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Find video protocols related to scientific articles indexed in Pubmed.
Imaging the distribution of polymyxins in the kidney.
J. Antimicrob. Chemother.
PUBLISHED: 11-08-2014
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Dose-limiting nephrotoxicity remains the Achilles' heel of polymyxin B and polymyxin E (also known as colistin), which are important last-line antibiotics used against infections caused by MDR Gram-negative 'superbugs'. An understanding of the mechanisms of nephrotoxicity, including renal tissue distribution, is crucial for the development of safer polymyxin lipopeptide antibiotics. This is the first study to visualize the kidney distribution of polymyxin B using a mouse nephrotoxicity model and in situ immunostaining of kidney sections.
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Lymph Node Ratio-based Staging System Outperforms the Seventh AJCC System for Gastric Cancer: Validation Analysis With National Taiwan University Hospital Cancer Registry.
Am. J. Clin. Oncol.
PUBLISHED: 08-05-2014
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On the basis of SEER data, in which most gastric cancer patients had limited lymph node dissection, node ratio-based staging system (TNrM) has been shown to have better accuracy than the AJCC TNM system. This study is to validate the result with patients from Taiwan, where D2 lymphadenectomy is routinely performed.
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Functional genetic approach identifies MET, HER3, IGF1R, INSR pathways as determinants of lapatinib unresponsiveness in HER2-positive gastric cancer.
Clin. Cancer Res.
PUBLISHED: 06-27-2014
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Targeting human epidermal growth factor receptor 2 (HER2) therapy is currently considered as the standard treatment for HER2-positive (HER2+) advanced gastric cancer. However, as seen in recent clinical trials, most of HER2+ gastric cancer are actually unresponsive to HER2-targeted agents, including lapatinib. The aim of this study is to identify the responsible receptor tyrosine kinases (RTK) potentially conferring lapatinib unresponsiveness in HER2+ gastric cancer and elucidate the molecular mechanism underlying this RTKs-induced resistance.
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Using Dynamic (99m)T c-GSA SPECT/CT Fusion Images for Hepatectomy Planning and Postoperative Liver Failure Prediction.
Ann. Surg. Oncol.
PUBLISHED: 06-24-2014
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Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure.
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Safety and Efficacy of Radiation Dose Delivered via Iodine-125 Brachytherapy Mesh Implantation for Deep Cavity Sarcomas.
Ann. Surg. Oncol.
PUBLISHED: 05-19-2014
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Radiation delivered as brachytherapy (BRT) via catheters placed during extremity soft tissue sarcoma (STS) resection results in acceptable local control rates; however, there are limitations in deep cavities. (125)I seeds embedded in mesh provide a flexible BRT platform that may be contoured to irregular deep cavities surfaces, but the risks and benefits are unknown.
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Teaching 'old' polymyxins new tricks: new-generation lipopeptides targeting gram-negative 'superbugs'.
ACS Chem. Biol.
PUBLISHED: 03-17-2014
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The antimicrobial lipopeptides polymyxin B and E (colistin) are being used as a 'last-line' therapy for infections caused by multidrug-resistant Gram-negative pathogens. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections caused by the Gram-negative 'superbugs'. This report details the structure-activity relationships (SAR) based design, in toto synthesis, and preclinical evaluation of a series of novel polymyxin lipopeptides with better antibacterial activity against polymyxin-resistant Gram-negative bacteria.
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Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.
Mol. Cell
PUBLISHED: 02-18-2014
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Many mutant p53 proteins (mutp53s) exert oncogenic gain-of-function (GOF) properties, but the mechanisms mediating these functions remain poorly defined. We show here that GOF mutp53s inhibit AMP-activated protein kinase (AMPK) signaling in head and neck cancer cells. Conversely, downregulation of GOF mutp53s enhances AMPK activation under energy stress, decreasing the activity of the anabolic factors acetyl-CoA carboxylase and ribosomal protein S6 and inhibiting aerobic glycolytic potential and invasive cell growth. Under conditions of energy stress, GOF mutp53s, but not wild-type p53, preferentially bind to the AMPK? subunit and inhibit AMPK activation. Given the importance of AMPK as an energy sensor and tumor suppressor that inhibits anabolic metabolism, our findings reveal that direct inhibition of AMPK activation is an important mechanism through which mutp53s can gain oncogenic function.
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Effects of Colistin on the Sensory Nerve Conduction Velocity and F-wave in Mice.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 01-22-2014
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The aim of this study was to examine the changes of sensory nerve conduction velocity (SNCV) and F-wave for colistin-induced peripheral neurotoxicity using a mouse model. Mice were administered with colistin 5, 7.5 and 15 mg/kg/day via a 3-min. intravenous infusion. The sensory nerve conduction velocity (SNCV) and F-wave were measured using the bipolar recording electrodes. The SNCV and F-wave latency changed in a dose- and time-dependent manner. The significant increase of F-wave latency and significant decrease of SNCV appeared on day 3 (p < 0.05 and 0.01, respectively) in the 15 mg/kg/day group, and they were markedly changed on day 7 in the 7.5 mg/kg/day (p < 0.01 and 0.05, respectively) and 15 mg/kg/day groups (both p < 0.01). In addition, F-wave latency also significantly increased on day 7 in the 5 mg/kg/day group (p < 0.05) without any clinical signs. These results indicate that SNCV and F-wave latency were more sensitive in colistin-induced neurotoxicity in mice, which highlights the early monitoring tool of polymyxins neurotoxicity in the clinic.
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Human miR-1228 as a stable endogenous control for the quantification of circulating microRNAs in cancer patients.
Int. J. Cancer
PUBLISHED: 01-21-2014
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Circulating microRNAs are promising biomarkers for non-invasive testing and dynamic monitoring in cancer patients. However, no consensus exists regarding the normalization of circulating microRNAs in the quantification, making the results incomparable. We investigated global circulating microRNA profiles to identify a stable endogenous control for quantifying circulating microRNAs using three cohorts (n?=?544), including 168 control individuals (healthy subjects and those with chronic hepatitis B and cirrhosis) and 376 cancer patients (hepatocellular, colorectal, lung, esophageal, gastric, renal, prostate, and breast cancer patients). GeNorm, NormFinder, and coefficient of variability (CV) were used to select the most stable endogenous control, whereas Ingenuity Pathway Analysis (IPA) was adopted to explore its signaling pathways. Seven candidates (miR-1225-3p, miR-1228, miR-30d, miR-939, miR-940, miR-188-5p, and miR-134) from microarray analysis and four commonly used controls (miR-16, miR-223, let-7a, and RNU6B) from literature were subjected to real-time quantitative reverse transcription-polymerase chain reaction validation using independent cohorts. MiR-1228 (CV?=?5.4%) with minimum M value and S value presented as the most stable endogenous control across eight cancer types and three controls. IPA showed miR-1228 to be involved extensively in metabolism-related signal pathways and organ morphology, implying that miR-1228 functions as a housekeeping gene. Functional network analysis found that "hematological system development" was on the list of the top networks that associate with miR-1228, implying that miR-1228 plays an important role in the hematological system. The results explained the steady expression of miR-1228 in the blood. In conclusion, miR-1228 is a promising stable endogenous control for quantifying circulating microRNAs in cancer patients.
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Polyandric acid A, a clerodane diterpenoid from the Australian medicinal plant Dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo.
J. Nat. Prod.
PUBLISHED: 01-08-2014
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Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I'yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1? production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis.
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Estrogen receptor ? or ? loss in the colon of Min/+ mice promotes crypt expansion and impairs TGF? and HNF3? signaling.
Carcinogenesis
PUBLISHED: 10-08-2013
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Adenomatous polyposis coli (APC)-regulated Wnt and transforming growth factor-? (TGF?) signaling cooperate in the intestine to maintain normal enterocyte functions. Human clinical trials showed that estrogen [17?-estradiol (E2)], the ligand of nuclear receptors estrogen receptor ? (ER?) and ER?, inhibited colorectal cancer (CRC) in women. Consistent with this finding, we reported that E2, ER? and ER? suppressed intestinal tumorigenesis in the C57BL/6J-Min/+ (Min/+) mouse, a CRC model. Here, we extended our results with further comparisons of colon and small intestine from intact female Apc (+/+) (WT), Min/+ and ER-deficient Min/+ mice. In the colon of ER-deficient Min/+ mice, ER loss reduced TGF? signaling in crypt base cells as evidenced by minimal expression of the effectors Smad 2, 3 and 4 in these strains. We also found reduced expression of Indian hedgehog (Ihh), bone morphogenetic protein 4 and hepatocyte nuclear factor 3? or FoxA2, factors needed for paracrine signaling between enterocytes and mesenchyme. In proximal colon, ER loss produced a >10-fold increased incidence of crypt fission, a marker for wound healing and tumor promotion. These data, combined with our previous work detailing the specific roles of E2, ER? and ER? in the colon, suggest that ER activity helps to maintain the intestinal stem cell (ISC) microenvironment by modulating epithelial-stromal crosstalk in ways that regulate cytokine, Wnt and Ihh availability in the extracellular matrix (ECM).
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[Expression of yeast acyl-delta9 desaturase for fatty acid biosynthesis in tobacco].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-10-2013
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Palmitoleic acid (16:1delta9), an unusual monounsaturated fatty acid, is highly valued for human nutrition, medication and industry. Plant oils containing large amounts of palmitoleic acid are the ideal resource for biodiesel production. To increase accumulation of palmitoleic acid in plant tissues, we used a yeast (Saccharomyees cerevisiae) acyl-CoA-delta9 desaturase (Scdelta9D) for cytosol- and plastid-targeting expression in tobacco (Nicotiana tabacum L.). By doing this, we also studied the effects of the subcellular-targeted expression of this enzyme on lipid synthesis and metabolism in plant system. Compared to the wild type and vector control plants, the contents of monounsaturated palmitoleic (16:1delta9) and cis-vaccenic (18:1delta11) were significantly enhanced in the Scdelta9D-transgenic leaves whereas the levels of saturated palmitic acid (16:0) and polyunsaturated linoleic (18:2) and linolenic (18:3) acids were reduced in the transgenics. Notably, the contents of 16:1delta9 and 18:1delta11 in the Scdelta9D plastidal-expressed leaves were 2.7 and 1.9 folds of that in the cytosolic-expressed tissues. Statistical analysis appeared a negative correlation coefficient between 16:0 and 16:1delta9 levels. Our data indicate that yeast cytosolic acyl-CoA-delta9 desaturase can convert palmitic (16:0) into palmitoleic acid (16:1delta9) in high plant cells. Moreover, this effect of the enzyme is stronger with the plastid-targeted expression than the cytosol-target expression. The present study developed a new strategy for high accumulation of omega-7 fatty acids (16:1delta9 andl8:1delta11) in plant tissues by protein engineering of acyl-CoA-delta9 desaturase. The findings would particularly benefit the metabolic assembly of the lipid biosynthesis pathway in the large-biomass vegetative organs such as tobacco leaves for the production of high-quality biodiesel.
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Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens.
Clin. Infect. Dis.
PUBLISHED: 05-22-2013
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Polymyxin B is a last-line therapy for multidrug-resistant gram-negative bacteria. There is a dearth of pharmacokinetic data to guide dosing in critically ill patients.
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Colistin powders with high aerosolisation efficiency for respiratory infection: preparation and in vitro evaluation.
J Pharm Sci
PUBLISHED: 05-16-2013
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In many respiratory infections caused by multi-drug-resistant Gram-negative bacteria, colistin is often the last-line drug for treatment despite its nephrotoxicity when administered parenterally. Inhalation therapy of colistin has great potential to improve the efficacy while reducing adverse effects. In this study, inhalable powder formulations of colistin (sulphate) were produced via spray drying. The colistin powders were found to have intact antimicrobial activity against Acinetobacter baumannii measured by broth micro-dilution. Both the raw material and spray-dried formulations were amorphous and absorbed significant amount of water up to 30% (w/w) at relative humidity (RH) of at least 70%. The spray-dried formulations were physically stable in the amorphous form at 60% RH and 25°C, having a high aerosol efficiency (emitted dose >86% and fine particle fraction total >83%) which remained unchanged after a 3-month storage. Storage at an elevated RH of 75% resulted in the aerosolisation performance significantly decreased, and at RH 90%, the formulation particles fused together (but without re-crystallisation). Although spray drying has been extensively used for generating inhalable drug particles, this is the first report that colistin powder can be physically stable in the amorphous form at ambient conditions, indicating that spray-drying approach is suitable for producing inhalable colistin powder formulation.
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Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma.
J. Clin. Oncol.
PUBLISHED: 11-21-2011
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More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) -related HCC.
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The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion.
Life Sci.
PUBLISHED: 06-09-2011
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The aim of present study was to investigate the effects of isosteviol on hyperglycemia and hyperlipidemia in rats fed with high-fat emulsion (HFE).
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Aphallia in an adult male with 46, XY karyotype.
Int. J. Urol.
PUBLISHED: 05-25-2011
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Aphallia is a rare urogenital anomaly with an estimated incidence of 1 in 10-30 million. We report a case of aphallia in a male, who had two well-developed testicles, but lacked a penis. Digital rectal examination revealed the urethral meatus was opening to the anterior wall of the rectum posterior to the sphincter. Magnetic resonance imaging showed complete absence of penile development with normal testis and scrotum, as well as the urethra running posterior to the prostatic apex and corpus spongiosum in sagittal and coronal T2-weighted images. Chromosome karyotype confirmed 46,XY, and the polymerase chain reaction method tested no azoospermic factor (AZF) or sex-determining region Y (SRY) gene deletion. Taking into account the physical and psychosocial conditions, seeking a female without sexual desire as his wife was recommended.
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In vivo activity of benzoyl ester clerodane diterpenoid derivatives from Dodonaea polyandra.
J. Nat. Prod.
PUBLISHED: 03-07-2011
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Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8?-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8?-(benzoyloxy)methyl-2?-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8?-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2?-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 ?mol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses.
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Differential disposition of intra-renal generated and preformed glucuronides: studies with 4-methylumbelliferone and 4-methylumbelliferyl glucuronide in the filtering and nonfiltering isolated perfused rat kidney.
J. Pharm. Pharmacol.
PUBLISHED: 03-01-2011
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This study was designed to investigate the renal disposition of 4-methylumbelliferone (4MU) and 4-methylumbelliferyl glucuronide (4MUG) to characterise the contribution of excretion and metabolic clearance to total clearance in the kidney.
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Organic anion and cation transporters are possibly involved in renal excretion of entecavir in rats.
Life Sci.
PUBLISHED: 02-22-2011
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The purpose of the present study was to investigate the roles of transporters in the renal excretion of entecavir.
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Evaluation of the anti-inflammatory properties of Dodonaea polyandra, a Kaanju traditional medicine.
J Ethnopharmacol
PUBLISHED: 03-19-2010
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Extracts of the medicinal plant species Dodonaea polyandra were investigated as part of a collegial research partnership between Northern Kaanju traditional owners represented by Chuulangun Aboriginal Corporation (centred on the Wenlock and Pascoe Rivers, Cape York Peninsula, Queensland, Australia) and university-based researchers. D. polyandra, known as "Uncha" in Kaanju language, is used in Northern Kaanju Traditional Medicine for relief from pain associated with toothache and related ailments. The species has a restricted distribution in Cape York Peninsula and there has been no previous Western scientific investigation of its pharmacology or chemistry.
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Inhibition of morphine metabolism by ketamine.
Drug Metab. Dispos.
PUBLISHED: 02-02-2010
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Clinical observation of a synergistic effect of ketamine on morphine analgesia remains controversial. Although a pharmacodynamic basis for an interaction has been explored in animal and clinical studies, the possibility of a pharmacokinetic mechanism has not been investigated. Whereas both morphine and morphine-6-glucuronide are effective analgesics, morphine-3-glucuronide (M3G) lacks activity. Thus, changes in the metabolism and disposition of morphine may result in an altered response. First, we investigated the interaction between morphine and ketamine in the isolated perfused rat liver preparation. The clearance of morphine was decreased from 16.8 +/- 4.6 ml/min in the control period to 7.7 +/- 2.8 ml/min in the ketamine-treatment period, with the formation clearance of M3G decreasing from 8.0 +/- 4.1 ml/min to 2.1 +/- 1.1 ml/min. Fractional conversion of morphine to M3G was significantly decreased from 0.46 +/- 0.17 in the control period to 0.28 +/- 0.14 upon the addition of ketamine. The possible mechanism of the interaction was further investigated in vitro with rat liver microsomes as the enzyme source. The formation of M3G followed single-enzyme Michaelis-Menten kinetics, with a mean apparent K(m) of 2.18 +/- 0.45 mM and V(max) of 8.67 +/- 0.59 nmol/min/mg. Ketamine inhibited morphine 3-glucuronidation noncompetitively, with a mean K(i) value of 33.3 +/- 7.9 microM. The results demonstrate that ketamine inhibits the glucuronidation of morphine in a rat model.
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Disposition of isosteviol in the rat isolated perfused liver.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 01-17-2010
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1. The aim of the present study was to investigate the mechanisms involved in the clearance of isosteviol using the rat isolated perfused liver. 2. Six livers from male Sprague-Dawley rats were perfused with 15.7 mumol isosteviol in a recirculating system. Perfusate and bile samples were collected for 60 min and the liver was collected at the end of the perfusion. All samples collected were incubated with alpha-glucuronidase. Isosteviol-glucuronide was determined as equivalent isosteviol. Isosteviol concentrations were determined using a previously developed liquid chromatography-tandem mass spectrometry method. The final isosteviol liver/perfusate (L/P), bile/liver (B/L) and isosteviol-glucuronide in bile/liver (B(G)/L(G)) ratios were determined. 3. Isosteviol has a high clearance (21.4 +/- 4.8 mL/min) from the perfusate, with a short half-life (13 +/- 4 min). alpha-Glucuronidase incubation revealed that isosteviol is conjugated in the liver and excreted into the bile. There was no isosteviol-glucuronide detected in perfusate samples. The total recovery of the rat isolated perfused liver system is 74 +/- 14% and glucuronidated isosteviol accounted for 23 +/- 4% of the administered dose. 4. In conclusion, we are the first to characterize the metabolism of isosteviol using rat isolated liver perfusion. Our results strongly suggest that the liver is the main organ of isosteviol elimination and that isosteviol is glucuronidated in the liver before it is excreted into the bile.
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Expression and characterization of Kunitz domain 3 and C-terminal of human tissue factor pathway inhibitor-2.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 11-11-2009
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Human tissue factor pathway inhibitor-2 (hTFPI-2) is a serine protease inhibitor and its inhibitory activity is enhanced by heparin. The Kunitz domain 3 and Cterminal of hTFPI-2 (hTFPI-2/KD3C), which has the activity toward heparin calcium, have been successfully expressed in Pichia pastoris and purified by SPSepharose and heparin-Sepharose chromatography. The Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, and circular dichroism (CD) experiment results implied that hTFPI-2/KD3C contained small contents of alpha-helix and beta-strand, but large amounts of random coil and two kinds of disulfide bonds, gauche-gauche-gauche (ggg) and trans-gauchetrans (tgt). The interaction of hTFPI-2/KD3C with heparin calcium was investigated by CD. It was found that heparin calcium induced b-strands in hTFPI-2/ KD3C to different extents depending on the ratio of hTFPI-2/KD3C and heparin calcium.
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ERM protein moesin is phosphorylated by advanced glycation end products and modulates endothelial permeability.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 04-24-2009
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Advanced glycation end products (AGEs) accumulated in different pathological conditions have the potent capacity to alter cellular properties that include endothelial structural and functional regulations. The disruption of endothelial barrier integrity may contribute to AGE-induced microangiopathy and macrovasculopathy. Previous studies have shown that AGEs induced the rearrangement of actin and subsequent hyperpermeability in endothelial cells (ECs). However, the mechanisms involved in this AGE-evoked EC malfunction are not well understood. This study directly evaluated the involvement of moesin phosphorylation in AGE-induced alterations and the effects of the RhoA and p38 MAPK pathways on this process. Using immortalized human dermal microvascular ECs (HMVECs), we first confirmed that the ezrin/radixin/moesin (ERM) protein moesin is required in AGE-induced F-actin rearrangement and hyperpermeability responses in ECs by knockdown of moesin protein expression with small interfering RNA. We then detected AGE-induced moesin phosphorylation by Western blot analysis. The mechanisms involved in moesin phosphorylation were analyzed by blocking AGE receptor binding and inhibiting Rho and MAPK pathways. AGE-treated HMVECs exhibited time- and dose-dependent increases in the Thr(558) phosphorylation of moesin. The increased moesin phosphorylation was attenuated by preadministrations of AGE receptor antibody, Rho kinase (ROCK), or p38 inhibitor. Suppression of p38 activation via the expression of dominant negative mutants with Ad.MKK6b or Ad.p38alpha also decreased moesin phosphorylation. The activation of the p38 pathway by transfection of HMVECs with an adenoviral construct of dominant active MKK6b resulted in moesin phosphorylation. These results suggest a critical role of moesin phosphorylation in AGE-induced EC functional and morphological regulations. Activation of the ROCK and p38 pathways is required in moesin phosphorylation.
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Renal disposition of colistin in the isolated perfused rat kidney.
Antimicrob. Agents Chemother.
PUBLISHED: 04-20-2009
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Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 microg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CL(R)) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CL(R)/(f(u) x GFR), where f(u) is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 microM), Gly-Gly (833 microM), and HCl (2,500, 5,000, and 10,000 microM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.
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Should total number of lymph nodes be used as a quality of care measure for stage III colon cancer?
Ann. Surg.
PUBLISHED: 03-21-2009
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To assess whether TNODS is an independent prognostic factor after adjusting for the lymph node ratio (LNR).
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Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis.
J. Antimicrob. Chemother.
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To evaluate the pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis (CVVHD) after intravenous administration of unadjusted dosage regimens.
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Much of the genetic risk of colorectal cancer is likely to be mediated through susceptibility to adenomas.
Gastroenterology
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Several single-nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) susceptibility. Most CRCs arise from adenomas, and SNPs therefore might affect predisposition to CRC by increasing adenoma risk. We found that 8 of 18 known CRC-associated SNPs (rs10936599, rs6983267, rs10795668, rs3802842, rs4444235, rs1957636, rs4939827, and rs961253) were over-represented in CRC-free patients with adenomas, compared with controls. Ten other CRC-associated SNPs (rs6691170, rs6687758, rs16892766, rs7136702, rs11169552, rs4779584, rs9929218, rs10411210, rs4813802, and rs4925386) were not associated significantly with adenoma risk. Genetic susceptibility to CRC in the general population is likely to be mediated in part by predisposition to adenomas.
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Effects of glycyrrhizin on biliary transport and hepatic levels of glutathione in rats.
Biopharm Drug Dispos
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The purpose of the current study was to determine whether glycyrrhizin (GL) maintains hepatic glutathione (GSH) levels by inhibiting GSH biliary secretion in normal rats. The effects of glycyrrhizin on hepatic glutathione content, bile flow and biliary secretion of glutathione were examined. Because glutathione is a substrate for multidrug resistance associated protein-2 (Mrp2/ABCC2), the inhibitory effects of GL on Mrp2 in isolated perfused rat liver and in Mrp2-expressing Sf9 membrane vesicles were also examined using the Mrp2 substrate methotrexate (MTX) and estradiol-17-?-glucuronide (E2 17G). The hepatic content of glutathione in rats following GL perfusion (43.7?µmol/l) in isolated liver perfusion and GL intravenous treatment (25?mg/kg) was significantly higher than that for the control. A marked and dose-dependent decrease in the excretion of glutathione was observed. In addition, the secretion rate of MTX was decreased by 57% in isolated liver perfusion in GL-treated rats. Moreover the ATP-dependent uptake of E2 17G by Mrp2 membrane vesicles was decreased by 75.9% in the 20?µm GL group and by 60.5% in the 2?µm GL group. In conclusion, glycyrrhizin increases hepatic glutathione content possibly through inhibition of Mrp2 which then reduces the biliary excretion of glutathione.
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Intratumoral IL-17? cells and neutrophils show strong prognostic significance in intrahepatic cholangiocarcinoma.
Ann. Surg. Oncol.
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Inflammatory reactions at a tumor site have both detrimental and beneficial effects on tumor progression. This study was designed to assess the clinical significance of tumor-infiltrating inflammatory cells in patients with intrahepatic cholangiocarcinoma (ICC).
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Comparison of a lymph node ratio-based staging system with the 7th AJCC system for gastric cancer: analysis of 18,043 patients from the SEER database.
Ann. Surg.
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The American Joint Committee on Cancer (AJCC) staging system for gastric cancer bases N status on absolute number of metastatic nodes, regardless of the number of examined nodes. We examined a modified staging system utilizing node ratio (Nr), the ratio of metastatic to examined nodes.
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Cue-elicited craving in heroin addicts at different abstinent time: an fMRI pilot study.
Subst Use Misuse
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We evaluated the effect of short-term and long-term heroin abstinence on brain responses to heroin-related cues using functional magnetic resonance imaging (fMRI).
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RhoA/ROCK-dependent moesin phosphorylation regulates AGE-induced endothelial cellular response.
Cardiovasc Diabetol
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The role of advanced glycation end products (AGEs) in the development of diabetes, especially diabetic complications, has been emphasized in many reports. Accumulation of AGEs in the vasculature triggers a series of morphological and functional changes in endothelial cells (ECs) and induces an increase of endothelial permeability. This study was to investigate the involvement of RhoA/ROCK-dependent moesin phosphorylation in endothelial abnormalities induced by AGEs.
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A plasma microRNA panel for early detection of colorectal cancer.
Int. J. Cancer
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Colonoscopy remains the standard screening method for detecting colorectal cancer (CRC) at an early stage. However, many people avoid having a colonoscopy because of the fear for its potential complications. Our study aimed to identify plasma microRNAs for preliminarily screening CRC in general population, so that some unnecessary colonoscopies can be avoided. We investigated plasma microRNA expression in 3 independent cohorts including the discovery (n=80), training (n=112) and validation (n=49) phases recruited at 2 medical centers. Microarrays were used for screening 723 microRNAs in 80 plasma samples to identify candidate microRNAs. Quantitative reverse-transcriptase PCR was performed on the 161 training and validation plasma samples to evaluate the candidate microRNAs discovered from microarrays. A logistic regression model was constructed based on the training cohort and then verified by using the validation dataset. Area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified a panel of miR-409-3p, miR-7 and miR-93 that yielded high diagnostic accuracy in discriminating CRC from healthy group (AUC 0.866 and 0.897 for training and validation dataset, respectively). Moreover, the diagnostic performance of the microRNA panel persisted in non-metastasis CRC stages (Dukes A-B, AUC 0.809 and 0.892 for training and validation dataset, respectively) and in metastasis CRC stages (Dukes C-D, AUC 0.917 and 0.865 for training and validation dataset, respectively). In conclusion, our study reveals a plasma microRNA panel that has potential clinical value in early CRC detection and would play a critical role on preliminarily screening CRC in general population. © 2013 Wiley Periodicals, Inc.
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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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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.