](VL)). The results demonstrated that the Y-C group had higher levels of cardiac output, ?[THb](FC), and ?[THb](VL) during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater Ve-Vo(2) slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, ?[THb](FC), and ?[THb](VL) during exercise were directly related to the OUES and Vo(2peak) and inversely related to the Ve-Vco(2) slope. Moreover, cardiac output or ?[THb](FC) was an effect modifier, which modulated the correlation status between ?[THb](VL) and Ve-Vco(2) slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with ventilatory abnormality, which reduces functional capacity in patients with HF.
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Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses.
J. Vasc. Surg.
PUBLISHED: 01-26-2011
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Substantial progress has been made in cell therapy strategies and in gene- and cytokine-introduced angiogenesis using a variety of mouse models, such as hind limb ischemia models. Endothelial function is an important target in evaluating the effects and outcomes of these potential therapies. Although animal models have been established for estimating endothelium-dependent function by measuring the blood flow responses in carotid and renal arteries and the abdominal aorta, a model specific for an indicated hind limb by measuring femoral artery blood flow (FABF) has not yet been established.
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Tgf-beta type I receptor (Alk5) kinase inhibitors in oncology.
Curr Pharm Biotechnol
PUBLISHED: 01-24-2011
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The TGF? type I receptor kinase (ALK5) is an attractive target for intervention in TGF? signaling due to its druggability as well as its centrality and specificity in the pathway. A number of potent, selective ALK5 inhibitors have been discovered which interact with the ATP-binding site of ALK5. Crystallographic studies of these molecules bound to ALK5 have provided an understanding of potency and selectivity achieved by these inhibitors. ALK5 kinase inhibitors are potently active in models of cancer due to mechanisms of action similar to those for other TGF? inhibitory agents. Recent insights into the function of TGF? in human tumors as well as in preclinical models of cancer are helping to identify potential target patient populations and drug combinations for the development of ALK5 kinase inhibitors and other TGF?- targeted therapeutics. Differences in the toxicological effects, pharmacokinetics and clinical side effects of ALK5 kinase inhibitors and other TGF?-targeted agents provide a useful and differentiated set of TGF? signaling inhibitory agents to investigate in clinical studies.
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Differentiation profile of peripheral blood-derived vascular progenitor cell predicts intimal hyperplasia after coronary stenting.
Heart Vessels
PUBLISHED: 01-14-2011
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In-stent restenosis is largely due to intimal hyperplasia (IH). The number of vascular progenitor cells (VPCs) mobilized at the acute phase after stenting is associated with IH. This study sought to determine whether the differentiation profile of VPC predicts the development of IH. Peripheral blood was collected in 58 patients after bare-metal stenting to culture VPCs. Intravascular ultrasound was performed to estimate the area of IH 6 months after stenting. VPC differentiation was determined using flow cytometry. VE-cadherin (VE-Cad) and ?-smooth muscle actin (?-SMA) were used to identify endothelial and smooth muscle cell lineages, respectively. After culturing, VPCs differentiated into four different phenotypes (?-SMA(-)VE-Cad(+), ?-SMA(+)VE-cad(high), ?-SMA(+)VE-cad(low), and ?-SMA(+)VE-Cad(-)). IH was correlated with gender (P = 0.04), smoking status (P = 0.04), reference diameter (P = 0.03), minimal lumen diameter (P = 0.03), stent area (P < 0.0001), and parameters in the VPC differentiation profile (P < 0.05). Multivariate analysis controlling for stent area, smoking status, and gender revealed that IH was positively and independently associated with the number of differentiated ?-SMA(+)VE-Cad (low/-) VPCs (P < 0.0001), and the ratio of ?-SMA(+)VE-Cad (low/-) VPCs to ?-SMA(-)VE-Cad(+) VPCs (P = 0.001). These parameters in the VPC differentiation profile independently predicted the IH and provided additive information to traditional risk factors. In conclusion, the profile of VPC differentiation predicts the severity of post-stent IH and may be a potential tool in the future for clinicians to identify patients at risk of post-stent restenosis.
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Factors associated with purity, biological function, and activation potential of endothelial colony-forming cells.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 12-15-2010
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Endothelial colony-forming cells (ECFCs) are undergoing extensive investigations to tackle certain deliberating cardiovascular diseases. However, the success of this approach depends on a thorough understanding of ECFC biology. This study sought to determine the factors associated with the purity, biological function, and activation potential of ex vivo expanded ECFCs. Seventy-three patients with newly diagnosed coronary artery disease (CAD) and 24 controls were studied. ECFCs were cultured for up to 10 passages to investigate changes in and the impact of coronary risk factors on ECFC biological functions and the atherogenic potential. Passages 3-5 of ECFCs exhibited higher endothelial phenotype expression and better biological functions, in terms of nitric oxide secretion and tubular formation, but lower activation potentials compared with later passages (P <0.05). Studies on passage 3 showed that endothelial phenotype expression and biological functions were impaired, and the activation potentials of the ECFCs were significantly upregulated in subjects with coronary risk factors and especially those with CAD (P < 0.05). Furthermore, ECFCs were already activated before inflammatory stimulation in subjects with diabetes mellitus, hypertension, and CAD. Atorvastatin upregulated the endothelial nitric oxide synthase expression of ECFCs in CAD patients (P < 0.01), although not up to the baseline level of controls. In conclusion, the passage number and a variety of coronary risk factors were associated with the purity, biological function, and activation potential of ex vivo-expanded ECFCs. Functional assessments and manipulations of ECFCs have to be pursued in patients with extensive risk factors.
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Interactions among gender, age, hypertension and C-reactive protein in coronary vasospasm.
Eur. J. Clin. Invest.
PUBLISHED: 08-16-2010
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Coronary vasospasm (CVsp) has been reported to be an inflammatory disease, reflected by elevated high-sensitivity C-reactive protein (hs-CRP). We investigated the interactions among gender, age, hypertension and hs-CRP in patients with CVsp.
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Echocardiographic assessment of structural and functional cardiac remodeling in patients with predialysis chronic kidney disease.
Echocardiography
PUBLISHED: 04-16-2010
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Cardiac remodeling has been demonstrated in patients on hemodialysis and in predialysis patients with chronic kidney disease (CKD). Using functional echocardiographic parameters to study the association of hemodynamic status and predialysis CKD has not yet been established.
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Interleukin-6 inhibits endothelial nitric oxide synthase activation and increases endothelial nitric oxide synthase binding to stabilized caveolin-1 in human vascular endothelial cells.
J. Hypertens.
PUBLISHED: 04-09-2010
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We hypothesized a possible mechanism for atherosclerosis in which interleukin-6 (IL-6) might affect the endothelial nitric oxide synthase (eNOS)-caveolin-1 interaction and result in decreased nitric oxide bioavailability in the setting of low-grade inflammation.
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Controlled microscale diffusion gradients in quiescent extracellular fluid.
Biomed Microdevices
PUBLISHED: 03-23-2010
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Microchannels offer a means of establishing concentration gradients of soluble factors over micron length scales representative of those in tissues. Here, we report the development of a microfluidic channel system wherein a hydrogel has been patterned to generate temporally and spatially stable concentration gradients of multiple solutes in quiescent extracellular fluid. The fluorophore Alexa Fluor 488 and a fluorescent glucose analog are used as probes to illustrate the generation of stable, reproducible, and linear probe concentration gradients. A method is described for estimating the diffusivity and hydrogel permeability of a solute from in situ imaging data. Concentration gradients are also generated in the presence of a mouse insulinoma cell line to demonstrate the compatibility of the system with living cells. The net transport and metabolism rate of the glucose analog is found to be heterogeneous and independent of the applied extracellular gradient. This system may be suitable for the study of cell response to various extracellular gradients of soluble factors.
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Ventricular function and all-cause mortality in chronic kidney disease patients with angiographic coronary artery disease.
J. Nephrol.
PUBLISHED: 02-02-2010
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Coronary artery disease (CAD) and chronic kidney disease (CKD) lead to high morbidity and mortality rates. Traditional and nontraditional risk factors, hypertension, fluid overloading and anemia can lead to myocardial ischemia, chamber hypertrophy and dilatation, and low left ventricular ejection fraction (LVEF) in CKD patients. The angiographic feature, ventriculographic LVEF and its relationship to all-cause mortality are unclear in patients with different stages of CKD who are not yet on dialysis.
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Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-31-2010
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Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (-)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability.
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Interaction between cigarette smoking and high-sensitivity C-reactive protein in the development of coronary vasospasm in patients without hemodynamically significant coronary artery disease.
Am. J. Med. Sci.
PUBLISHED: 12-17-2009
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Interaction between 2 major risk factors, cigarette smoking and high-sensitivity C-reactive protein (hs-CRP), has not been evaluated in patients with coronary vasospasm (CV) without hemodynamically significant coronary artery disease.
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Strategies for TGF-beta modulation: a review of recent patents.
Expert Opin Ther Pat
PUBLISHED: 11-27-2009
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TGF-beta has been identified as a key factor in the progression of various diseases, in particular cancer and fibrosis. The signaling of TGF-beta can be modulated through three distinct strategies: using antisense nucleotides that block TGF-beta mRNA (trabedersen (AP 12009)), using monoclonal antibodies to block TGF-beta isoforms (lerdelimumab, metelimumab) or using small molecule inhibitors of the TGF-beta receptor 1 (TGF-betaR1 or ALK-5).
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Pyrazolone based TGFbetaR1 kinase inhibitors.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-26-2009
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Interruption of TGFbeta signaling through inhibition of the TGFbetaR1 kinase domain may prove to have beneficial effect in both fibrotic and oncological diseases. Herein we describe the SAR of a novel series of TGFbetaR1 kinase inhibitors containing a pyrazolone core. Most TGFbetaR1 kinase inhibitors described to date contain a core five-membered ring bearing N as H-bond acceptor. Described herein is a novel strategy to replace the core structure with pyrazolone ring, in which the carbonyl group is designed as an H-bond acceptor to interact with catalytic Lys 232.
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Real-time three-dimensional echocardiography provides advanced haemodynamic information associated with intra-dialytic hypotension in patients with autonomic dysfunction.
Nephrol. Dial. Transplant.
PUBLISHED: 08-08-2009
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Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate and effective tool for assessing left ventricular (LV) function, compared to traditional two-dimensional (2D) methods. In this study, we used this new tool to revise the controversial relationship between LV function and intra-dialytic hypotension.
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Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction.
Int Heart J
PUBLISHED: 07-18-2009
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After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.
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An orally active small molecule TGF-beta receptor I antagonist inhibits the growth of metastatic murine breast cancer.
Anticancer Res.
PUBLISHED: 06-17-2009
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Transforming growth factor beta (TGF-beta) plays a complex role in breast carcinogenesis. Initially functioning as a tumor suppressor, this cytokine later contributes to the progression of malignant cells by enhancing their invasive and metastatic potential as well as suppressing antitumor immunity. The purpose of this study was to investigate the efficacy of SM16, a novel small molecule ALK5 kinase inhibitor, to treat a highly metastatic, TGF-beta-producing murine mammary carcinoma (4T1).
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Identification of legionella species by use of an oligonucleotide array.
J. Clin. Microbiol.
PUBLISHED: 03-04-2009
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The genus Legionella contains a diverse group of motile, asaccharolytic, nutritionally fastidious gram-negative rods. Legionella pneumophila is the most important human pathogen, followed by L. micdadei, L. longbeachae, L. dumoffii, and other rare species. Accurate identification of Legionella spp. other than L. pneumophila is difficult because of biochemical inertness and phenotypic identity of different species. The feasibility of using an oligonucleotide array for identification of 18 species of Legionella was evaluated in this study. The method consisted of PCR amplification of the macrophage infectivity potentiator mip gene, followed by hybridization of the digoxigenin-labeled PCR products to a panel of 30 oligonucleotide probes (16- to 24-mers) immobilized on a nylon membrane. A collection of 144 target strains (strains we aimed to identify) and 50 nontarget strains (44 species) were analyzed by the array. Both test sensitivity (144/144 strains) and specificity (50/50 strains) of the array were 100%. The whole procedure for identification of Legionella species by the array can be finished within a working day, starting from isolated colonies. It was concluded that species identification of clinically relevant Legionella spp. by the array method is very reliable and can be used as an accurate alternative to conventional or other molecular methods for identification of Legionella spp.
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In-situ measurement of cellular microenvironments in a microfluidic device.
Lab Chip
PUBLISHED: 01-21-2009
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We report on the integration of optical microsensors into a cell culture microchannel device. We demonstrate the possibility of measuring the glucose and oxygen concentrations in the microenvironment of the mammalian cells cultured in a microchannel device. Furthermore, cell proliferation and morphology could be monitored microscopically while these measurements were being made. Through the use of multiple sensors along the length of the microchannel, concentration gradients of various metabolites, such as oxygen, as well as the effects of cell uptake and perfusion rate of growth medium on these gradients could be studied. As such, the system allowed real-time observations of the cells response to their chemical microenvironment. Our approach allows cell culture and cell assays to be performed simultaneously in an integrated microchannel system with potential applications as a research tool or drug screening method.
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2-Aminoimidazoles inhibitors of TGF-beta receptor 1.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-13-2009
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The 4-(5-fluoro-6-methyl-pyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-ylamine 3 is a potent and selective inhibitor of TGF-betaR1. Substitution of the amino group of 3 typically led to a slight decrease in the affinity for the receptor and in TGF-beta-inducted PAI-luciferase reporter activity. However, 2-acetamidoimidazoles were identified as attractive candidates for further optimization as a result of their significant activity combined to their superior pharmacokinetic profile.
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Non-invasive cardiac index monitoring during cardiopulmonary functional testing provides additional prognostic value in patients after acute heart failure.
Int Heart J
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The prognostic value of parameters derived from a cardiopulmonary exercise test (CPET) is well established in patients stabilized after acute heart failure (HF). Under multidisciplinary disease management, this study sought to test whether noninvasive cardiac output (CO) monitoring (NICOM) during the CPET provides additional prognostic value. In total, 131 patients stabilized after acute HF agreed to undergo the CPET with NICOM. Outcome follow-up focused on composite events of death and HF-related rehospitalization. Patients with a peak cardiac index (CI) of ? 4.5 L/minute/ m(2) (n = 32), compared to those with a peak CI of > 4.5 L/minute/m(2) (n = 99), had higher incidences of diabetes mellitus (DM) and hypertension, but had lower hemoglobin levels, estimated glomerular filtration rates (eGFR), oxygen uptake efficiency slope (OUES), and peak oxygen uptake (VO(2)). During the 1.2 ± 0.7 years of follow-up, there were 8 (6.1%) deaths, and 16 (12.2%) HF-related rehospitalizations. In a Cox univariable analysis, a lower event-free survival was associated with a history of DM, a higher Ve/VCO(2) slope, lower peak VCO(2) and eGFR, and a peak CI of ? 4.5 L/minute/ m(2) (P < 0.05). The Cox multivariable analysis showed that the Ve/VCO(2) slope (hazard ratio (HR) = 1.08, 95% confidence interval (CI): 1.01~1.16, P = 0.02) and peak CI of ? 4.5 L/minute/m(2 )(HR = 3.26, 95% CI: 1.18~9.01, P = 0.02) were significant independent predictors. In conclusion, NICOM during the CPET was demonstrated to provide prognostic information in addition to traditional risk factors, biomarkers, and other well-established CPET parameters.
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Effect of aerobic interval training on erythrocyte rheological and hemodynamic functions in heart failure patients with anemia.
Int. J. Cardiol.
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Anemia disturbs hemorheological/hemodynamic properties, whereas aerobic interval training (AIT) achieves a superior aerobic fitness in patients with heart failure (HF). This study investigated whether AIT influences functional capacity by modulating hemorheological/hemodynamic functions in HF patients with/without anemia.
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Surface markers of heterogeneous peripheral blood-derived smooth muscle progenitor cells.
Arterioscler. Thromb. Vasc. Biol.
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Smooth muscle progenitor cells (SMPCs) were intriguingly shown to act as a double-edged sword in the pathogenesis of atherosclerosis. To fully clarify the roles of SMPCs in atherosclerosis, a distinct panel of SMPC surface markers is mandatory to be developed.
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A novel microfluidics-based method for probing weak protein-protein interactions.
Lab Chip
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We report the use of a novel microfluidics-based method to detect weak protein-protein interactions between membrane proteins. The tight junction protein, claudin-2, synthesised in vitro using a cell-free expression system in the presence of polymer vesicles as membrane scaffolds, was used as a model membrane protein. Individual claudin-2 molecules interact weakly, although the cumulative effect of these interactions is significant. This effect results in a transient decrease of average vesicle dispersivity and reduction in transport speed of claudin-2-functionalised vesicles. Polymer vesicles functionalised with claudin-2 were perfused through a microfluidic channel and the time taken to traverse a defined distance within the channel was measured. Functionalised vesicles took 1.19 to 1.69 times longer to traverse this distance than unfunctionalised ones. Coating the channel walls with protein A and incubating the vesicles with anti-claudin-2 antibodies prior to perfusion resulted in the functionalised vesicles taking 1.75 to 2.5 times longer to traverse this distance compared to the controls. The data show that our system is able to detect weak as well as strong protein-protein interactions. This system offers researchers a portable, easily operated and customizable platform for the study of weak protein-protein interactions, particularly between membrane proteins.
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Exertional periodic breathing potentiates erythrocyte rheological dysfunction by elevating pro-inflammatory status in patients with anemic heart failure.
Int. J. Cardiol.
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Exertional periodic breathing (EPB) or anemia is associated with an adverse prognosis in advanced heart failure (HF). The disturbed rheological properties of erythrocytes may contribute to circulatory disorders. This study investigated whether EPB with/without anemia influences rheological/hemodynamic functions in patients with HF.
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Edema index-guided disease management improves 6-month outcomes of patients with acute heart failure.
Int Heart J
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The efficacy of heart failure (HF) management programs is compromised by the challenge of early identification of patients at imminent risk. Segmental multifrequency bioelectrical impedance analysis can generate an "edema index" (EI) as a surrogate for the body fluid status. In this study, we tested whether integration of EI-guided management improved the 6-month outcomes of HF patients under multidisciplinary care. In total, 159 patients with acute HF were randomized into control, case management (CM), and EI-guided CM (EI) groups (n = 53 in each group). In the EI group, a management algorithm was designed based on the measured EI. The analyzed endpoints included HF-related and all cause-related events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%) deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause-related rehospitalizations. Compared to the control (26.4%) and CM groups (15.1%), the EI group had a lower rate of HF-related death and rehospitalization (3.8%, P = 0.004). Multivariate analysis revealed that EI-guided management was an independent predictor of a lower HF-related event rate (hazard ratio = 0.15, 95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were older, had lower blood albumin and hemoglobin levels, and had a higher functional class and incidences of diabetes mellitus and chronic kidney disease. An increase in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P = 0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion, an EI-based HF management program demonstrated an event-lowering effect superior to traditional nurse-led multidisciplinary care in 6 months after an acute HF episode.
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Edema index established by a segmental multifrequency bioelectrical impedance analysis provides prognostic value in acute heart failure.
J Cardiovasc Med (Hagerstown)
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A segmental multifrequency bioelectrical impedance analysis (SMBIA) is a noninvasive and reproducible modality for estimating the fluid state. The aim of this study was to test whether the SMBIA-derived edema index provides prognostic value in patients hospitalized due to acute heart failure (AHF).
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Increased leukocyte Rho-associated coiled-coil containing protein kinase activity predicts the presence and severity of coronary vasospastic angina.
Atherosclerosis
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Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications.
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Levels of blood periostin decrease after acute myocardial infarction and are negatively associated with ventricular function after 3 months.
J. Investig. Med.
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A recent study showed that periostin (PN) induced reentry of differentiated cardiomyocytes into the cell cycle and improved heart function after acute myocardial infarction (AMI). This study sought to investigate whether PN levels increase after AMI and whether they provide prognostic value.
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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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.