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Find video protocols related to scientific articles indexed in Pubmed.
Functional characterization of 5-oxoproline transport via SLC16A1/MCT1.
J. Biol. Chem.
PUBLISHED: 11-06-2014
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Thyrotropin-releasing hormone is a tri-peptide that consists of 5-oxoproline, histidine and proline. The peptide is rapidly metabolized by various enzymes. 5-Oxoproline is produced by enzymatic hydrolysis in a variety of peptides. Previous studies showed that 5-oxoproline could become a possible biomarker for autism spectrum disorders. Here we demonstrate the involvement of SLC16A1 in the transport of 5-oxoproline. An SLC16A1 polymorphism (rs1049434) was recently identified. However, there is no information about the effect of the polymorphism on SLC16A1 function. In this study, the polymorphism caused observable change in 5-oxoproline and lactate transport via SLC16A1. The Michaelis constant (Km) was increased in an SLC16A1 mutant compared with that in the wild type. In addition, the proton concentration required to produce half-maximal activation of transport activity (K0.5, H+) was increased in the SLC16A1 mutant compared with that in the wild type. Furthermore, we examined the transport of 5-oxoproline in T98G cells as an astrocyte cell model. Despite the fact that 5-oxoproline is an amino acid derivative, Na+-dependent and amino acid transport systems scarcely contributed to 5-oxoproline transport. Based on our findings, we conclude that H+-coupled 5-oxoproline transport is mediated solely by SLC16A1 in the cells.
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Outcomes and treatments of mal fractures caused by the split-crest technique in the mandible.
Kobe J Med Sci
PUBLISHED: 10-24-2014
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In this study, we investigated cases of mal fracture occurring during the split-crest procedure. In all subjects (six patients), the free cortical bone segment caused by the mal fracture was carefully maintained in the lateral position without fixation using a titanium plate or screw. On pre- and postoperative multiplanar reconstruction CT, the average total alveolar increase was 5.0 mm in the lower portion 1 mm from the top of the alveolar ridge, and the average total alveolar increase in the lower portion 11 mm from the top of the alveolar ridge was 2.2 mm. A total of 11 dental implants were placed immediately at the same time as the split-crest procedure, while three dental implants were placed after a waiting period of 4-11 months from bone augmentation. During an average follow-up of 27.8 months, there were no complications or cases of failed implants. Consequently, among the patients who experienced mal fracture during the split-crest technique, a sufficient volume of alveolar bone was obtained without the need for rigid fixation of the free bone segment, and the dental implants placed within the area of the mal fracture showed a good prognosis.
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Nitrogen as a key regulator of flowering in Fagus crenata: understanding the physiological mechanism of masting by gene expression analysis.
Ecol. Lett.
PUBLISHED: 08-07-2014
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The role of resource availability in determining the incidence of masting has been widely studied, but how floral transition and initiation are regulated by the resource level is unclear. We tested the hypothesis that floral transition is stimulated by high resource availabiltiy in Fagus crenata based on a new technique, the expression analyses of flowering genes. We isolated F. crenata orthologues of FLOWERING LOCUS T, LEAFY and APETALA1, and confirmed their functions using transgenic Arabidopsis thaliana. We monitored the gene expression levels for 5 years and detected a cycle of on and off years, which was correlated with fluctuations of the shoot-nitrogen concentration. Nitrogen fertilisation resulted in the significantly higher expression of flowering genes than the control, where all of the fertilised trees flowered, whereas the control did not. Our findings identified nitrogen as a key regulator of mast flowering, thereby providing new empirical evidence to support the resource budget model.
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Soluble vascular endothelial-cadherin levels in patients with sepsis treated with direct hemoperfusion with a polymyxin B-immobilized fiber column.
Ther Apher Dial
PUBLISHED: 06-27-2014
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Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)-cadherin internalization by vascular endothelial growth factor (VEGF)-induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and trans-endothelial permeability. We investigated serum soluble VE-cadherin levels in septic patients. An enzyme-linked immunoassay was used to measure serum soluble VE-cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The serum soluble VE-cadherin level of septic patients before PMX-DHP was 3424.1?±?2033.0?ng/mL, which was significantly lower than that of the controls (5862.0?±?1521.2?ng/mL; P?
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Intestinal P-glycoprotein expression is multimodally regulated by intestinal ischemia-reperfusion.
J Pharm Pharm Sci
PUBLISHED: 06-18-2014
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Reactive oxygen species (ROS) have multiple physiological effects that are amount-dependent. ROS are one of the causes of intestinal ischemia-reperfusion (I/R) injury. In this study, we investigated whether the amount of ROS and the degree of intestinal I/R injury affect the expression level of P-glycoprotein (P-gp).
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Sirt1 rescues the obesity induced by insulin-resistant constitutively-nuclear FoxO1 in POMC neurons of male mice.
Obesity (Silver Spring)
PUBLISHED: 05-19-2014
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The hypothalamus is the brain center that controls the energy balance. Anorexigenic proopiomelanocortin (POMC) neurons and orexigenic AgRP neurons in the arcuate nucleus of the hypothalamus plays critical roles in energy balance regulation. FoxO1 is a transcription factor regulated by insulin signaling that is deacetylated by Sirt1, a nicotinamide adenine dinucleotide- (NAD(+) -) dependent deacetylase. Overexpression of insulin-resistant constitutively-nuclear FoxO1 (CN-FoxO1) in POMC neurons leads to obesity, whereas Sirt1 overexpression in POMC neurons leads to leanness. Whether overexpression of Sirt1 in POMC neurons could rescue the obesity caused by insulin-resistant CN-FoxO1 was tested here.
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Hyperthyroidism associated with obesity-related glomerulopathy-like pathologic features.
Intern. Med.
PUBLISHED: 05-01-2014
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Thyroid dysfunction is related to many kidney diseases. We herein present the case of a 39-year-old woman who exhibited obesity-related glomerulopathy-like pathologic features in combination with hyperthyroidism. She displayed hyperthyroidism in spite of receiving anti-thyroid drug treatment, with massive proteinuria (4.5 g/gCr). A renal biopsy demonstrated glomerular hypertrophy (average diameter, 280 ?m) and an increased number of capillary vessels, both of which are compatible with a diagnosis of obesity-related glomerulopathy. Following thyroidectomy, the proteinuria gradually decreased in association with an improvement in hyperphagia and normalization of the thyroid function. Obesity-related nephropathy associated with hyperthyroidism is very rare. In this report, we discuss the relationship between hyperthyroidism and obesity-related glomerulopathy-like pathologic features.
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Alteration of pharmacokinetics of grepafloxacin in type 2 diabetic rats.
J Pharm Pharm Sci
PUBLISHED: 04-17-2014
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Patients with type 2 diabetes are generally treated with various pharmacological compounds and are exposed to a high risk of drug-drug interactions. However, alterations of pharmacokinetics in a type 2 diabetes model have been obscure. The present study was undertaken to investigate the effects of type 2 diabetes on the pharmacokinetics of the fluoroquinolone grepafloxacin (GPFX) and the expression level of P-glycoprotein (P-gp), one of the drug efflux transporters.
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Quantification of intracellular and extracellular eicosapentaenoic acid-derived 3-series prostanoids by liquid chromatography/electrospray ionization tandem mass spectrometry.
Prostaglandins Leukot. Essent. Fatty Acids
PUBLISHED: 03-18-2014
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3-Series prostanoids are bioactive lipid mediators synthesized from eicosapentaenoic acid (EPA). Determination of intracellular and extracellular levels of prostanoids is needed to elucidate the mechanism of action, and we therefore developed a method for quantification of intracellular and extracellular levels of 3-series prostanoids (including prostaglandin E3 (PGE3), PGD3, PGF3?, thromboxane B3 (TXB3), and ?(17)-6-keto PGF1?) by using liquid chromatography/electrospray ionization tandem mass spectrometry. The separation of prostanoids was performed with a CAPCELL PAK C18 MG II column (2.0mm×150mm, 3µm) with an isocratic flow of acetonitrile/water/acetic acid (40:60:0.1, v/v/v). This method was validated for measurement of both extracellular and intracellular samples with high levels of precision and accuracy. We applied this method to human lung epithelial A549 cells stimulated with calcium ionophore A23187 under the condition of arachidonic acid or EPA treatment and we could measure PGE3 in both intracellular and extracellular samples.
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Immunoprotective effect of epigallocatechin-3-gallate on oral anticancer drug-induced ?-defensin reduction in Caco-2 cells.
Biol. Pharm. Bull.
PUBLISHED: 03-04-2014
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The aim of this study was to determine the effect of interaction between tegafur (FT) and epigallocatechin-3-gallate (EGCG) on the expression of ?-defensins (HD-5: human ?-defensin 5, HD-6: human ?-defensin 6) by using a Caco-2 cell line as a model of human intestinal epithelial cells. This is the first study in which the effect of interaction of an oral anticancer drug and functional food on the innate immune system was examined. ?-Defensins are abundant constituents of mouse and human paneth cells and play a role in the innate immune system in intestine. We detected HD-5 and HD-6 mRNA in Caco-2 cells and evaluated the effects of FT and EGCG on these mRNA levels. HD-5 and HD-6 mRNA levels were decreased by exposure to FT. Production of reactive oxygen species (ROS) was induced by exposure to FT as well as H2O2 exposure, and EGCG suppressed FT-induced production of ROS. Furthermore, FT-induced decrease in HD-5 and HD-6 mRNA levels was almost completely suppressed by EGCG. These results indicate that EGCG restored the decrease of ?-defensins induced by FT at the transcriptional level in Caco-2 cells, suggesting that EGCG can be used as adjunctive therapy in chemotherapy.
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Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology.
J. Neurol.
PUBLISHED: 02-19-2014
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Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.
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Targeting misuse of 2-amino-N-ethyl-1-phenylbutane in urine samples: in vitro-in vivo correlation of metabolic profiles and development of LC-TOF-MS method.
Drug Test Anal
PUBLISHED: 02-15-2014
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A phenyethylamine derivative, 2-amino-N-ethyl-1-phenylbutane (2-AEPB), has recently been detected in doping control and drugs-of-abuse samples, and identified as a non-labelled ingredient in a dietary supplement. To facilitate efficient control of this substance we have studied the in vitro metabolic behaviour of 2-AEPB with human liver preparation, compared these results with in vivo pathways in human, and finally propose an analytical strategy to target the potential misuse of 2-AEPB for toxicological, forensic and doping control purposes. The major in vitro formed metabolites originated from desethylation (M1) and monohydroxylation (M2). A minor metabolite with hydroxylation/N-oxidation was also observed (M3). In vitro-in vivo correlation was studied in an excretion study with a single, oral dose of 2-AEPB-containing supplement. An unmodified substance was the most abundant target compound and detected until the last point of sample collection (72?h), and the detection of M1 (40?h) and M2 (27?h) demonstrated good correlation to in vitro results. In the study with authentic cases (n?=?6), 2-AEPB and M1 were mainly found in free urinary fraction, whereas higher inter-individual variability was observed for M2. It was predominantly conjugated and already within this limited number of cases, the ratio between glucuronide- and sulpho-conjugated fractions varied significantly. As a conclusion, hydrolysis is not mandatory in the routine sample preparation, and as the separation can be based on either gas chromatography or liquid chromatography, this study verifies that routine mass spectrometric detection methods targeted to amphetamine derivatives can be easily extended to control the misuse of 2-AEPB. Copyright © 2014 John Wiley & Sons, Ltd.
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Detection and control of combustion instability based on the concept of dynamical system theory.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 02-11-2014
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We propose an online method of detecting combustion instability based on the concept of dynamical system theory, including the characterization of the dynamic behavior of combustion instability. As an important case study relevant to combustion instability encountered in fundamental and practical combustion systems, we deal with the combustion dynamics close to lean blowout (LBO) in a premixed gas-turbine model combustor. The relatively regular pressure fluctuations generated by thermoacoustic oscillations transit to low-dimensional intermittent chaos owing to the intermittent appearance of burst with decreasing equivalence ratio. The translation error, which is characterized by quantifying the degree of parallelism of trajectories in the phase space, can be used as a control variable to prevent LBO.
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Differential mechanisms of action of the novel ?-aminobutyric acid receptor antagonist ectoparasiticides fluralaner (A1443) and fipronil.
Pest Manag. Sci.
PUBLISHED: 01-22-2014
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Fluralaner (A1443) is an isoxazoline ectoparasiticide that is a novel antagonist of ?-aminobutyric acid (GABA) receptors (GABARs), with a potency comparable to that of fipronil, a phenylpyrazole ectoparasiticide. To clarify the biological effectiveness of fluralaner against fipronil-resistant pests, differences in the actions of fluralaner and fipronil on GABARs that possess resistance to dieldrin (rdl)-type mutations were evaluated.
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Selective Probing of the OH or OD Stretch Vibration in Liquid Water Using Resonant Inelastic Soft-X-Ray Scattering.
Phys. Rev. Lett.
PUBLISHED: 11-08-2013
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High-resolution O 1s resonant inelastic x-ray scattering spectra of liquid H_{2}O, D_{2}O, and HDO, obtained by excitation near the preedge resonance show, in the elastic line region, well-separated multiple vibrational structures corresponding to the internal OH stretch vibration in the ground state of water. The energy of the first-order vibrational excitation is strongly blueshifted with respect to the main band in the infrared or Raman spectra of water, indicating that water molecules with a highly weakened or broken donating hydrogen bond are correlated with the preedge structure in the x-ray absorption spectrum. The vibrational profile of preedge excited HDO water is well fitted with 50%±20% greater OH-stretch contribution compared to OD, which strongly supports a preference for OH being the weakened or broken H-bond in agreement with the well-known picture that D_{2}O makes stronger H-bonds than H_{2}O. Accompanying path-integral molecular dynamics simulations show that this is particularly the case for strongly asymmetrically H-bonded molecules, i.e., those that are selected by preedge excitation.
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ATF3 expression is induced by low glucose in pancreatic ? and ? cells and regulates glucagon but not insulin gene transcription.
Endocr. J.
PUBLISHED: 10-20-2013
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The pancreas is critical for maintaining glucose homeostasis. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. There are major discrepancies in previous reports on pancreatic ATF3; therefore, its role in the pancreas is unclear. To better elucidate the role of ATF3 in the pancreas, we conducted in vitro studies using pancreatic ? and ? cell lines, and also evaluated the use of ATF3 antibodies for immunohistochemistry. We determined ATF3 expression was increased by low glucose and decreased by high glucose in both ?TC-1.6 and ?TC3 cells. We also showed that adenovirus-mediated ATF3 overexpression increased glucagon promoter activity and glucagon mRNA levels in ?TC-1.6 cells; whereas, it had no effect on insulin promoter activity and insulin mRNA levels in ?TC3 cells. Although immunostaining with the C-19 ATF3 antibody demonstrated predominant expression in ? cells rather than ? cells, ATF3 staining was still detected in ATF3 knockout mice as clearly as in control mice. On the other hand, another ATF3 antibody (H-90) detected ATF3 in both ? cells and ? cells, and was clearly diminished in ATF3 knockout mice. These results indicate that previous discrepancies in ATF3 expression patterns in the pancreas were caused by the varying specificities of the ATF3 antibodies used, and that ATF3 is actually expressed in both ? cells and ? cells.
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Megalin contributes to kidney accumulation and nephrotoxicity of colistin.
Antimicrob. Agents Chemother.
PUBLISHED: 10-07-2013
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Interest has recently been shown again in colistin because of the increased prevalence of infections caused by multidrug-resistant Gram-negative bacteria. Although the potential for nephrotoxicity is a major dose-limiting factor in colistin use, little is known about the mechanisms that underlie colistin-induced nephrotoxicity. In this study, we focused on an endocytosis receptor, megalin, that is expressed in renal proximal tubules, with the aim of clarifying the role of megalin in the kidney accumulation and nephrotoxicity of colistin. We examined the binding of colistin to megalin by using a vesicle assay. The kidney accumulation, urinary excretion, and concentrations in plasma of colistin in megalin-shedding rats were also evaluated. Furthermore, we examined the effect of megalin ligands and a microtubule-depolymerizing agent on colistin-induced nephrotoxicity. We found that cytochrome c, a typical megalin ligand, inhibited the binding of colistin to megalin competitively. In megalin-shedding rats, renal proximal tubule colistin accumulation was decreased (13.5 ± 1.6 and 21.3 ± 2.6 ?g in megalin-shedding and control rats, respectively). Coadministration of colistin and cytochrome c or albumin fragments resulted in a significant decrease in urinary N-acetyl-?-d-glucosaminidase (NAG) excretion, a marker of renal tubular damage (717.1 ± 183.9 mU/day for colistin alone, 500.8 ± 102.4 mU/day for cytochrome c with colistin, and 406.7 ± 156.7 mU/day for albumin fragments with colistin). Moreover, coadministration of colistin and colchicine, a microtubule-depolymerizing agent, resulted in a significant decrease in urinary NAG excretion. In conclusion, our results indicate that colistin acts as a megalin ligand and that megalin plays a key role in the accumulation in the kidney and nephrotoxicity of colistin. Megalin ligands may be new targets for the prevention of colistin-induced nephrotoxicity.
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Highly sensitive imaging for ultra-weak photon emission from living organisms.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 09-29-2013
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Spontaneous ultra-weak photon emissions (UPEs) are from living organisms. Often designated as biophoton emissions, they are associated with reactive oxygen species production. They have long been explored for use in the extraction of pathophysiological information of living bodies. Because of its potential non-invasiveness and because it is completely passive, it has been anticipated for application to human diagnosis. However, because of the weakness of its signal and the complexity of the mechanisms, practical applications of UPE and efforts have remained restricted. Imaging of UPE is a powerful tool for the practical application of UPE. Furthermore, efforts to develop imaging technique have been made from the early period of UPE study. This report explains the history of UPE study, particularly describing the development of imaging technology and its application covering agriculture and medicine are reviewed. Furthermore, the issue of what was achieved and what is necessary for the additional advancement of UPE will be discussed for practical application.
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Regulation of the expression and activity of glucose and lactic acid metabolism-related genes by protein kinase C in skeletal muscle cells.
Biol. Pharm. Bull.
PUBLISHED: 09-03-2013
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Protein kinase C (PKC) modulators are very attractive therapeutic targets in cancer. Since most cancer cells display increased glycolysis, elucidations of the effects of PKC activation on glycolysis is necessary for the development of effective medicine. In the present study, to clarify the role of PKC in the regulation of glycolysis, we examined the effect of phorbol 12-myristate 13-acetate (PMA), a PKC activator, on the expression and activity of glucose and lactic acid metabolism-related genes in human rhabdomyosarcoma cells (RD cells). In parallel to increases in glucose uptake and mRNA levels of glucose transporters (GLUTs) induced by PMA treatment for 6 h, the hexokinase (HK) mRNA level and activity were also significantly increased in RD cells. On the other hand, a significant increase in lactate dehydrogenase (LDH) mRNA level and activity was seen when the cells were incubated with PMA for 24 h, but not for 6 or 12 h, and was associated with lactic acid production. These effects by PMA treatment were markedly suppressed by Bisindolylmaleimide (BIM), a PKC inhibitor. Furthermore, chetomin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, completely abrogated the increment of LDH mRNA level and activity as well as monocarboxylate transporter (MCT) 4, a lactic acid efflux transporter. In conclusion, we found that HK and LDH activity induced by PKC activation was associated with the glucose uptake and lactic acid level and that LDH and MCT4 are modulated by a common factor, HIF-1.
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Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates.
Endocr. J.
PUBLISHED: 08-30-2013
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Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown adipocyte cell line. Miglitol prevented diet-induced obesity by stimulating energy expenditure without affecting food intake in mice. Long-term miglitol treatment dose-dependently prevented diet-induced obesity and induced mitochondrial gene expression in brown adipose tissue. The anti-obesity effect was independent of preventing carbohydrate digestion in the gastrointestinal tract. Miglitol effectively stimulated energy expenditure in mice fed a high-fat high-monocarbohydrate diet, and intraperitoneal injection of miglitol was sufficient to stimulate energy expenditure in mice. Acarbose, which is a non-absorbable alpha glucosidase inhibitor, also prevented diet-induced obesity, but through a different mechanism: it did not stimulate energy expenditure, but caused indigestion, leading to less energy absorption. Miglitol promoted adrenergic signaling in brown adipocytes in vitro. These data indicate that circulating miglitol stimulates brown adipose tissue and increases energy expenditure, thereby preventing diet-induced obesity. Further optimizing miglitols effect on brown adipose tissue could lead to a novel anti-obesity drug.
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Contribution of multidrug resistance-associated proteins (MRPs) to the release of prostanoids from A549 cells.
Prostaglandins Other Lipid Mediat.
PUBLISHED: 08-07-2013
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Previous studies indicated that several members of the multidrug resistance-associated protein (MRP) family mediate the transport of prostanoids. However, theimportance of MRPs in the release process of prostanoids has not been fully elucidated. In this study, we investigated the contribution of MRPs, including MRP1, MRP2, and MRP4, to the release process of the prostanoids from human lung adenocarcinoma epithelial A549 cells. The extracellular levels of PGE2, PGF2?, and TXB2 (a metabolite of TXA2) were decreased by treatment with MRP inhibitors (dipyridamole, MK571, and probenecid). The studies using membrane vesicle suggest that the effects of the inhibitors were in part by inhibiting MRP4 function. The effects of knockdown of each MRP (MRP1, MRP2, and MRP4) were also investigated. The extracellular levels of PGE2 and PGF2? were significantly decreased after MRP4 knockdown. Our results suggest that MRPs including MRP4 contribute the release process of prostanoids in A549 cells.
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Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice.
Diabetologia
PUBLISHED: 07-27-2013
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Obesity is associated with ageing and increased energy intake, while restriction of energy intake improves health and longevity in multiple organisms; the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1) is implicated in this process. Pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus (ARC) of the hypothalamus are critical for energy balance regulation, and the level of SIRT1 protein decreases with age in the ARC. In the current study we tested whether conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevents age-associated weight gain and diet-induced obesity.
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Laparoscopic repair of a post-myomectomy spontaneous uterine perforation accompanied by a bizarre tumor resembling polypoid endometriosis.
J Minim Invasive Gynecol
PUBLISHED: 04-22-2013
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Among various long-term complications after previous myomectomy, increasing risk of uterine rupture or dehiscence during pregnancy, and in particular during labor, has been widely recognized. In contrast, the world literature includes no case report of spontaneous uterine perforation or rupture after myomectomy in a nonpregnant woman, and only 1 case of iatrogenic uterine perforation after uterine artery embolization has been reported. Recently, we encountered an extremely rare case of spontaneous uterine perforation after previous myomectomy accompanied by a bizarre tumor resembling polypoid endometriosis, which was successfully treated via laparoscopic surgery. The patient reported genital bleeding and lower abdominal pain. Preoperative magnetic resonance imaging and intraoperative findings clearly demonstrated the presence of a uterine wall defect and a multicystic tumor that had developed from the perforated portion of the uterus. The patient underwent successful laparoscopic surgery for repair of the perforated uterus and resection of the tumor. The clinicopathologic diagnosis of the tumor was tentatively confirmed as an endometriosis-like lesion resembling polypoid endometriosis. We speculate that the cause of the tumor was retrograde menstruation, as in the pathogenesis of endometriosis.
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Angiographic findings after vaginal gauze packing: New insight into an old technique.
J. Obstet. Gynaecol. Res.
PUBLISHED: 04-03-2013
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We had a transferred case of cervical ectopic pregnancy with hemorrhagic shock at 6 weeks of gestation. Upon arrival at hospital, we performed tight and full vaginal gauze packing to push the uterus upward to control the patients hemorrhage. Following stabilization of her general condition, she was treated with uterine artery embolization. Using angiography, the effectiveness of vaginal gauze packing for emergency hemostasis by the presumed mechanism of impairing blood flow through the uterine artery was demonstrated. To our knowledge, there are no reports that have previously demonstrated angiographic findings similar to ours after vaginal gauze packing. Vaginal gauze packing is an effective, rapid, and convenient hemostatic procedure able to be carried out in a time-sensitive and challenging situation. As a result, this procedure gives clinicians more time to improve the patients general status and arrange for transfusion and further definitive treatment.
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Mass flowering of the tropical tree Shorea beccariana was preceded by expression changes in flowering and drought-responsive genes.
Mol. Ecol.
PUBLISHED: 04-02-2013
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Community-level mass flowering, known as general flowering, which occurs in South-East Asia at supra-annual irregular intervals, is considered a particularly spectacular phenomenon in tropical ecology. Recent studies have proposed several proximate factors inducing general flowering, such as drought and falls in minimum temperature. However, limited empirical data on the developmental and physiological processes have been available to test the significance of such factors. To overcome this limitation and test the hypotheses that general flowering is triggered by the proposed factors, we conducted an ecological transcriptome study of a mass flowering species, Shorea beccariana, comparing meteorological data with genome-wide expression patterns obtained using next-generation sequencing. Among the 98 flowering-related genes identified, the homologs of a floral pathway integrator, SbFT, and a floral repressor, SbSVP, showed dramatic transcriptional changes before flowering, and their flowering functions were confirmed using transgenic Arabidopsis thaliana. Expression in drought-responsive and sucrose-induced genes also changed before flowering. All these expression changes occurred when the flowering-inducing level of drought was reached, as estimated using data from the preceding 10 years. These genome-wide expression data support the hypothesis that drought is a trigger for general flowering.
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Evaluation of a novel artificial pancreas: closed loop glycemic control system with continuous blood glucose monitoring.
Artif Organs
PUBLISHED: 03-18-2013
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A closed-loop glycemic control system using an artificial pancreas has been applied with many clinical benefits in Japan since 1987. To update this system incorporating user-friendly features, we developed a novel artificial pancreas (STG-55). The purpose of this study was to evaluate STG-55 for device usability, performance of blood glucose measurement, glycemic control characteristics in vivo in animal experiments, and evaluate its clinical feasibility. There are several features for usability improvement based on the design concepts, such as compactness, display monitor, batteries, guidance function, and reduction of the preparation time. All animal study data were compared with a clinically available artificial pancreas system in Japan (control device: STG-22). We examined correlations of both blood glucose levels between two groups (STG-55 vs. control) using Clarkes error grid analysis, and also compared mean glucose infusion rate (GIR) during glucose clamp. The results showed strong correlation in blood glucose concentrations (Pearsons product-moment correlation coefficient: 0.97; n?=?1636). Clarkes error grid analysis showed that 98.4% of the data fell in Zones A and B, which represent clinically accurate or benign errors, respectively. The difference in mean GIRs was less than 0.2?mg/kg/min, which was considered not significant. Clinical feasibility study demonstrated sufficient glycemic control maintaining target glucose range between 80 and 110 (mg/dL), and between 140 and 160 without any hypoglycemia. In conclusion, STG-55 was a clinically acceptable artificial pancreas with improved interface and usability. A closed-loop glycemic control system with STG-55 would be a useful tool for surgical and critical patients in intensive care units, as well as diabetic patients.
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Regulation of multidrug resistance protein 2 (MRP2, ABCC2) expression by statins: involvement of SREBP-mediated gene regulation.
Int J Pharm
PUBLISHED: 03-13-2013
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Multidrug resistance protein 2 (MRP2, ABCC2) is localized to the apical membrane of hepatocytes and played an important role in the biliary excretion of a broad range of endogenous and xenobiotic compounds and drugs, such as pravastatin. However, the effects of statins on MRP2 in the liver and the precise mechanisms of their actions have been obscure. The goal of this study was to determine the regulatory molecular mechanism for statin-induced MRP2 expression in hepatocytes. In vitro and in vivo studies suggested that pitavastatin increased MRP2 expression. Pitavastatin promoted liver X receptor (LXR) ?/? translocation from the cytosol to nuclei, resulting in LXR activation. Deletion and mutational analysis suggested that the potential sterol regulatory element (SRE) played a major role in the observed modulation of MRP2 expression by pitavastatin. Furthermore pitavastatin increased the protein-DNA complex, and when SRE was mutated, stimulation of the protein-DNA complex by pitavastatin was decreased. It was demonstrated that pitavastatin upregulated MRP2 expression by an SREBP regulatory pathway in hepatocytes and that the actions of statins may lead to improve the biliary excretion of MRP2 substrates.
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Perioperative glycemic control using an artificial endocrine pancreas in patients undergoing total pancreatectomy: tight glycemic control may be justified in order to avoid brittle diabetes.
Biomed Mater Eng
PUBLISHED: 02-28-2013
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I dedicate this paper to the late Prof. Yukihiko Nosé with all my heart. In 2001, under the direction of Prof. Nosé and Prof. Brunicardi at Baylor College of Medicine, we published a review article entitled "Artificial endocrine pancreas" in JACS. Subsequently, we reported that perioperative tight glycemic control (TGC) using an artificial pancreas (AP) with a closed-loop system could stably maintain near-normoglycemia in total-pancreatectomized dogs. Based on this experimental study in Houston, since 2006, we have introduced perioperative TGC using an AP into clinical use in Kochi. As of 2011, this novel TGC method has provided safe and stable blood glucose levels in more than 400 surgical patients. In this paper, we report new clinical findings regarding perioperative TGC using an AP in total-pancreatectomized patients. TGC using an AP enables us to achieve stable glycemic control not only without hypoglycemia and hyperglycemia but also with less variation in blood glucose concentration from the target blood glucose range, even in patients with the most serious form of diabetes, so-called "brittle diabetes", undergoing total pancreatectomy. To the best of our knowledge, this is the first clinical report of TGC using an AP in patients undergoing total pancreatic resection.
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Anorectal abscess during pregnancy.
J. Obstet. Gynaecol. Res.
PUBLISHED: 02-05-2013
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Anorectal symptoms and complaints caused by hemorrhoids or anal fissures are common during pregnancy. It is known that one-third of pregnant women complain of anal pain in the third trimester. Anal pain may be caused by a wide spectrum of conditions, but if it begins gradually and becomes excruciating within a few days it may indicate anorectal abscess. We experienced a case of anorectal abscess during pregnancy which was diagnosed by magnetic resonance imaging and treated by incision and seton drainage at 36 weeks of gestation, followed by a normal spontaneous delivery at 38 weeks of gestation. To our knowledge, this is the first case report of anorectal abscess during pregnancy in the English-language published work. The clinical course of our case and clinical considerations of anorectal abscesses are discussed.
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Complex Müllerian malformation without any present classification: unilateral ovarian and tubal absence with an arcuate uterus.
Asian J Endosc Surg
PUBLISHED: 01-26-2013
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Müllerian duct anomalies are known to cause infertility and reproductive problems. The true incidence of such abnormalities is not well defined. The most widely accepted method of classification for a Müllerian duct anomaly is the American Society of Reproductive Medicine classification (1988). However, there are some rare anomalies inconsistent with the current classification. Herein, we report a rare case of Müllerian duct anomaly, unilateral ovarian and tubal absence with an arcuate uterus. The failure of the Müllerian ducts to canalize can also lead to the development of a unicornuate uterus and adnexal agenesis. An arcuate uterus indicates incomplete septal absorption after normal fusion of the Müllerian ducts. Therefore, its coexistence with adnexal absence and an arcuate uterus is considered to be extremely unlikely.
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Rupture of renal artery aneurysm during the early post-partum period.
J. Obstet. Gynaecol. Res.
PUBLISHED: 01-23-2013
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Rupture of renal artery aneurysm associated with pregnancy is an uncommon condition. It is known that almost all previously reported cases have occurred during pregnancy. We experienced a case of rupture of renal artery aneurysm during the early post-partum period which was diagnosed by computed tomography and treated by angiographic embolization. To our knowledge, only two cases of rupture of renal artery aneurysm during the post-partum period have been reported in the English-language published work. An early diagnosis of rupture of renal artery aneurysm during the post-partum period is very challenging because the clinical symptoms of this condition are acute abdominal, flank or back pain, which are relatively common signs caused by more common post-partum complications. However, rupture of renal artery aneurysm is a life-threatening emergency condition requiring prompt diagnosis and treatment. The possibility of a rupture of renal artery aneurysm should be considered in any pregnant women with symptoms of an acute abdomen with hemorrhagic shock.
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Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells.
PLoS ONE
PUBLISHED: 01-23-2013
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Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated ?-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia-retinoic acid receptor ? (PML-RAR-?) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-? activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-? does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.
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The observational study of delayed wound healing after tooth extraction in patients receiving oral bisphosphonate therapy.
J Craniomaxillofac Surg
PUBLISHED: 01-16-2013
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In this study, we investigated whether such a discontinuation of oral bisphosphonate (BP) for 3 months might influence the incidence of BP-related osteonecrosis of the jaw (BRONJ) and wound healing after tooth extraction in patients receiving oral BP therapy.
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Increase of N1, N12-diacetylspermine in tissues from colorectal cancer and its liver metastasis.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-09-2013
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N (1),N (12)-Diacetylspermine (DiAcSpm) is a tumor marker featured by increase in the urine of patients with cancers, including early colorectal cancer, but where and how DiAcSpm is made remains unclear. We aimed to clarify whether colorectal cancer tissues produce increased amounts of DiAcSpm, and if they do, to examine whether tissue DiAcSpm level may serve as a criterion of tissue malignancy.
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Common amino acid sequences deduced from coding exons of the porcine FGF4 gene in two breeds and production of the encoded protein in Escherichia coli.
Biosci. Biotechnol. Biochem.
PUBLISHED: 01-07-2013
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Fibroblast growth factor 4 (FGF4) is considered a crucial gene in the development of mammalian embryos. Here we identified common amino acid sequences predicted from coding exons of the FGF4 gene in five pigs of two breeds, and HispFGF4, a 6× histidine-tagged porcine FGF4, was produced in Escherichia coli. HispFGF4 was purified efficiently from the supernatant of cell lysate by heparin column chromatography. In a porcine embryonic fibroblast cell line, HispFGF4 showed significant mitogenic activities at concentrations as low as 0.001 nM (p<0.01). To the best of our knowledge, this is the first report describing the complete nucleotide sequence of coding exons for the porcine FGF4 protein in two breeds, together with the production of a recombinant, bioactive porcine FGF4 derivative.
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Imaging of Ultra-Weak Photon Emission in a Rheumatoid Arthritis Mouse Model.
PLoS ONE
PUBLISHED: 01-01-2013
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Ultra-weak photon emission (UPE) of a living system received scientific attention because of its potential for monitoring increased levels of reactive oxygen species (ROS) in the pathogenesis of rheumatoid arthritis (RA). In this study, a highly sensitive cryogenic charge-coupled device (CCD) camera was used to monitor in a RA mouse model the photon emission both without and with luminol. For that purpose, arthritis was induced in mice utilizing a repeated co-administration of type II collagen with lipopolysaccharide. Quantitative imaging of ultra-weak photon emission of the front and back paws of the animals was initiated 70 days after the first injection. All of the animals were measured once without luminol and once again immediately after luminol injection. Data illustrated a higher UPE intensity after initiating arthritis by CII-injection of the animals. The increase in UPE intensity was measured with and without using luminol indicating that this imaging technology may be useful for the future study of human RA.
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A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting.
PLoS ONE
PUBLISHED: 01-01-2013
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During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the (125)I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis.
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Crucial residue involved in L-lactate recognition by human monocarboxylate transporter 4 (hMCT4).
PLoS ONE
PUBLISHED: 01-01-2013
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Monocarboxylate transporters (MCTs) transport monocarboxylates such as lactate, pyruvate and ketone bodies. These transporters are very attractive therapeutic targets in cancer. Elucidations of the functions and structures of MCTs is necessary for the development of effective medicine which targeting these proteins. However, in comparison with MCT1, there is little information on location of the function moiety of MCT4 and which constituent amino acids govern the transport function of MCT4. The aim of the present work was to determine the molecular mechanism of L-lactate transport via hMCT4.
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Overexpression of FoxO1 in the hypothalamus and pancreas causes obesity and glucose intolerance.
Endocrinology
PUBLISHED: 12-20-2011
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Recent studies have revealed that insulin signaling in pancreatic ?-cells and the hypothalamus is critical for maintaining nutrient and energy homeostasis, the failure of which are hallmarks of metabolic syndrome. We previously reported that forkhead transcription factor forkhead box-containing protein of the O subfamily (FoxO)1, a downstream effector of insulin signaling, plays important roles in ?-cells and the hypothalamus when we investigated the roles of FoxO1 independently in the pancreas and hypothalamus. However, because metabolic syndrome is caused by the combined disorders in hypothalamus and pancreas, to elucidate the combined implications of FoxO1 in these organs, we generated constitutively active FoxO1 knockin (KI) mice with specific activation in both the hypothalamus and pancreas. The KI mice developed obesity, insulin resistance, glucose intolerance, and hypertriglyceridemia due to increased food intake, decreased energy expenditure, and impaired insulin secretion, which characterize metabolic syndrome. The KI mice also had increased hypothalamic Agouti-related protein and neuropeptide Y levels and decreased uncoupling protein 1 and peroxisome proliferator-activated receptor ? coactivator 1? levels in adipose tissue and skeletal muscle. Impaired insulin secretion was associated with decreased expression of pancreatic and duodenum homeobox 1 (Pdx1), muscyloaponeurotic fibrosarcoma oncogene homolog A (MafA), and neurogenic differentiation 1 (NeuroD) in islets, although ?-cell mass was paradoxically increased in KI mice. Based on these results, we propose that uncontrolled FoxO1 activation in the hypothalamus and pancreas accounts for the development of obesity and glucose intolerance, hallmarks of metabolic syndrome.
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[Collection of information regarding implants, internal and external metallic objects for MRI examinations].
Nihon Hoshasen Gijutsu Gakkai Zasshi
PUBLISHED: 10-27-2011
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In Japan, various types of MRI equipment, having varying magnetic field strengths, are widely used. However, the biggest problem encountered while utilizing an MRI is the scarcity of information and guidelines pertaining to implants, internal, and external metallic objects. This leads to uncertainty when an unspecified object is encountered during an examination andcreates the possibility of performing an ambiguous MRI. Therefore, this study classified a range of objects into 12 categories using database management software. An attempt was made to create an environment where reference and comparison of products could be performed. This study also investigated the ways and extent to which medical equipment package inserts reference the MRI. With the co-operation of various corporations and the use of information such as medical equipment package inserts, product information was collected and an environment for the reference and comparison of products became available. In addition, it became apparent while examining these package inserts that orthopedic products had the least information available. It is likely that this information will be useful in medical settings and this kind of database will become increasingly necessary in the future.
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Angiopoietin balance in septic shock patients with acute lung injury: effect of direct hemoperfusion with polymyxin B-immobilized fiber.
Ther Apher Dial
PUBLISHED: 09-03-2011
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Acute lung injury (ALI) in sepsis is characterized by an increase in microvascular permeability, resulting in pulmonary edema. Several studies have suggested that angiopoietin-1 and -2 play a contributory role in the pathogenesis of ALI. Polymyxin B-immobilized fiber column hemoperfusion is effective for sepsis-induced ALI. We investigated the angiopoietin levels before and after direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) therapy. Enzyme-linked immunoassay was used to measure the serum angiopoietin-1 and -2 levels in 25 patients with septic shock treated with PMX. Eleven of the 25 patients were diagnosed with ALI. There was a significant positive correlation between the angiopoietin-1 level and the PaO(2) /FiO(2) ratio, but there was a significant inverse correlation between the angiopoietin-2 level and the PaO(2) /FiO(2) ratio. The mean angiopoietin-1 level before PMX therapy in the ALI group was significantly lower and the mean angiopoietin-2 level was significantly higher than in the non-ALI group. The mean angiopoietin-1 level of the ALI patients in response to PMX therapy was increased during PMX therapy, but that of the non-ALI patients with newly occurring ALI showed a decreased angiopoietin-1 level. On the other hand, the mean angiopoietin-2 level of the responders was decreased during PMX therapy, but that of patients with newly occurring ALI showed an increased angiopoietin-2 level. This result suggested that each angiopoietin-1 and -2 level may play a role in the pathogenesis of ALI and that PMX therapy ameliorates the angiopoietin balance in patients with ALI in sepsis.
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Serum TNF-related and weak inducer of apoptosis levels in septic shock patients.
Ther Apher Dial
PUBLISHED: 09-03-2011
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Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8 ± 230.5 pg/mL) than in controls (84.1 ± 28.7 pg/mL, P = 0.043). Between 11 survivors and 10 non-survivors, there was no significant difference in the serum TWEAK levels before the DHP-PMX therapy. During DHP-PMX therapy, however, the serum TWEAK levels were significantly increased in non-survivors (142.2 ± 88.1 pg/mL to 399.0 ± 307.1 pg/mL, P = 0.022). There was a significant correlation between the serum TWEAK levels and white blood cell counts (r = 0.393, P < 0.001), platelet counts (r = 0.418, P < 0.001), or serum CRP levels (r = 0.259, P = 0.029), but there was no correlation between the serum TWEAK levels and blood pressure. The serum TWEAK levels were also correlated with the ratio of angiopoietin-2 to -1 (r = 0.464, P < 0.001). TWEAK may be a suitable marker of disease severity and mortality in septic patients, and TWEAK levels may be associated with vascular permeability via angiopoietin balance.
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Protective effect of soy isoflavone genistein on ischemia-reperfusion in the rat small intestine.
Biol. Pharm. Bull.
PUBLISHED: 09-02-2011
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Ischemia-reperfusion (I/R) injury of the intestine is an important factor associated with high rates of morbidity and mortality. Intestinal I/R is a common clinical problem in the settings of severe burns, circulatory shock and strangulation ileus. Intestinal I/R damages remote organs and promotes multi-organ failure. It has been shown that enteral feeding before ischemic insults is beneficial for reducing organ injury and improving survival after intestinal I/R. In that study, the authors used a standard complex enteral diet and they suggested that it is important to find new nutrient formulas. Since reactive oxygen species are responsible for intestinal I/R injury, we focused on a dietary polyphenol, the soy isoflavone genistein. Genistein has a wide spectrum of biochemical and pharmacological activities. However, the possibility of a protective effect of genistein as enteral nutrition on I/R injury has not been investigated. We therefore investigated the protective effect of genistein on oxidative injury using intestinal I/R model rats. We found that genistein, which has combined antioxidant activity from radical scavenging, xanthine oxidase inhibition and chain-breaking effects, exhibits a protective effect on intestinal I/R injury. The results suggest that genistein, a soy isoflavone, has the possibility as a new nutrient formula of enteral feeding.
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Plant sexual reproduction during climate change: gene function in natura studied by ecological and evolutionary systems biology.
Ann. Bot.
PUBLISHED: 08-17-2011
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It is essential to understand and predict the effects of changing environments on plants. This review focuses on the sexual reproduction of plants, as previous studies have suggested that this trait is particularly vulnerable to climate change, and because a number of ecologically and evolutionarily relevant genes have been identified.
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Quantification of intracellular and extracellular prostanoids stimulated by A23187 by liquid chromatography/electrospray ionization tandem mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 07-19-2011
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Prostanoids are bioactive substances that contribute to various biological and pathological processes. To evaluate both extracellular and intracellular levels of prostanoids at the same time, we developed methods for quantification of extracellular and intracellular levels of prostanoids, including prostaglandin E(2) (PGE(2)), PGD(2), PGF(2?), 6-keto PGF(1?), and TXB(2), in cultured cells using liquid chromatography/tandem mass spectrometry (LC/MS/MS), and we validated the LC/MS/MS methods. A solid-phase extraction cartridge was used for extraction of prostanoids. The prostanoids were separated by a C(18) column with an isocratic flow of acetonitrile/water/acetic acid (40:60:0.1, v/v/v). Calibration curves of extracellular measurement for the prostanoids were linear in the range from 0.1 to 100 ng/mL (r(2)>0.999), and those of intracellular measurement were linear in the range from 0.05 to 50 ng (r(2)>0.999). Validation assessment showed that both methods of extracellular and intracellular measurements were highly reliable with good accuracy and precision. We also applied the methods to human airway epithelial Calu-3 cells and human lung adenocarcinoma epithelial A549 cells.
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Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus.
Nat Commun
PUBLISHED: 04-18-2011
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Synchronous oscillations of thousands of cellular clocks in the suprachiasmatic nucleus (SCN), the circadian centre, are coordinated by precisely timed cell-cell communication, the principle of which is largely unknown. Here we show that the amount of RGS16 (regulator of G protein signalling 16), a protein known to inactivate G?i, increases at a selective circadian time to allow time-dependent activation of intracellular cyclic AMP signalling in the SCN. Gene ablation of Rgs16 leads to the loss of circadian production of cAMP and as a result lengthens circadian period of behavioural rhythm. The temporally precise regulation of the cAMP signal by clock-controlled RGS16 is needed for the dorsomedial SCN to maintain a normal phase-relationship to the ventrolateral SCN. Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour.
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Regulation mechanism of ABCA1 expression by statins in hepatocytes.
Eur. J. Pharmacol.
PUBLISHED: 03-28-2011
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ATP-binding cassette transporter A1 (ABCA1) is predicted to be involved in the control of apolipoprotein AI-mediated cholesterol efflux: biosynthesis of high-density lipoprotein (HDL). However, the effects of HMG-CoA reductase inhibitors (statins) on ABCA1 in the liver and the precise mechanisms of their actions have been obscure. The aims of this study were to determine whether statins (atorvastatin (Ato) and pitavastatin (Pit)) affect hepatic ABCA1 expression and to clarify the mechanisms of their actions using HepG2 cells and the rat liver. We examined alterations in mRNA and protein levels of ABCA1 and peroxisome proliferator-activated receptors (PPARs) by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. In vitro and in vivo studies suggested that Pit increases ABCA1 mRNA level, but not Ato. Pit greatly increased Abca1 mRNA level and also increased the amount of plasma HDL and the mRNA level of PPAR?. Clofibrate (PPAR? agonist) increased ABCA1 expression in HepG2 cells and rat primary hepatocytes more than did PPAR ?/? and ? agonists. Pit-induced ABCA1 expression alteration was blocked by GW6471 (PPAR? antagonist) and by PPAR? knockdown. In this study, we demonstrated that Pit affect ABCA1 expression via PPAR? in hepatocytes. The strategy to target a PPAR? agonist in the liver can lead to increases in ABCA1 expression and HDL level.
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In situ enzyme activity in the dissolved and particulate fraction of the fluid from four pitcher plant species of the genus Nepenthes.
PLoS ONE
PUBLISHED: 03-16-2011
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The genus Nepenthes, a carnivorous plant, has a pitcher to trap insects and digest them in the contained fluid to gain nutrient. A distinctive character of the pitcher fluid is the digestive enzyme activity that may be derived from plants and dwelling microbes. However, little is known about in situ digestive enzymes in the fluid. Here we examined the pitcher fluid from four species of Nepenthes. High bacterial density was observed within the fluids, ranging from 7×10(6) to 2.2×10(8) cells ml(-1). We measured the activity of three common enzymes in the fluid: acid phosphatases, ?-D-glucosidases, and ?-D-glucosaminidases. All the tested enzymes detected in the liquid of all the pitcher species showed activity that considerably exceeded that observed in aquatic environments such as freshwater, seawater, and sediment. Our results indicate that high enzyme activity within a pitcher could assist in the rapid decomposition of prey to maximize efficient nutrient use. In addition, we filtered the fluid to distinguish between dissolved enzyme activity and particle-bound activity. As a result, filtration treatment significantly decreased the activity in all enzymes, while pH value and Nepenthes species did not affect the enzyme activity. It suggested that enzymes bound to bacteria and other organic particles also would significantly contribute to the total enzyme activity of the fluid. Since organic particles are themselves usually colonized by attached and highly active bacteria, it is possible that microbe-derived enzymes also play an important role in nutrient recycling within the fluid and affect the metabolism of the Nepenthes pitcher plant.
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An Mdm2 antagonist, Nutlin-3a, induces p53-dependent and proteasome-mediated poly(ADP-ribose) polymerase1 degradation in mouse fibroblasts.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-10-2011
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Nutlin-3a (Nutlin) is an Mdm2 inhibitor and is potent to stabilize p53, which is a tumor-suppressor involved in various biological processes such as cell cycle regulation, DNA repair, and apoptosis. Here we demonstrate that Nutlin treatment in mouse fibroblast cell lines reduces the protein levels of poly(ADP-ribose) polymerase1 (Parp1). Parp1 functions in DNA repair, replication, and transcription and has been regarded as a target molecule for anti-cancer therapy and protection from ischemia/reperfusion injury. In this study, first we found that Nutlin, but not DNA damaging agents such as camptothecin (Cpt), induced a decrease in the Parp1 protein levels. This reduction was not associated with cell death and not observed in p53 deficient cells. Next, because Nutlin treatment did not alter Parp1 mRNA levels, we expected that a protein degradation pathway might contribute to this phenomenon. Predictably, a proteasome inhibitor, MG132, inhibited the Nutlin-induced decrease in the levels of Parp1 protein. These results show that Nutlin induces the proteasomal degradation of Parp1 in a p53-dependent manner. Thus, this study demonstrates characterization of a novel regulatory mechanism of Parp1 protein. This novel regulatory mechanism of Parp1 protein level could contribute to development of inhibitors of the Parp1 signaling pathway.
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Alteration of P-gp expression after intestinal ischemia-reperfusion following 16-h fasting in rats.
Yakugaku Zasshi
PUBLISHED: 03-05-2011
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Alteration of P-glycoprotein (P-gp) expression influences the pharmacokinetics of P-gp substrates after intestinal ischemia-reperfusion (I/R). Fasting before intestinal I/R affects intestinal I/R injury. However, the effect of fasting on the alteration of P-gp expression after intestinal I/R has not been clarified. We previously reported that P-gp expression was altered after intestinal I/R following feeding. In the present study, we investigated the expression of P-gp after intestinal I/R following 16-h fasting. The mdr1a levels were decreased at 6 h in the jejunum, at 1 h in the ileum, at 6 and 24 h in the liver and at 6 h in the kidney. The mdr1b levels were decreased at 6 h in the ileum and at 1 and 6 h in the kidney. The mdr1b level in the liver was increased at 1 and 6 h. The expression of P-gp was decreased at 6 h in the jejunum, at 1, 6 and 24 h in the ileum, and at 6 h in the kidney. These alterations were different to those after intestinal I/R following feeding. In particular, the decrease in P-gp expression in the 16-h fasting I/R rats occurred at an early time during reperfusion compared with that in the feeding I/R rats. In conclusion, feeding condition affects the alteration of P-gp expression after intestinal I/R. Therefore, it is important to understand the patients feeding condition for safe drug therapy.
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Pharmacokinetic properties of lutein emulsion after oral administration to rats and effect of food intake on plasma concentration of lutein.
Biopharm Drug Dispos
PUBLISHED: 02-15-2011
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Lutein is a carotenoid found mainly in green leafy vegetables and is located in the macula lutea in the human eye. An intake of lutein as food is needed since humans cannot synthesize it de novo. Although lutein has received much attention recently due to its antioxidant activities, little information about the pharmacokinetic properties of lutein is available. Lutein emulsion formulation was used and the pharmacokinetics of lutein emulsion after oral administration to rats was investigated. The bioavailability of lutein using this formulation was calculated to be 5.20%. It was found that a large amount of lutein was accumulated in the intestinal mucosa. The absorption of orally administered compounds in the intestine can be enhanced by interaction with food or food components. Thus, the effect of food intake on the intestinal absorption of lutein was investigated. The plasma concentration of lutein after oral administration of the emulsion formulation was improved significantly by food intake. It is possible that the absorption of lutein in the intestine is improved significantly by some food components. Bile acids may also play important roles in the intestinal absorption of lutein since the absorption of lipophilic compounds such as cholesterol is related to bile acids. The results of these studies should contribute to an improvement of lutein absorption and provide important information for obtaining more effective pharmacological effects of lutein.
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Serum levels of BAFF and APRIL in myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated renal vasculitis: association with disease activity.
Nephron Clin Pract
PUBLISHED: 02-03-2011
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A proliferation-inducing ligand (APRIL) and the B cell activation factor belonging to the tumor necrosis factor family (BAFF) have proven to be key factors in the selection and survival of B cells, and a higher concentration of BAFF has been shown to contribute to autoreactive B cell survival and elevated autoantibody production. Here, serum BAFF and APRIL levels were investigated to analyze their association with disease activity in myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated renal vasculitis.
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Association of Th1/Th2-related chemokine receptors in peripheral T cells with disease activity in patients with multiple sclerosis and neuromyelitis optica.
Eur. Neurol.
PUBLISHED: 01-17-2011
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We evaluated 30 patients with clinically definite multiple sclerosis (MS) and 8 patients with neuromyelitis optica (NMO) to investigate correlations between Th1/Th2 balance, disease activity, effects of interferon (IFN)-? treatment, and expressions of chemokine receptors CXCR3 and CCR4 on CD4+ and CD8+ T cells in peripheral blood. MS and NMO patients in the relapsing phase showed a significantly increased CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio compared with respective patients in the remission phase. After IFN-? treatment, the CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio were significantly decreased compared with the relapsing phase and slightly lower than in the remission phase. The CD8+CXCR3+/CD8+CCR4+ ratio showed a more marked change associated with disease activity than CD4+ T cells in MS and NMO patients. Moreover, in patients in the relapsing phase of NMO, the CD4+CXCR3+/CD4+CCR4+ ratio and CD8+CXCR3+/CD8+CCR4+ ratio were significantly higher than in MS patients in the relapsing phase. We confirmed marked changes in the CD8+CXCR3+/CD8+CCR4+ ratio according to disease activity and treatment of MS and NMO. Furthermore, this ratio was more strongly linked to immune and inflammatory activity in NMO patients than in MS patients, and may represent an important factor in differentiating the pathogenesis of MS and NMO.
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Age estimation using cytochrome c oxidase activity analysis.
Forensic Sci. Int.
PUBLISHED: 01-15-2011
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Recently, in the field of forensic medicine the number of unidentified cadavers has increased due to mass disasters and international terrorism. In addition to the conventional anthropological methods, a simple and precise method to estimate the age of these unidentified cadavers to assist in the personal identification is necessary. On the other hand, many researchers have reported that mitochondrial respiratory activity decreases with aging because of the production of reactive oxidative species in the process of ATP generation. Therefore, it may be possible for us to estimate human age by analyzing mitochondrial activity. In this report we attempted to analyze cytochrome c oxidase (CCO) activity, and the amount of protein and mRNA expression in various aged rats. The age of human subjects was estimated through the analysis of human CCO activity from 28 actual forensic cases. The CCO activity, the amount of protein and the mRNA expression increased in the 3rd week and decreased afterwards in rats. Furthermore, human CCO activity was decreased gradually with aging. Therefore, CCO activity analysis may be useful for age estimation in forensic cases.
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Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-04-2011
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Systemic injections of AAV vectors generally transduce to the liver more effectively than to cardiac and skeletal muscles. The short hairpin RNA (shRNA)-expressing AAV9 (shRNA-AAV9) can also reduce target gene expression in the liver, but not enough in cardiac or skeletal muscles. Higher doses of shRNA-AAV9 required for inhibiting target genes in cardiac and skeletal muscles often results in shRNA-related toxicity including microRNA oversaturation that can induce fetal liver failure. In this study, we injected high-dose shRNA-AAV9 to neonates and efficiently silenced genes in cardiac and skeletal muscles without inducing liver toxicity. This is because AAV is most likely diluted or degraded in the liver than in cardiac or skeletal muscle during cell division after birth. We report that this systemically injected shRNA-AAV method does not induce any major side effects, such as liver dysfunction, and the dose of shRNA-AAV is sufficient for gene silencing in skeletal and cardiac muscle tissues. This novel method may be useful for generating gene knockdown in skeletal and cardiac mouse tissues, thus providing mouse models useful for analyzing diseases caused by loss-of-function of target genes.
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Pleuritis caused by Campylobacter jejuni subspecies jejuni in a patient undergoing long-term hemodialysis.
Intern. Med.
PUBLISHED: 11-15-2010
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A 73-year-old female hemodialysis patient experienced fever, shortness of breath on effort, and chest discomfort. A decrease in breath sounds in the right lung field, leukocytosis, elevated CRP level, and a right massive pleural effusion were observed. The patient was diagnosed with bacterial pleuritis based on leukocyte-predominant exudative pleural effusion, and treated with ceftriaxone. Her symptoms, however, were not improved, so thoracic drainage was attempted. Campylobacter species were isolated from cultured pleural fluid samples, and Campylobacter jejuni subspecies jejuni was detected on the multiplex PCR assay. The antibiotic was therefore changed to minocycline following pazufloxacin, and her symptoms were improved.
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Effects of calcium phosphate cement on the peripheral nerve fibers.
Kobe J Med Sci
PUBLISHED: 09-18-2010
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Calcium phosphate cement (CPC) is a bioactive ceramic substance. To clarify the effects of CPC on the peripheral nerve, we applied CPC on the peripheral nerve fibers of experimental animals and investigated the nerve fibers by electron microscopy and by immunoblotting analysis using an anti-myelin-associated glycoprotein (anti-MAG) antibody. The results showed that there was neither axonal sprouting at the nodes of Ranvier nor down-regulation of MAG beyond the normal level in the nerve fibers. These findings suggest that there is no harm in using CPC near the peripheral nerve fibers.
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Analysis of 472 Brånemark system TiUnite implants:a retrospective study.
Kobe J Med Sci
PUBLISHED: 09-18-2010
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The purpose of this retrospective study was to determine the success of Brånemark System TiUnite implants (Nobel Biocare/Sweden) placed in partially or completely edentulous jaws restored with fixed or removable prostheses.
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Regulation of monocarboxylate transporter 1 in skeletal muscle cells by intracellular signaling pathways.
Biol. Pharm. Bull.
PUBLISHED: 09-09-2010
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Skeletal muscle is the major producer of lactic acid in the body, but its oxidative fibers also use lactic acid as a respiratory fuel. Monocarboxylate transporter (MCT) 1 has been suggested to play a major role in influx of L-lactic acid for oxidation. The regulation mechanism of MCT1 was characterized utilizing rhabdomyosarcoma cells as an in vitro skeletal muscle model. The uptake of L-lactic acid via MCT1 was studied in the presence of various intracellular regulatory pathways, including pathways mediated by protein kinases A, C and G (PKA, PKC and PKG), protein tyrosine kinase (PTK), and Ca2+/calmodulin modulators. The results showed that PKG-, PTK-, and Ca2+/calmodulin-mediated regulatory pathways play no role in the regulation of L-lactic acid uptake, but a role for PKC- and PKA-mediated pathways was apparent. Uptake of L-lactic acid appeared to be stimulated by phorbol 12-myristate 13-acetate (PMA, a PKC activator) via an increase in Vmax of transport processes with no alteration in Km. In parallel, PMA treatment also resulted in an increase in the level of MCT1 expression. On the other hand, exposure to 8-Br-cAMP, a cAMP analog, and to forskolin, an adenylyl cyclase activator, resulted in a significant decrease in L-lactic acid uptake. Additionally, 8-Br-cAMP reduced Vmax but not Km values. Parallel to the decrease in Vmax of L-lactic acid uptake, the level of MCT1 expression was decreased in response to incubation with 8-Br-cAMP. These results indicate the possible involvement of a PKC- and PKA-mediated pathway associated with expression of MCT1 and lactate transport.
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Methicillin-resistant Staphylococcus-aureus-associated glomerulonephritis on the decline: decreased incidence since the 1990s.
Clin. Exp. Nephrol.
PUBLISHED: 08-30-2010
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We believe that bacterial-infection-associated glomerulonephritis (GN), so-called methicillin-resistant Staphylococcus aureus (MRSA)-GN, was exterminated in Japan. The control of bacterial infection is the most important part of infection-associated GN. In 1990s Japan, hospital-associated MRSA (HA-MRSA) caused MRSA-GN outbreaks. On the other hand, MRSA-GN incidence has been quite limited since 2000. This epidemiological transition suggests that antibacterial therapies and health programs for HA-MRSA infection in Japan were effective against MRSA-GN. Moreover, it appears that staphylococcal superantigens act in the pathogenesis of GN. The change of superantigen production might have influenced to the disappearance of MRSA-GN. If HA-MRSA-producing superantigen outbreaks occur in developing countries, our experience in Japan can provide guiding principles for preventing and eradicating GN.
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Serum ratio of soluble triggering receptor expressed on myeloid cells-1 to creatinine is a useful marker of infectious complications in myeloperoxidase-antineutrophil cytoplasmic antibody-associated renal vasculitis.
Nephrol. Dial. Transplant.
PUBLISHED: 08-13-2010
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The contribution of infections to the mortality of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients is important and should induce early and careful control of these events. However, the differentiation of infection from active vasculitis is often difficult. The usefulness of serum-soluble triggering receptor expressed on myeloid cells-1 (TREM-1) for detecting the presence of infectious complications regardless of disease activity was investigated.
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AMP-activated protein kinase regulates the expression of monocarboxylate transporter 4 in skeletal muscle.
Life Sci.
PUBLISHED: 07-15-2010
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The aim of this study was to determine the effect of 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, on monocarboxylate transporter 4 (MCT4) expression in rat skeletal muscle and a prototypic embryonal rhabdomyosarcoma cell line (RD cells).
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In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid.
Int J Pharm
PUBLISHED: 07-06-2010
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Dietary polyphenols are thought to be beneficial for human health as antioxidants. Coffee beans contain a common polyphenol, chlorogenic acid. Chlorogenic acid is the ester of caffeic acid and quinic acid. Although these polyphenols have received much attention, there is little evidence indicating a relationship between the effect and the rate of absorption. In this study, we focused on the beneficial effects of chlorogenic acid and caffeic acid, a major metabolite of chlorogenic acid. We carried out in vitro and in vivo experiments. In the in vitro study, caffeic acid had stronger antioxidant activity than that of chlorogenic acid. The uptake of chlorogenic acid by Caco-2 cells was much less than that of caffeic acid. The physiological importance of an orally administered compound depends on its availability for intestinal absorption and subsequent interaction with target tissues. We then used an intestinal ischemia-reperfusion model to evaluate antioxidant activities in vivo. We found that both chlorogenic acid and caffeic acid had effects on intestinal ischemia-reperfusion injury. Since caffeic acid has a stronger antioxidant activity than that of chlorogenic acid and chlorogenic acid is hydrolyzed into caffeic acid in the intestine, it is possible that caffeic acid plays a major role in the protective effect of chlorogenic acid against ischemia-reperfusion injury.
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Exceptional reducibility of complex-valued neural networks.
IEEE Trans Neural Netw
PUBLISHED: 06-14-2010
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A neural network is referred to as minimal if it cannot reduce the number of hidden neurons that maintain the input-output map. The condition in which the number of hidden neurons can be reduced is referred to as reducibility. Real-valued neural networks have only three simple types of reducibility. It can be naturally extended to complex-valued neural networks without bias terms of hidden neurons. However, general complex-valued neural networks have another type of reducibility, referred to herein as exceptional reducibility. In this paper, another type of reducibility is presented, and a method by which to minimize complex-valued neural networks is proposed.
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Robust control of the seasonal expression of the Arabidopsis FLC gene in a fluctuating environment.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-07-2010
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Plants flower in particular seasons even in natural, fluctuating environments. The molecular basis of temperature-dependent flowering-time regulation has been extensively studied, but little is known about how gene expression is controlled in natural environments. Without a memory of past temperatures, it would be difficult for plants to detect seasons in natural, noisy environments because temperature changes occurring within a few weeks are often inconsistent with seasonal trends. Our 2-y census of the expression of a temperature-dependent flowering-time gene, AhgFLC, in a natural population of perennial Arabidopsis halleri revealed that the regulatory system of this flowering-time gene extracts seasonal cues as if it memorizes temperatures over the past 6 wk. Time-series analysis revealed that as much as 83% of the variation in the AhgFLC expression is explained solely by the temperature for the previous 6 wk, but not by the temperatures over shorter or longer periods. The accuracy of our model in predicting the gene expression pattern under contrasting temperature regimes in the transplant experiments indicates that such modeling incorporating the molecular bases of flowering-time regulation will contribute to predicting plant responses to future climate changes.
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The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein.
Mol Neurodegener
PUBLISHED: 05-20-2010
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Parkinsons disease (PD) involves the selective damage of dopaminergic neuron cells resulting from the accumulation and fibril formation of alpha-synuclein. Recently, it has been shown that not only full-length alpha-synuclein, but also C-terminal truncated forms exist in the normal brain, as well as Lewy bodies, which are cytoplasmic inclusions in PD. It is known that truncated alpha-synuclein has a much higher ability to aggregate and fibrillate than full-length alpha-synuclein. Since the fibrils and precursor oligomers of alpha-synuclein are cytotoxic to the neuron, inhibitors that prevent the formation of oligomers and/or fibrils might open the way to a novel therapeutic approach to PD. However, no inhibitor for truncated alpha-synuclein has been reported yet.
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Pharmacokinetics of oral and intravenous administration of digoxin after intestinal ischemia-reperfusion.
Biol. Pharm. Bull.
PUBLISHED: 05-13-2010
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Intestinal ischemia-reperfusion (I/R) causes gut dysfunction characterized by decreased basement membrane integrity and decreased barrier function. Indeed, it has been reported that the absorption of several drugs is altered after intestinal I/R. Intestinal I/R also promotes multi-organ failure (MOF). The liver and kidney can be affected by MOF after intestinal I/R. However, little is known about the alteration of pharmacokinetics after intravenous administration in intestinal I/R injury. In the present study, we investigated pharmacokinetics of digoxin after oral administration and intravenous administration in intestinal I/R injury. Plasma digoxin concentration in I/R rats after oral administration was not significantly altered at any time compared with that in sham-operated rats. Plasma digoxin concentration in rats reperfused for 1 h after intravenous administration was significantly higher than that in sham-operated rats. Plasma digoxin concentrations in rats reperfused for 6 and 24 h were the same as those in sham-operated rats. The area under the concentration.time curve after intravenous administraion (AUC(i.v.)) and total clearance (CL(tot)) in rats reperfused for 1 h was 1.89- and 0.57-fold higher than that in sham-operated rats. However, elimination rate (k(e)) and half-life (t(1/2)) in rats reperfused for 1 h were not altered. Distribution volume (V(d)) in rats reperfused for 1 h was decreased than that in sham-operated rats, but there was not statistical difference. These results suggest that intestinal I/R affected the V(d) of digoxin, and plasma concentration of digoxin was increased. The present study suggests that understanding pharmacokinetics of drug after intravenous administration in intestinal I/R injury is important to provide valuable information for safe drug therapy for intestinal I/R patients.
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Uniform silica coated fluorescent nanoparticles: synthetic method, improved light stability and application to visualize lymph network tracer.
PLoS ONE
PUBLISHED: 05-12-2010
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The sentinel lymph node biopsy (SLNB) was developed as a new modality in the surgical diagnosis of lymph node metastases. Dye and radioisotope are major tracers for the detection of sentinel lymph nodes (SLN). Dye tends to excessively infiltrate into the interstitium due to their small size (less than several nanometers), resulting in difficulties in maintaining clear surgical fields. Radioisotopes are available in limited number of hospitals. Fluorescent nanoparticles are good candidates for SLN tracer to solve these problems, as we can choose suitable particle size and fluorescence wavelength of near-infrared. However, the use of nanoparticles faces safety issues, and many attempts have been performed by giving insulating coats on nanoparticles. In addition, the preparation of the uniform insulating layer is important to decrease variations in the quality as an SLN tracer.
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Blood compatibility of the adsorptive device filled with poly arylate beads.
Biomed Mater Eng
PUBLISHED: 05-08-2010
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The clinical treatments with blood purification therapy is most suitable in which a blood compatible adsorbent is employed. In the present study, two kinds of adsorber with different filling ratio (% rate with a bulk volume in the column volume (v)) with 83% (PAB-83) and 100% (PAB-100) were prepared, respectively. The adsorbent (PAB - Poly Arylate Beads), which was filled up in the column, was prepared with the phase-inversion method. Usually the major problems of blood purification therapy are blood clotting and the residual blood in the column during/after therapy process. The therapy should be interrupted when the internal pressure of the column dramatically go up by such problems. We concluded that PAB does not affect the blood clotting formation in terms of endogenous clotting parameters, i.e., activated partial thromboplastin time (APTT), prothrombin time (PT) and the amount of fibrinogen (Fib). They lead to not dramatically decreasing of the essential protein. These adsorbers might be available to use as the adsorptive device for the blood purification therapy.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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