Sample records for hinh vung hoat
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Uwai, Yuichi; Taniguchi, Risa; Motohashi, Hideyuki; Saito, Hideyuki; Okuda, Masahiro; Inui, Ken-ichi
2004-10-01
Human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8) are responsible for renal tubular secretion of an antifolic acid methotrexate, and are considered to be involved in drug interaction of methotrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). In our hospital, a delay of methotrexate elimination was experienced in a patient with Hodgkin's disease, who took loxoprofen, a commonly used NSAID in Japan, which suggested a cause. In this study, we examined the drug interaction via hOAT1 and hOAT3, using Xenopus laevis oocytes. hOAT1 and hOAT3 mediated the methotrexate transport with low affinity (K(m) of 724.0 muM) and high affinity (K(m) of 17.2 muM), respectively. Loxoprofen and its trans-OH metabolite, an active major metabolite, markedly inhibited the methotrexate transport by both transporters. Their inhibition concentrations (IC(50)) were in the range of the therapeutic levels. These findings suggest that loxoprofen retards the elimination of methotrexate, at least in part, by inhibiting hOAT1 and hOAT3.
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Uwai, Yuichi; Honjo, Hiroaki; Iwamoto, Kikuo
2010-01-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) delay renal excretion of antifolate methotrexate by inhibiting human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8). In this study, we performed uptake experiments using Xenopus laevis oocytes to assess the inhibitory effect of selective cyclooxygenase-2 inhibitors on hOAT1 and hOAT3. The uptake of methotrexate into oocytes was increased by the injection of hOAT1 and hOAT3 cRNA, and transport was strongly inhibited by lumiracoxib. The apparent 50% inhibitory concentrations of lumiracoxib were estimated to be 3.3 µM and 1.9 µM for uptake of p-aminohippurate by hOAT1 and of estrone sulfate by hOAT3, respectively. Eadie-Hofstee plot analysis showed that lumiracoxib inhibited hOAT1 and hOAT3 in a competitive manner. For other cyclooxygenase-2 inhibitors celecoxib, etoricoxib, rofecoxib and valdecoxib, slight to moderate inhibition of hOAT3 only was observed. These findings show that lumiracoxib has inhibitory potential toward hOAT1 and hOAT3, comparable to that of nonselective NSAIDs.
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Race, J E; Grassl, S M; Williams, W J; Holtzman, E J
1999-02-16
The cloned organic anion transporters from rat, mouse, and winter flounder (rOAT1, mOAT1, fROAT) mediate the coupled exchange of alpha-ketoglutarate with multiple organic anions, including p-aminohippurate (PAH). We have isolated two novel gene products from human kidney which bear significant homology to the known OATs and belong to the amphiphilic solute facilitator (ASF) family. The cDNAs, hOAT1 and hOAT3, encode for 550- and 568-amino-acid residue proteins, respectively. hOAT1 and hOAT3 mRNAs are expressed strongly in kidney and weakly in brain. Both genes map to chromosome 11 region q11.7. PAH uptake by Xenopus laevis oocytes injected with hOAT1 mRNA is increased 100-fold compared to water-injected oocytes. PAH uptake is chloride dependent and is not further increased by preincubation of oocytes in 5 mM glutarate. Uptake of PAH is inhibited by probenicid, alpha-ketoglutarate, bumetanide, furosemide, and losartan, but not by salicylate, urate, choline, amilioride, and hydrochlorothiazide. Copyright 1999 Academic Press.
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Honjo, Hiroaki; Uwai, Yuichi; Iwamoto, Kikuo
2011-04-01
It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) delay the elimination of methotrexate. One of the mechanisms is thought to be inhibition of methotrexate uptake via human organic anion transporter 3 (hOAT3, SLC22A8) in the renal proximal tubule by NSAIDs. In this study, we evaluated the inhibitory effects of selective cyclooxygenase-2 inhibitor etoricoxib on hOAT3 by uptake experiments using Xenopus laevis oocytes. The injection of hOAT3 cRNA stimulated the uptake of methotrexate into the oocytes, and its transport was inhibited by etoricoxib. Etoricoxib inhibited estrone sulfate uptake by hOAT3 dose dependently, and the 50% inhibitory concentration was estimated to be 9.8 µM. Eadie-Hofstee plot analysis showed that etoricoxib inhibited hOAT3 in a competitive manner. These findings show that etoricoxib has inhibitory effect on hOAT3, and that the potential is comparable to that of traditional NSAIDs. ©2011 Bentham Science Publishers Ltd.
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The role of dileucine in the expression and function of human organic anion transporter 1 (hOAT1)
Zhang, Qiang; Wu, Jinwei; Pan, Zui; You, Guofeng
2011-01-01
Human organic anion transporter hOAT1 plays a critical role in the body disposition of environmental toxins and clinically important drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. In the current study, we investigated the role of dileucine (L6L7) at the amino terminus of hOAT1 in the expression and function of the transporter. We substituted L6L7 with alanine (A) simultaneously. The resulting mutant transporter L6A/L7A showed no transport activity due to its complete loss of expression at the cell surface. Such loss of surface expression of L6A/L7A was consistent with a complete loss of an 80 kDa mature form and a dramatic decrease in a 60 kDa immature form of the mutant transporter in the total cell lysates. Treatment of L6A/L7A-expressing cells with proteasomal inhibitor resulted in a significant increase in the immature form of hOAT1, but not its mature form, whereas treatment of these cells with lysosomal inhibitor had no effect on the expression of the mutant transporters, suggesting that the mutant transporter was degraded through proteasomal pathway. The accumulation of mutant transporter in the endoplasmic reticulum (ER) was confirmed by coimmunolocalization of L6L7 with calnexin, an ER marker. Furthermore, treatment of L6A/L7A-expressing cells with sodium 4-phenylbutyrate (4PBA) and glycerol, two chemical chaperones, could not promote the exit of the immature form of the mutant transporter from the ER. Our data suggest that L6L7 are critical for the stability and ER export of hOAT1. PMID:21494320
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The Role of Dileucine in the Expression and Function of Human Organic Anion Transporter 1 (hOAT1).
Zhang, Qiang; Wu, Jinwei; Pan, Zui; You, Guofeng
2011-01-01
Human organic anion transporter hOAT1 plays a critical role in the body disposition of environmental toxins and clinically important drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. In the current study, we investigated the role of dileucine (L6L7) at the amino terminus of hOAT1 in the expression and function of the transporter. We substituted L6L7 with alanine (A) simultaneously. The resulting mutant transporter L6A/L7A showed no transport activity due to its complete loss of expression at the cell surface. Such loss of surface expression of L6A/L7A was consistent with a complete loss of an 80 kDa mature form and a dramatic decrease in a 60 kDa immature form of the mutant transporter in the total cell lysates. Treatment of L6A/L7A-expressing cells with proteasomal inhibitor resulted in a significant increase in the immature form of hOAT1, but not its mature form, whereas treatment of these cells with lysosomal inhibitor had no effect on the expression of the mutant transporters, suggesting that the mutant transporter was degraded through proteasomal pathway. The accumulation of mutant transporter in the endoplasmic reticulum (ER) was confirmed by coimmunolocalization of L6L7 with calnexin, an ER marker. Furthermore, treatment of L6A/L7A-expressing cells with sodium 4-phenylbutyrate (4PBA) and glycerol, two chemical chaperones, could not promote the exit of the immature form of the mutant transporter from the ER. Our data suggest that L6L7 are critical for the stability and ER export of hOAT1.
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Nicolette, John; Neft, Robin E; Vanosdol, Jessica; Murray, Joel
2016-04-01
The peptide bond-forming reagents 1-hydroxy-7-azabenzotriazole (HOAt, CAS 39968-33-7) and O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, CAS 148893-10-1) either have structural alerts, unclassified features or are considered out of domain when evaluated for potential mutagenicity with in silico programs DEREK and CaseUltra. Since they are commonly used reagents in pharmaceutical drug syntheses, they may become drug substance or drug product impurities and would need to be either controlled to appropriately safe levels or tested for mutagenicity. Both reagents were tested in the bacterial reverse mutation (Ames) test at Covance, under GLP conditions, following the OECD test guideline and ICH S2(R1) recommendations and found to be negative. Our data show that HOAt and HATU-common pharmaceutical synthesis reagents-are not mutagenic, and can be treated as ordinary drug impurities. © 2016 Wiley Periodicals, Inc.
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Duan, Peng; Li, Shanshan; Ai, Ni; Hu, Longqin; Welsh, William J.; You, Guofeng
2012-01-01
Transporter-mediated drug-drug interactions in the kidney dramatically influence the pharmacokinetics and other clinical effects of drugs. Human organic anion transporters 1 (hOAT1) and 3 (hOAT3) are the major transporters in the basolateral membrane of kidney proximal tubules, mediating the rate-limiting step in the elimination of a broad spectrum of drugs. In the present study, we screened two clinical drug libraries against hOAT1 and hOAT3. Of the 727 compounds screened, 92 compounds inhibited hOAT1 and 262 compounds inhibited hOAT3. When prioritized based on the peak unbound plasma concentrations of these compounds, three inhibitors for hOAT1 and seven inhibitors for hOAT3 were subsequently identified with high inhibitory potency (>95%). Computational analyses revealed that inhibitors and non-inhibitors can be differentiated from each other on the basis of several physico-chemical features, including: number of hydrogen-bond donors, number of rotatable bonds, and topological polar surface area (TPSA) for hOAT1; and molecular weight, number of hydrogen-bond donors and acceptors, TPSA, partition coefficient (Log P7.4), and polarizability for hOAT3. Pharmacophore modeling identified two common structural features associated with inhibitors for hOAT1 and hOAT3, viz., an anionic hydrogen-bond acceptor atom, and an aromatic center separated by ~5.7 Å. Such model provides mechanistic insights for predicting new OAT inhibitors. PMID:22973893
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Duan, Peng; Li, Shanshan; Ai, Ni; Hu, Longqin; Welsh, William J; You, Guofeng
2012-11-05
Transporter-mediated drug-drug interactions in the kidney dramatically influence the pharmacokinetics and other clinical effects of drugs. Human organic anion transporters 1 (hOAT1) and 3 (hOAT3) are the major transporters in the basolateral membrane of kidney proximal tubules, mediating the rate-limiting step in the elimination of a broad spectrum of drugs. In the present study, we screened two clinical drug libraries against hOAT1 and hOAT3. Of the 727 compounds screened, 92 compounds inhibited hOAT1 and 262 compounds inhibited hOAT3. When prioritized based on the peak unbound plasma concentrations of these compounds, three inhibitors for hOAT1 and seven inhibitors for hOAT3 were subsequently identified with high inhibitory potency (>95%). Computational analyses revealed that inhibitors and noninhibitors can be differentiated from each other on the basis of several physicochemical features, including number of hydrogen-bond donors, number of rotatable bonds, and topological polar surface area (TPSA) for hOAT1; and molecular weight, number of hydrogen-bond donors and acceptors, TPSA, partition coefficient (log P(7.4)), and polarizability for hOAT3. Pharmacophore modeling identified two common structural features associated with inhibitors for hOAT1 and hOAT3, viz., an anionic hydrogen-bond acceptor atom, and an aromatic center separated by ∼5.7 Å. Such model provides mechanistic insights for predicting new OAT inhibitors.
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Paudel, Prakash; Ramson, Prasidh; Naduvilath, Thomas; Wilson, David; Phuong, Ha Thanh; Ho, Suit M; Giap, Nguyen V
2014-04-01
To assess the prevalence of vision impairment and refractive error in school children 12-15 years of age in Ba Ria - Vung Tau province, Vietnam. Prospective, cross-sectional study. 2238 secondary school children. Subjects were selected based on stratified multistage cluster sampling of 13 secondary schools from urban, rural and semi-urban areas. The examination included visual acuity measurements, ocular motility evaluation, cycloplegic autorefraction, and examination of the external eye, anterior segment, media and fundus. Visual acuity and principal cause of vision impairment. The prevalence of uncorrected and presenting visual acuity ≤6/12 in the better eye were 19.4% (95% confidence interval, 12.5-26.3) and 12.2% (95% confidence interval, 8.8-15.6), respectively. Refractive error was the cause of vision impairment in 92.7%, amblyopia in 2.2%, cataract in 0.7%, retinal disorders in 0.4%, other causes in 1.5% and unexplained causes in the remaining 2.6%. The prevalence of vision impairment due to myopia in either eye (-0.50 diopter or greater) was 20.4% (95% confidence interval, 12.8-28.0), hyperopia (≥2.00 D) was 0.4% (95% confidence interval, 0.0-0.7) and emmetropia with astigmatism (≥0.75 D) was 0.7% (95% confidence interval, 0.2-1.2). Vision impairment due to myopia was associated with higher school grade and increased time spent reading and working on a computer. Uncorrected refractive error, particularly myopia, among secondary school children in Vietnam is a major public health problem. School-based eye health initiative such as refractive error screening is warranted to reduce vision impairment. © 2013 The Authors. Clinical & Experimental Ophthalmology published by Wiley Publishing Asia Pty Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.
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Wang, Li; Sweet, Douglas H
2012-10-15
Phenolic acids exert beneficial health effects such as anti-oxidant, anti-carcinogenic, and anti-inflammatory activities and show systemic exposure after consumption of common fruits, vegetables, and beverages. However, knowledge regarding which components convey therapeutic benefits and the mechanism(s) by which they cross cell membranes is extremely limited. Therefore, we determined the inhibitory effects of nine food-derived phenolic acids, p-coumaric acid, ferulic acid, gallic acid, gentisic acid, 4-hydroxybenzoic acid, protocatechuic acid, sinapinic acid, syringic acid, and vanillic acid, on human organic anion transporter 1 (hOAT1), hOAT3, and hOAT4. In the present study, inhibition of OAT-mediated transport of prototypical substrates (1 μM) by phenolic acids (100 μM) was examined in stably expressing cell lines. All compounds significantly inhibited hOAT3 transport, while just ferulic, gallic, protocatechuic, sinapinic, and vanillic acid significantly blocked hOAT1 activity. Only sinapinic acid inhibited hOAT4 (~35%). For compounds exhibiting inhibition > ~60%, known clinical plasma concentration levels and plasma protein binding in humans were examined to select compounds to evaluate further with dose-response curves (IC(50) values) and drug-drug interaction (DDI) index determinations. IC(50) values ranged from 1.24 to 18.08 μM for hOAT1 and from 7.35 to 87.36 μM for hOAT3. Maximum DDI indices for gallic and gentisic acid (≫0.1) indicated a very strong potential for DDIs on hOAT1 and/or hOAT3. This study indicates that gallic acid from foods or supplements, or gentisic acid from salicylate-based drug metabolism, may significantly alter the pharmacokinetics (efficacy and toxicity) of concomitant therapeutics that are hOAT1 and/or hOAT3 substrates. Copyright © 2012 Elsevier Inc. All rights reserved.
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Zhang, Qiang; Suh, Wonmo; Pan, Zui; You, Guofeng
2012-01-01
Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate that PKC plays critical roles in the trafficking and the stability of hOAT3. PMID:22773962
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Paudel, Prakash; Ramson, Prasidh; Naduvilath, Thomas; Wilson, David; Phuong, Ha Thanh; Ho, Suit M; Giap, Nguyen V
2014-01-01
Background To assess the prevalence of vision impairment and refractive error in school children 12–15 years of age in Ba Ria – Vung Tau province, Vietnam. Design Prospective, cross-sectional study. Participants 2238 secondary school children. Methods Subjects were selected based on stratified multistage cluster sampling of 13 secondary schools from urban, rural and semi-urban areas. The examination included visual acuity measurements, ocular motility evaluation, cycloplegic autorefraction, and examination of the external eye, anterior segment, media and fundus. Main Outcome Measures Visual acuity and principal cause of vision impairment. Results The prevalence of uncorrected and presenting visual acuity ≤6/12 in the better eye were 19.4% (95% confidence interval, 12.5–26.3) and 12.2% (95% confidence interval, 8.8–15.6), respectively. Refractive error was the cause of vision impairment in 92.7%, amblyopia in 2.2%, cataract in 0.7%, retinal disorders in 0.4%, other causes in 1.5% and unexplained causes in the remaining 2.6%. The prevalence of vision impairment due to myopia in either eye (–0.50 diopter or greater) was 20.4% (95% confidence interval, 12.8–28.0), hyperopia (≥2.00 D) was 0.4% (95% confidence interval, 0.0–0.7) and emmetropia with astigmatism (≥0.75 D) was 0.7% (95% confidence interval, 0.2–1.2). Vision impairment due to myopia was associated with higher school grade and increased time spent reading and working on a computer. Conclusions Uncorrected refractive error, particularly myopia, among secondary school children in Vietnam is a major public health problem. School-based eye health initiative such as refractive error screening is warranted to reduce vision impairment. PMID:24299145
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The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1
Xu, Da; Wang, Haoxun; Gardner, Carol; Pan, Zui; Zhang, Ping L.; Zhang, Jinghui
2016-01-01
Human organic anion transporter 1 (hOAT1), expressed at the basolateral membrane of kidney proximal tubule cells, mediates the active renal secretion of a diverse array of clinically important drugs, including anti-human immunodeficiency virus therapeutics, antitumor drugs, antibiotics, antihypertensives, and anti-inflammatories. We have previously demonstrated that posttranslational modification of hOAT1 by ubiquitination is an important mechanism for the regulation of this transporter. The present study aimed at identifying the ubiquitin ligase for hOAT1 and its mechanism of action. We showed that overexpression of neural precursor cell expressed, developmentally downregulated (Nedd)4-1, an E3 ubiquitin ligase, enhanced hOAT1 ubiquitination, decreased hOAT1 expression at the cell surface, and inhibited hOAT1 transport activity. In contrast, overexpression of the ubiquitin ligase-dead mutant Nedd4-1/C867S was without effects on hOAT1. Furthermore, knockdown of endogenously expressed Nedd4-1 by Nedd4-1-specific small interfering RNA reduced hOAT1 ubiquitination. Immunoprecipitation experiments in cultured cells and rat kidney slices and immunofluorescence experiments in rat kidney slices showed that there was a physical interaction between OAT1 and Nedd4-1. Nedd4-1 contains four protein-protein interacting WW domains. When these WW domains were inactivated by mutating two amino acid residues in each of the four WW domains (Mut-WW1: V210W/H212G, Mut-WW2: V367W/H369G, Mut-WW3: I440W/H442G, and Mut-WW4: I492W/H494G, respectively), only Mut-WW2 and Mut-WW3 significantly lost their ability to bind and to ubiquitinate hOAT1. As a result, Mut-WW2 and Mut-WW3 were unable to suppress hOAT1-mediated transport as effectively as wild-type Nedd4-1. In conclusion, this is the first demonstration that Nedd4-1 regulates hOAT1 ubiquitination, expression, and transport activity through its WW2 and WW3 domains. PMID:27226107
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The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1.
Xu, Da; Wang, Haoxun; Gardner, Carol; Pan, Zui; Zhang, Ping L; Zhang, Jinghui; You, Guofeng
2016-08-01
Human organic anion transporter 1 (hOAT1), expressed at the basolateral membrane of kidney proximal tubule cells, mediates the active renal secretion of a diverse array of clinically important drugs, including anti-human immunodeficiency virus therapeutics, antitumor drugs, antibiotics, antihypertensives, and anti-inflammatories. We have previously demonstrated that posttranslational modification of hOAT1 by ubiquitination is an important mechanism for the regulation of this transporter. The present study aimed at identifying the ubiquitin ligase for hOAT1 and its mechanism of action. We showed that overexpression of neural precursor cell expressed, developmentally downregulated (Nedd)4-1, an E3 ubiquitin ligase, enhanced hOAT1 ubiquitination, decreased hOAT1 expression at the cell surface, and inhibited hOAT1 transport activity. In contrast, overexpression of the ubiquitin ligase-dead mutant Nedd4-1/C867S was without effects on hOAT1. Furthermore, knockdown of endogenously expressed Nedd4-1 by Nedd4-1-specific small interfering RNA reduced hOAT1 ubiquitination. Immunoprecipitation experiments in cultured cells and rat kidney slices and immunofluorescence experiments in rat kidney slices showed that there was a physical interaction between OAT1 and Nedd4-1. Nedd4-1 contains four protein-protein interacting WW domains. When these WW domains were inactivated by mutating two amino acid residues in each of the four WW domains (Mut-WW1: V210W/H212G, Mut-WW2: V367W/H369G, Mut-WW3: I440W/H442G, and Mut-WW4: I492W/H494G, respectively), only Mut-WW2 and Mut-WW3 significantly lost their ability to bind and to ubiquitinate hOAT1. As a result, Mut-WW2 and Mut-WW3 were unable to suppress hOAT1-mediated transport as effectively as wild-type Nedd4-1. In conclusion, this is the first demonstration that Nedd4-1 regulates hOAT1 ubiquitination, expression, and transport activity through its WW2 and WW3 domains. Copyright © 2016 the American Physiological Society.
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The activity of organic anion transporter-3: Role of dexamethasone.
Wang, Haoxun; Liu, Chenchang; You, Guofeng
2018-02-01
Human organic anion transporter-3 (hOAT3) is richly expressed in the kidney, where it plays critical roles in the secretion, from the blood to urine, of clinically important drugs, such as anti-viral therapeutics, anti-cancer drugs, antibiotics, antihypertensives, and anti-inflammatories. In the current study, we examined the role of dexamethasone in hOAT3 transport activity in the kidney HEK293 cells. Cis-inhibition study showed that dexamethasone exhibited a concentration-dependent inhibition of hOAT3-mediated uptake of estrone sulfate, a prototypical substrate for the transporter, with IC 50 value of 49.91 μM. Dixon plot analysis revealed that inhibition by dexamethasone was competitive with a Ki = 47.08 μM. In contrast to the cis-inhibition effect of dexamethasone, prolonged incubation (6 h) of hOAT3-expressing cells with dexamethasone resulted in an upregulation of hOAT3 expression and transport activity, kinetically revealed as an increase in the maximum transport velocity V max without meaningful alteration in substrate-binding affinity K m . Such upregulation was abrogated by GSK650394, a specific inhibitor for serum- and glucocorticoid-inducible kinases (sgk). Dexamethasone also enhanced sgk1 phosphorylation. Our study demonstrated that dexamethasone exhibits dual effects on hOAT3: it is a competitive inhibitor for hOAT3-mediated transport, and interestingly, when entering the cells, it stimulates hOAT3 expression and transport activity through sgk1. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
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Yuan, Yuan; Yang, Hua; Kong, Linghua; Li, Yuan; Li, Ping; Zhang, Hongjian; Ruan, Jianqing
2017-11-01
Rhein, a major bioactive compound of many medicinal herbs and the prodrug of diacerein, is often used with low dose of methotrexate as drug combination to treat rheumatoid arthritis. In this study, potential drug-drug interaction between methotrexate and rhein was investigated based on organic anion transporters (OAT). Our study demonstrated that rhein acyl glucuronide (RAG), the major metabolite of rhein in the human blood circulation, significantly inhibited the uptake of p-aminohippurate in hOAT1 transfected cells with IC 50 value of 691 nM and estrone sulfate uptake in hOAT3 transfected cells with IC 50 value of 78.5 nM. As the substrate of both hOAT1 and hOAT3, the methotrexate transport was significantly inhibited by RAG in hOAT1 transfected cells at 50 μM and hOAT3 transfected cells at 1 μM by 69% and 87%, respectively. Further in vivo study showed that after co-administrated with RAG in rats the AUC 0-24 values of methotrexate increased from 3109 to 5370 ng/mL*hr and the t 1/2 was prolonged by 40.5% (from 7.4 to 10.4 h), demonstrating the inhibitory effect of RAG on methotrexate excretion. In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. The combination use of rhein, diacerein or other rhein-containing herbs with methotrexate may cause obvious drug-drug interaction and require close monitoring for potential drug interaction in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.
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Zalups, Rudolfs K; Ahmad, Sarfaraz
2005-11-01
Recently, the activity of the organic anion transporter 1 (OAT1) protein has been implicated in the basolateral uptake of inorganic mercuric species in renal proximal tubular cells. Unfortunately, very little is known about the role of OAT1 in the renal epithelial transport of organic forms of mercury, such as methylmercury (CH(3)Hg(+)). Homocysteine (Hcy) S-conjugates of methylmercury [(S)-(3-amino-3-carboxypropylthio)(methyl)mercury (CH(3)Hg-Hcy)] have been identified recently as being potentially important biologically relevant forms of mercury. Thus, the present study was designed to characterize the transport of CH(3)Hg-Hcy in Madin-Darby canine kidney (MDCK) cells (which are derived from the distal nephron) that were transfected stably with the human isoform of OAT1 (hOAT1). Data on saturation kinetics, time dependence, substrate specificity, and temperature dependence demonstrated that CH(3)Hg-Hcy is a transportable substrate of hOAT1. However, substrate-specificity data from the control MDCK cells also showed that CH(3)Hg-Hcy is a substrate of one or more transporter(s) that is/are not hOAT1. Additional findings indicated that at least one amino acid transport system was probably responsible for this transport. It is noteworthy that the activity of amino acid transporters accounted for the greatest level of uptake of CH(3)Hg-Hcy in the hOAT1-expressing cells. Furthermore, rates of survival of the hOAT1-transfected MDCK cells were significantly lower than those of corresponding control MDCK cells when they were exposed to cytotoxic concentrations of CH(3)Hg-Hcy. Collectively, the present data indicate that CH(3)Hg-Hcy is a transportable substrate of OAT1 and amino acid transporters and, thus, is probably a transportable mercuric species taken up in vivo by proximal tubular epithelial cells.
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Maeda, Akimitsu; Tsuruoka, Shuichi; Ushijima, Kentarou; Kanai, Yoshikatsu; Endou, Hitoshi; Saito, Kazuyuki; Miyamoto, Etsuko; Fujimura, Akio
2010-08-25
Methotrexate has a clinically important pharmacokinetic interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) mainly through its competition for tubular secretion via the renal organic anion transporter 3 (OAT3). We have previously reported the usefulness of OAT3-transfected renal tubular cells for screening of the drugs which interfere with the pharmacokinetics of methotrexate. Celecoxib, a cyclooxygenase (COX) 2 inhibitor, has not been reported to interact with methotrexate, but the mechanisms are unclear why the interaction did not occur. The purpose of this study was to evaluate the effect of celecoxib on methotrexate tubular secretion using a renal cell line stably expressing human OAT3 (S2-hOAT3), and to evaluate the pharmacokinetic interaction of the two drugs in rats. [3H]methotrexate uptake into S2-hOAT3 cells was significantly inhibited by celecoxib in a concentration-dependent manner and the Ki value was 35.3 microM. However, methotrexate serum concentrations and urinary excretion of methotrexate over 24 h in rats were not affected by celecoxib (50, 200 mg/kg). Celecoxib serum concentrations were increased by the increase in celecoxib dosage and the maximum drug concentration (Cmax) was 20.6 microM (celecoxib 200 mg/kg), which did not reach the Ki value obtained in the in vitro study. These results indicated that celecoxib inhibited the secretion of methotrexate via hOAT3, which suggested that celecoxib was a substrate of hOAT3. However, co-administration of the two drugs at clinical dosage did not affect the pharmacokinetics of methotrexate, because the serum concentrations did not reach the Ki value. Although the accumulation study using S2-hOAT3 cells was useful to predict the interaction between the new drug and methotrexate in vivo, a comparison of the Ki value with the Cmax in clinical dosage was necessary to evaluate the degree of this interaction. Copyright (c) 2010 Elsevier B.V. All rights reserved.
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ERIC Educational Resources Information Center
Sandgren, Olof; Andersson, Richard; van de Weijer, Joost; Hansson, Kristina; Sahlén, Birgitta
2014-01-01
Purpose: To investigate gaze behavior during communication between children with hearing impairment (HI) and normal-hearing (NH) peers. Method: Ten HI-NH and 10 NH-NH dyads performed a referential communication task requiring description of faces. During task performance, eye movements and speech were tracked. Using verbal event (questions,…
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Han, Shu-Fen; Jiao, Jun; Zhang, Wei; Xu, Jia-Ying; Zhang, Weiguo; Fu, Chun-Ling; Qin, Li-Qiang
2017-01-01
Dietary fiber consumption is associated with reduced risk for the development of noncommunicable diseases. The aim of the present study was to evaluate the effects of cereal dietary fiber on the levels of proteins involved in lipolysis and thermogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT) of C57 BL/6 J mice fed a high-fat diet (HFD). Male C57BL/6 J mice were fed normal chow diet (Chow), HFD, HFD plus oat fiber (H-oat), or HFD plus wheat bran fiber (H-wheat) for 24 wk. Body weight and food intake were recorded weekly. Serum adiponectin was assayed by an enzyme-linked immunosorbent assay kit. Western blotting was used to assess the protein expressions of adipose triacylglycerol lipase (ATGL), cAMP protein kinase catalytic subunit (cAMP), protein kinase A (PKA), perilipin A, hormone-sensitive lipase (HSL), uncoupling protein 1 (UCP1), fibroblast growth factor 21 (FGF-21), β3-adrenergic receptor (β3AR), and proliferator-activated receptor gamma coactivator-1 α (PGC-1 α) in the WAT and BAT. At the end of the feeding period, body and adipose tissues weight in both H-oat and H-wheat groups were lower than in the HFD group. Mice in the H-oat and H-wheat groups showed an increasing trend in serum adiponectin level. Compared with the HFD group, cereal dietary fiber increased protein expressions involved in the lipolysis and browning process. Compared with the H-wheat group, H-oat was more effective in protein expressions of PKA, PGC-1 α, and UCP1 of the WAT samples. Compared with the H-oat group, H-wheat was more effective in protein expressions of PKA, ATGL, UCP1, β3AR, and FGF-21 of the BAT samples. Taken together, our results suggested that cereal dietary fiber enhanced adipocyte lipolysis by the cAMP-PKA-HSL pathway and promoted WAT browning by activation of UCP1, and consequently reduced visceral fat mass in response to HFD feeding. Copyright © 2016 Elsevier Inc. All rights reserved.
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U. S. Naval Forces, Vietnam Monthly Historical Supplement for June 1968
1969-02-18
some of the cargo, and a Harbor Clearance Unit to assist in rigging beach gear CQk MT1IAL 90 7777 77- CO0N I P waWi usL on the John C. As the tugs which...personnel in Vietnam, a mooring buoy was moved from Ben Tre to Dong Tau. !LLC-l, with Harbor Clearance Team THREE embarked, soiled from Vung Tan on 27 June
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U. S. Naval Forces, Vietnam Monthly Historical Supplement for April 1968
1968-10-11
CHNAVVLAT (Code 04)(2) COMSEVENTFLT (Hist. Team ) Pres, NAVWARCOL .. ". COMPHIBLANT COMWHIBPAC COMCBPAC COMBLANT COI4NAVFACENGCOM U...ganda Team with a Australian Advisor, about 31 miles north of Vinh Lcng. PbR 87 landed the troops embarked and the Australian 0 Advisor, but when PBR...responded to the situation and apprehended one man who was turned over to the Vietnamese National Police, The Royal Australian diving team at Vung - Tau
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Immunological Interrelationships of Coliform Heat-Labile and Heat-Stable Enterotoxins
1981-09-01
FA, Engert RF: Immunological interrelationships between cholera toxin and the heat -labile and hoat-stable enterotoxins of coliform bacteria. Infec...Immun 18:110, 1977 2. Klipstein FA, Engert RF: Immunological relationship of different preparations of coliform enterotoxins. Infec Immun 21:771, 1978...3. Klipstein FA, Engert RF: Reversal of jejunal water secretion by glucose in rats exposed to coliform enterotoxins. Gastroenteroloj y 75:255, 1978 4
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Research Investigation of Armor Plate Steels
1942-02-20
heats at three different hardness levels, The results were plotbed as curves which are given in Figures 84 to 99 inclusive. Jominy hardonability ...inclusive) were selected, along with the 27 heats listed in the Febri ry 6 report, to indicate the hardonability characteristics of the original...are shown as Figures 84 to 99, inclusive. G. Jominy Hardonability Study. End quench hardenability tests wore made on the remaining hoats studied to date
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Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin
2014-06-01
This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp
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P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jia, Yongming
The purpose of present study was to investigate the effect of resveratrol (Res) on altering methotrexate (MTX) pharmacokinetics and clarify the related molecular mechanism. Res significantly increased rat intestinal absorption of MTX in vivo and in vitro. Simultaneously, Res inhibited MTX efflux transport in MDR1-MDCK and MRP2-MDCK cell monolayers, suggesting that the target of drug interaction was MDR1 and MRP2 in the intestine during the absorption process. Furthermore, there was a significant decrease in renal clearance of MTX after simultaneous intravenous administration. Similarly, MTX uptake was markedly inhibited by Res in rat kidney slices and hOAT1/3-HEK293 cell, indicating that OAT1more » and OAT3 were involved in the drug interaction in the kidney. Additionally, concomitant administration of Res decreased cytotoxic effects of MTX in hOAT1/3-HEK293 cells, and ameliorated nephrotoxicity caused by MTX in rats. Conversely, intestinal damage caused by MTX was not exacerbated after Res treatment. In conclusion, Res enhanced MTX absorption in intestine and decreased MTX renal elimination by inhibiting P-gp, MRP2, OAT1 and OAT3 in vivo and in vitro. Res improved MTX-induced renal damage without increasing intestinal toxicity. - Highlights: • DDI between MTX and Res will occur when they are co-administered. • The first targets of the DDI are P-gp and MRP2 located in intestine. • The second targets of the DDI are OAT1 and OAT3 in kidney. • Res improved MTX-induced renal damage without increasing intestinal toxicity.« less
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Neutrophil extracellular traps can activate alternative complement pathways.
Wang, H; Wang, C; Zhao, M-H; Chen, M
2015-09-01
The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg-EGTA)-treated human serum. After incubation of serum with supernatants enriched in ANCA-induced NETs, levels of complement components in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b-9 on NETs incubated with heat-inactivated normal human serum (Hi-NHS) or EGTA-treated Hi-NHS (Mg-EGTA-Hi-NHS) were significantly less than that on NETs incubated with NHS or EGTA-treated NHS (Mg-EGTA-NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b-9 concentration decreased from 800·42 ± 244·81 ng/ml, 7·68 ± 1·50 ng/ml, 382·15 ± 159·75 ng/ml in the supernatants enriched in ANCA induced NETs to 479·07 ± 156·2 ng/ml, 4·86 ± 1·26 ng/ml, 212·65 ± 44·40 ng/ml in the supernatants of DNase I-degraded NETs (P < 0·001, P = 0·008, P < 0·001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV. © 2015 British Society for Immunology.
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Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid.
Nakagawa, Hatsuki; Hirata, Taku; Terada, Tomohiro; Jutabha, Promsuk; Miura, Daisaku; Harada, Kouji H; Inoue, Kayoko; Anzai, Naohiko; Endou, Hitoshi; Inui, Ken-Ichi; Kanai, Yoshikatsu; Koizumi, Akio
2008-07-01
Perfluorooctanoic acid, an environmental contaminant, is found in both wild animals and human beings. There are large species and sex differences in the renal excretion of perfluorooctanoic acid. In the present study, we aimed to characterize organic anion transporters 1-3 (OAT1-3) in human beings and rats to investigate whether the species differences in the elimination kinetics of perfluorooctanoic acid from the kidneys can be attributed to differences in the affinities of these transporters for perfluorooctanoic acid. We used human (h) and rat (r) OAT transient expression cell systems and measured the [(14)C] perfluorooctanoic acid transport activities. Both human and rat OAT1 and OAT3 mediated perfluorooctanoic acid transport to similar degrees. Specifically, the kinetic parameters, K(m), were 48.0 +/- 6.4 microM for h OAT1; 51.0 +/- 12.0 microM for rOAT1; 49.1 +/- 21.4 microM for hOAT3 and 80.2 +/- 17.8 microM for rOAT3, respectively. These data indicate that both human and rat OAT1 and OAT3 have high affinities for perfluorooctanoic acid and that the species differences in its renal elimination are not attributable to affinity differences in these OATs between human beings and rats. In contrast, neither hOAT2 nor rOAT2 transported perfluorooctanoic acid. In conclusion, OAT1 and OAT3 mediated perfluorooctanoic acid transport in vitro, suggesting that these transporters also transport perfluorooctanoic acid through the basolateral membrane of proximal tubular cells in vivo in both human beings and rats. Neither human nor rat OAT2 mediated perfluorooctanoic acid transport. Collectively, the difference between the perfluorooctanoic acid half-lives in human beings and rats is not likely to be attributable to differences in the affinities of these transporters for perfluorooctanoic acid.
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Weiss, Julia; Terry, Marta I; Martos-Fuentes, Marina; Letourneux, Lisa; Ruiz-Hernández, Victoria; Fernández, Juan A; Egea-Cortines, Marcos
2018-02-14
Cowpea (Vigna unguiculata) is an important source of protein supply for animal and human nutrition. The major storage globulins VICILIN and LEGUMIN (LEG) are synthesized from several genes including LEGA, LEGB, LEGJ and CVC (CONVICILIN). The current hypothesis is that the plant circadian core clock genes are conserved in a wide array of species and that primary metabolism is to a large extent controlled by the plant circadian clock. Our aim was to investigate a possible link between gene expression of storage proteins and the circadian clock. We identified cowpea orthologues of the core clock genes VunLHY, VunTOC1, VunGI and VunELF3, the protein storage genes VunLEG, VunLEGJ, and VunCVC as well as nine candidate reference genes used in RT-PCR. ELONGATION FACTOR 1-A (ELF1A) resulted the most suitable reference gene. The clock genes VunELF3, VunGI, VunTOC1 and VunLHY showed a rhythmic expression profile in leaves with a typical evening/night and morning/midday phased expression. The diel patterns were not completely robust and only VungGI and VungELF3 retained a rhythmic pattern under free running conditions of darkness. Under field conditions, rhythmicity and phasing apparently faded during early pod and seed development and was regained in ripening pods for VunTOC1 and VunLHY. Mature seeds showed a rhythmic expression of VunGI resembling leaf tissue under controlled growth chamber conditions. Comparing time windows during developmental stages we found that VunCVC and VunLEG were significantly down regulated during the night in mature pods as compared to intermediate ripe pods, while changes in seeds were non-significant due to high variance. The rhythmic expression under field conditions was lost under growth chamber conditions. The core clock gene network is conserved in cowpea leaves showing a robust diel expression pattern except VunELF3 under growth chamber conditions. There appears to be a clock transcriptional reprogramming in pods and seeds compared to
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Nguyen, Tri; Stewart, Donald Edwin; Lee, Chiao Tzu Patricia; Dang, Thi Nhu Hang
2017-08-01
Female sex workers (FSWs) are at heightened risk of HIV infection. This research aims to determine the prevalence of HIV and relevant risk factors and related behavior among FSWs in Ba Ria - Vung Tau, a southeast province of Vietnam. 420 FSWs were interviewed using a structured questionnaire and biological samples tested for HIV. 2.6 % were found to be HIV positive. HIV infection was significantly higher in FSWs who had low income (≤AUD 200 per month), have had anal sex, have had sex with injecting drug users, and had a low level of HIV/AIDS-related knowledge. Improved employment opportunities and income are important to reduce the pressure for young women to engage in sex work for income purposes, but in public health terms, existing HIV treatment, prevention and intervention programs needs better targeting and improvements to reduce the risk of HIV infection.
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Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.
Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario
2016-08-08
DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.
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Sandgren, Olof; Andersson, Richard; van de Weijer, Joost; Hansson, Kristina; Sahlén, Birgitta
2014-06-01
To investigate gaze behavior during communication between children with hearing impairment (HI) and normal-hearing (NH) peers. Ten HI-NH and 10 NH-NH dyads performed a referential communication task requiring description of faces. During task performance, eye movements and speech were tracked. Using verbal event (questions, statements, back channeling, and silence) as the predictor variable, group characteristics in gaze behavior were expressed with Kaplan-Meier survival functions (estimating time to gaze-to-partner) and odds ratios (comparing number of verbal events with and without gaze-to-partner). Analyses compared the listeners in each dyad (HI: n = 10, mean age = 12;6 years, mean better ear pure-tone average = 33.0 dB HL; NH: n = 10, mean age = 13;7 years). Log-rank tests revealed significant group differences in survival distributions for all verbal events, reflecting a higher probability of gaze to the partner's face for participants with HI. Expressed as odds ratios (OR), participants with HI displayed greater odds for gaze-to-partner (ORs ranging between 1.2 and 2.1) during all verbal events. The results show an increased probability for listeners with HI to gaze at the speaker's face in association with verbal events. Several explanations for the finding are possible, and implications for further research are discussed.
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Viet Nam steps up offshore E and D push
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1992-06-22
This paper reports on Viet Nam's offshore exploration and development. Hanoi tentatively awarded three of five remaining blocks of prime offshore South China Sea acreage to companies from Europe and the Far East, with a fourth such award reported imminent. And state owned Petrovietnam signed a production sharing contract (PSC) covering acreage in the same area to a combine of British Petroleum Co. plc and Norway's Den norske stats oljeselskap AS. Retention of one block in the area covered by Viet Nam's second bidding round fueled speculation Hanoi is holding it in reserve for U.S. companies to enter bidding, pendingmore » easing of U.S. trade sanctions against Viet Nam, Agence France France (AFP) reported. Second round blocks have been carved from a concession held by Vietsovpetro, a joint venture of Petrovietnam and the former Soviet Union. All are in the southern Con Sun basin of the South China Sea off the port of Vung Tao and on trend with Viet Nam's only producing oil fields.« less
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Vassilieva, Anna B; Gogoleva, Svetlana S; Poyarkov, Nikolay A Jr
2016-06-24
We present new data on the distribution, reproduction, larval morphology and vocalization of Rhacophorus helenae (Rhacophoridae), a narrowly distributed frog from southern Vietnam. Two new populations of R. helenae were discovered during field surveys in the lowland monsoon forests in Dong Nai and Ba Ria-Vung Tau provinces in 2010-2013. Spawning was observed in May 2013. Egg clutches containing small (2.3±0.1 mm) unpigmented eggs were embedded in a foam nest and suspended high on trees above temporary ponds. The tadpoles of R. helenae have a morphology typical of pond-dwelling Rhacophorus larvae with a moderate tail length and a labial tooth row formula of 5(2-5)/3. Postmetamorphic juveniles differed from adult frogs in the features of their coloration and less developed webbing. The complex vocal repertoire of R. helenae included five types of tonal, wideband and pulsed calls and several transitional signal types differentiated by frequency and amplitude parameters. Calls were uttered as singular signals (pulsed calls) or within non-stereotyped series of variable duration (other call types). The complex structure of the advertisement call markedly distinguishes R. helenae from other members of the Rhacophorus reinwardtii species complex.
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Paudel, Prakash; Kovai, Vilas; Naduvilath, Thomas; Phuong, Ha Thanh; Ho, Suit May; Giap, Nguyen Viet
2016-01-01
To assess validity of teacher-based vision screening and elicit factors associated with accuracy of vision screening in Vietnam. After brief training, teachers independently measured visual acuity (VA) in 555 children aged 12-15 years in Ba Ria - Vung Tau Province. Teacher VA measurements were compared to those of refractionists. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for uncorrected VA (UVA) and presenting VA (PVA) 20/40 or worse in either eye. Chi-square, Fisher's exact test and multivariate logistic regression were used to assess factors associated with accuracy of vision screening. Level of significance was set at 5%. Trained teachers in Vietnam demonstrated 86.7% sensitivity, 95.7% specificity, 86.7% positive predictive value and 95.7% negative predictive value in identifying children with visual impairment using the UVA measurement. PVA measurement revealed low accuracy for teachers, which was significantly associated with child's age, sex, spectacle wear and myopic status, but UVA measurement showed no such associations. Better accuracy was achieved in measurement of VA and identification of children with visual impairment using UVA measurement compared to PVA. UVA measurement is recommended for teacher-based vision screening programs.
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A new species of the genus Leptolalax (Anura: Megophryidae) from southern Vietnam
Van Duong, Tang; Do, Dang Trong; Ngo, Chung Dac; Nguyen, Truong Quang; Poyarkov, Nikolay A.
2018-01-01
We describe a new species of megophryid frog from Phu Yen Province in southern Vietnam. Leptolalax macrops sp. nov. is distinguished from its congeners by a combination of the following morphological attributes: (1) body size medium (SVL 28.0–29.3 mm in three adult males, 30.3 mm in single adult female); (2) supra-axillary glands present, creamy white; ventrolateral glands indistinct; (3) tympanum externally distinct; (4) dorsal skin roughly granular with larger tubercles, dermal ridges on dorsum absent; (5) rudimentary webbing present between fingers I–II and II–III; rudimentary webbing between all toes; fingers and toes without dermal fringes; (6) in life ventral surface greyish-violet with white speckling; (7) supratympanic fold distinct, dark brown in life; (8) iris bicolored, typically golden in upper half, fading to golden green in lower half; (9) tibia short (TbL/SVL 0.44–0.45 in males); and (10) eyes large and protuberant (ED/SVL 0.15–0.16 in males). From all congeners for which comparable sequences are available, the new species differs markedly in the 16S rRNA mitochondrial gene sequence (P-distance>5.7%). The new species is currently known only from montane evergreen tropical forests of Song Hinh District, Phu Yen Province, and M’Drak District of Dak Lak Province at elevations of 470–630 m a.s.l.. We suggest the new species should be considered as Data Deficient following the IUCN’s Red List categories. We also report a previously unknown Leptolalax mtDNA lineage from an evergreen tropical forest in the Hoa Thinh District of Phu Yen Province, which may also represent an undescribed species. PMID:29643325
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A new species of the genus Leptolalax (Anura: Megophryidae) from southern Vietnam.
Duong, Tang Van; Do, Dang Trong; Ngo, Chung Dac; Nguyen, Truong Quang; Poyarkov, Nikolay A
2018-05-18
We describe a new species of megophryid frog from Phu Yen Province in southern Vietnam. Leptolalax macrops sp. nov. is distinguished from its congeners by a combination of the following morphological attributes: (1) body size medium (SVL 28.0-29.3 mm in three adult males, 30.3 mm in single adult female); (2) supra-axillary glands present, creamy white; ventrolateral glands indistinct; (3) tympanum externally distinct; (4) dorsal skin roughly granular with larger tubercles, dermal ridges on dorsum absent; (5) rudimentary webbing present between fingers I-II and II-III; rudimentary webbing between all toes; fingers and toes without dermal fringes; (6) in life ventral surface greyish-violet with white speckling; (7) supratympanic fold distinct, dark brown in life; (8) iris bicolored, typically golden in upper half, fading to golden green in lower half; (9) tibia short (TbL/SVL 0.44-0.45 in males); and (10) eyes large and protuberant (ED/SVL 0.15-0.16 in males). From all congeners for which comparable sequences are available, the new species differs markedly in the 16S rRNA mitochondrial gene sequence (P-distance>5.7%). The new species is currently known only from montane evergreen tropical forests of Song Hinh District, Phu Yen Province, and M'Drak District of Dak Lak Province at elevations of 470-630 m a.s.l. We suggest the new species should be considered as Data Deficient following the IUCN's Red List categories. We also report a previously unknown Leptolalax mtDNA lineage from an evergreen tropical forest in the Hoa Thinh District of Phu Yen Province, which may also represent an undescribed species.
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Fan, Lijun; Hou, Xiang-Yu; Zhao, Jingzhou; Sun, Jiandong; Dingle, Kaeleen; Purtill, Rhonda; Tapp, Sam; Lukin, Bill
2016-02-09
There has been considerable publicity regarding population ageing and hospital emergency department (ED) overcrowding. Our study aims to investigate impact of one intervention piloted in Queensland Australia, the Hospital in the Nursing Home (HiNH) program, on reducing ED and hospital attendances from residential aged care facilities (RACFs). A quasi-experimental study was conducted at an intervention hospital undertaking the program and a control hospital with normal practice. Routine Queensland health information system data were extracted for analysis. Significant reductions in the number of ED presentations per 1000 RACF beds (rate ratio (95 % CI): 0.78 (0.67-0.92); p = 0.002), number of hospital admissions per 1000 RACF beds (0.62 (0.50-0.76); p < 0.0001), and number of hospital admissions per 100 ED presentations (0.61 (0.43-0.85); p = 0.004) were noticed in the experimental hospital after the intervention; while there were no significant differences between intervention and control hospitals before the intervention. Pre-test and post-test comparison in the intervention hospital also presented significant decreases in ED presentation rate (0.75 (0.65-0.86); p < 0.0001) and hospital admission rate per RACF bed (0.66 (0.54-0.79); p < 0.0001), and a non-significant reduction in hospital admission rate per ED presentation (0.82 (0.61-1.11); p = 0.196). Hospital in the Nursing Home program could be effective in reducing ED presentations and hospital admissions from RACF residents. Implementation of the program across a variety of settings is preferred to fully assess the ongoing benefits for patients and any possible cost-savings.
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Qiao, Xiaoqiang; Sun, Liangliang; Chen, Lingfan; Zhou, Yuan; Yang, Kaiguang; Liang, Zhen; Zhang, Lihua; Zhang, Yukui
2011-03-15
Piperazine-based derivatives, including 1-(2-pyridyl)piperazine (2-PP), 1-(2-pyrimidyl)piperazine (2-PMP), 1-(4-pyridyl)piperazine (4-PP), and 1-(1-methyl-4-piperidinyl)piperazine (M-PP), were used for the derivatization of carboxyl groups on peptides with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 1-hydroxy-7-azabenzotriazole (HOAt) as coupling reagents, and trifluoroacetic acid (TFA) as activator. Taking synthetic peptides RVYVHPI (RI-7) and APGDRIYVHPF (AF-11) as samples, the yields of derivatized peptides by 2-PP, 2-PMP and 4-PP were higher than 94%. The effect of piperazine derivatives on the signals of tryptic digests of α-transferrin and bovine serum albumin (BSA) was investigated, and it was found that peptides derivatized by 2-PP and 2-PMP exhibited obviously improved ionization efficiency. Furthermore, comparison of identified peptides before and after derivatization showed that peptides with low molecular weight (MW) and high pI value were preferably detected after derivatization. In addition, after derivatization with 2-PP and 2-PMP, protein myelin basic protein S, 20 kDa protein, and histone H were confidently identified from the tryptic digests of two fractions of rat brain protein separated by reversed-phase high-performance liquid chromatography (HPLC), indicating the potential application of 2-PP and 2-PMP for the highly sensitive determination of peptides in comprehensive proteome analysis. Copyright © 2011 John Wiley & Sons, Ltd.
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Appearance of reassortant European avian-origin H1 influenza A viruses of swine in Vietnam.
Takemae, N; Nguyen, P T; Le, V T; Nguyen, T N; To, T L; Nguyen, T D; Pham, V P; Vo, H V; Le, Q V T; Do, H T; Nguyen, D T; Uchida, Y; Saito, T
2018-03-06
Three subtypes-H1N1, H1N2 and H3N2-of influenza A viruses of swine (IAVs-S) are currently endemic in swine worldwide, but there is considerable genotypic diversity among each subtype and limited geographical distribution. Through IAVs-S monitoring in Vietnam, two H1N2 influenza A viruses were isolated from healthy pigs in Ba Ria-Vung Tau Province, Southern Vietnam, on 2 December 2016. BLAST and phylogenetic analyses revealed that their HA and NA genes were derived from those of European avian-like H1N2 IAVs-S that contained avian-origin H1 and human-like N2 genes, and were particularly closely related to those of IAVs-S circulating in the Netherlands, Germany or Denmark. In addition, the internal genes of these Vietnamese isolates were derived from human A(H1N1)pdm09 viruses, suggesting that the Vietnamese H1N2 IAVs-S are reassortants between European H1N2 IAVs-S and human A(H1N1)pdm09v. The appearance of European avian-like H1N2 IAVs-S in Vietnam marks their first transmission outside Europe. Our results and statistical analyses of the number of live pigs imported into Vietnam suggest that the European avian-like H1N2 IAVs-S may have been introduced into Vietnam with their hosts through international trade. These findings highlight the importance of quarantining imported pigs to impede the introduction of new IAVs-S. © 2018 Blackwell Verlag GmbH.
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Zhang, Ru; Jiao, Jun; Zhang, Wei; Zhang, Zheng; Zhang, Weiguo; Qin, Li-Qiang; Han, Shu-Fen
2016-01-01
Cereal fiber is reported to be associated with obesity and metabolic diseases. However, whether cereal fiber improves leptin resistance and sensitivity remains unclear. For 24 weeks, 48 male C57BL/6J mice were randomly given a normal chow diet (Chow), high-fat/cholesterol diet (HFD), HFD with 0.8% oat fiber (H-oat) or HFD with 0.8% wheat bran fiber (H-wheat). At the end of feeding period, both the serum insulin and leptin levels were determined by ELISA kits. Western blotting was used to assess the protein expressions of the leptin receptor (LepR) and the leptin-signaling pathway in the adipose tissues. Our results suggested that mice fed oat or wheat bran fiber exhibited lower body weight, serum lipids, as well as insulin and leptin levels. The two cereal fibers potently increased the protein expressions of LepR in the adipose tissue. In addition, protein expressions of Janus kinase 2 (JAK2) and transcription 3 (STAT3) (induced by LepR), which enhances leptin signaling, were significantly higher and the expression of cytokine signaling-3 (SOCS3), which inhibits leptin signaling, was significantly lower in the two cereal fiber groups than in the HFD group. Taken together, our findings suggest that cereal fiber can improve leptin resistance and sensitivity by the JAK2/STAT3 pathway in C57BL/6J mice fed a HFD; furthermore, oat fiber is more effective in the improvement of leptin sensitivity than wheat bran fiber, in this murine model.
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Weaver ant role in cashew orchards in Vietnam.
Peng, Renkang; Lan, La Pham; Christian, Keith
2014-08-01
Cashew (Anacardium occidentale L.) is a very important source of income for more than 200,000 farmer households in Vietnam. The present cashew productivity in Vietnam is low and unstable, and pest damage is partly responsible for this. Cashew farmers rely on pesticides to minimize the damage, resulting in adverse impacts on farm environment and farmers' health. Weaver ants (Oecophylla spp) are effective biocontrol agents of a range of cashew insect pests in several cashew-growing countries, and these ants are widely distributed in Vietnam. The aim of this study is to evaluate the potential of weaver ants in cashew orchards in Vietnam. Field surveys and field experiment were conducted in five cashew orchards from July 2006 to January 2008 in Binh Phuoc, Dong Nai, and Ba Ria Vung Tau provinces, Vietnam. Based on the field surveys, the most important pests that damage flushing foliar and floral shoots and young cashew fruits and nuts were mosquito bugs, brown shoot borers, blue shoot borers, and fruit-nut borers. The damage caused by each of these pests was significantly lower on trees with weaver ants compared with trees without the ants, showing that the ants were able to keep these pest damages under the control threshold. Regular monitoring of the field experiment showed that weaver ants were similar to insecticides for controlling mosquito bugs, blue shoot borers, fruit-nut borers, leaf rollers, and leaf miners. Aphids did not become major pests in plot with weaver ants. To manage insect pest assemblage in cashew orchards, an integrated pest management using weaver ants as a major component is discussed.
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Effect of school eye health promotion on children's eye health literacy in Vietnam.
Paudel, Prakash; Yen, Phung Thi; Kovai, Vilas; Naduvilath, Thomas; Ho, Suit May; Giap, Nguyen Viet; Holden, Brien A
2017-10-06
Health promotion intervention in schools is a useful strategy to improve students' health awareness. The purpose of this study was to assess the effect of eye health promotion interventions on eye health literacy in school children in Vietnam. A piloted questionnaire was administered to 300 children from five secondary schools in Ba Ria-Vung Tau, Vietnam at baseline and re-administered after the eye health promotion interventions. McNemar chi-square and logistic regression were used for statistical analysis. A total of 300 children aged 12-15 years (mean, 13.3 ± 1.3 years; 60% female) participated in the baseline survey. The participation rate in the post-health promotion survey was 94.7%. After the health promotion interventions, number of children who had correct eye health knowledge increased by 10-20% (60-75% to 70-95%), more children reported having had an eye examination (63.3% to 84.7%; p < 0.001) and more reported wearing spectacles (36.1% to 43.4%; p = 0.04). Children in urban schools were twice as likely to have improved knowledge of vision loss compared with children in rural schools (odds ratio, 2.1-4.1; p = 0.01 to p < 0.001). Children from rural schools had significantly higher odds of visiting doctor after the eye problems worsened (odds ratio, 4.5; p < 0.001). These results imply that eye health promotion interventions significantly improve eye health knowledge, attitudes and practices of school children. Additionally, participation of parents and teachers as change agents may further improve children's health literacy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Hashemi, H; Miraftab, M; Asgari, S
2014-09-01
To compare the visual outcomes between PRK-MMC and phakic IOL in patients with more than 8 diopter (D) of myopia. This comparative study was performed on 23 eyes under treatment with Artiflex (group A) and 23 eyes under treatment with PRK-MMC (group B). Artiflex phakic IOL (Ophtec BV) was used in group A, and the VISX STAR S4 Excimer Laser (Abbott) was used for PRK-MMC in group B. The safety index was 1.11 ± 0.23 and 1.05 ± 0.25 (P = 0.100) and the efficacy index was 1.02 ± 0.11 and 0.98 ± 0.10 (P = 0.266) in group A and B, respectively. At 1 year after surgery, the manifest refraction spherical equivalent was -0.17 ± 1.18 and -0.25 ± 0.18 D in group A and B, respectively (P = 0.471). Mesopic CS showed no significant difference between the two groups in any spatial frequency. Total coma was 0.24 ± 0.17 and 0.67 ± 0.40 μm (P < 0.001), spherical aberration was -0.11 ± 0.11 and 0.41 ± 0.18 μm (P < 0.001), and RMS HOAT was 0.50 ± 0.20 and 0.96 ± 0.45 μm (P<0.001) in group A and B, respectively. Phakic IOL implantation was better than PRK-MMC in the correction of high myopia in terms of visual quality, but the two methods had no difference with regard to visual acuity. Therefore, PRK-MMC can be used when the anterior chamber depth is a limiting factor in the implantation of phakic IOLs.
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NASA Astrophysics Data System (ADS)
Bui, H. T.; Ho, L. T.; Ushijima, K.; Nur, A.
2006-12-01
Determination of porosity and permeability plays a key role either in characterization of a reservoir or in development of an oil field. Their distribution helps to predict the major faults or fractured zones that are related to high porosity area in order to reduce drilling hazards. Porosity and permeability of the rock can be determined directly from the core sample or obtained from well log data such as: sonic, density, neutron or resistivity. These input parameters depend not only on porosity (?) but also on the rock matrix, fluids contained in the rocks, clay mineral component, or geometry of pore structures. Therefore, it is not easy to estimate exactly porosity and permeability since having corrected those values by conventional well log interpretation method. In this study, the Artificial Neural Networks (ANNs) have been used to derive porosity and permeability directly from well log data for Vung Dong oil prospect, southern offshore Vietnam. Firstly, we designed a training patterns for ANNs from neutron porosity, bulk density, P-sonic, deep resistivity, shallow resistivity and MSFL log curves. Then, ANNs were trained by core samples data for porosity and permeability. Several ANNs paradigms have been tried on a basis of trial and error. The batch back- propagation algorithm was found more proficient in training porosity network meanwhile the quick propagation algorithm is more effective in the permeability network. Secondly, trained ANNs was tested and applied for real data set of some wells to calculate and reveal the distribution maps of porosity or permeability. Distributions of porosity and permeability have been correlated with seismic data interpretation to map the faults and fractured zones in the study. The ANNs showed good results of porosity and permeability distribution with high reliability, fast, accurate and low cost features. Therefore, the ANNs should be widely applied in oil and gas industry.
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Hashemi, H; Miraftab, M; Asgari, S
2014-01-01
Purpose To compare the visual outcomes between PRK-MMC and phakic IOL in patients with more than 8 diopter (D) of myopia. Methods This comparative study was performed on 23 eyes under treatment with Artiflex (group A) and 23 eyes under treatment with PRK-MMC (group B). Artiflex phakic IOL (Ophtec BV) was used in group A, and the VISX STAR S4 Excimer Laser (Abbott) was used for PRK-MMC in group B. Results The safety index was 1.11±0.23 and 1.05±0.25 (P=0.100) and the efficacy index was 1.02±0.11 and 0.98±0.10 (P=0.266) in group A and B, respectively. At 1 year after surgery, the manifest refraction spherical equivalent was −0.17±1.18 and −0.25±0.18 D in group A and B, respectively (P=0.471). Mesopic CS showed no significant difference between the two groups in any spatial frequency. Total coma was 0.24±0.17 and 0.67±0.40 μm (P<0.001), spherical aberration was −0.11±0.11 and 0.41±0.18 μm (P<0.001), and RMS HOAT was 0.50±0.20 and 0.96±0.45 μm (P<0.001) in group A and B, respectively. Conclusion Phakic IOL implantation was better than PRK-MMC in the correction of high myopia in terms of visual quality, but the two methods had no difference with regard to visual acuity. Therefore, PRK-MMC can be used when the anterior chamber depth is a limiting factor in the implantation of phakic IOLs. PMID:24993326
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Zhang, Melvyn Wb; Tran, Bach Xuan; Le, Huong Thi; Nguyen, Hinh Duc; Nguyen, Cuong Tat; Tran, Tho Dinh; Latkin, Carl A; Ho, Roger Cm
2017-09-07
perceptions of the information and the consequential use of that information. ©Melvyn WB Zhang, Bach Xuan Tran, Huong Thi Le, Hinh Duc Nguyen, Cuong Tat Nguyen, Tho Dinh Tran, Carl A Latkin, Roger CM Ho. Originally published in the Interactive Journal of Medical Research (http://www.i-jmr.org/), 07.09.2017.
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NASA Astrophysics Data System (ADS)
Chang, C.; Shen, C.; Chen, Y.; Chiang, H.; Lam, D. D.; Ngai, N.
2007-12-01
Monthly-resolution geochemical proxies, including δ18O, δ13C, Sr/Ca, and Ba/Ca, in a living Porites coral head, collected from Son Tra Island, a near-shore island located at the north tip of Vung Da Nang Bay, central Vietnam (16°12'59.4", 108°1'57.1"), was used to quantitatively reconstruct records of sea surface temperature (SST), sea surface salinity (SSS), seasonality of rainfall, and regional terrestrial input during a period of 1978-2004 AD. By comparing the 1/4-century geochemical data, five features are exhibited. (1) The coral Sr/Ca-inferred summer SSTs correspond well with the 1°x1° instrumental data to suggest that the regional SST record can be retrieved from this local coral head. (2) Interannual variation of coral winter SST data does not follow regional instrumental values. The harmonic phenomenon between coral inferred winter SST dynamic and the surface pressure difference, between the southern South China Sea (SCS) (0-10°N, 105-115°E) and the northern SCS (22.5-32.5°N, 112-122°E), indicating that the cold local SST induced by East Asian winter monsoon was addressed in the Son Tra coral. (3) 1‰ seasonal anomaly of δ18O residual (Δδ18O) suggests a 2-4-psu seasonal salinity change between dry and wet seasons. (4) The synchronous intra-annual changes of δ18O and Ba/Ca data suggest that the rainy season is from late summer to winter, which is consistent with the meteorological record. (5) The high Ba/Ca background level of 10 μmol/mol in 1992-2004, 2-3 times larger than the averaged value of 4 μmol/mol in 1978-1992, indicates an enhanced terrestrial sediment discharge into the bay over the past 10 years. Ba records probably reflect an impact of human activity on hydrological change since the Vietnam War.
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NASA Astrophysics Data System (ADS)
Heath, Garvin A.; Nazaroff, William W.
In previous work, we showed that the intake fraction (iF) for nonreactive primary air pollutants was 20 times higher in central tendency for small-scale, urban-sited distributed electricity generation (DG) sources than for large-scale, central station (CS) power plants in California [Heath, G.A., Granvold, P.W., Hoats, A.S., Nazaroff, W.W., 2006. Intake fraction assessment of the air pollutant exposure implications of a shift toward distributed electricity generation. Atmospheric Environment 40, 7164-7177]. The present paper builds on that study, exploring pollutant- and technology-specific aspects of population inhalation exposure from electricity generation. We compare California's existing CS-based system to one that is more reliant on DG units sited in urban areas. We use Gaussian plume modeling and a GIS-based exposure analysis to assess 25 existing CSs and 11 DG sources hypothetically located in the downtowns of California's most populous cities. We consider population intake of three pollutants—PM 2.5, NO x and formaldehyde—directly emitted by five DG technologies—natural gas (NG)-fired turbines, NG internal combustion engines (ICE), NG microturbines, diesel ICEs, and fuel cells with on-site NG reformers. We also consider intake of these pollutants from existing CS facilities, most of which use large NG turbines, as well as from hypothetical facilities located at these same sites but meeting California's best-available control technology standards. After systematically exploring the sensitivity of iF to pollutant decay rate, the iFs for each of the three pollutants for all DG and CS cases are estimated. To efficiently compare the pollutant- and technology-specific exposure potential on an appropriate common basis, a new metric is introduced and evaluated: the intake-to-delivered-energy ratio (IDER). The IDER expresses the mass of pollutant inhaled by an exposed population owing to emissions from an electricity generation unit per quantity of electric
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Knetsch, Peter A.; Zhai, Chuangyan; Rangger, Christine; Blatzer, Michael; Haas, Hubertus; Kaeopookum, Piriya; Haubner, Roland; Decristoforo, Clemens
2015-01-01
Over the last years Gallium-68 (68Ga) has received tremendous attention for labeling of radiopharmaceuticals for positron emission tomography (PET). 68Ga labeling of biomolecules is currently based on bifunctional chelators containing aminocarboxylates (mainly DOTA and NOTA). We have recently shown that cyclic peptide siderophores have very good complexing properties for 68Ga resulting in high specific activities and excellent metabolic stabilities, in particular triacetylfusarinine-C (TAFC). We postulated, that, starting from its deacetylated form (Fusarinine-C (FSC)) trimeric bioconjugates are directly accessible to develop novel targeting peptide based 68Ga labeled radiopharmaceuticals. As proof of principle we report on the synthesis and 68Ga-radiolabeling of a trimeric FSC-RGD conjugate, [68Ga]FSC-(RGD)3, targeting αvβ3 integrin, which is highly expressed during tumor-induced angiogenesis. Synthesis of the RGD peptide was carried out applying solid phase peptide synthesis (SPPS), followed by the coupling to the siderophore [Fe]FSC via in situ activation using HATU/HOAt and DIPEA. Subsequent demetalation allowed radiolabeling of FSC-(RGD)3 with 68Ga. The radiolabeling procedure was optimized regarding peptide amount, reaction time, temperature as well buffer systems. For in vitro evaluation partition coefficient, protein binding, serum stability, αvβ3 integrin binding affinity, and tumor cell uptake were determined. For in vitro tests as well as for the biodistribution studies αvβ3 positive human melanoma M21 and αvβ3 negative M21-L cells were used. [68Ga]FSC-(RGD)3 was prepared with high radiochemical yield (> 98%). Distribution coefficient was − 3.6 revealing a hydrophilic character, and an IC50 value of 1.8 ± 0.6 nM was determined indicating a high binding affinity for αvβ3 integrin. [68Ga]FSC-(RGD)3 was stable in PBS (pH 7.4), FeCl3- and DTPA-solution as well as in fresh human serum at 37 °C for 2 hours. Biodistribution assay confirmed