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Find video protocols related to scientific articles indexed in Pubmed.
High red blood cell distribution width is closely associated with nonalcoholic fatty liver disease.
Eur J Gastroenterol Hepatol
PUBLISHED: 08-29-2014
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The red blood cell distribution width (RDW) has been reported to be a risk marker of morbidity and mortality for cardiovascular diseases in various study populations. Nonalcoholic fatty liver disease (NAFLD) is also a risk factor for cardiovascular diseases. However, the relationship between RDW and NAFLD is less certain.
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Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing.
Biol. Chem.
PUBLISHED: 07-03-2014
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Abstract Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a 4-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.
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p27 kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation.
Sci Rep
PUBLISHED: 06-10-2014
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p27(kip1) (p27) is widely known as a potent cell cycle inhibitor in several organs, especially in the heart. However, its role has not been fully defined during the early phase of myocardial infarction (MI). In this study, we investigated the relationships between p27, vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) and NF-?B in post-MI cardiac function repair both in vivo and in the hypoxia/ischemia-induced rat myocardiocyte model. In vivo, haplo-insufficiency of p27 improved cardiac function, diminished the infarct zone, protected myocardiocytes and increased angiogenesis by enhancing the production of VEGF/HGF. In vitro, the presence of conditioned medium from hypoxia/ischemia-induced p27 knockdown myocardiocytes reduced the injury caused by hypoxia/ischemia in myocardiocytes, and this effect was reversed by VEGF/HGF neutralizing antibodies, consistent with the cardioprotection being due to VEGF/HGF secretion. We also observed that p27 bound to IKK and that p27 haplo-insufficiency promoted IKK/p65 activation both in vivo and in vitro, thereby inducing the NF-?B downstream regulator, VEGF/HGF. Furthermore, IKKi and IKK inhibitor negated the effect of VEGF/HGF. Therefore, we conclude that p27 haplo-insufficiency protects against heart injury by VEGF/HGF mediated cardioprotection and increased angiogenesis through promoting IKK activation.
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Nine-month angiographic and two-year clinical follow-up of polymer-free sirolimus-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease: the Nano randomized trial.
Chin. Med. J.
PUBLISHED: 06-04-2014
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First generation drug-eluting stents (DES) were associated with a high incidence of late stent thrombosis (ST), mainly due to delayed healing and re-endothelization by the durable polymer coating. This study sought to assess the safety and efficacy of the Nano polymer-free sirolimus-eluting stent (SES) in the treatment of patients with de novo coronary artery lesions.
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Efficacy and safety of cilostazol based triple antiplatelet treatment versus dual antiplatelet treatment in patients undergoing coronary stent implantation: an updated meta-analysis of the randomized controlled trials.
J. Thromb. Thrombolysis
PUBLISHED: 05-30-2014
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The aim of this study was to obtain best estimates of the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAPT: aspirin, clopidogrel and cilostazol) compared with dual antiplatelet therapy (DAPT: aspirin and clopidogrel) in patients undergoing coronary stent implantation. We searched the literature to identify all randomized clinical trials examining efficacy and safety of TAPT versus DAPT in patients undergoing coronary stent implantation. Major efficacy outcomes were death, non-fatal myocardial infarction (MI), ischemic stroke and stent thrombosis (ST) and the safety outcome was bleeding. Data were analyzed using the Review Manager 5.0.0 software. A total of 19 trials involving 7,464 patients were included. TAPT and DAPT were associated with similar rates of death, non-fatal MI, ischemic stroke and ST, but compared with DAPT, TAPT had lower rates of target lesion revascularization (TLR) (RR 0.67, 95 % CI 0.56-0.82, P < 0.0001) and target vessel revascularization (TVR) (RR 0.65, 95 % CI 0.55-0.77, P < 0.00001), as well as less late loss of minimal lumen diameter (mean difference -0.14, 95 % CI -0.17--0.11, P < 0.00001), and less binary angiographic restenosis (RR 0.54, 95 % CI 0.45-0.65, P < 0.00001). TAPT and DAPT had similar rates of bleeding, but TAPT had significantly higher rates of headache, palpitation, rash and gastrointestinal side-effects. Cilostazol-based TAPT compared with DAPT is associated with improved angiographic outcomes and decreased risk of TLR and TVR but does not reduce major cardiovascular events and is associated with an increase in minor adverse events.
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Genetic analysis of SNCA coding mutation in Chinese Han patients with Parkinson disease.
Acta Neurol Belg
PUBLISHED: 05-18-2014
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Parkinson disease (PD) is the second most common progressive neurodegenerative disorder. It is characterized by selective loss of dopamine-producing neurons and aggregation of alpha-synuclein (SNCA) in neurons of particular brain regions. At least 20 loci and 15 disease-causing genes have been identified. Rare missense or multiplication mutations in the SNCA gene have been reported to be involved in some familial and sporadic cases of PD. More recently, two novel pathogenic missense mutations (p.H50Q and p.G51D) were identified in the SNCA gene. To evaluate whether mutation(s) in the coding region of SNCA gene is related to PD in Chinese population, we investigated the SNCA gene in 502 PD patients of Chinese Han ethnicity from Mainland China. No pathogenic mutation was identified in the coding region of the gene. A known G to A transition (c.306 + 66G>A, rs10005233) in the intron 4, which does not potentially change splicing, was identified. Our data indicate that mutations in the coding region of the SNCA gene are not likely to be a common cause of PD in Chinese population.
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Evidence of type-II band alignment in III-nitride semiconductors: experimental and theoretical investigation for In 0.17 Al 0.83 N/GaN heterostructures.
Sci Rep
PUBLISHED: 05-13-2014
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Type-II band alignment structure is coveted in the design of photovoltaic devices and detectors, since it is beneficial for the transport of photogenerated carriers. Regrettably, for group-III-nitride wide bandgap semiconductors, all existing devices are limited to type-I heterostructures, owing to the unavailable of type-II ones. This seriously restricts the designing flexibility for optoelectronic devices and consequently the relevant performance of this material system. Here we show a brandnew type-II band alignment of the lattice-matched In 0.17 Al 0.83 N/GaN heterostructure from the perspective of both experimental observations and first-principle theoretical calculations. The band discontinuity is dominated by the conduction band offset ?EC, with a small contribution from the valence band offset ?EV which equals 0.1 eV (with E(AlInN(VBM) being above E(GaN)(VBM)). Our work may open up new prospects to realize high-performance III-Nitrides optoelectronic devices based on type-II energy band engineering.
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Clopidogrel improves aspirin response after off-pump coronary artery bypass surgery.
J Biomed Res
PUBLISHED: 04-01-2014
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We sought to assess the incidence of aspirin resistance after off-pump coronary artery bypass (OPCAB) surgery, and investigate whether clopidogrel can improve aspirin response and be safely applied early after OPCAB surgery. Sixty patients who underwent standard OPCAB surgery were randomized into two groups. One group (30 patients) received mono-antiplatelet treatment (MAPT) with aspirin 100?mg daily and the other group received dual antiplatelet treatment (DAPT) with aspirin 100?mg daily plus clopidogrel 75?mg daily. Platelet aggregations in response to arachidonic acid (PLAA) and adenosine diphosphate (ADP) (PLADP) were measured preoperatively and on days 1 to 6, 8 and 10 after the antiplatelet agents were administered. A PLAA level above 20% was defined as aspirin resistance. Postoperative bleeding and other perioperative variables were also recorded. There were no significant differences between the two groups in baseline characteristics, average number of distal anastomosis, operation time, postoperative bleeding, ventilation time and postoperative hospital stay. However, the incidence of aspirin resistance was significantly lower in the DAPT group than that in the MAPT group on the first and second day after antiplatelet agents were given (62.1% vs. 32.1%, 34.5% vs. 10.7%, respectively, both P < 0.05). There was no significant difference in postoperative complication between the two groups. DAPT with aspirin and clopidogrel can be safely applied to OPCAB patients early after the procedure. Moreover, clopidogrel reduces the incidence of OPCAB-related aspirin resistance.
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Stimulated emission in GaN-based laser diodes far below the threshold region.
Opt Express
PUBLISHED: 03-26-2014
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We identify that the stimulated emission of GaN laser diodes (LDs) emerges far below the traditionally recognized threshold from both optical and electrical experiments. Below the threshold, the linear-polarized stimulated emission has been the dominating part of overall emission and closely related to resonant cavity. Its intensity increases super linearly with current while that of spontaneous emission increases almost linearly. Moreover, the separation of quasi-Fermi levels of electrons and holes across the active region has already exceeded the photon emission energy, namely, realized the population-inversion.
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Relationship between brachial-ankle pulse wave velocity and metabolic syndrome components in a Chinese population.
J Biomed Res
PUBLISHED: 03-16-2014
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The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), and the presence of the metabolic syndrome (MS) in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in our study population was 21.7%, 17.2% and 25.6% for the general population, males and females, respectively. With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein (LDL) cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), glucose (P < 0.001), high-density lipoprotein (HDL) cholesterol (P ?=? 0.04), and triglycerides (P < 0.001), but no relationship with waist circumference (P ?=? 0.25). With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.
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Targeted contrast-enhanced ultrasound imaging of angiogenesis in an orthotopic mouse tumor model of renal carcinoma.
Ultrasound Med Biol
PUBLISHED: 03-07-2014
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Previous studies have reported that microbubbles bearing targeting ligands to molecular markers of angiogenesis can be successfully detected by ultrasound imaging in various animal models of solid cancer. In the present study, we sought to investigate the activity of microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in an orthotopic model of renal cell carcinoma (RCC). Microbubbles conjugated to an anti-VEGFR2 antibody (MBV) were compared with microbubbles conjugated to an isotype control antibody (MBC) or naked microbubbles (MBN). An orthotopic mouse model of human RCC was established by surgically implanting an established tumor within the renal capsule in mice. Tumor growth and blood flow were verified by B-mode and color Doppler ultrasound imaging. VEGFR2 expression within the tumor and renal parenchyma was detected by immunohistochemistry. The duration of contrast enhancement of MBV was much longer than those of MBN and MBC when assessed over 10 min. The baseline-subtracted contrast intensity within the tumor was higher for MBV than for MBC and MBN (p < 0.01). Additionally, the contrast intensity for MBV was significantly higher in the tumor region than in normal parenchyma (p < 0.01). Microbubbles targeting VEGFR2 exhibit suitable properties for imaging angiogenesis in orthotopic models of renal cell carcinoma, with potential applications in life science research and clinical medicine.
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Diagnostic and prognostic value of minor elevated cardiac troponin levels for percutaneous coronary intervention-related myocardial injury: a prospective, single-center and double-blind study.
J Biomed Res
PUBLISHED: 02-10-2014
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Cardiac troponin-I (cTnI) and -T (cTnT) are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention (PCI)-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT (cTns) in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26±9 months to observe the incidence of major adverse cardiac events (MACEs). Our results showed that post-PCI cTnI and/or cTnT levels were increased to more than the 99(th) percentile upper reference limit (URL) in 133 (13.2%) patients, among which 22 (2.2%) were more than 5 × 99(th) percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 (P ?=? 0.33, 95%CI: 0.74-2.46). In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.
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Cardiac-specific expression of the hepatocyte growth factor (HGF) under the control of a TnIc promoter confers a heart protective effect after myocardial infarction (MI).
Curr Gene Ther
PUBLISHED: 02-04-2014
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Uncontrolled therapeutic gene expression and neovascularization in non-specific tissues has lowered the safety of gene therapy. The aim of the study was to identify a cardiac-specific promoter to control target gene expression in heart tissue in vitro and in vivo.
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Genome-wide analysis of radiation-induced mutations in rice (Oryza sativa L. ssp. indica).
Mol Biosyst
PUBLISHED: 01-24-2014
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Radiation has been efficiently used for rice germplasm innovation. However, the molecular mechanisms by which radiation induces mutations are still unclear. In this study, we performed whole genome sequencing to reveal the comprehensive mutations in rice treated with radiation. Red-1 (a rice rich in beneficial ingredients for human health) was derived from rice 9311 after ?-radiation. Solexa sequencing technology was applied to uncover the mutations. Compared with the 9311 genome, 9.19% of genome sequences were altered in the Red-1 genome. Among these alterations, there were 381,403 SNPs, 50,116 1-5 bp Indels, 1279 copy number variations, and 10,026 presence/absence variations. These alterations were located in 14,493 genes, the majority of which contained a kinase domain, leucine rich repeats, or Cyt_P450. Point mutations were the main type of variation in the Red-1 genome. Gene ontology clustering revealed that genes that are associated with cell components, binding function, catalytic activity and metabolic processes were susceptible to ?-radiation. It was also predicted that 8 mutated genes were involved in the biosynthetic pathways of beneficial products or pigment accumulation. We conclude that genome-wide analysis of mutations provides novel insights into the mechanisms by which radiation improves the beneficial ingredients in rice Red-1.
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Ultrasonic approach to the synthesis of HMX@TATB core-shell microparticles with improved mechanical sensitivity.
Ultrason Sonochem
PUBLISHED: 01-18-2014
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To improve the safety of sensitive explosive HMX while maintaining explosion performance, a moderately powerful but insensitive explosive TATB was used to coat HMX microparticles via a facile ultrasonic method. By using Estane as surface modifier and nano-sized TATB as the shell layer, the HMX@TATB core-shell microparticles with a monodisperse size and compact shell structure were successfully constructed. Both scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) results confirmed the formation of perfect core-shell structured composites. Based on a systematic and comparative study of the effect of experimental conditions, a possible formation mechanism of core-shell structure was proposed in detail. Moreover, the perfect core-shell HMX@TATB microparticles exhibited a unique thermal behavior and significantly improved mechanical sensitivity compared with that of the physical mixture.
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Anti-tumor efficacy of ultrasonic cavitation is potentiated by concurrent delivery of anti-angiogenic drug in colon cancer.
Cancer Lett.
PUBLISHED: 01-09-2014
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This study investigated the efficacy of concurrent delivery of an anti-angiogenic drug and ultrasonic cavitation therapy in a mouse model of human colon cancer. A biotinylated form of the anti-angiogenic drug Endostar was conjugated to a streptavidin-coated microbubble (MB). Mice bearing subcutaneous tumors (HT29) were divided into 4 groups. Group 1 served as an untreated control. Group 2 served as a cavitation control and received naked microbubbles and sham ultrasonic cavitation (MB+sham cavitation). Group 3 received naked microbubbles and ultrasonic cavitation (MB+cavitation). Group 4 received Endostar loaded microbubbles and ultrasonic cavitation (Endostar-MB+cavitation). Ultrasonic cavitation was performed using a high-power custom built sonicator. Contrast-enhanced ultrasound imaging (CEUS) was used to measure tumor blood flow before and after ultrasonic cavitation. In vivo fluorescence imaging was performed to monitor changes in tumor volume. Immunohistochemistry was performed to assess CD31, VEGFR-2 and alpha-v beta-3 integrin expression within the tumor. Apoptosis of the tumor cells was determined by TUNEL assay, and ultrastructural changes within the tumor were examined by electron microcopy. Ultrasonic cavitation with Endostar-MB demonstrated a significantly greater inhibition of tumor blood flow on day 7 and tumor growth on day 16 compared with naked MB and control groups. The Endostar-MB treated mice showed significantly decreased expression VEGFR-2 and alpha-v beta-3 integrin, and increased apoptosis of tumor cells and degradation of the tumor ultrastructure. Our findings indicated that the anti-vascular and anti-tumor effects of ultrasonic cavitation could be potentiated by simultaneously delivering an anti-angiogenic drug in colon cancer.
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Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction.
Int. J. Mol. Med.
PUBLISHED: 01-02-2014
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Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)??1, tumor necrosis factor (TNF)-?, interleukin (IL)-1? and nuclear factor (NF)-?B. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.
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Association of admission serum calcium levels and in-hospital mortality in patients with acute ST-elevated myocardial infarction: an eight-year, single-center study in China.
PLoS ONE
PUBLISHED: 01-01-2014
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The relationship between admission serum calcium levels and in-hospital mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) has not been well definitively explored. The objective was to assess the predictive value of serum calcium levels on in-hospital mortality in STEMI patients.
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Genetic analysis of the S100B gene in Chinese patients with Parkinson disease.
Neurosci. Lett.
PUBLISHED: 07-22-2013
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There is growing evidence that genetic abnormalities play an important role in the pathogenesis of Parkinson disease (PD). At least 18 genetic loci and 13 disease-related genes for parkinsonism have been identified. The S100 calcium-binding beta (S100B), which is expressed and secreted by astrocytes, has been found to be associated with PD. To evaluate whether the S100B variants are related to PD in Chinese Han population, we conducted genetic examination of the S100B gene in 502 PD patients from Mainland China. We did identify two known variants c.279+4T>C (rs187503470) and c.99C>G (p.Leu33Leu, rs1051169) in our patients. Neither of these two variants is predicted to change amino acid or splice site, indicating that they are not pathogenic mutations. Our results suggest that mutations in the coding region or intron/exon boundaries of the S100B gene play little or no role in the development of PD in Chinese population.
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Anxiety and adverse coronary artery disease outcomes in Chinese patients.
Psychosom Med
PUBLISHED: 06-20-2013
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To investigate the impact of anxiety on the prognosis of coronary artery disease (CAD) in patients of Chinese Han ethnicity and to explore the correlation between anxiety and the severity of coronary atherosclerosis.
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Paclitaxel nanosuspensions for targeted chemotherapy - nanosuspension preparation, characterization, and use.
Pharm Dev Technol
PUBLISHED: 04-25-2013
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Abstract Objective: The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models. Materials and method: Paclitaxel nanosuspensions were prepared using a homogenization process and coated with excipients. Surface charge was measured by zeta potential, potency by high-performance liquid chromatography, and solubility using an in-line UV probe. Cellular uptake studies were performed via flow cytometry. In vivo experiments were performed to determine residence time, maximum tolerated dose, and the efficacy of paclitaxel nanosuspensions (Paclitaxel-NS). Results: A stable paclitaxel nanosuspension was prepared and coated with various excipients. Studies in mice showed that the nanosuspension was well-tolerated and at least as effective as the IV Taxol control in prolonging mouse survival in a head and neck cancer model as well as an ovarian cancer model with a lower overall drug dose than the traditional IV administration route. Conclusions: The paclitaxel nanosuspension is suitable for cellular uptake. The nanosuspension was effective in prolonging life in two separate xenograft orthotopic murine cancer models through two separate routes of administration.
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Magnetic navigation system and CT roadmap-assisted percutaneous coronary intervention: a comparison to the conventional approach.
J Invasive Cardiol
PUBLISHED: 04-04-2013
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Computed tomography coronary angiography (CTCA) has been successfully integrated with the magnetic navigation system (MNS) to facilitate a roadmap-assisted percutaneous coronary intervention (PCI). The aim of this study was to compare this new approach of PCI versus conventional PCI regarding the difference of contrast usage, x-ray exposure, procedure success, and in-hospital expenses.
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Intraoperative imaging of metastatic lymph nodes using a fluorophore-conjugated antibody in a HER2/neu-expressing orthotopic breast cancer mouse model.
Anticancer Res.
PUBLISHED: 02-09-2013
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We investigated in this study whether fluorescence imaging with a fluorophore-conjugated anti-human epidermal growth factor receptor 2 (HER2)/neu probe could be used to differentiate metastatic lymph nodes (LN) from normal LN to guide surgical resection. A fluorescent probe for detecting HER2/neu-expressing cells was generated by conjugation of the humanized anti-HER2/neu antibody trastuzumab with rhodamine. The green fluorescent protein-expressing breast cancer cell line 4T1-GFP was used for in vitro binding analysis and for the establishment of a model of HER2/neu expressing LN-metastatic breast cancer. All tumor-bearing mice were given a single intravenous injection of either rhodamine-conjugated anti-HER2/neu probe, or conjugated control IgG antibody, when LN metastasis developed. Each animal was imaged with both green and red fluorescence to assess in vivo binding of the rhodamine-conjugated anti-HER2/neu probe to the tumors and LN metastases. Hematoxylin and eosin (H&E) staining and immunohistochemistry was performed to confirm the presence of tumor and metastasis as well as HER2/neu expression. The imaging probe was able to bind to HER2/neu-expressing 4T1-GFP tumor cells in vitro. The primary tumors and LN metastases from the animals which were treated with rhodamine-conjugated anti-HER2/neu probe exhibited a visible red fluorescence signal. The fluorescent axillary LN metastasis was easily distinguishable from the surrounding normal tissue and normal LN. Sensitivity of 78% (14 out of 18) and specificity of 100% (20 out of 20) could be achieved with the rhodamine-conjugated anti-HER2/neu probe for the detection of LN metastasis. These data support further investigation of the fluorophore-conjugated anti-HER2/neu antibody to detect LN metastasis in the surgical setting.
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VEGF-C ShRNA inhibits pancreatic cancer growth and lymphangiogenesis in an orthotopic fluorescent nude mouse model.
Anticancer Res.
PUBLISHED: 02-09-2013
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The aim of this study was to assess the inhibitory efficacy of short hairpin RNA (ShRNA) targeting vascular endothelial growth factor C (VEGF-C) in an orthotopic pancreatic cancer mouse model. BxPC-3 human pancreatic cancer cells expressing green fluorescent protein (GFP) were orthotopically implanted onto the pancreas of nude mice. All mice were randomly divided into four groups when the average tumor size had reached 100 mm(3) and were treated with either vehicle or gemcitabine at 150 mg/kg; or intravenous VEGF-C ShRNA at 150 mg/kg; or intratumoral VEGF-C ShRNA at 150 ?g/kg. In vivo fluorescence imaging was performed to monitor tumor growth and metastasis during the study. Real-time quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein level of VEGF-C in tumor tissues. Lymphatic vessel marker D2-40, blood vessel marker CD31 and proliferation marker Ki67 expression of the tumor tissues were analyzed by immunohistochemistry staining. Intravenous and intratumoral VEGF-C ShRNA treatment significantly inhibited tumor growth, downregulated the expression of VEGF-C mRNA, reduced tumor microlymphatic vessel density (MLVD), and inhibited cancer cell proliferation. Gemcitabine, as the standard treatment for pancreatic cancer, demonstrated a stronger inhibitory effect on tumor growth, with less inhibition of MLVD and more inhibition of microvessel density (MVD) and proliferation than VEGF-C ShRNA. These results indicate that different mechanisms are associated with the efficacy of gemcitabine and VEGF-C ShRNA.
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Catheter-based intramyocardial delivery (NavX) of adenovirus achieves safe and accurate gene transfer in pigs.
PLoS ONE
PUBLISHED: 01-03-2013
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Hepatocyte growth factor (HGF) is one of the major angiogenic factors being studied for the treatment of ischemic heart diseases. Our previous study demonstrated adenovirus-HGF was effective in myocardial ischemia models. The first clinical safety study showed a positive effect in patients with severe and diffused triple coronary disease.
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Catalytic dehydration of carbohydrates on in situ exfoliatable layered niobic acid in an aqueous system under microwave irradiation.
ChemSusChem
PUBLISHED: 01-02-2013
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A simple and efficient microwave-assisted HNb(3)O(8) catalytic process is proposed for the dehydration of carbohydrates in the aqueous phase. A 5-hydroxymethylfurfural (HMF) yield of 55.9 % was achieved at a high substrate/catalyst weight ratio of 50 from a 10 wt % fructose solution, which is close to the yield achieved by homogeneous aqueous systems. The critical factor for this performance is the fast in situ exfoliation of layered HNb(3)O(8) with the aid of microwave irradiation, which leads to quasi-homogeneous catalytic behavior. Importantly, the catalytic system is also applicable for the one-pot production of HMF from di- and polysaccharides, such as inulin, through a consecutive hydrolysis-dehydration reaction. Additionally, the unique restacking feature of the exfoliated HNb(3)O(8) ensures the good reusability of the catalyst.
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Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2013
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The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B) has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI) in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD) coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.
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Initial experience with a magnetic navigation system for invasive treatment in patients with non-ST-segment elevation acute coronary syndromes.
J Interv Cardiol
PUBLISHED: 08-25-2011
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Magnetic navigation system (MNS) assisted percutaneous coronary intervention (MPCI) has been demonstrated an advantage over conventional PCI (CPCI) in complex lesions and tortuous vessels. However, the benefits of MNS in clinical unstable and vulnerable lesions were little studied. The aim of this study is to evaluate the feasibility and benefits of MPCI versus CPCI in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS).
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Integration of dual source computed tomography with magnetic navigation system for percutaneous coronary intervention: a feasibility study.
Catheter Cardiovasc Interv
PUBLISHED: 05-04-2011
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To investigate the feasibility of integration of the dual source computed tomography (DSCT) and magnetic navigation system (MNS) to guide percutaneous coronary intervention (PCI).
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An improved transplantation strategy for mouse mesenchymal stem cells in an acute myocardial infarction model.
PLoS ONE
PUBLISHED: 03-03-2011
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To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1(st) BM-MSCs) and 5(th) passage BM-MSCs from ?-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6(th) week, animals/tissues from the 1(st) BM-MSCs group, the 5(th) passage BM-MSCs group, control group were examined. Our results revealed that, compared to the 5(th) passage BM-MSCs, the 1(st) BM-MSCs had better therapeutic effects in the mouse MI model. The 1(st) BM-MSCs maintained greater differentiation potentials towards cardiomocytes or vascular endothelial cells in vitro. This is indicated by higher expressions of cardiomyocyte and vascular endothelial cell mature markers in vitro. Furthermore, we identified that 24 proteins were down-regulated and 3 proteins were up-regulated in the 5(th) BM-MSCs in comparison to the 1(st) BM-MSCs, using mass spectrometry following two-dimensional electrophoresis. Our data suggest that transplantation of the 1(st) BM-MSCs may be an effective therapeutic strategy for cardiac tissue regeneration following AMI, and altered protein expression profiles between the 1(st) BM-MSCs and 5(th) passage BM-MSCs may account for the difference in their maintenance of stemness and their therapeutic effects following AMI.
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Toxic effects of a high dose of non-ionic iodinated contrast media on renal glomerular and aortic endothelial cells in aged rats in vivo.
Toxicol. Lett.
PUBLISHED: 02-16-2011
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Iodinated contrast media (CM) can induce apoptosis and necrosis of renal tubular cells. The injuries of endothelial cells induced by CM on the systemic condition have not been fully understood. To assess the toxic effects of non-ionic CM on the glomerular and aortic endothelial cells, iopromide and iodixanol, two kinds of representative non-ionic CM, were used for the in vivo study. Sixty aged rats were respectively received the agents or normal sodium intravascularly. No obvious apoptosis and morphological change was detected in the glomerular and aortic endothelial cells apart from renal tubules after CM administration. However, expressions of the nitric oxide synthase (eNOS) in glomerular endothelium were decreased at 12h after CM injection. Furthermore, plasma creatinine and endothelin-1 were increased and plasma nitric oxide (NO) was decreased significantly after CM administration. However, we failed to observe the significant increase of plasma von Willebrand Factor. These results suggest that non-ionic iodinated CM do not induce apoptosis and necrosis of glomerular and aortic endothelial cells in vivo. Decreased eNOS expression and increased plasma endothelin-1 may be involved in non-ionic iodinated CM-induced endothelial dysfunction and kidney injury.
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Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-18-2011
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VEGF and angiopoietin-1 (Ang1) are two major angiogenic factors being investigated for the treatment of myocardial infarction (MI). Targeting VEGF and Ang1 expression in the ischemic myocardium can increase their local therapeutic effects and reduce possible adverse effects. Adeno-associated viral vectors (AAVs) expressing cardiac-specific and hypoxia-inducible VEGF [AAV-myosin light chain-2v (MLC)VEGF] and Ang1 (AAV-MLCAng1) were coinjected (VEGF/Ang1 group) into six different sites of the porcine myocardium at the peri-infarct zone immediately after ligating the left descending coronary artery. An identical dose of AAV-Cytomegalovirus (CMV)LacZ or saline was injected into control animals. AAV genomes were detected in the liver in addition to the heart. RT-PCR, Western blotting, and ELISA analyses showed that VEGF and Ang1 were predominantly expressed in the myocardium in the infarct core and border of the infarct heart. Gated single-photon emission computed tomography analyses showed that the VEGF/Ang1 group had better cardiac function and myocardial perfusion at 8 wk than at 2 wk after vector injection. Compared with the saline and LacZ controls, the VEGF/Ang1 group expressed higher phosphorylated Akt and Bcl-xL, less Caspase-3 and Bad, and had higher vascular density, more proliferating cardiomyocytes, and less apoptotic cells in the infarct and peri-infarct zones. Thus, cardiac-specific and hypoxia-induced coexpression of VEGF and Ang1 improves the perfusion and function of porcine MI heart through the induction of angiogenesis and cardiomyocyte proliferation, activation of prosurvival pathways, and reduction of cell apoptosis.
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Zinc supplementation results in improved therapeutic potential of bone marrow-derived mesenchymal stromal cells in a mouse ischemic limb model.
Cytotherapy
PUBLISHED: 09-15-2010
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We wanted to determine whether zinc supplementation can inhibit bone marrow-derived mesenchymal stromal cell (MSC) apoptosis and enhance their tissue regenerative potential a in mouse ischemic hindlimb model.
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A superficial colon tumor model involving subcutaneous colon translocation and orthotopic transplantation of green fluorescent protein-expressing human colon tumor.
Tumour Biol.
PUBLISHED: 09-08-2010
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The orthotopic transplantation model of human tumor has been demonstrated to be more patient-like animal tumor model. However, observations of tumor progression and metastasis are limited by the deep location of the colon or limited deep penetration ability of fluorescence through tissue. The purpose of this study is to establish a superficial orthotopic model to allow easier real-time visualization and more sensitive monitoring of fluorescent orthotopic colon tumor. Human colon cancer HT-29 cells were transduced with a pLPCX expression retroviral vector containing green fluorescent protein and neomycin resistance genes. For superficial orthotopic transplantation model, the cecum was identified and pulled out of the peritoneal cavity, the space between the cecum and peritoneum was sutured, the cecum was pulled to subcutaneous tissue, and incision was made on the cecal serosa followed by the implantation of a 1-mm tumor tissue to the cecum. For comparison, a conventional orthotopic transplantation model was established in a separate group of mice simultaneously. When tumor sizes reached 5 mm in diameter, half the mice in each model received 5-FU treatment. Primary tumor and metastases were monitored by fluorescent imaging or caliber measurement. Tumor fluorescence was observed as early as 3 days (median time of 4.7?±?1.3 days) post-transplantation in the superficial orthotopic transplantation model, which was much earlier than 21 days (median time of 26.2?±?9.9 days) in conventional orthotopic transplantation model. Although tumor growth of 5-FU-treated mice in conventional orthotopic model was lower than those of the untreated mice, the difference was not significant. However, in superficial orthotopic model, tumor growth was significantly inhibited in 5-FU-treated mice relative to the untreated mice. Fluorescence imaging showed similar metastasis incidence between the superficial and conventional orthotopic transplantation models. The fluorescent superficial orthotopic transplantation colon model allows easier real-time visualization and more sensitive monitoring of tumor growth as well as convenient repeated sampling. It is a valuable orthotopic implantation model for study of colon cancer and evaluation of new anti-cancer therapy.
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Activation of calcium-sensing receptors is associated with apoptosis in a model of simulated cardiomyocytes ischemia/reperfusion.
J Biomed Res
PUBLISHED: 07-01-2010
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Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation. Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP3 signaling transduction. However, little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes.
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Retrieval of dislodged coronary stent from left renal artery by gooseneck snare.
J Biomed Res
PUBLISHED: 06-25-2010
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A rapamycin-eluting stent was dislodged during attempt of implantation at the proximal right coronary artery, which was found by fluoroscopy to have migrated into the anterior trunk of the left renal artery. We chose a 5 mm diameter Amplatz gooseneck snare and successfully retrieved the lost stent from the lodging vessel.
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Mobilization of bone marrow stem cells with StemEnhance improves muscle regeneration in cardiotoxin-induced muscle injury.
Cell Cycle
PUBLISHED: 05-17-2010
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Bone marrow-derived stem cells have the ability to migrate to sites of tissue damage and participate in tissue regeneration. The number of circulating stem cells has been shown to be a key parameter in this process. Therefore, stimulating the mobilization of bone marrow stem cells may accelerate tissue regeneration in various animal models of injury. In this study we investigated the effect of the bone marrow stem cells mobilizer StemEnhance (SE), a water-soluble extract of the cyanophyta Aphanizomenon flos-aquae (AFA), on hematopoietic recovery after myeloablation as well as recovery from cardiotoxin-induced injury of the anterior tibialis muscle in mice. Control and SE-treated female mice were irradiated, and then transplanted with GFP(+) bone marrow stem cells and allowed to recover. Immediately after transplant, animals were gavaged daily with 300 mg/kg of SE in PBS or a PBS control. After hematopoietic recovery (23 days), mice were injected with cardiotoxin in the anterior tibialis muscle. Five weeks later, the anterior tibialis muscles were analyzed for incorporation of GFP(+) bone marrow-derived cells using fluorescence imaging. SE significantly enhanced recovery from cardiotoxin-injury. However, StemEnhance did not affect the growth of the animal and did not affect hematopoietic recovery after myeloablation, when compared to control. This study suggests that inducing mobilization of stem cells from the bone marrow is a strategy for muscle regeneration.
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HGF percutaneous endocardial injection induces cardiomyocyte proliferation and rescues cardiac function in pigs.
J Biomed Res
PUBLISHED: 05-10-2010
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To investigate the effect of cardiomyocyte proliferation induced by human hepatocyte growth factor (HGF) in pigs with chronic myocardial infarction (CMI).
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High antimetastatic efficacy of MEN4901/T-0128, a novel camptothecin carboxymethyldextran conjugate.
J. Surg. Res.
PUBLISHED: 04-17-2010
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The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need.
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[Establishment of orthotopic lung cancer model expressing enhanced green fluorescent protein].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 04-16-2010
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In vivo molecular imaging with mouse model could continuously and in real-time monitor the changes of the tumor. The aim of this study is to establish stable enhanced green fluorescent protein (EGFP) expressing NCI-H460 cell lines and relevant mouse model via orthotopic transplantation, and to study the characteristic of this model and the quantitative detection method of the primary tumor and metastatic lesions.
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Inhibitory effect of hepatocyte growth factor on cardiomyocytes apoptosis is partly related to reduced calcium sensing receptor expression during a model of simulated ischemia/reperfusion.
Mol. Biol. Rep.
PUBLISHED: 04-05-2010
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Calcium-sensing receptors (CaSR) are G-protein coupled receptors which maintain systemic calcium haemeostasis, participate in hormone secretion, activation of iron channel, cell apoptosis, proliferation and differentiation. Previous studies have show CaSR induce apoptosis in isolated rat adult heart and in normal rat neonatal cardiomyocytes by G-protein-PLC-IP3 signaling transinduction. A few of studies had demonstrated that CaSR induce apoptosis in cultured neonatal rat cardiomyocytes during ischemia/reperfusion. Hepatocyte growth factor (HGF), as a mesenchymally derived heterodimeric glycoprotein, play vital role in mitogenesis, angiogenesis, cellular motility and growth and anti-apoptosis after postinfarction heart failure via activation of transmembrane tyrosine kinase cell surface receptor c-Met. However, little knowledge exists about whether anti-apoptotic role of HGF in preventing cardiomyocytes injury induced by ischemia/reperfusion is associated with downregulation of CaSR expression. We incubated primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic solution for 2 h, then reincubated them in normal culture medium for 24 h to establish a model of simulated ischemia/reperfusion (I/R). Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, we analyzed the expression of Caspase-3, Bcl-2 and Phosphoinositide 3-kinase (PI3K) by Western blotting. The simulated I/R enhances the expression of CaSR and cardiomyocyte apoptosis. GdCl3, a specific activator of CaSR, further increase the expression of CaSR and Cardiomyocyte apoptosis, along with upregulation of Caspase-3, downregulation of Bcl-2 and inhibiting PI3K phosphorylation. Combination of GdCl3 with LY294002 (a selective PI3K inhibitor) increased Cardiomyocytes apoptosis but did not increased CaSR expression. Treatment of HGF decreased I/R- and GdCl3-induced apoptosis by suppressing Caspase-3 and promoting Bcl-2 and PI3K phosphorylation expression in accordance with downregulation of CaSR expression. HGF exerts protective role in I/R-induced apoptosis at least in part by inhibiting CaSR expression along with promoting Bcl-2, suppressing Caspase-3 expression and stimulating PI3K phosphorylation signaling pathway.
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A novel approach to transplanting bone marrow stem cells to repair human myocardial infarction: delivery via a noninfarct-relative artery.
Cardiovasc Ther
PUBLISHED: 03-27-2010
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Bone marrow stem cells are able to repair infarcted human myocardium following intracoronary transplantation via the infarct-relative artery. However, traditional reperfusion strategies fail to open the artery in some patients, making effective delivery impossible. Our previous study demonstrated a safe and efficient approach to delivering bone marrow stem cells via a noninfarcted artery in an animal myocardial infarction model. The objective of the present study was to evaluate the safety and feasibility of autologous bone marrow mesenchymal stem cell transplantation via such an approach in patients with acute myocardial infarction (AMI). Sixteen patients with anterior AMI who had successfully undergone percutaneous coronary intervention (PCI) were enrolled in this pilot, randomized study. Three weeks after PCI, cultured bone marrow mesenchymal stem cells were injected into the myocardium via either the infarct-relative artery (left anterior descending branch artery, LAD) or a noninfarct-relative artery (right coronary artery, RCA). The safety and feasibility of the cell infusion were evaluated during the procedure and during 6 months of follow-up. In addition, 2D echocardiography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) and 18F-deoxyglucose single photon emission computed tomography were employed to examine cardiac function, myocardial perfusion, and viable cardiomyocytes, respectively, at day 4 after PCI and 6 months after the cell infusion. There were no arrhythmia and any other side-effects, including infections, allergic reactions or adverse clinical events, during, immediately after, or 6 months after cell transplantation. Cardiac function and myocardial perfusion had improved 6 months after PCI/bone marrow stem cells transplantation. Viable cardiomyocytes metabolism was detected in the infarcted areas in both groups after the cell infusion, as demonstrated by 18F-deoxyglucose. Intracoronary infusion of autologous bone marrow mesenchymal stem cells via a noninfarct-relative artery appears safe and feasible in the treatment of patients with AMI.
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Immediate and long-term results of coronary angioplasty in patients aged 80 years and older.
Cardiol Res Pract
PUBLISHED: 03-10-2010
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Objectives. To observe the short- and long-term outcomes after percutaneous coronary intervention (PCI) in octogenarians (>80 y.o.) at our institution. Method. All octogenarians who underwent PCI during the study period were retrospectively retrieved from our database and clinically followed. Major adverse cardiac (and cerebral) events (MAC(C)E) was considered as primary outcome. Results. From January 2003 to December 2007, 140 octogenarians (mean age: 85+/-3 y.o., 79% of male) underwent PCI and were clinically followed 14+/-11 months. Procedural success was obtained in 100 percent of patients with single vessel disease, in 96 percent of patients with double vessel disease, and in 75 percent of patients with triple vessel disease. In-hospital, 30 days, and one year MACE rates were 5%, 5%, and 10.7%, respectively. Impaired left ventricular (LV) ejection fraction (hazard ratio (HR) = 0.909, 95% confidence interval (CI) = 0.856 to 0.964, P = .002), diabetes mellitus (HR = 5.792, 95% CI = 1.785 to 18.796, P = .003), and low GFR (HR = 2.943, 95% CI = 1.161, to 7.464, P = .023) were independently associated with an increase risk of MACE at long-term followup. Conclusion. Coronary angiography can be successfully performed in elderly patients with single and double vessel disease. The results in triple vessel disease are encouraging. Low LV function, diabetes, and impaired renal function increase the risk of long-term major adverse cardiac events.
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Detection of early colorectal cancer imaged with peanut agglutinin-immobilized fluorescent nanospheres having surface poly(N-vinylacetamide) chains.
Eur J Pharm Biopharm
PUBLISHED: 01-05-2010
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Peanut agglutinin (PNA)-immobilized fluorescent nanospheres were designed as a novel imaging agent for colonoscopy. PNA is a targeting moiety that binds to beta-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells. The in vivo performance of the imaging agent was evaluated using a human colorectal cancer orthotopic animal model. Human colorectal adenocarcinoma cell lines, HT-29, HCT-116, and LS174T, were implanted on the cecal serosa of immune-deficient mice. A loop of the tumor-bearing cecum was made, and the luminal side was treated with the imaging agent. Strong fluorescence was observed at several sites of the cecal mucosa, irrespective of cancer cell type. Microscopic histological evaluation of the cecal mucosa revealed that bright areas with fluorescence derived from the imaging agent and dark areas without the fluorescence well denoted the presence and absence, respectively, of the invasion of implanted cancer cells on the mucosal side. This good correlation showed that PNA-immobilized fluorescent nanospheres recognized millimeter-sized tumors on the cecal mucosa with high affinity and specificity.
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Comparison of dual-source CT coronary angiography and conventional coronary angiography for detecting coronary artery disease.
Int J Cardiovasc Imaging
PUBLISHED: 01-05-2010
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To evaluate the diagnostic accuracy of dual-source CT coronary angiography for detecting coronary artery stenosis. From February 2008 to January 2009, dual-source CT coronary CT angiography (DSCT-CCTA) and conventional coronary angiography (CAG) were both performed in 84 patients who had either clinical symptoms or a high risk of coronary artery disease. The diagnostic accuracy of DSCT-CCTA was evaluated by comparing it with that of CAG, which was regarded as the gold standard for making the diagnosis of coronary artery disease. Occlusion or stenosis of various degrees was revealed by DSCT-CCTA in 244 segments of 84 patients. Compared to CAG, segment-based sensitivity, specificity, positive predictive value and negative predictive value of DSCT-CCTA were 97.4, 97.8, 92.2 and 100%, respectively. The diagnostic accuracy of DSCT-CCTA for the detection of coronary artery stenosis was 96.5%. The paired chi2 tests revealed no significant difference between DSCT-CCTA and CAG for making the diagnosis of coronary artery disease (P = 0.076). The diagnostic performance of DSCT-CCTA is generally as accurate as that of CAG. Thus, DSCT-CCTA is a reliable non-invasive method for detecting coronary artery stenosis.
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Efficacy of dietary antioxidants combined with a chemotherapeutic agent on human colon cancer progression in a fluorescent orthotopic mouse model.
Anticancer Res.
PUBLISHED: 07-15-2009
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We report here the efficacy of dietary antioxidants in combination with chemotherapy on tumor growth in the orthotopic COLO-205-green fluorescent protein (GFP) human colon cancer mouse model. The orthotopically-transplanted nude mice used for the study were randomly divided into 5 groups (A-E) after surgical orthotopic implantation (SOI) of tumor tissue. The following diets were given: Diet A, modified AIN-93M mature rodent diet with 4% fish oil; Diet B, modified AIN-93M which contains added antioxidants vitamin A, vitamin E, and selenium at levels present in the standard AIN-93M diet; Diet C, Diet A without added antioxidants vitamin A, vitamin E, or selenium; Diet D, Diet A with 5 times the amount of added antioxidants vitamin A, vitamin E, and selenium present in Diet B. Cisplatin, 7 mg/kg, was administered intraperitoneally on day 16 after SOI. Throughout the course of treatment, noninvasive whole-body imaging, based on the GFP expression of the tumor, permitted visualization of tumor progression. At sacrifice, the mean tumor weights showed significant statistical differences in all of the treated groups compared to the negative control (no cisplatin treatment) (p
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CXC-chemokine/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer.
Int. J. Cancer
PUBLISHED: 05-12-2009
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Angiogenesis is essential for tumor growth and metastasis. Although ELR(+)-CXC-chemokines and their corresponding receptor, CXC-receptor 2 (CXCR2), are known mediators of angiogenesis, little is known about their role in pancreatic cancer (PaCa). The aim of our study was to determine the role of ELR(+)-CXC-chemokine/CXCR2 biological axis in promoting PaCa angiogenesis. We prospectively collected secretin-stimulated exocrine pancreatic secretions (SSEPS) from normal individuals (NP) and PaCa patients. We showed that summed concentrations of ELR(+)-CXC-chemokines in SSEPS from PaCa patients were significantly higher than in those from NP (p = 0.002). We measured ELR(+)-CXC-chemokine levels in supernatants from multiple PaCa cell lines and confirmed that BxPC-3, Colo-357 and Panc-28 had significantly higher expression compared with an immortalized human pancreatic ductal epithelial (HPDE) cell line. After confirming lack of autocrine effects of ELR(+)-CXC-chemokines on PaCa cells (due to absence of CXCR2 expression), we investigated paracrine effects of these chemokines on human umbilical vein endothelial cells (HUVEC). Both recombinant ELR(+)-CXC-chemokines and co-culturing with BxPC-3 significantly enhanced proliferation, invasion, and tube formation of HUVEC (p < 0.05). These biological effects were significantly inhibited by treatment with a neutralizing antibody against CXCR2 (anti-CXCR2 Ab) (p < 0.05). Finally, anti-CXCR2 Ab significantly reduced tumor volume (p < 0.05), Ki-67 proliferation index (p = 0.043) and Factor VIII(+) microvessel density (p = 0.004) in an orthotopic nude mouse PaCa model. Our results show that ELR(+)-CXC-chemokines promote PaCa tumor-associated angiogenesis through CXCR2, suggesting that CXCR2 is an anti-angiogenic target in PaCa.
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In vitro/in vivo biorecognition of lectin-immobilized fluorescent nanospheres for human colorectal cancer cells.
J Control Release
PUBLISHED: 04-11-2009
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Peanut agglutinin (PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) (PNVA) chains encapsulating coumarin 6 were designed as a novel colonoscopic imaging agent. PNA was a targeting moiety that binds to beta-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells. PNVA was immobilized with the aim of reducing nonspecific interactions between imaging agents and normal tissues. Coumarin 6 was encapsulated into nanosphere cores to provide endoscopically detectable fluorescence intensity. After incubation of imaging agents with human cells, the fluorescence intensity of imaging agent-bound cells was estimated quantitatively. The average fluorescence intensity of any type of colorectal cancer cell used in this study was higher than that of small intestinal epithelial cells that had not exposed the carbohydrate. The in vivo performance of imaging agents was subsequently evaluated using a human colorectal cancer orthotopic animal model. Imaging agent-derived strong fluorescence was observed at several sites of the large intestinal mucosa in the tumor-implanted nude mice after the luminal side of the colonic loop was contacted with imaging agents. In contrast, when mice that did not undergo tumor implantation were used, the fluorescence intensity on the mucosal surface was extremely low. Data indicated that imaging agents bound to colorectal cancer cells and the cancer cell-derived tumors with high affinity and specificity.
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The stem cell mobilizer StemEnhance does not promote tumor growth in an orthotopic model of human breast cancer.
Anticancer Res.
PUBLISHED: 04-01-2009
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Bone marrow-derived stem cells (BMDSC) have been implicated in tumor formation, though it is not clear whether they contribute to tumor growth. A novel mobilizer of BMDSC (StemEnhance; SE) was used to investigate whether its daily administration promotes tumor growth. Forty mice were surgically transplanted with human MDA-MB-435-GFP breast cancer into the mammary fat pad of nude mice, The mice were gavaged for six weeks with 300 mg/kg of SE. Tumor growth was monitored using live whole-body fluorescence imaging. At the end of the study, tumors were excised and weighed. At the start of the feeding trial, tumor areas for both control and experimental group were statistically identical. Tumor growth rate was slower in the SE group (p = 0.014) when compared to the control group. After 6 weeks, tumor areas were 40% larger in the control p < 0.01) and mean tumor weight was 35% smaller in the SE-treated group (0.44 g vs. 0.68 g; p = 0.031). Feeding of SE did not promote tumor growth but rather reduced the growth of human MDA-MB-435 breast cancer.
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[Determination of rhodamine B in spices by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry].
Se Pu
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Rhodamine B (RB), as an unlawful colour, is forbidden to add into foods by Chinese government. A solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for the determination of RB in spices has been developed. The sample was extracted by acetonitrile and then centrifugated, purified and enriched with a strong positive ion exchange SPE column (Bond Elut Plexa PCX SPE column) after adding 10 mL 1% trichloroacetic acid solution. The HPLC separation was performed on a Pursuit C18 column (100 mm x 2.0 mm, 3 microm) by gradient elution with 0.1% (v/v) formic acid solution and methanol as the mobile phase. The analyte was detected by electrospray ionization in positive ion mode-MS/MS in multiple reaction monitoring (MRM) mode. The good linearity (R2 > 0.99) was obtained over the range of 0.6-6 microg/L. The limit of quantification (LOQ) for RB was 1.2 microg/kg. The average recoveries were ranged from 80% to 121% at the spiked levels of 1.197, 2.992 and 5.985 microg/L, and the relative standard deviations (RSDs) were not more than 15%. The conditions of mobile phase elution gradients, extraction solvents, and SPE columns were optimized. This method is highly selective and has weak matrix effect for qualitative and quantitative analyses of RB in spices.
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Beneficial effects of ginsenoside-Rg1 on ischemia-induced angiogenesis in diabetic mice.
Acta Biochim. Biophys. Sin. (Shanghai)
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Neovascularization and the formation of collateral vessels are often impaired in diabetes mellitus (DM) population compared with non-diabetics. Alterations in vascular endothelial growth factor (VEGF) signaling and endothelial nitric oxide synthase (eNOS) dysfunction have been confirmed to play a crucial role in impaired neovascularization in diabetic mice. Accumulating data have suggested that Rg1, a main component of Panax ginseng, has the ability to promote tubulogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, and that the mechanism involves increased expression level of VEGF as well as increased eNOS activation. Thus, we speculated that Rg1 might also have therapeutic effects on the impairment of neovascularization in diabetic individuals. The aim of the present study was to investigate whether Rg1 could improve angiogenesis in ischemic hindlimb of diabetic mice in vivo. Our data demonstrated that Rg1 treatment resulted in improved angiogenesis in the diabetic ischemic hindlimb, and the potential mechanism might involve increased eNOS activation, upregulated VEGF expression, and inhibited apoptosis. Our results suggest that Rg1 may be used as a novel and useful adjunctive drug for the therapy of peripheral arterial disease in DM.
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A generalized Irving-Kirkwood formula for the calculation of stress in molecular dynamics models.
J Chem Phys
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In non-equilibrium molecular dynamics simulations, continuum mechanics quantities can be computed from the position and momentum of the particles based on the classical Irving-Kirkwood formalism. For practical purposes, the implementations of Irving-Kirkwood formulas often involve a spatial averaging using a smooth kernel function. The resulting formula for the stress has been known as Hardy stress. Usually results obtained this way still need to be further processed to reduce the fluctuation, e.g., by ensemble or time averaging. In this paper we extend Hardys formulas by systematically incorporating both spatial and temporal averaging into the expression of continuum quantities. The derivation follows the Irving-Kirkwood formalism, and the average quantities still satisfy conservation laws in continuum mechanics. We will discuss the selection of kernel functions and present several numerical tests.
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[Establishment of a malignant pleural effusion mouse model with Lewis lung carcinoma cell lines expressing enhanced green fluorescent protein].
Zhongguo Fei Ai Za Zhi
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Malignant pleural effusion (MPE) is a poor prognosis factor in patients with advanced lung cancer. The aim of this study is to establish a mouse model of MPE using Lewis lung carcinoma (LLC) cell lines expressing enhanced green fluorescent protein (EGFP).
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Efficacy of the Chinese traditional medicinal herb Celastrus orbiculatus Thunb on human hepatocellular carcinoma in an orthothopic fluorescent nude mouse model.
Anticancer Res.
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This study aimed to explore the inhibitory effect of Celastrus orbiculatus Thunb. (COT) on tumor growth, metastasis and antiogenesis of hepatocelluar carcinoma (HCC) in an orthotopic nude mouse model using fluorescence imaging technology. Human HCC Hep-G2 cells expressing red fluorescent protein (RFP) were orthotopically implanted onto the liver of nude mice. One group of mice was treated with ethyl acetate extract of COT p.o. at a dose of 20 mg/kg starting on day 3 post-tumor implantation (early treatment). All other mice were randomized into four groups from day 20 post-tumor implantation and received either no treatment, oxaliplatin (25 mg/kg), or low-dose (20 mg/kg) or high-dose (40 mg/kg) COT. Real-time whole-body fluorescence imaging was performed to measure tumor growth and monitor metastasis development during the study. Vascular endothelial growth factor(VEGF) expression in the tumors collected at autopsy was analyzed by immunohistochemical staining and reverse transcription-polymerase chain reaction(RT-PCR). High-dose treatments, early treatment with COT, demonstrated significant efficacy on controlling tumor volume and tumor weight in the human HCC Hep-G2 orthotopic tumor model. No significant differences were found for metastasis incidence among the different study groups. VEGF expression in the tumors was significantly reduced by oxaliplatin and COT treatment. This study demonstrates the inhibitory efficacy of COT on the growth of HCC tumor. VEGF inhibition may contribute in part to the inhibition of HCC tumor growth. The results of the present report suggest COT has potential to treat HCC.
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Improvement of arterial stiffness by reducing oxidative stress damage in elderly hypertensive patients after 6 months of atorvastatin therapy.
J Clin Hypertens (Greenwich)
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Atorvastatin is postulated to improve arterial stiffness in patients with diabetes mellitus or hypercholesterolemia; however, in elderly hypertensive patients, its effect on arterial stiffness and the possible mechanisms are unknown. A total of 73 elderly hypertensive patients were enrolled to receive atorvastatin for 6 months. Brachial-ankle pulse wave velocity (baPWV) and circulating biomarkers were measured before and after the intervention. After 6 months of treatment, the patients experienced a 19.66% reduction in low-density lipoprotein cholesterol (2.90±0.58 vs 2.33±0.56 mmol/L, P<.01) and a 10.63% reduction in baPWV (2100.89±513.21 vs 1877.56±432.06 cm/s, P=.01). In addition, a 21.79% reduction in circulating N-(epsilon)-carboxymethyl-lysine and a 20% reduction in Von Willebrand factor level were observed after treatment. Meanwhile, the activity of copper/zinc-containing superoxide dismutase (Cu/Zn SOD) was increased by 26.64% (5.04±1.01 vs 6.87±1.83 U/L, P<.001). Correlation analysis demonstrated that the increase of Cu/Zn SOD activity was related to the reductions of arterial stiffness (r=-0.340, P=.003). Taken together, these findings suggest that atorvastatin can improve arterial stiffness possibly by reducing oxidative stress levels in elderly hypertensive patients.
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DNp73 improves generation efficiency of human induced pluripotent stem cells.
BMC Cell Biol.
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Recent studies have found that p53 and its associated cell cycle pathways are major inhibitors of human induced pluripotent stem (iPS) cell generation. In the same family as p53 is p73, which shares sequence similarities with p53. However, p73 also has distinct properties of its own, such as two alternative promoters to express transactivation of p73 (TAp73) and N terminal deleted p73 (DNp73). Functionally, TAp73 acts similarly to p53 in tumor suppression. However, DNp73, on the other hand acts as an oncogene to suppress p53 and p73 induced apoptosis. Therefore, how can p73 have opposing roles in human iPS cell generation?
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Effect of the calcium sensing receptor on rat bone marrow-derived mesenchymal stem cell proliferation through the ERK1/2 pathway.
Mol. Biol. Rep.
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Migration and proliferation of bone marrowderived mesenchymal stem cells (BMSCs) is critical to treatment of ischemic injury. The calcium sensing receptor (CaSR) has an important role in maintaining systemic calcium homeostasis, which is related to cell proliferation, apoptosis and paracrine signaling. We hypothesize that CaSR may enhance BMSC proliferation. Rat BMSCs were incubated with various calcium concentrations for 48 h in vitro to activate CaSR. To investigate potential mechanisms responsible for growth enhancement by calcium, the rat BMSC cell cycle progression was analyzed by fluorescence-activated cell sorting (FACS), and induction of apoptosis confirmed by cytofluorimetric analysis using propidium iodide and Annexin V-FITC double staining. Since the mitogen-activated protein kinase (MAPK) signaling pathway was one of the most significantly affected by CaSR, MAPK activation was measured by western blotting. Calcium exposure significantly enhanced rat BMSCs proliferation, as well as the proportion of the population in S phase, in a dose-dependent manner, effects which were abolished by NPS2390 (a CaSR antagonist) and U0126 (a MEK1/2 inhibitor). These results demonstrate that CaSR is involved in rat BMSC proliferation, as seen by an increased proliferation index, decreased apoptosis, and ERK1/2 activation, and provide important insight into the cellular and molecular mechanisms by which CaSR affects cell proliferation. A CaSR agonist may prove useful to enhance BMSC survival during transplantation.
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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.