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Find video protocols related to scientific articles indexed in Pubmed.
Alcohol-related hospitalisations of trauma patients in Southern Taiwan: a cross-sectional study based on a trauma registry system.
BMJ Open
PUBLISHED: 11-02-2014
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To provide an overview of the demographic characteristics of patients with positive blood alcohol concentration (BAC) and to investigate the performance of brain CT scans in these patients.
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Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells.
Molecules
PUBLISHED: 07-08-2014
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Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.
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Nosocomial extended-spectrum beta-lactamase-producing Klebsiella pneumoniae bacteremia in hemodialysis patients and the implications for antibiotic therapy.
Int. J. Infect. Dis.
PUBLISHED: 05-28-2014
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In the face of increasing treatment options for extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) hemodialysis (HD) access-related bacteremia, the difference in clinical effectiveness between ertapenem and flomoxef remains unclear. We conducted this retrospective study to determine their efficacies and treatment outcomes.
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Two-dimensional hybrid photonic/plasmonic crystal cavities.
Opt Express
PUBLISHED: 04-11-2014
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We present a 2-D plasmonic crystal design with visible band-gap by combining a 2-D photonic crystal with TM band-gap and a silver surface. Simulations show that the presence of the silver surface gives rise to an expanded band-gap. A plasmonic crystal defect cavity with Q ~300 and mode volume ~1.9x10(-2) (?/n) (3) can be formed using our design. The total Q of such a cavity is determined by both the radiative loss of the dielectric component, as well as absorption loss to the metal. We provide design criteria for the optimization of the total Q to allow high radiative or extraction efficiency.
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Optogenetic control of selective neural activity in multiple freely moving Drosophila adults.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-24-2014
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We present an automated laser tracking and optogenetic manipulation system (ALTOMS) for studying social memory in fruit flies (Drosophila melanogaster). ALTOMS comprises an intelligent central control module for high-speed fly behavior analysis and feedback laser scanning (?40 frames per second) for targeting two lasers (a 473-nm blue laser and a 593.5-nm yellow laser) independently on any specified body parts of two freely moving Drosophila adults. By using ALTOMS to monitor and compute the locations, orientations, wing postures, and relative distance between two flies in real time and using high-intensity laser irradiation as an aversive stimulus, this laser tracking system can be used for an operant conditioning assay in which a courting male quickly learns and forms a long-lasting memory to stay away from a freely moving virgin female. With the equipped lasers, channelrhodopsin-2 and/or halorhodopsin expressed in selected neurons can be triggered on the basis of interactive behaviors between two flies. Given its capacity for optogenetic manipulation to transiently and independently activate/inactivate selective neurons, ALTOMS offers opportunities to systematically map brain circuits that orchestrate specific Drosophila behaviors.
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Co-opting sulphur-carrier proteins from primary metabolic pathways for 2-thiosugar biosynthesis.
Nature
PUBLISHED: 03-18-2014
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Sulphur is an essential element for life and is ubiquitous in living systems. Yet how the sulphur atom is incorporated into many sulphur-containing secondary metabolites is poorly understood. For bond formation between carbon and sulphur in primary metabolites, the major ionic sulphur sources are the persulphide and thiocarboxylate groups on sulphur-carrier (donor) proteins. Each group is post-translationally generated through the action of a specific activating enzyme. In all reported bacterial cases, the gene encoding the enzyme that catalyses the carbon-sulphur bond formation reaction and that encoding the cognate sulphur-carrier protein exist in the same gene cluster. To study the production of the 2-thiosugar moiety in BE-7585A, an antibiotic from Amycolatopsis orientalis, we identified a putative 2-thioglucose synthase, BexX, whose protein sequence and mode of action seem similar to those of ThiG, the enzyme that catalyses thiazole formation in thiamine biosynthesis. However, no gene encoding a sulphur-carrier protein could be located in the BE-7585A cluster. Subsequent genome sequencing uncovered a few genes encoding sulphur-carrier proteins that are probably involved in the biosynthesis of primary metabolites but only one activating enzyme gene in the A. orientalis genome. Further experiments showed that this activating enzyme can adenylate each of these sulphur-carrier proteins and probably also catalyses the subsequent thiolation, through its rhodanese domain. A proper combination of these sulphur-delivery systems is effective for BexX-catalysed 2-thioglucose production. The ability of BexX to selectively distinguish sulphur-carrier proteins is given a structural basis using X-ray crystallography. This study is, to our knowledge, the first complete characterization of thiosugar formation in nature and also demonstrates the receptor promiscuity of the A. orientalis sulphur-delivery system. Our results also show that co-opting the sulphur-delivery machinery of primary metabolism for the biosynthesis of sulphur-containing natural products is probably a general strategy found in nature.
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AlgaePath: comprehensive analysis of metabolic pathways using transcript abundance data from next-generation sequencing in green algae.
BMC Genomics
PUBLISHED: 02-26-2014
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Algae are important non-vascular plants that have many research applications, including high species diversity, biofuel sources, and adsorption of heavy metals and, following processing, are used as ingredients in health supplements. The increasing availability of next-generation sequencing (NGS) data for algae genomes and transcriptomes has made the development of an integrated resource for retrieving gene expression data and metabolic pathway essential for functional analysis and systems biology. In a currently available resource, gene expression profiles and biological pathways are displayed separately, making it impossible to easily search current databases to identify the cellular response mechanisms. Therefore, in this work the novel AlgaePath database was developed to retrieve transcript abundance profiles efficiently under various conditions in numerous metabolic pathways.
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Increase of Zinc Finger Protein 179 in Response to CCAAT/Enhancer Binding Protein Delta Conferring an Antiapoptotic Effect in Astrocytes of Alzheimer's Disease.
Mol. Neurobiol.
PUBLISHED: 02-08-2014
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Reactive astrogliosis is a cellular manifestation of neuroinflammation and occurs in response to all forms and severities of the central nervous system (CNS)'s injury and disease. Both astroglial proliferation and antiapoptotic processes are aspects of astrogliosis. However, the underlying mechanism of this response remains poorly understood. In addition, little is known about why activated astrocytes are more resistant to stress and inflammation. CCAAT/enhancer binding protein delta (CEBPD) is a transcription factor found in activated astrocytes that surround ?-amyloid plaques. In this study, we found that astrocytes activation was attenuated in the cortex and hippocampus of APPswe/PS1 E9 (AppTg)/Cebpd (-/-)mice. Furthermore, an increase in apoptotic astrocytes was observed in AppTg/Cebpd (-/-)mice, suggesting that CEBPD plays a functional role in enhancing the antiapoptotic ability of astrocytes. We found that Zinc Finger Protein 179 (ZNF179) was a CEBPD-regulated gene that played an antiapoptotic, but not proliferative, role in astrocytes. The transcriptions of the proapoptotic genes, insulin-like growth factor binding protein 3 (IGFBP3) and BCL2-interacting killer (BIK), were suppressed by ZNF179 via its interaction with the promyelocytic leukemia zinc finger (PLZF) protein in astrocytes. This study provides the first evidence that ZNF179, PLZF, IGFBP3, and BIK contributed to the novel CEBPD-induced antiapoptotic feature of astrocytes.
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Regulation of tumor progression via the Snail-RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma.
Head Neck
PUBLISHED: 02-04-2014
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Background: Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. Methods: An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cell and anti-apoptosis was performed. Results: Long-term NNK exposure dose-dependently enhances migration and invasion with morphological alterations. Furthermore, NNK exposure also up-regulates snail, promotes sphere-forming ability and overexpresses ALDH1, Nanog, OCT4, ABCG2 and MDR1. Conclusions: The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that ?7-nAChR inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC. Head Neck, 2014.
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Inhibitory Effects of the Areca Nut Extract on Expression of Complement Receptors and Fc Receptors in Human Neutrophils.
J. Periodontol.
PUBLISHED: 12-19-2013
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Background: Areca quid chewing increases the prevalence of periodontal diseases. Areca nut extract (ANE) inhibits the phagocytic activity of human neutrophils. This in vitro study investigated the effects of ANE on complement and antibody-opsonized phagocytosis by neutrophils. Expression of complement receptors, Fc receptors and F-actin in ANE-treated neutrophils was also analyzed. Methods: The viability of ANE-treated neutrophils was determined using the propidium iodide staining method. The possible effects of ANE on the expression of complement receptors and Fc receptors were examined using an immunofluorescence staining method followed by flow cytometry and confocal laser scanning microscopy. The phagocytic activity of neutrophils against complement or immunoglobulin (IgG)-opsonized fluorescent beads was analyzed using flow cytometry. Expression of F-actin was determined using confocal laser scanning microscopy. Results: ANE significantly inhibited the production of complement receptor (CR1, CR3 and CR4) and Fc receptors (Fc?RII and Fc?RIII) in a concentration-dependent manner. Treatment of neutrophils with ANE significantly impaired their ability to phagocytose fluorescent beads. ANE also inhibited phagocytosis of fluorescent beads that were opsonized by complement or IgG. Moreover, expression of F-actin was inhibited after ANE treatment. Conclusions: ANE inhibited the complement and IgG-mediated neutrophil phagocytosis which may result from reduction of the expression of complement receptors, Fc receptors and F-actin formation after ANE treatment. The findings suggest that areca nut chewing may jeopardize the defensive functions of neutrophils and affect the periodontal health.
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Heme oxygenase-1 aggravates heat stress-induced neuronal injury and decreases autophagy in cerebellar Purkinje cells of rats.
Exp. Biol. Med. (Maywood)
PUBLISHED: 06-20-2013
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We previously reported that heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain. Heme oxygenase (HO)-1 is a stress protein and can be induced by heat stress (HS). Cerebellar Purkinje cells are selectively vulnerable to heat-induced injury. In this study, we first validated an animal model of HS (38°C for 4 h) in which sustained increase of Purkinje cell injury, HO-1 expression up to 24 h post HS (HS??), and hyperthermia reaching a rectal temperature 41.52 ± 0.32 were observed. In subsequent experiments, we investigated the effects of HO-1 on HS-induced Purkinje cell injury. Rats were divided into four groups: one normothermic control group receiving saline vehicle (1 mL/kg, intraperitoneal [i.p.]) and exposed to 25 for 4 h; and three HS groups receiving saline, or HO-1 inducer haemin (30 mg/kg, i.p.) or HO-1 inhibitor tin protoporphyrin (SnPP, 30 mg/kg, i.p.), respectively, at 12 h prior to HS. HS-induced Purkinje cell injury was further enhanced by HO-1 inducer but attenuated by HO-1 inhibitor as evaluated by immunoreactivity of apoptosis marker (active caspase-3) as well as Fluoro-Jade B histochemistry (staining for degenerating neurons), suggesting a detrimental role of HO-1. Interestingly, the protective autophagy was reduced by HO-1 inducer but enhanced by HO-1 inhibitor as demonstrated by autophagy markers including Beclin-1 and microtubule-associated protein light chain 3 in Purkinje cells. Double immunofluorescent labelling of Beclin-1 or 8-hydroxydeoxyguanosine (an oxidative DNA damage marker) with HO-1 immunoreactivity not only demonstrated their co-localization, but also confirmed that HO-1 negatively regulated Beclin-1 but increased oxidative stress in the same Purkinje cell. Taken together, our results indicate that HO-1 aggravates HS injury in cerebellar Purkinje cells. Our findings shed new light on cell damage mechanisms by HS in central nervous system and may help to provide potential therapeutic foci.
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Postural and muscular responses while viewing different heights of screen.
Int J Occup Saf Ergon
PUBLISHED: 06-14-2013
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This study aimed to examine the effects of visual display terminal (VDT) viewing angle on human postural angle and muscular activity. The participants neck, thoracic bending, and trunk inclination angles; and the activity of sternocleidomastoid, trapezius, splenius capitis, and erector spinae at 5 viewing angles (+40°, +20°, 0°, -20°, and -40°) of a VDT screen were collected for 1 min. This study showed that neck and thoracic bending angles increased with viewing angle, while viewing angle did not significantly affect trunk inclination angle. In addition, the activity of trapezius and erector spinae increased when viewing a higher or lower VDT screen height compared with viewing a horizontal VDT screen height; however, the activity of splenius capitis decreased with viewing angle.
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Comparison of prognostic models for patients with diffuse large B-cell lymphoma in the rituximab era.
Ann. Hematol.
PUBLISHED: 05-25-2013
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Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1?×?10?/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13 %, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies.
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Changing blood lead levels and oxidative stress with duration of residence among Taiwan immigrants.
J Immigr Minor Health
PUBLISHED: 04-06-2013
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Immigrants lack appropriate health care access and other resources needed to reduce their exposure to preventable environmental health risks. Little is known about the impact of lead exposure and oxidative stress among immigrants. Thus, this study was to examine the differences between the blood lead levels (BLLs) and oxidative stress levels of immigrants and non-immigrants, and to investigate the determinants of increased BLLs or oxidative stress levels among immigrants. We collected demographic data of 239 immigrant women and 189 non-immigrant women who resettled in the central area of Taiwan. Each study participant provided blood samples for genotyping and for measuring blood metal levels and oxidative stress. Recent immigrants were at risk for elevated BLLs. Decreased BLLs, malondialdehyde (MDA), and increased blood selenium levels were significantly associated with duration of residence in Taiwan. Elevated BLLs and MDA in recent immigrants may serve as a warning sign for the health care system. The nations health will benefit from improved regulation of living environments, thereby improving the health of immigrants.
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A microwave-assisted fluorescent labeling method for the separation and detection of amphetamine-like designer drugs by capillary electrophoresis.
Forensic Sci. Int.
PUBLISHED: 02-22-2013
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A microwave-assisted fluorescence labeling method for use in CE-LIF (capillary electrophoresis-laser induced fluorescence) is described. Six amphetamine-like designer drugs, namely, o-, m-, p-chloro- and o-, m-, p-fluoro-amphetamine derivatives, were synthesized and used as model compounds. FITC (fluorescein isothiocyanate isomer I) and a blue-laser were used as the fluorescent labeling reagent and excitation source, respectively. When a microwave oven was used, the reaction was complete within ?5 min, while the classical method required at least 20 h (usually, an overnight reaction). A mimic oral fluid sample was obtained by spiking oral fluid from a volunteer with the six standards, and after liquid-liquid extraction and microwave-derivatization, it was possible to process the analytes by CE-LIF within a period of ?10 min; the wavelength of the blue-laser used was 473 nm. For comparison, data obtained using classical methods, including CZE-UV (capillary zone electrophoresis-UV absorbance detection), sweeping-MEKC-UV (micellar electrokinetic chromatography-UV absorbance detection) and LC-Q-TOFMS (liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry) are also reported.
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Areca nut procyanidins ameliorate streptozocin-induced hyperglycemia by regulating gluconeogenesis.
Food Chem. Toxicol.
PUBLISHED: 01-16-2013
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Hepatic gluconeogenesis is a major contributor to blood glucose in diabetes mellitus. Our previous study indicated that areca nut extract enriched with catechin-based procyanidins from oligomers to polymers gave rise to anti-inflammatory effects in vitro and in vivo. Here we have surveyed the molecular features of areca nut procyanidins (ANPs) using quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) and the resulting mass spectrum accurately described ANP from monomer to hexadecamer. Furthermore, the potential of ANP in terms of blood glucose homeostasis was explored using cyclic adenosine monophosphate (cAMP)/dexamethasone stimulated primary mouse hepatocytes and multiple low dose streptozocin (MLD-STZ) treated mice. With the primary hepatocytes, ANP dose-dependently inhibited gluconeogenesis and reduced the mRNA expression of two gluconeogenic key enzymes, phosphoenol-pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Intragastrically feeding of 10mg/kg ANP for 4weeks reduced the levels of fasting blood glucose, PEPCK and G6Pase in MLD-STZ mice. In additional, the level of 5-AMP-activated protein kinase (AMPK) expression showed a trend towards being restored in the ANP treated MLD-STZ-mice. This study indicated that ANP has the potential to improve hyperglycemia by regulating gluconeogenic related kinases in MLD-STZ-mice.
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Oxidative stress and increased formation of vasoconstricting F2-isoprostanes in patients with reversible cerebral vasoconstriction syndrome.
Free Radic. Biol. Med.
PUBLISHED: 01-13-2013
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The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is unknown. Oxidative stress is detrimental to endothelial function and vascular reactivity. We hypothesized that the oxidative stress marker 8-iso-prostaglandin F2?, which is also a potent vasoconstrictor, might contribute to the pathogenesis of RCVS. Recruited participants included 103RCVS patients, 53 patients with primary headache with acute severe attacks, and 54 healthy controls. Subjects recruited prior to 2009 were discovery cohort, whereas those after 2009, replication cohort. Urine samples were obtained from all patients at registration and from 79 patients with RCVS again at remission stage. Urine 8-iso-prostaglandin F2? was analyzed by liquid chromatography-tandem mass spectrometry. Patients with RCVS received magnetic resonance angiography and transcranial color-coded sonography. In RCVS patients, the urine 8-iso-prostaglandin F2? level was higher than that in the other groups in discovery, replication, and combined cohorts (RCVS, 0.29±0.18; primary headache with acute severe attacks, 0.21±0.19; control, 0.18±0.09ng/mg creatinine; P<0.001), and it was positively correlated with the flow velocities of major intracranial arteries, especially within the first week of disease onset (middle cerebral artery, Spearmans correlation coefficient [rs]=0.580, P=0.002; anterior cerebral artery, rs=0.472, P=0.042; posterior cerebral artery, rs=0.457, P=0.022; basilar artery, rs= 0.530, P=0.002). The 8-iso-prostaglandin F2? level decreased from the ictalto remission stage in RCVS patients (0.31±0.21 vs 0.16±0.10ng/mg creatinine, P<0.001). 8-Iso-prostaglandin F2? was higher in patients with RCVS and correlated with the severity of vasoconstrictions. Further studies are required to explore its potential pathogenic role.
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Manganese-catalyzed cross-coupling of thiols with aryl iodides.
Chem Asian J
PUBLISHED: 01-13-2013
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A manganese-catalyzed cross-coupling reaction of thiols with aryl iodides, furnishing aryl thioethers in good to excellent yields has been reported; the system shows good functional group tolerance and enables the sterically demanding aryl iodides to couple with thiols.
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Protein kinase m? is necessary for cocaine-induced synaptic potentiation in the ventral tegmental area.
Biol. Psychiatry
PUBLISHED: 06-22-2011
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Much progress has been made in our understanding of brain regions and specific receptors that are involved in the action of cocaine addiction. Although long-term modifications of mesolimbic reward circuit following cocaine exposure are responsible for cocaine-addicted behaviors, the underlying molecular mechanism at the cellular level is still obscure. Here, we investigated the possible participation of protein kinase M? (PKM?) in synaptic potentiation following cocaine exposure.
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How consumers respond to the behavior of missing a free gift promotion: inaction inertia effect on products offered as free gifts.
J Soc Psychol
PUBLISHED: 06-17-2011
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Inaction inertia describes the phenomenon that an individual is unlikely to act on an attractive opportunity after having bypassed an even more attractive one. The results of two experiments indicate that after missing an initial opportunity to obtain a product as a free gift during a promotional period, the inaction inertia effect reduces the likelihood of consumers buying the product at a discounted price (second, inferior opportunity), particularly if the free gift has a high regular price. Additionally, according to the results of Experiment 2, those consumers are less likely to buy a product that has been offered previously as a free gift when a greater total quantity of the free gift is offered during a promotional period. Moreover, the mediation analysis results indicate that anticipated regret and valuation significantly impact the mediating role of inaction inertia.
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Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes.
Clinics (Sao Paulo)
PUBLISHED: 05-10-2011
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Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection.
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Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factor-?B.
Breast Cancer Res.
PUBLISHED: 03-29-2011
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Heat shock proteins (HSPs) are normally induced under environmental stress to serve as chaperones for maintenance of correct protein folding but they are often overexpressed in many cancers, including breast cancer. The expression of Hsp27, an ATP-independent small HSP, is associated with cell migration and drug resistance of breast cancer cells. Breast cancer stem cells (BCSCs) have been identified as a subpopulation of breast cancer cells with markers of CD24-CD44+ or high intracellular aldehyde dehydrogenase activity (ALDH+) and proved to be associated with radiation resistance and metastasis. However, the involvement of Hsp27 in the maintenance of BCSC is largely unknown.
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Mechanism-based inhibition of cytochrome P450 (CYP)2A6 by chalepensin in recombinant systems, in human liver microsomes and in mice in vivo.
Br. J. Pharmacol.
PUBLISHED: 03-23-2011
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Chalepensin is a pharmacologically active furanocoumarin compound found in rue, a medicinal herb. Here we have investigated the inhibitory effects of chalepensin on cytochrome P450 (CYP) 2A6 in vitro and in vivo.
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Association between areca-stimulated vimentin expression and the progression of head and neck cancers.
Head Neck
PUBLISHED: 03-07-2011
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Areca nut chewing is a common oral habit of Asians that is closely associated with the high incidence of head and neck carcinoma. The purpose of this study was to investigate the impacts of areca nut chewing on neoplastic process of head and neck carcinoma.
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Clinical significance of genome-wide minimally deleted regions in oral squamous cell carcinomas.
Genes Chromosomes Cancer
PUBLISHED: 01-18-2011
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Oral squamous cell carcinoma (OSCC) has the highest rate of increase among male cancers in Taiwan. An understanding of the molecular pathogenesis of this disease as well as the development of prognostic markers for the clinical management of this disease is very important. Thus, a systematic loss of heterozygosity (LOH) analysis was performed to define minimally deleted regions (MDRs) in 63 male OSCCs using 400 polymorphic microsatellite markers. For increasing reliability, genomic DNA was extracted from >90% tumor cells that had been purified by LCM, and only when a microsatellite marker provided LOH information in >30% of the OSCCs was there considered to be successful allelotyping. A correlation of the various MDRs with clinicopathological parameters and prognosis was carried out. In total, 32 MDRs were identified and ten were noted as novel. In addition, six MDRs were found to be associated with cigarette smoking. Among these markers, a loss of MDR c7r2 (7q32.2-q35) was significantly associated with poor disease-free survival (DFS) and ten MDRs were associated with allelic imbalance (AI) in tumors. Among the latter, a loss of MDR c14r1 (14q24.2-q32.12) and c11r1 (11q13.4-q25) had a synergistic effect on poor DFS and were able to reduce further the DFS rate in patients with MDR c7r2 loss. Taken together, the results generated in this study provide new insights that help with exploring the molecular mechanisms associated with OSCC tumorigenesis and cigarette smoking. They also should aid the development of potential prognostic markers for the clinical management of OSCC.
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Insights into the mechanism of Piper betle leaf-induced contact leukomelanosis using C57BL/6 mice as the animal model and tyrosinase assays.
Australas. J. Dermatol.
PUBLISHED: 01-12-2011
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Steamed piper betle leaves (PBL) were once used by many Taiwanese women to treat pigment disorders on the face. Most women claimed a quick, favourable response at first, only to be overcome with facial leukomelanosis later.
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Sorafenib overcomes TRAIL resistance of hepatocellular carcinoma cells through the inhibition of STAT3.
Clin. Cancer Res.
PUBLISHED: 09-30-2010
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Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent. However, many hepatocellular carcinoma (HCC) cells show resistance to TRAIL-induced apoptosis. Here, we report that sorafenib improves the antitumor effect of TRAIL-related agents in resistant HCC.
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Heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain.
Shock
PUBLISHED: 09-09-2010
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Heat stroke (HS) is defined clinically as a condition when core body temperature rises above 40°C and is accompanied by central nervous system abnormalities. In this study, we established a rat model of HS by exposing anesthetized rats to elevated ambient temperature (40°C) until core temperature reaching 40.5°C (HS onset). The rat was immediately removed from heating chamber, allowed recovery for various time periods, and killed for histological and biochemical studies. Our results indicated neuronal shrinkage and pyknosis of the nucleus and sustained up to 12 h recovery time in cerebral cortex. Elevated expression of autophagy-related proteins, including microtubule associated protein light chain 3 and beclin 1 in cortical tissue at various times (3, 6, 12 h) of recovery was observed. In addition, the number of autophagosomes stained by monodansylcadaverine, a specific autophagosome marker, increased after heat exposure but was reduced by pretreatment with 3-methyladenine, an autophagy inhibitor. Furthermore, heat exposure increased neuronal degeneration in cortical tissue, as evidenced by staining with the fluorescent dye Fluoro-Jade B for degenerating neuron. Pretreatment with 3-methyladenine in HS rats aggravated neurodegeneration. Taken together, these results suggest that HS induces autophagy as a protection mechanism against neurodegeneration. Modulation of autophagy may provide a potential therapeutic approach for HS and await further research.
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Areca nut extract induced oxidative stress and upregulated hypoxia inducing factor leading to autophagy in oral cancer cells.
Autophagy
PUBLISHED: 08-19-2010
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Areca (betel) chewing was tightly linked to oral tumorigenesis in Asians. Areca nut was a recently confirmed group I carcinogen and a popular addictive substance used by Asians. Meanwhile, the pathogenetic impact of areca on oral epithelial cells was still unclear. This study investigated the association between the induction of autophagy by areca nut extract (ANE) and the molecular regulation underlying this induction in oral cancer cells. Oral cancer cells were treated with ANE to incite the signaling changes underlying phenotypic alterations. The NFkappaB activation and reactive oxygen species (ROS) genesis were induced by ANE and the NFkappaB activation could be the basis of the ROS genesis. Furthermore, p38 activation and upregulation of MKP-1 phosphatase occurred following ANE treatment. These effects can be inhibited by ROS blockers. ANE treatment induced autophagy among oral cancer cells, which was characterized by LC3-II accumulation, genesis of autophagosomes and the appearance of EGFP-LC3 puncta. This induction was mediated through the activation of p38, MKP-1 and HIF-1alpha. Knockdown of ANE-modulated HIF-1alpha expression reduced autophagy. Blockage of ANE-induced autophagy increased the proportion of oral cancer cells undergoing apoptotic death. This study identified for the first time that ANE modulates a signaling cascade that induces HIF-1alpha expression in oral cancer cells. The eventual induction of autophagy was beneficial to cell survival from ANE-induced apoptosis.
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Quantitative determination of 8-isoprostaglandin F(2?) in human urine using microfluidic chip-based nano-liquid chromatography with on-chip sample enrichment and tandem mass spectrometry.
J Chromatogr A
PUBLISHED: 07-26-2010
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Urinary 8-isoprostaglandin F(2?) (8-isoPGF(2?)) has been reported as an important biomarker to indicate the oxidative stress status in vivo. In order to quantitatively determine the low contents of 8-isoPGF(2?) (in sub- to low ng mL(-1) range) in physiological fluids, a sensitive detection method has become an important issue. In this study, we employed a microfluidic chip-based nano liquid chromatography (chip-nanoLC) with on-chip sample enrichment coupled to triple quadrupole mass spectrometer (QqQ-MS) for the quantitative determination of 8-isoPGF(2?) in human urine. This chip-nanoLC unit integrates a microfluidic switch, a chip column design having a pre-column (enrichment column) for sample enrichment prior to an analytical column for separation, as well as a nanospray emitter on a single polyimide chip. The introduction of enrichment column offers the advantages of online sample pre-concentration and reducing matrix influence on MS detection to improve sensitivity. In this study, the chip-nanoLC consisting of Zorbax 300A SB-C18 columns and Agilent QqQ Mass spectrometer were used for determining 8-isoPGF(2?) in human urine. Gradient elution was employed for effective LC separation and multiple reaction monitoring (MRM) was utilized for the quantitative determination of 8-isoPGF(2?) (m/z 353?193). We employed liquid-liquid extraction (LLE)/solid-phase extraction (SPE) for extracting analyte and reducing matrix effect from urine sample prior to chip-nanoLC/QqQ-MS analysis for determining urinary 8-isoPGF(2?). Good recoveries were found to be in the range of 83.0-85.3%. The linear range was 0.01-2 ng mL(-1) for urinary 8-isoPGF(2?). In addition, the proposed method showed good precision and accuracy for 8-isoPGF(2?) spiked synthetic urine samples. Intra-day and inter-day precisions were 1.8-5.0% and 4.3-5.8%, respectively. The method accuracy for intra-day and inter-day assays ranged from 99.3 to 99.9% and 99.4 to 99.7%, respectively. Due to its rapidity, enhanced sensitivity, and high recovery, this chip-nanoLC/QqQ-MS system was successfully utilized to determine the physiological biomarkers such as 8-isoPGF(2?) in human urine for clinical diagnosis.
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Quantification of urinary 8-iso-prostaglandin F2alpha using liquid chromatography-tandem mass spectrometry during cardiac valve surgery.
J. Clin. Lab. Anal.
PUBLISHED: 07-14-2010
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Oxidative stress is an unavoidable event during many complex surgical procedures. 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a reliable biomarker for the evaluation of oxidative stress in vivo. The aim of this study is to develop simple and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the detection of urinary 8-iso-PGF(2alpha) in samples collected from patients who received a cardiopulmonary bypass (CPB) during cardiac valve surgery. Urine samples of 14 patients with cardiac valve diseases were collected before, during, and after CPB. The level of 8-iso-PGF(2alpha) was detected via selected-reaction monitoring triple quadrupole MS/MS and the result was compared with 12 healthy volunteers. The methods detection limit (3S/N) was 0.25 pg for 8-iso-PGF(2alpha), with a linear working range of 0.25-20 ng/ml. For patients with cardiac valve disease, the 8-iso-PGF(2alpha) levels before the bypasses were the same as those of healthy individuals (P>0.05) and the 8-iso-PGF(2alpha) levels during and after CPB were significantly higher than those before the bypasses (P<0.05). In conclusion, we present a simple and specific protocol for LC-MS/MS quantification of urinary 8-iso-PGF(2alpha) collected during CPB. Using this technique, it would be feasible to assess the levels of oxidative stress during cardiac surgery and thereby helpful for the management of oxidative injury.
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p16(INK4A) promoter hypermethylation is associated with invasiveness and prognosis of oral squamous cell carcinoma in an age-dependent manner.
Oral Oncol.
PUBLISHED: 05-18-2010
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Oral squamous cell carcinoma (OSCC) is a common cancer worldwide that is highly lethal due to its recurrence and metastasis. Our candidate-based study aimed to link promoter CpG island hypermethylation to OSCC risk assessment. We examined the promoter hypermethylation status of p16(INK4A) (p16), glutathione S-transferase pi (GSTP1), O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase 1 (DAPK1), RAS-association domain family 1, isoform A (RASSF1A), and E-cadherin (CDH1) genes in OSCC tumors. Quantitative methylation-specific PCR analysis showed a significant increase in promoter hypermethylation of p16 and CDH1 in OSCC tumors relative to paired non-tumorous tissues. The mean age of patients with hypermethylated p16 was lesser than those without (P=0.027). Multiple logistic regression predicted patients with hypermethylated p16 have higher risks of lymph node invasion (adjusted OR=6.21, P=0.030) in young patients and distant metastasis (adjusted OR=19.23, P=0.007) in older patients. Moreover, p16 promoter hypermethylation was significantly associated with shortened disease-free survival (P=0.034) in older patients. Our results suggested that p16 hypermethylation was associated with early incidence of OSCC, increased lymph node invasion in young patients, and poor prognosis in older patients. Further, p16 hypermethylation may also be implicated in age-related tumor invasion in carcinogenesis.
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Effect of beta-hydroxy-beta-methylbutyrate on protein metabolism in bed-ridden elderly receiving tube feeding.
Asia Pac J Clin Nutr
PUBLISHED: 05-13-2010
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Malnutrition and muscle loss are common in bed-ridden elderly nursing home residents. Supplementation of beta-hydroxy-beta-methylbutyrate (HMB) has been shown to prevent muscle loss in several catabolic conditions. The aim of this study was to investigate the effect of HMB supplementation on body composition and protein metabolism in bed-ridden elderly nursing home residents receiving tube feeding. The subjects were randomly assigned to HMB (n=39, 2 g/d) or control group (n=40). Anthropometry measurements, blood sampling, and 24-hr urine collection were performed on the day before and 14 days after the start of the study. A subgroup of subjects (HMB: n=19, control: n=20) continued the study for another 14 days. Changes in body weight and BMI were not significantly different between the groups after 14 or 28 days after controlling for baseline BMI. Blood urea nitrogen significantly decreased in the HMB group, while it remained unchanged in the control group after 14 days. Urinary urea nitrogen excretion significantly decreased in the HMB group, while it showed a trend of increase in the control group after 14 and 28 days, respectively. Changes in blood urea nitrogen and urinary urea nitrogen excretion were significantly different between the groups after controlling for baseline BMI. This study suggested that HMB supplementation for 2-4 weeks could reduce muscle breakdown in bed-ridden elderly nursing home residents receiving tube feeding.
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Stimulatory effects of areca nut extracts on prostaglandin E2 production by human polymorphonuclear leukocytes.
J. Periodontol.
PUBLISHED: 05-01-2010
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Areca quid chewing increases the prevalence of periodontal diseases. Areca nut extract (ANE) inhibits the defensive functions of human polymorphonuclear leukocytes (PMNs). This in vitro study investigates the effects of ANE on the production of cyclooxygenase (COX)-2 and the inflammatory mediator prostaglandin E(2) (PGE(2)) by PMNs.
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miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma.
Cancer Res.
PUBLISHED: 02-09-2010
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MicroRNAs (miRNA) are endogenously expressed noncoding RNAs with important biological and pathological functions that are yet to be fully defined. This study investigated alterations in miRNA expression in head and neck squamous cell carcinoma (HNSCC), the incidence of which is rising throughout the world. Initial screening and subsequent analysis identified a panel of aberrantly expressed miRNAs in HNSCC tissues, with miR-31 among the most markedly upregulated. Ectopic expression of miR-31 increased the oncogenic potential of HNSCC cells under normoxic conditions in cell culture or tumor xenografts. Conversely, blocking miR-31 expression reduced the growth of tumor xenografts. The in silico analysis suggested that miR-31 may target the 3 untranslated region (UTR) of factor-inhibiting hypoxia-inducible factor (FIH), a hypoxia-inducible factor (HIF) regulatory factor that inhibits the ability of HIF to act as a transcriptional regulator under normoxic conditions. In support of this likelihood, miR-31 expression repressed FIH expression and mutations within the predictive miR-31 target site in the FIH 3 UTR abrogated FIH repression. Furthermore, miR-31 expression increased HIF transactivation activity. We found that FIH suppressed oncogenic phenotypes under normoxic conditions and that this activity was abrogated by functional mutations. Lastly, increased miR-31 expression was correlated with decreased levels of FIH in tumor tissues. Our findings suggest that miR-31 contributes to the development of HNSCC by impeding FIH to activate HIF under normoxic conditions.
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The implication of osteopontin (OPN) expression and genetic polymorphisms of OPN promoter in oral carcinogenesis.
Oral Oncol.
PUBLISHED: 01-22-2010
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Osteopontin (OPN) is an extracellular matrix protein in hard tissues. The polymorphism in promoter region of OPN gene correlates to different gene expression and might implicate potential roles in tumor progression and metastasis. Immunohistochemistry (IHC) was utilized to detect the OPN expression in 58 oral squamous cell carcinoma (OSCC) tissues and adjacent normal oral mucosa. The differential OPN expression was further analyzed in relation to clinico-pathological features. Genomic DNA was obtained from isolated leukocytes of blood samples of OSCC patients (n=100), and healthy individuals (n=97) from Taiwan. The OPN gene polymorphism was analyzed by direct sequencing. Our result showed OPN expression was significantly higher in OSCC tissues than in the paired adjacent normal tissues (p<0.01). The expression of OPN was significantly associated with nodal metastasis and the more advanced clinical stage (p<0.05). More prevalent -156 insGG/insGG genotype and -443 T/T genotype was found in OSCC patients (p<0.05). A significant difference in -443T/-156GG/-66T and -443C/-156G/-66T haplotypes between OSCC and controls (p<0.05) was also noted. The OPN expression in tumor tissues significantly correlated with -156 insGG/insGG and -156 G/G+insGG/G genotypes (p<0.05). The conclusion is tissue OPN expression correlates to OSCC progression. -156 insGG/insGG genotype is associated with OSCC susceptibility and higher OPN expression.
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Generic lossless visible watermarking--a new approach.
IEEE Trans Image Process
PUBLISHED: 01-19-2010
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A novel method for generic visible watermarking with a capability of lossless image recovery is proposed. The method is based on the use of deterministic one-to-one compound mappings of image pixel values for overlaying a variety of visible watermarks of arbitrary sizes on cover images. The compound mappings are proved to be reversible, which allows for lossless recovery of original images from watermarked images. The mappings may be adjusted to yield pixel values close to those of desired visible watermarks. Different types of visible watermarks, including opaque monochrome and translucent full color ones, are embedded as applications of the proposed generic approach. A two-fold monotonically increasing compound mapping is created and proved to yield more distinctive visible watermarks in the watermarked image. Security protection measures by parameter and mapping randomizations have also been proposed to deter attackers from illicit image recoveries. Experimental results demonstrating the effectiveness of the proposed approach are also included.
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Differentiation of pancreatic acinar cells to hepatocytes requires an intermediate cell type.
Gastroenterology
PUBLISHED: 01-06-2010
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The appearance of hepatic foci in pancreas has been well-documented in animal experiments and in patients with pancreatic cancer. We previously demonstrated that transdifferentiation of pancreatic exocrine cells to hepatocytes required members of the CCAAT enhancer binding protein family. Although the molecular basis of hepatic transdifferentiation is understood, the early cellular events remain to be defined.
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Safety evaluation of disposable baby diapers using principles of quantitative risk assessment.
J. Toxicol. Environ. Health Part A
PUBLISHED: 12-23-2009
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Baby diapers are complex products consisting of multiple layers of materials, most of which are not in direct contact with the skin. The safety profile of a diaper is determined by the biological properties of individual components and the extent to which the baby is exposed to each component during use. Rigorous evaluation of the toxicological profile and realistic exposure conditions of each material is important to ensure the overall safety of the diaper under normal and foreseeable use conditions. Quantitative risk assessment (QRA) principles may be applied to the safety assessment of diapers and similar products. Exposure to component materials is determined by (1) considering the conditions of product use, (2) the degree to which individual layers of the product are in contact with the skin during use, and (3) the extent to which some components may be extracted by urine and delivered to skin. This assessment of potential exposure is then combined with data from standard safety assessments of components to determine the margin of safety (MOS). This study examined the application of QRA to the safety evaluation of baby diapers, including risk assessments for some diaper ingredient chemicals for which establishment of acceptable and safe exposure levels were demonstrated.
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No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes.
J. Nutr. Biochem.
PUBLISHED: 10-23-2009
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Arginine supplementation has been shown to alleviate endothelial dysfunction and improve exercise performance through increasing nitric oxide production in patients with cardiopulmonary diseases. In addition, arginine supplementation could decrease accumulations of lactate and ammonia, metabolites involved in development of muscular fatigue. The aim of this study was to investigate the effect of short-term arginine supplementation on performance in intermittent anaerobic exercise and the underlying mechanism in well-trained male athletes. Ten elite male college judo athletes participated with a randomized crossover, placebo-controlled design. The subjects consumed 6 g/day arginine (ARG trial) or placebo (CON trial) for 3 days then performed an intermittent anaerobic exercise test on a cycle ergometer. Blood samples were collected before supplementation, before and during exercise and 0, 3, 6, 10, 30 and 60 min after exercise. ARG trial had significantly higher arginine concentrations than CON trial at the same time point before, during and after exercise. In both trials, nitrate and nitrite concentration was significantly higher during and 6 min after exercise comparing to the basal concentration. The increase in nitrate and nitrite concentration during exercise in both trials was parallel to the increase in plasma citrulline concentrations. There was no significant difference between the 2 trials in plasma nitrate and nitrite, lactate and ammonia concentrations and peak and average power in the exercise. The results of this study suggested that short-term arginine supplementation had no effect on nitric oxide production, lactate and ammonia metabolism and performance in intermittent anaerobic exercise in well-trained male athletes.
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Importance of cyclooxygenase 2-mediated low-grade inflammation in the development of fructose-induced insulin resistance in rats.
Chin J Physiol
PUBLISHED: 09-22-2009
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This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.
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Development of spray deposition/MALDI-TOFMS and its application to the rapid screening of hydrolysis products derived from nitrogen mustards.
Anal Sci
PUBLISHED: 07-18-2009
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A novel method for preparing samples for use in MALDI-TOFMS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) is described. Seven hydrolysis products derived from nitrogen mustards and CHCA (alpha-cyano-4-hydroxycinnamic acid) were selected as model compounds and the matrix, respectively. A capillary atomizer was used for evaporative and spray deposition of the sample/matrix solution, leading to the formation of a freestanding film that coated and accumulated on the MALDI substrate (i.e., sample plate). Compared to the traditional method for MALDI, which involves the production of dried droplets, the surface roughness was reduced, resulting in the accumulation of the sample-doped matrix on the sample plate. This resulted in an increase in the limit of detection of 1 - 2 orders of magnitude. In order to compare the structures of the sample-doped matrices obtained by the traditional dried droplet method versus the spray deposition method (developed in this study), the matrices were examined by SEM (scanning electron microscopy). The design of the capillary atomizer and details of the experimental conditions are reported. The application of this method to the above seven degradation products was successful, suggesting that it has great potential for use as a routine monitoring tool.
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Effects of Areca catechu L. containing procyanidins on cyclooxygenase-2 expression in vitro and in vivo.
Food Chem. Toxicol.
PUBLISHED: 07-06-2009
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Polyphenols are widely distributed in plants and known for antioxidant and anti-inflammatory properties. Areca nut, rich in polyphenols, is the major component of betel quid and we have previously shown that the extract of areca nut can induce oxidative stress in vitro. In this study, we have further pinpointed that areca nut extract (ANE) contains catechin based procyanidins which range from dimers to decamers and polymers; this was carried out by HPLC and electrospray ionization/mass spectrometry (ESI/MS). To quantify their antioxidant potential, oligomeric and polymeric procyanidins of ANE were separated and evaluated using the Trolox equivalent antioxidant capacity (TEAC) assay. The results clearly demonstrated that the antioxidant capacity of the ANE procyanidins increased with the degree of polymerization. The anti-inflammatory potential of ANE was also tested using 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated human oral cancer SAS cells. ANE inhibited TPA-induced cyclooxygenase-2 (COX-2) protein expression at low doses, which correlated with the inhibition of ERK phosphorylation in the SAS cells. Furthermore, feeding rats with ANE at 1 and 10mg/kg/day for 5days significantly repressed carrageenan-induced inflammatory exudates and PGE(2) formation. In conclusion, ANE, which contains catechins based oligomeric and polymeric procyanidins, regulates COX-2 expression in vitro and possess anti-inflammatory potential in vivo.
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Simultaneous separation and detection of 18 phenethylamine/tryptamine derivatives by liquid chromatography-UV absorption and -electrospray ionization mass spectrometry.
Anal Sci
PUBLISHED: 06-18-2009
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The optimal conditions for the separation and detection of a mixture of 18 phenethylamine/tryptamine derivatives were determined, using liquid chromatography/UV-absorption (LC/UV) and liquid chromatography/electrospray ionization mass spectrometry (LC/ESI MS) methods, respectively. Complete separation could be achieved within approximately 25 min using gradient elution (A, 0.1% formic acid aqueous solution/pH 2.5; B, acetonitrile). The limit of detection (LOD at S/N = 3) obtained by LC/UV-absorption (absorption wavelength, 280 nm) was in the range from 0.3 to 3 microg/mL. In contrast, when the LC/ESI MS method was used, the LODs for primary, secondary and tertiary amines were in the ranges 0.1-3.0, 0.1-0.2, and 0.05-1.8 microg/mL, respectively. The lower LOD obtained for a tertiary amine can be attributed to the fact that its ionization efficiency (during the ESI process) is better than the others. In order to improve the LOD of a primary/secondary amine, a derivatization procedure was used in which the chemical structure was altered to a secondary/tertiary amine, via a reaction with acetic anhydride. As a result, the LODs for primary/secondary amines could be significantly improved. The characteristic mass fragmentations of the 18 phenethylamine/tryptamine derivatives, as well as the products of the reaction with acetic anhydride, were investigated, and the data were reported. A urine sample was obtained by spiking urine from a volunteer with the 18 derivatives, and after liquid-liquid extraction the sample was examined by LC/UV and LC/ESI MS, respectively. The extraction procedures used for the urine sample and the experimental conditions for the separation and detection were optimized.
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Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation.
J. Oral Pathol. Med.
PUBLISHED: 05-28-2009
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In Taiwan, it is well documented that cigarette smoking and areca nut chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role of phosphorylated Akt (p-Akt) in oral carcinogenesis induced by nicotine and alkaline environments was investigated.
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Detection and screening of oral cancer and pre-cancerous lesions.
J Chin Med Assoc
PUBLISHED: 05-27-2009
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Oral cancer is a fatal disease, accounting for the fourth highest incidence of malignancy in males and the seventh in females in Taiwan. The relatively high prevalence of oral cancer in Taiwan is mainly because there is a high-risk group of 2.5 million people with the habit of smoking and betel nut chewing. Unfortunately, 50% of new cases in our medical center who present with TNM stage III or IV lesions have a shorter than 5-year survival after treatment. This highlights the need for: (1) early treatment of fresh oral cancer cases; (2) screening of the high-risk population to detect new lesions; (3) careful follow-up of cases after treatment; and (4) detection of occult early neck nodal adenopathy in surgical cases. It is generally accepted that prevention and screening of oral cancer are equally important to treatment due to its location. In this review article, we describe the nature of oral cancer and highlight the various conventional and novel methods of screening for this disease and ongoing important related research. Related literature is reviewed and future work that needs to be done is detailed.
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Human single-donor composite skin substitutes based on collagen and polycaprolactone copolymer.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-17-2009
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The development and characterization of an enhanced composite skin substitute based on collagen and poly(epsilon-caprolactone) are reported. Considering the features of excellent biocompatibility, easy-manipulated property and exempt from cross-linking related toxicity observed in the 1:20 biocomposites, skin substitutes were developed by seeding human single-donor keratinocytes and fibroblasts alone on both sides of the 1:20 biocomposite to allow for separation of two cell types and preserving cell signals transmission via micro-pores with a porosity of 28.8 +/- 16.1 microm. The bi-layered skin substitute exhibited both differentiated epidermis and fibrous dermis in vitro. Less Keratinocyte Growth Factor production was measured in the co-cultured skin model compared to fibroblast alone condition indicating a favorable microenvironment for epidermal homeostasis. Moreover, fast wound closure, epidermal differentiation, and abundant dermal collagen deposition were observed in composite skin in vivo. In summary, the beneficial characteristics of the new skin substitutes exploited the potential for pharmaceutical screening and clinical application.
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Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation.
J. Hepatol.
PUBLISHED: 04-24-2009
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Previously we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. Here we report that combined treatment with sorafenib and bortezomib shows synergistic effects in HCC.
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Performance of phosphoric acid activated montmorillonite as buffer materials for radioactive waste repository.
J. Hazard. Mater.
PUBLISHED: 04-09-2009
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In this study, the performance of phosphoric acid activated montmorillonite (PAmmt) was evaluated by cesium ions adsorption experiments. The PAmmt samples were obtained by activating with 1, 3 and 5 mol L(-1) of phosphoric acid, respectively under reflux for 3, 12, and 24h. Experimental results demonstrated that the treatment of raw K-10 montmorillonite with phosphoric acid increased the materials affinity for Cs uptake and no significant amount of suspension solids were produced. A relatively insignificant variation in the CEC value was observed. Furthermore, PAmmt also showed high adsorption selectivity toward Cs ions. The improved sorptive properties were mainly related to the increased surface area and the relatively higher surface charge density. Increased specific surface area was the resulted from partial decomposition of lamellar structure of mmt; while the higher surface charge density was caused by the protonation of octahedral Al-OH sites during the acid activation. Generally speaking, stronger acid concentration and longer activation times would produce relatively more decomposed PAmmt particles. However, as the activation exceeds 3h, the precipitation of Si(4+) would passivate PAmmt against further acid attacks. Based upon our results, acid activation by phosphoric acid could produce PAmmt samples with high sorption capacity and selectivity, and good structural integrity, which are beneficial to be used at radioactive waste repository.
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Asb6 upregulation by Areca nut extracts is associated with betel quid-induced oral carcinogenesis.
Oral Oncol.
PUBLISHED: 02-28-2009
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Betel quit (BQ) chewing is a popular habit, especially in southern and southeastern Asia. Areca nut extracts (ANE), the major components of BQ, have been documented to induce reactive oxygen species, and consequently to cause genetic damage. ANE usage is tightly linked to oral cancer; however, the details of the molecular mechanism that results in carcinogenesis remain unclear. Previously, we successfully established HaCaT cells surviving from the long-term exposure of sublethal doses of ANE (Lai KC, Lee TC. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutat Res 2006;599:66-75). Here, we identified the upregulation of Asb6, a coupling protein to the APS adapter protein, which is involved in insulin signaling for glucose transportation, of normal keratinocytes and oral cancer cells under ANE treatment. Immunohistochemical analyses of Asb6 on oral squamous cell carcinoma (OSCC) tissues (n=57) demonstrated the positive correlation between Asb6 upregulation (cancerous tissues versus adjacent normal tissues) and clinicopathological features. We showed that the combination of ANE-enhanced Asb6 expression in vitro and Asb6 upregulation in OSCC patients leads to poor survival status. In conclusion, our results suggest that upregulated Asb6 could act as a prognostic marker for oral cancer.
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Determination of nitroaromatic explosives residue at military shooting ranges using a sweeping-MEKC method.
Electrophoresis
PUBLISHED: 02-21-2009
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We report on the application of sweeping-MEKC, for the first time, using the Environmental Protection Agency Method 8330 stock standard (a mixture of 14 explosives). The use of a traditional MEKC mode provided the LODs (at S/N=3) ranging from 1.5 to 2.9 microg/mL for the 14 explosives standards, which were improved by as low as 3.1-6.5 ng/mL when a sweeping-MEKC technique was used. A set of 21 soil samples were collected from surface soil at military shooting ranges located at Kinmen County in Taiwan, and the findings showed that hexahydro-1,3,5-trini-tro-1,3,5-triazine and 2,4,6-trinitrotoluene made up the explosives residue present at the highest concentrations. This study is very useful for determining current levels of explosives residue and as a reference for making appropriate recommendations concerning future site characterization techniques.
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Highly oligomeric procyanidins from areca nut induce lymphocyte apoptosis via the depletion of intracellular thiols.
Toxicol In Vitro
PUBLISHED: 01-16-2009
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Procyanidins are plant-derived polyphenolic compounds possessing a variety of biological activities, such as immunomodulation, and induction of tumor cell apoptosis. We previously reported that total extract of areca nut exhibited a suppressive effect on the metabolic activity and cytokine expression in normal splenic lymphocytes. As areca nut contains a rich amount of polyphenols, the objective of the present study was to investigate the pro-apoptotic effect of polyphenol-enriched areca nut extract (PANE) and its fractionated oligomeric procyanidins in splenic lymphocytes. Our data showed that PANE markedly induced lymphocyte apoptosis in a concentration- and time-dependent manner. Notably, the fractionated oligomeric procyanidins from pentamers to decamers were active in inducing the apoptosis, whereas monomers to tetramers were inactive. In addition, a marked diminishment in the level of intracellular thiols was revealed in lymphocytes treated with pentamers to decamers. Pretreatment with N-acetyl-L-cysteine, a precursor of glutathione, resulted in significant attenuation of both apoptosis and thiol diminishment induced by areca procyanidins. Taken together, our results indicated that highly oligomeric procyanidins derived from areca nut exhibited a chain length-dependent pro-apoptotic effect in primary lymphocytes, which is mediated, at least in part, by the diminishment of intracellular thiols.
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Involvement of the mitochondrion-dependent pathway and oxidative stress in the apoptosis of murine splenocytes induced by areca nut extract.
Toxicol In Vitro
PUBLISHED: 01-16-2009
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Areca quid chewing is a major risk factor for oral submucous fibrosis and oral cancer. Clinical evidence suggests that the pathophysiology of the oral diseases is closely associated with immune deterioration. The objective of the present studies was to investigate the pro-apoptotic effect of areca nut extract (ANE) in lymphocytes. Exposure of naïve splenic lymphocytes to ANE significantly enhanced apoptosis in a time- and concentration-dependent manner. Results from Hoechst staining confirmed the morphological features characteristic of apoptosis in ANE-treated cells. ANE treatment induced the depolarization of mitochondrial membrane potential (Deltapsi(m)), which preceded the occurrence of apoptosis. In parallel with the disruption of Deltapsi(m), ANE induced the release of cytochrome c, and the activation of caspase-9, indicating the activation of the mitochondrion-dependent pathway. Moreover, an increased level in the intracellular reactive oxygen species was detected in ANE-treated lymphocytes undergoing apoptosis. ANE-mediated apoptosis, caspase-9 activation and ROS production, but not Deltapsi(m) depolarization, were partially but significantly attenuated in the presence of the antioxidant N-acetyl-L-cysteine (NAC). Collectively, these results demonstrated the pro-apoptotic effect of ANE in primary lymphocytes, which was mediated, at least in part, by the activation of the mitochondrion-dependent pathway and oxidative stress.
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Optimization of separation and online sample concentration of N,N-dimethyltryptamine and related compounds using MEKC.
J Sep Sci
PUBLISHED: 01-13-2009
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The optimal separation conditions and online sample concentration for N,N-dimethyltryptamine (DMT) and related compounds, including alpha-methyltryptamine (AMT), 5-methoxy-AMT (5-MeO-AMT), N,N-diethyltryptamine (DET), N,N-dipropyltryptamine (DPT), N,N-dibutyltryptamine (DBT), N,N-diisopropyltryptamine (DiPT), 5-methoxy-DMT (5-MeO-DMT), and 5-methoxy-N,N-DiPT (5-MeO-DiPT), using micellar EKC (MEKC) with UV-absorbance detection are described. The LODs (S/N = 3) for MEKC ranged from 1.0 1.8 microg/mL. Use of online sample concentration methods, including sweeping-MEKC and cation-selective exhaustive injection-sweep-MEKC (CSEI-sweep-MEKC) improved the LODs to 2.2 8.0 ng/mL and 1.3 2.7 ng/mL, respectively. In addition, the order of migration of the nine tryptamines was investigated. A urine sample, obtained by spiking urine collected from a human volunteer with DMT, was also successfully examined.
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Sulfotransferase 1A1 haplotypes associated with oral squamous cell carcinoma susceptibility in male Taiwanese.
Carcinogenesis
PUBLISHED: 01-06-2009
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We have previously demonstrated that betel quid containing safrole induced DNA adducts are highly associated with the development of oral squamous cell carcinoma (OSCC) in Taiwan. Sulfotransferase (SULT) is essential for the formation of these adducts. To elucidate the effects of SULT1A1 haplotypes on OSCC susceptibility, 160 male OSCC cases and 218 age- and sex-matched controls were screened for single-nucleotide polymorphisms within the coding region of SULT1A1 by sequencing. We found that 445C>T (His149Tyr) and 507C>T polymorphisms were significantly associated with increased risk of OSCC. Based on the genotype analysis, haplotypes were constructed for 445C>T (His149Tyr), 507C>T, 600G>C and 638G>A (Arg213His) using GENECOUNTING software. After adjustment for age, cigarette smoking and betel quid chewing, we found that haplotype c containing 445C>T (His149Tyr), 507C>T or 600G>C but not 638G>A (Arg213His) variant was significantly associated with increased risk of OSCC (odds ratio, 3.24; 95% confidence interval, 1.57-6.68) when compared with the haplotype a (wild-type). We analyzed the activity in sulfonation of 2-naphthol and 1-hydroxysafrole of recombinant His149Tyr (445C>T) variant, which led to 51 and 33% reduced activity, respectively; Arg213His (638G>A) variant led to 72 and 54% reduced activity, respectively, when compared with the wild-type. Taken together, haplotype analysis provides a novel evaluation of the SULT1A1 gene as a risk modifier on environmental carcinogen in OSCC and the association of SULT1A1 haplotypes with the risk of OSCC might be modified by betel quid chewing.
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Factors influencing weight gain in an Asian population of psychiatric inpatients: A retrospective study in Taiwan.
Asia Pac Psychiatry
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The aim of this study was to investigate the factors associated with weight gain by psychiatric inpatients in short-term treatment.
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Image quality assessment using multi-method fusion.
IEEE Trans Image Process
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A new methodology for objective image quality assessment (IQA) with multi-method fusion (MMF) is presented in this paper. The research is motivated by the observation that there is no single method that can give the best performance in all situations. To achieve MMF, we adopt a regression approach. The new MMF score is set to be the nonlinear combination of scores from multiple methods with suitable weights obtained by a training process. In order to improve the regression results further, we divide distorted images into three to five groups based on the distortion types and perform regression within each group, which is called "context-dependent MMF" (CD-MMF). One task in CD-MMF is to determine the context automatically, which is achieved by a machine learning approach. To further reduce the complexity of MMF, we perform algorithms to select a small subset from the candidate method set. The result is very good even if only three quality assessment methods are included in the fusion process. The proposed MMF method using support vector regression is shown to outperform a large number of existing IQA methods by a significant margin when being tested in six representative databases.
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The interactive effects of selenomethionine and methylmercury on their absorption, disposition, and elimination in juvenile white sturgeon.
Aquat. Toxicol.
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Selenium (Se) and mercury (Hg) are prevalent pollutants of industrialized watersheds. However, when co-administered, Se has protective effects on organisms from Hg. The mechanism is not fully understood, but it is thought that Se reduces Hg availability, either by forming biologically inert complexes and/or associating with selenoproteins. Despite concerns with aquatic contaminations, relatively little information is available on the interaction in aquatic organisms. In the present study, the interactive effects of Se and Hg on their absorption, disposition, and elimination were examined in juvenile white sturgeon, a benthic fish species at high risk to exposures of both contaminants. Selenium and Hg were provided as L-selenomethionine (SeMet) and methylmercury (MeHg), respectively. Groups of 10 sturgeon were orally intubated with a single dose of either 0 (control), SeMet (500 ?g Se/kg body weight; BW), MeHg (850 ?g Hg/kg BW), or their combination (Se/Hg; 500 ?g Se/kg and 850 ?g Hg/kg BW). The blood was repeatedly sampled and urine collected from the fish, over a 48 h post intubation period. At 48 h, the fish were sacrificed for Se and Hg tissue concentration and distribution. The co-administration of SeMet and MeHg significantly (p<0.05) lowered blood concentrations of both Se and Hg and tissue Se concentrations. Similarly, assimilation of Se and Hg was also reduced significantly. The interaction has a more quantitative effect on Se metabolism because the reduction in the overall tissue Se is a consequence of reduced Se absorption at the gut and not from the metabolic effects after absorption. In contrast, given the pulse increase in blood Hg concentration, tissue redistribution, and increased urinary elimination, the interactive effect on tissue Hg concentration is likely to be post-absorption. Even in the absence of exogenous SeMet, Se and Hg co-accumulated in tissue at a Se:Hg molar ratio greater than 1. Thus, similar to mammals, maintaining at least a 1:1 molar ratio of Se and Hg is of great physiological importance in the white sturgeon. Interestingly, SeMet did not divert Hg from the brain. Allocation of Se from the kidneys may have occurred in order to maintain the high Se:Hg molar ratios in the brain of white sturgeon. In the current study, the combined use of kinetic analysis and that of the conventional approach of measuring tissue concentration changes provided a comprehensive understanding of the interactive effect of SeMet and MeHg on their respective metabolic processes in juvenile white sturgeon.
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Rapid screening and determination of 4-chloroamphetamine in saliva by paper spray-mass spectrometry and capillary electrophoresis-mass spectrometry.
Electrophoresis
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A novel drug-screening system, consisting of paper spray-MS (PS-MS) and a CE-ESI-MS method was developed. This system can be easily switched either to PS-MS for rapidly screening samples or to the traditional CE-ESI-MS method for separation and to obtain detailed mass spectral information, while sharing the same mass spectrometer. In the former case, when a sharp (15°-tip) chromatography paper was used, the optimized distance from the paper tip to the mass inlet was 7.7 mm, whereas the optimized distance for the CE-ESI tip was ?13.5 mm. Using 4-chloroamphetamine as a model compound, the LODs for PS-MS and CE-ESI-MS were determined to ?0.1 and 0.25 ppm, respectively. Comparisons of results obtained using PS-MS and CE-ESI-MS and the experimental conditions are described.
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Rapid screening and determination of designer drugs in saliva by a nib-assisted paper spray-mass spectrometry and separation technique.
J Sep Sci
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A method for the rapid screening and determination of amphetamine-type designer drugs in saliva by a novel nib-assisted paper spray-mass spectrometry procedure is described. Under optimized conditions, the limit of detections for amphetamine derivatives (model samples: o-, m-, p-chloroamphetamine and o-, m-, p-fluoroamphetamine, respectively) were determined to 0.1 ?g/mL by the nib-assisted paper spray-mass spectrometry method. This method is easier and has a higher sensitivity than similar methodologies, including atmospheric pressure/matrix-assisted laser desorption ionization mass spectrometry and electrospray-assisted laser desorption ionization/mass spectrometry. Data obtained using more classical separation methods, including liquid chromatography and capillary electrophoresis, are also reported.
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Patients with diffuse large B cell lymphoma in partial response or stable disease after first-line R-CHOP: the prognostic value of the absolute lymphocyte count and impact of autologous stem cell transplantation.
Ann. Hematol.
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Certain portions of patients with diffuse large B cell lymphoma (DLBCL) do not achieve a complete remission after first-line rituximab combining chemotherapy. This retrospective study aimed to characterize the outcome of patients with DLBCL that achieved partial remission or had stable disease after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). The effects of subsequent treatments and factors associated with event-free survival (EFS) after second-line treatments were analyzed. A total of 103 patients were enrolled and 81 (76.8 %) patients received intensive chemotherapy, whereas the others (23.2 %) received either palliative chemotherapy or supportive care post first-line treatment. Patients receiving intensive chemotherapy had significantly higher EFS (median 7.9 months) than the others; 28 (34.6 %) patients in this group received autologous stem cell transplantation (ASCT), which may have further improved the EFS. An International Prognostic Index (IPI) >2 and absolute lymphocyte count (ALC) at diagnosis <1,000/UL were significant prognostic factors associated with worse EFS. The survival advantage of ASCT remained significant after adjustment for these factors. The results suggest intensive chemotherapy plus ASCT may provide modest disease control in patients with DLBCL who achieve PR or SD to first-line R-CHOP, particularly in those with a higher IPI score and/or low ALC at diagnosis.
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Laparoscopic appendectomy for complicated acute appendicitis does not result in increased surgical complications.
Asian J Surg
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Septic postoperative complications are debated in patients with complicated acute appendicitis treated with laparoscopic appendectomy (LA). The aim of this study was to investigate the results of LA in both complicated and uncomplicated cases of acute appendicitis.
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Absorption, distribution, and elimination of graded oral doses of methylmercury in juvenile white sturgeon.
Aquat. Toxicol.
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Mercury (Hg) is toxic and is released into the environment from a wide variety of anthropogenic sources. Methylmercury (MeHg), a product of microbial methylation, enables rapid Hg bioaccumulation and biomagnification in the biota. Methylmercury is sequestered and made available to the rest of the biota through the benthic-detrital component leading to the high risk of exposure to benthic fish species, such as white sturgeon (Acipenser transmontanus). In the present study, a combined technique of stomach intubation, dorsal aorta cannulation, and urinary catheterization was utilized to characterize the absorption, distribution, and elimination of Hg in white sturgeon over a 48h exposure. Mercury, as methylmercury chloride, at either 0, 250, 500, or 1000 ?g Hg/kg body weight, was orally intubated into white sturgeon, in groups of five. The blood was repeatedly sampled and urine collected from the fish over the 48h post intubation period, and at 48h, the fish were sacrificed for Hg tissue concentration and distribution determinations. The fractional rate of absorption (K), blood Hg concentration (?g/ml), tissue concentration (?g/g dry weight) and distribution (%), and urinary Hg elimination flux (?g/kg/h) are significantly different (p<0.05) among the MeHg doses. Complete blood uptake of Hg was observed in all MeHg treated fish by 12h. The maximal observed blood Hg concentration peaks are 0.56±0.02, 0.70±0.02, and 2.19±0.07 ?g/ml (mean±SEM) for the 250, 500, and 1000 ?gHg/kg body weight dose groups, respectively. Changes in blood Hg profiles can be described by a monomolecular function in all of the MeHg treated fish. The Hg concentration asymptote (A) and K are dose dependent. The relationship between A and the intubation dose, however, is nonlinear. Mercury levels in certain tissues are comparable to field data and longer-term study, indicating that the lower doses used in the current study are ecologically relevant for the species. Tissue Hg concentrations are in the following decreasing order: gastro-intestinal tract>kidney>spleen>gill>heart>liver>brain>white muscle and remaining whole body. At 48h, Hg was found to be preferentially distributed to metabolically active tissues. Digestibility is highest at the lowest MeHg dose. Measurable urinary Hg was observed in the fish treated with the highest MeHg dose, and a significant increase in the elimination flux was observed between 3 and 12h post intubation.
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Highly regioselective synthesis of aryl chalcogenides through C-H functionalization of arenes.
Chem. Commun. (Camb.)
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We report here the regioselective synthesis of aryl chalcogenides through the iridium-catalyzed meta C-H borylation followed by copper-catalyzed C-S coupling reaction with chalcogenide sources in one pot, giving the 3,5-disubstituted aryl chalcogenides with high regioselectivity and good yields.
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Serum creatinine determined by Jaffe, enzymatic method, and isotope dilution-liquid chromatography-mass spectrometry in patients under hemodialysis.
J. Clin. Lab. Anal.
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Serum creatinine is an important clinical marker for renal clearance. However, the Jaffe method had much interference and the accuracy had not been tested in patients under hemodialysis (HD) with standard isotope dilution-liquid chromatography-mass spectrometry (IDLCMS) method. The validity of enzymatic method is also unknown.
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Nonsurgical management of delayed splenic rupture after blunt trauma.
J Trauma Acute Care Surg
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Delayed splenic rupture (DSR) is a rare manifestation of blunt splenic trauma, and splenectomy remains the primary treatment for patients with DSR. The purpose of this study was to review our experience with nonsurgical management of DSR with the use of splenic artery embolization (SAE) as an adjunct treatment.
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