Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

Science.gov (United States)

Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

2012-09-01

P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

Synthesis of fully and partially sulfonated polyanilines derived from ortanilic acid: An electrochemical and electromicrogravimetric study

International Nuclear Information System (INIS)

Cano Marquez, Abraham Guadalupe; Torres Rodriguez, Luz Maria; Montes Rojas, Antonio

2007-01-01

The electrochemical polymerization of 2-aminobenzene sulfonic acid, also called ortanilic acid (o-ASA), on a gold electrode precoated with polyaniline (PANI), has been carried out. We proved that the electropolymerization of o-ASA is enhanced on PANI electrodes, resulting in thicker films obtained in aqueous media at room temperature. The electrosynthesized film (P(o-ASA)) was characterized by cyclic voltammetry, FTIR and nuclear magnetic resonance. The compensation of P(o-ASA) charge was evaluated using electrochemical quartz crystal microbalance combined with cyclic voltammetry, which showed that the electroneutralization process mainly involves cations. Additionally, copolymers of aniline and o-ASA were electrosynthesized, using a metallic electrode modified with PANI also as a working electrode. The degree of sulfanation of copolymers has been modulated with the proportions of monomers in the electrosynthesis solution. The studies reveal a more important participation of cations in fully sulfonated polyaniline than in partially sulfonated polyaniline

Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response.

Science.gov (United States)

Liu, Wen; Guo, Wenjie; Guo, Lele; Gu, Yanhong; Cai, Peifen; Xie, Ning; Yang, Xiaoling; Shu, Yongqian; Wu, Xuefeng; Sun, Yang; Xu, Qiang

2014-06-01

Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting condition of inflammation involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies for the treatment of IBD are desperately needed. In the present study, we aimed to examine the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Andrographolide sulfonate was administrated through intraperitoneal injection to mice with TNBS-induced colitis. TNBS-induced body weight loss, myeloperoxidase activity, shortening of the colon and colonic inflammation were significantly ameliorated by andrographolide sulfonate. Both the mRNA and protein levels of pro-inflammatory cytokines were reduced by andrographolide sulfonate administration. Moreover, andrographolide sulfonate markedly suppressed the activation of p38 mitogen-activated protein kinase as well as p65 subunit of nuclear factor-κB (NF-κB). Furthermore, CD4(+) T cell infiltration as well as the differentiation of Th1 (CD4(+)IFN-γ(+)) and Th17 (CD4(+)IL17A(+)) subset were inhibited by andrographolide sulfonate. In summary, these results suggest that andrographolide sulfonate ameliorated TNBS-induced colitis in mice through inhibiting Th1/Th17 response. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Sensitive electrochemical determination of trace cadmium on a stannum film/poly(p-aminobenzene sulfonic acid)/electrochemically reduced graphene composite modified electrode

International Nuclear Information System (INIS)

Wang, Zhiqiang; Wang, Hui; Zhang, Zhihao; Yang, Xiaojing; Liu, Gang

2014-01-01

In this study, a novel stannum film/poly(p-aminobenzene sulfonic acid)/graphene composite modified glassy carbon electrode (GCE) was prepared by using electrodeposition of exfoliated graphene oxide, electropolymerization of p-aminobenzene sulfonic acid (p-ABSA) and in situ plating stannum fim methods, successively. This sensor was further used for sensitive determination of trace cadmium ions by square wave anodic stripping voltammetry (SWASV). The morphologies and electrochemistry properties of the modified electrode were characterized by scanning electron microscopy, Raman spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy and linear sweep voltammetry. It was found that the formed graphene layer on the top of GCE could remarkably facilitate the electron transfer and enlarge the specific surface area of the electrode. While the poly(p-ABSA) film could effectively increase the adhesion and stability of graphene layer, enhance ion-exchange capacity and prevent the macromolecule in real samples absorbing on the surface of electrode. By combining co-deposits ability with heavy metals of stannum film, the obtained electrode exhibited a good stripping performance for the analysis of Cd(II). Under the optimum conditions, a linear response was observed in the range from 1.0 to 70.0 μgL −1 with a detection limit of 0.05 μgL −1 (S/N = 3). The sensor was further applied to the determination of cadmium ions in real water samples with satisfactory results

Nitric Acid Dehydration Using Perfluoro Carboxylate and Mixed Sulfonate/Carboxylate Membranes

Energy Technology Data Exchange (ETDEWEB)

Ames, Richard L. [Colorado School of Mines, Golden, CO (United States)

2004-09-01

Perfluoro ionomer membranes are tetrafluoro ethylene-based materials with microheterogeneous structures consisting of a hydrophobic polymer backbone and a hydrophilic side-chain cluster region. Due to the ionomer cluster morphology, these films exhibit unique transport properties. Recent investigations with perfluoro sulfonate and perfluoro sulfonate/carboxylate composite polymers have demonstrated their value in the dehydration of nitric acid and they show potential as an alternative to conventional, energy intensive unit operations in the concentration of acid feeds. As a result, investigations were conducted to determine the feasibility of using pure perfluoro carboxylate and mixed perfluoro sulfonate/carboxylate films for the dehydration of nitric acid because of the speculation of improved water selectivity of the carboxylate pendant chain. During the first phase of these investigations the effort was focused on generating a thin, solution cast perfluoro carboxylate ionomer film, to evaluate the general, chemical and physical characteristics of the polymer, and to assess the material's aqueous transport performance (flux and nitrate separation efficiencies) in pervaporation and high-pressure environments. Results demonstrated that generating robust solution-cast films was difficult yet a number of membranes survived high trans-membrane pressures up to 700 psig. General characterization of the solution cast product showed reduced ion exchange capacities when compared with thicker, ''as received'' perfluoro carboxylate and similar sulfonate films. Small angle x-ray scattering analysis results suggested that the solution cast carboxylate films contained a small fraction of sulfonate terminated side-chains. Aqueous transport experimentation showed that permeate fluxes for both pure water and nitric acid were approximately two orders of magnitude smaller for the carboxylate solution cast membranes when compared to their sulfonate

Sulfonated poly(ether sulfone)s containing pyridine moiety for PEMFC.

Science.gov (United States)

Jang, Hohyoun; Islam, Md Monirul; Lim, Youngdon; Hossain, Md Awlad; Cho, Younggil; Joo, Hyunho; Kim, Whangi; Jeon, Heung-Seok

2014-10-01

Sulfonated poly(ether sulfone)s with varied degree of sulfonation (DS) were prepared via post-sulfonation of synthesized pyridine based poly(ether sulfone) (PPES) using concentrated sulfuric acid as sulfonating agent. The DS was varied with different mole ratio of 4,4'-(2,2-diphenylethenylidene)diphenol, DHTPE in the polymer unit. PPES copolymers were synthesized by direct polycondensation of pyridine unit with bis-(4-fluorophenyl)-sulfone, 4, 4'-sulfonyldiphenol and DHTPE. The structure of the resulting PPES copolymer membranes with different sulfonated units were studied by 1H NMR spectroscopy and thermogravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymer with water. The ion exchange capacity (IEC) and proton conductivity were evaluated according to the increase of DS. The water uptake (WU) of the resulting membranes was in the range of 17-58%, compared to that of Nafion 211 28%. The membranes provided proton conductivities of 65-95 mS/cm in contrast to 103 mS/cm of Nafion 211.

Biocompatibility of polypropylene non-woven fabric membrane via UV-induced graft polymerization of 2-acrylamido-2-methylpropane sulfonic acid

Energy Technology Data Exchange (ETDEWEB)

Song Lingjie [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Zhao Jie; Yang Huawei; Jin Jing; Li Xiaomeng [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Stagnaro, Paola [Istituto per Io Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, Via de Marini 6, 16149 Genova (Italy); Yin Jinghua, E-mail: yinjh@ciac.jl.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

2011-10-15

This work described the graft polymerization of a sulfonic acid terminated monomer, 2-acrylamido-2-methylpropane sulfonic acid (AMPS), onto the surface of polypropylene non-woven (NWF PP) membrane by O{sub 2} plasma pretreatment and UV-induced photografting method. The chemical structure and composition of the modified surfaces were analyzed by FTIR-ATR and XPS, respectively. The wettability was investigated by water contact angle and equilibrium water adsorption. And the biocompatibility of the modified NWF PP membranes was evaluated by protein adsorption and platelet adhesion. It was found that the graft density increased with prolonging UV irradiation time and increasing AMPS concentration; the water contact angles of the membranes decreased from 124{sup o} to 26{sup o} with the increasing grafting density of poly(AMPS) from 0 to 884.2 {mu}g cm{sup -2}, while the equilibrium water adsorption raised from 5 wt% to 75 wt%; the protein absorption was effectively suppressed with the introduction of poly(AMPS) even at the low grafting density (132.4 {mu}g cm{sup -2}); the number of platelets adhering to the modified membrane was dramatically reduced when compared with that on its virgin surface. These results indicated that surface modification of NWF PP membrane with AMPS was a facile approach to construct biocompatible surface.

Preparation and characterization of sulfonated amine-poly(ether sulfone)s for proton exchange membrane fuel cell

Energy Technology Data Exchange (ETDEWEB)

Seo, Dong-Wan; Lim, Young-Don; Lee, Soon-Ho; Jeong, Young-Gi; Kim, Whan-Gi [Department of Applied Chemistry/RIC-ReSEM, Konkuk University, Chungju-si, Chungbuk 380-701 (Korea, Republic of); Hong, Tae-Whan [Department of Materials Sci and Engineering/RIC-ReSEM, Chungju National University, Chungju, Chungbuk (Korea, Republic of)

2010-12-15

Sulfonated amine-poly(ether sulfone)s (S-APES)s were prepared by nitration, reduction and sulfonation of poly(ether sulfone) (ultrason {sup registered} -S6010). Poly(ether sulfone) was reacted with ammonium nitrate and trifluoroacetic anhydride to produce the nitrated poly(ether sulfone), and was followed by reduction using tin(II)chloride and sodium iodide as reducing agents to give the amino-poly(ether sulfone). The S-APES was obtained by reaction of 1,3-propanesultone and the amino-poly(ether sulfone) (NH{sub 2}-PES) with sodium methoxide. The different degrees of nitration and reduction of poly(ether sulfone) were successfully synthesized by an optimized process. The reduction of nitro group to amino was done quantitatively, and this controlled the contents of the sulfonic acid group. The films were converted from salt to acid forms with dilute hydrochloric acid. Different contents of sulfonated unit of the S-APES were studied by FT-IR, {sup 1}H NMR spectroscopy, differential scanning calorimetry (DSC), and thermo gravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymers with water and methanol. The ion exchange capacity (IEC), a measure of proton conductivity, was evaluated. The S-APES membranes exhibit conductivities (25 C) from 1.05 x 10{sup -3} to 4.83 x 10{sup -3} S/cm, water swell from 30.25 to 66.50%, IEC from 0.38 to 0.82 meq/g, and methanol diffusion coefficients from 3.10 x 10{sup -7} to 4.82 x 10{sup -7} cm{sup 2}/S at 25 C. (author)

Gene expression profiling identifies mechanisms of protection to recurrent trinitrobenzene sulfonic acid colitis mediated by probiotics

NARCIS (Netherlands)

Mariman, R.; Kremer, S.H.A.; Erk, M. van; Lagerweij, T.; Koning, F.; Nagelkerken, L.

2012-01-01

Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis

The effect of Saccharomyces boulardii on human colon cells and inflammation in rats with trinitrobenzene sulfonic acid-induced colitis.

Science.gov (United States)

Lee, Sang Kil; Kim, Youn Wha; Chi, Sung-Gil; Joo, Yeong-Shil; Kim, Hyo Jong

2009-02-01

Saccharomyces boulardii (S. boulardii) has beneficial effects in the treatment of intestinal inflammation; however, little is known about the mechanisms by which these effects occur. We investigated the effects of S. boulardii on the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and interleukin-8 (IL-8), using human HT-29 colonocytes and a rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. The effect of S. boulardii on gene expression was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Northern blot and Western blot assays. Pharmacological inhibitors for various signaling pathways were used to determine the signaling pathways implicated in the S. boulardii regulation of PPAR-gamma and IL-8. We found that S. boulardii up-regulated and down-regulated PPAR-gamma and IL-8 expression at the transcription level, both in vitro and in vivo (P Saccharomyces boulardii blocked tumor necrosis factor-alpha (TNF-alpha) regulation of PPAR-gamma and IL-8 through disruption of TNF-alpha-mediated nuclear factor kappa B (NF-kappaB) activation. Furthermore, S. boulardii suppressed colitis and expression of pro-inflammatory cytokine genes in vivo (P boulardii reduces colonic inflammation and regulates inflammatory gene expression.

Radiation-induced crosslinking of poly(styrene–butadiene–styrene) block copolymers and their sulfonation

Energy Technology Data Exchange (ETDEWEB)

Lee, Sun-Young [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Song, Ju-Myung; Sohn, Joon-Yong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Shul, Yong-Gun [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Shin, Junhwa, E-mail: shinj@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of)

2013-12-01

Highlights: • The c-SBS films were prepared using a gamma ray or electron beam. • The crosslinking degree of the c-SBS films were increased with the irradiation dose. • The prepared c-SBS films were sulfonated with various concentration of CSA. • The sulfonation of the c-SBS film is largely dependent on the concentration of CSA. • The sulfonation process is progressed from the surface to the inner part of c-SBS film. -- Abstract: Several crosslinked poly(styrene–butadiene–styrene) (c-SBS) block copolymer films were prepared using a gamma ray or electron beam with various irradiation doses and the prepared c-SBS film was then subjected to sulfonation using a chlorosulfonic acid (CSA) solution to introduce a sulfonic acid group. To estimate the degree of crosslinking, the gel fractions and FT-IR spectra of the c-SBS films were used and the results indicate that the degree of crosslinking is increased with an increase in the radiation dose. The surface morphology and mechanical property of the c-SBS films were observed using SEM and UTM instruments, respectively. The sulfonated c-SBS films were investigated by measuring the ion exchange capacity (IEC) and by observing the cross-sectional distribution patterns of sulfonic acid group using an SEM-EDX instrument. The IEC and SEM-EDX studies indicate that the sulfonated c-SBS membranes can be successfully prepared through the radiation crosslinking of the SBS film and the subsequent sulfonation with a diluted CSA solution.

Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways.

Science.gov (United States)

Peng, Shuang; Hang, Nan; Liu, Wen; Guo, Wenjie; Jiang, Chunhong; Yang, Xiaoling; Xu, Qiang; Sun, Yang

2016-05-01

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

Directory of Open Access Journals (Sweden)

Shuang Peng

2016-05-01

Full Text Available Acute lung injury (ALI or acute respiratory distress syndrome (ARDS is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection, on lipopolysaccharide (LPS-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK as well as p65 subunit of nuclear factor-κB (NF-κB. In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

Preparation of 131I-asialo-α1-acid glycoprotein

International Nuclear Information System (INIS)

Rijk, P.P. van

1975-01-01

α 1 -Acid glycoprotein (orosomucoid) was prepared from a byproduct of the ethanol plasma fractionation by means of ion-exchange procedures. Immunoelectrophoresis suggested a high degree of purity; the purified protein contained 13.5% sialic acid and 17.8% hexose. The α 1 -acid glycoprotein was modified by removal of sialic acid with neurominidase (E.C. 3.2.1.18) followed by iodination with 131 I. The purpose of the preparation, its potential use as a pharmacon for liver-function studies in nuclear medicine, is the subject of further study

Silica-supported sulfonic acids as recyclable catalyst for esterification of levulinic acid with stoichiometric amounts of alcohols

Directory of Open Access Journals (Sweden)

Raimondo Maggi

2016-10-01

Full Text Available Converting biomass into value-added chemicals holds the key to sustainable long-term carbon resource management. In this context, levulinic acid, which is easily obtained from cellulose, is valuable since it can be transformed into a variety of industrially relevant fine chemicals. Here we present a simple protocol for the selective esterification of levulinic acid using solid acid catalysts. Silica supported sulfonic acid catalysts operate under mild conditions and give good conversion and selectivity with stoichiometric amounts of alcohols. The sulfonic acid groups are tethered to the support using organic tethers. These tethers may help in preventing the deactivation of the active sites in the presence of water.

Removal of N-linked glycosylations at acidic pH by PNGase a facilitates hydrogen/deuterium exchange mass spectrometry analysis of N-Linked glycoproteins

DEFF Research Database (Denmark)

Jensen, Pernille Foged; Comamala, Gerard; Trelle, Morten Beck

2016-01-01

for analysis of the conformational dynamics of N-linked glycoproteins that utilizes the enzyme PNGase A for deglycosylation of labeled peptic N-linked glycopeptides at HDX quench conditions, i.e., acidic pH and low temperature. PNGase A-based deglycosylation is thus performed after labeling (post...

Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

International Nuclear Information System (INIS)

Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

2008-01-01

Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

Directory of Open Access Journals (Sweden)

Nian Yu

2011-01-01

Full Text Available This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA- induced seizure rats. Male SD rats were divided into saline control group (NS group, KA induced epilepsy group (EP group, and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group or with dexamethasone (DEX group. No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.

Constitutive ω-3 fatty acid production in fat-1 transgenic mice and docosahexaenoic acid administration to wild type mice protect against 2,4,6-trinitrobenzene sulfonic acid-induced colitis.

Science.gov (United States)

Yum, Hye-Won; Kang, Jing X; Hahm, Ki Baik; Surh, Young-Joon

2017-06-10

Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are known to have strong anti-inflammatory effects. In the present study, we investigated the protective effects of ω-3 PUFAs on experimentally induced murine colitis. Intrarectal administration of 2.5% 2,4,6-trinitrobenzene sulfonic acid (TNBS) caused inflammation in the colon of wild type mice, but this was less severe in fat-1 transgenic mice that constitutively produce ω-3 PUFAs from ω-6 PUFAs. The intraperitoneal administration of docosahexaenoic acid (DHA), a representative ω-3 PUFA, was also protective against TNBS-induced murine colitis. In addition, endogenously formed and exogenously introduced ω-3 PUFAs attenuated the production of malondialdehyde and 4-hydroxynonenal in the colon of TNBS-treated mice. The effective protection against inflammatory and oxidative colonic tissue damages in fat-1 and DHA-treated mice was associated with suppression of NF-κB activation and cyclooxygenase-2 expression and with elevated activation of Nrf2 and upregulation of its target gene, heme oxygenase-1. Taken together, these results provide mechanistic basis of protective action of ω-3 fatty PUFAs against experimental colitis. Copyright © 2017. Published by Elsevier Inc.

Comparative hepatotoxicity of 6:2 fluorotelomer carboxylic acid and 6:2 fluorotelomer sulfonic acid, two fluorinated alternatives to long-chain perfluoroalkyl acids, on adult male mice.

Science.gov (United States)

Sheng, Nan; Zhou, Xiujuan; Zheng, Fei; Pan, Yitao; Guo, Xuejiang; Guo, Yong; Sun, Yan; Dai, Jiayin

2017-08-01

Due to their structural similarities, 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and 6:2 fluorotelomer carboxylic acid (6:2 FTCA) are often used as alternatives to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), respectively. With limited health risk data and 6:2 FTSA detection in water and sludge, the toxicity of these chemicals is of growing concern. Here, adult male mice were exposed with 5 mg/kg/day of 6:2 FTCA or 6:2 FTSA for 28 days to investigate their hepatotoxicological effects. In contrast to 6:2 FTCA, 6:2 FTSA was detected at high and very high levels in serum and liver, respectively, demonstrating bioaccumulation potential and slow elimination. Furthermore, 6:2 FTSA induced liver weight increase, inflammation, and necrosis, whereas 6:2 FTCA caused no obvious liver injury, with fewer significantly altered genes detected compared with that of 6:2 FTSA (39 vs. 412). Although PFOA and PFOS commonly activate peroxisome proliferator-activated receptor α (PPARα), 6:2 FTSA induced an increase in PPARγ and related proteins, but not in lipid metabolism-related genes such as PPARα. Our results showed that 6:2 FTCA and 6:2 FTSA exhibited weak and moderate hepatotoxicity, respectively, compared with that reported for legacies PFOA and PFOS.

Structure and properties of compositions based on petroleum sulfonic acids

Energy Technology Data Exchange (ETDEWEB)

Tutorskii, I.A.; Sultanova, A.S.; Belkina, E.V.; Fomin, A.G. [Lomonosov Academy of Fine Chemical Technology, Moscow (Russian Federation)

1995-03-01

Colloidal characteristics of compositions based on petroleum sulfonic acids were studied. Neutralized heavy oil residue exhibits surface-active properties and contains an ultradisperse filler. Analysis of the compositions by size-exclusion-chromatography shows deep structural changes in the heavy acid residue upon neutralization with calcium carbonate.

In silico approach to investigating the adsorption mechanisms of short chain perfluorinated sulfonic acids and perfluorooctane sulfonic acid on hydrated hematite surface.

Science.gov (United States)

Feng, Hongru; Lin, Yuan; Sun, Yuzhen; Cao, Huiming; Fu, Jianjie; Gao, Ke; Zhang, Aiqian

2017-05-01

Short chain perfluorinated sulfonic acids (PFSAs) that were introduced as alternatives for perfluorooctane sulfonic acid (PFOS) have been widely produced and used. However, few studies have investigated the environmental process of short chain PFSAs, and the related adsorption mechanisms still need to be uncovered. The water-oxide interface is one of the major environmental interfaces that plays an important role in affecting the adsorption behaviour and transport potential of the environmental pollutant. In this study, we performed molecular dynamics simulations and quantum chemistry calculations to investigate the adsorption mechanisms of five PFSAs and their adsorption on hydrated hematite surface as well. Different to the vertical configuration reported for PFOS on titanium oxide, all PFSAs share the same adsorption configuration as the long carbon chains parallel to the surface. The formation of hydrogen bonds between F and inter-surface H helps to stabilize the unique configuration. As a result, the sorption capacity increases with increasing C-F chain length. Moreover, both calculated adsorption energy and partial density of states (PDOS) analysis demonstrate a PFSAs adsorption mechanism in between physical and chemical adsorption because the hydrogen bonds formed by the overlap of F (p) orbital and H (s) orbital are weak intermolecular interactions while the physical adsorption are mainly ascribed to the electrostatic interactions. This massive calculation provides a new insight into the pollutant adsorption behaviour, and in particular, may help to evaluate the environmental influence of pollutants. Copyright © 2017. Published by Elsevier Ltd.

Synthesis and properties of sulfonated poly(phenylene sulfone)s without ether linkage by Diels–Alder reaction for PEMFC application

International Nuclear Information System (INIS)

Lim, Youngdon; Lee, Hyunchul; Lee, Soonho; Jang, Hohyoun; Hossain, Md. Awlad; Cho, Younggil; Kim, Taeho; Hong, Youngtaik; Kim, Whangi

2014-01-01

A new sulfonated poly(phenylene sulfone) polymer (SPPS) was synthesized by Diels-Alder polymerization from 1,4-bis(2,4,5-triphenylcyclopentadienone)benzene (BTPCPB) and 4,4′-diethynylphenylsulfone, and followed by sulfonation reaction with chlorosulfuric acid. A series of sulfonated poly(phenylene sulfone)s (SPPS) with different degrees of sulfonation was prepared in a controllable manner with chlorosulfuric acid. These polymers showed good solubility in aprotic polar solvents, dimethyl acetamide (DMAC) and dimethyl sulfoxide (DMSO). Three different polymer membranes were studied by 1 H NMR spectroscopy, and thermogravimetric analysis (TGA). The ion exchange capacity (IEC) and proton conductivity of SPPS were evaluated according to the degrees of sulfonation. The water uptake (WU) of the synthesized SPPS membranes ranged from 38%∼75%, compared with 32% for Nafion 211 ® at 80 °C. The SPPS membranes exhibited proton conductivities (at 80 °C under 90% RH) of 110.2 mS/cm compared with 102.7 mS/cm for Nafion 211 ® . Power density was performed by single cell and showed similar to Nafion value

THE USE OF CHLOROSULFONIC ACID ON SULFONATION OF cPTFE FILM GRAFTED STYRENE FOR PROTON EXCHANGE MEMBRANE

Directory of Open Access Journals (Sweden)

Yohan Yohan

2010-06-01

Full Text Available Sulfonation of g-ray iradiated and styrene-grafted crosslinked polytetrafluoro ethylene film (cPTFE-g-S film have been done. The aim of the research was to make hydrophyl membrane as proton exchange membrane fuel cell. Sulfonation was prepared by using chlorosulfonic acid in chloroethane under various conditions. The impact of the percentage of grafting, the concentration of chlorosulfonic acid, the reaction time,and the reaction temperature on the properties of sulfonated film were examined. The results show that sulfonation of surface-grafted films was incomplete at room temperature. Increasing concentration of chlorosulfonic acid and reaction temperature accelerate the reaction but they also favor side reactions. These lead to the decrease of the ion-exchange capacity, water uptake, and proton conductivity but the increase of the resistance to oxidation in a perhydrol solution. The resulted cPTFE-g-SS membraneis stabile in a H2O2 30% solution for 20 h.   Keywords: Chorosulfonic acid, sulfonation, PTFE film, proton excange membrane.

Reaction kinetics of free fatty acids esterification in palm fatty acid distillate using coconut shell biochar sulfonated catalyst

Science.gov (United States)

Hidayat, Arif; Rochmadi, Wijaya, Karna; Budiman, Arief

2015-12-01

Recently, a new strategy of preparing novel carbon-based solid acids has been developed. In this research, the esterification reactions of Palm Fatty Acid Distillate (PFAD) with methanol, using coconut shell biochar sulfonated catalyst from biomass wastes as catalyst, were studied. In this study, the coconut shell biochar sulfonated catalysts were synthesized by sulfonating the coconut shell biochar using concentrated H2SO4. The kinetics of free fatty acid (FFA) esterification in PFAD using a coconut shell biochar sulfonated catalyst was also studied. The effects of the mass ratio of catalyst to oil (1-10%), the molar ratio of methanol to oil (6:1-12:1), and the reaction temperature (40-60°C) were studied for the conversion of PFAD to optimize the reaction conditions. The results showed that the optimal conditions were an methanol to PFAD molar ratio of 12:1, the amount of catalyst of 10%w, and reaction temperature of 60°C. The proposed kinetic model shows a reversible second order reaction and represents all the experimental data satisfactorily, providing deeper insight into the kinetics of the reaction.

Bis-sulfonic Acid Ionic Liquids for the Conversion of Fructose to 5-Hydroxymethyl-2-furfural

Directory of Open Access Journals (Sweden)

Sangho Koo

2012-10-01

Full Text Available Homogenous bis-sulfonic acid ionic liquids (1 mol equiv. in DMSO (10 mol equiv. at 100 °C efficiently mediated the conversion of D-fructose into 5-hydroxymethyl-2-furfural in 75% isolated yield, which was roughly a 10% increment compared to the case of the mono-sulfonic acid ionic liquids.

p-toluene sulfonic acid doped polyaniline carbon nanotube composites: synthesis via different routes and modified properties

Directory of Open Access Journals (Sweden)

ASHOK K. SHARMA

2013-04-01

Full Text Available Composites of polyaniline and carbon nanotube (CNT were prepared by in-situ chemical polymerization method using various aniline concentrations in the initial polymerization solution with p-toluene sulfonic acid (PTS as secondary dopant and mechanical mixing of the PANI and CNT using different weight ratios of PANI and CNTs. The structural characterizations of the composites were done by Fourier transform infrared (FTIR and Ultra violet visible spectroscopy (UV-Visible. Scanning electron microscopy (SEM was used to characterize the surface morphology of the composites. It was found that the composites prepared by in-situ chemical polymerization had smoother surface morphology in comparison to the composites obtained by mechanical mixing. The capacitive studies reveal that the in-situ composite has synergistic effect and the specific capacitance of the composite calculated from cyclic voltammogram (CV was 385.1 F/g. Thermal studies indicate that the composites are stable as compared to PANI alone showing that the CNT contributes towards thermal stability in the PANI-CNT composites.

Determination of P-Glycoprotein Expression by Flow Cytometry in Hematological Malignancies

Directory of Open Access Journals (Sweden)

Berkay Saraymen

2016-03-01

Full Text Available Objective: Determination the expression of P-glycoprotein is especially problematic for normal tissues because immuno­logical methods are limited in terms of sensitivity. We aimed to determine the expression of P-glycoprotein and CD34 by flow cytometry, and to evaluate the level of expression of P-glycoprotein and CD34 with unresponsive to treatment in pa­tients diagnosed with hematologic malignancy. Methods: Our study included fifty patients diagnosed with acute myeloblastic leukemia and acute lymphoblastic leuke­mia, and twenty healthy controls who were admitted to Erci­yes University Hematology-Oncology Hospital. The suspend­ed cells from bone marrow samples of patients and the pe­ripheral blood samples of healthy people were marked with P-glycoprotein phycoerythrin and CD34 FITC or PerCP Cy 5.5; and then surface expression was measured by means of flow cytometry. Results: In 6 of 30 acute myeloblastic leukemia patients P-glycoprotein and CD34 expression, in 6 of 20 acute lympho­blastic leukemia patients P-glycoprotein, in 5 of them CD34 expression were determined. A significant relation between P-glycoprotein and CD34 expressions in acute myeloblas­tic leukemia and acute lymphoblastic leukemia bone marrow samples was reported. Conclusion: Our data indicate that flow cytometry is more reliable, precise and faster than molecular methods for mea­suring P-glycoprotein expression and suggests the pos­sibility of a significant relationship between P-glycoprotein and CD34 expressions in acute myeloblastic leukemia and acute lymphoblastic leukemia bone marrow samples. The blast cells expressing CD34 on their surface along with P-glycoprotein simultaneously show that multi drug resistance 1 gene is mostly active in immature cells.

Preparation of sulfonic acid-containing rubbers from natural rubber vulcanizates

Science.gov (United States)

Poonsawat, Worapong; Poompradub, Sirilux; Ngamcharussrivichai, Chawalit

2014-06-01

In this work, a series of sulfonic acid-containing rubbers were prepared by aqueous phase oxidation of natural rubber vulcanizates in the presence of hydrogen peroxide (H2O2) and formic acid (HCOOH). The starting vulcanizates were neatly prepared via an efficient vulcanization (EV) system by varying mass ratio of N-cyclohexyl-2-benzothiazole sulfonamide (CBS), as an accelerator, to sulfur. The oxidation conditions were controlled at the molar ratio of H2O2: HCOOH = 1:1, the concentration of H2O2 = 15 wt.%, the temperature = 50 °C, and the reaction time = 3 h. The rubber materials before and after the oxidation were characterized for their physicochemical properties by using Fourier transform infrared spectroscopy, bomb calorimetry, acid-base titration and swelling measurements. The results indicated the presence of sulfonic acid group in the oxidized rubbers, generated by the oxidative cleaves of sulfide crosslinks in the rubber vulcanizates. The oxidation decreased the sulfur content of the rubber in which the level of sulfur loss was determined by the CBS/sulfur ratio. Moreover, the acidity of the oxidized products was correlated with the amount of sulfur remaining.

Synthesis of sulfonated porous carbon nanospheres solid acid by a facile chemical activation route

Energy Technology Data Exchange (ETDEWEB)

Chang, Binbin, E-mail: changbinbin806@163.com; Guo, Yanzhen; Yin, Hang; Zhang, Shouren; Yang, Baocheng, E-mail: baochengyang@yahoo.com

2015-01-15

Generally, porous carbon nanospheres materials are usually prepared via a template method, which is a multi-steps and high-cost strategy. Here, we reported a porous carbon nanosphere solid acid with high surface area and superior porosity, as well as uniform nanospheical morphology, which prepared by a facile chemical activation with ZnCl{sub 2} using resorcinol-formaldehyde (RF) resins spheres as precursor. The activation of RF resins spheres by ZnCl{sub 2} at 400 °C brought high surface area and large volume, and simultaneously retained numerous oxygen-containing and hydrogen-containing groups due to the relatively low processing temperature. The presence of these functional groups is favorable for the modification of –SO{sub 3}H groups by a followed sulfonation treating with sulphuric acid and organic sulfonic acid. The results of N{sub 2} adsorption–desorption and electron microscopy clearly showed the preservation of porous structure and nanospherical morphology. Infrared spectra certified the variation of surface functional groups after activation and the successful modification of –SO{sub 3}H groups after sulfonation. The acidities of catalysts were estimated by an indirect titration method and the modified amount of –SO{sub 3}H groups were examined by energy dispersive spectra. The results suggested sulfonated porous carbon nanospheres catalysts possessed high acidities and –SO{sub 3}H densities, which endowed their significantly catalytic activities for biodiesel production. Furthermore, their excellent stability and recycling property were also demonstrated by five consecutive cycles. - Graphical abstract: Sulfonated porous carbon nanospheres with high surface area and superior catalytic performance were prepared by a facile chemical activation route. - Highlights: • Porous carbon spheres solid acid prepared by a facile chemical activation. • It owns high surface area, superior porosity and uniform spherical morphology. • It possesses

Use of radioactive glucosamine in the perfused rat liver to prepare α1-acid glycoprotein (orosomucoid) with 3H- or 14C-labelled sialic acid and N-acetylglucosamine residues

International Nuclear Information System (INIS)

Aronson, N.N. Jr.

1982-01-01

A method was developed whereby [1- 14 C]glucosamine was used in a perfused rat liver system to prepare over 2 mg of α 1 -acid glycoprotein with highly radioactive sialic acid and glucosamine residues. The liver secreted radioactive α 1 -acid glycoprotein over a 4-6 h period, and this glycoprotein was purified from the perfusate by chromatography on DEAE-cellulose at pH3.6. The sialic acid on the isolated glycoprotein had a specific radioactivity of 3.1 Ci/mol, whereas the glucosamine-specific radioactivity was 4.3 Ci/mole. The latter amino-sugar residues on the isolated protein were only 13-fold less radioactive than the initially added [1- 14 C]glucosamine. Orosomucoid with a specific radioactivity of 31.3 μCi/mg of protein was obtainable by using [6- 3 H]glucosamine. Many other radioactive glycoproteins were found to be secreted into the perfusate by the liver. Thus this experimental system should prove useful for obtaining other serum glycoproteins with highly radioactive sugar moieties. (author)

Degradation and contamination of perfluorinated sulfonic acid membrane due to swelling-dehydration cycles

DEFF Research Database (Denmark)

Andersen, Shuang Ma; Morgen, Per; Skou, Eivind Morten

Formation of sulfonic anhydride S-O-S (from the condensation of sulfonic acids) was known one of the important degradation mechanisms [i] for Nafion membrane under hydrothermal aging condition, which is especially critical for hydrogen fuel cells. Similar mechanism would also have be desirable...... to the membrane degradation in direct methanol fuel cells (DMFCs), where liquid water has direct contact with the electrolyte. An ex-situ experiment was established with swelling-dehydration cycles on the membrane. However, formation of sulfonic anhydride was not detected during the entire treatment; instead...

Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

OpenAIRE

Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

2003-01-01

Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery.Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells.To assess the role of calcium in t...

Polyaniline nanotubes and their dendrites doped with different naphthalene sulfonic acids

International Nuclear Information System (INIS)

Zhang Zhiming; Wei Zhixiang; Zhang Lijuan; Wan Meixiang

2005-01-01

Polyaniline (PANI) nanotubes (130-250 nm in average diameter) doped with α-naphthalene sulfonic acid (α-NSA), β-naphthalene sulfonic acid (β-NSA) and 1,5-naphthalene disulfonic acid were synthesized via a self-assembly process. It was found that the formation yield, morphology (hollow or solid), size, crystalline and electrical properties of the nanostructures are affected by the position and number of -SO 3 H groups attached to the naphthalene ring of NSA as well as the synthesis conditions. Moreover, these nanotubes aggregate to form a dendritic morphology when the polymerization is performed at a static state. The micelles composed of dopant or dopant/anilinium cations might act in a template-like fashion in forming self-assembled PANI nanotubes, which was further confirmed by X-ray diffraction measurements, while the aggregated morphology of the nanotubes might result from polymer chain interactions including π-π interactions, hydrogen and ionic bonds

P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

NARCIS (Netherlands)

Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

2007-01-01

The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

Sorption of perfluorooctanoic acid, perfluorooctane sulfonate and perfluoroheptanoic acid on granular activated carbon.

Science.gov (United States)

Zhang, Di; Luo, Qi; Gao, Bin; Chiang, Sheau-Yun Dora; Woodward, David; Huang, Qingguo

2016-02-01

The sorption of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoroheptanoic acid (PFHpA) on granular activated carbon (GAC) was characterized and compared to explore the underlying mechanisms. Sorption of the three perfluoroalkyl acids (PFAAs) on GAC appeared to be a rapid intra-particle diffusion process, which were well represented by the pseudo-second-order rate model with the sorption rate following the order PFOS > PFOA > PFHpA. Sorption isotherm data were well fitted by the Freundlich model with the sorption capacity (Kf) of PFOS, PFOA and PFHpA being 4.45, 2.42 and 1.66 respectively. This suggests that the hydrophilic head group on PFAAs, i.e. sulfonate vs carboxylic, has a strong influence on their sorption. Comparison between PFOA and PFHpA revealed that hydrophobicity could also play a role in the sorption of PFAAs on GAC when the fluorocarbon chain length is different. Analyses using Attenuated Total Reflection (ATR)-Fourier Transform Infrared (FTIR) spectroscopy suggested possible formation of a negative charge-assisted H-bond between PFAAs and the functionalities on GAC surfaces, including non-aromatic ketones, sulfides, and halogenated hydrocarbons. Copyright © 2015 Elsevier Ltd. All rights reserved.

P-glycoprotein targeted nanoscale drug carriers

KAUST Repository

Li, Wengang; Abu Samra, Dina Bashir Kamil; Merzaban, Jasmeen; Khashab, Niveen M.

2013-01-01

Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug

Strategies to overcome or circumvent P-glycoprotein mediated multidrug resistance.

Science.gov (United States)

Yuan, Hongyu; Li, Xun; Wu, Jifeng; Li, Jinpei; Qu, Xianjun; Xu, Wenfang; Tang, Wei

2008-01-01

Cancer patients who receive chemotherapy often experience intrinsic or acquired resistance to a broad spectrum of chemotherapeutic agents. The phenomenon, termed multidrug resistance (MDR), is often associated with the over-expression of P-glycoprotein, a transmembrane protein pump, which can enhance efflux of a various chemicals structurally unrelated at the expense of ATP depletion, resulting in decrease of the intracellular cytotoxic drug accumulation. The MDR has been a big threaten to the human health and the war fight for it continues. Although several other mechanisms for MDR are elucidated in recent years, considerable efforts attempting to inverse MDR are involved in exploring P-glycoprotein modulators and suppressing P-glycoprotein expression. In this review, we will report on the recent advances in various strategies for overcoming or circumventing MDR mediated by P-glycoprotein.

Development and characterization of acid-doped polybenzimidazole/sulfonated polysulfone blend polymer electrolytes for fuel cells

DEFF Research Database (Denmark)

Hasiotis, C.; Li, Qingfeng; Deimede, V.

2001-01-01

Polymeric membranes from blends of sulfonated polysulfones (SPSF) and polybenzimidazole (PBI) doped with phosphoric acid were developed as potential high-temperature polymer electrolytes for fuel cells and other electrochemical applications. The water uptake and acid doping of these polymeric...... membranes were investigated. Ionic conductivity of the membranes was measured in relation to temperature, acid doping level, sulfonation degree of SPSF, relative humidity, and blend composition. The conductivity of SPSF was of the order of 10/sup -3/ S cm/sup -1/. In the case of blends of PBI and SPSF...

Synthesis and properties of novel sulfonated poly(arylene ether sulfone) ionomers for vanadium redox flow battery

Energy Technology Data Exchange (ETDEWEB)

Chen, Dongyang; Wang, Shuanjin; Xiao, Min; Meng, Yuezhong [The Key Laboratory of Low-carbon Chemistry and Energy Conservation of Guangdong Province, Institute of Optoelectronic and Functional Composite Materials, Sun Yat-Sen University, Guangzhou 510275 (China)

2010-12-15

Novel sulfonated poly(arylene ether sulfone)s with electron-withdrawing sulfone groups in each repeat unit were synthesized via step polymerization followed by post-sulfonation using chlorosulfonic acid. The sulfonation degree can be readily controlled by adjusting the feed ratio of the repeat unit of polymers to chlorosulfonic acid. The synthesized polymers are soluble in common aprotic solvents such as dimethyl sulfoxide, N,N'-dimethylacetamide and dimethylformamide, and can be cast into transparent membranes from their solutions. The ion exchange capacity, water uptake, swelling ratio, sulfonation degree, mechanical property, oxidative property, thermal property and proton conductivity were investigated in detail using different methodologies. As an objective to apply these polymers as separators for vanadium redox flow battery, the VO{sup 2+} permeability and cell performance for the single cell were examined and assessed. (author)

Synthesis and properties of novel sulfonated poly(arylene ether sulfone) ionomers for vanadium redox flow battery

Energy Technology Data Exchange (ETDEWEB)

Chen Dongyang [Key Laboratory of Low-carbon Chemistry and Energy Conservation of Guangdong Province, Institute of Optoelectronic and Functional Composite Materials, Sun Yat-Sen University, Guangzhou 510275 (China); Wang Shuanjin, E-mail: wangshj@mail.sysu.edu.c [Key Laboratory of Low-carbon Chemistry and Energy Conservation of Guangdong Province, Institute of Optoelectronic and Functional Composite Materials, Sun Yat-Sen University, Guangzhou 510275 (China); Xiao Min [Key Laboratory of Low-carbon Chemistry and Energy Conservation of Guangdong Province, Institute of Optoelectronic and Functional Composite Materials, Sun Yat-Sen University, Guangzhou 510275 (China); Meng Yuezhong, E-mail: mengyzh@mail.sysu.edu.c [Key Laboratory of Low-carbon Chemistry and Energy Conservation of Guangdong Province, Institute of Optoelectronic and Functional Composite Materials, Sun Yat-Sen University, Guangzhou 510275 (China)

2010-12-15

Novel sulfonated poly(arylene ether sulfone)s with electron-withdrawing sulfone groups in each repeat unit were synthesized via step polymerization followed by post-sulfonation using chlorosulfonic acid. The sulfonation degree can be readily controlled by adjusting the feed ratio of the repeat unit of polymers to chlorosulfonic acid. The synthesized polymers are soluble in common aprotic solvents such as dimethyl sulfoxide, N,N'-dimethylacetamide and dimethylformamide, and can be cast into transparent membranes from their solutions. The ion exchange capacity, water uptake, swelling ratio, sulfonation degree, mechanical property, oxidative property, thermal property and proton conductivity were investigated in detail using different methodologies. As an objective to apply these polymers as separators for vanadium redox flow battery, the VO{sup 2+} permeability and cell performance for the single cell were examined and assessed.

Preparation and Characterization of Sulfonic Acid Functionalized Silica and Its Application for the Esterification of Ethanol and Maleic Acid

Science.gov (United States)

Sirsam, Rajkumar; Usmani, Ghayas

2016-04-01

The surface of commercially available silica gel, 60-200 mesh size, was modified with sulfonic acid through surface activation, grafting of 3-Mercaptopropyltrimethoxysilane, oxidation and acidification of 3-Mercaptopropylsilica. Sulfonic Acid Functionalization of Silica (SAFS) was confirmed by Fourier Transform Infra-red (FTIR) spectroscopy and thermal gravimetric analysis. Acid-base titration was used to estimate the cation exchange capacity of the SAFS. Catalytic activity of SAFS was judged for the esterification of ethanol with maleic acid. An effect of different process parameters viz. molar ratio, catalyst loading, speed of agitation and temperature were studied and optimized by Box Behnken Design (BBD) of Response Surface Methodology (RSM). Quadratic model developed by BBD-RSM reasonably satisfied an experimental and predicted values with correlation coefficient value R2 = 0.9504.

Analysis of perfluorinated phosponic acids and perfluorooctane sulfonic acid in water, sludge and sediment by LC-MS/MS

NARCIS (Netherlands)

Esperza, X.; Moyano, E.; de Boer, J.; Galceran, M.T.; van Leeuwen, S.P.J.

2011-01-01

Residues of perfluorinated phosphonic acids (PFPAs) and perfluorooctane sulfonic acid (PFOS) were investigated in various Dutch surface waters, sludge and sediments. For this purpose, a liquid chromatographic (LC) method was optimized by testing several columns with different mobile phases.

Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats.

Science.gov (United States)

Latha, M; Pari, L

2005-02-01

The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.

Characterization of pH-sensitive molecular switches that trigger the structural transition of vesicular stomatitis virus glycoprotein from the postfusion state toward the prefusion state.

Science.gov (United States)

Ferlin, Anna; Raux, Hélène; Baquero, Eduard; Lepault, Jean; Gaudin, Yves

2014-11-01

Vesicular stomatitis virus (VSV; the prototype rhabdovirus) fusion is triggered at low pH and mediated by glycoprotein G, which undergoes a low-pH-induced structural transition. A unique feature of rhabdovirus G is that its conformational change is reversible. This allows G to recover its native prefusion state at the viral surface after its transport through the acidic Golgi compartments. The crystal structures of G pre- and postfusion states have been elucidated, leading to the identification of several acidic amino acid residues, clustered in the postfusion trimer, as potential pH-sensitive switches controlling the transition back toward the prefusion state. We mutated these residues and produced a panel of single and double mutants whose fusion properties, conformational change characteristics, and ability to pseudotype a virus lacking the glycoprotein gene were assayed. Some of these mutations were also introduced in the genome of recombinant viruses which were further characterized. We show that D268, located in the segment consisting of residues 264 to 273, which refolds into postfusion helix F during G structural transition, is the major pH sensor while D274, D395, and D393 have additional contributions. Furthermore, a single passage of recombinant virus bearing the mutation D268L (which was demonstrated to stabilize the G postfusion state) resulted in a pseudorevertant with a compensatory second mutation, L271P. This revealed that the propensity of the segment of residues 264 to 273 to refold into helix F has to be finely tuned since either an increase (mutation D268L alone) or a decrease (mutation L271P alone) of this propensity is detrimental to the virus. Vesicular stomatitis virus enters cells via endocytosis. Endosome acidification induces a structural transition of its unique glycoprotein (G), which mediates fusion between viral and endosomal membranes. G conformational change is reversible upon increases in pH. This allows G to recover its native

[Saccharomyces boulardii reduced intestinal inflammation in mice model of 2,4,6-trinitrobencene sulfonic acid induced colitis: based on microarray].

Science.gov (United States)

Lee, Sang Kil; Kim, Hyo Jong; Chi, Sung Gil

2010-01-01

Saccharomyces boulardii has been reported to be beneficial in the treatment of inflammatory bowel disease. The aim of this work was to evaluate the effect of S. boulardii in a mice model of 2,4,6-trinitrobencene sulfonic acid (TNBS) induced colitis and analyze the expression of genes in S. boulardii treated mice by microarray. BALB/c mice received TNBS or TNBS and S. boulardii treatment for 4 days. Microarray was performed on total mRNA form colon, and histologic evaluation was also performed. In mice treated with S. boulardii, the histological appearance and mortality rate were significantly restored compared with rats receiving only TNBS. Among 330 genes which were altered by both S. boulardii and TNBS (>2 folds), 193 genes were down-regulated by S. boulardii in microarray. Most of genes which were down-regulated by S. bouardii were functionally classified as inflammatory and immune response related genes. S. boulardii may reduce colonic inflammation along with regulation of inflammatory and immune responsive genes in TNBS-induced colitis.

Thermal and Dielectric Behavior Studies of Poly(Arylene Ether Sulfones with Sulfonated and Phosphonated Pendants

Directory of Open Access Journals (Sweden)

Shimoga D. Ganesh

2016-01-01

Full Text Available The present paper discusses the aspects of the synthesizing valeric acid based poly(ether sulfones with active carboxylic acid pendants (VALPSU from solution polymerization technique via nucleophilic displacement polycondensation reaction among 4,4′-dichlorodiphenyl sulfone (DCDPS and 4,4′-bis(4-hydroxyphenyl valeric acid (BHPA. The conditions necessary to synthesize and purify the polymer were investigated in some detail. The synthesized poly(ether sulfones comprise sulfone and ether linkages in addition to reactive carboxylic acid functionality; these active carboxylic acid functional groups were exploited to hold the phenyl sulphonic acid and phenyl phosphonic acid pendants. The phenyl sulphonic acid pendants in VALPSU were easily constructed by altering active carboxylic acid moieties by sulfanilic acid using N,N′-dicyclohexylcarbodiimide (DCC mediated mild synthetic route, whereas the latter one was built in two steps. Initially, polyphosphoric acid condensation with VALPSU by 4-bromoaniline and next straightforward palladium catalyzed synthetic route, in both of which acidic pendants are clenched by polymer backbone via amide linkage. Without impairing the primary polymeric backbone modified polymers were prepared by varying the stoichiometric ratios of respective combinations. All the polymers were physicochemically characterized and pressed into tablets; electrical contacts were established to study the dielectric properties. Finally, the influence of the acidic pendants on the dielectric properties was examined.

Patterning of electrically conductive poly(aniline-co-aniline sulfonic acid) and its application in the immobilization of cytochrome c

International Nuclear Information System (INIS)

Oh, Se Young; Oh, Il Soo; Choi, Jeong-Woo

2004-01-01

We have synthesized poly(aniline-co-aniline sulfonic acid) and then investigated the feasibility of application as a specific and electrically conductive binding template for biomolecules. Poly(aniline-co-aniline sulfonic acid)s were prepared by oxidation polymerization of aniline and aniline sulfonic acid under various ratios. A fine pattern of the conducting copolyaniline was obtained by using a deep UV lithographic technique. Cytochrome c was immobilized onto the photochemically patterned conducting copolyaniline with a self-assembly method. Physical and electrochemical properties of the self-assembled cytochrome c monolayer were studied from atomic force microscopy and cyclic voltammetry. The self-assembled cytochrome c monolayer immobilized onto the copolyaniline with a high electrical conductivity showed a high electrochemical activity

Side-chain sulfonated poly(ether sulfone)s for PEM applications

Energy Technology Data Exchange (ETDEWEB)

Meier-Haack, J.; Butwilowski, W.; Quetschke, A.; Vogel, C. [Leibniz Institute of Polymer Research Dresden, Dresden (Germany)

2010-07-01

Copoly(arylene ether sulfone)s from bis-(4-fluoro phenyl)sulfone (DFDPhS), bis(4-trimethylsiloxy phenyl)sulfone (DHDPhS), and 2,5-diphenylhydroquinone trimethylsilylether (Bis-TMS-DPhHQ) were obtained by nucleophilic displacement polycondensation with high molecular weights (M{sub n} up to 70,000 g/mol; {eta}{sub inh} up to 0.93 dl/g) and narrow molecular weight distributions (2.1 - 2.9). All copolymers showed a single glass-transition temperature (T{sub g}) around 230 C. Upon sulfonation with concentrated sulfuric acid, the T{sub g}s (from samples in the protonated form) were shifted to higher temperatures (+ 35 {+-} 5 C). NMR spectra and the determined ion-exchange capacities (IEC; 1.46 - 2.05 mmol/g), which were close to the theoretical values, indicating that only the pendant phenyl rings of the 2,5- diphenylhydroquinone moieties in the polymer backbone were sulfonated. Membranes prepared from N-methyl- 2-pyrrolidone (NMP) solutions were transparent and soft. The water-uptake at room temperature increased from 30% to 80% with increasing IEC. Samples from random copolymers with an IEC {>=} 1.8 mmol/g were soluble in water at 90 C. While the proton conductivity of the low IEC samples (random copolymer) (1.46 mmol/g) was lower than that of Nafion {sup registered}, the conductivities of the high IEC samples were superior to Nafion {sup registered}. In general membranes from blockcopolymers showed lower water-uptake, higher dimensional stability and higher proton conductivities as compared to samples from random copolymers with similar monomer composition and ion-exchange capacities. (orig.)

Boronic Acid-Based Approach for Separation and Immobilization of Glycoproteins and Its Application in Sensing

Directory of Open Access Journals (Sweden)

Lin Liu

2013-10-01

Full Text Available Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols in the oligosaccharide chains of glycoproteins to form five- or six-membered cyclic esters. Based on this interaction, boronic acid-based ligands and materials have attracted much attention in both chemistry and biology as the recognition motif for enrichment and chemo/biosensing of glycoproteins in recent years. In this work, we reviewed the progress in the separation, immobilization and detection of glycoproteins with boronic acid-functionalized materials and addressed its application in sensing.

Synthesis, structural, solubility and anticancer activity studies of salts using nucleobases and sulfonic acids coformer

Science.gov (United States)

Singh, Neetu; Singh, Udai P.; Nikhil, Kumar; Roy, Partha; Singh, Hariji

2017-10-01

The reactions of natural and unnatural nucleobases (cytosine (Cyt), adenine (Ade), 5-aminouracil (AU) and caffeine (Caff)) with sulfonic acids coformer (1,5-naphthalenedisulfonic acid, NDSA; 5-sulfosalicylic acid, SSA) resulted in the formation of salts viz. [NDSA.Cyt] (1), [NDSA.Ade] (2), [NDSA.AU] (3), [NDSA.Caff] (4), [SSA.Cyt] (5), [SSA.Ade] (6), [SSA.AU] (7), and [SSA.Caff] (8). The structural analysis revealed that salts 1, 4, 6 and 7 have intermolecular interactions between adjacent nucleobases which form two different homodimer shown in R22 (8) motif and assembled via complementary Nsbnd H⋯O and Nsbnd H⋯N interactions. However, in all other salts an intermediate supramolecular synthon pattern was observed between nucleobases and sulfonic acids. The lattice energy was also calculated by DFT to investigate whether salts were thermodynamically more stable than its coformer. The same was further confirmed by differential scanning calorimetry-thermogravimetric (DSC-TG) analysis. The anticancer activity study of individual nucleobases and their NDSA salts were also performed on human breast (MCF-7) and lung (A 549) cancer cell. The salts formation of nucleobases with sulfonic acids improved their solubility, thereby demonstrating up to 8-fold increase in solubility of nucleobases.

Synthesis and characterization of sulfonated cardo poly(arylene ether sulfone)s for fuel cell proton exchange membrane application

Energy Technology Data Exchange (ETDEWEB)

Islam, M.M.; Jang, H.H.; Lim, Y.D.; Seo, D.W.; Kim, W.G. [Department of Applied Chemistry, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, T.H.; Hong, Y.T. [Energy Material Research Center, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Kim, D.M. [Material Engineering and Science, Hongik Univ, Jochiwon-eup, Yeongi-gun, Chungnam (Korea, Republic of)

2012-12-15

Sulfonated cardo poly(arylene ether sulfone)s (SPPA-PES) with various degrees of sulfonation (DS) were prepared by post-sulfonation of synthesized phenolphthalein anilide (PPA; N-phenyl-3,3'-bis(4-hydroxyphenyl)-1-isobenzopyrolidone) poly(arylene ether sulfone)s (PPA-PES) by using concentrated sulfuric acid. PPA-PES copolymers were synthesized by direct polycondensation of PPA with bis-(4-fluorophenyl)-sulfone and 4,4'-sulfonyldiphenol. The DS was varied with different mole ratios of PPA (24, 30, 40, 50 mol.%) in the polymer. The structure of the resulting SPPA-PES copolymers and the different contents of the sulfonated unit were studied by Fourier transform infrared (FT-IR) spectroscopy, {sup 1}H NMR spectroscopy, and thermogravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymer with water. The ion exchange capacity (IEC) and proton conductivity of SPPA-PES were evaluated according to the increase of DS. The water uptake (WU) of the resulting SPPA-PES membranes was in the range of 20-72%, compared with 28% for Nafion 211 registered. The SPPA-PES membranes showed proton conductivities of 23-82 mS cm{sup -1}, compared with 194 mS cm{sup -1} for Nafion 211 registered, under 100% relative humidity (RH) at 80 C. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

P-glycoprotein in autoimmune rheumatic diseases.

Science.gov (United States)

García-Carrasco, M; Mendoza-Pinto, C; Macias Díaz, S; Vera-Recabarren, M; Vázquez de Lara, L; Méndez Martínez, S; Soto-Santillán, P; González-Ramírez, R; Ruiz-Arguelles, A

2015-07-01

P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

HIV-1 integrase inhibitors are substrates for the multidrug transporter MDR1-P-glycoprotein

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Cara Andrea

2007-03-01

Full Text Available Abstract Background The discovery of diketoacid-containing derivatives as inhibitors of HIV-1 Integrase (IN (IN inhibitors, IINs has played a major role in validating this enzyme as an important target for antiretroviral therapy. Since the in vivo efficacy depends on access of these drugs to intracellular sites where HIV-1 replicates, we determined whether the IINs are recognized by the multidrug transporter MDR1-P-glycoprotein (P-gp thereby reducing their intracellular accumulation. To address the effect of IINs on drug transport, nine quinolonyl diketo acid (DKA derivatives active on the HIV-1 IN strand transfer (ST step and with EC50 ranging from 1.83 to >50 μm in cell-based assays were tested for their in vitro interaction with P-gp in the CEM-MDR cell system. IINs were investigated for the inhibition and induction of the P-gp function and expression as well as for multidrug resistance (MDR reversing ability. Results The HIV-1 IINs act as genuine P-gp substrates by inhibiting doxorubicin efflux and inducing P-gp functional conformation changes as evaluated by the modulation of UIC2 mAb epitope. Further, IINs chemosensitize MDR cells to vinblastine and induce P-gp expression in drug sensitive revertants of CEM-MDR cells. Conclusion To our knowledge, this is the first demonstration that HIV-1 IINs are P-gp substrates. This biological property may influence the absorption, distribution and elimination of these novels anti HIV-1 compounds.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

International Nuclear Information System (INIS)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang; Huang, Changjiang; Yang, Dongren

2016-01-01

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: yangdongren@yahoo.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)

2016-07-15

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

INFLUENCE OF ALPHA-1-ACID GLYCOPROTEIN UPON PRODUCTION OF CYTOKINES BY PERIPHERAL BLOOD MONONUCLEARS

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М. V. Osikov

2007-01-01

Full Text Available Abstract. Alpha-1-acid glycoprotein (orosomucoid is a multifunctional acute phase reactant belonging to the family of lipocalines from plasma alpha-2 globulin fraction. In present study, we investigated dosedependent effects of orosomucoid upon secretion of IL-1â, IL-2, IL-3, IL-4 by mononuclear cells from venous blood of healthy volunteers. Mononuclear cells were separated by means of gradient centrifugation, followed by incubation for 24 hours with 250, 500, or 1000 mcg of orosomucoid per ml RPMI-1640 medium (resp., low, medium and high dose. The levels of cytokine production were assayed by ELISA technique. Orosomucoid-induced secretion of IL-1â and IL-4 was increased, whereas IL-3 secretion was inhibited. IL-2 production was suppressed at low doses of orosomucoid, and stimulated at medium and high doses. The effect of alpha-1-acid glycoprotein upon production of IL-2, IL-3 and IL-4 was dose-dependent. Hence, these data indicate that orosomucoid is capable of modifying IL-1â, IL-2, IL-3, and IL-4 secretion by blood mononuclear cells.

Monoclonal antibody to an external epitope of the human mdr1 P-glycoprotein

NARCIS (Netherlands)

Arceci, R. J.; Stieglitz, K.; Bras, J.; Schinkel, A.; Baas, F.; Croop, J.

1993-01-01

A membrane glycoprotein, termed P-glycoprotein, has been shown to be responsible for cross-resistance to a broad range of structurally and functionally distinct cytotoxic agents. P-glycoprotein, encoded in humans by the mdr1 gene, functions as an energy-dependent efflux pump to exclude these

Crystallization and preliminary X-ray analysis of Chandipura virus glycoprotein G

International Nuclear Information System (INIS)

Baquero, Eduard; Buonocore, Linda; Rose, John K.; Bressanelli, Stéphane; Gaudin, Yves; Albertini, Aurélie A.

2012-01-01

Chandipura virus glycoprotein ectodomain (Gth) was purified and crystallized at pH 7.5. X-ray diffraction data set was collected to a resolution of 3.1 Å. Fusion in members of the Rhabdoviridae virus family is mediated by the G glycoprotein. At low pH, the G glycoprotein catalyzes fusion between viral and endosomal membranes by undergoing a major conformational change from a pre-fusion trimer to a post-fusion trimer. The structure of the G glycoprotein from vesicular stomatitis virus (VSV G), the prototype of Vesiculovirus, has recently been solved in its trimeric pre-fusion and post-fusion conformations; however, little is known about the structural details of the transition. In this work, a soluble form of the ectodomain of Chandipura virus G glycoprotein (CHAV G th ) was purified using limited proteolysis of purified virus; this soluble ectodomain was also crystallized. This protein shares 41% amino-acid identity with VSV G and thus its structure could provide further clues about the structural transition of rhabdoviral glycoproteins induced by low pH. Crystals of CHAV G th obtained at pH 7.5 diffracted X-rays to 3.1 Å resolution. These crystals belonged to the orthorhombic space group P2 1 2 1 2, with unit-cell parameters a = 150.3, b = 228.2, c = 78.8 Å. Preliminary analysis of the data based on the space group and the self-rotation function indicated that there was no trimeric association of the protomers. This unusual oligomeric status could result from the presence of fusion intermediates in the crystal

A Potato cDNA Encoding a Homologue of Mammalian Multidrug Resistant P-Glycoprotein

Science.gov (United States)

Wang, W.; Takezawa, D.; Poovaiah, B. W.

1996-01-01

A homologue of the multidrug resistance (MDR) gene was obtained while screening a potato stolon tip cDNA expression library with S-15-labeled calmodulin. The mammalian MDR gene codes for a membrane-bound P-glycoprotein (170-180 kDa) which imparts multidrug resistance to cancerous cells. The potato cDNA (PMDR1) codes for a polypeptide of 1313 amino acid residues (ca. 144 kDa) and its structural features are very similar to the MDR P-glycoprotein. The N-terminal half of the PMDR1-encoded protein shares striking homology with its C-terminal half, and each half contains a conserved ATP-binding site and six putative transmembrane domains. Southern blot analysis indicated that potato has one or two MDR-like genes. PMDR1 mRNA is constitutively expressed in all organs studied with higher expression in the stem and stolon tip. The PMDR1 expression was highest during tuber initiation and decreased during tuber development.

Foam supported sulfonated polystyrene as a new acidic material for catalytic reactions

NARCIS (Netherlands)

Ordomskiy, V.; Schouten, J.C.; Schaaf, van der J.; Nijhuis, T.A.

2012-01-01

Polystyrene was grafted on carbon foam with a melted polypropylene film predeposited on the surface. Polystyrene was subsequently sulfonated by chlorosulfonic acid. The effect of the temperature, time of grafting and concentration of radical initiator was studied. The materials were characterized by

Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells

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Yaqiong Zu

2014-08-01

Full Text Available P-glycoprotein (P-gp is a major factor in multidrug resistance (MDR which is a serious obstacle in chemotherapy. P-gp has also been implicated in causing apoptosis of tumor cells, which was shown to be another important mechanism of MDR recently. To study the influence of P-gp in tumor cell apoptosis, K562/A cells (P-gp+ and K562/S cells (P-gp− were subjected to doxorubicin (Dox, serum withdrawal, or independent co-incubation with multiple P-gp inhibitors, including valspodar (PSC833, verapamil (Ver and H108 to induce apoptosis. Apoptosis was simultaneously detected by apoptotic rate, cell cycle by flow cytometry and cysteine aspartic acid-specific protease 3 (caspase 3 activity by immunoassay. Cytotoxicity and apoptosis induced by PSC833 were evaluated through an MTT method and apoptosis rate, and cell cycle combined with caspase 3 activity, respectively. The results show that K562/A cells are more resistant to apoptosis and cell cycle arrest than K562/S cells after treatment with Dox or serum deprivation. The apoptosis of K562/A cells increased after co-incubation with each of the inhibitors of P-gp. P-gp inhibitors also enhanced cell cycle arrest in K562/A cell. PSC833 most strikingly decreased viability and led to apoptosis and S phase arrest of cell cycle in K562/A cells. Our study demonstrates that P-gp inhibits the apoptosis of tumor cells in addition to participating in the efflux of intracellular chemotherapy drugs. The results of the caspase 3 activity assay also suggest that the role of P-gp in apoptosis avoidance is caspase-related.

Adsorption behavior of perfluorinated sulfonic acid ionomer on highly graphitized carbon nanofibers and their thermal stabilities

DEFF Research Database (Denmark)

Andersen, Shuang Ma; Borghei, Maryam; Dhiman, Rajnish

2014-01-01

A systematic adsorption study of perfluorinated sulfonic acid Nafion® ionomer on ribbon type highly graphitized carbon nanofibers (CNFs) was carried out using 19 fluorine nuclear magnetic resonance spectroscopy. Based on the values obtained for the equilibrium constant (Keq., derived from Langmuir....... The ionomer is probably adsorbed via the polar sulfonic group on hydrophilic Vulcan, whereas, it is adsorbed primarily via hydrophobic -CF2- backbone on the highly hydrophobic pristine CNFs. Ionomer adsorption behavior is gradually altered from apolar to polar group adsorption for the acid modified CNFs...

Treating shale oil to obtain sulfonates

Energy Technology Data Exchange (ETDEWEB)

Schaeffer, H

1921-01-21

The process shows as its principal characteristics: (1) treating the oil with chlorsulfonic acid at a temperature of about 100/sup 0/C; (2) the transformation of the sulfonic acid obtained into salts; (3) as new industrial products, the sulfonates obtained and their industrial application as disinfectants for hides and wood.

Co-treatment by docetaxel and vinblastine breaks down P-glycoprotein mediated chemo-resistance

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Mahsa Mohseni

2016-03-01

Results: Combination treatment of the cells with docetaxel and vinblastine decreased the IC50 values for docetaxel from (30±3.1 to (15±2.6 nM and for vinblastine from (30±5.9 to (5±5.6 nM (P≤0.05.               P-glycoprotein mRNA expression level showed a significant up-regulation in the cells incubated with each drug alone (P≤0.001. Incubation of the cells with combined concentrations of both agents neutralized P-glycoprotein overexpression (P≤0.05. Adding verapamil, a P-glycoprotein inhibitor caused a further increase in the percentage of apoptotic cells when the cells were treated with both agents.  Conclusion:Our results suggest that combination therapy along with P-glycoprotein inhibition can be considered as a novel approach to improve the efficacy of chemotherapeutics in cancer patients with high P-glycoprotein expression.

Sulfonation of vulcanized ethylene-propylene-diene terpolymer membranes

International Nuclear Information System (INIS)

Barroso-Bujans, F.; Verdejo, R.; Lozano, A.; Fierro, J.L.G.; Lopez-Manchado, M.A.

2008-01-01

In the present work, sulfonation of previously vulcanized ethylene propylene diene terpolymer (EPDM) membranes was developed in a swelling solvent with acetyl sulfate. This procedure avoids the need to pre-dissolve the raw polymer. The reaction conditions were optimized in terms of solvent type, reaction time, acetyl sulfate concentration and film thickness to obtain the maximum degree of sulfonation of the polymer. The sulfonation procedure presented in this study yields a degree of sulfonation comparable to the chlorosulfonic acid procedure. Sulfonic acid groups were detected by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy, and quantified by titrations. Proton conductivity and water uptake were measured by means of impedance spectroscopy and swelling measurements, respectively, and were correlated with the degree of sulfonation. Tensile strength and Young's modulus of sulfonated EPDM increased with the degree of sulfonation, while elongation at break remained constant. Thermal stability of the sulfonated EPDM was studied by simultaneous thermogravimetry-mass spectroscopy

Amplified voltammetric detection of glycoproteins using 4-mercaptophenylboronic acid/biotin-modified multifunctional gold nanoparticles as labels.

Science.gov (United States)

Liu, Lin; Xing, Yun; Zhang, Hui; Liu, Ruili; Liu, Huijing; Xia, Ning

2014-01-01

Ultrasensitive detection of protein biomarkers is essential for early diagnosis and therapy of many diseases. Glycoproteins, differing from other types of proteins, contain carbohydrate moieties in the oligosaccharide chains. Boronic acid can form boronate ester covalent bonds with diol-containing species. Herein, we present a sensitive and cost-effective electrochemical method for glycoprotein detection using 4-mercaptophenylboronic acid (MBA)/biotin-modified gold nanoparticles (AuNPs) (MBA-biotin-AuNPs) as labels. To demonstrate the feasibility and sensitivity of this method, recombinant human erythropoietin (rHuEPO) was tested as a model analyte. Specifically, rHuEPO was captured by the anti-rHuEPO aptamer-covered electrode and then derivatized with MBA-biotin-AuNPs through the boronic acid-carbohydrate interaction. The MBA-biotin-AuNPs facilitated the attachment of streptavidin-conjugated alkaline phosphatase for the production of electroactive p-aminophenol from p-aminophenyl phosphate substrate. A detection limit of 8 fmol L(-1) for rHuEPO detection was achieved. Other glycosylated and non-glycosylated proteins, such as horseradish peroxidase, prostate specific antigen, metallothionein, streptavidin, and thrombin showed no interference in the detection assay.

Mesomorphic structure of poly(styrene)-block-poly(4-vinylpyridine) with oligo(ethylene oxide)sulfonic acid side chains as a model for molecularly reinforced polymer electrolyte

NARCIS (Netherlands)

Kosonen, H; Valkama, S; Hartikainen, J; Eerikainen, H; Torkkeli, M; Jokela, K; Serimaa, R; Sundholm, F; ten Brinke, G; Ikkala, O; Eerikäinen, Hannele

2002-01-01

We report self-organized polymer electrolytes based on poly(styrene)-block-poly(4-vinylpyridine) (PS-block-P4VP). Liquidlike ethylene oxide (EO) oligomers with sulfonic acid end groups are bonded to the P4VP block, leading to comb-shaped supramolecules with the PS-block-P4VP backbone. Lithium

Annotating Human P-Glycoprotein Bioassay Data.

Science.gov (United States)

Zdrazil, Barbara; Pinto, Marta; Vasanthanathan, Poongavanam; Williams, Antony J; Balderud, Linda Zander; Engkvist, Ola; Chichester, Christine; Hersey, Anne; Overington, John P; Ecker, Gerhard F

2012-08-01

Huge amounts of small compound bioactivity data have been entering the public domain as a consequence of open innovation initiatives. It is now the time to carefully analyse existing bioassay data and give it a systematic structure. Our study aims to annotate prominent in vitro assays used for the determination of bioactivities of human P-glycoprotein inhibitors and substrates as they are represented in the ChEMBL and TP-search open source databases. Furthermore, the ability of data, determined in different assays, to be combined with each other is explored. As a result of this study, it is suggested that for inhibitors of human P-glycoprotein it is possible to combine data coming from the same assay type, if the cell lines used are also identical and the fluorescent or radiolabeled substrate have overlapping binding sites. In addition, it demonstrates that there is a need for larger chemical diverse datasets that have been measured in a panel of different assays. This would certainly alleviate the search for other inter-correlations between bioactivity data yielded by different assay setups.

Spectrophotometric Determination of Zinc Using 7-(4-Nitrophenylazo-8-Hydroxyquinoline-5-Sulfonic Acid

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Korn Maria das Graças Andrade

1999-01-01

Full Text Available A sensitive and selective spectrophotometric method is proposed for the rapid determination of zinc(II using an 8-hydroxyquinoline derivative, 7-(4-nitrophenylazo-8-hydroxyquinoline-5-sulfonic acid (p-NIAZOXS, as a new spectrophotometric reagent. The reaction between the p-NIAZOXS and zinc(II is instantaneous at pH 9.2 (borax buffer and the absorbance remains stable for over 24 h. The method allows the determination of zinc over the range of 0.05-1.0 mug mL-1 with a molar absorptivity of 3.75x10(4 L mol-1 cm-1 and features a detection limit of 15 ng mL-1. The proposed method has been successfully applied to the determination of zinc in several pharmaceutical preparations and copper alloys. The precision (R.S.D. < 2% and the accuracy obtained were satisfactory.

Appearance and cellular distribution of lectin-like receptors for alpha 1-acid glycoprotein in the developing rat testis

DEFF Research Database (Denmark)

Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

1996-01-01

A histochemical avidin-biotin technique with three different alpha 1-acid glycoprotein glycoforms showed pronounced alterations in the cellular localization of two alpha 1-acid glycoprotein lectin-like receptors during cell differentiation in the developing rat testis. The binding of alpha 1-acid...

Microstructures of the Sulfonic Acid-Functionalized Ionic Liquid/Sulfuric Acid and Their Interactions: A Perspective from the Isobutane Alkylation.

Science.gov (United States)

Zheng, Weizhong; Huang, Chizhou; Sun, Weizhen; Zhao, Ling

2018-02-01

The all-atom force field for concentrated sulfuric acid (98.30 wt %) was developed in this work based on ab initio calculations. The structural and dynamical properties of sulfuric acid and the mixing behaviors of sulfuric acid with ionic liquids (ILs), i.e., SFIL (1-methyl-3-(propyl-3-sulfonate) imidazolium bisulfate ([PSMim][HSO 4 ])) and non-SFIL (1-methyl-3-propyl imidazolium bisulfate ([PMim][HSO 4 ])), were investigated using a molecular dynamics simulation. For sulfuric acid, most H 3 O + ions were found beside HSO 4 - ions, forming a contact ion pair with the HSO 4 - ions, and three-dimensional hydrogen-bonding networks existed in the sulfuric acid. Analyses indicate that both ILs could be miscible with sulfuric acid with a strong exothermic character. The new strong interaction site between the sulfonic acid group of SFIL and an H 2 SO 4 molecule through a strong hydrogen-bonding interaction was observed, which was beneficial to the catalytic activity and stability of the sulfuric acid. This observation is in good agreement with the experimental results that indicate SFILs could enhance the reusability of sulfuric acid for the isobutane alkylation about 4-fold compared to that of non-SFILs. Hopefully this work will provide insights into the screening and designing of new isobutane alkylation catalysts based on sulfuric acid and SFILs.

Separation of transition-metal and 8-hydroxyquinoline-5-sulfonic acid complexes using ion-pair liquid chromatography

International Nuclear Information System (INIS)

Basova, E.M.; Demurov, L.M.; Shpigun, O.A.; Van Iyuchun'

1994-01-01

The retention of chelates of Fe(3), Cu(2), Co(2), Ni(2), Zn(2), Cd(2), Hg(2), and Pb)(2) with 8-hydroxyquinoline-5-sulfonic acid depending on the concentration of cetyltrimethylammonium bromide, acetonitrile, and pH of the mobile phase was investigated using the ion-pair reversed-phase high-performance liquid chromatography on separon C 18 . Under the optimum conditions, the separation of mixtures of Fe(3), Co(2) and Ni(2) is performed within 8 to 12 min

Physicochemical pretreatments and hydrolysis of furfural residues via carbon-based sulfonated solid acid.

Science.gov (United States)

Ma, Bao Jun; Sun, Yuan; Lin, Ke Ying; Li, Bing; Liu, Wan Yi

2014-03-01

Potential commercial physicochemical pretreatment methods, NaOH/microwave and NaOH/ultrasound were developed, and the carbon-based sulfonated solid acid catalysts were prepared for furfural residues conversion into reducing sugars. After the two optimum pretreatments, both the content of cellulose increased (74.03%, 72.28%, respectively) and the content of hemicellulose (94.11%, 94.17% of removal rate, respectively) and lignin (91.75%, 92.09% of removal rate, respectively) decreased in furfural residues. The reducing sugar yields of furfural residues with the two physicochemical pretreatments on coal tar-based solid acid reached 33.94% and 33.13%, respectively, higher than that pretreated via NaOH alone (27%) and comparable to that pretreated via NaOH/H2O2 (35.67%). The XRD patterns, IR spectra and SEM images show microwave and ultrasound improve the pretreatment effect. The results demonstrate the carbon-based sulfonated solid acids and the physicochemical pretreatments are green, effective, low-cost for furfural residues conversion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots.

Science.gov (United States)

Bosilkovska, M; Samer, C F; Déglon, J; Rebsamen, M; Staub, C; Dayer, P; Walder, B; Desmeules, J A; Daali, Y

2014-09-01

The suitability of the capillary dried blood spot (DBS) sampling method was assessed for simultaneous phenotyping of cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp) using a cocktail approach. Ten volunteers received an oral cocktail capsule containing low doses of the probes bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and fexofenadine (P-gp) with coffee/Coke (CYP1A2) on four occasions. They received the cocktail alone (session 1), and with the CYP inhibitors fluvoxamine and voriconazole (session 2) and quinidine (session 3). In session 4, subjects received the cocktail after a 7-day pretreatment with the inducer rifampicin. The concentrations of probes/metabolites were determined in DBS and plasma using a single liquid chromatography-tandem mass spectrometry method. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. Important modulation of CYP and P-gp activities was observed in the presence of inhibitors and the inducer. Minimally invasive one- and three-point (at 2, 3, and 6 h) DBS-sampling methods were found to reliably reflect CYP and P-gp activities at each session.

Synthesis and properties of poly(aryl sulfone benzimidazole) and its copolymers for high temperature membrane electrolytes for fuel cells

DEFF Research Database (Denmark)

Yang, Jingshuai; Li, Qingfeng; Cleemann, Lars Nilausen

2012-01-01

Poly(aryl sulfone benzimidazole) (SO2PBI) and its copolymers with poly[2,2′-p-(phenylene)-5,5′-bibenzimidazole] (pPBI), termed as Co-SO2PBI, were synthesized with varied feeding ratios of 4,4′-sulfonyldibenzoic acid (SDBA) to terephthalic acid (TPA). Incorporation of the stiff para-phenylene and ......Poly(aryl sulfone benzimidazole) (SO2PBI) and its copolymers with poly[2,2′-p-(phenylene)-5,5′-bibenzimidazole] (pPBI), termed as Co-SO2PBI, were synthesized with varied feeding ratios of 4,4′-sulfonyldibenzoic acid (SDBA) to terephthalic acid (TPA). Incorporation of the stiff para...

Meso- and macroporous sulfonated starch solid acid catalyst for esterification of palm fatty acid

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Ibrahim M. Lokman

2016-03-01

Full Text Available In the present work, a heterogeneous solid acid catalyst was successfully developed from starch. The catalyst was prepared by a significant two-step process; the initial step was incomplete carbonization of starch (ICS at 400 °C for 12 h and consequently followed by sulfonation process using concentrated H2SO4 to produce sulfonated-incomplete carbonized starch (ICS-SO3H. The characterization of the ICS-SO3H catalyst was done for chemical and physical properties such as X-ray diffraction (XRD, ammonia-temperature programmed desorption (NH3-TPD, surface area analysis, thermal gravimetric analysis (TGA, elemental analysis and morphology analysis by scanning electron microscope (SEM. BET results showed the structure of ICS-SO3H consists of meso- and macro-porous properties, which allowed high density of the SO3H group attached on its carbon networks. The catalytic activity of ICS-SO3H catalyst was determined by analyzing the catalyst performance to esterify palm fatty acid distillate (PFAD and sequentially produced methyl ester. The maximum free fatty acid (FFA conversion and FAME yield were as high as 94.6% and 90.4%, respectively, at 75 °C using 10:1 methanol-to-PFAD molar ratio and 2 wt.% of catalyst within 3 h. The catalyst has sufficient potential to recycle up to 6 reactions without reactivation step and any remarkable loss of catalytic activity. It revealed that the heterogeneous ICS-SO3H catalyst exhibits high stability, reusability and catalytic activity.

Alcohol-induced structural transitions in the acid-denatured Bacillus licheniformis α-amylase

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Adyani Azizah Abd Halim

2017-01-01

Full Text Available Alcohol-induced structural changes in the acid-denatured Bacillus licheniformis α-amylase (BLA at pH 2.0 were studied by far-ultra violet circular dichroism, intrinsic, three-dimensional and 8-anilino-1-naphthalene sulfonic acid (ANS fluorescence, acrylamide quenching and thermal denaturation. All the alcohols used in this study produced partial refolding in the acid-denatured BLA as evident from the increased mean residue ellipticity at 222 nm, increased intrinsic fluorescence and decreased ANS fluorescence. The order of effectiveness of these alcohols to induce a partially folded state of BLA was found to be: 2,2,2-trifluoroethanol/tert-butanol > 1-propanol/2-propanol > 2-chloroethanol > ethanol > methanol. Three-dimensional fluorescence and acrylamide quenching results obtained in the presence of 5.5 M tert-butanol also suggested formation of a partially folded state in the acid-denatured BLA. However, 5.5 M tert-butanol-induced state of BLA showed a non-cooperative thermal transition. All these results suggested formation of a partially folded state of the acid-denatured BLA in the presence of these alcohols. Furthermore, their effectiveness was found to be guided by their chain length, position of methyl groups and presence of the substituents.

Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity.

Science.gov (United States)

Vauzour, David; Corona, Giulia; Spencer, Jeremy P E

2010-09-01

Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-)-epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids. Copyright © 2010. Published by Elsevier Inc.

Identification of oligo-N-glycolylneuraminic acid residues in mammal-derived glycoproteins by a newly developed immunochemical reagent and biochemical methods.

Science.gov (United States)

Sato, C; Kitajima, K; Inoue, S; Inoue, Y

1998-01-30

The occurrence of the alpha2-->8-linked oligomeric form of N-glycolylneuraminic acid (oligo-Neu5Gc) residues in mammalian glycoproteins was unequivocally demonstrated using a newly developed anti-oligo/poly-Neu5Gc monoclonal antibody as well as by chemical and biochemical methods. First, the antibody, designated mAb.2-4B, which specifically recognized oligo/poly-Neu5Gc with a degree of polymerization of >2, was developed by establishing a hybridoma cell line from P3U1 myeloma cells fused with splenocytes from an MRL autoimmune mouse immunized with dipalmitoylphosphatidylethanolamine-conjugated oligo/poly-Neu5Gc. Second, oligo-Neu5Gc was shown to occur in glycoproteins derived from pig spleen by Western blot analysis using mAb.2-4B, which was also confirmed by fluorometric high performance liquid chromatographic analysis of the product of periodate oxidation/reduction/acid hydrolysis of the purified glycopeptide fractions and by TLC and 600-MHz 1H NMR spectroscopic analysis of their mild acid hydrolysates. Finally, the ubiquitous occurrence of oligo-Neu5Gc chains as glycoproteinaceous components in Wistar rat tissue was immunochemically indicated. This is the first example demonstrating the diversity in oligo/poly-Sia structure in mammalian glycoproteins, where only poly-N-acetylneuraminic acid is known to occur. Such diversity in oligo/poly-Sia structure also implicates a diverged array of biological functions of this glycan unit in glycoproteins.

Proton Conductivity of Nafion/Ex-Situ Sulfonic Acid-Modified Stöber Silica Nanocomposite Membranes As a Function of Temperature, Silica Particles Size and Surface Modification

Science.gov (United States)

Muriithi, Beatrice; Loy, Douglas A.

2016-01-01

The introduction of sulfonic acid modified silica in Nafion nanocomposite membranes is a good method of improving the Nafion performance at high temperature and low relative humidity. Sulfonic acid-modified silica is bifunctional, with silica phase expected to offer an improvement in membranes hydration while sulfonic groups enhance proton conductivity. However, as discussed in this paper, this may not always be the case. Proton conductivity enhancement of Nafion nanocomposite membranes is very dependent on silica particle size, sometimes depending on experimental conditions, and by surface modification. In this study, Sulfonated Preconcentrated Nafion Stober Silica composites (SPNSS) were prepared by modification of Stober silica particles with mercaptopropyltriethoxysilane, dispersing the particles into a preconcentrated solution of Nafion, then casting the membranes. The mercapto groups were oxidized to sulfonic acids by heating the membranes in 10 wt % hydrogen peroxide for 1 h. At 80 °C and 100% relative humidity, a 20%–30% enhancement of proton conductivity was only observed when sulfonic acid modified particle less than 50 nm in diameter were used. At 120 °C, and 100% humidity, proton conductivity increased by 22%–42% with sulfonated particles with small particles showing the greatest enhancement. At 120 °C and 50% humidity, the sulfonated particles are less efficient at keeping the membranes hydrated, and the composites underperform Nafion and silica-Nafion nanocomposite membranes. PMID:26828525

A durable alternative for proton-exchange membranes: sulfonated poly(benzoxazole thioether sulfone)s

Energy Technology Data Exchange (ETDEWEB)

Zhao, Dan [Center for Innovative Fuel Cell and Battery Technologies, School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States); Lab of PEMFC Key Materials and Technologies, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Liaoning, Dalian 116023 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100039 (China); Li, Jinhuan [Center for Innovative Fuel Cell and Battery Technologies, School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States); College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016 (China); Song, Min-Kyu; Liu, Meilin [Center for Innovative Fuel Cell and Battery Technologies, School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245 (United States); Yi, Baolian; Zhang, Huamin [Lab of PEMFC Key Materials and Technologies, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Liaoning, Dalian 116023 (China)

2011-03-18

To develop a durable proton-exchange membrane (PEM) for fuel-cell applications, a series of sulfonated poly(benzoxazole thioether sulfone)s (SPTESBOs) are designed and synthesized, with anticipated good dimensional stability (via acid-base cross linking), improved oxidative stability against free radicals (via incorporation of thioether groups), and enhanced inherent stability (via elimination of unstable end groups) of the backbone. The structures and the degree of sulfonation of the copolymers are characterized using Fourier-transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy ({sup 1}H NMR and {sup 19}F NMR). The electrochemical stabilities of the monomers are examined using cyclic voltammetry in a typical three-electrode cell configuration. The physicochemical properties of the membranes vital to fuel-cell performance are also carefully evaluated under conditions relevant to fuel-cell operation, including chemical and thermal stability, proton conductivity, solubility in different solvents, water uptake, and swelling ratio. The new membranes exhibit low dimensional change at 25 C to 90 C and excellent thermal stability up to 250 C. Upon elimination of unstable end groups, the co-polymers display enhanced chemical resistance and oxidative stability in Fenton's test. Further, the SPTESBO-HFB-60 (HFB-60=hexafluorobenzene, 60 mol% sulfone) membrane displays comparable fuel-cell performance to that of an NRE 212 membrane at 80 C under fully humidified condition, suggesting that the new membranes have the potential to be more durable but less expensive for fuel-cell applications. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa.

Science.gov (United States)

Linardi, R L; Stokes, A M; Andrews, F M

2013-02-01

Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability for 120 min, and the flux of methadone across the jejunal membrane (mucosal to submucosal direction) was calculated based on the relative drug concentration measured by ELISA. The flux of methadone was significantly higher only in the presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane of the jejunal epithelial cells (enterocytes), mainly located in the tip of the villi compared to cells of the crypts. P-glycoprotein is present in the equine jejunum and may possibly mediate the intestinal transport of methadone. This study suggests that P-glycoprotein may play a role in the poor intestinal absorption of methadone in vivo. © 2012 Blackwell Publishing Ltd.

Visceral hypersensitivity is provoked by 2,4,6-trinitrobenzene sulfonic acid-induced ileitis in rats

Directory of Open Access Journals (Sweden)

Manoj Kumar Shah

2016-07-01

Full Text Available Background and Aims: Crohn’s Disease (CD, a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48, an equal volume of 30% Ethanol (n = 24 and Saline (n = 24, respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6, and dorsal root ganglia (T11 for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05 VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05 in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral

Biofilm behavior on sulfonated poly(ether-ether-ketone) (sPEEK)

Energy Technology Data Exchange (ETDEWEB)

Montero, Juan F.D. [Center for Research on Dental Implants (CEPID), School of Dentistry (ODT), Federal University of Santa Catarina - UFSC, Florianópolis, SC 88040-900 (Brazil); Tajiri, Henrique A.; Barra, Guilherme M.O.; Fredel, Márcio C. [Department of Mechanical Engineering (EMC), Federal University of Santa Catarina (UFSC), Florianópolis, SC 88040-900 (Brazil); Benfatti, Cesar A.M.; Magini, Ricardo S. [Center for Research on Dental Implants (CEPID), School of Dentistry (ODT), Federal University of Santa Catarina - UFSC, Florianópolis, SC 88040-900 (Brazil); Pimenta, Andréa L. [Integrated Laboratories Technologies (InteLAB), Dept. Chemical Engineering (EQA), Federal University of Santa Catarina - UFSC, Florianópolis, SC 88040-970 (Brazil); Department of Biologie, Université de Cergy Pontoise, 2, Av. Adolphe Chauvin, 95302 Cergy Pontoise (France); Souza, Júlio C.M., E-mail: julio.c.m.souza@ufsc.br [Center for Research on Dental Implants (CEPID), School of Dentistry (ODT), Federal University of Santa Catarina - UFSC, Florianópolis, SC 88040-900 (Brazil); Center for Microelectromechanical Systems (CMEMS), Dept. Mechanical Engineering (DEM), Campus Azurém, 4800-058 Guimarães (Portugal)

2017-01-01

Poly(ether-ether-ketone) (PEEK) has also shown to be very attractive for incorporating therapeutic compounds thanks to a sulfonation process which modifies the material structure resulting in a sulfonated-PEEK (sPEEK). Concerning biomedical applications, the objective of this work was to evaluate the influence of different sulfonation degree of sPEEK on the biofilm growth. PEEK samples were functionalized by using sulphuric acid (98%) and then dissolved into dimethyl-sulfoxide. A dip coating technique was used to synthesize sPEEK thin films. The sulfonation degree of the materials was analyzed by FT-IR, H NMR, TG and IEC. The surfaces were characterized by scanning electron microscopy, profilometry and contact angle analyses. Subsequently, the biofilm formation on sulfonated-PEEK based on Streptococcus mutans and Enterococcus faecalis was measured by spectrophotometry, colony forming units (CFU mL{sup −1}) and SEM. Results obtained from thermal and chemical analyses showed an intensification in sulfonation degree for sPEEK at 2 and 2.5 h. The E. faecalis or S. mutans biofilm growth revealed statistically significant differences (p < 0.05) between 2 and 3 h sulfonation groups. A significant decrease (p < 0.05) in CFU mL{sup −1} was recorded for S. mutans or E. faecalis biofilm grown on 2.5 or 3 h sPEEK. Regarding the thermal-chemical and microbiologic analyses, the sulfonation degree of sPEEK ranging from 2 up to 3 h was successful capable to decrease the biofilm growth. That revealed an alternative strategy to embed anti-biofilm and therapeutic compounds into PEEK avoiding infections in biomedical applications. - Highlights: • PEEK can be dissolved to incorporate therapeutic compounds. • High sulfonation degree on sPEEK affected the biofilm growth. • The sulfonation degree must be controlled to maintain the properties of sPEEK.

Biofilm behavior on sulfonated poly(ether-ether-ketone) (sPEEK)

International Nuclear Information System (INIS)

Montero, Juan F.D.; Tajiri, Henrique A.; Barra, Guilherme M.O.; Fredel, Márcio C.; Benfatti, Cesar A.M.; Magini, Ricardo S.; Pimenta, Andréa L.; Souza, Júlio C.M.

2017-01-01

Poly(ether-ether-ketone) (PEEK) has also shown to be very attractive for incorporating therapeutic compounds thanks to a sulfonation process which modifies the material structure resulting in a sulfonated-PEEK (sPEEK). Concerning biomedical applications, the objective of this work was to evaluate the influence of different sulfonation degree of sPEEK on the biofilm growth. PEEK samples were functionalized by using sulphuric acid (98%) and then dissolved into dimethyl-sulfoxide. A dip coating technique was used to synthesize sPEEK thin films. The sulfonation degree of the materials was analyzed by FT-IR, H NMR, TG and IEC. The surfaces were characterized by scanning electron microscopy, profilometry and contact angle analyses. Subsequently, the biofilm formation on sulfonated-PEEK based on Streptococcus mutans and Enterococcus faecalis was measured by spectrophotometry, colony forming units (CFU mL −1 ) and SEM. Results obtained from thermal and chemical analyses showed an intensification in sulfonation degree for sPEEK at 2 and 2.5 h. The E. faecalis or S. mutans biofilm growth revealed statistically significant differences (p < 0.05) between 2 and 3 h sulfonation groups. A significant decrease (p < 0.05) in CFU mL −1 was recorded for S. mutans or E. faecalis biofilm grown on 2.5 or 3 h sPEEK. Regarding the thermal-chemical and microbiologic analyses, the sulfonation degree of sPEEK ranging from 2 up to 3 h was successful capable to decrease the biofilm growth. That revealed an alternative strategy to embed anti-biofilm and therapeutic compounds into PEEK avoiding infections in biomedical applications. - Highlights: • PEEK can be dissolved to incorporate therapeutic compounds. • High sulfonation degree on sPEEK affected the biofilm growth. • The sulfonation degree must be controlled to maintain the properties of sPEEK.

Glucose Modulation Induces Lysosome Formation and Increases Lysosomotropic Drug Sequestration via the P-Glycoprotein Drug Transporter.

Science.gov (United States)

Seebacher, Nicole A; Lane, Darius J R; Jansson, Patric J; Richardson, Des R

2016-02-19

Pgp is functional on the plasma membrane and lysosomal membrane. Lysosomal-Pgp can pump substrates into the organelle, thereby trapping certain chemotherapeutics (e.g. doxorubicin; DOX). This mechanism serves as a "safe house" to protect cells against cytotoxic drugs. Interestingly, in contrast to DOX, lysosomal sequestration of the novel anti-tumor agent and P-glycoprotein (Pgp) substrate, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), induces lysosomal membrane permeabilization. This mechanism of lysosomal-Pgp utilization enhances cytotoxicity to multidrug-resistant cells. Consequently, Dp44mT has greater anti-tumor activity in drug-resistant relative to non-Pgp-expressing tumors. Interestingly, stressors in the tumor microenvironment trigger endocytosis for cell signaling to assist cell survival. Hence, this investigation examined how glucose variation-induced stress regulated early endosome and lysosome formation via endocytosis of the plasma membrane. Furthermore, the impact of glucose variation-induced stress on resistance to DOX was compared with Dp44mT and its structurally related analogue, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC). These studies showed that glucose variation-induced stress-stimulated formation of early endosomes and lysosomes. In fact, through the process of fluid-phase endocytosis, Pgp was redistributed from the plasma membrane to the lysosomal membrane via early endosome formation. This lysosomal-Pgp actively transported the Pgp substrate, DOX, into the lysosome where it became trapped as a result of protonation at pH 5. Due to increased lysosomal DOX trapping, Pgp-expressing cells became more resistant to DOX. In contrast, cytotoxicity of Dp44mT and DpC was potentiated due to more lysosomes containing functional Pgp under glucose-induced stress. These thiosemicarbazones increased lysosomal membrane permeabilization and cell death. This mechanism has critical implications for drug-targeting in

Human umbilical cord mesenchymal stem cells ameliorate mice trinitrobenzene sulfonic acid (TNBS)-induced colitis.

Science.gov (United States)

Liang, Lu; Dong, Chunlan; Chen, Xiaojun; Fang, Zhihong; Xu, Jie; Liu, Meng; Zhang, Xiaoguang; Gu, Dong Sheng; Wang, Ding; Du, Weiting; Zhu, Delin; Han, Zhong Chao

2011-01-01

Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-γ and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-γ expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis.

Nanostructured membranes and electrodes with sulfonic acid functionalized carbon nanotubes

KAUST Repository

Tripathi, Bijay Prakash; Schieda, Mauricio; Shahi, Vinod Kumar; Nunes, Suzana Pereira

2011-01-01

Herein we report the covalent functionalization of multiwall carbon nanotubes by grafting sulfanilic acid and their dispersion into sulfonated poly(ether ether ketone). The nanocomposites were explored as an option for tuning the proton and electron conductivity, swelling, water and alcohol permeability aiming at nanostructured membranes and electrodes for application in alcohol or hydrogen fuel cells and other electrochemical devices. The nanocomposites were extensively characterized, by studying their physicochemical and electrochemical properties. They were processed as self-supporting films with high mechanical stability, proton conductivity of 4.47 × 10 -2 S cm-1 at 30 °C and 16.8 × 10-2 S cm-1 at 80 °C and 100% humidity level, electron conductivity much higher than for the plain polymer. The methanol permeability could be reduced to 1/20, keeping water permeability at reasonable values. The ratio of bound water also increases with increasing content of sulfonated filler, helping in keeping water in the polymer in conditions of low external humidity level. © 2010 Elsevier B.V.

Nanostructured membranes and electrodes with sulfonic acid functionalized carbon nanotubes

KAUST Repository

Tripathi, Bijay Prakash

2011-02-01

Herein we report the covalent functionalization of multiwall carbon nanotubes by grafting sulfanilic acid and their dispersion into sulfonated poly(ether ether ketone). The nanocomposites were explored as an option for tuning the proton and electron conductivity, swelling, water and alcohol permeability aiming at nanostructured membranes and electrodes for application in alcohol or hydrogen fuel cells and other electrochemical devices. The nanocomposites were extensively characterized, by studying their physicochemical and electrochemical properties. They were processed as self-supporting films with high mechanical stability, proton conductivity of 4.47 × 10 -2 S cm-1 at 30 °C and 16.8 × 10-2 S cm-1 at 80 °C and 100% humidity level, electron conductivity much higher than for the plain polymer. The methanol permeability could be reduced to 1/20, keeping water permeability at reasonable values. The ratio of bound water also increases with increasing content of sulfonated filler, helping in keeping water in the polymer in conditions of low external humidity level. © 2010 Elsevier B.V.

Toxicology and carcinogenesis studies of p,p'-dichlorophenyl sulfone (CAS No. 80-07-9) in F344/N rats and B6C3F1 mice (feed studies).

Science.gov (United States)

2001-09-01

diets containing 0, 30, 100, or 300 ppm p,pN-dichlorodiphenyl sulfone for 105 to 106 weeks. Dietary concentrations of 30, 100, and 300 ppm delivered average daily doses of approximately 4, 13, and 40 mg/kg to males and approximately 3, 10, and 33 mg/kg to females. Additional groups of 10 male and 10 female mice were fed the same p,pN-dichlorodiphenyl sulfone-containing diets for up to 12 months;three mice in each group were bled for plasma determinations of p,pN-dichloro-diphenyl sulfone at approximately 2 weeks or 3 or 12 months. Survival of all exposed groups of male and female mice was similar to that of the control groups. Mean body weights of 300 ppm mice were less than those of the controls throughout most of the study. Feed consumption by the exposed groups was similar to that by the controls throughout the study. The incidences of centrilobular hepatocyte hypertrophy in all exposed groups of male mice and in 100 and 300 ppm females were significantly greater than those in the controls. The incidence of eosinophilic foci in 300 ppm females was significantly increased. No neoplasms were related to chemical exposure. PHARMACOKINETICS OF p,pN-DICHLORODIPHENYL SULFONE: p,pN-Dichlorodiphenyl sulfone is rapidly absorbed from the gut and metabolized by a saturable process. Although some p,pN-dichlorodiphenyl sulfone is eliminated unchanged in feces and urine, most of the elimination is via metabolism. Mathematical modeling of the toxicokinetics supports the view that p,pN-dichlorodiphenyl sulfone induces enzymes involved in its metabolism. p,pN-Dichlorodiphenyl sulfone was not mutagenic in any of several strains of Salmonella typhimurium, with or without metabolic activation enzymes (S9). Results of the sister chromatid exchange test in cultured Chinese hamster ovary cells were judged to be negative in the presence of S9 and equivocal in the absence of S9, but no induction of chromosomal aberrations was noted, with or without S9. In contrast to the in vitro results

Sodium butyrate attenuates soybean oil-based lipid emulsion-induced increase in intestinal permeability of lipopolysaccharide by modulation of P-glycoprotein in Caco-2 cells

International Nuclear Information System (INIS)

Yan, Jun-Kai; Gong, Zi-Zhen; Zhang, Tian; Cai, Wei

2017-01-01

Down-regulation of intestinal P-glycoprotein (P-gp) by soybean oil-based lipid emulsion (SOLE) may cause elevated intestinal permeability of lipopolysaccharide (LPS) in patients with total parenteral nutrition, but the appropriate preventative treatment is currently limited. Recently, sodium butyrate (NaBut) has been demonstrated to regulate the expression of P-gp. Therefore, this study aimed to address whether treatment with NaBut could attenuate SOLE-induced increase in intestinal permeability of LPS by modulation of P-gp in vitro. Caco-2 cells were exposed to SOLE with or without NaBut. SOLE-induced down-regulation of P-gp was significantly attenuated by co-incubation with NaBut. Nuclear recruitment of FOXO 3a in response to NaBut was involved in P-gp regulation. Transport studies revealed that SOLE-induced increase in permeability of LPS was significantly attenuated by co-incubation with NaBut. Collectively, our results suggested that NaBut may be a potentially useful medication to prevent SOLE-induced increase in intestinal permeability of LPS. - Highlights: • Caco-2 cells were used as models for studying parenteral nutrition in vitro. • NaBut restored SOLE-induced down-regulation of P-gp in Caco-2 cells. • Regulation of P-gp by NaBut was mediated via nuclear recruitment of FOXO 3a. • NaBut modulated the permeability of LPS by P-gp function, not barrier function.

Global analysis of myocardial peptides containing cysteines with irreversible sulfinic and sulfonic Acid post-translational modifications

DEFF Research Database (Denmark)

Paulech, Jana; Liddy, Kiersten A; Engholm-Keller, Kasper

2015-01-01

) and others (Cys sulfinic [Cys-SO2H] and sulfonic [Cys-SO3H] acids) that are considered "irreversible." We developed an enrichment method to isolate Cys-SO2H/SO3H-containing peptides from complex tissue lysates that is compatible with tandem mass spectrometry (MS/MS). The acidity of these post...

Analysis of glycoprotein-derived oligosaccharides in glycoproteins detected on two-dimensional gel by capillary electrophoresis using on-line concentration method.

Science.gov (United States)

Kamoda, Satoru; Nakanishi, Yasuharu; Kinoshita, Mitsuhiro; Ishikawa, Rika; Kakehi, Kazuaki

2006-02-17

Capillary electrophoresis (CE) is an effective tool to analyze carbohydrate mixture derived from glycoproteins with high resolution. However, CE has a disadvantage that a few nanoliters of a sample solution are injected to a narrow capillary. Therefore, we have to prepare a sample solution of high concentration for CE analysis. In the present study, we applied head column field-amplified sample stacking method to the analysis of N-linked oligosaccharides derived from glycoprotein separated by two-dimensional gel electrophoresis. Model studies demonstrated that we achieved 60-360 times concentration effect on the analysis of carbohydrate chains labeled with 3-aminobenzoic acid (3-AA). The method was applied to the analysis of N-linked oligosaccharides from glycoproteins separated and detected on PAGE gel. Heterogeneity of alpha1-acid glycoprotein (AGP), i.e. glycoforms, was examined by 2D-PAGE and N-linked oligosaccharides were released by in-gel digestion with PNGase F. The released oligosaccharides were derivatized with 3-AA and analyzed by CE. The results showed that glycoforms having lower pI values contained a larger amount of tetra- and tri-antennary oligosaccharides. In contrast, glycoforms having higher pI values contained bi-antennary oligosaccharides abundantly. The result clearly indicated that the spot of a glycoprotein glycoform detected by Coomassie brilliant blue staining on 2D-PAGE gel is sufficient for quantitative profiling of oligosaccharides.

Irradiation of rat brain reduces P-glycoprotein expression and function

NARCIS (Netherlands)

Bart, J.; Nagengast, W. B.; Coppes, R. P.; Wegman, T. D.; van der Graaf, W. T. A.; Groen, H. J. M.; Vaalburg, W.; de Vries, E. G. E.; Hendrikse, N. H.

2007-01-01

The blood - brain barrier ( BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P- glycoprotein ( P- gp), expressed on brain capillary endothelial cells, is part of the BBB. P- gp expression on capillary endothelium decreases 5 days after brain

MDR1 P-glycoprotein transports endogenous opioid peptides

NARCIS (Netherlands)

Oude Elferink, R. P.; Zadina, J.

2001-01-01

MDR1 P-glycoprotein is generally regarded as an efflux pump for amphipathic toxic compounds. The question remains, however, whether certain endogenous compounds are also substrates for this transporter. Certain peptides have been shown to interact with MDR1 Pgp as well and we have therefore

Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression

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Viera Bohacova

2018-05-01

Full Text Available The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family, represents a frequently observed molecular cause of multidrug resistance (MDR. This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR. Here, we showed that triorganotin derivatives—tributyltin-chloride (TBT-Cl, tributyltin-bromide (TBT-Br, tributyltin-iodide (TBT-I and tributyltin-isothiocyanate (TBT-NCS or triphenyltin-chloride (TPT-Cl and triphenyltin-isothiocyanate (TPT-NCS—could induce the death of L1210 mice leukemia cells at a submicromolar concentration independently of P-gp overexpression. The median lethal concentration obtained for triorganotin derivatives did not exceed 0.5 µM in the induction of cell death of either P-gp negative or P-gp positive L1210 cells. Apoptosis related to regulatory pathway of Bcl-2 family proteins seems to be the predominant mode of cell death in either P-gp negative or P-gp positive L1210 cells. TBT-Cl and TBT-Br were more efficient with L1210 cells overexpressing P-gp than with their counterpart P-gp negative cells. In contrast, TBT-I and TPT-NCS induced a more pronounced cell death effect on P-gp negative cells than on P-gp positive cells. Triorganotin derivatives did not affect P-gp efflux in native cells measured by calcein retention within the cells. Taken together, we assumed that triorganotin derivatives represent substances suitable for suppressing the viability of P-gp positive malignant cells.

Glycoprotein on cell surfaces

International Nuclear Information System (INIS)

Muramatsu, T.

1975-01-01

There are conjugated polysaccharides in cell membranes and outside of animal cells, and they play important role in the control of cell behavior. In this paper, the studies on the glycoprotein on cell surfaces are reported. It was found that the glycoprotein on cell surfaces have both N-glycoside type and O-glycoside type saccharic chains. Therefore it can be concluded that the basic structure of the saccharic chains in the glycoprotein on cell surfaces is similar to that of blood serum and body fluid. The main glycoprotein in the membranes of red blood corpuscles has been studied most in detail, and it also has both types of saccharic chains. The glycoprotein in liver cell membranes was found to have only the saccharic chains of acid type and to be in different pattern from that in endoplasmic reticula and nuclear membranes, which also has the saccharic chains of neutral type. The structure of the saccharic chains of H-2 antigen, i.e. the peculiar glycoprotein on the surfaces of lymph system cells, has been studied, and it is similar to the saccharic chains of glycoprotein in blood serum. The saccharic chain structures of H-2 antigen and TL antigen are different. TL, H-2 (D), Lna and H-2 (K) are the glycoprotein on cell surfaces, and are independent molecules. The analysis of the saccharic chain patterns on cell surfaces was carried out, and it was shown that the acid type saccharic chains were similar to those of ordinary glycoprotein, because the enzyme of pneumococci hydrolyzed most of the acid type saccharic chains. The change of the saccharic chain patterns of glycoprotein on cell surfaces owing to canceration and multiplication is complex matter. (Kako, I.)

Interaction of multi-walled carbon nanotubes with perfluorinated sulfonic acid ionomers and surface treatment studies

DEFF Research Database (Denmark)

Andersen, Shuang Ma; Dhiman, Rajnish; Borghei, Maryam

2014-01-01

The interaction between high surface area nano-carbon catalyst supports for proton exchange membrane fuel cells (PEMFCs) and perfluorinated sulfonic acid (Nafion®) ionomer was studied 19 fluorine nuclear magnetic resonance spectroscopy (19F-NMR). The method was developed and improved for more...

Pumping of drugs by P-glycoprotein

DEFF Research Database (Denmark)

Litman, Thomas; Skovsgaard, Torben; Stein, Wilfred D

2003-01-01

The apparent inhibition constant, Kapp, for the blockade of P-glycoprotein (P-gp) by four drugs, verapamil, cyclosporin A, XR9576 (tariquidar), and vinblastine, was measured by studying their ability to inhibit daunorubicin and calcein-AM efflux from four strains of Ehrlich cells with different...... levels of drug resistance and P-gp content. For daunorubicin as a transport substrate, Kapp was independent of [P-gp] for verapamil but increased strictly linearly with [P-gp] for vinblastine, cyclosporin A, and XR9576. A theoretical analysis of the kinetics of drug pumping and its reversal shows...... but rather, in serial, i.e., a drug that is pumped from the cytoplasmic phase has to pass the preemptive route upon leaving the cell. Our results are consistent with the Sauna-Ambudkar two-step model for pumping by P-gp. We suggest that the vinblastine/cyclosporin A/XR9576-binding site accepts daunorubicin...

Oil recovery with vinyl sulfonic acid-acrylamide copolymers

Energy Technology Data Exchange (ETDEWEB)

Norton, C.J.; Falk, D.O.

1973-12-18

An aqueous polymer flood containing sulfomethylated alkali metal vinyl sulfonate-acrylamide copolymers was proposed for use in secondary or tertiary enhanced oil recovery. The sulfonate groups on the copolymers sustain the viscosity of the flood in the presence of brine and lime. Injection of the copolymer solution into a waterflooded Berea core, produced 30.5 percent of the residual oil. It is preferred that the copolymers are partially hydrolyzed.

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

Directory of Open Access Journals (Sweden)

Xing Hua Tang

Full Text Available We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs.Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

Sulfonated 1,3-bis(4-pyridylpropane

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Ore Kuyinu

2011-06-01

Full Text Available In the title compound, 4-[3-(3-sulfonatopyridin-1-ium-4-ylpropyl]pyridin-1-ium-3-sulfonate, C13H14N2O6S2, the molecule is zwitterionic, with the sulfonic acid proton transfered to the basic pyridine N atom. Also, the structure adopts a butterfly-like conformation with the sulfonate groups on opposite sides of the `wings'. The dihedral angle between the two pyridinium rings is 83.56 (7°, and this results in the molecule having a chiral conformation and packing. There is strong intermolecular hydrogen bonding between the pyridinium H and sulfonate O atoms of adjoining molecules. In addition, there are weaker intermolecular C—H...O interactions.

Histochemical and structural analysis of mucous glycoprotein secreted by the gill of Mytilus edulis

International Nuclear Information System (INIS)

Ahn, Hae-Young.

1988-01-01

Studies were carried out to characterized various mucous cells in the gill filament, to ascertain structural characteristics of the secreted mucous glycoproteins, and to determine the ability of the gill epithelium to incorporate [ 14 C]glucosamine as a precursor in the biosynthesis and secretion of mucous glycoproteins. Using histochemical staining techniques, mucous cells containing neutral and acidic mucins were found in the lateral region, whereas mucous cells containing primarily neutral or sulfated mucins were found in the postlateral region. Serotonin, but not dopamine, stimulated the mucous secretion. In tissues pretreated with [ 14 C]glucosamine, the secreted glycoproteins contain incorporated radiolabel. Analysis by column chromatography using Bio-Gel P-2 and P-6 shows that the secretion contains two glycoprotein populations. Glycoprotein II has a molecular weight of 2.3 x 10 4 daltons. Upon alkaline reductive borohydride cleavage of the O-glycosidic linkages of glycoprotein I, about 70% of the radiolabel was removed from the protein. Gas chromatographic analysis of the carbohydrate composition shows that the glycoproteins contains N-acetylglucosamine (GluNAc), N-acetylgalactosamine (GalNAc), and galactose, fucose and mannose. Amino acid analysis shows that the glycoproteins are rich in serine, threonine and proline

Sulfonic acid-functionalized golf nanoparticles: A colloid-bound catalyst for soft lithographic application on self-assembled monolayers

NARCIS (Netherlands)

Li, X.; Paraschiv, V.; Huskens, Jurriaan; Reinhoudt, David

2003-01-01

In this report, we present a new lithographic approach to prepare patterned surfaces. Self-assembled monolayers (SAMs) of the acid-labile trimethylsilyl ether (TMS-OC11H22S)2 (TMS adsorbate) was formed on gold. 5-Mercapto-2-benzimidazole sulfonic acid sodium salt (MBS-Na+) was used as a ligand for

An efficient and highly selective ortho-tert-butylation of p-cresol with methyl tert-butyl ether catalyzed by sulfonated ionic liquids

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Alamdari Reza Fareghi

2014-01-01

Full Text Available A novel series of sulfonic acid-functionalized ionic liquids (SFILs was found to act as efficient catalysts for ortho-tert-butylation of p-cresol with methyl tert-butyl ether (MTBE as the tert-butylating agent without an added solvent. The mono o-tert-butylated product was obtained in up to 80.4% isolated yield and 95.2% selectivity under such green conditions. No O-tert-butylated byproducts were formed.

Luminescent hybrid lanthanide sulfates and lanthanide sulfonate-carboxylates with 1,10-phenanthroline involving in-situ oxidation of 2-mercaptonbenzoic acid

International Nuclear Information System (INIS)

Zhong, Jie-Cen; Wan, Fang; Sun, Yan-Qiong; Chen, Yi-Ping

2015-01-01

A series of lanthanide sulfates and lanthanide sulfonate-carboxylates, [Ln 2 (phen) 2 (SO 4 ) 3 (H 2 O) 2 ] n (I:Ln=Nd(1a), Sm(1b), Eu(1c), phen=1,10-phenanthroline) and [Ln(phen)(2-SBA)(BZA)] n (II: Ln=Sm(2a), Eu(2b), Dy(2c), 2-SBA=2-sulfobenzoate, BZA=benzoate) have been hydrothermally synthesized from lanthanide oxide, 2-mercaptonbenzoic acid with phen as auxiliary ligand and characterized by single-crystal X-ray diffraction, elemental analyses, IR spectra, TG analyses and luminescence spectroscopy. Interestingly, SO 4 2− anions in I came from the in situ deep oxidation of thiol groups of 2-mercaptonbenzoic acid while 2-sulfobenzoate and benzoate ligands in II from the middle oxidation and desulfuration reactions of 2-mercaptonbenzoic acid. Compounds I are organic–inorganic hybrid lanthanide sulfates, which have rare one-dimensional column-like structures. Complexes II are binuclear lanthanide sulfonate-carboxylates with 2-sulfobenzoate and benzoate as bridges and 1,10-phenanthroline as terminal. Photoluminescence studies reveal that complexes I and II exhibit strong lanthanide characteristic emission bands in the solid state at room temperature. - Graphical abstract: Lanthanide sulfates and lanthanide sulfonate-carboxylates have been hydrothermally synthesized. Interestingly, sulfate anions, 2-sulfobenzoate and benzoate ligands came from the in situ oxidation and desulfuration reactions of 2-mercaptonbenzoic acid. - Highlights: • In situ oxidation and desulfuration reactions of 2-mercaptonbenzoic acid. • The organic–inorganic hybrid lanthanide sulfates with one-dimensional column-like structure. • The dinuclear lanthanide sulfonate-carboxylates. • The emission spectra exhibit the characteristic transition of 5 D 0 → 7 F J (J=0–4) of the Eu(III)

Propagation/depropagation equilibrium and structural factors in the radiation degradation of poly(olefin sulfone)s

International Nuclear Information System (INIS)

Bowmer, T.N.; O'Donnell, J.H.

1981-01-01

The principal volatile products observed after γ irradiation of nine different poly(olefin sulfone)s in the solid state were the two comonomers, i.e., the respective olefin and sulfur dioxide. An exponential increase in yield, G (volatile products), with increasing irradiation temperature, T/sub irr/, was observed for each copolymer through the ceiling temperature, T/sub c/, for the corresponding propagation/depropagation equilibrium. Thus the G value increased by ca. 3 orders of magnitude from T/sub irr/ = 0.7 T/sub c/ to T/sub irr/ = 1.3 T/sub c/ for all of the poly(olefin sulfone)s. Depropagation sensitivity was considered to be best measured by G(SO 2 ) since radiation induced, cationic homopolymerization of the product olefin occurred to a variable extent. Five of the poly(olefin sulfone)s had similar rates of depropagation at their respective T/sub c's/ but the polysulfones of 1-hexene, cyclohexene and 2-butene showed anomalously high depropagation rates. This may be related to greater steric hinderance to segmental chain mobility in the polysulfones of the 1,2 disubstituted olefins. Poly(1-hexene sulfone) appears to be anomalous, as in other respects

Electrochemical detection of dopamine using water-soluble sulfonated graphene

International Nuclear Information System (INIS)

Li, Su-Juan; He, Jun-Zhi; Zhang, Meng-Jie; Zhang, Rong-Xia; Lv, Xia-Lei; Li, Shao-Hua; Pang, Huan

2013-01-01

Graphical abstract: DPV responses of dopamine (DA) at sulfonated graphene based glassy carbon electrode in the presence of ascorbic acid (AA) and uric acid (UA). The separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 227 mV, 125 mV and 352 mV, which allowed selectively determining DA. -- Abstract: In the present study, a biosensor was prepared using the water-soluble sulfonated graphene with the aim of achieving the selective and sensitive determination of dopamine (DA) in the presence of ascorbic acid (AA) and uric acid (UA). The aromatic π–π stacking and electrostatic attraction between positively charged DA and negatively charged sulfonated graphene can accelerate the electron transfer whereas weakening AA and UA oxidation on the sulfonated graphene-modified electrode. Fourier transform infrared spectra (FTIR), energy dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to characterize the successful synthesis of sulfonated graphene sheets. Differential pulse voltammetry was used for electrochemical detection, the separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 227 mV, 125 mV and 352 mV, which allowed selectively determining DA. A broad linear range, low detection limit, along with good ability to suppress the background current from large excess ascorbic acid (AA) and uric acid (UA) were obtained. The as-prepared sulfonated graphene sheets exhibited superior performance over conventional negatively charged Nafion films, such as flexible film thickness, unique nanostructure, excellent anti-interference ability, high sensitivity and selectivity. The proposed method was used to detect DA in real hydrochloride injection sample, human urine and serum samples with satisfactory recovery results

The immune system modulator a1-acid glycoprotein inhibits insulin and IGF1 induced protein synthesis in C2C12 myotubes

Science.gov (United States)

Alpha-1 acid glycoprotein (AGP) has previously been demonstrated by our laboratory to be negatively correlated with growth rate in newborn piglets. However, a mechanism of action for AGP in growth has not been identified. Previous research has demonstrated that AGP can modify adipose tissue metabo...

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

Science.gov (United States)

Abdel-Moneim, Adel; Yousef, Ahmed I; Abd El-Twab, Sanaa M; Abdel Reheim, Eman S; Ashour, Mohamed B

2017-08-01

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

Electrooxidative Tandem Cyclization of Activated Alkynes with Sulfinic Acids To Access Sulfonated Indenones

Energy Technology Data Exchange (ETDEWEB)

Wen, Jiangwei [The; Center; Shi, Wenyan [The; Zhang, Fan [The; Liu, Dong [The; Tang, Shan [The; Wang, Huamin [The; Lin, Xiao-Min [Center; Lei, Aiwen [The

2017-05-25

An,electrooxidative direct arylsulfonlylation of yones sulfintc acids via a radical tandem cyclization strategy has been developed for the construction of sulfonated ilicIenones:under oxidant, free conditions. This method provides a simple and efficient approach to prepare various sulfonylindenones in good to,excellent:Tyidds,, demonstrating the tremendous prospect of utilizing electrocatalysis in oxidative coupling, Notably, this reaction could Be easily scaled up with good, efficiency.

Synthesis,crystal structure and properties of inorganic-organic hybrid polymers based on 8-hydroxylquinoline-5-sulfonic acid

Institute of Scientific and Technical Information of China (English)

无

2009-01-01

Two new inorganic-organic hybrid polymers, Mn(QS)(H2O) (1) and Co(QS)(H2O)2 (2) (H2QS=8-hydroxyl-quinoline-5-sulfonic acid), based on 8-hydroxylquinoline-5-sulfonate ligand, have been synthesized under solvothermal conditions and their structures were solved by single-crystal X-ray diffraction analysis. Compound 1 is a three-dimensional open framework with rutile topology structure, and compound 2 is a three-dimensional supramolecular structure. These compounds were characterized by powder XRD, infrared spectroscopy, thermogravimetric analysis, fluorescence properties and magnetism properties.

Overview of P-glycoprotein inhibitors: a rational outlook

Directory of Open Access Journals (Sweden)

Kale Mohana Raghava Srivalli

2012-09-01

Full Text Available P-glycoprotein (P-gp, a transmembrane permeability glycoprotein, is a member of ATP binding cassette (ABC super family that functions specifically as a carrier mediated primary active efflux transporter. It is widely distributed throughout the body and has a diverse range of substrates. Several vital therapeutic agents are substrates to P-gp and their bioavailability is lowered or a resistance is induced because of the protein efflux. Hence P-gp inhibitors were explored for overcoming multidrug resistance and poor bioavailability problems of the therapeutic P-gp substrates. The sensitivity of drug moieties to P-gp and vice versa can be established by various experimental models in silico, in vitro and in vivo. Ever since the discovery of P-gp, the research plethora identified several chemical structures as P-gp inhibitors. The aim of this review was to emphasize on the discovery and development of newer, inert, non-toxic, and more efficient, specifically targeting P-gp inhibitors, like those among the natural herb extracts, pharmaceutical excipients and formulations, and other rational drug moieties. The applications of cellular and molecular biology knowledge, in silico designed structural databases, molecular modeling studies and quantitative structure-activity relationship (QSAR analyses in the development of novel rational P-gp inhibitors have also been mentioned.Glicoproteína-p (P-gp, uma glicoproteína de transmembrana permeável, é um membro da superfamília (ABC de cassete de gene de ligação de ATP que funciona especificamente como um carreador mediado pelo transportador de efluxo ativo primário. É amplamente distribuído por todo o corpo e apresenta uma gama diversificada de substratos. Diversos agentes terapêuticos vitais são substratos para P-gp e sua biodisponibilidade é reduzida ou a resistência é induzida devido ao efluxo de proteínas. Portanto, os inibidores da P-gp foram explorados para a superação da resistência a

Study on properties of cation-exchange membranes containing sulfonate groups

International Nuclear Information System (INIS)

Zu Jianhua; Wu Minghong; Qiu Shilong; Yao Side; Ye Yin

2004-01-01

Strong acid cation-exchange membranes were obtained by irradiation grafting of acrylic acid (AA) and sodium styrene sulfonate (SSS) onto high-density polyethylene (HDPE). Thermal and chemical stability of the cation-exchange membranes was investigated. The effectiveness of sulfonate-containing films was conformed in inducing high resistance to oxidative degradation. Thermal stability of the grafted HDPE was weaker than HDPE as detected by TGA analyzing technique. Char residue by TGA of the grafted HDPE is greater than that of HDPE. It shows that the branch chains including -SO 3 Na and -COOH was grafted onto the backbone of HDPE, and thus give a catalytic impetus to the charing. Crystallinity of the grafted membranes decreased with increasing grafting yield of the membrane samples. It is supposed that the decreased crystallinity is due to collective effects of the inherent crystallinity dilution by the amorphous grafted chains and disruption of spherulitic crystallites of the HDPE component

Demographic, reproductive, and dietary determinants of perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations in human colostrum

NARCIS (Netherlands)

Jusko, T.A.; Oktapodas, M.; Palkovičová Murinová, L.; Babjaková, J.; Verner, M.A.; DeWitt, J.C.; Babinská, K.; Thevenet-Morrison, K.; Čonka, K.; Drobná, B.; Thurston, S.W.; Lawrence, B.P.; Dozier, A.M.; Jarvinen-Seppo, K.M.; Patayová, H.; Trnovec, T.; Legler, J.; Hertz-Picciotto, I.; Lamoree, M.H.

2016-01-01

To determine demographic, reproductive, and maternal dietary factors that predict perfluoroalkyl substance (PFAS) concentrations in breast milk, we measured perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations, using liquid chromatography-mass spectrometry, in 184

Sulfonated reduced graphene oxide as a highly efficient catalyst for direct amidation of carboxylic acids with amines using ultrasonic irradiation.

Science.gov (United States)

Mirza-Aghayan, Maryam; Tavana, Mahdieh Molaee; Boukherroub, Rabah

2016-03-01

Sulfonated reduced graphene oxide nanosheets (rGO-SO3H) were prepared by grafting sulfonic acid-containing aryl radicals onto chemically reduced graphene oxide (rGO) under sonochemical conditions. rGO-SO3H catalyst was characterized by Fourier-transform infrared (FT-IR) spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS). rGO-SO3H catalyst was successfully applied as a reusable solid acid catalyst for the direct amidation of carboxylic acids with amines into the corresponding amides under ultrasonic irradiation. The direct sonochemical amidation of carboxylic acid takes place under mild conditions affording in good to high yields (56-95%) the corresponding amides in short reaction times. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiolytical Preparation of a Poly(Vinylbenzyl Sulfonic Acid)-Grafted FEP Membrane and Characterization as Polymer Electrolytes for Direct Methanol Fuel Cells

Energy Technology Data Exchange (ETDEWEB)

Nho, Y -C; Shin, J; Sohn, J -Y; Fei, G [Radiation Research Division for Industry and Environment, Korea Atomic Energy Research Institute, 1266 Sinjeong-dong, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of)

2012-09-15

In this study, a novel polymer electrolyte membrane, poly(vinylbenzyl sulfonic acid)-grafted poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP-g-PVBSA), has been successfully prepared by simultaneous irradiation grafting of vinylbenzyl chloride(VBC) monomer onto a FEP film and taking subsequent chemical modification steps to modify the benzyl chloride moiety to the benzyl sulfonic acid moiety. The chemical reactions for the sulfonation were carried out via the formation of thiouronium salt with thiourea, base-catalyzed hydrolysis for the formation of thiol, and oxidation with hydrogen peroxide. Each chemical conversion process was confirmed by FTIR, elemental analysis, and SEM-EDX. A chemical stability study performed with Fenton's reagent (3% H{sub 2}O{sub 2} solution containing 4 ppm of Fe{sup 2+}) at 70 deg. C revealed that FEP-g-PVBSA has a higher chemical stability than the poly(styrene sulfonic acid)-grafted membranes (FEP-g-PSSA). An EDX analysis was also used to observe the cross-sectional distribution behaviors of the hydrophilic sulfonic acid groups and hydrophobic fluorine groups. The characteristics of an ion-exchange capacity (IEC), water and methanol uptake, methanol permeability, and proton conductivity as a function of the degree of grafting were also studied. The IECs and water uptakes of membranes with different degrees of grafting (36-102%) were measured to be in the range of 0.8-1.62 meq/g, and 10-30%, respectively. When the degree of grafting reached 60% the proton conductivity was higher than that of a Nafion (registered) 212 membrane (6.1E-02 S/cm). The methanol permeability and uptake of the FEP-g-PVBSA membrane was significantly lower than that of the Nafion (registered) 212 membrane, and even the degree of grafting reached 102%. (author)

Proton-transfer compounds of 8-hydroxy-7-iodoquinoline-5-sulfonic acid (ferron) with 4-chloroaniline and 4-bromoaniline.

Science.gov (United States)

Smith, Graham; Wermuth, Urs D; Healy, Peter C

2007-07-01

The crystal structures of the proton-transfer compounds of ferron (8-hydroxy-7-iodoquinoline-5-sulfonic acid) with 4-chloroaniline and 4-bromoaniline, namely 4-chloroanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)ClN(+) x C(9)H(5)INO(4)S(-) x H(2)O, and 4-bromoanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)BrN(+) x C(9)H(5)INO(4)S(-) x H(2)O, have been determined. The compounds are isomorphous and comprise sheets of hydrogen-bonded cations, anions and water molecules which are extended into a three-dimensional framework structure through centrosymmetric R(2)(2)(10) O-H...N hydrogen-bonded ferron dimer interactions.

Total glucosides of peony attenuates 2,4,6-trinitrobenzene sulfonic acid/ethanol-induced colitis in rats through adjustment of TH1/TH2 cytokines polarization.

Science.gov (United States)

Zhang, Yabing; Zhou, Rui; Zhou, Feng; Cheng, Hong; Xia, Bing

2014-01-01

The present study is to investigate effects of total glucosides of peony (TGP) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol-induced colitis in rats and to explore potential clinical use of TGP for treatment of inflammatory bowel disease. Sixty Sprague-Dawley rats were randomly grouped into normal controls, model controls, sulfasalazine (SASP) controls (100 mg/kg/day), and low, medium, and high-dose TGP groups (25, 50, and 100 mg/kg/day, respectively). 24 h following colonic instillation of TNBS, TGP, and SASP were given by gastric gavage three times a day for 7 days. Disease activity index (DAI), colon macroscopic damage index (CMDI), histopathological score (HPS), and myeloperoxidase (MPO) activity were evaluated. Levels of serum TNF-α, IL-1β, and IL-10 were measured by ELISA, and expression of TNF-α, IL-1β, and IL-10 mRNA and protein in colonic tissues was detected by RT-PCR and western blot, respectively. Compared with rats in the model controls, TGP (50 or 100 mg/kg/day)-treated rats with TNBS/ethanol-induced colitis showed significant improvements of DAI, CMDI, HPS, and MPO activity. Moreover, administration of TGP (50 or 100 mg/kg/day) decreased the up-regulated levels of serum TNF-α and IL-1β, and expression of TNF-α and IL-1β mRNA and protein in colonic tissues, and increased the serum IL-10 and colonic IL-10 mRNA and protein level. And there was no significant difference compared with administration of SASP (P > 0.05). TGP attenuates TNBS/ethanol-induced colitis in rats and its efficacy is similar to SASP, the potential mechanism might be related to the adjustment of Th1/Th2 cytokines polarization by decreasing pro-inflammatory cytokine TNF-α and IL-1β, and increasing anti-inflammatory cytokine IL-10.

A novel curcumin derivative which inhibits P-glycoprotein, arrests cell cycle and induces apoptosis in multidrug resistance cells.

Science.gov (United States)

Lopes-Rodrigues, Vanessa; Oliveira, Ana; Correia-da-Silva, Marta; Pinto, Madalena; Lima, Raquel T; Sousa, Emília; Vasconcelos, M Helena

2017-01-15

Cancer multidrug resistance (MDR) is a major limitation to the success of cancer treatment and is highly associated with the overexpression of drug efflux pumps such as P-glycoprotein (P-gp). In order to achieve more effective chemotherapeutic treatments, it is important to develop P-gp inhibitors to block/decrease its activity. Curcumin (1) is a secondary metabolite isolated from the turmeric of Curcuma longa L.. Diverse biological activities have been identified for this compound, particularly, MDR modulation in various cancer cell models. However, curcumin (1) has low chemical stability, which severely limits its application. In order to improve stability and P-gp inhibitory effect, two potential more stable curcumin derivatives were synthesized as building blocks, followed by several curcumin derivatives. These compounds were then analyzed in terms of antitumor and anti-P-gp activity, in two MDR and sensitive tumor lines (from chronic myeloid leukemia and non-small cell lung cancer). We identified from a series of curcumin derivatives a novel curcumin derivative (1,7-bis(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)hepta-1,6-diene-3,5-dione, 10) with more potent antitumor and anti-P-gp activity than curcumin (1). This compound (10) was shown to promote cell cycle arrest (at the G2/M phase) and induce apoptosis in the MDR chronic myeloid leukemia cell line. Therefore it is a really interesting P-gp inhibitor due to its ability to inhibit both P-gp function and expression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mucus glycoprotein secretion by tracheal explants: effects of pollutants

International Nuclear Information System (INIS)

Last, J.A.; Kaizu, T.

1980-01-01

Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with [3H] glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques

Colitis induced by sodium polystyrene sulfonate in sorbitol: A report of six cases.

Science.gov (United States)

Jacob, Sheba S K; Parameswaran, Ashok; Parameswaran, Sarojini Ashok; Dhus, Ubal

2016-03-01

Drug-related injury has been noted in virtually all organ systems, and recognition of the patterns of injury associated with medication enables modification of treatment and reduces the morbidity associated with the side effects of drugs. With the large number of new drugs being developed, documentation of the morphology of the changes seen as an adverse effect becomes important to characterize the pattern of injury. The pathologist is often the first to identify these abnormalities and correlate them with a particular drug. Kayexalate or sodium polystyrene sulfonate (SPS), a linear polymer derived from polystyrene containing sulfonic acid and sulfonate functional groups is used to treat hyperkalemia. It is usually administered with an osmotic laxative sorbitol orally or as retention enema. This combination has been implicated in causing damage to different parts of the gastrointestinal (GI) tract especially the colon and causes an established pattern of injury, recognizable by the presence of characteristic crystals, is presented to create a greater awareness of the Kayexalate colitis. This entity should be included in the differential diagnosis of lower GI mucosal injury in a setting of uremia and hyperkalemia.

Oleanolic and maslinic acid sensitize soft tissue sarcoma cells to doxorubicin by inhibiting the multidrug resistance protein MRP-1, but not P-glycoprotein.

Science.gov (United States)

Villar, Victor Hugo; Vögler, Oliver; Barceló, Francisca; Gómez-Florit, Manuel; Martínez-Serra, Jordi; Obrador-Hevia, Antònia; Martín-Broto, Javier; Ruiz-Gutiérrez, Valentina; Alemany, Regina

2014-04-01

The pentacyclic triterpenes oleanolic acid (OLA) and maslinic acid (MLA) are natural compounds present in many plants and dietary products consumed in the Mediterranean diet (e.g., pomace and virgin olive oils). Several nutraceutical activities have been attributed to OLA and MLA, whose antitumoral effects have been extensively evaluated in human adenocarcinomas, but little is known regarding their effectiveness in soft tissue sarcomas (STS). We assessed efficacy and molecular mechanisms involved in the antiproliferative effects of OLA and MLA as single agents or in combination with doxorubicin (DXR) in human synovial sarcoma SW982 and leiomyosarcoma SK-UT-1 cells. As single compound, MLA (10-100 μM) was more potent than OLA, inhibiting the growth of SW982 and SK-UT-1 cells by 70.3 ± 1.11% and 68.8 ± 1.52% at 80 μM, respectively. Importantly, OLA (80 μM) or MLA (30 μM) enhanced the antitumoral effect of DXR (0.5-10 μM) by up to 2.3-fold. On the molecular level, efflux activity of the multidrug resistance protein MRP-1, but not of the P-glycoprotein, was inhibited. Most probably as a consequence, DXR accumulated in these cells. Kinetic studies showed that OLA behaved as a competitive inhibitor of substrate-mediated MRP-1 transport, whereas MLA acted as a non-competitive one. Moreover, none of both triterpenes induced a compensatory increase in MRP-1 expression. In summary, OLA or MLA sensitized cellular models of STS to DXR and selectively inhibited MRP-1 activity, but not its expression, leading to a higher antitumoral effect possibly relevant for clinical treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Solvent extraction of hafnium(IV) by dinonylnaphthalene sulfonic acid from mixed aqueous-organic media

International Nuclear Information System (INIS)

Hala, J.; Piperkovova, H.

1979-01-01

The extraction of hafnium(IV) by heptane and toluene solutions of dinonylnaphthalene sulfonic acid (HD) from mixed aqueous-organic solutions has been studied. Alcohols, ketones, carboxylic acids, cyclic ethers, dimethylsulfoxide and dimethylformamide were used as the organic component of the mixed phase. Methanol, ethanol, formic acid and dioxane increased the extractability of Hf(IV) whereas other solvents showed only an antagonistic effect. The results were discussed from the point of view of the changes in micellar structure of HD, and compared with the uptake of Hf(IV) by resinous cation exchangers. The solubilization by HD of alcohols, carboxylic acids and dimethylsulfoxide was demonstrated by using the corresponding 14 C and 35 S labelled compounds. (author)

Chemical mechanical polishing of hard disk substrate with {alpha}-alumina-g-polystyrene sulfonic acid composite abrasive

Energy Technology Data Exchange (ETDEWEB)

Lei Hong, E-mail: hong_lei2005@yahoo.com.c [Research Center of Nano-science and Nano-technology, Shanghai University, Shanghai 200444 (China); Bu Naijing; Chen Ruling; Hao Ping [Research Center of Nano-science and Nano-technology, Shanghai University, Shanghai 200444 (China); Neng Sima; Tu Xifu; Yuen Kwok [Shenzhen Kaifa Magnetic Recording Co., LTD, Shenzhen, 518035 (China)

2010-05-03

{alpha}-Alumina-g-polystyrene sulfonic acid ({alpha}-Al{sub 2}O{sub 3}-g-PSS) composite abrasive was prepared by surface activation, graft polymerization and sulfonation, successively. The composition, dispersibility and morphology of the product were characterized by Fourier transformed infrared spectroscopy, laser particle size analysis and scanning electron microscopy, respectively. The chemical mechanical polishing (CMP) performances of the composite abrasive on hard disk substrate with nickel-phosphorous plating were investigated. The microscopy images of the polished surfaces show that {alpha}-Al{sub 2}O{sub 3}-g-PSS composite abrasive results in improved CMP and post-CMP cleaning performances than pure {alpha}-alumina abrasive under the same testing conditions.

Preparation of a Carbon-Based Solid Acid Catalyst by Sulfonating Activated Carbon in a Chemical Reduction Process

Directory of Open Access Journals (Sweden)

Xiao-Yan Liu

2010-10-01

Full Text Available Sulfonated (SO3H-bearing activated carbon (AC-SO3H was synthesized by an aryl diazonium salt reduction process. The obtained material had a SO3H density of 0.64 mmol·g-1 and a specific surface area of 602 m2·g-1. The catalytic properties of AC-SO3H were compared with that of two commercial solid acid catalysts, Nafion NR50 and Amberlyst-15. In a 10-h esterification reaction of acetic acid with ethanol, the acid conversion with AC-SO3H (78% was lower than that of Amberlyst-15 (86%, which could be attributed to the fact that the SO3H density of the sulfonated carbon was lower than that of Amberlyst-15 (4.60 mmol·g-1. However, AC-SO3H exhibited comparable and even much higher catalytic activities than the commercial catalysts in the esterification of aliphatic acids with longer carbon chains such as hexanoic acid and decanoic acid, which may be due to the large specific surface area and mesoporous structures of the activated carbon. The disadvantage of AC-SO3H is the leaching of SO3H group during the reactions.

The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

Directory of Open Access Journals (Sweden)

Peng-Fei Yu

2011-01-01

Full Text Available Danshensu (3-(3, 4-dihydroxyphenyl lactic acid, a water-soluble active component isolated from the root of Salvia miltiorrhiza Bunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1 (verapamil group or the same volume of normal saline (control group. Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1 by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS. The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

Serotonin transporter protein (SERT) and P-glycoprotein (P-gp) binding activity of montanine and coccinine from three species of Haemanthus L. (Amaryllidaceae)

DEFF Research Database (Denmark)

Stafford, Gary Ivan; Birer, C.; Brodin, Birger

2013-01-01

The alkaloid rich extracts from an acid/base extraction of bulb material of Haemanthus coccineus L., H. montanus Baker and H. sanguineus Jacq. revealed that two montanine type Amaryllidaceae alkaloids, montanine (1) and coccinine (2) were the major alkaloid constituents. Together these two...... to the relative proportions of coccinine and montanine in the extracts and thus are likely to be due to more potent unidentified minor constituents. Both alkaloids exhibited low binding affinity to P-glycoprotein (P-gp) as demonstrated by low inhibition of calcein-AM efflux in the MDCK-MDR1 cell line....... This indicates that P-gp efflux will not be limiting for blood-brain-barrier passage of the alkaloids....

Role of post-sulfonation of poly(ether ether sulfone) in proton conductivity and chemical stability of its proton exchange membranes for fuel cell

Energy Technology Data Exchange (ETDEWEB)

Unveren, Elif Erdal; Erdogan, Tuba; Inan, Tulay Y. [Chemistry Institute, TUBITAK Marmara Research Center, 41470, Gebze, Kocaeli (Turkey); Celebi, Serdar S. [Professor Emeritus, Chemical Engineering Department, Hacettepe University, 06800, Beytepe, Ankara (Turkey)

2010-04-15

Commercially available poly(ether ether sulfone), PEES, was directly sulfonated using concentrated sulfuric acid at low temperatures by minimizing degradation during sulfonation. The sulfonation reaction was performed in the temperature range of 5-25 C. Sulfonated polymers were characterized by FTIR, {sup 1}H NMR spectroscopy and ion exchange capacity (IEC) measurements. Degradation during sulfonation was investigated by measuring intrinsic viscosity, glass transition temperature and thermal decomposition temperature of sulfonated polymers. Sulfonated PEES, SPEES, membranes were prepared by solvent casting method and characterized in terms of IEC, proton conductivity and water uptake. The effect of sulfonation conditions on chemical stability of membranes was also investigated via Fenton test. Optimum sulfonation condition was determined to be 10 C with conc. H{sub 2}SO{sub 4} based on the characteristics of sulfonated polymers and also the chemical stability of their membranes. SPEES membranes exhibited proton conductivity up to 185.8 mS cm{sup -1} which is higher than that of Nafion 117 (133.3 mS cm{sup -1}) measured at 80 C and relative humidity 100%. (author)

Protective Effect of Prosopis cineraria Against N-Nitrosodiethylamine Induced Liver Tumor by Modulating Membrane Bound Enzymes and Glycoproteins

Directory of Open Access Journals (Sweden)

Naina Mohamed Pakkir Maideen

2012-06-01

Full Text Available Purpose: The objective of the present study was to evaluate the protective effect of methanol extract of Prosopis cineraria (MPC against N-nitrosodiethylamine (DEN, 200mg/kg induced Phenobarbital promoted experimental liver tumors in male Wistar rats. Methods: The rats were divided into four groups, each group consisting of six animals. Group 1 served as control animals. Liver tumor was induced in group 2, 3, and 4 and Group 3 animals received MPC 200mg/kg and Group 4 animals received MPC 400mg/kg. Results: Administration of DEN has brought down the levels of membrane bound enzymes like Na+/ K+ ATPase, Mg2+ ATPase and Ca2+ATPase which were later found to be increased by the administration of Prosopis cineraria (200 and 400mg/kg in dose dependent manner. The MPC extract also suppressed the levels of glycoproteins like Hexose, Hexosamine and Sialic acid when compared to liver tumor bearing animals. Conclusions: Our study suggests that MPC may extend its protective role by modulating the levels of membrane bound enzymes and suppressing glycoprotein levels.

Comparison of α1-Antitrypsin, α1-Acid Glycoprotein, Fibrinogen and NOx as Indicator of Subclinical Mastitis in Riverine Buffalo (

Directory of Open Access Journals (Sweden)

Anirban Guha

2013-06-01

Full Text Available Mastitis set apart as clinical and sub clinical is a disease complex of dairy cattle, with sub clinical being the most important economically. Of late, laboratories showed interest in developing biochemical markers to diagnose sub clinical mastitis (SCM in herds. Many workers reported noteworthy alternation of acute phase proteins (APPs and nitric oxide, (measured as nitrate+nitrite = NOx in milk due to intra-mammary inflammation. But, the literature on validation of these parameters as indicators of SCM, particularly in riverine milch buffalo (Bubalus bubalis milk is inadequate. Hence, the present study focused on comparing several APPs viz. α1- anti trypsin, α1- acid glycoprotein, fibrinogen and NOx as indicators of SCM in buffalo milk. These components in milk were estimated using standardized analytical protocols. Somatic cell count (SCC was done microscopically. Microbial culture was done on 5% ovine blood agar. Of the 776 buffaloes (3,096 quarters sampled, only 347 buffaloes comprising 496 quarters were found positive for SCM i.e. milk culture showed growth in blood agar with SCC≥2×105 cells/ml of milk. The cultural examination revealed Gram positive bacteria as the most prevalent etiological agent. It was observed that α1- anti trypsin and NOx had a highly significant (p<0.01 increase in SCM milk, whereas, the increase of α1- acid glycoprotein in infected milk was significant (p<0.05. Fibrinogen was below detection level in both healthy and SCM milk. The percent sensitivity, specificity and accuracy, predictive values and likelihood ratios were calculated taking bacterial culture examination and SCC≥2×105 cells/ml of milk as the benchmark. Udder profile correlation coefficient was also used. Allowing for statistical and epidemiological analysis, it was concluded that α1- anti trypsin indicates SCM irrespective of etiology, whereas α1- acid glycoprotein better diagnosed SCM caused by gram positive bacteria. NOx did not prove to

A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.

Science.gov (United States)

Toklu, H Z; Kabasakal, L; Imeryuz, N; Kan, B; Celikel, C; Cetinel, S; Orun, O; Yuksel, M; Dulger, G A

2013-08-01

The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances

Comparison of α1-Antitrypsin, α1-Acid Glycoprotein, Fibrinogen and NOx as Indicator of Subclinical Mastitis in Riverine Buffalo (Bubalus bubalis).

Science.gov (United States)

Guha, Anirban; Guha, Ruby; Gera, Sandeep

2013-06-01

Mastitis set apart as clinical and sub clinical is a disease complex of dairy cattle, with sub clinical being the most important economically. Of late, laboratories showed interest in developing biochemical markers to diagnose sub clinical mastitis (SCM) in herds. Many workers reported noteworthy alternation of acute phase proteins (APPs) and nitric oxide, (measured as nitrate+nitrite = NOx) in milk due to intra-mammary inflammation. But, the literature on validation of these parameters as indicators of SCM, particularly in riverine milch buffalo (Bubalus bubalis) milk is inadequate. Hence, the present study focused on comparing several APPs viz. α1- anti trypsin, α1- acid glycoprotein, fibrinogen and NOx as indicators of SCM in buffalo milk. These components in milk were estimated using standardized analytical protocols. Somatic cell count (SCC) was done microscopically. Microbial culture was done on 5% ovine blood agar. Of the 776 buffaloes (3,096 quarters) sampled, only 347 buffaloes comprising 496 quarters were found positive for SCM i.e. milk culture showed growth in blood agar with SCC≥2×10(5) cells/ml of milk. The cultural examination revealed Gram positive bacteria as the most prevalent etiological agent. It was observed that α1- anti trypsin and NOx had a highly significant (pSCM milk, whereas, the increase of α1- acid glycoprotein in infected milk was significant (pSCM milk. The percent sensitivity, specificity and accuracy, predictive values and likelihood ratios were calculated taking bacterial culture examination and SCC≥2×10(5) cells/ml of milk as the benchmark. Udder profile correlation coefficient was also used. Allowing for statistical and epidemiological analysis, it was concluded that α1- anti trypsin indicates SCM irrespective of etiology, whereas α1- acid glycoprotein better diagnosed SCM caused by gram positive bacteria. NOx did not prove to be a good indicator of SCM. It is recommended measuring both α1- anti trypsin and α1

Effect of expression of P-glycoprotein on technetium-99m methoxyisobutylisonitrile single photon emission computed tomography of brain tumors

Energy Technology Data Exchange (ETDEWEB)

Shibata, Yasushi; Matsumura, Akira; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

2002-08-01

The expression of P-glycoprotein was investigated imunohistochemically in 26 brain tumor tissues and compared with the findings of technetium-99m methoxyisobutylisonitrile single photon emission computed tomography ({sup 99m}Tc-MIBI SPECT) to clarify the effect of P-glycoprotein on the diagnostic accuracy. P-glycoprotein labeling index of both tumor cells and vascular endothelial cells showed no clear relationship with the findings of {sup 99m}Tc-MIBI SPECT imaging. Expression of P-glycoprotein has no effect on the diagnostic accuracy of {sup 99m}Tc-MIBI SPECT. (author)

Two-step sulfonation process for the conversion of polymer fibers to carbon fibers

Science.gov (United States)

Barton, Bryan E.; Patton, Jasson T.; Hukkanen, Eric J.; Bernius, Mark T.

2017-11-14

Disclosed herein are processes for preparing carbon fibers, comprising: sulfonating a polymer fiber with a sulfonating agent that is fuming sulfuric acid, sulfuric acid, chlorosulfonic acid, or a combination thereof; treating the sulfonated polymer with a heated solvent, wherein the temperature of the heated solvent is at least 95.degree. C.; and carbonizing the resulting product by heating it to a temperature of 501-3000.degree. C. Carbon fibers prepared according to these methods are also disclosed herein.

Novel sulfonated poly (ether ether keton)/polyetherimide acid-base blend membranes for vanadium redox flow battery applications

International Nuclear Information System (INIS)

Liu, Shuai; Wang, Lihua; Ding, Yue; Liu, Biqian; Han, Xutong; Song, Yanlin

2014-01-01

Highlights: • SPEEK/PEI acid-base blend membranes are prepared for VRB applications. • The acid-base blend membranes have much lower vanadium ion permeability. • The energy efficiency of SPEEK/PEI maintain around 86.9% after 50 cycles. - Abstract: Novel acid-base blend membranes composed of sulfonated poly (ether ether ketone) (SPEEK) and polyetherimide (PEI) were prepared for vanadium redox flow battery (VRB). The blend membranes were characterized by Fourier transform infrared spectroscopy (FT-IR) and scanning electronic microscopy (SEM). The ion exchange capacity (IEC), proton conductivity, water uptake, vanadium ion permeability and mechanical properties were measured. As a result, the acid-base blend membranes exhibit higher water uptake, IEC and lower vanadium ion permeability compared to Nafion117 membranes and all these properties decrease with the increase of PEI. In VRB single cell test, the VRB with blend membranes shows lower charge capacity loss, higher coulombic efficiency (CE) and energy efficiency (EE) than Nafion117 membrane. Furthermore, the acid-base blend membranes present stable performance up to 50 cycles with no significant decline in CE and EE. All experimental results indicate that the SPEEK/PEI (S/P) acid-base blend membranes show promising prospects for VRB

A STUDY ON THE DEGRADATION MECHANISM OF PHOTOCROSSLINKING PRODUCTS FORMED BY CYCLIZED POLYISOPRENE-DIAZIDE SYSTEM UNDER THE INFLUENCE OF ALKYL BENZENE SULFONIC ACIDS

Institute of Scientific and Technical Information of China (English)

HUANG Junlian; SUN Meng

1989-01-01

The degradation mechanism of photocrosslinking products formed by cyclized polyisoprene-diazide system under the influence of the different alkyl benzene sulfonic acids was studied. The effects ofalkyl chain length and the concentration of alkyl benzene sulfonic acids on the rate of degradation reaction were discussed. It was found that in the initial stage of degradation, the cyclicity ratio and the average fused ring number did not change considerably, but the percentage of uncyclized parts content varied significantly. The suitable mechanism was supposed.

Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis

DEFF Research Database (Denmark)

Andersen, U O; Kirkeby, S; Bøg-Hansen, T C

1997-01-01

Three glycoforms of alpha 1-acid glycoprotein (AGP) were biotinylated to examine their binding in mouse testis by light microscopy. The transition from one stage to another in the spermatogenic cycle is marked with an appearance of a receptor for the Concanavalin A (Con A) non-reactive glycoform...

Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance.

Science.gov (United States)

Muñoz-Martínez, Francisco; Lu, Peihua; Cortés-Selva, Fernando; Pérez-Victoria, José María; Jiménez, Ignacio A; Ravelo, Angel G; Sharom, Frances J; Gamarro, Francisco; Castanys, Santiago

2004-10-01

Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-beta-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential

P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity.

Science.gov (United States)

Silva, Renata; Palmeira, Andreia; Carmo, Helena; Barbosa, Daniel José; Gameiro, Mariline; Gomes, Ana; Paiva, Ana Mafalda; Sousa, Emília; Pinto, Madalena; Bastos, Maria de Lourdes; Remião, Fernando

2015-10-01

The induction of P-glycoprotein (P-gp), an ATP-dependent efflux pump, has been proposed as a strategy against the toxicity induced by P-gp substrates such as the herbicide paraquat (PQ). The aim of this study was to screen five newly synthetized thioxanthonic derivatives, a group known to interact with P-gp, as potential inducers of the pump's expression and/or activity and to evaluate whether they would afford protection against PQ-induced toxicity in Caco-2 cells. All five thioxanthones (20 µM) caused a significant increase in both P-gp expression and activity as evaluated by flow cytometry using the UIC2 antibody and rhodamine 123, respectively. Additionally, it was demonstrated that the tested compounds, when present only during the efflux of rhodamine 123, rapidly induced an activation of P-gp. The tested compounds also increased P-gp ATPase activity in MDR1-Sf9 membrane vesicles, indicating that all derivatives acted as P-gp substrates. PQ cytotoxicity was significantly reduced in the presence of four thioxanthone derivatives, and this protective effect was reversed upon incubation with a specific P-gp inhibitor. In silico studies showed that all the tested thioxanthones fitted onto a previously described three-feature P-gp induction pharmacophore. Moreover, in silico interactions between thioxanthones and P-gp in the presence of PQ suggested that a co-transport mechanism may be operating. Based on the in vitro activation results, a pharmacophore model for P-gp activation was built, which will be of further use in the screening for new P-gp activators. In conclusion, the study demonstrated the potential of the tested thioxanthonic compounds in protecting against toxic effects induced by P-gp substrates through P-gp induction and activation.

Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex

DEFF Research Database (Denmark)

Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

1999-01-01

receptor was located in the cytoplasm of glomerulosa and outer fasciculata cells. The intensity of the reaction product decreased in the fasciculata, and no staining was seen in inner fasciculata and reticularis. Inhibition with the simple sugars, mannose and GlcNAc confirmed a lectin-like reaction...... specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution...

Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.

Science.gov (United States)

Müller, Mario M; Lehmann, Roland; Klassert, Tilman E; Reifenstein, Stella; Conrad, Theresia; Moore, Christoph; Kuhn, Anna; Behnert, Andrea; Guthke, Reinhard; Driesch, Dominik; Slevogt, Hortense

2017-04-12

Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.

Properties of polypyrrole doped with alkylbenzene sulfonates

DEFF Research Database (Denmark)

Bay, Lasse; Skaarup, Steen; West, Keld

2001-01-01

-standing 10 mu m thick film is prepared electrochemically at a constant current from an aqueous solution of pyrrole and sodium alkylbenzene sulfonate. The mechanical properties of the film (tensile strength and Young's modulus) and the reversible linear elongation between the oxidised and reduced states...... are measured. Alkylbenzene sulfonates with alkyl chain lengths between 1 and 22 carbon atoms are used as dopant anion. The films made with the different anions have highly different properties and are here compared to outline the influence of the size of the anion. A maximum in linear elongation is found for p......-(n-octyl)benzene sulfonate and in conductivity for p-(n-butyl)benzene sulfonate....

Multiblock copolymers with highly sulfonated blocks containing di- and tetrasulfonated arylene sulfone segments for proton exchange membrane fuel cell applications

Energy Technology Data Exchange (ETDEWEB)

Takamuku, Shogo; Jannasch, Patric [Polymer and Materials Chemistry, Department of Chemistry, Lund University (Sweden)

2012-01-15

Multiblock copoly(arylene ether sulfone)s with different block lengths and ionic contents are tailored for durable and proton-conducting electrolyte membranes. Two series of fully aromatic copolymers are prepared by coupling reactions between non-sulfonated hydrophobic precursor blocks and highly sulfonated hydrophilic precursor blocks containing either fully disulfonated diarylsulfone or fully tetrasulfonated tetraaryldisulfone segments. The sulfonic acid groups are exclusively introduced in ortho positions to the sulfone bridges to impede desulfonation reactions and give the blocks ion exchange capacities (IECs) of 4.1 and 4.6 meq. g{sup -1}, respectively. Solvent cast block copolymer membranes show well-connected hydrophilic nanophase domains for proton transport and high decomposition temperatures above 310 C under air. Despite higher IEC values, membranes containing tetrasulfonated tetraaryldisulfone segments display a markedly lower water uptake than the corresponding ones with disulfonated diarylsulfone segments when immersed in water at 100 C, presumably because of the much higher chain stiffness and glass transition temperature of the former segments. The former membranes have proton conductivities in level of a perfluorosulfonic acid membrane (NRE212) under fully humidified conditions. A membrane with an IEC of 1.83 meq. g{sup -1} reaches above 6 mS cm{sup -1} under 30% relative humidity at 80 C, to be compared with 10 mS cm{sup -1} for NRE212 under the same conditions. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

A review on the relation between the brain-serum concentration ratio of drugs and the influence of P-glycoprotein

DEFF Research Database (Denmark)

Ejsing, Thomas Broeng; Morling, Niels; Linnet, Kristian

2007-01-01

This overview on the brain-serum relationship for drugs illustrates the importance of the drug transporter P-glycoprotein at the blood-brain barrier. Generally, an inverse relationship exists between the magnitude of the brain-serum ratio and the influence of P-glycoprotein. Concerning the pharma...... the pharmacogenomics of P-glycoprotein, no clear effect of single nucleotide polymorphisms (SNPs) has been demonstrated in humans....

P-glycoprotein targeted nanoscale drug carriers

KAUST Repository

Li, Wengang

2013-02-01

Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug carrying processes that shuttle the drugs out of tumor cells. Thus, P -gp inhibitors have attracted a lot of attention as they can stop cancer drugs from being pumped out of target cells with the consumption of ATP. Using quantitive structure activity relationship (QSAR), we have successfully synthesized a series of novel P -gp inhibitors. The obtained dihydropyrroloquinoxalines series were fully characterized and then tested against bacterial and tumor assays with over-expressed P -gps. All compounds were bioactive especially compound 1c that had enhanced antibacterial activity. Furthermore, these compounds were utilized as targeting vectors to direct drug delivery vehicles such as silica nanoparticles (SNPs) to cancerous Hela cells with over expressed P -gps. Cell uptake studies showed a successful accumulation of these decorated SNPs in tumor cells compared to undecorated SNPs. The results obtained show that dihydropyrroloquinoxalines constitute a promising drug candidate for targeting cancers with MDR. Copyright © 2013 American Scientific Publishers All rights reserved.

On the Importance of Purification of Sodium Polystyrene Sulfonate

OpenAIRE

Sen, Akhil K.; Roy, Sandip; Juvekar, Vinay A.

2012-01-01

Ion exchange is commonly employed for purification of sodium polystyrene sulfonate (NaPSS), a molecule widely used as a model polyelectrolyte. However, the present work demonstrates that the ion exchange process itself may introduce some extraneous species into NaPSS samples by two possible mechanisms: (i) chemical transformation of polystyrene sulfonic acid (HPSS), a relatively unstable intermediate formed during ion exchange and (ii) release of small amount of “condensed” acid from cationic...

Fully Aromatic Block Copolymers for Fuel Cell Membranes with Densely Sulfonated Nanophase Domains

DEFF Research Database (Denmark)

Takamuku, Shogo; Jannasch, Patrick; Lund, Peter Brilner

Two multiblock copoly(arylene ether sulfone)s with similar block lengths and ion exchange capacities (IECs) were prepared by a coupling reaction between a non-sulfonated precursor block and a highly sulfonated precursor block containing either fully disulfonated diarylsulfone or fully...... tetrasulfonated tetraaryldisulfone segments. The latter two precursor blocks were sulfonated via lithiation-sulfination reactions whereby the sulfonic acid groups were exclu- sively placed in ortho positions to the many sulfone bridges, giving these locks IECs of 4.1 and 4.6 meqg1, respectively. Copolymer...

Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

Science.gov (United States)

Qian, Yong; Ducatman, Alan; Ward, Rebecca; Leonard, Steve; Bukowski, Valerie; Lan Guo, Nancy; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent

2010-01-01

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis.

Science.gov (United States)

Tsujimura, Shizuyo; Saito, Kazuyoshi; Nakayamada, Shingo; Tanaka, Yoshiya

2010-04-01

P-glycoprotein (P-gp) on activated lymphocytes is an adenosine triphosphate (ATP)-binding cassette transporter that causes drug resistance by exclusion of intracellular drugs in patients with active rheumatoid arthritis (RA). However, infliximab with methotrexate (MTX) can overcome P-gp-mediated drug resistance. We encounter patients who cannot continue infliximab or MTX. Here we tested how etanercept affected P-gp-mediated drug resistance in such intractable RA patients. Peripheral lymphocytes of 11 RA patients (3 switched from infliximab and 8 who could not be treated with MTX) were analyzed for P-gp expression by flow cytometry and for drug exclusion using radioisotope-labeled dexamethasone. Activated lymphocytes of RA patients overexpressed P-gp and coexpressed CD69. Incubation of these lymphocytes with dexamethasone in vitro reduced intracellular dexamethasone levels. Two-week etanercept therapy significantly reduced P-gp expression and eliminated such P-gp- and CD69-high-expressing subgroup. The reduction in P-gp resulted in recovery of intracellular dexamethasone levels in lymphocytes and improvement of disease activity, thus allowing tapering of corticosteroids. None of the patients experienced any severe adverse effects. Etanercept is useful for overcoming P-gp-mediated treatment resistance in intractable RA patients who have to discontinue infliximab or are intolerant to MTX.

Esterification free fatty acid in palm fatty acid distillate using sulfonated rice husk ash catalyst

Science.gov (United States)

Hidayat, Arif; Sutrisno, Bachrun

2017-01-01

Indonesia, as one of the biggest palm oil producers and exporters in the world, is producing large amounts of low-grade oil such as Palm Fatty Acid Distillate (PFAD) from palm oil industries. The use of PFAD can reduce the cost of biodiesel production significantly, which makes PFAD a highly potential alternative feedstock for biodiesel production. In this paper, the esterification of free fatty acid (FFA) on PFAD was studied using rice husk ash (RHA) as heterogeneous catalyst. The rice husk ash catalyst was synthesized by sulfonation using concentrated sulfuric acid. The RHA catalyst were characterized by using different techniques, such as porosity analysis, Fourier transform infrared (FT-IR) spectroscopy, total number of acid sites and elemental analysis. The effects of the molar ratio of methanol to PFAD (1-10%), the molar ratio of methanol to PFAD (4:1-10:1), and the reaction temperature (40-60°C) were studied for the conversion of FFA to optimize the reaction conditions. The results showed that the optimal conditions were an methanol to PFAD molar ratio of 10:1, the catalyst amount of 10 wt% of PFAD, and reaction temperature of 60°C.

Asymmetric synthesis of allylic sulfonic acids: enantio- and regioselective iridium-catalyzed allylations of Na2SO3.

Science.gov (United States)

Liu, Wei; Zhao, Xiao-ming; Zhang, Hong-bo; Zhang, Liang; Zhao, Ming-zhu

2014-12-15

An enantioselective allylation reaction of allylic carbonates with sodium sulfite (Na2 SO3 ) catalyzed by Ir complex was accomplished, providing allylic sulfonic acids in good to excellent yields with a high level of enantio- and regioselectivities. (R)-2-Phenyl-2-sulfoacetic acid, a key intermediate for the synthesis of Cefsulodin and Sulbenicillin, was synthesized as well. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

Science.gov (United States)

Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

2017-02-01

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gamma-radiolysis of some glycoproteins in dilute aqueous solutions

Energy Technology Data Exchange (ETDEWEB)

Nagrani, S

1981-01-01

A study has been made of the radiation-induced damage of some glycoproteins in dilute aqueous solutions. By use of specific radical scavengers, the roles of the individual free radicals, formed by ..gamma..-radiolysis, in causing damage has been assessed. The most effective radical in causing damage to human and porcine glycopolypeptide is the OH radical. The structure of the different blood group glycopolypeptides determines the sensitivity towards the free radical attack. The glycopolypeptide shows depolymerization and a characteristic absorption at approximately 270 nm due to the formation of additional products on irradiation. Chemical changes of the irradiated glycopolypeptide solutions revealed significant damage to the oligosaccharide chain and the polypeptide core of the glycopolypeptide. The radiation-induced inactivation of another glycoprotein, external yeast invertase, due to different radical species at pH 7.0 decreases in the following order: ea-barq > OH radical > (SCN) radical/sub 2//sup -/ > Br radical/sub 2//sup -/. The structure of this enzyme, accounts for the mechanism of enzyme inactivation and the relative damage of carbohydrate and amino acid residues. The irradiated enzyme solutions show significant changes in their electrophoretic behaviour on cellogel electrophoresis due to the formation of radiolysis products, which also show characteristic absorption maxima at approximately 275 nm. (author).

Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

Energy Technology Data Exchange (ETDEWEB)

Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

2015-10-09

Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

International Nuclear Information System (INIS)

Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

2015-01-01

Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

Esterification of oil adsorbed on palm decanter cake into methyl ester using sulfonated rice husk ash as heterogeneous acid catalyst

Science.gov (United States)

Hindryawati, Noor; Erwin, Maniam, Gaanty Pragas

2017-02-01

Palm Decanter cake (PDC) which is categorized as the waste from palm oil mill has been found to contain residual crude palm oil. The oil adsorbed on the PDC (PDC-oil) can be extracted and potentially used as feedstock for biodiesel production. Feedstock from waste like PDC-oil is burdened with high free fatty acids (FFAs) which make the feedstock difficult to be converted into biodiesel using basic catalyst. Therefore, in this study, a solid acid, RHA-SO3H catalyst was synthesized by sulfonating rice husk ash (RHA) with concentrated sulfuric acid. The RHA-SO3H prepared was characterized with TGA, FTIR, BET, XRD, FE-SEM, and Hammett indicators (methyl red, bromophenol blue, and crystal violet). PDC was found to have about 11.3 wt. % oil recovered after 1 hour extraction using ultrasound method. The presence of sulfonate group was observed in IR spectrum, and the surface area of RHA-SO3H was reduced to 37 m2.g-1 after impregnation of sulfonate group. The RHA-SO3H catalyst showed that it can work for both esterification of free fatty acid which is present in PDC-oil, and transesterification of triglycerides into methyl ester. The results showed highest methyl ester content of 70.2 wt.% at optimal conditions, which was 6 wt.% catalyst amount, methanol to oil molar ratio of 17:1 for 5 hours at 120 °C.

Design and synthesis of aryl ether and sulfone hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

Science.gov (United States)

Pabba, Chittari; Gregg, Brian T; Kitchen, Douglas B; Chen, Zhen Jia; Judkins, Angela

2011-01-01

A series of novel hydroxamic acid based histone deacetylases (HDAC) inhibitors with aryl ether and aryl sulfone residues at the terminus of a substituted, unsaturated 5-carbon spacer moiety have been synthesized for the first time and evaluated. Compounds with meta- and para-substitution on the aryl ring of ether hydroxamic acids 19c, 20c, 19e, 19f and 19g are potent HDAC inhibitors with activities at low nanomolar levels. Copyright © 2010 Elsevier Ltd. All rights reserved.

Mutagenic and Cytotoxic Properties of 6-Thioguanine, S6-Methylthioguanine, and Guanine-S6-sulfonic Acid*S⃞

OpenAIRE

Yuan, Bifeng; Wang, Yinsheng

2008-01-01

Thiopurine drugs, including 6-thioguanine (SG), 6-mercaptopurine, and azathioprine, are widely employed anticancer agents and immunosuppressants. The formation of SG nucleotides from the thiopurine prodrugs and their subsequent incorporation into nucleic acids are important for the drugs to exert their cytotoxic effects. SG in DNA can be methylated by S-adenosyl-l-methionine to give S6-methylthioguanine (S6mG) and oxidized by UVA light to render guanine-S6-sulfonic acid ...

p-Coumaric acid enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments.

Science.gov (United States)

Kim, Hyun-Bum; Lee, Seok; Hwang, Eun-Sang; Maeng, Sungho; Park, Ji-Ho

2017-10-21

Due to the improvement of medical level, life expectancy increased. But the increased incidence of cognitive disorders is an emerging social problem. Current drugs for dementia treatment can only delay the progress rather than cure. p-Coumaric acid is a phenylpropanoic acid derived from aromatic amino acids and known as a precursor for flavonoids such as resveratrol and naringenin. It was shown to reduce oxidative stress, inhibit genotoxicity and exert neuroprotection. Based on these findings, we evaluated whether p-coumaric acid can protect scopolamine induced learning and memory impairment by measuring LTP in organotypic hippocampal slice and cognitive behaviors in rats. p-Coumaric acid dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In addition, while scopolamine shortened the step-through latency in the passive avoidance test and prolonged the latency as well as reduced the latency in the target quadrant in the Morris water maze test, co-treatment of p-coumaric acid improved avoidance memory and long-term retention of spatial memory in behavioral tests. Since p-coumaric acid improved electrophysiological and cognitive functional deterioration by scopolamine, it may have regulatory effects on central cholinergic synapses and is expected to improve cognitive problems caused by abnormality of the cholinergic nervous system. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of time and temperature exposition in the crystallinity degree of sulfonated poly-(styrene acrylic acid) (PSAA-S)

International Nuclear Information System (INIS)

Duarte, G.W.; Becker, E.B.; Silva, L.; Naspolini, A.M.; Consenso, E.C.; Paula, M.M.S.; Fiori, M.A.; Silveira, F.Z.

2010-01-01

Polymers with special properties have been increasingly applied in the development of technological devices. For example, polymeric materials with special electric properties, such as sulfonated poly-(styrene-acrylic acid) - PSAA-S, are of great interest for showing different conductivities depending on the environment where they are applied. The special properties of PSAA are obtained only after sulfonation step in acidic media. The present work aimed to evaluate the effect of time and temperature exposition in the crystallinity degree of PSAA-S, through a statistical experimental factorial planning. The samples of PSAA-S were submitted to FT-IR and DRX tests. The results showed that the temperature and the time of exposition are significant factors in the crystallinity degree of PSAA-S, considering that the crystal lattices created during the polymerization are damaged by the action of time and temperature at which the polymer is exposed. (author)

Effect of time and temperature exposition in the crystallinity degree of sulfonated poly-(styrene acrylic acid) (PSAA-S)

Energy Technology Data Exchange (ETDEWEB)

Duarte, G.W.; Becker, E.B.; Silva, L.; Naspolini, A.M.; Consenso, E.C.; Paula, M.M.S.; Fiori, M.A., E-mail: glau_bn@hotmail.co [University of Extreme South of Santa Catarina Criciuma, SC (Brazil). Dept. of Materials Engineering; Silveira, F.Z. [Federal University of Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. of Chemical Engineering

2010-07-01

Polymers with special properties have been increasingly applied in the development of technological devices. For example, polymeric materials with special electric properties, such as sulfonated poly-(styrene-acrylic acid) - PSAA-S, are of great interest for showing different conductivities depending on the environment where they are applied. The special properties of PSAA are obtained only after sulfonation step in acidic media. The present work aimed to evaluate the effect of time and temperature exposition in the crystallinity degree of PSAA-S, through a statistical experimental factorial planning. The samples of PSAA-S were submitted to FT-IR and DRX tests. The results showed that the temperature and the time of exposition are significant factors in the crystallinity degree of PSAA-S, considering that the crystal lattices created during the polymerization are damaged by the action of time and temperature at which the polymer is exposed. (author)

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine.

Science.gov (United States)

Yi, Zhihua; Xie, Lihui; Zhou, Congfa; Yuan, Huilong; Ouyang, Shuai; Fang, Zhi; Zhao, Shanhong; Jia, Tianyu; Zou, Lifang; Wang, Shouyu; Xue, Yun; Wu, Bing; Gao, Yun; Li, Guilin; Liu, Shuangmei; Xu, Hong; Xu, Changshui; Zhang, Chunping; Liang, Shangdong

2018-03-01

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5'-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

Controlled sulfonation of poly(ether sulfone using phthalic anhydride as catalyst and its membrane performance for fuel cell application

Directory of Open Access Journals (Sweden)

Seikh Jiyaur Rahaman

2016-09-01

Full Text Available Proton exchange membrane (PEM fuel cells are one of the most emerging alternative energy technologies under development. A novel proton exchange membrane sulfonated polyethersulfone (SPES was developed by homogeneous method using phthalic anhydride as catalyst and chlorosulfonic acid as sulfonating agent to control the sulfonation reaction. The method of sulfonation was optimized by varying the reaction time and concentration of the catalyst. The structure of the SPES was studied by 1H-Nuclear Magnetic Resonance, Fourier Transform Infra Red Spectroscopy and X-ray diffraction. The extent of sulfonation was determined by ion exchange capacity studies. The thermal and mechanical stabilities were studied using thermogravimetric analysis (TGA and Dynamic Mechanical Analysis (DMA respectively. DMA results show that the storage modulus increased with increase in degree of sulfonation (DS and water uptake of SPES increased with DS. The proton conductivity of SPES (34% DS measured by impedance spectroscopy was found to be 0.03S/cm at 80%RH and 100°C. Also, current-voltage polarization characteristics of SPES membranes offer a favourable alternative PEM due to the thermal stability and cost effective than perfluorinated ionomers.

Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport

Energy Technology Data Exchange (ETDEWEB)

Padilla, S.; Lyerly, D.L.; Pope, C.N.

1992-01-01

Organic solvants, as a class, have been implicated as neurotoxic agents in humans and laboratory animals. The study was designed to assess the interaction between subacute ingestion of moderate levels of ethanol and the p-xylene-induced decreases in protein and glycoprotein synthesis and axonal transport in the rat optic system. The results indicated that animals maintained on 10% ethanol as a drinking liquid show less p-xylene-induced neurotoxicity than animals receiving no ethanol supplement.

A Novel Fiber Optic Surface Plasmon Resonance Biosensors with Special Boronic Acid Derivative to Detect Glycoprotein

Directory of Open Access Journals (Sweden)

Yang Zhang

2017-10-01

Full Text Available We proposed and demonstrated a novel tilted fiber Bragg grating (TFBG-based surface plasmon resonance (SPR label-free biosensor via a special boronic acid derivative to detect glycoprotein with high sensitivity and selectivity. TFBG, as an effective sensing element for optical sensing in near-infrared wavelengths, possess the unique capability of easily exciting the SPR effect on fiber surface which coated with a nano-scale metal layer. SPR properties can be accurately detected by measuring the variation of transmitted spectra at optical communication wavelengths. In our experiment, a 10° TFBG coated with a 50 nm gold film was manufactured to stimulate SPR on a sensor surface. To detect glycoprotein selectively, the sensor was immobilized using designed phenylboronic acid as the recognition molecule, which can covalently bond with 1,2- or 1,3-diols to form five- or six-membered cyclic complexes for attaching diol-containing biomolecules and proteins. The phenylboronic acid was synthetized with long alkyl groups offering more flexible space, which was able to improve the capability of binding glycoprotein. The proposed TFBG-SPR sensors exhibit good selectivity and repeatability with a protein concentration sensitivity up to 2.867 dB/ (mg/mL and a limit of detection (LOD of 15.56 nM.

Mechanisms of P-Glycoprotein Modulation by Semen Strychni Combined with Radix Paeoniae Alba

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Li-Li Liu

2017-01-01

Full Text Available Semen Strychni has been extensively used as a Chinese herb, but its therapeutic window is narrowed by the strong toxicity of the compound, which limits its effectiveness. Radix Paeoniae Alba has been reported to reduce the toxic effects and increase the therapeutic effects of Semen Strychni, but the underlying mechanism remains unknown. This research aimed to explore the mechanism through which P-glycoprotein (P-gp is modulated by Semen Strychni combined with Radix Paeoniae Alba in vitro. An MTT assay was used to study cytotoxicity in an MDCK-MDR1 cell model. Rh123 efflux and accumulation were measured to assess P-gp function. The expression levels of MDR1 mRNA and P-gp protein in MDCK-MDR1 cells were investigated. A P-gp ATPase activity assay kit was applied to detect the effect on P-gp ATPase activity. Semen Strychni combined with Radix Paeoniae Alba could induce P-gp-mediated drug transport by inhibiting brucine and strychnine transport in MDCK-MDR1 cells, enhancing the P-gp efflux function, upregulating the P-gp expression and MDR1 mRNA levels, and stimulating P-gp ATPase activity.

Effect of perfluorooctane sulfonate on the conformation of wheat germ acid phosphatase.

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Xu, Dongmei; Jin, Jianchang; Shen, Tong; Wang, Yanhua

2013-11-01

Fluorescence spectroscopy was used to study the quenching mechanism, the type of force and the binding sites of perfluorooctane sulfonate (PFOS) on wheat germ acid phosphatase (ACPase). The results showed that the quenching effect of PFOS on ACPase was mainly due to a static quenching mechanism that occurred via the formation of hydrogen bonds and van der Waals forces. The results from synchronous fluorescence spectroscopy demonstrated that PFOS interacts with ACPase close to the tryptophan residues. In addition, synchronous fluorescence spectroscopy also showed that PFOS increases the hydrophobicity of the microenvironment of the tyrosine residues, hence decreasing the local polarity.

pH-Induced Lignin Surface Modification to Reduce Nonspecific Cellulase Binding and Enhance Enzymatic Saccharification of Lignocelluloses

Science.gov (United States)

Hongming Lou; J.Y. Zhu; Tian Qing Lan; Huranran Lai; Xueqing Qiu

2013-01-01

We studied the mechanism of the significant enhancement in the enzymatic saccharification of lignocelluloses at an elevated pH of 5.5–6.0. Four lignin residues with different sulfonic acid contents were isolated from enzymatic hydrolysis of lodgepole pine pretreated by either dilute acid (DA) or sulfite pretreatment to overcome recalcitrance of lignocelluloses (SPORL...

Syn-Selective Synthesis of β-Branched α-Amino Acids by Alkylation of Glycine-Derived Imines with Secondary Sulfonates.

Science.gov (United States)

Lou, Sha; McKenna, Grace M; Tymonko, Steven A; Ramirez, Antonio; Benkovics, Tamas; Conlon, David A; González-Bobes, Francisco

2015-10-16

A syn-selective synthesis of β-branched α-amino acids has been developed based on the alkylation of glycine imine esters with secondary sulfonates. The potassium counterion for the enolate, the solvent, and the leaving group on the electrophile were key levers to maximize the diasteroselectivity of the alkylation. The optimized conditions enabled a straightforward preparation of a number of β-branched α-amino acids that can be challenging to obtain.

Curcumin as a Modulator of P-Glycoprotein in Cancer: Challenges and Perspectives

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Vanessa Lopes-Rodrigues

2016-11-01

Full Text Available Multidrug resistance (MDR presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp is a drug efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no P-gp inhibitors being used in the current clinical practice, due to toxicity problems, drug interactions, or pharmacokinetic issues. Therefore, it is important to identify novel inhibitors of P-gp activity or expression. Curcumin is a secondary metabolite isolated from the turmeric of Curcuma longa L. which has been associated with several biological activities, particularly P-gp modulatory activity (by inhibiting both P-gp function and expression. However, curcumin shows extensive metabolism and instability, which has justified the recent and intensive search for analogs of curcumin that maintain the P-gp modulatory activity but have enhanced stability. This review summarizes and compares the effects of curcumin and several curcumin analogs on P-glycoprotein function and expression, emphasizing the potential of these molecules for the possible development of safe and effective inhibitors of P-gp to overcome MDR in human cancer.

Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia : A PET study with [C-11]verapamil as a probe for P-glycoprotein function

NARCIS (Netherlands)

de Klerk, Onno L.; Willemsen, Antoon T. M.; Bosker, Fokko J.; Bartels, Anna L.; Hendrikse, N. Harry; den Boer, Johan A.; Dierckx, Rudy A.

2010-01-01

P-glycoprotein (P-gp), a major efflux pump in the blood-brain barrier (BBB) has a profound effect on entry of drugs, peptides and other substances into the central nervous system (CNS). The brain's permeability can be negatively influenced by modulation of the transport function of P-gp.

3-[(3-(Trimethoxysilylpropylthio]propane-1-oxy-sulfonic acid: An efficient recyclable heterogeneous catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H-ones/thiones

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Srinivasa Rao Jetti

2017-05-01

Full Text Available An efficient method for the synthesis of 3,4-dihydropyrimidin-2(1H-ones and thiones through one-pot three-component reaction of ethyl acetoacetate, aryl aldehyde and urea or thiourea in ethanol using 3-[(3-(trimethoxysilylpropylthio]propane-1-oxy-sulfonic acid as catalyst is described. The use of 3-[(3-(trimethoxysilylpropylthio]propane-1-oxy-sulfonic acid as a catalyst offers several advantages such as high yields, short reaction times, mild reaction condition and a recyclable catalyst with a very easy work up.

Determination of perfluoroalkyl carboxylic, sulfonic, and phosphonic acids in food.

Science.gov (United States)

Ullah, Shahid; Alsberg, Tomas; Vestergren, Robin; Berger, Urs

2012-11-01

A sensitive and accurate method was developed and validated for simultaneous analysis of perfluoroalkyl carboxylic acids, sulfonic acids, and phosphonic acids (PFPAs) at low picograms per gram concentrations in a variety of food matrices. The method employed extraction with acetonitrile/water and cleanup on a mixed-mode co-polymeric sorbent (C8 + quaternary amine) using solid-phase extraction. High-performance liquid chromatographic separation was achieved on a C18 column using a mobile phase gradient containing 5 mM 1-methyl piperidine for optimal chromatographic resolution of PFPAs. A quadrupole time-of-flight high-resolution mass spectrometer operating in negative ion mode was used as detector. Method detection limits were in the range of 0.002 to 0.02 ng g(-1) for all analytes. Sample preparation (extraction and cleanup) recoveries at a spiking level of 0.1 ng g(-1) to a baby food composite were in the range of 59 to 98 %. A strong matrix effect was observed in the analysis of PFPAs in food extracts, which was tentatively assigned to sorption of PFPAs to the injection vial in the solvent-based calibration standard. The method was successfully applied to a range of different food matrices including duplicate diet samples, vegetables, meat, and fish samples.

Analysis of metolachlor ethane sulfonic acid chirality in groundwater: A tool for dating groundwater movement in agricultural settings

Science.gov (United States)

Chemical chirality of pesticides can be a useful tool for studying environmental processes. The chiral forms of metolachlor ethane sulfonic acid (MESA), an abundant metabolite of metolachlor, and metolachlor were examined over a 6 year period in groundwater and a groundwater-fed stream in a riparia...

P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

Science.gov (United States)

Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

2014-01-01

The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

P-glycoprotein activity and biological response

International Nuclear Information System (INIS)

Vaalburg, W.; Hendrikse, N.H.; Elsinga, P.H.; Bart, J.; Waarde, A. van

2005-01-01

P-glycoprotein (P-gp) is a transmembrane drug efflux pump encoded by the MDR-1 gene in humans. Most likely P-gp protects organs against endogenous and exogenous toxins by extruding toxic compounds such as chemotherapeutics and other drugs. Many drugs are substrates for P-gp. Since P-gp is also expressed in the blood-brain barrier, P-gp substrates reach lower concentrations in the brain than in P-gp-negative tissues. Failure of response to chemotherapy of malignancies can be due to intrinsic or acquired drug resistance. Many tumors are multidrug resistant (MDR); resistant to several structurally unrelated chemotherapeutic agents. Several mechanisms are involved in MDR of which P-gp is studied most extensively. P-gp extrudes drugs out of tumor cells resulting in decreased intracellular drug concentrations, leading to the MDR phenotype. Furthermore, the MDR-1 gene exhibits several single nucleotide polymorphisms, some of which result in different transport capabilities. P-gp functionality and the effect of P-gp modulation on the pharmacokinetics of novel and established drugs can be studied in vivo by positron emission tomography (PET) using carbon-11 and fluorine-18-labeled P-gp substrates and modulators. PET may demonstrate the consequences of genetic differences on tissue pharmacokinetics. Inhibitors such as calcium-channel blockers (verapamil), cyclosporin A, ONT-093, and XR9576 can modulate the P-gp functionality. With PET the effect of P-gp modulation on the bioavailability of drugs can be investigated in humans in vivo. PET also allows the measurement of the efficacy of newly developed P-gp modulators

Overcoming of P-glycoprotein mediated vincristine resistance of L1210/VCR mouse leukemic cells could be induced by pentoxifylline but not by theophylline and caffeine

International Nuclear Information System (INIS)

Stefankova, Z.; Barancik, M.; Breier, A.

1996-01-01

Effects of xanthine derivatives (pentoxifylline (PTX), caffeine, theophylline, 1-methyl-3-isobutylxanthine) on P-glycoprotein mediated vincristine resistance of L1210/VCR mouse leukemic cell sub-line were studied. From the applied xanthines only PTX was found to reverse the vincristine resistance of the above cells. Moreover, only PTX, but not other xanthine, increased the accumulation of [ 3 H]vincristine by L1210/VCR cells. Thus it may be concluded that PTX-induced reversal of vincristine (VCR) resistance could not be explained from the point of known pharmacological effects of PTX that are common for other xanthines such as inhibition of phosphodiesterase activity, calcium mobilizing effect, inhibition of tumor necrosis factor α (TNF), etc. (author)

Preparation of a Sulfonated Carbonaceous Material from Lignosulfonate and Its Usefulness as an Esterification Catalyst

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Duckhee Lee

2013-07-01

Full Text Available Sulfonated carbonaceous material useful as a solid acid catalyst was prepared from lignosulfonate, a waste of the paper-making industry sulfite pulping process, and characterized by 13C-NMR, FT-IR, TGA, SEM and elemental analysis, etc. The sulfonic acid group density and total density of all acid groups in the sulfonated carbonaceous material was determined by titration to be 1.24 mmol/g and 5.90 mmol/g, respectively. Its catalytic activity in the esterification of cyclohexanecarboxylic acid with anhydrous ethanol was shown to be comparable to that of the ionic exchange resin Amberlyst-15, when they were used in the same amount. In the meantime, the sulfonic acid group was found to be leached out by 26%–29% after it was exposed to hot water (95 °C for 5 h. The catalytic usefulness of the prepared carbonaceous material was investigated by performing esterifications.

Modeling of boldine alkaloid adsorption onto pure and propyl-sulfonic acid-modified mesoporous silicas. A comparative study

Energy Technology Data Exchange (ETDEWEB)

Geszke-Moritz, Małgorzata, E-mail: Malgorzata.Geszke-Moritz@amu.edu.pl [NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Moritz, Michał, E-mail: michal.moritz@put.poznan.pl [Poznan University of Technology, Faculty of Chemical Technology, Institute of Chemistry and Technical Electrochemistry, Berdychowo 4, 60-965 Poznań (Poland)

2016-12-01

The present study deals with the adsorption of boldine onto pure and propyl-sulfonic acid-functionalized SBA-15, SBA-16 and mesocellular foam (MCF) materials. Siliceous adsorbents were characterized by nitrogen sorption analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy and thermogravimetric analysis. The equilibrium adsorption data were analyzed using the Langmuir, Freundlich, Redlich-Peterson, and Temkin isotherms. Moreover, the Dubinin-Radushkevich and Dubinin-Astakhov isotherm models based on the Polanyi adsorption potential were employed. The latter was calculated using two alternative formulas including solubility-normalized (S-model) and empirical C-model. In order to find the best-fit isotherm, both linear regression and nonlinear fitting analysis were carried out. The Dubinin-Astakhov (S-model) isotherm revealed the best fit to the experimental points for adsorption of boldine onto pure mesoporous materials using both linear and nonlinear fitting analysis. Meanwhile, the process of boldine sorption onto modified silicas was described the best by the Langmuir and Temkin isotherms using linear regression and nonlinear fitting analysis, respectively. The values of adsorption energy (below 8 kJ/mol) indicate the physical nature of boldine adsorption onto unmodified silicas whereas the ionic interactions seem to be the main force of alkaloid adsorption onto functionalized sorbents (energy of adsorption above 8 kJ/mol). - Graphical abstract: Modeling of boldine adsorption onto unmodified and propyl-sulfonic acid-modified mesoporous adsorbents. - Highlights: • The process of boldine adsorption onto SBA-15, SBA-16 and MCF silicas was examined. • Siliceous adsorbents were functionalized with propyl-sulfonic acid groups. • The equilibrium adsorption data were analyzed using several isotherm models. • Both linear regression and nonlinear fitting analysis were carried out. �

Synergic extraction of some lanthanide and actinide elements by a mixture of bis(2-ethyl hexyl) phosphoric acid and dinonylnapthalene - sulfonic acid in aromatic diluents

International Nuclear Information System (INIS)

Raieh, M.A.; El-Dessouky, M.M.

1985-01-01

Extraction of lanthanides and actinides were found to be synergetically enhanced by a mixture of bis(2-ethyl hexyl) phosphoric acid (HA) and dinonylnaphthalene sulfonic acid (HD) in aromatic diluents covering a wide range of dielectric constants. The main extracted species is found to be MAsub(2)Hsub(m-1)Dsub(m). Experimental results indicate that the extraxtion mechanism is governed by the extraction of HD in the organic phase. (author)

Optimization of irinotecan chronotherapy with P-glycoprotein inhibition

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Filipski, Elisabeth; Berland, Elodie [INSERM, U776 “Rythmes biologiques et cancers”, CAMPUS CNRS, 7 rue Guy Môquet, F-94801 Villejuif (France); Univ Paris-Sud, UMR-S0776, Orsay F-91405 (France); Ozturk, Narin [INSERM, U776 “Rythmes biologiques et cancers”, CAMPUS CNRS, 7 rue Guy Môquet, F-94801 Villejuif (France); Univ Paris-Sud, UMR-S0776, Orsay F-91405 (France); Istanbul University Faculty of Pharmacy, Department of Pharmacology, Beyazit TR-34116, Istanbul (Turkey); Guettier, Catherine [Assistance Publique-Hôpitaux de Paris, Unité de Chronothérapie, Département de Cancérologie, Hôpital Paul Brousse, Villejuif F-94807 (France); Horst, Gijsbertus T.J. van der [Department of Genetics, Erasmus University Medical Center, 3000 CA Rotterdam (Netherlands); Lévi, Francis [INSERM, U776 “Rythmes biologiques et cancers”, CAMPUS CNRS, 7 rue Guy Môquet, F-94801 Villejuif (France); Univ Paris-Sud, UMR-S0776, Orsay F-91405 (France); Assistance Publique-Hôpitaux de Paris, Unité de Chronothérapie, Département de Cancérologie, Hôpital Paul Brousse, Villejuif F-94807 (France); and others

2014-02-01

The relevance of P-glycoprotein (P-gp) for irinotecan chronopharmacology was investigated in female B6D2F{sub 1} mice. A three-fold 24 h change in the mRNA expression of Abcb1b was demonstrated in ileum mucosa, with a maximum at Zeitgeber Time (ZT) 15 (p < 0.001). No rhythm was found for abcb1a in ileum mucosa, or for Abcb1a/b in Glasgow osteosarcoma (GOS), a mouse tumor cell line moderately sensitive to irinotecan. Non-tumor-bearing mice received irinotecan (50 mg/kg/day i.v. × 4 days) as a single agent or combined with P-gp inhibitor PSC833 (6.25 mg/kg/day i.p. × 4 days) at ZT3 or ZT15, respectively corresponding to the worst or the best irinotecan tolerability. Endpoints involved survival, body weight change and hematologic toxicity. Antitumor efficacy was studied in GOS-bearing mice receiving irinotecan (25, 30 or 40 mg/kg/day × 4 days) and +/− PSC833 at ZT3 or ZT15, with survival, body weight change, and tumor growth inhibition as endpoints. Non-tumor bearing mice lost an average of 17% or 9% of their body weight according to irinotecan administration at ZT3 or ZT15 respectively (p < 0.001). Dosing at ZT15 rather than ZT3 reduced mean leucopenia (9% vs 53%; p < 0.001). PSC833 aggravated irinotecan lethal toxicity from 4 to ∼ 60%. In tumor-bearing mice, body weight loss was ∼ halved in the mice on irinotecan or irinotecan–PSC833 combination at ZT15 as compared to ZT3 (p < 0.001). PSC833–irinotecan at ZT15 increased tumor inhibition by ∼ 40% as compared to irinotecan only at ZT15. In conclusion, P-gp was an important determinant of the circadian balance between toxicity and efficacy of irinotecan. - Highlights: • Irinotecan chronotolerance and chronoefficacy change as drug was applied with PSC833. • P-glycoprotein is an important player of the toxicity and efficacy of irinotecan. • Timing should be considered if chemotherapy is performed with a MDR1 inhibitor.

Isoelectric focusing of dansylated amino acids in immobilized pH gradients

Science.gov (United States)

Bianchi-Bosisio, Adriana; Righetti, Pier Giorgio; Egen, Ned B.; Bier, Milan

1986-01-01

The 21 free amino acids commonly encountered in proteins have been transformed into 'carrier ampholyte' species by reacting their primary amino groups with dansyl chloride. These derivatives can thus be focused in an immobilized pH gradient covering the pH interval 3.1 to 4.1, except for arginine, which still retains a pI of 8.8. Due to their inherent fluorescence, the dansyl derivatives are revealed in UV light, with a sensitivity of the order of 2-4 ng/sq mm. All nearest neighbors are separated except for the following couples: Asn-Gln, Gly-Thr, Val-Ile and Cys-Cys2, with a resolving power, in a Delta(pI) scale, of the order of 0.0018 pH units. Except for a few cases (notably the aromatic amino acids), the order of pI values is well correlated with the pK values of carboxyl groups, suggesting that the latter are not altered by dansylation. From the set of pK(COOH)-pI values of the different amino acids, the pK of the tertiary amino group in the dansyl label has been calculated to be 5.11 + or - 0.06. Knowing the pK of the amino-dansyl and the pI of the excess, free dansyl label (pI = 3.34), a pK of 1.57 is derived for its sulfonic acid group.

Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike.

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Thomas A Bowden

Full Text Available The genus Orthobunyavirus within the family Bunyaviridae constitutes an expanding group of emerging viruses, which threaten human and animal health. Despite the medical importance, little is known about orthobunyavirus structure, a prerequisite for understanding virus assembly and entry. Here, using electron cryo-tomography, we report the ultrastructure of Bunyamwera virus, the prototypic member of this genus. Whilst Bunyamwera virions are pleomorphic in shape, they display a locally ordered lattice of glycoprotein spikes. Each spike protrudes 18 nm from the viral membrane and becomes disordered upon introduction to an acidic environment. Using sub-tomogram averaging, we derived a three-dimensional model of the trimeric pre-fusion glycoprotein spike to 3-nm resolution. The glycoprotein spike consists mainly of the putative class-II fusion glycoprotein and exhibits a unique tripod-like arrangement. Protein-protein contacts between neighbouring spikes occur at membrane-proximal regions and intra-spike contacts at membrane-distal regions. This trimeric assembly deviates from previously observed fusion glycoprotein arrangements, suggesting a greater than anticipated repertoire of viral fusion glycoprotein oligomerization. Our study provides evidence of a pH-dependent conformational change that occurs during orthobunyaviral entry into host cells and a blueprint for the structure of this group of emerging pathogens.

Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters.

Science.gov (United States)

Wang, Fun-In; Deng, Ming-Chung; Huang, Yu-Liang; Chang, Chia-Yi

2015-06-29

Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on viral pathogenicity in cells in culture and in animal hosts. E2 is the most important structural protein as it interacts with cell surface receptors that determine cell tropism and induces neutralizing antibody and cytotoxic T-lymphocyte responses. All three glycoproteins are involved in virus attachment and entry into target cells. E1-E2 heterodimers are essential for viral entry and infectivity. Erns is unique because it possesses intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferons and assist in the development of persistent infections. These glycoproteins are localized to the virion surface; however, variations in amino acids and antigenic structures, disulfide bond formation, glycosylation, and RNase activity can ultimately affect the virulence of pestiviruses in animals. Along with mutations that are driven by selection pressure, antigenic differences in glycoproteins influence the efficacy of vaccines and determine the appropriateness of the vaccines that are currently being used in the field.

Analysis of metolachlor ethane sulfonic acid (MESA) chirality in groundwater: A tool for dating groundwater movement in agricultural settings.

Science.gov (United States)

Rice, Clifford P; McCarty, Gregory W; Bialek-Kalinski, Krystyna; Zabetakis, Kara; Torrents, Alba; Hapeman, Cathleen J

2016-08-01

To better address how much groundwater contributes to the loadings of pollutants from agriculture we developed a specific dating tool for groundwater residence times. This tool is based on metolachlor ethane sulfonic acid, which is a major soil metabolite of metolachlor. The chiral forms of metolachlor ethane sulfonic acid (MESA) and the chiral forms of metolachlor were examined over a 6-year period in samples of groundwater and water from a groundwater-fed stream in a riparian buffer zone. This buffer zone bordered cropland receiving annual treatments with metolachlor. Racemic (rac) metolachlor was applied for two years in the neighboring field, and subsequently S-metolachlor was used which is enriched by 88% with the S-enantiomer. Chiral analyses of the samples showed an exponential increase in abundance of the S-enantiomeric forms for MESA as a function of time for both the first order riparian buffer stream (R(2)=0.80) and for groundwater within the riparian buffer (R(2)=0.96). However, the S-enrichment values for metolachlor were consistently high indicating different delivery mechanisms for MESA and metolachlor. A mean residence time of 3.8years was determined for depletion of the initially-applied rac-metolachlor. This approach could be useful in dating groundwater and determining the effectiveness of conservation measures. A mean residence time of 3.8years was calculated for groundwater feeding a first-order stream by plotting the timed-decay for the R-enantiomer of metolachlor ethane sulfonic acid. Published by Elsevier B.V.

ANALYSIS OF SULFONATES IN AQUEOUS SAMPLES BY ION-PAIR LC/ESI-MS/MS WITH IN-SOURCE CID FOR ADDUCT PEAK ELIMINATION

Energy Technology Data Exchange (ETDEWEB)

OUYANG,S.; VAIRAVAMURTHY,M.A.

1999-06-13

Determination of low-molecular-weight organic sulfonates (e.g. taurine and cysteic acid) in aqueous solutions is important in many applications of biological, environmental and pharmaceutical sciences. These compounds are difficult to be determined by commonly used reversed-phase liquid chromatographic separation combined with UV-Visible detection because of their high solubility and the lack chromophoric moieties. Here the authors report a method combining ion-pair liquid chromatography and electrospray ionization tandem mass spectrometry (IPLC/ESI-MS/MS)for determining sulfonates. The ability of low-molecular-weight sulfonates to form ion-pairs with quaternary ammonium cations in aqueous solutions allowed LC separation with a C{sub 18} column. Detection of the sulfonates was accomplished with ESI-MS that lends a universal mode of mass detection for polar, water soluble compounds. An in-source collision induced dissociation (CID) was applied to eliminate the adduct peaks in mass spectra. Characteristic marker ions showed in the second stage mass spectra lent a method for identifying sulfonates.

Sensing and adaptation to low pH mediated by inducible amino acid decarboxylases in Salmonella.

Science.gov (United States)

Viala, Julie P M; Méresse, Stéphane; Pocachard, Bérengère; Guilhon, Aude-Agnès; Aussel, Laurent; Barras, Frédéric

2011-01-01

During the course of infection, Salmonella enterica serovar Typhimurium must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments. Three low pH inducible amino acid decarboxylases were annotated in the genome of S. Typhimurium, AdiA, CadA and SpeF, which are specific for arginine, lysine and ornithine, respectively. In this study, we characterized and compared the contributions of those enzymes in response to acidic challenges. Individual mutants as well as a strain deleted for the three genes were tested for their ability (i) to survive an extreme acid shock, (ii) to grow at mild acidic pH and (iii) to infect the mouse animal model. We showed that the lysine decarboxylase CadA had the broadest range of activity since it both had the capacity to promote survival at pH 2.3 and growth at pH 4.5. The arginine decarboxylase AdiA was the most performant in protecting S. Typhimurium from a shock at pH 2.3 and the ornithine decarboxylase SpeF conferred the best growth advantage under anaerobiosis conditions at pH 4.5. We developed a GFP-based gene reporter to monitor the pH of the environment as perceived by S. Typhimurium. Results showed that activities of the lysine and ornithine decarboxylases at mild acidic pH did modify the local surrounding of S. Typhimurium both in culture medium and in macrophages. Finally, we tested the contribution of decarboxylases to virulence and found that these enzymes were dispensable for S. Typhimurium virulence during systemic infection. In the light of this result, we examined the genomes of Salmonella spp. normally responsible of systemic infection and observed that the genes encoding these enzymes were not well conserved, supporting the idea that these enzymes may be not required during systemic infection.

Sensing and adaptation to low pH mediated by inducible amino acid decarboxylases in Salmonella.

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Julie P M Viala

Full Text Available During the course of infection, Salmonella enterica serovar Typhimurium must successively survive the harsh acid stress of the stomach and multiply into a mild acidic compartment within macrophages. Inducible amino acid decarboxylases are known to promote adaptation to acidic environments. Three low pH inducible amino acid decarboxylases were annotated in the genome of S. Typhimurium, AdiA, CadA and SpeF, which are specific for arginine, lysine and ornithine, respectively. In this study, we characterized and compared the contributions of those enzymes in response to acidic challenges. Individual mutants as well as a strain deleted for the three genes were tested for their ability (i to survive an extreme acid shock, (ii to grow at mild acidic pH and (iii to infect the mouse animal model. We showed that the lysine decarboxylase CadA had the broadest range of activity since it both had the capacity to promote survival at pH 2.3 and growth at pH 4.5. The arginine decarboxylase AdiA was the most performant in protecting S. Typhimurium from a shock at pH 2.3 and the ornithine decarboxylase SpeF conferred the best growth advantage under anaerobiosis conditions at pH 4.5. We developed a GFP-based gene reporter to monitor the pH of the environment as perceived by S. Typhimurium. Results showed that activities of the lysine and ornithine decarboxylases at mild acidic pH did modify the local surrounding of S. Typhimurium both in culture medium and in macrophages. Finally, we tested the contribution of decarboxylases to virulence and found that these enzymes were dispensable for S. Typhimurium virulence during systemic infection. In the light of this result, we examined the genomes of Salmonella spp. normally responsible of systemic infection and observed that the genes encoding these enzymes were not well conserved, supporting the idea that these enzymes may be not required during systemic infection.

Recent Progress in Electrochemical Biosensors for Glycoproteins

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Uichi Akiba

2016-12-01

Full Text Available This review provides an overview of recent progress in the development of electrochemical biosensors for glycoproteins. Electrochemical glycoprotein sensors are constructed by combining metal and carbon electrodes with glycoprotein-selective binding elements including antibodies, lectin, phenylboronic acid and molecularly imprinted polymers. A recent trend in the preparation of glycoprotein sensors is the successful use of nanomaterials such as graphene, carbon nanotube, and metal nanoparticles. These nanomaterials are extremely useful for improving the sensitivity of glycoprotein sensors. This review focuses mainly on the protocols for the preparation of glycoprotein sensors and the materials used. Recent improvements in glycoprotein sensors are discussed by grouping the sensors into several categories based on the materials used as recognition elements.

Human intestinal P-glycoprotein activity estimated by the model substrate digoxin

DEFF Research Database (Denmark)

Larsen, U L; Hyldahl Olesen, L; Nyvold, Charlotte Guldborg

2007-01-01

P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (MDR...

Suberoyl bis-hydroxamic acid induces p53-dependent apoptosis of MCF-7 breast cancer cells

Institute of Scientific and Technical Information of China (English)

Zhi-gang ZHUANG; Fei FEI; Ying CHEN; Wei JIN

2008-01-01

Aim: To study the effects of suberoyl bis-hydroxamic acid (SBHA), an inhibitor of histone deacetylases, on the apoptosis of MCF-7 breast cancer cells. Meth-ods: Apoptosis in MCF-7 cells induced by SBHA was demonstrated by flow cytometric analysis, morphological observation, and DNA ladder. Mitochondrial membrane potential (△ψm) was measured using the fluorescent probe JC-1. The expressions of p53, p21, Bax, and PUMA were determined using RT-PCR or Western blotting analysis after the MCF-7 cells were treated with SBHA or p53 siRNA. Results: SBHA induced apoptosis in MCF-7 cells. The expressions of p53, p21, Bax, and PUMA were induced, and △ψm collapsed after treatment with SBHA. p53 siRNA abrogated the SBHA-induced apoptosis and the expressions of p53, p21, Bax, and PUMA. Conclusion: The activation of the p53 pathway is involved in SBHA-induced apoptosis in MCF-7 cells.

Intercellular transfer of P-glycoprotein from the drug resistant human bladder cancer cell line BIU-87 does not require cell-to-cell contact.

Science.gov (United States)

Zhou, Hui-liang; Zheng, Yong-jun; Cheng, Xiao-zhi; Lv, Yi-song; Gao, Rui; Mao, Hou-ping; Chen, Qin

2013-09-01

The efflux activity of transmembrane P-glycoprotein prevents various therapeutic drugs from reaching lethal concentrations in cancer cells, resulting in multidrug resistance. We investigated whether drug resistant bladder cancer cells could transfer functional P-glycoprotein to sensitive parental cells. Drug sensitive BIU-87 bladder cancer cells were co-cultured for 48 hours with BIU-87/ADM, a doxorubicin resistant derivative of the same cell line, in a Transwell® system that prevented cell-to-cell contact. The presence of P-glycoprotein in recipient cell membranes was established using fluorescein isothiocyanate, laser scanning confocal microscopy and Western blot. P-glycoprotein mRNA levels were compared between cell types. Rhodamine 123 efflux assay was done to confirm that P-glycoprotein was biologically active. The amount of P-glycoprotein protein in BIU-87 cells co-cultured with BIU-87/ADM was significantly higher than in BIU-87 cells (0.44 vs 0.25) and BIU-87/H33342 cells (0.44 vs 0.26, each p transfer. P-glycoprotein mRNA expression was significantly higher in BIU-87/ADM cells than in co-cultured BIU-87 cells (1.28 vs 0.30), BIU-87/H33342 (0.28) and BIU-87 cells (0.25, each p <0.001), ruling out a genetic mechanism. After 30 minutes of efflux, rhodamine 123 fluorescence intensity was significantly lower in BIU-87/ADM cells (5.55 vs 51.45, p = 0.004) and co-cultured BIU-87 cells than in BIU-87 cells (14.22 vs 51.45, p <0.001), indicating that P-glycoprotein was functional. Bladder cancer cells can acquire functional P-glycoprotein through a nongenetic mechanism that does not require direct cell contact. This mechanism is consistent with a microparticle mediated process. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A glycoprotein with anti-inflammatory properties secreted by an Aspergillus nidulans modified strain

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J. C. F. Queiroz

2007-01-01

Full Text Available Total RNA from lipopolysaccharide (LPS-stimulated rat macrophages used to treat protoplasts from an Aspergillus nidulans strain originated the RT2 regenerated strain, whose culture supernatant showed anti-inflammatory activity in Wistar rats. The protein fraction presenting such anti-inflammatory activity was purified and biochemically identified. The screening of the fraction responsible for such anti-inflammatory property was performed by evaluating the inhibition of carrageenan-induced paw edema in male Swiss mice. Biochemical analyses of the anti-inflammatory protein used chromatography, carbohydrates quantification of the protein sample, amino acids content analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Total sugar quantification revealed 32% glycosylation of the protein fraction. Amino acid analysis of such fraction showed a peculiar pattern presenting 29% valine. SDS-PAGE revealed that the protein sample is pure and its molecular weight is about 40kDa. Intravenous injection of the isolated substance into mice significantly inhibited carrageenan-induced paw edema. The isolated glycoprotein decreased carrageenan-induced paw edema in a prostaglandin-dependent phase, suggesting an inhibitory effect of the isolated glycoprotein on prostaglandin synthesis.

Sulfonation of cPTFE Film grafted Styrene for Proton Exchange Membrane Fuel Cell

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Yohan Yohan

2010-10-01

Full Text Available Sulfonation of γ-ray iradiated and styrene-grafted crosslinked polytetrafluoroethylene film (cPTFE-g-S film have been done. The aim of the research is to make hydropyl membrane as proton exchange membrane fuel cell. Sulfonation was prepared with chlorosulfonic acid in chloroethane under various conditions. The impact of the percent of grafting, the concentration of chlorosulfonic acid, the reaction time,and the reaction temperature on the properties of sulfonated film is examinated. The results show that sulfonation of surface-grafted films is incomplete at room  temperature. The increasing of concentration of chlorosulfonic acid and reaction temperature accelerates the reaction but they also add favor side reactions. These will lead to decreasing of the ion-exchange capacity, water uptake, and proton conductivity but increasing the resistance to oxidation in a perhidrol solution. The cPTFE-g-SS membrane which is resulted has stability in a H2O2 30% solution for 20 hours.

Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model

DEFF Research Database (Denmark)

Andersson, O.; Badisco, L.; Hansen, A. H.

2014-01-01

In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain b...... has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery.......In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain...

Proton-conducting membranes based on benzimidazole-containing sulfonated poly(ether ether ketone) compared with their carboxyl acid form

Energy Technology Data Exchange (ETDEWEB)

Li, Hongtao; Wu, Jing; Zhao, Chengji; Zhang, Gang; Zhang, Yang; Shao, Ke; Xu, Dan; Lin, Haidan; Han, Miaomiao; Na, Hui [Alan G MacDiarmid Institute, College of Chemistry, Jilin University, Changchun 130012 (China)

2009-10-15

A series of sulfonated poly(ether ether ketone) containing pendant carboxyl (C-SPEEKs) have been synthesized using a nucleophilic polycondesation reaction. A condensation reaction between 1,2-diaminobenzene and carboxyl resulted in a new series of copolymers containing benzimidazole groups (SPEEK-BIms). The expected structures of the sulfonated copolymers are confirmed by {sup 1}H NMR. The dependence of ion exchange capacity, water uptake, proton conductivity and methanol diffusion coefficient of SPEEK-BIm membranes has been studied and compared with their carboxyl acid form. The results suggest that the introduction of benzimidazole groups may be responsible for many excellent properties of the membranes for fuel cell. It is noticeable that the markedly improved oxidative stability is benefit for the application of membrane. (author)

Visible light driven photocatalytic degradation of methylene blue using novel camphor sulfonic acid doped polycarbazole/g-C3N4 nanocomposite

Science.gov (United States)

Praveena, P.; Dhanavel, S.; Sangamithirai, D.; Narayanan, V.; Stephen, A.

2018-04-01

A novel polycabazole(PCz)/graphitic carbon nitride(g-C3N4) nanocomposite was synthesized via chemical oxidative polymerization method. In the present work, camphor sulfonic acid (CSA) was used as a dopantand ammonium peroxydisulphate (APS) was used as an oxidizing agent. The PCz/g-C3N4 nanocompositewas characterizedusing X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and UV-Visible spectroscopy (UV-Vis). The obtained results confirm the successful formation of PCz/g-C3N4 nanocomposite. Visible light induced photocatalytic activity of the novel catalyst was demonstrated using methylene blue as a target pollutant. The results suggestthat PCz/g-C3N4 nanocomposite can be used as an effective catalyst for the degradation of organic pollutants from waste water.

Theoretical stusy of the reaction between 2,2',4' - trihydroxyazobenzene-5-sulfonic acid and zirconium

Science.gov (United States)

Fletcher, Mary H.

1960-01-01

Zirconium reacts with 2,2',4'-trihydroxyazobenzene-5-sulfonic acid in acid solutions to Form two complexes in which the ratios of dye to zirconium are 1 to 1 and 2 to 1. Both complexes are true chelates, with zirconium acting as a bridge between the two orthohydroxy dye groups. Apparent equilibrium constants for the reactions to form each of the complexes are determined. The reactions are used as a basis for the determination of the active component in the dye and a graphical method for the determination of reagent purity is described. Four absorption spectra covering the wave length region from 350 to 750 mu are given, which completely define the color system associated with the reactions in solutions where the hydrochloric acid concentration ranges from 0.0064N to about 7N.

Poly(vinylbenzyl sulfonic acid)-grafted poly(ether ether ketone) membranes

Energy Technology Data Exchange (ETDEWEB)

Hwang, Mi-Lim; Choi, Jisun; Woo, Hyun-Su; Kumar, Vinod; Sohn, Joon-Yong; Shin, Junhwa, E-mail: shinj@kaeri.re.kr

2014-02-15

Highlights: • PEEK-g-PVBSA, a polymer electrolyte membrane was prepared by a radiation grafting technique. • Poly(ether ether ketone) (PEEK), an aromatic hydrocarbon polymer was used as a grafting backbone film. • The water uptake, proton conductivity, and methanol permeability of the membranes were evaluated. • PEEK-g-PVBSA membranes show considerably lower methanol permeability compared to a Nafion membrane. -- Abstract: In this study, an aromatic hydrocarbon based polymer electrolyte membrane, poly(vinylbenzyl sulfonic acid)-grafted poly(ether ether ketone) (PEEK-g-PVBSA), has been prepared by the simultaneous irradiation grafting of vinylbenzyl chloride (VBC) monomer onto a PEEK film and subsequent sulfonation. Each chemical conversion was monitored by FT-IR and SEM–EDX instruments. The physicochemical properties including IEC, water uptake, proton conductivity, and methanol permeability of the prepared membranes were also investigated and found that the values of these properties increase with the increase of degree of grafting. It was observed that the IEC values of the prepared PEEK-g-PVBSA membranes with 32%, 58%, and 80% DOG values were 0.50, 1.05, and 1.22 meq/g while the water uptakes were 14%, 20%, and 21%, respectively. The proton conductivities (0.0272–0.0721 S/cm at 70 °C) were found to be somewhat lower than Nafion 212 (0.126 S/cm at 70 °C) at a relative humidity of 90%. However, the prepared membranes showed a considerably lower methanol permeability (0.61–1.92 × 10{sup −7} cm{sup 2}/s) compared to a Nafion 212 membrane (5.37 × 10{sup −7} cm{sup 2}/s)

Synthesis and Characterization of Sulfonated Graphene Oxide Reinforced Sulfonated Poly (Ether Ether Ketone (SPEEK Composites for Proton Exchange Membrane Materials

Directory of Open Access Journals (Sweden)

Ning Cao

2018-03-01

Full Text Available As a clean energy utilization device, full cell is gaining more and more attention. Proton exchange membrane (PEM is a key component of the full cell. The commercial-sulfonated, tetrafluoroethylene-based fluoropolymer-copolymer (Nafion membrane exhibits excellent proton conductivity under a fully humidified environment. However, it also has some disadvantages in practice, such as high fuel permeability, a complex synthesis process, and high cost. To overcome these disadvantages, a low-cost and novel membrane was developed. The sulfonated poly (ether ether ketone (SPEEK was selected as the base material of the proton exchange membrane. Sulfonated graphene (SG was cross-linked with SPEEK through the elimination reaction of hydrogen bonds. It was found that the sulfonic acid groups and hydrophilic oxygen groups increased obviously in the resultant membrane. Compared with the pure SPEEK membrane, the SG-reinforced membrane exhibited better proton conductivity and methanol permeability prevention. The results indicate that the SG/SPEEK could be applied as a new proton exchange membrane in fuel cells.

Characterization of carbohydrates using highly fluorescent 2-aminobenzoic acid tag following gel electrophoresis of glycoproteins.

Science.gov (United States)

Anumula, K R; Du, P

1999-11-15

Application of the most sensitive fluorescent label 2-aminobenzoic acid (anthranilic acid, AA) for characterization of carbohydrates from the glycoproteins ( approximately 15 pmol) separated by polyacrylamide gel electrophoresis is described. AA label is used for the determination of both monosaccharide composition and oligosaccharide map. For the monosaccharide determination, bands containing the glycoprotein of interest are excised from the polyvinylidene fluoride (PVDF) membrane blots, hydrolyzed in 20% trifluoroacetic acid, derivatized, and analyzed by C-18 reversed-phase high-performance liquid chromatography. For the oligosaccharide mapping, bands were digested with peptide N-glycosidase F (PNGase F) in order to release the N-linked oligosaccharides, derivatized, and analyzed by normal-phase anion-exchange chromatography. For convenience, the PNGase F digestion was performed in 1:100 diluted ammonium hydroxide overnight. The oligosaccharide yield from ammonium hydroxide-PNGase F digestion was better or equal to all the other reported procedures, and the presumed "oligosaccharide-amine" product formed in the reaction mixture did not interfere with labeling of the oligosaccharides under the conditions used for derivatization. Sequencing of oligosaccharides can be performed using the same mapping method following treatment with an array of glycosidases. In addition, the mapping method is useful for determining the relative and simultaneous distribution of sialic acid and fucose. Copyright 1999 Academic Press.

The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression

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Gao W

2014-07-01

Full Text Available Wei Gao,1 Zhiqiang Lin,1 Meiwan Chen,2 Xiucong Yang,1 Zheng Cui,1 Xiaofei Zhang,1 Lan Yuan,3 Qiang Zhang11State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 3Medical and Healthy Analytical Center, Peking University, Beijing, People's Republic of China Introduction: P-glycoprotein (P-gp inhibitors are usually used to treat tumors that overexpress P-gps. However, most common types of breast cancers, such as Luminal A, are low-P-gp expressing, at least during the initial phases of treatment. Therefore, it would be interesting to know if P-gp inhibitors are still useful in treating low-P-gp-expressing tumors. Methods: In the study reported here, the human breast-cancer cell line MCF-7, chosen as a model of Luminal A, was found to be low-P-gp expressing. We designed a novel doxorubicin (DOX sterically stabilized liposome system co-loaded with the low-dose P-gp inhibitor cyclosporine A (CsA (DOX/CsA/SSL. Results: The co-delivery system showed good size uniformity, high encapsulation efficiency, and a desirable release profile. The cell-uptake and cytotoxicity studies demonstrated that CsA could significantly enhance the intracellular accumulation and toxicity of free DOX and the liposomal DOX in MCF-7 cells. The confocal microscopy and in vivo imaging study confirmed the intracellular and in vivo targeting effect of DOX/CsA/SSL, respectively. Finally, the in vivo study proved that DOX/CsA/SSL could achieve significantly better antitumor effect against MCF-7 tumor than controls, without inducing obvious systemic toxicity. Conclusion: This study demonstrated that the co-delivery of a low-dose P-gp inhibitor and liposomal DOX could improve the therapy of low-P-gp-expressing cancer, which is of significance in clinical tumor therapy. Keywords: liposomes, low-P

The acidic pH-induced structural changes in apo-CP43 by spectral methodologies and molecular dynamics simulations

Science.gov (United States)

Wang, Wang; Li, Xue; Wang, Qiuying; Zhu, Xixi; Zhang, Qingyan; Du, Linfang

2018-01-01

CP43 is closely associated with the photosystem II and exists the plant thylakoid membranes. The acidic pH-induced structural changes had been investigated by fluorescence spectrum, ANS spectrum, RLS spectrum, energy transfer experiment, acrylamide fluorescence quenching assay and MD simulation. The fluorescence spectrum indicated that the structural changes in acidic pH-induced process were a four-state model, which was nature state (N), partial unfolding state (PU), refolding state (R), and molten-globule state (M), respectively. Analysis of ANS spectrum illustrated that inner hydrophobic core exposed partially to surface below pH 2.0 and inferred also that the molten-globule state existed. The RLS spectrum showed the aggregation of apo-CP43 around the pI (pH 4.5-4.0). The alterations of apo-CP43 secondary structure with different acidic treatments were confirmed by FTIR spectrum. The energy transfer experiment and quenching research demonstrated structural change at pH 4.0 was loosest. The RMSF suggested two terminals played an important function in acidic denaturation process. The distance of two terminals shown slight difference in acidic pH-induced process during the unfolding process, both N-terminal and C-terminal occupied the dominant role. However, the N-terminal accounted for the main part in the refolding process. All kinds of SASA values corresponded to spectral results. The tertiary and secondary structure by MD simulation indicated that the part transmembrane α-helix was destroyed at low pH.

Liquid chromatography-tandem mass spectrometry analysis of perfluorooctane sulfonate and perfluorooctanoic Acid in fish fillet samples.

Science.gov (United States)

Paiano, Viviana; Fattore, Elena; Carrà, Andrea; Generoso, Caterina; Fanelli, Roberto; Bagnati, Renzo

2012-01-01

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic (PFOA) acid are persistent contaminants which can be found in environmental and biological samples. A new and fast analytical method is described here for the analysis of these compounds in the edible part of fish samples. The method uses a simple liquid extraction by sonication, followed by a direct determination using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The linearity of the instrumental response was good, with average regression coefficients of 0.9971 and 0.9979 for PFOS and PFOA, respectively, and the coefficients of variation (CV) of the method ranged from 8% to 20%. Limits of detection (LOD) were 0.04 ng/g for both the analytes and recoveries were 90% for PFOS and 76% for PFOA. The method was applied to samples of homogenized fillets of wild and farmed fish from the Mediterranean Sea. Most of the samples showed little or no contamination by perfluorooctane sulfonate and perfluorooctanoic acid, and the highest concentrations detected among the fish species analyzed were, respectively, 5.96 ng/g and 1.89 ng/g. The developed analytical methodology can be used as a tool to monitor and to assess human exposure to perfluorinated compounds through sea food consumption.

Liquid Chromatography-Tandem Mass Spectrometry Analysis of Perfluorooctane Sulfonate and Perfluorooctanoic Acid in Fish Fillet Samples

Directory of Open Access Journals (Sweden)

Viviana Paiano

2012-01-01

Full Text Available Perfluorooctane sulfonate (PFOS and perfluorooctanoic (PFOA acid are persistent contaminants which can be found in environmental and biological samples. A new and fast analytical method is described here for the analysis of these compounds in the edible part of fish samples. The method uses a simple liquid extraction by sonication, followed by a direct determination using liquid chromatography-tandem mass spectrometry (LC-MS/MS. The linearity of the instrumental response was good, with average regression coefficients of 0.9971 and 0.9979 for PFOS and PFOA, respectively, and the coefficients of variation (CV of the method ranged from 8% to 20%. Limits of detection (LOD were 0.04 ng/g for both the analytes and recoveries were 90% for PFOS and 76% for PFOA. The method was applied to samples of homogenized fillets of wild and farmed fish from the Mediterranean Sea. Most of the samples showed little or no contamination by perfluorooctane sulfonate and perfluorooctanoic acid, and the highest concentrations detected among the fish species analyzed were, respectively, 5.96 ng/g and 1.89 ng/g. The developed analytical methodology can be used as a tool to monitor and to assess human exposure to perfluorinated compounds through sea food consumption.

Synthesis and characterization of sulfonated polyesters derived from glycerol; Sintese e caracterizacao de poliesteres sulfonados obtidos a partir do glicerol

Energy Technology Data Exchange (ETDEWEB)

Fiuza, R.A.; Jose, N.M.; Boaventura, J.S. [Universidade Federal da Bahia (IQ/UFBA), Salvador, BA (Brazil). Inst. de Quimica; Fiuza, R.P. [Universidade Federal da Bahia (EP/UFBA), Salvador, BA (Brazil). Escola Politecnica. Curso de Mestrado em Engenharia Quimica

2010-07-01

In this work were synthesized polyesters from glycerol and acid sulfonated phthalic previously. The materials were characterized by DSC, TGA, FTIR, SEM, XRD and XRF. The results showed effective sulfonation of phthalic acid. The presence of sulfonic groups promoted strong changes in the crystallinity of the new material makes the lens. The polyesters made from phthalic acid sulfonated combine characteristics such as heat resistance and groups that drivers potentiate the electrolyte for application in fuel cells proton exchange membrane and also for gas separation. (author)

Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion

International Nuclear Information System (INIS)

Petit, Chad M.; Melancon, Jeffrey M.; Chouljenko, Vladimir N.; Colgrove, Robin; Farzan, Michael; Knipe, David M.; Kousoulas, K.G.

2005-01-01

The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion

Particle size effects of sulfonated graphene supported Pt nanoparticles on ethanol electrooxidation

International Nuclear Information System (INIS)

Sun, Chia-Liang; Tang, Jui-Shiang; Brazeau, Nicolas; Wu, Jhing-Jhou; Ntais, Spyridon; Yin, Chung-Wei; Chou, Hung-Lung; Baranova, Elena A.

2015-01-01

Highlights: • Pt colloidal nanoparticles with five mean diameters are synthesized. • Size-selected Pt nanoparticles are loaded on sulfonated graphene (sG). • Sulfonic acid functional groups atop graphene donate charge to Pt. • Pt-sG catalysts are used for ethanol oxidation reaction (EOR). • Pt-sG(2.5 nm) has the highest peak current density in EOR. - Abstract: Fuel cells are promising alternative in automobile and stationary power generation. Direct ethanol fuel cells (DEFCs) offer significant advantages due to the non-toxicity and renewability of ethanol as well as its high power density. Development of the efficient catalysts for ethanol oxidation reaction (EOR) has attracted great attention and represents one of the major challenges in electrocatalysis. Graphene, one-atom thick nanocarbon materials, has attracted much attention recently in a variety of applications. The sulfonation of graphene is able to make it hydrophilic, which enhances its dispersibility in aqueous solvents. Furthermore, sulfonation increases the adsorption and uniform distribution of the Pt nanoparticles, which increases both the electrocatalytic activity and the durability. In this study, theoretical calculations demonstrated that the sulfonate functional group can donate charge to Pt, enhanced the adsorption energy of Pt, and then reduce the adsorption energy of CO on Pt. Then experimentally five kinds of Pt/sulfonated-graphene (Pt/sG) catalysts were synthesized via the control of pH values during the preparation of five-selected colloidal nanoparticles. Among all catalysts, Pt-sG(2.5 nm) has the highest peak current density in EOR

Targeting P-selectin glycoprotein ligand-1/P-selectin interactions as a novel therapy for metabolic syndrome.

Science.gov (United States)

Patel, Madhukar S; Miranda-Nieves, David; Chen, Jiaxuan; Haller, Carolyn A; Chaikof, Elliot L

2017-05-01

Obesity-induced insulin resistance and metabolic syndrome continue to pose an important public health challenge worldwide as they significantly increase the risk of type 2 diabetes and atherosclerotic cardiovascular disease. Advances in the pathophysiologic understanding of this process has identified that chronic inflammation plays a pivotal role. In this regard, given that both animal models and human studies have demonstrated that the interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin is not only critical for normal immune response but also is upregulated in the setting of metabolic syndrome, PSGL-1/P-selectin interactions provide a novel target for preventing and treating resultant disease. Current approaches of interfering with PSGL-1/P-selectin interactions include targeted antibodies, recombinant immunoglobulins that competitively bind P-selectin, and synthetic molecular therapies. Experimental models as well as clinical trials assessing the role of these modalities in a variety of diseases have continued to contribute to the understanding of PSGL-1/P-selectin interactions and have demonstrated the difficulty in creating clinically relevant therapeutics. Most recently, however, computational simulations have further enhanced our understanding of the structural features of PSGL-1 and related glycomimetics, which are responsible for high-affinity selectin interactions. Leveraging these insights for the design of next generation agents has thus led to development of a promising synthetic method for generating PSGL-1 glycosulfopeptide mimetics for the treatment of metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters

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Fun-In Wang

2015-06-01

Full Text Available Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on viral pathogenicity in cells in culture and in animal hosts. E2 is the most important structural protein as it interacts with cell surface receptors that determine cell tropism and induces neutralizing antibody and cytotoxic T-lymphocyte responses. All three glycoproteins are involved in virus attachment and entry into target cells. E1-E2 heterodimers are essential for viral entry and infectivity. Erns is unique because it possesses intrinsic ribonuclease (RNase activity that can inhibit the production of type I interferons and assist in the development of persistent infections. These glycoproteins are localized to the virion surface; however, variations in amino acids and antigenic structures, disulfide bond formation, glycosylation, and RNase activity can ultimately affect the virulence of pestiviruses in animals. Along with mutations that are driven by selection pressure, antigenic differences in glycoproteins influence the efficacy of vaccines and determine the appropriateness of the vaccines that are currently being used in the field.

Sulfonic-based precursors (SAPs for silica mesostructures: Advances in synthesis and applications

Directory of Open Access Journals (Sweden)

Sadegh Rostamnia*

2016-01-01

Full Text Available Sulfonic acid-based precursors (SAP play an important role in tailoring mesoporous silica’s and convert them to a solid acid catalyst with a Bronsted-type nature. These kinds of solid acids contribute to sustainable and green chemistry by their heterogeneous, recyclable, and high efficiency features. Therefore, knowing the properties and reactivity of SAPs can guide us to manufacture a sulfonated mesostructures compatible with reaction type and conditions. In the present review, some of the important SAPs, their reactivity and mechanism of functionalization are discussed.

Synthesis and Preclinical Evaluation of Novel PET Probes for P-Glycoprotein Function and Expression

NARCIS (Netherlands)

van Waarde, Aren; Ramakrishnan, Nisha K.; Rybczynska, Anna A.; Elsinga, Philip H.; Berardi, Francesco; de Jong, Johan R.; Kwizera, Chantal; Perrone, Roberto; Cantore, Mariangela; Sijbesma, Jurgen W. A.; Dierckx, Rudi A.; Colabufo, Nicola A.

2009-01-01

P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against xenobiotics. A P-gp substrate (7) and an inhibitor (6) were labeled with (11)C, resulting in potential tracers of P-gp function and expression. Methods: 6 and 7 were labeled using (11)CH(3)I. (11)C-verapamil was

Enchansing the Ionic Purity of Hydrophilic Channels by Blending Fully Sulfonated Graft Copolymers with PVDF Homopolymer

DEFF Research Database (Denmark)

Nielsen, Mads Møller; Ching-Ching Yang, Ami; Jankova Atanasova, Katja

2013-01-01

The influence of tuning the ionic content of membranes by blending, as opposed to varying the degree of sulfonation, is evaluated. Membranes of fully sulfonated poly(vinylidene fluoride-co-chlorotrifluoroethylene)-g-poly(styrene sulfonic acid) blended with PVDF were prepared and investigated...

Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

Science.gov (United States)

Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

2012-01-01

Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

Evaluation of sulfonated carbon as catalyst in reactive distillation

International Nuclear Information System (INIS)

Orjuela, Alvaro; Civetta, Nicolas; Rivera, Jairo; Boyaca, Alejandro; Diaz, Jesus

2004-01-01

A packed bed using sulfonated coal catalytic pellets was prepared using a Colombian anthracitic coal. Such pellets were introduced in a semi batch distillation column to which acetic acid and ethanol were fed in order to determine experimentally the feasibility of obtaining ethyl acetate by reactive distillation operation. The carbonaceous catalytic packing was characterized by total exchange capacity, potentiometric titration and BET area. Experimental tests were carried out using three acid/alcohol ratios. Results of such process are shown by reaction conversion and concentration in distillate and bottom products. The sulfonated coal showed catalytic activity in this esterification reaction, with conversions between 29-45%

Perfluorooctanoic acid and perfluorooctane sulfonate in Michigan and New York waters

Energy Technology Data Exchange (ETDEWEB)

Sinclair, E.; Kannan, K. [Wadsworth Center, Albany, NY (United States); Taniyasu, Sachi; Yamashita, Nobuyoshi [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan)

2004-09-15

Perfluorooctane sulfonate (PFOS), a perfluorinated organic contaminant, has become the subject of many recent investigations. PFOS and its precursor compounds have been used in a wide variety of consumer and industrial products. Other related perfluorinated compounds have also been reported to occur in the environment. For example, perfluorohexane sulfonate (PFHxS) is an impurity associated with PFOS. Perfluorooctanoic acid (PFOA) has found widespread use as an emulsifier for polymerization of fluoropolymers. These perfluorinated alkylated substances (PASs) are known to be resistant to degradation. Water analysis of PFOS and PFOA has been carried out with several methods. The most commonly used methods involve solid phase extraction (SPE) followed by HPLC-MS-MS. Method detection limits for PFOS and PFOA varied between 5 and 17 ng/L and 9 and 25 ng/L respectively. Generally PFOS and PFOA concentrations in ambient waters, with no point source of pollution, are less than 5 ng/L. We have developed a method using the Oasis HLB solid phase cartridge to achieve the required method detection limits. We have measured PFOS and PFOA concentration in surface waters collected from Michigan and New York. PFOS and PFOA have been detected in the blood and liver of fish at {mu}g/L concentrations both in Japan and the USA. The current ion-pairing, liquid/liquid extraction method is suitable for these concentrations and we have measured PFOS and PFOA in the livers of fish from Michigan and New York waters. We have compared the data for fish and water concentrations and calculated bioaccumulation factors.

Chondrogenesis on sulfonate-coated hydrogels is regulated by their mechanical properties.

Science.gov (United States)

Kwon, Hyuck Joon; Yasuda, Kazunori

2013-01-01

Many studies have demonstrated that sulfur-containing acidic groups induce chondrogenesis in vitro and in vivo. Recently, it is increasingly clear that mechanical properties of cell substrates largely influence cell differentiation. Thus, the present study investigated how mechanical properties of sulfonate-coated hydrogels influences chondrogenesis of mesenchymal stem cells (MSCs). Sulfonate-coated polyacrylamide gels (S-PAAm gels) which have the elastic modulus, E, of about 1, 15 and 150 kPa, were used in this study. MSCs cultured on the high stiffness S-PAAm gels (E=∼150 kPa) spread out with strong expression of stress fibers, while MSCs cultured on the low stiffness S-PAAm gels (E=∼1 kPa) had round shapes with less stress fibers but more cortical actins. Importantly, even in the absence of differentiation supplements, the lower stiffness S-PAAm gels led to the higher mRNA levels of chondrogenic markers such as Col2a1, Agc and Sox9 and the lower mRNA levels of an undifferentiation marker Sca1, indicating that the mechanical properties of S-PAAm gels strongly influence chondrogenesis. Blebbistatin which blocks myosin II-mediated mechanical sensing suppressed chondrogenesis induced by the low stiffness S-PAAm gels. The present study demonstrates that the soft S-PAAm gels effectively drive MSC chondrogenesis even in the absence of soluble differentiation factors and thus suggests that sulfonate-containing hydrogels with low stiffness could be a powerful tool for cartilage regeneration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Protein Complexation and pH Dependent Release Using Boronic Acid Containing PEG-Polypeptide Copolymers.

Science.gov (United States)

Negri, Graciela E; Deming, Timothy J

2017-01-01

New poly(L-lysine)-b-poly(ethylene glycol) copolypeptides have been prepared, where the side-chain amine groups of lysine residues are modified to contain ortho-amine substituted phenylboronic acid, i.e., Wulff-type phenylboronic acid (WBA), groups to improve their pH responsive, carbohydrate binding properties. These block copolymers form nanoscale complexes with glycosylated proteins that are stable at physiological pH, yet dissociate and release the glycoproteins under acidic conditions, similar to those found in endosomal and lysosomal compartments within cells. These results suggest that WBA modified polypeptide copolymers are promising for further development as degradable carriers for intracellular protein delivery. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Removal of emerging perfluorooctanoic acid and perfluorooctane sulfonate contaminants from lake water.

Science.gov (United States)

Pramanik, Biplob Kumar; Pramanik, Sagor Kumar; Sarker, Dipok Chandra; Suja, Fatihah

2017-08-01

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the major polyfluoroalkyl substances (PFASs) contaminating global water environment. This study investigated the efficiency of granular activated carbon (GAC), ultrafiltration (UF) and nanofiltration (NF) treatment for removing PFOS and PFOA contaminants from lake water. NF gave greater removal of all contaminant types (in terms of organic matter, PFOS and PFOA) than GAC treatment which in turn was greater than UF treatment. The lower removal by UF was due to larger pore size of the membrane compared to the size of the target contaminants. For all treatment processes, lower pH (4) in the feedwater showed greater rejection of the organics and selected PFASs. This was likely due to increase in the electrostatic repulsion between solute and sorbent. It could be observed that on increasing the concentration of organics in the feed solution, the rejection of PFOA/PFOS decreased which was due to competition between organics and PFOS/PFOA for binding sites on the membrane/activated carbon surface. It was also noted that protein content led to greater influence for lower rejection of the PFOA/PFOS than carbohydrate or DOC content. This study demonstrated the potential use of membrane processes for removing emerging persistent organic pollutant removal from lake water.

P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

DEFF Research Database (Denmark)

Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

2005-01-01

P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

Energy Technology Data Exchange (ETDEWEB)

Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

2006-03-01

In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

Ammonia transport in the kidney by Rhesus glycoproteins

Science.gov (United States)

Verlander, Jill W.

2014-01-01

Renal ammonia metabolism is a fundamental element of acid-base homeostasis, comprising a major component of both basal and physiologically altered renal net acid excretion. Over the past several years, a fundamental change in our understanding of the mechanisms of renal epithelial cell ammonia transport has occurred, replacing the previous model which was based upon diffusion equilibrium for NH3 and trapping of NH4+ with a new model in which specific and regulated transport of both NH3 and NH4+ across renal epithelial cell membranes via specific membrane proteins is required for normal ammonia metabolism. A major advance has been the recognition that members of a recently recognized transporter family, the Rhesus glycoprotein family, mediate critical roles in renal and extrarenal ammonia transport. The erythroid-specific Rhesus glycoprotein, Rh A Glycoprotein (Rhag), was the first Rhesus glycoprotein recognized as an ammonia-specific transporter. Subsequently, the nonerythroid Rh glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), were cloned and identified as ammonia transporters. They are expressed in specific cell populations and membrane domains in distal renal epithelial cells, where they facilitate ammonia secretion. In this review, we discuss the distribution of Rhbg and Rhcg in the kidney, the regulation of their expression and activity in physiological disturbances, the effects of genetic deletion on renal ammonia metabolism, and the molecular mechanisms of Rh glycoprotein-mediated ammonia transport. PMID:24647713

Luminescent hybrid lanthanide sulfates and lanthanide sulfonate-carboxylates with 1,10-phenanthroline involving in-situ oxidation of 2-mercaptonbenzoic acid

Science.gov (United States)

Zhong, Jie-Cen; Wan, Fang; Sun, Yan-Qiong; Chen, Yi-Ping

2015-01-01

A series of lanthanide sulfates and lanthanide sulfonate-carboxylates, [Ln2(phen)2(SO4)3(H2O)2]n (I:Ln=Nd(1a), Sm(1b), Eu(1c), phen=1,10-phenanthroline) and [Ln(phen)(2-SBA)(BZA)]n (II: Ln=Sm(2a), Eu(2b), Dy(2c), 2-SBA=2-sulfobenzoate, BZA=benzoate) have been hydrothermally synthesized from lanthanide oxide, 2-mercaptonbenzoic acid with phen as auxiliary ligand and characterized by single-crystal X-ray diffraction, elemental analyses, IR spectra, TG analyses and luminescence spectroscopy. Interestingly, SO4 2 - anions in I came from the in situ deep oxidation of thiol groups of 2-mercaptonbenzoic acid while 2-sulfobenzoate and benzoate ligands in II from the middle oxidation and desulfuration reactions of 2-mercaptonbenzoic acid. Compounds I are organic-inorganic hybrid lanthanide sulfates, which have rare one-dimensional column-like structures. Complexes II are binuclear lanthanide sulfonate-carboxylates with 2-sulfobenzoate and benzoate as bridges and 1,10-phenanthroline as terminal. Photoluminescence studies reveal that complexes I and II exhibit strong lanthanide characteristic emission bands in the solid state at room temperature.

The hydroxyapatite-binding regions of a rat salivary glycoprotein.

Science.gov (United States)

Embery, G; Green, D R

1989-09-01

The regions of a salivary sulphated glycoprotein which are involved in its attachment to hydroxyapatite (Biogel HTP) have been characterised. The sulphated glycoprotein, a 35S-labelled preparation from mixed palatal and buccal minor gland secretions of the rat was bound onto hydroxyapatite and the resultant glycoprotein-hydroxyapatite complex was sequentially digested with pronase E and alpha-L-fucosidase, a treatment which released 86.8% +/- 1.7% of the radioactivity of the initially bound glycoprotein. The fragments which remained attached to the hydroxyapatite after enzymic digestion were fractionated on Sephadex G-25 and analysed for carbohydrate and amino acid components. A range of amino acids were detected which could reflect both glycosylated and non-glycosylated-binding regions. Sialic acid, although considered to be involved in the attachment process was not detected in any of the fragments remaining after enzymic digestion, a finding which provides indirect evidence that the enzymically liberated products do not subsequently re-attach to the hydroxyapatite surface. The notable feature of the fractions with average Mr estimated at 1000 or less is the high proportion of N-acetylhexosamine and N-acetylgalactosamine. It is apparent that the hexosamine residues, which normally bear the ester sulphate moieties of sulphated glycoproteins, play an important role in the attachment of sulphated glycoproteins to hydroxyapatite.

Molecularly imprinted polyaniline-ferrocene-sulfonic acid-Carbon dots modified pencil graphite electrodes for chiral selective sensing of D-Ascorbic acid and L-Ascorbic acid: A clinical biomarker for preeclampsia

International Nuclear Information System (INIS)

Pandey, Indu; Jha, Shashank Shekhar

2015-01-01

Highlights: • Pencil graphite electrode was non-covalently functionalized by C-dots. • Electrochemically synthesized ferrocene-sulfonic acid doped PANI film was used as chiral recognition element. • Electrochemical chiral sensing of L-ascorbic acid and D-ascorbic acid was carried out. • L-ascorbic acid determination was done in aqueous, biological and pharmaceutical samples at nM level. - Abstract: A simple and novel method is proposed for chiral separation of L-ascorbic acid and D-ascorbic acid in human cerebrospinal fluids and blood plasma samples. Electro-polymerized molecularly imprinted poly-aniline ferrocenesulfonic acid-C-dots modified pencil graphite electrodes was successfully applied for separation and quantification of D-/L-ascorbic acid in aqueous and some biological samples. Parameters, important to control the performance of the electrochemical sensor were investigated and optimized, including the effects of pH, monomer- template ratios, electropolymerization cycles and scan rates. The molecularly imprinted film exhibited a high chiral selectivity and sensitivity towards D-ascorbic acid and L-ascorbic acid respectively. The surface morphologies and electrochemical properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry, chrono-amperometry and electrochemical impedance spectroscopy. L-ascorbic acid selective sensor shows excellent selectivity towards the L-ascorbic acid in comparison to D- ascorbic acid vice versa for D- ascorbic acid selective sensor. Under optimal conditions the linear range of the calibration curve for L- ascorbic acid and D- ascorbic acid was 6.0–165.0 nM and 6.0–155.0 nM, with the detection limit of 0.001 nM and 0.002 nM. Chiral detection of L-ascorbic acid was successfully carried out in pharmaceuticals and human plasma samples (pregnant women and non pregnant women) via proposed sensor with good selectivity and sensitivity.

Up-regulation of P-glycoprotein expression by catalase via JNK activation in HepG2 cells.

Science.gov (United States)

Li, Lin; Xu, Jianfeng; Min, Taishan; Huang, Weida

2006-01-01

Overexpression of the MDR1 gene is one of the reasons for multidrug resistance (MDR). Some studies suggested that antioxidants could down-regulate MDR1 expression as a possible cancer treatment. In this report, we try to determine the effects of antioxidants (catalase or N-acetylcysteine [NAC]) on the regulation of intrinsic MDR1 overexpression in HepG2 cells. Adding catalase or N-acetylcysteine to the HepG2 culture led to a significant increase of MDR1 mRNA and P-glycoprotein drug transporter activity. After catalase or NAC treatment, a reduced intracellular reactive oxygen species (ROS) was observed. The JNK inhibitor SP600125 abolished the positive effects of catalase on drug transporter activity in a dose-dependent manner. Furthermore, the up-regulation of P-glycoprotein functions by catalase was only observed in HepG2 cells but not in other cell lines tested (MCF-7, A549, A431). These data suggested that catalase can up-regulate P-glycoprotein expression in HepG2 cells via reducing intracellular ROS, and JNK may mediate this process.

The glycoprotein of measles virus

International Nuclear Information System (INIS)

Anttonen, O.; Jokinen, M.; Salmi, A.; Vainionpaeae, R.; Gahmberg, C.G.

1980-01-01

Measles virus was propagated in VERO cells and purified from the culture supernatants by two successive tartrate-density-gradient centrifugations. Surface carbohydrates were labelled both in vitro and in vivo with 3 H after treatment with galactose oxidase/NaB 3 H 4 or with [ 3 H]glucosamine. The major labelled glycoprotein in measles virions had a mol.wt. of 79000. After labelling with periodate/NaB 3 H 4 , which would result in specific labelling of sialic acid residues, the 79000-mol.wt. glycoprotein was very weakly labelled. This suggested that there is no or a very low amount of sialic acid in the virions. Further analysis of the glycoprotein showed that galactose is the terminal carbohydrate unit in the oligosaccharide, and the molecular weight of the glycopeptide obtained after Pronase digestion is about 3000. The oligosaccharide is attached to the polypeptide through an alkali-stable bond, indicating a N-glycosidic asparagine linkage. (author)

Enhanced antifouling and antibacterial properties of poly (ether sulfone) membrane modified through blending with sulfonated poly (aryl ether sulfone) and copper nanoparticles

Science.gov (United States)

Zhang, Jingjing; Xu, Ya'nan; Chen, Shouwen; Li, Jiansheng; Han, Weiqing; Sun, Xiuyun; Wu, Dihua; Hu, Zhaoxia; Wang, Lianjun

2018-03-01

A series of novel blend ultrafiltration (UF) membranes have been successfully prepared from commercial poly (ether sulfone), lab-synthesized sulfonated poly (aryl ether sulfone) (SPAES, 1 wt%) and copper nanoparticles (0 ∼ 0.4 wt%) via immersion precipitation phase conversion. The micro-structure and separation performance of the membranes were characterized by field emission scanning electron microscopy (SEM) and cross-flow filtration experiments, respectively. Sodium alginate, bovine serum albumin and humic acid were chosen as model organic foulants to investigate the antifouling properties, while E. coil was used to evaluate the antibacterial property of the fabricated membranes. By the incorporation with SPAES and copper nanoparticles, the hydrophilicity, antifouling and antibacterial properties of the modified UF membranes have been profoundly improved. At a copper nanoparticles content of 0.4 wt%, the PES/SPAES/nCu(0.4) membrane exhibited a high pure water flux of 193.0 kg/m2 h, reaching the smallest contact angle of 52°, highest flux recovery ratio of 79% and largest antibacterial rate of 78.9%. Furthermore, the stability of copper nanoparticles inside the membrane matrix was also considerably enhanced, the copper nanoparticles were less than 0.08 mg/L in the effluent during the whole operation.

Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

Science.gov (United States)

Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y; Löscher, Wolfgang

2014-01-01

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

Drug-Induced Trafficking of P-Glycoprotein in Human Brain Capillary Endothelial Cells as Demonstrated by Exposure to Mitomycin C

Science.gov (United States)

Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y.; Löscher, Wolfgang

2014-01-01

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

Catalytic Upgrading of bio-oil using 1-octene and 1-butanol over sulfonic acid resin catalysts

Energy Technology Data Exchange (ETDEWEB)

Zhang, Zhijun; Wang, Qingwen; Tripathi, Prabhat; Pittman, Charles U.

2011-02-04

Raw bio-oil from fast pyrolysis of biomass must be refined before it can be used as a transporation fuel, a petroleum refinery feed or for many other fuel uses. Raw bio-oil was upgraded with the neat model olefin, 1-octene, and with 1-octene/1-butanol mixtures over sulfonic acid resin catalysts frin 80 to 150 degrees celisus in order to simultaneously lower water content and acidity and to increase hydrophobicity and heating value. Phase separation and coke formation were key factors limiting the reaction rate during upgrading with neat 1-octene although octanols were formed by 1-octene hydration along with small amounts of octyl acetates and ethers. GC-MS analysis confirmed that olefin hydration, carboxylic acid esterification, acetal formation from aldehydes and ketones and O- and C-alkylations of phenolic compounds occurred simultaneously during upgrading with 1-octene/1-butanol mixtures. Addition of 1-butanol increased olefin conversion dramatically be reducing mass transfer restraints and serving as a cosolvent or emulsifying agent. It also reacted with carboxylic acids and aldehydes/ketones to form esters, and acetals, respectively, while also serving to stabilize bio-oil during heating. 1-Butanol addition also protected the catalysts, increasing catalyst lifetime and reducing or eliminationg coking. Upgrading sharply increased ester content and decreased the amounts of levoglucosan, polyhydric alcohols and organic acids. Upgrading lowered acidity (pH value rise from 2.5 to >3.0), removed the uppleasant ordor and increased hydrocarbon solubility. Water content decreased from 37.2% to < 7.5% dramatically and calorific value increased from 12.6 MJ kg to about 30.0 MJ kg.

Comparison of salicylic acid, benzoic acid and p-hydroxybenzoic acid for their ability to induce flowering in Lemna Gibba G3

International Nuclear Information System (INIS)

Cleland, F.C.; Kang, B.G.; Khurana, J.P.

1986-01-01

The long-day plant Lemna gibba G3 fails to flower under continuous light on NH 4 + -free 0.5 H medium. This inhibition is completely reversed by 10 μM salicyclic acid (SA) or 32 μM benzoic acid (BA). By contrast, p-hydroxybenzoic acid (p-OH-BA) has virtually no effect on flowering at levels as high as 320 μM. Uptake rates for the three compounds are comparable. Competition studies using 14 C-SA indicate that, compared to SA, BA is about 10-fold less effective and p-OH-BA is nearly 100-fold less effective in competing against 14 C-SA uptake. Both the effectiveness of SA for inducing flowering and the uptake of 14 C-SA are substantially increased as the pH of the medium is lowered from 8 to 4.5. Under a nitrogen atmosphere the uptake of 14 C-SA is partially inhibited above pH 5. Phosphate metabolism may be important for flowering since increasing the phosphate level in the medium 10-15 fold results in substantial flowering, and suboptimal levels of Sa and phosphate interact synergistically to stimulate flowering. The interaction of phosphate with BA and p-OH-BA will be presented

(11) C- and (18) F-Labeled Radioligands for P-Glycoprotein Imaging by Positron Emission Tomography.

NARCIS (Netherlands)

Cantore, Mariangela; Benadiba, Marcel; Elsinga, Philippus; Kwizera, Chantal; Dierckx, Rudi; Colabufo, Nicola A.; Luurtsema, Geert

2016-01-01

P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by

Mechanistic Insight into Bunyavirus-Induced Membrane Fusion from Structure-Function Analyses of the Hantavirus Envelope Glycoprotein Gc.

Directory of Open Access Journals (Sweden)

Pablo Guardado-Calvo

2016-10-01

Full Text Available Hantaviruses are zoonotic viruses transmitted to humans by persistently infected rodents, giving rise to serious outbreaks of hemorrhagic fever with renal syndrome (HFRS or of hantavirus pulmonary syndrome (HPS, depending on the virus, which are associated with high case fatality rates. There is only limited knowledge about the organization of the viral particles and in particular, about the hantavirus membrane fusion glycoprotein Gc, the function of which is essential for virus entry. We describe here the X-ray structures of Gc from Hantaan virus, the type species hantavirus and responsible for HFRS, both in its neutral pH, monomeric pre-fusion conformation, and in its acidic pH, trimeric post-fusion form. The structures confirm the prediction that Gc is a class II fusion protein, containing the characteristic β-sheet rich domains termed I, II and III as initially identified in the fusion proteins of arboviruses such as alpha- and flaviviruses. The structures also show a number of features of Gc that are distinct from arbovirus class II proteins. In particular, hantavirus Gc inserts residues from three different loops into the target membrane to drive fusion, as confirmed functionally by structure-guided mutagenesis on the HPS-inducing Andes virus, instead of having a single "fusion loop". We further show that the membrane interacting region of Gc becomes structured only at acidic pH via a set of polar and electrostatic interactions. Furthermore, the structure reveals that hantavirus Gc has an additional N-terminal "tail" that is crucial in stabilizing the post-fusion trimer, accompanying the swapping of domain III in the quaternary arrangement of the trimer as compared to the standard class II fusion proteins. The mechanistic understandings derived from these data are likely to provide a unique handle for devising treatments against these human pathogens.

A study of the effect of polystyrene sulfonation on the performance of terephthaloyl chloride-dihydroxydiphenyl sulfone copolymer/polystyrene system

Science.gov (United States)

Kahraman, R.; Kahn, K. A.; Ali, S. A.; Hamid, S. H.; Sahin, A. Z.

1998-12-01

Thermal, morphological, and mechanical properties of composites of a liquid crystalline copolymer (LCP) poly(terephthaloyl chloride)-co-(p,p’-dihydroxydiphenyl sulfone) with polystyrene (PS) and sulfonated polystyrene (SPS) are presented and discussed. Sulfonation of polystyrene was expected to improve the interfacial adhesion by introducing hydrogen bonding in the LCP/PS system. The degree of sulfonation was 11 %. The incompatibility (lack of proper interfacial adhesion) of the LCP/PS system resulted in sharp decrease in the composite tensile strength with LCP addition. The performance of the system did not change when processed at a higher temperature (270 °C instead of 225 °C). While a composite plate of 25% LCP/PS could not be fabricated, it was possible for LCP/SPS (processed at 215 °C), indicating some improvement in interfacial bonding by sulfonation. Sulfonation of PS resulted in fracture with some degree of plastic deformation for pure SPS matrix and also the LCP/SPS system with the lowest LCP content (1 wt%), whereas plastic deformation was not observed for PS used as received. The strength of the LCP/SPS system also decreased with increase in LCP content, indicating that 11% sulfonation is not sufficient to introduce significant compatibility, but it was not as dramatic as that for LCP/PS. The performance of the LCP/SPS system was not affected significantly by heat treatment at the process temperature.

Application of sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H in the green one-pot synthesis of triazoloquinazolinones and benzimidazoquinazolinones

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Ghodsi Mohammadi Ziarani

2015-01-01

Full Text Available Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H with a pore size of 6 nm was proven to be an efficient heterogeneous nanoporous solid acid catalyst in the green one-pot synthesis of triazoloquinazolinones and benzimidazoquinazolinones from the reaction of aromatic aldehydes with 3-amino-1,2,4-triazole (or 2-aminobenzimidazole and dimedone under solvent free conditions.

Preparation and Characterization of Sulfonated Poly (ether ether ...

African Journals Online (AJOL)

NJD

2007-08-10

Aug 10, 2007 ... Preparation and Characterization of Sulfonated Poly (ether ... Currently perfluori- ... with phosphoric acid solution according to the method described earlier.11,12 ... where A is the membrane area available for diffusion; CA is.

Carbon Source-Dependent Inducible Metabolism of Veratryl Alcohol and Ferulic Acid in Pseudomonas putida CSV86

Science.gov (United States)

Mohan, Karishma

2017-01-01

ABSTRACT Pseudomonas putida CSV86 degrades lignin-derived metabolic intermediates, viz., veratryl alcohol, ferulic acid, vanillin, and vanillic acid, as the sole sources of carbon and energy. Strain CSV86 also degraded lignin sulfonate. Cell respiration, enzyme activity, biotransformation, and high-pressure liquid chromatography (HPLC) analyses suggest that veratryl alcohol and ferulic acid are metabolized to vanillic acid by two distinct carbon source-dependent inducible pathways. Vanillic acid was further metabolized to protocatechuic acid and entered the central carbon pathway via the β-ketoadipate route after ortho ring cleavage. Genes encoding putative enzymes involved in the degradation were found to be present at fer, ver, and van loci. The transcriptional analysis suggests a carbon source-dependent cotranscription of these loci, substantiating the metabolic studies. Biochemical and quantitative real-time (qRT)-PCR studies revealed the presence of two distinct O-demethylases, viz., VerAB and VanAB, involved in the oxidative demethylation of veratric acid and vanillic acid, respectively. This report describes the various steps involved in metabolizing lignin-derived aromatic compounds at the biochemical level and identifies the genes involved in degrading veratric acid and the arrangement of phenylpropanoid metabolic genes as three distinct inducible transcription units/operons. This study provides insight into the bacterial degradation of lignin-derived aromatics and the potential of P. putida CSV86 as a suitable candidate for producing valuable products. IMPORTANCE Pseudomonas putida CSV86 metabolizes lignin and its metabolic intermediates as a carbon source. Strain CSV86 displays a unique property of preferential utilization of aromatics, including for phenylpropanoids over glucose. This report unravels veratryl alcohol metabolism and genes encoding veratric acid O-demethylase, hitherto unknown in pseudomonads, thereby providing new insight into the

Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein

NARCIS (Netherlands)

Mayer, U; Wagenaar, E; Beijnen, J.H; Smit, J.W; Meijer, D.K F; van Asperen, J.; Borst, P; Schinkel, A.H

1 We have used mice with a disrupted mdrla P-glycoprotein gene (mdrIa (-/-) mice) to study the role of P-glycoprotein in the pharmacokinetics of digoxin, a model P-glycoprotein substrate. 2 [K-3]-digoxin at a dose of 0.2 mg kg(-1) was administered as a single i.v. or oral bolus injection. We

Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives

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Dong Cai

2015-09-01

Full Text Available A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities.

Synthesis and properties of a novel sulfonated poly(arylene ether ketone sulfone) membrane with a high β-value for direct methanol fuel cell applications

International Nuclear Information System (INIS)

Xu, Jingmei; Ma, Li; Han, Hailan; Ni, Hongzhe; Wang, Zhe; Zhang, Huixuan

2014-01-01

Highlights: • Introduction of carboxyl groups into copolymers resulted in extensive hydrogen bond. • The C-SPAEKS membranes had obviously hydrophilic/hydrophobic phase separation. • The membranes showed low methanol permeability and high β values. • The membranes exhibited good thermal property and desirable mechanical performance. - Abstract: Sulfonated poly(arylene ether ketone sulfone) membranes containing carboxylic acid groups (C-SPAEKS) with different degrees of sulfonation were synthesized by the nucleophilic aromatic substitution reactions of 4-carboxylphenyl hydroquinone (4C-PH), bisphenol A, 3,3′-disulfonated 4,4′-dichlorodiphenyl sulfone, and 4,4′-difluorobenzophenone. The Fourier transform infrared and 1 H NMR analyses of C-SPAEKS revealed the presence of carboxylic acid groups in the C-SPAEKS membranes. The membranes exhibited a low swelling degree and methanol crossover level. The effects of different degrees of sulfonation on the water uptake, proton conductivity, and methanol permeability coefficient of the membranes were studied. The maximum proton conductivity of C-SPAEKS-80 membrane at room temperature was 0.069 S cm −1 , which was higher than that of Nafion ® 117 membrane. The methanol permeability coefficient of C-SPAEKS-80 membrane was 9.15 × 10 −7 cm 2 s −1 at 20 °C, much lower than that of Nafion 117 membrane (22.9 × 10 −7 cm 2 s −1 ). Furthermore, the carboxyl group-containing membranes exhibited a high β-value, further confirming that this series of membranes possess excellent comprehensive performance and can be applied in direct methanol fuel cells

Importance of the short cytoplasmic domain of the feline immunodeficiency virus transmembrane glycoprotein for fusion activity and envelope glycoprotein incorporation into virions

International Nuclear Information System (INIS)

Celma, Cristina C.P.; Paladino, Monica G.; Gonzalez, Silvia A.; Affranchino, Jose L.

2007-01-01

The mature form of the envelope (Env) glycoprotein of lentiviruses is a heterodimer composed of the surface (SU) and transmembrane (TM) subunits. Feline immunodeficiency virus (FIV) possesses a TM glycoprotein with a cytoplasmic tail of approximately 53 amino acids which is unusually short compared with that of the other lentiviral glycoproteins (more than 100 residues). To investigate the relevance of the FIV TM cytoplasmic domain to Env-mediated viral functions, we characterized the biological properties of a series of Env glycoproteins progressively shortened from the carboxyl terminus. All the mutant Env proteins were efficiently expressed in feline cells and processed into the SU and TM subunits. Deletion of 5 or 11 amino acids from the TM C-terminus did not significantly affect Env surface expression, fusogenic activity or Env incorporation into virions, whereas removal of 17 or 23 residues impaired Env-mediated cell-to-cell fusion. Further truncation of the FIV TM by 29 residues resulted in an Env glycoprotein that was poorly expressed at the cell surface, exhibited only 20% of the wild-type Env fusogenic capacity and was inefficiently incorporated into virions. Remarkably, deletion of the TM C-terminal 35 or 41 amino acids restored or even enhanced Env biological functions. Indeed, these mutant Env glycoproteins bearing cytoplasmic domains of 18 or 12 amino acids were found to be significantly more fusogenic than the wild-type Env and were efficiently incorporated into virions. Interestingly, truncation of the TM cytoplasmic domain to only 6 amino acids did not affect Env incorporation into virions but abrogated Env fusogenicity. Finally, removal of the entire TM cytoplasmic tail or deletion of as many as 6 amino acids into the membrane-spanning domain led to a complete loss of Env functions. Our results demonstrate that despite its relatively short length, the FIV TM cytoplasmic domain plays an important role in modulating Env-mediated viral functions

An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

International Nuclear Information System (INIS)

Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

2009-01-01

Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

Energy Technology Data Exchange (ETDEWEB)

Tiwari, Vaibhav [Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766 (United States); Darmani, Nissar A.; Thrush, Gerald R. [Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766 (United States); Shukla, Deepak, E-mail: dshukla@uic.edu [Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States)

2009-12-18

Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

pH-jump induced α-helix folding of poly-L-glutamic acid

International Nuclear Information System (INIS)

Donten, Mateusz L.; Hamm, Peter

2013-01-01

Highlights: ► pH-jump as truly biomimetic tool to initiate non-equilibrium dynamics of biomolecules. ► Design criteria to widen the applicability of pH-jumps are developed. ► Folding of poly-L-Glu in dependence of starting pH, pH jump size and helix length. ► Length dependence provides strong evidence for a nucleation–propagation scenario. - Abstract: pH jumps are a truly biomimetic technique to initiate non-equilibrium dynamics of biomolecules. In this work, the pH jump induced α-helix folding of poly-L-glutamic acid is investigated upon proton release from o-nitrobenzaldehyde. The aim of this work is twofold: On the one hand, design criteria of pH jump experiments are discussed, on the other hand, the folding mechanism of poly-L-glutamic acid is clarified by probing the IR response of the amide I band. Its folding kinetics is studied in dependence of the starting pD, the size of the pD jump and the length of the helix. While no dependence on the first two parameters could be detected, the folding time varies from 0.6 μs to 1.8 μs for helix lengths of 20 residue to 440 residue, respectively. It converges to a long-length limit at about 50 residue, a result which is attributed to a nucleation–propagation mechanism

A novel isoindoline, porritoxin sulfonic acid, from Alternaria porri and the structure-phytotoxicity correlation of its related compounds.

Science.gov (United States)

Horiuchi, Masayuki; Ohnishi, Keiichiro; Iwase, Noriyasu; Nakajima, Yoshikazu; Tounai, Kenji; Yamashita, Masakazu; Yamada, Yasumasa

2003-07-01

Novel zinniol-related compound 3, named porritoxin sulfonic acid, with an isoindoline skeleton was isolated from the culture liquid of Alternaria porri. The structure was determined to be 2-(2"-sulfoethyl)-4-methoxy-5-methyl-6-(3'-methyl-2'-butenyloxy)-2,3-dihydro-1H-isoindol-1-one. The phytotoxic activities of three isoindolines (1-3) were evaluated in a seedling-growth assay against stone leek and lettuce.

Adsorption Mechanisms of Dodecylbenzene Sulfonic Acid by Corn Straw and Poplar Leaf Biochars.

Science.gov (United States)

Zhao, Nan; Yang, Xixiang; Zhang, Jing; Zhu, Ling; Lv, Yizhong

2017-09-22

Biochar is an eco-friendly, renewable, and cost-effective material that can be used as an adsorbent for the remediation of contaminated environments. In this paper, two types of biochar were prepared through corn straw and poplar leaf pyrolysis at 300 °C and 700 °C (C300, C700, P300, P700). Brunaer-Emmett-Teller N₂ surface area, scanning electron microscope, elemental analysis, and infrared spectra were used to characterize their structures. These biochars were then used as adsorbents for the adsorption of dodecylbenzene sulfonic acid (DBSA). The microscopic adsorption mechanisms were studied by using infrared spectra, 13 C-nuclear magnetic resonance spectra, and electron spin resonance spectra. The surface area and pore volume of C700 (375.89 m²/g and 0.2302 cm³/g) were the highest among all samples. Elemental analysis results showed that corn straw biochars had a higher aromaticity and carbon to nitrogen (C/N) ratio than the poplar leaf biochars. High temperature caused the increase of carbon content and the decrease of oxygen content, which also gave the biochars a higher adsorption rate. Pseudo-second order kinetic provided a better fit with the experimental data. Adsorption isotherm experiments showed that the adsorption isotherm of C300 fit the linear model. For other biochars, the adsorption isotherms fitted Langmuir model. Biochars with high temperatures exhibited enhanced adsorption capacity compared with ones at low temperatures. The q max values of biochars to DBSA followed the order of P700 > C700 > P300. The adsorption mechanisms were complex, including partition, anion exchange, the formation of H bonds, covalent bonds, and charge transfer. The adsorption by covalent bonding might be the key mechanism determining the adsorption capacity of P700.

Adsorption Mechanisms of Dodecylbenzene Sulfonic Acid by Corn Straw and Poplar Leaf Biochars

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Nan Zhao

2017-09-01

Full Text Available Biochar is an eco-friendly, renewable, and cost-effective material that can be used as an adsorbent for the remediation of contaminated environments. In this paper, two types of biochar were prepared through corn straw and poplar leaf pyrolysis at 300 °C and 700 °C (C300, C700, P300, P700. Brunaer–Emmett–Teller N2 surface area, scanning electron microscope, elemental analysis, and infrared spectra were used to characterize their structures. These biochars were then used as adsorbents for the adsorption of dodecylbenzene sulfonic acid (DBSA. The microscopic adsorption mechanisms were studied by using infrared spectra, 13C-nuclear magnetic resonance spectra, and electron spin resonance spectra. The surface area and pore volume of C700 (375.89 m2/g and 0.2302 cm3/g were the highest among all samples. Elemental analysis results showed that corn straw biochars had a higher aromaticity and carbon to nitrogen (C/N ratio than the poplar leaf biochars. High temperature caused the increase of carbon content and the decrease of oxygen content, which also gave the biochars a higher adsorption rate. Pseudo-second order kinetic provided a better fit with the experimental data. Adsorption isotherm experiments showed that the adsorption isotherm of C300 fit the linear model. For other biochars, the adsorption isotherms fitted Langmuir model. Biochars with high temperatures exhibited enhanced adsorption capacity compared with ones at low temperatures. The qmax values of biochars to DBSA followed the order of P700 > C700 > P300. The adsorption mechanisms were complex, including partition, anion exchange, the formation of H bonds, covalent bonds, and charge transfer. The adsorption by covalent bonding might be the key mechanism determining the adsorption capacity of P700.

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

Science.gov (United States)

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

Solvent and irradiation doses effects on the ion exchange capacity of sulfonated styrene grafted PVDF

International Nuclear Information System (INIS)

Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B.

2011-01-01

Polymers exhibiting ion exchange capacity are studied for many years due to their application in several fields, such as membranes for proton exchange fuel cells, filtration membranes, heavy ions recovery and artificial muscles and sensors. Radiation induced grafting followed by sulfonation is a well-known way to obtain ion exchange polymers. Fluorinated polymers are frequently used as polymeric matrix for grafting due to their excellent physicochemical properties. Radiation induced grafting of styrene into poly (vinylidene fluoride) (PVDF) by simultaneous method in 1:1 styrene/toluene or styrene/N,N-dimethylformamide solutions was studied. Irradiations were performed under nitrogen atmosphere, room temperature and at doses of 5, 10 and 20 kGy with dose rate of 5 kGy.h -1 from a 60 Co gamma source. After washing, grafted materials were sulfonated in 10% chlorosulfonic acid/1,2-dichloroethane solutions for 4 h at room temperature. Characterization shows that increasing irradiation dose corresponds to increases in the grafting yield (GY %) gravimetrically calculated and these different solvents shows different grafting behaviors. Toluene allows no more than 3 % of grafting while DMF allows up to 55 % of grafting in the same condition. Grafting in toluene solution occurs on the surface and in DMF solution it occurs in the bulk, as confirmed by SEM. Both irradiation doses and solvent used have direct effects in the ion exchange capacities (calculated after titrations). FT-IR spectra exhibit new peaks after grafting and after sulfonation, attributed to grafted monomer and sulfonic groups attached to the styrene. DSC shows differences in thermal behavior of the polymer before and after each step. (author)

Solvent and irradiation doses effects on the ion exchange capacity of sulfonated styrene grafted PVDF

Energy Technology Data Exchange (ETDEWEB)

Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

Polymers exhibiting ion exchange capacity are studied for many years due to their application in several fields, such as membranes for proton exchange fuel cells, filtration membranes, heavy ions recovery and artificial muscles and sensors. Radiation induced grafting followed by sulfonation is a well-known way to obtain ion exchange polymers. Fluorinated polymers are frequently used as polymeric matrix for grafting due to their excellent physicochemical properties. Radiation induced grafting of styrene into poly (vinylidene fluoride) (PVDF) by simultaneous method in 1:1 styrene/toluene or styrene/N,N-dimethylformamide solutions was studied. Irradiations were performed under nitrogen atmosphere, room temperature and at doses of 5, 10 and 20 kGy with dose rate of 5 kGy.h{sup -1} from a {sup 60}Co gamma source. After washing, grafted materials were sulfonated in 10% chlorosulfonic acid/1,2-dichloroethane solutions for 4 h at room temperature. Characterization shows that increasing irradiation dose corresponds to increases in the grafting yield (GY %) gravimetrically calculated and these different solvents shows different grafting behaviors. Toluene allows no more than 3 % of grafting while DMF allows up to 55 % of grafting in the same condition. Grafting in toluene solution occurs on the surface and in DMF solution it occurs in the bulk, as confirmed by SEM. Both irradiation doses and solvent used have direct effects in the ion exchange capacities (calculated after titrations). FT-IR spectra exhibit new peaks after grafting and after sulfonation, attributed to grafted monomer and sulfonic groups attached to the styrene. DSC shows differences in thermal behavior of the polymer before and after each step. (author)

Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

Science.gov (United States)

Jallet, Corinne; Jacob, Yves; Bahloul, Chokri; Drings, Astrid; Desmezieres, Emmanuel; Tordo, Noël; Perrin, Pierre

1999-01-01

The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH2 half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another GT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6). PMID:9847325

Electrochemical characterization of mixed self-assembled films of water-soluble single-walled carbon nanotube-poly(m-aminobenzene sulfonic acid) and Iron(II) tetrasulfophthalocyanine

CSIR Research Space (South Africa)

Agboola, BO

2010-09-01

Full Text Available The redox activities of water-soluble iron(II) tetrasulfophthalocyanine (FeTSPc) and single-walled carbon nanotube-poly(m-aminobenzene sulfonic acid) (SWCNT-PABS) adsorbed on a gold surface precoated with a self-assembled monolayer (SAM) of 2...

Synthesis and Characterization of Sulfonated Poly(Phenylene Containing a Non-Planar Structure and Dibenzoyl Groups

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Hohyoun Jang

2016-02-01

Full Text Available Polymers for application as sulfonated polyphenylene membranes were prepared by nickel-catalyzed carbon-carbon coupling reaction of bis(4-chlorophenyl-1,2-diphenylethylene (BCD and 1,4-dichloro-2,5-dibenzoylbenzene (DCBP. Conjugated cis/trans isomer (BCD had a non-planar conformation containing four peripheral aromatic rings that facilitate the formation of π–π interactions. 1,4-Dichloro-2,5-dibenzoylbenzene was synthesized from the oxidation reaction of 2,5-dichloro-p-xylene, followed by Friedel-Crafts reaction with benzene. DCBP monomer had good reactivity in polymerization affecting the activity of benzophenone as an electron-withdrawing group. The polyphenylene was sulfonated using concentrated sulfuric acid. These polymers without any ether linkages on the polymer backbone were protected from nucleophilic attack by hydrogen peroxide, hydroxide anion, and radicals generated by polymer electrolyte membrane fuel cell (PEMFC operation systems. The mole fraction of the sulfonic acid groups was controlled by varying the mole ratio of bis(4-chlorophenyl-1,2-diphenylethylene in the copolymer. In comparison with Nafion 211® membrane, these SBCDCBP membranes showed ion exchange capacity (IEC ranging from 1.04 to 2.07 meq./g, water uptake from 36.5% to 69.4%, proton conductivity from 58.7 to 101.9 mS/cm, and high thermal stability.

Effect of dietary fat on hepatic liver X receptor expression in P-glycoprotein deficient mice: implications for cholesterol metabolism

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Lee Stephen D

2008-06-01

Full Text Available Abstract Pgp (P-glycoprotein, MDR1, ABCB1 is an energy-dependent drug efflux pump that is a member of the ATP-binding cassette (ABC family of proteins. Preliminary studies have reported that nonspecific inhibitors of Pgp affect synthesis and esterification of cholesterol, putatively by blocking trafficking of cholesterol from the plasma membrane to the endoplasmic reticulum, and that relative increases in Pgp within a given cell type are associated with increased accumulation of cholesterol. Several key efflux proteins involved in the cholesterol metabolic pathway are transcriptionally regulated by the nuclear hormone liver X receptor (LXR. Therefore, to examine the interplay between P-glycoprotein and the cholesterol metabolic pathway, we utilized a high fat, normal cholesterol diet to upregulate LXRα without affecting dietary cholesterol. Our research has demonstrated that mice lacking in P-glycoprotein do not exhibit alterations in hepatic total cholesterol storage, circulating plasma total cholesterol levels, or total cholesterol concentration in the bile when compared to control animals on either a normal (25% calories from dietary fat or high fat (45% calories from dietary fat diet. However, p-glycoprotein deficient mice (Mdr1a-/-/1b-/- exhibit increased hepatic LXRα protein expression and an elevation in fecal cholesterol concentration when compared to controls.

Determination of trace elements by neutron activation analysis using dinonylnaphtalene sulfonic acid as a preconcentrating agent

International Nuclear Information System (INIS)

Yang, M.H.; Chen, P.Y.; Tseng, C.L.; Yeh, S.J.; Weng, P.S.

1977-01-01

Dinonylnaphthalene sulfonic acid (HD) has been used as a preconcentrating agent to enrich trace metal ions and to separate the interfering elements such as Na, K, Cl and Br, which normally exist in the natural aqueous systems. Experiments were performed by extracting the ions in the aqueous medium with HD in n-hexane and subsequently backextracted into a minimal volume of acid solution. Factors influencing the extraction efficiency of the ions of interest were investigated. The preconcentration technique has been successfully applied to the determination by neutron activation analysis of trace elements in natural water and biological materials. Both short-lived nuclides (Mg, Al, Ca, Mn) and long-lived nuclides (Sm, Eu, Zn, La, Cr, Sc, Fe, Co) in the ppb-level concentrations were determined. (T.G.)

Colorimetric detection of Cd"2"+ using 1-amino-2-naphthol-4-sulfonic acid functionalized silver nanoparticles

International Nuclear Information System (INIS)

Huang, Pengcheng; Liu, Bowen; Jin, Weiwei; Wu, Fangying; Wan, Yiqun

2016-01-01

A colorimetric assay has been developed for facile, rapid, and sensitive detection of Cd"2"+ using 1-amino-2-naphthol-4-sulfonic acid functionalized silver nanoparticles (ANS-AgNPs). The presence of Cd"2"+ induces the aggregation of ANS-AgNPs through cooperative metal–ligand interaction. As a result, the characteristic surface plasmon resonance (SPR) peak of ANS-AgNPs at 390 nm was red-shifted to 580 nm, yielding a color change from bright yellow to reddish-brown. The color change is monitored by UV–Vis spectrometer and can be directly read out by the naked eye. Under the optimized conditions, a good linear relationship (correlation coefficient R = 0.997) was obtained between the ratio of the absorbance at 580 nm to that at 390 nm (A_5_8_0_n_m/A_3_9_0_n_m) and the concentration of Cd"2"+ over the range of 1.0–10 μM with detection limit of 87 nM. The proposed method is simple and efficient, which has been applied for determining Cd"2"+ in milk powder, serum, and lake water with satisfactory results.

Room temperature synthesis of biodiesel using sulfonated ...

Science.gov (United States)

Sulfonation of graphitic carbon nitride (g-CN) affords a polar and strongly acidic catalyst, Sg-CN, which displays unprecedented reactivity and selectivity in biodiesel synthesis and esterification reactions at room temperature. Prepared for submission to Royal Society of Chemistry (RSC) journal, Green Chemistry as a communication.

Isolation and Characterization of the 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) Radical Cation-Scavenging Reaction Products of Arbutin.

Science.gov (United States)

Tai, Akihiro; Ohno, Asako; Ito, Hideyuki

2016-09-28

Arbutin, a glucoside of hydroquinone, has shown strong 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation-scavenging activity, especially in reaction stoichiometry. This study investigated the reaction mechanism of arbutin against ABTS radical cation that caused high stoichiometry of arbutin in an ABTS radical cation-scavenging assay. HPLC analysis of the reaction mixture of arbutin and ABTS radical cation indicated the existence of two reaction products. The two reaction products were purified and identified to be a covalent adduct of arbutin with an ABTS degradation fragment and 3-ethyl-6-sulfonate benzothiazolone. A time-course study of the radical-scavenging reactions of arbutin and the two reaction products suggested that one molecule of arbutin scavenges three ABTS radical cation molecules to generate an arbutin-ABTS fragment adduct as a final reaction product. The results suggest that one molecule of arbutin reduced two ABTS radical cation molecules to ABTS and then cleaved the third ABTS radical cation molecule to generate two products, an arbutin-ABTS fragment adduct and 3-ethyl-6-sulfonate benzothiazolone.

Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates

DEFF Research Database (Denmark)

Abraham, E H; Shrivastav, B; Salikhova, A Y

2001-01-01

P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated...

Glycoprotein biosynthesis by human normal platelets

International Nuclear Information System (INIS)

Rodriguez, P.; Bello, O.; Apitz-Castro, R.

1987-01-01

Incorporation of radioactive Man, Gal, Fuc, Glc-N, and NANA into washed human normal platelets and endogenous glycoproteins has been found. Both parameters were time dependent. Analysis of hydrolyzed labeled glycoproteins by paper chromatography revealed that the radioactive monosaccharide incubated with the platelets had not been converted into other sugars. Acid hydrolysis demonstrates the presence of a glycosidic linkage. All the effort directed to the demonstration of the existence of a lipid-sugar intermediate in intact human platelets yielded negative results for Man and Glc-N used as precursors. The incorporation of these sugars into glycoproteins is insensitive to bacitracin, suggesting no involvement of lipid-linked saccharides in the synthesis of glycoproteins in human blood platelets. The absence of inhibition of the glycosylation process in the presence of cycloheximide suggests that the sugars are added to proteins present in the intact platelets. These results support the contention that glycoprotein biosynthesis in human blood platelets observed under our experimental conditions is effected through direct sugar nucleotide glycosylation

Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.

Directory of Open Access Journals (Sweden)

Jie-wei Wang

Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasingly regarded as a hepatic manifestation of metabolic syndrome. Though with high prevalence, the mechanism is poorly understood. This study aimed to investigate the effects of p21 on free fatty acid (FFA-induced steatosis in L02 cells. We therefore analyzed the L02 cells with MG132 and siRNA treatment for different expression of p21 related to lipid accumulation and lipotoxicity. Cellular total lipid was stained by Oil Red O, while triglyceride content, cytotoxicity assays, lipid peroxidation markers and anti-oxidation levels were measured by enzymatic kits. Treatment with 1 mM FFA for 48 hr induced magnificent intracellular lipid accumulation and increased oxidative stress in p21 overload L02 cells compared to that in p21 knockdown L02 cells. By increasing oxidative stress and peroxidation, p21 accelerates FFA-induced lipotoxic effect in L02 cells and might provide information about potentially new targets for drug development and treatments of NAFLD.

Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate

Directory of Open Access Journals (Sweden)

Seo JH

2015-07-01

Full Text Available Jae Hong Seo, Jung Bae Park, Woong-Kee Choi, Sunhwa Park, Yun Jin Sung, Euichaul Oh, Soo Kyung Bae College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea Objective: Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol.Methods: Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base.Results: The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base.Conclusion: This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and

An unusual dependence of human herpesvirus-8 Glycoproteins-induced cell-to-cell fusion on heparan sulfate

Science.gov (United States)

Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

2009-01-01

Human herpes virus 8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: 1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; 2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, 3) coexpression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis. PMID:19747451

Ionomeric membranes based on partially sulfonated poly(styrene) : synthesis, proton conduction and methanol permeation

NARCIS (Netherlands)

Picchioni, F.; Tricoli, V.; Carretta, N.

2000-01-01

Homogeneuosly sulfonated poly(styrene) (SPS) was prepared with various concentration of sulfonic acid groups in the base polymer. Membranes cast from these materials were investigated in relation to proton conductivity and methanol permeability in the temperature range from 20°C to 60°C. It was

Ionomeric membranes based on partially sulfonated poly(styrene): synthesis, proton conduction and methanol permeation

NARCIS (Netherlands)

Carretta, N.; Tricoli, V.; Picchioni, F.

2000-01-01

Homogeneuosly sulfonated poly(styrene) (SPS) was prepared with various concentration of sulfonic acid groups in the base polymer. Membranes cast from these materials were investigated in relation to proton conductivity and methanol permeability in the temperature range from 20°C to 60°C. It was

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

Science.gov (United States)

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of acidic polymers for the removal of cobalt from water solutions by polymer assisted ultrafiltration

Energy Technology Data Exchange (ETDEWEB)

Dambies, Laurent, E-mail: chemjobs@netcourrir.com [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Jaworska, Agnieszka, E-mail: a.jaworska@ichtj.waw.pl [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Zakrzewska-Trznadel, Grazyna; Sartowska, Bozena [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)

2010-06-15

In this study, three sulfonated water-soluble polymers based on poly(vinyl alcohol) of different molecular weights (10,000, 50,000 and 100,000 Da) were prepared and tested against commercially available poly(acrylic acid) for the removal of cobalt using polymer assisted ultrafiltration. High rejection rates were obtained between pH 3 and 6 with sulfonated poly(vinyl alcohol) (PVA 10,000 and 50,000 Da) whereas poly(acrylic acid) (PAA) of similar molecular weights performed rather poorly in this pH range. Sulfonation improved significantly sorption capability of PVA. Sulfonated PVA 10,000 was the best complexing agent with rejection rate above 95% between pH 3 and 6. For unmodified PVA the rejection rate was only 30-45% at pH 6 and there was no rejection at pH 3 at all. PAA rejection rate was above 90% at pH 6 and only about 10% at pH 3. Large scale experiment in cross-flow, continuous apparatus conducted by using PVA-SO{sub 3}H 10,000 Da to remove {sup 60}Co radioisotope from water solutions showed excellent results demonstrating the potential of this polymer to purify acidic radioactive wastes containing cobalt radioisotopes.

Ionomers based on multisulfonated perylene dianhydride: Synthesis and properties of water resistant sulfonated polyimides

Energy Technology Data Exchange (ETDEWEB)

Zhang, Feng; Li, Nanwen [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Suobo; Li, Shenghai [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022 (China)

2010-04-15

A novel locally and densely sulfonated dianhydride with four sulfonic acid groups, 1,6,7,12-tetra[4-(sulfonic acid)phenoxy]perylene-3,4,9,10-tetracarboxylic dianhydride (SPTDA), was successfully synthesized by direct sulfonation of the parent dianhydride, 1,6,7,12-tetraphenoxyperylene-3,4,9,10-tetracarboxylic dianhydride (PTDA). Sulfonated copolyimides were prepared from SPTDA, nonsulfonated dianhydride 4,4'-binaphthyl-1,1',8,8'-tetracarboxylic dianydride, 4,4'-diaminodiphenyl ether (a) or dodecane-1,12-diamine (b). The synthesized copolymers, with the -SO{sub 3}H group on the polymer side chain, possess high molecular weights and high viscosities, and they form tough, flexible membranes. The copolymer membrane with an ion exchange capacity of 2.69 mequiv. g{sup -1} had a proton conductivity of 0.126 S cm{sup -1} at 20 C and 0.292 S cm{sup -1} at 100 C; the latter is much higher than that of Nafion {sup registered} 117 under the same conditions. The mechanical properties of the copolymer membranes were almost unchanged after accelerated water stability testing at 140 C for 100 h; this indicates excellent hydrolytic stability of the synthesized copolyimides. (author)

Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats Is Not Attenuated by Dietary Choline Supplementation.

Science.gov (United States)

Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Zitzow, Jeremiah D; Parker, George A; Peters, Jeffrey M; Wallace, Kendall B; Butenhoff, John L

2017-12-01

Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100 ppm PFOS, or 100 ppm PFOS + CS diets for 3 weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TGs) on days 9, 16, and/or 23 and increased hepatic free fatty acids and TG (ie, steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic free fatty acid and TG at termination (ie, no steatosis). Liver PFOS concentrations were similar for both sexes. Liver choline concentrations were increased in male rats fed PFOS (±CS), but the increase was lower in the PFOS + CS group. Female liver choline concentrations were not altered by any diet. These findings demonstrate a clear sex-related difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (ie, nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100 ppm) induced hepatic steatosis in male, but not female, rats that was not attenuated by choline supplementation. The mechanism of lipid accumulation and the sex-related differences warrant further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions.

Science.gov (United States)

The human efflux transporter P-glycoprotein (P-gp; MDR1) functions an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure ass...

Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression.

Science.gov (United States)

Chen, Qiqing; Hu, Xialin; Wang, Rui; Yuan, Jin; Yin, Daqiang

2016-05-01

P-Glycoprotein (P-gp) can protect cells by pumping out toxic compounds, and has been found widely expressed in fish tissues. Here, we illustrate the P-gp efflux ability for benzo(a)pyrene (BaP) in the hepatocytes of common carp (Cyprinus carpio) after exposing to fullerene aqueous suspension (nC60). The results revealed that nC60 increased the membrane fluidity by decreasing the ratio of saturated to unsaturated fatty acids, and increased the cholesterol contents. These findings, combined with 10-38% and 70-75% down-regulation of P-gp mRNA and protein respectively, suggested that nC60 caused inhibition on P-gp efflux transport system. Therefore, we further investigated the cellular efflux ability for BaP. Results showed unequivocally that nC60 is a potent P-gp inhibitor. The retaining BaP amounts after efflux were elevated by 1.7-2.8 fold during the 10 day exposure. Meanwhile, 5mg/L humic acid (one of the important fractions of natural organic matter, which is ubiquitous in aquatic environment) alleviated the nC60 damage to hepatocytes in terms of oxidative damage, cholesterol increment, and P-gp content reduction; and finally attenuated the suppressed P-gp efflux ability. Collectively, this study provides the first evidence of nC60 toxicity to P-gp functionality in fish and illustrates the possible mechanism of the suppressed P-gp efflux ability for BaP. Copyright © 2016 Elsevier B.V. All rights reserved.

Do pH and flavonoids influence hypochlorous acid-induced catalase inhibition and heme modification?

Science.gov (United States)

Krych-Madej, Justyna; Gebicka, Lidia

2015-09-01

Hypochlorous acid (HOCl), highly reactive oxidizing and chlorinating species, is formed in the immune response to invading pathogens by the reaction of hydrogen peroxide with chloride catalyzed by the enzyme myeloperoxidase. Catalase, an important antioxidant enzyme, catalyzing decomposition of hydrogen peroxide to water and molecular oxygen, hampers in vitro HOCl formation, but is also one of the main targets for HOCl. In this work we have investigated HOCl-induced catalase inhibition at different pH, and the influence of flavonoids (catechin, epigallocatechin gallate and quercetin) on this process. It has been shown that HOCl-induced catalase inhibition is independent on pH in the range 6.0-7.4. Preincubation of catalase with epigallocatechin gallate and quercetin before HOCl treatment enhances the degree of catalase inhibition, whereas catechin does not affect this process. Our rapid kinetic measurements of absorption changes around the heme group have revealed that heme modification by HOCl is mainly due to secondary, intramolecular processes. The presence of flavonoids, which reduce active catalase intermediate, Compound I to inactive Compound II have not influenced the kinetics of HOCl-induced heme modification. Possible mechanisms of the reaction of hypochlorous acid with catalase are proposed and the biological consequences are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

The pH profile for acid-induced elongation of coleoptile and epicotyl sections is consistent with the acid-growth theory

Science.gov (United States)

Cleland, R. E.; Buckley, G.; Nowbar, S.; Lew, N. M.; Stinemetz, C.; Evans, M. L.; Rayle, D. L.

1991-01-01

The acid-growth theory predicts that a solution with a pH identical to that of the apoplast of auxin-treated tissues (4.5.-5.0) should induce elongation at a rate comparable to that of auxin. Different pH profiles for elongation have been obtained, however, depending on the type of pretreatment between harvest of the sections and the start of the pH-incubations. To determine the acid sensitivity under in vivo conditions, oat (Avena sativa L.) coleoptile, maize (Zea mays L.) coleoptile and pea (Pisum sativum L.) epicotyl sections were abraded so that exogenous buffers could penetrate the free space, and placed in buffered solutions of pH 3.5-6.5 without any preincubation. The extension, without auxin, was measured over the first 3 h. Experiments conducted in three laboratories produced similar results. For all three species, sections placed in buffer without pretreatment elongated at least threefold faster at pH 5.0 than at 6.0 or 6.5, and the rate elongation at pH 5.0 was comparable to that induced by auxin. Pretreatment of abraded sections with pH-6.5 buffer or distilled water adjusted to pH 6.5 or above gave similar results. We conclude that the pH present in the apoplast of auxin-treated coleoptile and stems is sufficiently low to account for the initial growth response to auxin.

Toward High-Performance Lithium-Sulfur Batteries: Upcycling of LDPE Plastic into Sulfonated Carbon Scaffold via Microwave-Promoted Sulfonation.

Science.gov (United States)

Kim, Patrick J; Fontecha, Harif D; Kim, Kyungho; Pol, Vilas G

2018-05-02

Lithium-sulfur batteries were intensively explored during the last few decades as next-generation batteries owing to their high energy density (2600 Wh kg -1 ) and effective cost benefit. However, systemic challenges, mainly associated with polysulfide shuttling effect and low Coulombic efficiency, plague the practical utilization of sulfur cathode electrodes in the battery market. To address the aforementioned issues, many approaches have been investigated by tailoring the surface characteristics and porosities of carbon scaffold. In this study, we first present an effective strategy of preparing porous sulfonated carbon (PSC) from low-density polyethylene (LDPE) plastic via microwave-promoted sulfonation. Microwave process not only boosts the sulfonation reaction of LDPE but also induces huge amounts of pores within the sulfonated LDPE plastic. When a PSC layer was utilized as an interlayer in lithium-sulfur batteries, the sulfur cathode delivered an improved capacity of 776 mAh g -1 at 0.5C and an excellent cycle retention of 79% over 200 cycles. These are mainly attributed to two materialistic benefits of PSC: (a) porous structure with high surface area and (b) negatively charged conductive scaffold. These two characteristics not only facilitate the improved electrochemical kinetics but also effectively block the diffusion of polysulfides via Coulomb interaction.

Multiple Drug Transport Pathways through Human P-Glycoprotein.

Science.gov (United States)

McCormick, James W; Vogel, Pia D; Wise, John G

2015-07-21

P-Glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11-12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methylpyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp is presented.

Preparation and studying acid - base properties of the compound a -mono thiosemicarbazide isatin-5-Sodium sulfonate (α-MTI-5-SO3Na)

International Nuclear Information System (INIS)

Al-Azrak, A.

2015-01-01

This research aims to prepare organic compounds containing functional groups and have analytical properties to use as analytical reagents for determination of metal ions by spectrophotometric methods as acid-base indicators and as indicators for metal ions in EDTA titrations in this paper was prepared the compound ((α-mono thiosemicarbazide isatien -5-sodium sulfonate) it showed analytical properties and significant practical applications this compound has in acidic medium yellow color while in the basic medium sharply changes its color to red color the value of pKa of this compound has been calculated by spectrophotometric method and was equal to (8.860±0.054) the pH transition range was between (8.20 to 9.8) the indicator was used for determination the end point of the titration standard samples of solution (0.1M, NaOH) with standard solution of 0.1M, HCI, and in titration standard samples of solution (0.1M, CH 3 COOH) with standard solution of 0.1M NaOH the results were compared with the results obtained by reference titrimetric methods the statistical treatment for allresults shows that the end point determination using acid - base ((α-MTI-5-SO 3 Na) is the most accurate. (author)

P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia

NARCIS (Netherlands)

de Vries, EGE; van Putten, WLJ; Verdonck, LF; Ossenkoppele, GJ; Verhoef, GEG; Vellenga, E

Despite treatment with intensive chemotherapy, a considerable number of patients with acute myeloid leukemia (AML) die from their disease due to the occurrence of resistance. Overexpression of the transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein (MRP) 1 has been identified

Purification and properties of protocatechuate 3,4-dioxygenase from Chaetomium piluliferum induced with p-hydroxybenzoic acid.

Science.gov (United States)

Wojtaś-Wasilewska, M; Trojanowski, J

1980-01-01

1. Protocatechuate 3,4-dioxygenase (protocatechuate : oxygen 3,4-oxidoreductase, EC 1.13.11.3) was isolated from mycelium of Chaetomium piluliferum induced with p-hydroxybenzoic acid. The enzyme was purified about 80-fold by ammonium sulphate fractionation and DEAE-cellulose and Sephadex G-200 chromatography, and was homogeneous on polyacrylamide-gel electrophoresis. 2. The enzyme showed high substrate specificity; its pH optimum was 7.5-8.0, and molecula weight about 76 000 as determined by filtration on Sephadex G-200. The Michaelis constant for protocatechuic acid was 11.1 microM.

Chitosan-silica complex membranes from sulfonic acid functionalized silica nanoparticles for pervaporation dehydration of ethanol-water solutions.

Science.gov (United States)

Liu, Ying-Ling; Hsu, Chih-Yuan; Su, Yu-Huei; Lai, Juin-Yih

2005-01-01

Nanosized silica particles with sulfonic acid groups (ST-GPE-S) were utilized as a cross-linker for chitosan to form a chitosan-silica complex membranes, which were applied to pervaporation dehydration of ethanol-water solutions. ST-GPE-S was obtained from reacting nanoscale silica particles with glycidyl phenyl ether, and subsequent sulfonation onto the attached phenyl groups. The chemical structure of the functionalized silica was characterized with FTIR, (1)H NMR, and energy-dispersive X-ray. Homogeneous dispersion of the silica particles in chitosan was observed with electronic microscopies, and the membranes obtained were considered as nanocomposites. The silica nanoparticles in the membranes served as spacers for polymer chains to provide extra space for water permeation, so as to bring high permeation rates to the complex membranes. With addition of 5 parts per hundred of functionalized silica into chitosan, the resulting membrane exhibited a separation factor of 919 and permeation flux of 410 g/(m(2) h) in pervaporation dehydration of 90 wt % ethanol aqueous solution at 70 degrees C.

Polymer sulfonation- a versatile route to prepare proton-conducting membrane material for advanced technologies

International Nuclear Information System (INIS)

Zaidi, S.M.J.

2003-01-01

Sulfonation of polymers is a viable method for making proton exchange membranes used in electrochemical devices. Polyether-ether ketone was modified by using concentrated sulfuric acid (97.4%) to produce ion-containing polymers bearing HSO3 groups. The sulfonated polymer was characterized for IEC, HNMR, DSC and water uptake etc. The degree of sulfonation of sulfonated PEEK was found to vary from 40 to 80 mol%. The PEEK became amorphous after sufonation (as evidenced from DSC and WXRD), which enhanced its solubility in organic solvents such as DMF. The glass transition temperature, Tg increased from 151C for pure PEEK to 217C upon sulfonation. The water uptake was also increased with sulfonation level, which provides formation of water-mediated pathways for protons involving SO3H groups. The membranes from these polymers have a high potential for use in electrochemical devices such as polymer fuel cell and electrodialysis. (author)

High power generation and COD removal in a microbial fuel cell operated by a novel sulfonated PES/PES blend proton exchange membrane

International Nuclear Information System (INIS)

Zinadini, S.; Zinatizadeh, A.A.; Rahimi, M.; Vatanpour, V.; Rahimi, Z.

2017-01-01

In this paper, firstly sulfonated polyethersulfone (SPES) was synthesized from polyethersulfone (PES) with sulfonation by chlorosulfonic acid as a sulfonating agent dissolved in concentrated sulfuric acid. PES/SPES blend proton exchange membranes (PEMs) were prepared at four different compositions with the non-solvent induced phase separation technique as alternative materials to Nafion membrane for application in a microbial fuel cell (MFC). The prepared PEMs were characterized by FTIR spectroscopy, AFM, SEM, contact angle, water uptake and oxygen permeability. Performances of the fabricated PEMs and commercial Nafion 117 were evaluated in a dual chamber MFC for treating of wastewater and electricity generation. Maximum generated power and current of the fabricated membranes were 58.726 mWm −2  at current density of 317.111 mAm −2 , while it was 45.512 mWm −2  at 228.673 mAm −2 for Nafion 117 at the similar experimental condition. The observed properties of low biofouling, low oxygen permeability, high power generation, high COD removal and coulombic efficiency (CE) indicated that the SPES membrane has potential to improve significantly the productivity of MFCs. - Highlights: • Sulfonated PES (SPES) was synthesized by chlorosulfonic acid in concentrated H 2 SO 4 . • PES/SPES blend proton exchange membranes (PEMs) were prepared for use in MFC. • Performance of PEMs and commercial Nafion 117 were tested to treat of wastewater. • Maximum generated power and current of SPES membrane was higher than Nafion 117.

Characterization of reactive intermediates in laser photolysis of nucleoside using of sodium salt anthraquinone-2-sulfonic acid as photosensitizer

International Nuclear Information System (INIS)

Ma Jianhua; Lin Weizhen; Wang Wenfeng; Han Zhenhui; Yao Side; Lin Nianyun

1999-01-01

The interaction of triplet state of sodium salt of anthraquinone-2-sulfonic acid (AQS) with nucleosides has been investigated in CH 3 CN using KrF(248 nm) laser flash photolysis. The transient absorption spectra and kinetics obtained from the interaction of triplet AQS and nucleoside demonstrated that the primary ionic radical pair, radical cation of nucleosides and radical anion of AQS has been detected simultaneously for the first time

Differential pulse polarographic determination of trace antimony in standard biological samples after preconcentration using 2-nitroso-1-naphthol-4-sulfonic acid

International Nuclear Information System (INIS)

Taher, M. A.

2003-01-01

A highly selective, rapid and economical differential polarographic method has been developed for the determination of trace amounts of antimony in various standard alloys and biological samples after of its 2-naphthol-4 sulfonic acid tetradecyl dimethylbenzylammonium chloride on microcrystalline naphthalene in the ph range of 7.5-11.0. After filtration, the solid mass is shaken with 8-10 ml of 1 M hydrochloric acid (with preconcentration factor of 10) and antimony is determined by differential pulse polarography. Antimony can alternatively be quantitatively absorbed on 2-nitroso-1-naphthol-4-sulfonic acid tetradecyl dimethylbenzylammonium-naphthalene absorbed packed in a column (with preconcentration factor of 30) and determined similarly. In this case, 1.5 μg of antimony can be concentrated in a column from 300 ml of aqueous sample, where its concentration is as low as 5 ng/ml. Characterization of the electro active process included an examination of the degree of reversibility. The results show that the irreversibility of antimony. Various parameters such as the effect of ph, volume of aqueous phase, HCl concentration, reagent concentration, naphthalene concentration, shaking time and interference of a number of metal ions on the determination of antimony have been studied in detail to optimize the conditions for determination in standard alloys and standard biological samples

Multi-drug resistance (MDR1 gene and P-glycoprotein influence on pharmacokinetic and pharmacodymanic of therapeutic drugs

Directory of Open Access Journals (Sweden)

Linardi Renata Lehn

2006-01-01

Full Text Available (MDR1 gene expressed in tumor cells and also in several normal tissues, such as intestine, liver, kidney, blood-brain barrier, spinal cord, and placenta. P-gp has been identified in mice, rat, bovine, monkey, rodents, and human beings and has been receiving a particular clinical relevance because this protein expression limits brain access and intestinal absorption of many drugs. This protein plays a role as a protective barrier against a wide variety of substrates, avoiding drug entry into the central nervous system. P-glycoprotein also interferes with drug bioavailability and disposition, including absorption, distribution, metabolization, and excretion, influencing pharmacokinetic and pharmacodynamic of drugs. Modulation of P-gp may help the efficacy of treatment of several diseases and can explain some adverse central nervous system effects induced by drugs after intravenous administration and the poor response of oral administration in patients. Alteration in P-gp expression or function has been associated with several diseases susceptibility in humans and animals. Furthermore, additional studies relating MDR1 and P-gp expression has an important clinical implication also in terms of treatment efficacy.

A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier

NARCIS (Netherlands)

Hendrikse, NH; de Vries, EGE; Eriks-Fluks, L; van der Graaf, WTA; Hospers, GAP; Willemsen, ATM; Vaalburg, W; Franssen, EJF

1999-01-01

Drug resistance is a major cause of chemotherapy failure in cancer treatment, One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR), In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp

A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics

DEFF Research Database (Denmark)

Saaby, Lasse; Brodin, Birger

2017-01-01

Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties...... and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may...... mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate...

Flexible, all-organic ammonia sensor based on dodecylbenzene sulfonic acid-doped polyaniline films

International Nuclear Information System (INIS)

Rizzo, G.; Arena, A.; Donato, N.; Latino, M.; Saitta, G.; Bonavita, A.; Neri, G.

2010-01-01

A stable chlorobenzene dispersion of conducting polyaniline (PANI) has been obtained by doping emeraldine base with dodecylbenzene sulfonic acid (DBSA) and studied by spectrophotometric measurements in the UV-vis-IR range. The electrical properties of PANI: DBSA films obtained from the above dispersion have been investigated under different temperature and relative humidity conditions. All-organic chemoresistive devices have been developed by spin-coating the PANI: DBSA dispersion on flexible substrates, and then by depositing electrodes on the top, from a carbon nanotube conducting ink. Sensing tests performed under exposition to calibrated amounts of ammonia reveal that these simple and inexpensive sensors are able to detect ammonia at room temperature in a reliable way, with a sensitivity linearly related to concentration in the range between 5 ppm and 70 ppm.

Sulfonation and characterization of styrene-indene copolymers for the development of proton conducting polymer membranes

Directory of Open Access Journals (Sweden)

Cristiane M. Becker

2012-01-01

Full Text Available The aim of this work is to obtain polymer precursors based on styrene copolymers with distinct degrees of sulfonation, as an alternative material for fuel cell membranes. Acetyl sulfate was used to carry out the sulfonation and the performance of the polyelectrolyte was evaluated based on the content of acid polar groups incorporated into the macromolecular chain. Polymeric films were produced by blending the sulfonated styrene-indene copolymer with poly(vinylidene fluoride. The degree of sulfonation of the polymer was strongly affected by the sulfonation reaction parameters, with a direct impact on the ionic exchange capacity and the ionic conductivity of the sulfonated polymers and the membranes obtained from them. The films produced with the blends showed more suitable mechanical properties, although the conductivity of the membranes was still lower than that of commercially available membranes used in fuel cells.

Evolutionary conservation of P-selectin glycoprotein ligand-1 primary structure and function

Directory of Open Access Journals (Sweden)

Schapira Marc

2007-09-01

Full Text Available Abstract Background P-selectin glycoprotein ligand-1 (PSGL-1 plays a critical role in recruiting leukocytes in inflammatory lesions by mediating leukocyte rolling on selectins. Core-2 O-glycosylation of a N-terminal threonine and sulfation of at least one tyrosine residue of PSGL-1 are required for L- and P-selectin binding. Little information is available on the intra- and inter-species evolution of PSGL-1 primary structure. In addition, the evolutionary conservation of selectin binding site on PSGL-1 has not been previously examined in detail. Therefore, we performed multiple sequence alignment of PSGL-1 amino acid sequences of 14 mammals (human, chimpanzee, rhesus monkey, bovine, pig, rat, tree-shrew, bushbaby, mouse, bat, horse, cat, sheep and dog and examined mammalian PSGL-1 interactions with human selectins. Results A signal peptide was predicted in each sequence and a propeptide cleavage site was found in 9/14 species. PSGL-1 N-terminus is poorly conserved. However, each species exhibits at least one tyrosine sulfation site and, except in horse and dog, a T [D/E]PP [D/E] motif associated to the core-2 O-glycosylation of a N-terminal threonine. A mucin-like domain of 250–280 amino acids long was disclosed in all studied species. It lies between the conserved N-terminal O-glycosylated threonine (Thr-57 in human and the transmembrane domain, and contains a central region exhibiting a variable number of decameric repeats (DR. Interspecies and intraspecies polymorphisms were observed. Transmembrane and cytoplasmic domain sequences are well conserved. The moesin binding residues that serve as adaptor between PSGL-1 and Syk, and are involved in regulating PSGL-1-dependent rolling on P-selectin are perfectly conserved in all analyzed mammalian sequences. Despite a poor conservation of PSGL-1 N-terminal sequence, CHO cells co-expressing human glycosyltransferases and human, bovine, pig or rat PSGL-1 efficiently rolled on human L- or P

St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.

NARCIS (Netherlands)

Ott, M.; Huls, M.; Cornelius, M.G.; Fricker, G.

2010-01-01

PURPOSE: The purpose of this study was to investigate the short-term signaling effects of St. John's Wort (SJW) extract and selected SJW constituents on the blood-brain barrier transporter P-glycoprotein and to describe the role of PKC in the signaling. METHODS: Cultured porcine brain capillary

The role of the polymorphic efflux transporter P-glycoprotein on the brain accumulation of d-methylphenidate and d-amphetamine.

Science.gov (United States)

Zhu, Hao-Jie; Wang, Jun-Sheng; DeVane, C Lindsay; Williard, Robin L; Donovan, Jennifer L; Middaugh, Lawrence D; Gibson, Brian B; Patrick, Kennerly S; Markowitz, John S

2006-07-01

The psychostimulant medications methylphenidate (MPH) and amphetamine (AMP), available in various ratios or enantiopure formulations of their respective active dextrorotary isomers, constitute the majority of agents used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Substantial interindividual variability occurs in their pharmacokinetics and tolerability. Little is known regarding the potential role of drug transporters such as P-glycoprotein (P-gp) in psychostimulant pharmacokinetics and response. Therefore, experiments were carried out in P-gp knockout (KO) mice versus wild-type (WT) mice after intraperitoneal dosing (2.5 mg/kg) of d-MPH or (3.0 mg/kg) of d-AMP. After the administration of each psychostimulant, locomotor activity was assessed at 30-min intervals for 2 h. Total brain-to-plasma drug concentration ratios were determined at 10-, 30-, and 80-min postdosing time-points. The results showed no statistically supported genotypic difference in d-AMP-induced locomotor activity stimulation or in brain-to-plasma ratio of d-AMP. As for d-MPH, the P-gp KO mice had 33% higher brain concentrations (p brain-to-plasma ratios (p brain concentrations, d-MPH-induced locomotor activity increase was attenuated for P-gp compared with that for WT mice. These data indicate that P-gp has no apparent effect on the pharmacokinetics and pharmacodynamics of d-AMP. In addition, d-MPH is a relatively weak P-gp substrate, and its entry into the brain may be limited by P-gp. Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated.

P-glycoprotein Inhibition Increases the Brain Distribution and Antidepressant-Like Activity of Escitalopram in Rodents

OpenAIRE

O'Brien, Fionn E; O'Connor, Richard M; Clarke, Gerard; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F

2013-01-01

Despite the clinical prevalence of the antidepressant escitalopram, over 30% of escitalopram-treated patients fail to respond to treatment. Recent gene association studies have highlighted a potential link between the drug efflux transporter P-glycoprotein (P-gp) and response to escitalopram. The present studies investigated pharmacokinetic and pharmacodynamic interactions between P-gp and escitalopram. In vitro bidirectional transport studies revealed that escitalopram is a transported subst...

RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells.

Science.gov (United States)

Maeda, Toyonobu; Yuzawa, Satoshi; Suzuki, Atsuko; Baba, Yuh; Nishimura, Yukio; Kato, Yasumasa

2016-03-01

Solid tumors are characterized by acidic extracellular pH (pHe). The present study examined the contribution of small GTP-binding proteins to phospholipase D (PLD) activation of acidic pHe-induced matrix metalloproteinase-9 (MMP-9) production. Acidic pHe-induced MMP-9 production was reduced by C3 exoenzyme, which inhibits the Rho family of GTPases; cytochalasin D, which inhibits actin reorganization; and simvastatin, which inhibits geranylgeranylation of Rho. Small interfering RNA (siRNA) against RhoA, but not against Rac1 or Cdc42, significantly inhibited acidic pHe induction of MMP-9. Pull-down assays showed that acidic pHe increased the activated form of RhoA. Forced expression of constitutively active RhoA induced MMP-9 production, even at neutral pHe. RhoA siRNA also reduced acidic pHe induced PLD activity. Specific inhibition of PLD1 and Pld1 gene knockout significantly reduced acidic pHe-induced MMP-9 expression. In contrast, PLD2 inhibition or knockout had no effect on MMP-9 expression. These findings suggested that RhoA-PLD1 signaling is involved in acidic pHe induction of MMP-9.

Colorimetric detection of Cd{sup 2+} using 1-amino-2-naphthol-4-sulfonic acid functionalized silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Huang, Pengcheng; Liu, Bowen; Jin, Weiwei; Wu, Fangying, E-mail: fywu@ncu.edu.cn; Wan, Yiqun [Nanchang University, College of Chemistry (China)

2016-11-15

A colorimetric assay has been developed for facile, rapid, and sensitive detection of Cd{sup 2+} using 1-amino-2-naphthol-4-sulfonic acid functionalized silver nanoparticles (ANS-AgNPs). The presence of Cd{sup 2+} induces the aggregation of ANS-AgNPs through cooperative metal–ligand interaction. As a result, the characteristic surface plasmon resonance (SPR) peak of ANS-AgNPs at 390 nm was red-shifted to 580 nm, yielding a color change from bright yellow to reddish-brown. The color change is monitored by UV–Vis spectrometer and can be directly read out by the naked eye. Under the optimized conditions, a good linear relationship (correlation coefficient R = 0.997) was obtained between the ratio of the absorbance at 580 nm to that at 390 nm (A{sub 580nm}/A{sub 390nm}) and the concentration of Cd{sup 2+} over the range of 1.0–10 μM with detection limit of 87 nM. The proposed method is simple and efficient, which has been applied for determining Cd{sup 2+} in milk powder, serum, and lake water with satisfactory results.

Composite electrolytes composed of Cs-substituted phosphotungstic acid and sulfonated poly(ether-ether ketone) for fuel cell systems

Energy Technology Data Exchange (ETDEWEB)

Oh, Song-Yul, E-mail: ms089203@tutms.tut.ac.jp [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Yoshida, Toshihiro; Kawamura, Go [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Muto, Hiroyuki [Department of Materials Science and Engineering, Kurume National College of Technology, 1-1-1 Komorino, Kurume, Fukuoka 830-8555 (Japan); Sakai, Mototsugu [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Matsuda, Atsunori, E-mail: matsuda@tutms.tut.ac.jp [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan)

2010-10-15

Composite electrolytes composed of cesium hydrogen sulfate containing phosphotungstic acids (CsHSO{sub 4}-H{sub 3}PW{sub 12}O{sub 40}) and sulfonated poly(ether-ether ketone) (SPEEK) were prepared by casting the corresponding precursor for application in fuel cells. Partially Cs-substituted phosphotungstic acids (Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40}) were formed in the CsHSO{sub 4}-H{sub 3}PW{sub 12}O{sub 40} system by mechanochemical treatment. SPEEK was prepared from PEEK by sulfonation using concentrated sulfuric acid. Flexible composite electrolytes were obtained and their electrochemical properties were markedly improved with the addition of Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40}, into the SPEEK matrix. A maximum power density of 213 mW cm{sup -2} was obtained from the single cell test for 50H{sub 3}PW{sub 12}O{sub 40}-50CsHSO{sub 4} in SPEEK (1/5 by weight) composite electrolyte at 80 deg. C and at 80 RH%. Electrochemical properties and transmission electron microscopy (TEM) results suggest that three-dimensional cluster particles were formed and homogeneously distributed in the SPEEK matrix. The mechanochemically synthesized Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40} incorporated into the SPEEK matrix increased the number of protonate sites in the electrolyte. The composite electrolytes were successfully formed with Cs{sub x}H{sub 3-x}PW{sub 12}O{sub 40}, which consist of hydrogen bonding between surface of inorganic solid acids and not only -HSO{sub 4}{sup -} dissociated from CsHSO{sub 4} but also -SO{sub 3}H groups in the SPEEK.

Effect of cesium salt of tungstophosphoric acid (Cs-TPA) on the properties of sulfonated polyether ether ketone (SPEEK) composite membranes for fuel cell applications

Energy Technology Data Exchange (ETDEWEB)

Dogan, Hacer; Inan, Tuelay Y.; Unveren, Elif [The Scientific and Technological Research Council of Turkey (TUeBiTAK), Marmara Research Center, Chemistry Institute, P.K. 21, 41470 Gebze-Kocaeli (Turkey); Kaya, Metin [DEMIRDOeKUeM A.S. 4 Eyluel Mah, ismet inoenue Cad. No:245 Bozueyuek/Bilecik (Turkey)

2010-08-15

We have prepared composite membranes for fuel cell applications. Cesium salt of tungstophosphoric acid (Cs-TPA) particles was synthesized by aqueous solutions of tungstophosphoric acid and cesium hydroxide and, Cs-TPA particles and sulfonated (polyether ether ketone) (SPEEK) with two sulfonation degrees (DS), 60 and 70%have been used. We examined both the effects of Cs-TPA in SPEEK membranes as functions of sulfonation degrees of SPEEK and the content of Cs-TPA. The performance of the composite membranes was evaluated in terms of water uptake, ion exchange capacity, proton conductivity, chemical stability, hydrolytic stability, thermal stability and methanol permeability. The morphology of the membranes was investigated with SEM micrographs. Increasing sulfonation degree of SPEEK from 60 to 70 caused agglomeration of the Cs-TPA particles. The methanol permeability was reduced to 4.7 x 10{sup -7} cm{sup 2}/s for SPEEK (DS: 60%)/Cs-TPA membrane with 10 wt.% Cs-TPA concentration, and acceptable proton conductivity of 1.3 x 10{sup -1} S/cm was achieved at 80 C under 100% RH. The weight loss at 900 C increased with the addition of inorganic particles, as expected. The hydrolytic stability of the SPEEK/Cs-TPA based composite membranes was improved with the incorporation of the Cs-TPA particles into the matrix. We also noted that SPEEK60/Cs-TPA composite membranes were hydrolytically more stable than SPEEK70/Cs-TPA composite membranes. On the other hand, Methanol, water vapor, and hydrogen permeability values of SPEEK60 composite membranes were found to be lower than that of Nafion {sup registered}. (author)

Differential effects of the enantiomers of tamsulosin and tolterodine on P-glycoprotein and cytochrome P450 3A4.

Science.gov (United States)

Doricakova, Aneta; Theile, Dirk; Weiss, Johanna; Vrzal, Radim

2017-01-01

The pregnane X receptor (PXR) is a transcription factor regulating P-glycoprotein (P-gp; ABCB1)-mediated transport and cytochrome P450 3A4 (CYP3A4)-mediated metabolism of xenobiotics thereby affecting the pharmacokinetics of many drugs and potentially modulating clinical efficacy. Thus, pharmacokinetic drug-drug interactions can arise from PXR activation. Here, we examined whether the selective α1-adrenoreceptor blocker tamsulosin or the antagonist of muscarinic receptors tolterodine affect PXR-mediated regulation of CYP3A4 and of P-gp at the messenger RNA (mRNA) and protein level in an enantiomer-specific way. In addition, the effect of tamsulosin and tolterodine on P-gp activity was evaluated. We used quantitative real-time PCR, gene reporter assay, western blotting, rhodamine efflux assay, and calcein assay for determination of expression, activity, and inhibition of P-glycoprotein. The studied compounds significantly and concentration-dependently increased PXR activity in the ABCB1-driven luciferase-based reporter gene assay. We observed much stronger induction of ABCB1 mRNA by S-tamsulosin as compared to the R or racemic form. R or racemic form of tolterodine and R-tamsulosin concentration-dependently increased P-gp protein expression; the latter also enhanced P-gp efflux function in a rhodamine-based efflux assay. R-tamsulosin and all forms of tolderodine slightly inhibited P-gp. The effect on CYP3A4 expression followed the same pattern but was much weaker. Taken together, tamsulosin and tolterodine are demonstrated to interfere with P-gp and CYP3A4 regulation in an enantiomer-specific way.

Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins

NARCIS (Netherlands)

Schinkel, A. H.; Mayer, U.; Wagenaar, E.; Mol, C. A.; van Deemter, L.; Smit, J. J.; van der Valk, M. A.; Voordouw, A. C.; Spits, H.; van Tellingen, O.; Zijlmans, J. M.; Fibbe, W. E.; Borst, P.

1997-01-01

The mdr1-type P-glycoproteins (P-gps) confer multidrug resistance to cancer cells by active extrusion of a wide range of drugs from the cell. To study their physiological roles, we have generated mice genetically deficient in the mdr1b gene [mdr1b (-/-) mice] and in both the mdr1a and mdr1b genes

Proton conductivity and fuel cell property of composite electrolyte consisting of Cs-substituted heteropoly acids and sulfonated poly(ether-ether ketone)

Energy Technology Data Exchange (ETDEWEB)

Oh, S.Y.; Yoshida, T.; Kawamura, G.; Sakai, M.; Matsuda, A. [Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 441-8580 (Japan); Muto, H. [Department of Materials Science and Engineering, Kurume National College of Technology, 1-1-1 Komorino, Kurume, Fukuoka 830-8555 (Japan)

2010-09-15

Inorganic-organic composite electrolytes were fabricated from partially Cs{sup +}-substituted heteropoly acids (Cs-HPAs) and sulfonated poly(ether-ether ketone) (SPEEK) for application in fuel cells. Heteropoly acids, such as phosphotungstic acid (H{sub 3}PW{sub 12}O{sub 40}:WPA), and silicotungstic acid (H{sub 4}SiW{sub 12}O{sub 40}:WSiA), were mechanochemically treated with cesium hydrogen sulfate (CsHSO{sub 4}) to obtain the form of Cs-HPAs. SPEEK was prepared from PEEK by sulfonation using concentrated sulfuric acid. Water durability and surface structure of HPAs were modified by introducing Cs{sup +} into HPAs. Flexible and hot water stable composite electrolytes were obtained, and their electrochemical properties were markedly improved with the addition of Cs-HPAs into the SPEEK matrix. Maximum power densities of 245 and 247 mW cm{sup -2} were obtained for 50WPA.50CsHSO{sub 4} and 50WSiA.50CsHSO{sub 4} in SPEEK (1/5 by weight) composite electrolytes, respectively, from single cell tests at 80 C and 80 RH%. These results suggest that a three-dimensional proton-conductive path was formed among homogeneously distributed Cs-HPAs particles in the SPEEK matrix. The Cs-HPAs incorporated into the SPEEK matrix increased the number of protonate sites in the electrolyte. These observations imply that the mechanochemically synthesized Cs-HPAs, which consist of hydrogen bondings between Cs-HPAs and -HSO{sub 4}{sup -}, dissociated from CsHSO{sub 4}, are promising materials as inorganic fillers in inorganic-organic composite. (author)

Sulfonated methyl esters of fatty acids in aqueous solutions: Interfacial and micellar properties.

Science.gov (United States)

Danov, Krassimir D; Stanimirova, Rumyana D; Kralchevsky, Peter A; Basheva, Elka S; Ivanova, Veronika I; Petkov, Jordan T

2015-11-01

The interest to sulfonated methyl esters of fatty acids (SME) has been growing during the last decade, because these surfactants are considered as an environmentally friendly and renewable alternative of the linear alkyl-benzene sulfonates (LAS). Here, we present a quantitative study on the properties of aqueous SME solutions, and especially on their surface tension isotherms, critical micelle concentration (CMC) and its dependence on the concentration of added NaCl. It is demonstrated that the CMC of an ionic surfactant determined by electrical conductivity is insensitive to the presence of a small nonionic admixture, so that the CMC values determined by conductivity represent the CMC of the pure surfactant. Using SME as an example, we have demonstrated the application of a new and powerful method for determining the physicochemical parameters of the pure ionic surfactant by theoretical data analysis ("computer purification") if the used surfactant sample contains nonionic admixtures, which are present as a rule. This method involves fits of the experimental data for surface tension and conductivity by a physicochemical model based on a system of mass-balance, chemical-equilibrium and electric-double-layer equations, which allows us to determine the adsorption and micellization parameters of C12-, C14-, C16- and C18-SME, as well the fraction of nonionic admixtures (if any). Having determined these parameters, we can further predict the interfacial and micellization properties of the surfactant solutions, such as surface tension, adsorption, degree of counterion binding, and surface electric potential at every surfactant, salt and co-surfactant concentrations. Copyright © 2015 Elsevier Inc. All rights reserved.

The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment

Directory of Open Access Journals (Sweden)

Alberto Lazarowski

2015-07-01

Full Text Available As described initially from clinical and experimental studies, P-glycoprotein (P-gp plays a central role in the pharmacoresistance of epilepsy, acting by efflux of AEDs mainly at blood brain barrier (BBB level. However, repetitive seizures can produce both brain and heart P-gp overexpression. Because P-gp activity induces membrane depolarization, its neuronal expression could be acting in the intrinsic mechanism of epileptogenesis, and its heart expression, can be a high risk factor of death, after severe-continuo convulsive stresses as in  fatal status epilepticus or in SUDEP. Additionally, because P-gp is also a stem cell marker, we suggests that its constitutive overexpression in dysplastic neurons from brain epileptogenic areas observed in patients with refractory epilepsies, should be addressed as a risk factor of seizures relapse after surgical treatment. Here we discuss these concepts, based on our own clinical and experimental experiences, and reviewing the current literature on these subjects.

Extracellular Glycoproteins in Embryogenic Culture of Pumpkin (Cucurbita pepo L.

Directory of Open Access Journals (Sweden)

Hana Čipčić Paljetak

2011-01-01

Full Text Available The extracellular proteins in three distinctly induced embryogenic lines of pumpkin (Cucurbita pepo L. cultivated in four MS media modified regarding the nitrogen composition or auxin presence/absence have been analyzed. Extracellular glycoproteins containing α-D-mannose were specifically detected by the lectine concavalin A. During the cultivation of embryogenic tissue in the medium supplemented with reduced nitrogen, the embryos were mostly arrested at preglobular and globular developmental stages, which coincide with the absence of protein secretion. Secreted glycoproteins of 76, 68, 37 and 34 kDa were detected only if any of the three lines were cultivated in the medium that stimulates embryo development, irrespectively of the addition of 2,4-dichlorophenoxyacetic acid or tunicamycin. The glycoprotein of 64 kDa was detected in all lines cultivated in hormone-free MS medium with conventional nitrogen sources and it appears to be associated with embryo maturation. Tunicamycin treatment did not influence embryogenesis, although it specifically affected glycosylation of proteins in the investigated lines. Our results show that besides auxin, the source of nitrate is of great importance for proper protein glycosylation, excretion and developmental transition of pumpkin somatic embryos.

Pomegranate seed oil: Effect on 3-nitropropionic acid-induced neurotoxicity in PC12 cells and elucidation of unsaturated fatty acids composition.

Science.gov (United States)

Al-Sabahi, Bushra N; Fatope, Majekodunmi O; Essa, Musthafa Mohamed; Subash, Selvaraju; Al-Busafi, Saleh N; Al-Kusaibi, Fatma S M; Manivasagam, Thamilarasan

2017-01-01

Seed oils are used as cosmetics or topical treatment for wounds, allergy, dandruff, and other purposes. Natural antioxidants from plants were recently reported to delay the onset or progress of various neurodegenerative conditions. Over one thousand cultivars of Punica granatum (Punicaceae) are known and some are traditionally used to treat various ailments. The effect of pomegranate oil on 3-nitropropionic acid- (3-NP) induced cytotoxicity in rat pheochromocytoma (PC12) neuronal cells was analyzed in this study. Furthermore, the analysis of unsaturated fatty acid composition of the seed oil of pomegranate by gas chromatography-electron impact mass spectrometry (GC-MS) was done. GC-MS study showed the presence of 6,9-octadecadiynoic acid (C18:2(6,9)) as a major component (60%) as 4,4-dimethyloxazoline derivative. The total extractable oil with light petroleum ether by Soxhlet from the dry seed of P. granatum was 4-6%. The oil analyzed for 48.90 ± 1.50 mg gallic acid equivalents/g of oil, and demonstrated radical-scavenging-linked antioxidant activities in various in vitro assays like the DPPH (2,2-diphenyl-l-picrylhydrazyl, % IP = 35.2 ± 0.9%), ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), % IP 2.2 ± 0.1%), and β-carotene bleaching assay (% IP = 26 ± 3%), respectively, which could be due the possible role of one methylene interrupted diynoic acid system for its radical-scavenging/antioxidant properties of oil. The oil also reduced lipid peroxidation, suppressed reactive oxygen species, extracellular nitric oxide, lactate/pyruvate ratio, and lactase dehydrogenase generated by 3-NP- (100 mM) induced neurotoxicity in PC12 cells, and enhanced the levels of enzymatic and non-enzymatic antioxidants at 40 μg of gallic acid equivalents. The protective effect of pomegranate seed oil might be due to the ability of an oil to neutralize ROS or enhance the expression of antioxidant gene and the exact mechanism of action yet to be elucidated.

Effect of bisphenol A on P-glycoprotein-mediated efflux and ultrastructure of the sea urchin embryo

International Nuclear Information System (INIS)

Bošnjak, Ivana; Borra, Marco; Iamunno, Franco; Benvenuto, Giovanna; Ujević, Ivana; Bušelić, Ivana; Roje-Busatto, Romana; Mladineo, Ivona

2014-01-01

Highlights: • Effects of BPA on embryonic development of Paracentrotus lividus were determined. • Transport assay, intracellular BPA measurements and gene expression surveys were made. • Multidrug efflux transporter P-gp/ABCB1 is involved in BPA elimination. • Endocrine disruption is inferred by orphan steroid hormone receptor (shr2) upregulation. • BPA delayed mitosis, inducing aberrant karyokinesis and dysfunctional microfilaments. - Abstract: Usage of bisphenol A (BPA) in production of polycarbonate plastics has resulted in global distribution of BPA in the environment. These high concentrations cause numerous negative effects to the aquatic biota, among which the most known is the induction of endocrine disruption. The focus of this research was to determine the effects of two experimentally determined concentrations of BPA (100 nM and 4 μM) on cellular detoxification mechanisms during the embryonic development (2-cell, pluteus) of the rocky sea urchin (Paracentrotus lividus), primarily the potential involvement of multidrug efflux transport in the BPA intercellular efflux. The results of transport assay, measurements of the intracellular BPA and gene expression surveys, for the first time indicate the importance of P-glycoprotein (P-gp/ABCB1) in defense against BPA. Cytotoxic effects of BPA, validated by the immunohistochemistry (IHC) and the transmission electron microscopy (TEM), induced the aberrant karyokinesis, and consequently, the impairment of embryo development through the first cell division and retardation

Effect of bisphenol A on P-glycoprotein-mediated efflux and ultrastructure of the sea urchin embryo

Energy Technology Data Exchange (ETDEWEB)

Bošnjak, Ivana [Laboratory for Biology and Microbial Genetics, Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, Pierottijeva 6, Zagreb (Croatia); Borra, Marco [Molecular Biology Service, Stazione Zoologica Anton Dohrn, Villa Comunale 80121, Napoli (Italy); Iamunno, Franco; Benvenuto, Giovanna [Electron Microscopy Service, Stazione Zoologica Anton Dohrn, Villa Comunale 80121, Napoli (Italy); Ujević, Ivana [Laboratory of Plankton and Shellfish Toxicity, Institute of Oceanography and Fisheries, Setaliste Ivana Mestrovica 63, 21000 Split (Croatia); Bušelić, Ivana [Laboratory for Aquaculture, Institute of Oceanography and Fisheries, Setaliste Ivana Mestrovica 63, 21000 Split (Croatia); Roje-Busatto, Romana [Laboratory of Plankton and Shellfish Toxicity, Institute of Oceanography and Fisheries, Setaliste Ivana Mestrovica 63, 21000 Split (Croatia); Mladineo, Ivona, E-mail: mladineo@izor.hr [Laboratory for Aquaculture, Institute of Oceanography and Fisheries, Setaliste Ivana Mestrovica 63, 21000 Split (Croatia); Assemble Marine Laboratory, Stazione Zoological Anton Dohrn, Villa Comunale, Naples (Italy)

2014-11-15

Highlights: • Effects of BPA on embryonic development of Paracentrotus lividus were determined. • Transport assay, intracellular BPA measurements and gene expression surveys were made. • Multidrug efflux transporter P-gp/ABCB1 is involved in BPA elimination. • Endocrine disruption is inferred by orphan steroid hormone receptor (shr2) upregulation. • BPA delayed mitosis, inducing aberrant karyokinesis and dysfunctional microfilaments. - Abstract: Usage of bisphenol A (BPA) in production of polycarbonate plastics has resulted in global distribution of BPA in the environment. These high concentrations cause numerous negative effects to the aquatic biota, among which the most known is the induction of endocrine disruption. The focus of this research was to determine the effects of two experimentally determined concentrations of BPA (100 nM and 4 μM) on cellular detoxification mechanisms during the embryonic development (2-cell, pluteus) of the rocky sea urchin (Paracentrotus lividus), primarily the potential involvement of multidrug efflux transport in the BPA intercellular efflux. The results of transport assay, measurements of the intracellular BPA and gene expression surveys, for the first time indicate the importance of P-glycoprotein (P-gp/ABCB1) in defense against BPA. Cytotoxic effects of BPA, validated by the immunohistochemistry (IHC) and the transmission electron microscopy (TEM), induced the aberrant karyokinesis, and consequently, the impairment of embryo development through the first cell division and retardation.

Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

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Adena S Spiro

Full Text Available The ABC transporters P-glycoprotein (P-gp, Abcb1 and breast cancer resistance protein (Bcrp, Abcg2 regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9-tetrahydrocannabinol (THC has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT mice. Abcb1a/b (-/-, Abcg2 (-/- and wild-type (WT mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/- and Abcg2 (-/- mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/- mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.

Flow cytometry protocol to evaluate ionizing radiation effects on P-glycoprotein activity

International Nuclear Information System (INIS)

Santos, Neyliane Goncalves dos; Amaral, Ademir; Cavalcanti, Mariana Brayner . E-mail; Neves, Maria Amelia Batista; Machado, Cintia Gonsalves de Faria

2008-01-01

The aim of this work was to establish a protocol to evaluate ionizing radiation effects on P-glycoprotein (P-gp) activity. For this, human peripheral blood samples were irradiated in vitro with different doses and P-gp activity was analyzed for CD4 and CD8 T lymphocytes through rhodamine123-efflux assay by flow cytometry. By simultaneous employment of percentage and mean fluorescence index parameters, subject-by-subject analysis pointed out changes in P-gp activity for some individuals and irradiated samples. Based on this work, the proposed protocol was considered adequate for evaluating P-gp activity on cells after radioactive stress. Besides, this research suggests that P-gp activity could be an important factor to define patient-specific protocols in combined chemo- and radiotherapy, particularly when radiation exposure precedes chemical treatment. (author)

Flow cytometry protocol to evaluate ionizing radiation effects on P-glycoprotein activity

Energy Technology Data Exchange (ETDEWEB)

Santos, Neyliane Goncalves dos; Amaral, Ademir; Cavalcanti, Mariana Brayner [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear]. E-mail; neylisantos@yahoo.com.br; Neves, Maria Amelia Batista; Machado, Cintia Gonsalves de Faria [Fundacao de Hematologia e Hemoterapia de Pernambuco, Recife, PE (Brazil). Unidade de Laboratorios Especializados. Lab. de Imunofenotipagem

2008-12-15

The aim of this work was to establish a protocol to evaluate ionizing radiation effects on P-glycoprotein (P-gp) activity. For this, human peripheral blood samples were irradiated in vitro with different doses and P-gp activity was analyzed for CD4 and CD8 T lymphocytes through rhodamine123-efflux assay by flow cytometry. By simultaneous employment of percentage and mean fluorescence index parameters, subject-by-subject analysis pointed out changes in P-gp activity for some individuals and irradiated samples. Based on this work, the proposed protocol was considered adequate for evaluating P-gp activity on cells after radioactive stress. Besides, this research suggests that P-gp activity could be an important factor to define patient-specific protocols in combined chemo- and radiotherapy, particularly when radiation exposure precedes chemical treatment. (author)

Cell wall O-glycoproteins and N-glycoproteins: biosynthesis and some functional aspects.

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Eric eNguema-Ona

2014-10-01

Full Text Available Cell wall O-glycoproteins and N-glycoproteins are two types of glycomolecules whose glycans are structurally complex. They are both assembled and modified within the endomembrane system, i.e., the endoplasmic reticulum (ER and the Golgi apparatus, before their transport to their final locations within or outside the cell. In contrast to extensin, the O-glycan chains of arabinogalactan proteins are highly heterogeneous consisting mostly of (i a short oligo-arabinoside chain of three to four residues, and (ii a larger -1,3-linked galactan backbone with -1,6-linked side chains containing galactose, arabinose and, often, fucose, rhamnose or glucuronic acid. The fine structure of arabinogalactan chains varies between, and within plant species, and is important for the functional activities of the glycoproteins. With regards to N-glycans, ER-synthesizing events are highly conserved in all eukaryotes studied so far since they are essential for efficient protein folding. In contrast, evolutionary adaptation of N-glycan processing in the Golgi apparatus has given rise to a variety of organism-specific complex structures. Therefore, plant complex-type N-glycans contain specific glyco-epitopes such as core 1,2-xylose, core 1,3-fucose residues and Lewisa substitutions on the terminal position of the antenna. Like O-glycans, N-glycans of proteins are essential for their stability and function. Mutants affected in the glycan metabolic pathways have provided valuable information on the role of N-/O-glycoproteins in the control of growth, morphogenesis and adaptation to biotic and abiotic stresses. With regards to O-glycoproteins only extensin and arabinogalactan proteins are considered herein. The biosynthesis of these glycoproteins and functional aspects are presented and discussed in this review.

Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages.

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Weibin Zha

Full Text Available HIV protease inhibitor (PI-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR, a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp in HIV PI-mediated accumulation of BBR in macrophages.Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT and human P-gp transfected (MDCK/P-gp cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123 efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect P-gp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp.HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic.

Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice

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Xin-Jing Yang

2018-01-01

Full Text Available Background. Tanshinone IIA sodium sulfonate (TSS is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS- induced intestinal injury is still unknown. Objective. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods. Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6 in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3 and Beclin-1 were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin

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Chia-Hao Chen

2012-01-01

Full Text Available Red yeast rice (RYR can reduce cholesterol through its active component, lovastatin. This study was to investigate the pharmacokinetic properties of lovastatin in RYR products and potential RYR-drug interactions. Extracts of three registered RYR products (LipoCol Forte, Cholestin, and Xuezhikang were more effective than pure lovastatin in inhibiting the activities of cytochrome P450 enzymes and P-glycoprotein. Among CYP450 enzymes, RYR showed the highest inhibition on CYP1A2 and CYP2C19, with comparable inhibitory potencies to the corresponding typical inhibitors. In healthy volunteers taking the RYR product LipoCol Forte, the pharmacokinetic properties of lovastatin and lovastatin acid were linear in the dose range of 1 to 4 capsules taken as a single dose and no significant accumulation was observed after multiple dosing. Concomitant use of one LipoCol Forte capsule with nifedipine did not change the pharmacokinetics of nifedipine. Yet, concomitant use of gemfibrozil with LipoCol Forte resulted in a significant increase in the plasma concentration of lovastatin acid. These findings suggest that the use of RYR products may not have effects on the pharmacokinetics of concomitant comedications despite their effects to inhibit the activities of CYP450 enzymes and P-gp, whereas gemfibrozil affects the pharmacokinetics of lovastatin acid when used concomitantly with RYR products.

Palmitoylation of the cysteine-rich endodomain of the SARS-coronavirus spike glycoprotein is important for spike-mediated cell fusion

International Nuclear Information System (INIS)

Petit, Chad M.; Chouljenko, Vladimir N.; Iyer, Arun; Colgrove, Robin; Farzan, Michael; Knipe, David M.; Kousoulas, K.G.

2007-01-01

The SARS-coronavirus (SARS-CoV) is the etiological agent of the severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. The cytoplasmic portion of the S glycoprotein contains four cysteine-rich amino acid clusters. Individual cysteine clusters were altered via cysteine-to-alanine amino acid replacement and the modified S glycoproteins were tested for their transport to cell-surfaces and ability to cause cell fusion in transient transfection assays. Mutagenesis of the cysteine cluster I, located immediately proximal to the predicted transmembrane, domain did not appreciably reduce cell-surface expression, although S-mediated cell fusion was reduced by more than 50% in comparison to the wild-type S. Similarly, mutagenesis of the cysteine cluster II located adjacent to cluster I reduced S-mediated cell fusion by more than 60% compared to the wild-type S, while cell-surface expression was reduced by less than 20%. Mutagenesis of cysteine clusters III and IV did not appreciably affect S cell-surface expression or S-mediated cell fusion. The wild-type S was palmitoylated as evidenced by the efficient incorporation of 3 H-palmitic acid in wild-type S molecules. S glycoprotein palmitoylation was significantly reduced for mutant glycoproteins having cluster I and II cysteine changes, but was largely unaffected for cysteine cluster III and IV mutants. These results show that the S cytoplasmic domain is palmitoylated and that palmitoylation of the membrane proximal cysteine clusters I and II may be important for S-mediated cell fusion

Effect of pH on radiation-induced apoptosis

International Nuclear Information System (INIS)

Chang, W. Song; Park, Heon J.; Lyons, John C.; Auger, Elizabeth A.; Lee, Hyung-Sik

1996-01-01

Purpose/Objective: The effect of environmental pH on the radiation-induced apoptosis in tumor cells in vitro was investigated. Materials and Methods: SCK mammary adenocarcinoma cells of A/J mice were irradiated with γ-rays using a 137 Cs irradiator and incubated in media of different pHs. After incubation at 37 degree sign C for 24-120 hrs., the extent of apoptosis was determined using agarose gel electrophoresis of DNA, in situ TUNEL staining, flow cytometry, and release of 3 H from 3 H-thymidine labeled cells. The membrane integrity, using the trypan blue exclusion method, and the clonogenicity of the cells were also determined. Results: Irradiation with 2-12 Gy of γ-rays induced apoptosis in pH 7.5 medium within 48 hrs. The radiation-induced apoptosis progressively declined as the medium pH was lowered so that little apoptosis occurred in 48 hrs. after irradiation with 12 Gy in pH 6.6 medium. However, when the cells were irradiated and incubated for 48 hrs. in pH 6.6 medium and then medium was replaced with pH 7.5 medium, apoptosis promptly occurred. Apoptosis also occurred even in pH 6.6 medium when the cells were irradiated and maintained in pH 7.5 medium for 8 hrs. or longer post-irradiation before incubation in pH 6.6 medium. Conclusion: An acidic environment markedly suppresses radiation-induced apoptosis probably by suppressing the expression of initial signals responsible for irradiation-induced apoptosis. Indications are that the signals persist in an acidic environment and trigger apoptosis when the environmental acidity is eased. Our results suggest that the acidic environment in human tumors may inhibit the apoptosis after irradiation. However, apoptosis may be triggered when reoxygenation occurs after irradiation, and thus, the intratumor environment becomes less acidic after irradiation. Not only the change in pO 2 but the change in pH during the course of fractionated radiotherapy may greatly influence the outcome of the treatment

The Initial Comparison Study of Sodium Lignosulfonate, Sodium Dodecyl Benzene Sulfonate, and Sodium p-Toluene Sulfonate Surfactant for Enhanced Oil Recovery

Science.gov (United States)

Khoirul Anas, Argo; Iman Prakoso, Nurcahyo; Sasvita, Dilla

2018-04-01

Surfactant (surface active agent) exhibit numerous interesting properties that enable their use as additional component in mobilising of residual oil from capillary pore after secondary recovery process using gas injection and water flooding. In this study, Sodium Lignosulfonate (SLS) surfactant was successfully synthesized by applying batch method using lignin from oil palm empty fruit bunches as precursor. Furthermore, its performance in reducing interfacial tension of crude oil and formation water colloidal system was compared with commercial available surfactant including Sodium Dodecyl Benzene Sulfonate (SDBS) and Sodium p-Toluene Sulfonate (SpTS). The synthesized SLS surfactant was characterized by using Fourier Transform Infrared (FTIR) spectroscopy. Meanwhile, its performance in reducing interfacial tension of crude oil and formation water colloidal system was analyzed by using compatibility test, phase behaviour analysis, and interfacial tension (IFT) measurement. The compatibility test shows that SLS, SDBS, and SpTS surfactants were compatible with formation water. In addition, the phase behaviour analysis shows that SLS surfactant was better than SpTS surfactant, while SDBS surfactant generates the highest performance proved by the best microemulsion formation resulted by SDBS. Furthermore, the optimum concentration of SLS, SDBS, and SpTS surfactants in reducing the interfacial tension of crude oil and formation water was 1.0%. The IFT measurement indicates that the performance of SLS with the value of 1.67 mN/m was also better than SpTS surfactant with the value of 3.59 mN/m. Meanwhile, SDBS surfactant shows the best performance with the IFT value of 0.47 mN/m.

Extreme ultraviolet (EUV) degradation of poly(olefin sulfone)s: Towards applications as EUV photoresists

International Nuclear Information System (INIS)

Lawrie, Kirsten; Blakey, Idriss; Blinco, James; Gronheid, Roel; Jack, Kevin; Pollentier, Ivan; Leeson, Michael J.; Younkin, Todd R.; Whittaker, Andrew K.

2011-01-01

Poly(olefin sulfone)s, formed by the reaction of sulfur dioxide (SO 2 ) and an olefin, are known to be highly susceptible to degradation by radiation and thus have been identified as candidate materials for chain scission-based extreme ultraviolet lithography (EUVL) resist materials. In order to investigate this further, the synthesis and characterisation of two poly(olefin sulfone)s namely poly(1-pentene sulfone) (PPS) and poly(2-methyl-1-pentene sulfone) (PMPS), was achieved and the two materials were evaluated for possible chain scission EUVL resist applications. It was found that both materials possess high sensitivities to EUV photons; however; the rates of outgassing were extremely high. The only observed degradation products were found to be SO 2 and the respective olefin suggesting that depolymerisation takes place under irradiation in a vacuum environment. In addition to depolymerisation, a concurrent conversion of SO 2 moieties to a sulfide phase was observed using XPS.

Physico-chemistry characterization of sulfonated polyacrylamide polymers for use in polymer flooding

Energy Technology Data Exchange (ETDEWEB)

Rashidi, Masoud

2010-07-01

Hydrolyzed polyacrylamide polymer (HPAM) as a feasible and effective viscosifier has been fully studied and used for polymer flooding processes in several oil field, e.g. Daqing oil field. It has been shown that Hydrolyzed polyacrylamide polymers (HPAM) may be a good choice for high temperature condition with no oxygen and no divalent ions presence. At high temperature and high salinity conditions, polymer may precipitates and loss their viscosyfing properties. Also adsorption and retention of polymer in porous medium may change rheological properties of polymers. Thus, the viscosyfing property of polymers is influenced by several important parameters, e.g. salinity, hardness, temperature, adsorption, retention, polymer structure, and etc. By replacing some of carboxylate group of HPAM with another monomer, e.g. sodium salt of acrylic acid and 2-acrylamido-2-methylpropane sulfonic acid (AMPS), effect of high salinity/hardness and temperature seems to be reduced specially for the samples with higher percentage of AMPS co-monomer. The ultimate aim of this work is to develop an understanding of the sulfonated polyacrylamide copolymers with a range of different sulfonation and molecular weight at high salinity and high temperature conditions. Most of the work in this thesis deals with viscosity and adsorption/retention measurements of the sulfonated copolymers and HPAM. The factors which may affect the viscosity of the polymers and have been identified in this work as most likely influencing also adsorption and retention of the polymers are shear rate, polymer concentration, sulfonation degree, molecular weight, NaCl concentration, divalent ion concentration, and temperature. (Author)

Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

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Thewarid Berkban

2015-06-01

Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

Well-Shaped Sulfonic Organosilica Nanotubes with High Activity for Hydrolysis of Cellobiose

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Jing Sun

2017-04-01

Full Text Available Sulfonic organosilica nanotubes with different acidity densities could be synthesized through the co-condensation of ethenyl- or phenylene-bridged organosilane and 3-mercaptopropyltrimethoxysilane followed by sulfhydryl (–SH oxidation. Transmission electron microscopy (TEM analysis and nitrogen adsorption-desorption experiment clearly exhibit the hollow nanotube structures with the diameters of about 5 nm. The compositions of the nanotube frameworks are confirmed by solid state 13C nuclear magnetic resonance (NMR while X-ray photoelectron spectroscopy (XPS shows that about 60–80% of SH groups were oxidized to sulfonic acid (SO3H. The acid contents were measured by both elemental analysis (CHNS mode and acid-base titration experiment, which revealed that the acid density was in the range of 0.74 to 4.37 μmol·m−2 on the solid. These nanotube-based acid catalysts exhibited excellent performances in the hydrolysis of cellobiose with the highest conversion of 92% and glucose selectivity of 96%. In addition, the catalysts could maintain high activity (65% conversion with 92% selectivity even after six recycles.

Glycoproteins and sialyl transferase of human B lymphoblastoid cell lines

International Nuclear Information System (INIS)

Lui, S.W.L.; Ng, M.H.

1980-01-01

We used two radiolabeling methods to study glycoproteins on the surface of lymphoblastoid cells. One of the methods affects tritiation of residues which are oxidized with galactose oxidase and the other causes tritiation of neuraminic acid residues. This approach was shown to allow a better resolution of cell surface glycoproteins than if either method were used alone. Glycoproteins of B 1 - 19 cells which harbor the Epstein-Barr virus genomes were compared with those of its parental cell line, BJAB, which does not harbor the viral genomes. These studies did not reveal a unique viral protein. A 28,000 mol. wt. glycoprotein was found to be the most prominent neuraminic acidlabeled product of B 1 - 19 cells and also of the two other cell lines, Raji and Ly38, which harbor the EBV genomes. A similar molecular weight species from BJAB cells identified by galactose oxidase labeling might be deficient in neuraminic acid residues as it was poorly labeled by the periodate oxidation method. The neuraminic acid content and level of sialyl transferase of BJAB cells were found to be lower than those of the other cell lines studied. (auth.)

Partially Fluorinated Sulfonated Poly(ether amide Fuel Cell Membranes: Influence of Chemical Structure on Membrane Properties

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Chulsung Bae

2011-01-01

Full Text Available A series of fluorinated sulfonated poly (ether amides (SPAs were synthesized for proton exchange membrane fuel cell applications. A polycondensation reaction of 4,4’-oxydianiline, 2-sulfoterephthalic acid monosodium salt, and tetrafluorophenylene dicarboxylic acids (terephthalic and isophthalic or fluoroaliphatic dicarboxylic acids produced SPAs with sulfonation degrees of 80–90%. Controlling the feed ratio of the sulfonated and unsulfonated dicarboxylic acid monomers afforded random SPAs with ion exchange capacities between 1.7 and 2.2 meq/g and good solubility in polar aprotic solvents. Their structures were characterized using NMR and FT IR spectroscopies. Tough, flexible, and transparent films were obtained with dimethylsulfoxide using a solution casting method. Most SPA membranes with 90% sulfonation degree showed high proton conductivity (>100 mS/cm at 80 °C and 100% relative humidity. Among them, two outstanding ionomers (ODA-STA-TPA-90 and ODA-STA-IPA-90 showed proton conductivity comparable to that of Nafion 117 between 40 and 80 °C. The influence of chemical structure on the membrane properties was systematically investigated by comparing the fluorinated polymers to their hydrogenated counterparts. The results suggest that the incorporation of fluorinated moieties in the polymer backbone of the membrane reduces water absorption. High molecular weight and the resulting physical entanglement of the polymers chains played a more important role in improving stability in water, however.

Removal of free fatty acid in Palm Fatty Acid Distillate using sulfonated carbon catalyst derived from biomass wastefor biodiesel production

Science.gov (United States)

Hidayat, Arif; Rochmadi; Wijaya, Karna; Budiman, Arief

2016-01-01

In this research, the esterification of PFAD using the sulfonatedcoconut shell biochar catalyst was studied. Carbon solid catalysts were prepared by a sulfonation of carbonized coconut shells. The performances of the catalysts were evaluated in terms of the reaction temperatures, the molar ratios of methanol to PFAD, the catalyst loading and the reaction times. The reusability of the solid acid carbon catalysts was also studied in this work. The results indicated that the FFA conversion was significantly increased with increasing catalyst loading and reaction times. It can be concluded that the optimal conditions were an PFAD to methanol molar ratio of 1:12, the amount of catalyst of 10%w, and reaction temperature of 60oC.At this optimum condition, the conversion to biodieselreached 88%.

P-Glycoprotein/MDR1 regulates pokemon gene transcription through p53 expression in human breast cancer cells.

Science.gov (United States)

He, Shengnan; Liu, Feng; Xie, Zhenhua; Zu, Xuyu; Xu, Wei; Jiang, Yuyang

2010-08-27

P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter and plays an important role in pharmacokinetics. In this study, we demonstrated that the pokemon promoter activity, the pokemon mRNA and protein expression can be significantly inhibited by Pgp. Chromatin immunoprecipitation assay showed that Pgp can bind the pokemon prompter to repress pokemon transcription activity. Furthermore, Pgp regulated pokemon transcription activity through expression of p53 as seen by use of p53 siRNA transfected MCF-7 cells or p53 mutated MDA-MB-231 cells. Moreover, p53 was detected to bind with Pgp in vivo using immunoprecipitation assay. Taken together, we conclude that Pgp can regulate the expression of pokemon through the presence of p53, suggesting that Pgp is a potent regulator and may offer an effective novel target for cancer therapy.

Radiation graft post-polymerization of sodium styrene sulfonate onto polyethylene

International Nuclear Information System (INIS)

Kitaeva, N.K.; Duflot, V.R.; Ilicheva, N.S.

2013-01-01

Post-irradiation grafting of sodium styrene sulfonate (SSS) in the presence of acrylic acid (AA) has been investigated on polyethylene (PE) pre-exposed to gamma radiation at room temperature in the air. Special attention was paid to the effect of low molecular weight salt additives on the kinetics of graft copolymerization of SSS and AA. The presence of SSS links in the grafted PE copolymers was detected by the methods of UV and FTIR spectroscopy. Based on the FTIR spectroscopy and element analysis data, a mechanism was proposed for graft copolymerization of SSS and AA onto PE. The mechanical properties of the graft copolymers were studied. It was established that PE copolymers grafted with sulfonic acid and carboxyl groups have higher strength characteristics (16.3 MPa) compared to the samples containing only carboxyl groups (11 MPa). (author)

Dual regulation of P-glycoprotein expression by Trichostatin A in cancer cell lines

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Balaguer Trinidad

2012-07-01

Full Text Available Abstract Background It has been reported that the histone deacetylase inhibitor (iHDAc trichostatin A (TSA induces an increase in MDR1 gene transcription (ABCB1. This result would compromise the use of iHDACs in combination with other cytotoxic agents that are substrates of P-glycoprotein (Pgp. It has also been reported the use of alternative promoters by the ABCB1 gene and the existence of a translational control of Pgp protein. Finally, the ABCB1 gene is located in a genetic locus with the nested gene RUNDC3B in the complementary DNA strand, raising the possibility that RUNDC3B expression could interfere with ABCB1 alternative promoter regulation. Methods A combination of RT-PCR, real time RT-PCR, Western blot and drug accumulation assays by flow cytometry has been used in this study. Results The iHDACs-induced increase in MDR1 mRNA levels is not followed by a subsequent increase in Pgp protein levels or activity in several pancreatic and colon carcinoma cell lines, suggesting a translational control of Pgp in these cell lines. In addition, the MDR1 mRNA produced in these cell lines is shorter in its 5′ end that the Pgp mRNA produced in cell lines expressing Pgp protein. The different size of the Pgp mRNA is due to the use of alternative promoters. We also demonstrate that these promoters are differentially regulated by TSA. The translational blockade of Pgp mRNA in the pancreatic carcinoma cell lines could be related to alterations in the 5′ end of the MDR1 mRNA in the Pgp protein expressing cell lines. In addition, we demonstrate that the ABCB1 nested gene RUNDC3B expression although upregulated by TSA is independent of the ABCB1 alternative promoter used. Conclusions The results show that the increase in MDR1 mRNA expression after iHDACs treatment is clinically irrelevant since this mRNA does not render an active Pgp protein, at least in colon and pancreatic cancer cell lines. Furthermore, we demonstrate that TSA in fact, regulates

Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier

NARCIS (Netherlands)

Doze, P; Van Waarde, A; Elsinga, P H; Hendrikse, N H; Vaalburg, W

Low cerebral uptake of some therapeutic drugs can be enhanced by modulation of P-glycoprotein (P-gp), an ATP-driven drug efflux pump at the blood-brain barrier (BBB). We investigated the possibility of increasing cerebral uptake of the beta-adrenergic ligands S-1'-[(18)F]-fluorocarazolol (FCAR) and

Surface activation of MnNb{sub 2}O{sub 6} nanosheets by oxalic acid for enhanced photocatalysis

Energy Technology Data Exchange (ETDEWEB)

Wu, Junshu; Wang, Jinshu, E-mail: wangjsh@bjut.edu.cn; Li, Hongyi; Li, Yongli; Du, Yucheng; Yang, Yilong; Jia, Xinjian

2017-05-01

Graphical abstract: Visible light driven photoreduction of Cr(VI) over MnNb{sub 2}O{sub 6} nanosheets is enhanced via oxalic acid surface complex to generate activation layer. - Highlights: • MnNb{sub 2}O{sub 6} nanosheets are crystallized by a surface capping route of sulfonate groups. • Oxalic acid on MnNb{sub 2}O{sub 6} nanosheets forms an excited surface complex hybrid layer. • Surface activation enhances visible-light induced reduction of Cr(VI) into Cr(III). - Abstract: MnNb{sub 2}O{sub 6} nanosheets (P-MNOs) is selectively crystallized by using surface capping ligand with functional sulfonate group (sodium dodecyl benzene sulphonate), which binds to the (131) surface of MnNb{sub 2}O{sub 6} inducing the morphology-controlled crystallization of MnNb{sub 2}O{sub 6} materials. Surface modification of photoactive P-MNOs with electron-rich oxalic acid ligands establishes an excited surface complex layer on phase-pure P-MNO as evidenced by spectroscopic analyses (FT-IR, UV–vis, Raman, PL, etc.), and thus more efficiently photocatalyzes the reduction of Cr(VI) into Cr(III) than solely P-MNOs or oxalic acid under visible light (λ > 420 nm) via a ligand-to-metal interfacial electron transfer pathway. However, the interaction between oxalic acid and MnNb{sub 2}O{sub 6} is highly dependent upon the morphology of solid MnNb{sub 2}O{sub 6} substrate due to the higher surface-area-to-volume ratio and higher surface activity of (131) planes in the sheet-like morphology. This study could assist the construction of stable niobate material systems to allow a versatile solid surface activation for establishing more energy efficient and robust catalysis process under visible light.

Effect of bisphenol A on P-glycoprotein-mediated efflux and ultrastructure of the sea urchin embryo.

Science.gov (United States)

Bošnjak, Ivana; Borra, Marco; Iamunno, Franco; Benvenuto, Giovanna; Ujević, Ivana; Bušelić, Ivana; Roje-Busatto, Romana; Mladineo, Ivona

2014-11-01

Usage of bisphenol A (BPA) in production of polycarbonate plastics has resulted in global distribution of BPA in the environment. These high concentrations cause numerous negative effects to the aquatic biota, among which the most known is the induction of endocrine disruption. The focus of this research was to determine the effects of two experimentally determined concentrations of BPA (100nM and 4μM) on cellular detoxification mechanisms during the embryonic development (2-cell, pluteus) of the rocky sea urchin (Paracentrotus lividus), primarily the potential involvement of multidrug efflux transport in the BPA intercellular efflux. The results of transport assay, measurements of the intracellular BPA and gene expression surveys, for the first time indicate the importance of P-glycoprotein (P-gp/ABCB1) in defense against BPA. Cytotoxic effects of BPA, validated by the immunohistochemistry (IHC) and the transmission electron microscopy (TEM), induced the aberrant karyokinesis, and consequently, the impairment of embryo development through the first cell division and retardation. Copyright © 2014 Elsevier B.V. All rights reserved.

A new hypercrosslinked supermicroporous polymer, with scope for sulfonation, and its catalytic potential for the efficient synthesis of biodiesel at room temperature.

Science.gov (United States)

Bhunia, Subhajit; Banerjee, Biplab; Bhaumik, Asim

2015-03-25

We have designed a new hypercrosslinked supermicroporous polymer (HMP-1) with a BET surface area of 913 m(2) g(-1) by FeCl3 via a catalyzed Friedel-Crafts alkylation reaction between carbazole and α,α'-dibromo-p-xylene. Upon sulfonation HMP-1 yielded a very efficient solid acid catalyst for the production of biodiesels via esterification/transesterification of free fatty acids (FFA)/esters at room temperature.

Evidence for P-Glycoprotein Involvement in Cell Volume Regulation Using Coulter Sizing in Flow Cytometry

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Jennifer Pasquier

2015-06-01

Full Text Available The regulation of cell volume is an essential function that is coupled to a variety of physiological processes such as receptor recycling, excitability and contraction, cell proliferation, migration, and programmed cell death. Under stress, cells undergo emergency swelling and respond to such a phenomenon with a regulatory volume decrease (RVD where they release cellular ions, and other osmolytes as well as a concomitant loss of water. The link between P-glycoprotein, a transmembrane transporter, and cell volume regulation is controversial, and changes in cells volume are measured using microscopy or electrophysiology. For instance, by using the patch-clamp method, our team demonstrated that chloride currents activated in the RVD were more intense and rapid in a breast cancer cell line overexpressing the P-glycoprotein (P-gp. The Cell Lab Quanta SC is a flow cytometry system that simultaneously measures electronic volume, side scatter and three fluorescent colors; altogether this provides unsurpassed population resolution and accurate cell counting. Therefore, here we propose a novel method to follow cellular volume. By using the Coulter-type channel of the cytometer Cell Lab Quanta SC MPL (multi-platform loading, we demonstrated a role for the P-gp during different osmotic treatments, but also a differential activity of the P-gp through the cell cycle. Altogether, our data strongly suggests a role of P-gp in cell volume regulation.

Analytical methodology for sulfonated lignins

NARCIS (Netherlands)

Brudin, S.; Schoenmakers, P.

2010-01-01

There is a significant need to characterize and classify lignins and sulfonated lignins. Lignins have so far received a good deal of attention, whereas this is not true for sulfonated lignins. There is a clear demand for a better understanding of sulfonated lignins on a chemical as well as physical

P-Glycoprotein/MDR1 Regulates Pokemon Gene Transcription Through p53 Expression in Human Breast Cancer Cells

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Wei Xu

2010-08-01

Full Text Available P-glycoprotein (Pgp, encoded by the multidrug resistance 1 (MDR1 gene, is an efflux transporter and plays an important role in pharmacokinetics. In this study, we demonstrated that the pokemon promoter activity, the pokemon mRNA and protein expression can be significantly inhibited by Pgp. Chromatin immunoprecipitation assay showed that Pgp can bind the pokemon prompter to repress pokemon transcription activity. Furthermore, Pgp regulated pokemon transcription activity through expression of p53 as seen by use of p53 siRNA transfected MCF-7 cells or p53 mutated MDA-MB-231 cells. Moreover, p53 was detected to bind with Pgp in vivo using immunoprecipitation assay. Taken together, we conclude that Pgp can regulate the expression of pokemon through the presence of p53, suggesting that Pgp is a potent regulator and may offer an effective novel target for cancer therapy.

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

Science.gov (United States)

Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-glycoprotein.

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Jianfang Chen

Full Text Available Multidrug resistance (MDR is one of the major reasons chemotherapy-based treatments fail. Hypoxia is generally associated with tumor chemoresistance. However, the correlation between the heterodimeric hypoxia-inducible factor-1 (HIF-1 and the multidrug resistance (MDR1 gene/transporter P-glycoprotein (P-gp remains unclear. This study aims to explore the molecular mechanisms of reversing colon cancer MDR by focusing on the target gene HIF-1α.A chemotherapeutic sensitivity assay was used to observe the efficiency of MDR reversal in LoVo multicellular spheroids (MCS. The apoptotic level induced by different drugs was examined by flow cytometry (FCM. Binding of HIF-1α to the MDR1 gene promoter was evaluated by Chromatin immunoprecipitation (ChIP. The relationship between HIF-1α/P-gp expression and sensitivity to chemotherapy was analyzed.The sensitivity of LoVo MCS to all four chemotherapy drugs was decreased to varying degrees under hypoxic conditions. After silencing the HIF-1α gene, the sensitivities of LoVo MCS to all four chemotherapy drugs were restored. The apoptotic levels that all the drugs induced were all decreased to various extents in the hypoxic group. After silencing HIF-1α, the apoptosis level induced by all four chemotherapy drugs increased. The expression of HIF-1α and P-gp was significantly enhanced in LoVo MCS after treatment with hypoxia. Inhibiting HIF-1α significantly decreased the expression of MDR1/P-gp mRNA or protein in both the LoVo monolayers and LoVo MCS. The ChIP assay showed that HIF-1α was bound to the MDR1 gene promoter. Advanced colon carcinoma patients with expression of both HIF-1α and P-gp were more resistant to chemotherapy than that with non expression.HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-gp. The expression of HIF-1α and MDR1/P-gp can be used as a predictive marker for chemotherapy resistance in colon cancer.

Partial sulfonation of PVdF-co-HFP: A preliminary study and characterization for application in direct methanol fuel cell

International Nuclear Information System (INIS)

Das, Suparna; Kumar, Piyush; Dutta, Kingshuk; Kundu, Patit Paban

2014-01-01

Highlights: • Synthesis of sulfonated PVdF-co-HFP by reacting with chlorosulfonic acid. • Maximum degree of sulfonation and best properties were obtained for 7 h reaction. • A maximum water uptake value of 20% was obtained. • A maximum IEC value of 0.42 meq g −1 was obtained. • A methanol permeability of 2.44 × 10 −7 cm 2 s −1 was obtained. - Abstract: Sulfonation of PVdF-co-HFP was conducted by treating the copolymer with chlorosulfonic acid. The efficiency of this sulfonated copolymer towards application as a polymer electrolyte membrane in direct methanol fuel cell (DMFC) was evaluated. For this purpose, we determined the thermal stability, water uptake, ion exchange capacity (IEC), methanol crossover, and proton conductivity of the prepared membranes as functions of duration and degree of sulfonation. The characteristic aromatic peaks obtained in the FT-IR spectra confirmed the successful sulfonation of PVdF-co-HFP. The effect of sulfonation on the semi-crystalline nature of pure PVdF-co-HFP was determined from XRD analysis. Water uptake results indicated that a sulfonation time of 7 h produced maximum water uptake value of about 20%, with a corresponding IEC and proton conductivity values of about 0.42 meq g −1 and 0.00375 S cm −1 respectively. The maximum current density was recorded to be 30 mA cm −2 at 0.2 V potential

Fe–Co/sulfonated polystyrene as an efficient and selective catalyst in heterogeneous Baeyer–Villiger oxidation reaction of cyclic ketones

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Yingting Wang

2018-02-01

Full Text Available A highly efficient catalyst Fe–Co/sulfonated polystyrene (Fe–Co/SPS was introduced and synthesized, which catalyzed BV oxidation of ketones with aqueous hydrogen peroxide to give the corresponding lactones in high yield and selectivity. Solid acid catalyst of Fe–Co/SPS has been prepared by using the 98-wt% sulfuric acid as the sulfonating agent and CoCl2 combined FeCl3 as sources of metal ions. Various physical–chemical characterizations including FT-IR, XRD, SEM and TGA, revealed that bimetallic ions Fe3+–Co2+ species in the sulfonated polystyrene framework were responsible for the catalytic activities. The BV reaction catalyzed by Fe–Co/SPS highlighted the special effects between metal ions and protonic acids as well as solvent-free heterogeneous catalytic oxidation with excellent conversion.

Molecular Cloning and Characterization of a P-Glycoprotein from the Diamondback Moth, Plutella xylostella (Lepidoptera: Plutellidae)

Science.gov (United States)

Tian, Lixia; Yang, Jiaqiang; Hou, Wenjie; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Zhou, Xuguo; Wu, Qingjun

2013-01-01

Macrocyclic lactones such as abamectin and ivermectin constitute an important class of broad-spectrum insecticides. Widespread resistance to synthetic insecticides, including abamectin and ivermectin, poses a serious threat to the management of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), a major pest of cruciferous plants worldwide. P-glycoprotein (Pgp), a member of the ABC transporter superfamily, plays a crucial role in the removal of amphiphilic xenobiotics, suggesting a mechanism for drug resistance in target organisms. In this study, PxPgp1, a putative Pgp gene from P. xylostella, was cloned and characterized. The open reading frame (ORF) of PxPgp1 consists of 3774 nucleotides, which encodes a 1257-amino acid peptide. The deduced PxPgp1 protein possesses structural characteristics of a typical Pgp, and clusters within the insect ABCB1. PxPgp1 was expressed throughout all developmental stages, and showed the highest expression level in adult males. PxPgp1 was highly expressed in midgut, malpighian tubules and testes. Elevated expression of PxPgp1 was observed in P. xylostella strains after they were exposed to the abamectin treatment. In addition, the constitutive expressions of PxPgp1 were significantly higher in laboratory-selected and field-collected resistant strains in comparison to their susceptible counterpart. PMID:24264038

Acid resistance and response to pH-induced stress in two Lactobacillus plantarum strains with probiotic potential.

Science.gov (United States)

Šeme, H; Gjuračić, K; Kos, B; Fujs, Š; Štempelj, M; Petković, H; Šušković, J; Bogovič Matijašić, B; Kosec, G

2015-01-01

Two new Lactobacillus plantarum strains, KR6-DSM 28780 and M5 isolated from sour turnip and traditional dried fresh cheese, respectively, were evaluated for species identity, antibiotic susceptibility, resistance to gastrointestinal conditions and adaptive response to low pH. Resistance mechanisms involved in the adaptation to acid-induced stress in these two strains were investigated by quantitative PCR of the atpA, cfa1, mleS and hisD genes. In addition to absence of antibiotic resistance, the two L. plantarum strains showed excellent survival rates at pH values as low as 2.4. Adaptive response to low pH was clearly observed in both strains; strain KR6 was superior to M5, as demonstrated by its ability to survive during 3 h incubation at pH 2.0 upon adaptation to moderately acidic conditions. In contrast, acid adaptation did not significantly affect the survival rate during simulated passage through the gastrointestinal tract. In both strains, induction of histidine biosynthesis (hisD) was upregulated during the acid adaptation response. In addition, significant upregulation of the cfa1 gene, involved in modulation of membrane fatty acid composition, was observed during the adaptation phase in strain KR6 but not in strain M5. Cells adapted to moderately acidic conditions also showed a significantly increased viability after the lyophilisation procedure, a cross-protection phenomenon providing additional advantage in probiotic application.

Multiple Drug Transport Pathways through human P-Glycoprotein(†)

Science.gov (United States)

McCormick, James W.; Vogel, Pia D.; Wise, John G.

2015-01-01

P-glycoprotein (P-gp) is a plasma membrane efflux pump that is commonly associated with therapy resistances in cancers and infectious diseases. P-gp can lower the intracellular concentrations of many drugs to subtherapeutic levels by translocating them out of the cell. Because of the broad range of substrates transported by P-gp, overexpression of P-gp causes multidrug resistance. We reported previously on dynamic transitions of P-gp as it moved through conformations based on crystal structures of homologous ABCB1 proteins using in silico targeted molecular dynamics techniques. We expanded these studies here by docking transport substrates to drug binding sites of P-gp in conformations open to the cytoplasm, followed by cycling the pump through conformations that opened to the extracellular space. We observed reproducible transport of two substrates, daunorubicin and verapamil, by an average of 11 to 12 Å through the plane of the membrane as P-gp progressed through a catalytic cycle. Methyl-pyrophosphate, a ligand that should not be transported by P-gp, did not show this movement through P-gp. Drug binding to either of two subsites on P-gp appeared to determine the initial pathway used for drug movement through the membrane. The specific side-chain interactions with drugs within each pathway seemed to be, at least in part, stochastic. The docking and transport properties of a P-gp inhibitor, tariquidar, were also studied. A mechanism of inhibition by tariquidar is presented that involves stabilization of an outward open conformation with tariquidar bound in intracellular loops or at the drug binding domain of P-gp. PMID:26125482

Destruction of gel sulfonated cation-exchangers of the KU-2 type under the influence of hydrogen peroxide

Energy Technology Data Exchange (ETDEWEB)

Roginskaya, B.S.; Zavadovskaya, A.S.; Znamenskii, Yu.P.; Paskhina, N.A.; Dobrova, E.I.

1988-10-20

The purpose of this work was to study the mechanism of interaction of Soviet sulfonated cation-exchangers of the KU-2 type with hydrogen peroxide. It is shown that under the influence of hydrogen peroxide sulfonated cation-exchangers begin, after a certain induction period, to lose capacity and to release destruction products into water; the length of the induction period increases with the degree of cross-linking. In a given time of contact between the resin and the solution the degree of destruction falls with increase of cross-linking. The principal product of destruction of sulfonated cation-exchangers is an aromatic sulfonic acid containing oxidized groups in the side chains.

40 CFR 721.2565 - Alkylated sulfonated diphenyl oxide, alkali and amine salts.

Science.gov (United States)

2010-07-01

..., alkali and amine salts. 721.2565 Section 721.2565 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.2565 Alkylated sulfonated diphenyl oxide, alkali and... substances identified as alkylated sulfonated diphenyl oxide, alkali salt (PMN P-93-352) and alkylated...

Intracellular localization of hydroxyproline-rich glycoprotein biosynthesis

International Nuclear Information System (INIS)

Robinson, D.G.; Andreae, M.; Glas, A.R.; Sauer, A.

1984-01-01

The structural proteins of plant cell walls are glycoproteins characterized by O-glucosidic linkages to hydroxyproline or serine. Proline, not hydroxyproline, is the translatable amino acid in hydroxyproline-rich glycoproteins (HRGP). Hydroxylation and arabinosylation of proline are sequential, post-translational events. Because of this, there is no a priori reason for expecting HRGP synthesis to follow the well-established route for secretory and plasma membrane (PM) glycoproteins, i.e., from endoplasmic reticulum (ER) via the Golgi apparatus (GA) to the PM. In this paper, two plausible alternatives for HRGO secretion are examined. Because a feature of the majority of dicotyledons is overlapping GA and PM regions in sucrose density gradients, the authors have used two monocotyledonous systems to determine the distribution of HRGP and enzyme activity

IR Laser Ablative Degradation of Poly(phenylene ether sulfone): Deposition of Films Containing Sulfone, Sulfoxide and Sulfide Groups

Czech Academy of Sciences Publication Activity Database

Blazevska-Gilev, J.; Bastl, Zdeněk; Šubrt, Jan; Stopka, Pavel; Pola, Josef

2009-01-01

Roč. 94, č. 2 (2009), s. 196-200 ISSN 0141-3910 R&D Projects: GA AV ČR IAA400720619 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z40400503; CEZ:AV0Z40320502 Keywords : laser ablation * laser-induced degradation * poly(1,4-phenylene ether-sulfone) Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 2.154, year: 2009

Inhibitory Effects of Neochamaejasmin B on P-Glycoprotein in MDCK-hMDR1 Cells and Molecular Docking of NCB Binding in P-Glycoprotein

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Lanying Pan

2015-02-01

Full Text Available Stellera chamaejasme L. (Thymelaeaceae is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010 as a toxic Traditional Chinese Medicine. It is claimed to have antivirus, antitumor and antibacterial properties in China and other Asian countries. Studies were carried out to characterize the inhibition of neochamaejasmin B (NCB on P-glycoprotein (P-gp, ABCB1, MDR1. Rhodamine-123 (R-123 transport and accumulation studies were performed in MDCK-hMDR1 cells. ABCB1 (MDR1 mRNA gene expression and P-gp protein expression were analyzed. Binding selectivity studies based on molecular docking were explored. R-123 transport and accumulation studies in MDCK-hMDR1 cells indicated that NCB inhibited the P-gp-mediated efflux in a concentration-dependent manner. RT-PCR and Western blot demonstrated that the P-gp expression was suppressed by NCB. To investigate the inhibition type of NCB on P-gp, Ki and Ki’ values were determined by double-reciprocal plots in R-123 accumulation studies. Since Ki was greater than Ki’, the inhibition of NCB on P-gp was likely a mixed type of competitive and non-competitive inhibition. The results were confirmed by molecular docking in our current work. The docking data indicated that NCB had higher affinity to P-gp than to Lig1 ((S-5,7-dihydroxy-2-(4-hydroxyphenylchroman-4-one.

Issues raised by the reference doses for perfluorooctane sulfonate and perfluorooctanoic acid.

Science.gov (United States)

Dong, Zhaomin; Bahar, Md Mezbaul; Jit, Joytishna; Kennedy, Bruce; Priestly, Brian; Ng, Jack; Lamb, Dane; Liu, Yanju; Duan, Luchun; Naidu, Ravi

2017-08-01

On 25th May 2016, the U.S. EPA released reference doses (RfDs) for Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) of 20ng/kg/day, which were much more conservative than previous values. These RfDs rely on the choices of animal point of departure (PoD) and the toxicokinetics (TK) model. At this stage, considering that the human evidence is not strong enough for RfD determination, using animal data may be appropriate but with more uncertainties. In this article, the uncertainties concerning RfDs from the choices of PoD and TK models are addressed. Firstly, the candidate PoDs should include more critical endpoints (such as immunotoxicity), which may lead to lower RfDs. Secondly, the reliability of the adopted three-compartment TK model is compromised: the parameters are not non-biologically plausible; and this TK model was applied to simulate gestation and lactation exposures, while the two exposure scenarios were not actually included in the model structure. Copyright © 2017. Published by Elsevier Ltd.

Separation of aliphatic carboxylic acids and benzenecarboxylic acids by ion-exclusion chromatography with various cation-exchange resin columns and sulfuric acid as eluent.

Science.gov (United States)

Ohta, Kazutoku; Ohashi, Masayoshi; Jin, Ji-Ye; Takeuchi, Toyohide; Fujimoto, Chuzo; Choi, Seong-Ho; Ryoo, Jae-Jeong; Lee, Kwang-Pill

2003-05-16

The application of various hydrophilic cation-exchange resins for high-performance liquid chromatography (sulfonated silica gel: TSKgel SP-2SW, carboxylated silica gel: TSKgel CM-2SW, sulfonated polymethacrylate resin: TSKgel SP-5PW, carboxylated polymethacrylate resins: TSKgel CM-5PW and TSKgel OA-Pak A) as stationary phases in ion-exclusion chromatography for C1-C7 aliphatic carboxylic acids (formic, acetic, propionic, butyric, isovaleric, valeric, isocaproic, caproic, 2-methylhexanoic and heptanoic acids) and benzenecarboxylic acids (pyromellitic, trimellitic, hemimellitic, o-phthalic, m-phthalic, p-phthalic, benzoic, salicylic acids and phenol) was carried out using diluted sulfuric acid as the eluent. Silica-based cation-exchange resins (TSKgel SP-2SW and TSKgel CM-2SW) were very suitable for the ion-exclusion chromatographic separation of these benzenecarboxylic acids. Excellent simultaneous separation of these benzenecarboxylic acids was achieved on a TSKgel SP-2SW column (150 x 6 mm I.D.) in 17 min using a 2.5 mM sulfuric acid at pH 2.4 as the eluent. Polymethacrylate-based cation-exchange resins (TSKgel SP-5PW, TSKgel CM-5PW and TSKgel OA-Pak A) acted as advanced stationary phases for the ion-exclusion chromatographic separation of these C1-C7 aliphatic carboxylic acids. Excellent simultaneous separation of these C1-C7 acids was achieved on a TSKgel CM-5PW column (150 x 6 mm I.D.) in 32 min using a 0.05 mM sulfuric acid at pH 4.0 as the eluent.

Assessment of perfluorooctanoic acid and perfluorooctane sulfonate in surface water - Tamil Nadu, India.

Science.gov (United States)

Sunantha, Ganesan; Vasudevan, Namasivayam

2016-08-15

As an emerging class of environmentally persistent organic pollutants, perfluorinated compounds (PFCs), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS); have been universally found in the environment. Wastewater and untreated effluents are likely the major causes for the accumulation of PFCs in surface water. There are very few reports on the contamination of PFCs in the developing countries, particularly in India. This study reports the quantitative analysis of PFOA and PFOS in Noyyal, Cauvery, and also lakes in and around Chennai, using Ultra-Fast liquid chromatograph. The concentration of PFOA and PFOS ranged from 4 to 93ng/L and 3 to 29ng/L, respectively. The concentration of PFOS was below detectable limit in Cauvery River. A reliable concentration of PFOA was recorded at all sites of River Cauvery (5ng/L). The present study could be useful for the assessment of future monitoring programs of PFOA and PFOS in the surface water. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

Directory of Open Access Journals (Sweden)

Anna Maisa

2009-06-01

Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

Sulfonic acid functionalized boron nitride nanomaterials as a microwave-assisted efficient and highly biologically active one-pot synthesis of piperazinyl-quinolinyl fused Benzo[c]acridine derivatives

Energy Technology Data Exchange (ETDEWEB)

Murugesan, Arul; Gengan, R.M., E-mail: genganrm@dut.ac.za; Krishnan, Anand

2017-02-15

Boron nitride nano material based solid acid catalyst was found to be an efficient and reusable sulfonic acid catalyst for the synthesis of one-pot Knoevenagel and Michael type reactions in 3, 3-dimethyl-9-(2-(4-methylpiperazin-1-yl) quinolin-3-yl)-3, 4, 9, 10-tetrahydroacridin-1(2H)-one derivatives under microwave irradiation conditions. The catalyst was prepared by mixing boron nitrile and (3-mercaptopropyl) trimethoxysilane. This is simple and safe method for the preparation of solid acid catalysts. The morphological properties of catalyst determined by using FT-IR, XRD, TEM, SEM and Raman spectroscopy. The synthesised catalyst was employed in Knoevenagel and Michael type reactions to synthesise novel piperazinyl-quinolinyl based acridine derivatives. Furthermore the newly-synthesised compounds have been used for molecular docking in DNA binding studies. The method developed in this study has the advantages of good yield, simplicity coupled with safety and short reaction time. Most importantly it was found that the solid acid catalyst can be recycled with only 5% loss of activity. - Highlights: • One-pot Synthesis of Knoevenagel and Michel type reactions. • Synthesis of Sulfonic acid Functionalized Boron nitride nano materials. • Synthesis of piperazinyl-quinolinyl fused Benzo[c]acridine derivatives under Microwave irradiation. • Molecular docking studies were performed on piperazinyl-quinolinyl acridine derivatives using DNA.

Sulfonated polyimides containing triphenylphosphine oxide for proton exchange membranes

Energy Technology Data Exchange (ETDEWEB)

Mandal, Arun Kumar; Bera, Debaditya; Banerjee, Susanta, E-mail: susanta@matsc.iitkgp.ernet.in

2016-09-15

A series of sulfonated co-polyimides (co-SPI) were prepared by one pot polycondensation reaction of a combination of diamines namely; 4,4′-diaminostilbene-2,2′-disulfonic acid (DSDSA) and prepared non-sulfonated diamine (DATPPO) containing triphenylphosphine oxide with 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA). All these soluble co-SPI gave flexible membranes with high thermal stability and showed good mechanical property. Transmission electron microscopy (TEM) analysis revealed the microphase separated morphology with well-dispersed hydrophilic (cluster size in the range of 5–55 nm) domains. The co-SPI membranes showed high oxidative and hydrolytic stability with higher proton conductivity. All these co-SPI membranes exhibited low water uptake and swelling ratio. The co-SPI membrane TPPO-60 (60% degree of sulfonation) with IEC{sub W} = 1.84 mequiv g{sup −1} showed high proton conductivity (99 mS cm{sup −1} at 80 °C and 107 mS cm{sup −1} at 90 °C) in water with high oxidative (20 h) and hydrolytic stability (only 5% degradation in 24 h). - Highlights: • Triphenylphosphine oxide containing sulfonated polyimides (SPIs) was synthesized. • The SPIs showed good oxidative and hydrolytic stability and high proton conductivity. • TEM analysis revealed well separated morphology of the SPIs.

In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [125I]MRK-16 monoclonal antibody

International Nuclear Information System (INIS)

Scott, Andrew M.; Rosa, Eddie; Mehta, Bippin M.; Divgi, Chaitanya R.; Finn, Ronald D.; Biedler, June L.; Tsuruo, Takashi; Kalaigian, Hovannes; Larson, Steven M.

1995-01-01

Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with 125 I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [ 125 ]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targeting of [ 125 I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g ± SD) (18.76 ± 2.94 vs 10.93 ± 0.96; p 125 I]MRK-16 was confirmed by comparison to [ 131 I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [ 125 I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors

ATP-binding cassette transporters P-glycoprotein and breast cancer related protein are reduced in capillary cerebral amyloid angiopathy

NARCIS (Netherlands)

Carrano, A.; Snkhchyan, H.; Kooij, G.; van der Pol, S.; van Horssen, J.; Veerhuis, R.; Hoozemans, J.J.M.; Rozemuller, A.J.M.; de Vries, H.E.

2014-01-01

Alzheimer's disease (AD) is the most common form of dementia and marked by deposition of amyloid-β (Aβ) within the brain. Alterations of Aβ transporters at the neurovasculature may play a role in the disease process. We investigated the expression of ABC transporters P-glycoprotein (P-gp) and breast

Perfluorooctane sulfonate adsorption on powder activated carbon: Effect of phosphate (P) competition, pH, and temperature.

Science.gov (United States)

Qian, Jin; Shen, Mengmeng; Wang, Peifang; Wang, Chao; Li, Kun; Liu, Jingjing; Lu, Bianhe; Tian, Xin

2017-09-01

Powdered activated carbon (PAC), as an adsorbent, was applied to remove perfluorooctane sulfonate (PFOS) from aqueous solution. Laboratory batch experiments were performed to investigate the influences of phosphate (P) competition, temperature, and pH for PFOS adsorption onto PAC. The results showed that higher temperature favored PFOS adsorption in single and binary systems. The kinetic data fitted very well to the pseudo second-order kinetic model. Thermodynamically, the endothermic enthalpy of the PFOS adsorption in single and binary systems were 125.07 and 21.25 kJ mol -1 , respectively. The entropy of the PFOS adsorption in single and binary systems were 0.479 and 0.092 kJ mol -1  K -1 , respectively. And the Gibbs constants were negative. These results indicated that the adsorption processes were spontaneous. The adsorption isotherms of PFOS agreed well with the Langmuir model. In the single system, PFOS adsorption decreased with increased pH value. The difference in the amount of PFOS adsorption between the single and binary systems increased at higher pH. Frustrated total internal reflection (FTIR) demonstrated that P competition increased the hydrophilicity of the PAC and the electrostatic repulsion between PFOS and PAC, then the PFOS adsorption amount decreased. It also demonstrated that, at higher temperature, increased PFOS adsorption was mainly due to the higher diffusion rate of PFOS molecules and greater number of active sites opened on the PAC surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

The radiation chemistry of aqueous solutions of sodium 9,10-anthraquinone-2-sulfonate

International Nuclear Information System (INIS)

Burchill, C.E.; Smith, D.M.; Charlton, J.L.

1976-01-01

The 60 Co γ-radiolysis of aqueous solutions of sodium 9,10-anthraquinone-2-sulfonate has been studied in acidic, unbuffered, and alkaline conditions and with addition of N 2 O and 2-propanol. Mechanisms are proposed to account for the yields of H 2 O 2 and hydroxylated anthraquinone sulfonates. In neutral solution, in the absence of O 2 , the OH and e - adducts undergo preferential cross termination. Reduction of the OH adduct leads to dehydration and regeneration of the quinone. (author)

Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).

Science.gov (United States)

Eggers Pedersen, Kathrine; Basu, Niladri; Letcher, Robert; Greaves, Alana K; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

2015-04-01

Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; rp=0.83, p=0.041, n=6) and across brain regions (e.g. ∑PFCA; rp=0.47, p=0.001, ∑PFSA; rp=0.44, p>0.001; n=50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp=0.33, p=0.02 and PFDoDA; rp=0.34, p=0.014; n=52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp=-0.95, p=0.013, n=5) and across brain regions (e.g. �

Exhaustive sampling of docking poses reveals binding hypotheses for propafenone type inhibitors of P-glycoprotein.

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Freya Klepsch

2011-05-01

Full Text Available Overexpression of the xenotoxin transporter P-glycoprotein (P-gp represents one major reason for the development of multidrug resistance (MDR, leading to the failure of antibiotic and cancer therapies. Inhibitors of P-gp have thus been advocated as promising candidates for overcoming the problem of MDR. However, due to lack of a high-resolution structure the concrete mode of interaction of both substrates and inhibitors is still not known. Therefore, structure-based design studies have to rely on protein homology models. In order to identify binding hypotheses for propafenone-type P-gp inhibitors, five different propafenone derivatives with known structure-activity relationship (SAR pattern were docked into homology models of the apo and the nucleotide-bound conformation of the transporter. To circumvent the uncertainty of scoring functions, we exhaustively sampled the pose space and analyzed the poses by combining information retrieved from SAR studies with common scaffold clustering. The results suggest propafenone binding at the transmembrane helices 5, 6, 7 and 8 in both models, with the amino acid residue Y307 playing a crucial role. The identified binding site in the non-energized state is overlapping with, but not identical to, known binding areas of cyclic P-gp inhibitors and verapamil. These findings support the idea of several small binding sites forming one large binding cavity. Furthermore, the binding hypotheses for both catalytic states were analyzed and showed only small differences in their protein-ligand interaction fingerprints, which indicates only small movements of the ligand during the catalytic cycle.

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

International Nuclear Information System (INIS)

Grose, C.; Jackson, W.; Traugh, J.A.

1989-01-01

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

Characterization of monomeric intermediates during VSV glycoprotein structural transition.

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Aurélie A Albertini

2012-02-01

Full Text Available Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformational changes of viral glycoproteins. Crystal structures provide static pictures of pre- and post-fusion conformations of these proteins but the transition pathway remains elusive. Here, using several biophysical techniques, including analytical ultracentrifugation, circular dichroïsm, electron microscopy and small angle X-ray scattering, we have characterized the low-pH-induced fusogenic structural transition of a soluble form of vesicular stomatitis virus (VSV glycoprotein G ectodomain (G(th, aa residues 1-422, the fragment that was previously crystallized. While the post-fusion trimer is the major species detected at low pH, the pre-fusion trimer is not detected in solution. Rather, at high pH, G(th is a flexible monomer that explores a large conformational space. The monomeric population exhibits a marked pH-dependence and adopts more elongated conformations when pH decreases. Furthermore, large relative movements of domains are detected in absence of significant secondary structure modification. Solution studies are complemented by electron micrographs of negatively stained viral particles in which monomeric ectodomains of G are observed at the viral surface at both pH 7.5 and pH 6.7. We propose that the monomers are intermediates during the conformational change and thus that VSV G trimers dissociate at the viral surface during the structural transition.

Study of Synthesis Polyethylene glycol oleate Sulfonated as an Anionic Surfactant for Enhanced Oil Recovery (EOR)

Science.gov (United States)

Sampora, Yulianti; Juwono, Ariadne L.; Haryono, Agus; Irawan, Yan

2017-11-01

Mechanical Enhanced Oil Recovery (EOR) through chemical injection is using an anionic surfactant to improve the recovery of oil residues, particularly in a reservoir area that has certain characteristics. This case led the authors to conduct research on the synthesis of an anionic surfactant based on oleic acid and polyethylene glycol 400 that could be applied as a chemical injection. In this work, we investigate the sulfonation of Polyethylene glycol oleate (PDO) in a sulfuric acid agent. PDO in this experiment was derived from Indonesian palm oil. Variation of mole reactant and reaction time have been studied. The surfactant has been characterized by measuring the interfacial tension, acid value, ester value, saponification value, iodine value, Fourier Transform Infrared (FTIR), and particle size analyzer. There is a new peak at 1170-1178 cm-1 indicating that S=O bond has formed. PDO sulfonate exhibits good surface activity due to interfacial tension of 0,003 mN/m. Thus, polyethylene glycol oleate sulfonate was successfully synthesized and it could be useful as a novel an anionic surfactant.

Increasing BMI is associated with reduced expression of P-glycoprotein (ABCB1 gene) in the human brain with a stronger association in African-Americans than Caucasians

DEFF Research Database (Denmark)

Nielsen, Julie Vendelbo; Olesen, Rasmus Hansen; Lauridsen, Jesper Krogh

2016-01-01

The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood-brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common sid...... online publication, 29 November 2016; doi:10.1038/tpj.2016.74....

Ursodeoxycholic acid protects cardiomyocytes against cobalt chloride induced hypoxia by regulating transcriptional mediator of cells stress hypoxia inducible factor 1α and p53 protein.

Science.gov (United States)

Mohamed, Anis Syamimi; Hanafi, Noorul Izzati; Sheikh Abdul Kadir, Siti Hamimah; Md Noor, Julina; Abdul Hamid Hasani, Narimah; Ab Rahim, Sharaniza; Siran, Rosfaiizah

2017-10-01

In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca 2+ ] i ), and sphingosine-1-phosphate (S1P)-receptor via Gα i -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca 2+ ] i , and S1P-Gα i -coupled-receptor. Cardiomyocytes were isolated from newborn rats (0-2 days), and hypoxia was induced by using cobalt chloride (CoCl 2 ). Cardiomyocytes were treated with UDCA and cotreated with either FTY720 (S1P-receptor agonist) or pertussis toxin (PTX; Gα i inhibitor). Cells were subjected for proliferation assay, beating frequency, QuantiGene Plex assay, western blot, immunofluorescence, and calcium imaging. Our findings showed that UDCA counteracted the effects of CoCl 2 on cell viability, beating frequency, HIF-1α, and p53 protein expression. We found that these cardioprotection effects of UDCA were similar to FTY720, S1P agonist. Furthermore, we observed that UDCA protects CMs against CoCl 2 -induced [Ca 2+ ] i dynamic alteration. Pharmacological inhibition of the Gα i -sensitive receptor did not abolish the cardioprotection of UDCA against CoCl 2 detrimental effects, except for cell viability and [Ca 2+ ] i . Pertussis toxin is partially effective in inhibiting UDCA protection against CoCl 2 effects on CM cell viability. Interestingly, PTX fully inhibits UDCA cardioprotection on CoCl 2 -induced [Ca 2+ ] i dynamic changes. We conclude that UDCA cardioprotection against CoCl 2 -induced hypoxia is similar to FTY720, and its actions are not fully mediated by the Gα i -coupled protein sensitive pathways. Ursodeoxycholic acid is the most hydrophilic bile

Acid monolayer functionalized iron oxide nanoparticle catalysts

Science.gov (United States)

Ikenberry, Myles

Superparamagnetic iron oxide nanoparticle functionalization is an area of intensely active research, with applications across disciplines such as biomedical science and heterogeneous catalysis. This work demonstrates the functionalization of iron oxide nanoparticles with a quasi-monolayer of 11-sulfoundecanoic acid, 10-phosphono-1-decanesulfonic acid, and 11-aminoundecanoic acid. The carboxylic and phosphonic moieties form bonds to the iron oxide particle core, while the sulfonic acid groups face outward where they are available for catalysis. The particles were characterized by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), potentiometric titration, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectrometry (XPS), and dynamic light scattering (DLS). The sulfonic acid functionalized particles were used to catalyze the hydrolysis of sucrose at 80° and starch at 130°, showing a higher activity per acid site than the traditional solid acid catalyst Amberlyst-15, and comparing well against results reported in the literature for sulfonic acid functionalized mesoporous silicas. In sucrose catalysis reactions, the phosphonic-sulfonic nanoparticles (PSNPs) were seen to be incompletely recovered by an external magnetic field, while the carboxylic-sulfonic nanoparticles (CSNPs) showed a trend of increasing activity over the first four recycle runs. Between the two sulfonic ligands, the phosphonates produced a more tightly packed monolayer, which corresponded to a higher sulfonic acid loading, lower agglomeration, lower recoverability through application of an external magnetic field, and higher activity per acid site for the hydrolysis of starch. Functionalizations with 11-aminoundecanoic acid resulted in some amine groups binding to the surfaces of iron oxide nanoparticles. This amine binding is commonly ignored in iron oxide

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

International Nuclear Information System (INIS)

Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro; Ogihara, Takuo

2016-01-01

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.

Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein

Energy Technology Data Exchange (ETDEWEB)

Tomono, Takumi [Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan); Kajita, Masahiro [Laboratory of Molecular Pharmaceutics and Technology, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan); Yano, Kentaro [Laboratory of Biopharmaceutics, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan); Ogihara, Takuo, E-mail: togihara@takasaki-u.ac.jp [Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033 (Japan)

2016-08-05

P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment. -- Highlights: •Adenovirus vector infection induced P-gp mRNA expression in three NSCLC cell lines. •Adenovirus vector infection enhanced P-gp-mediated doxorubicin efflux from the cells. •The increase of P-gp was not mediated by nuclear receptors (PXR, CAR) or COX-2.

Constituents of Propolis: Chrysin, Caffeic Acid, p-Coumaric Acid, and Ferulic Acid Induce PRODH/POX-Dependent Apoptosis in Human Tongue Squamous Cell Carcinoma Cell (CAL-27).

Science.gov (United States)

Celińska-Janowicz, Katarzyna; Zaręba, Ilona; Lazarek, Urszula; Teul, Joanna; Tomczyk, Michał; Pałka, Jerzy; Miltyk, Wojciech

2018-01-01

Propolis evokes several therapeutic properties, including anticancer activity. These activities are attributed to the action of polyphenols. Previously it has been demonstrated, that one of the most abundant polyphenolic compounds in ethanolic extracts of propolis are chrysin, caffeic acid, p -coumaric acid, and ferulic acid. Although their pro-apoptotic activity on human tongue squamous cell carcinoma cells (CAL-27) was established previously, the detailed mechanism of this process remains unclear. Considering the crucial role of proline metabolism and proline dehydrogenase/proline oxidase (PRODH/POX) in the regulation of cancer cell survival/apoptosis, we studied these processes in polyphenol-treated CAL-27 cells. All studied polyphenols evoked anti-proliferative activity, accompanied by increased PRODH/POX, P53, active caspases-3 and -9 expressions and decreased collagen biosynthesis, prolidase activity and proline concentration in CAL-27 cells. These data suggest that polyphenols of propolis induce PRODH/POX-dependent apoptosis through up-regulation of mitochondrial proline degradation and down-regulation of proline utilization for collagen biosynthesis.

HMGB1 Contributes to the Expression of P-Glycoprotein in Mouse Epileptic Brain through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products.

Directory of Open Access Journals (Sweden)

Yan Chen

Full Text Available The objective of the present study was to investigate the role of high-mobility group box-1 (HMGB1 in the seizure-induced P-glycoprotein (P-gp overexpression and the underlying mechanism. Kainic acid (KA-induced mouse seizure model was used for in vivo experiments. Male C57BL/6 mice were divided into four groups: normal saline control (NS group, KA-induced epileptic seizure (EP group, and EP group pretreated with HMGB1 (EP+HMGB1 group or BoxA (HMGB1 antagonist, EP+BoxA group. Compared to the NS group, increased levels of HMGB1 and P-gp in the brain were observed in the EP group. Injection of HMGB1 before the induction of KA further increased the expression of P-gp while pre-treatment with BoxA abolished this up-regulation. Next, the regulatory role of HMGB1 and its potential involved signal pathways were investigated in mouse microvascular endothelial bEnd.3 cells in vitro. Cells were treated with HMGB1, HMGB1 plus lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS [toll-like receptor 4 (TLR4 antagonist], HMGB1 plus FPS-ZM1 [receptor for advanced glycation end products (RAGE inhibitor], HMGB1 plus SN50 [nuclear factor-kappa B (NF-κB inhibitor], or vehicle. Treatment with HMGB1 increased the expression levels of P-gp, TLR4, RAGE and the activation of NF-κB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-κB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene in endothelial cells. These data indicate that HMGB1 contributes to the overexpression of P-gp in mouse epileptic brain tissues via activation of TLR4/RAGE receptors and the downstream transcription factor NF-κB in brain microvascular endothelial cells.

Simultaneous determination of caffeine and paracetamol by square wave voltammetry at poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode.

Science.gov (United States)

Tefera, Molla; Geto, Alemnew; Tessema, Merid; Admassie, Shimelis

2016-11-01

Poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode (poly(AHNSA)/GCE) was prepared for simultaneous determination of caffeine and paracetamol using square-wave voltammetry. The method was used to study the effects of pH and scan rate on the voltammetric response of caffeine and paracetamol. Linear calibration curves in the range of 10-125μM were obtained for both caffeine and paracetamol in acetate buffer solution of pH 4.5 with a correlation coefficient of 0.9989 and 0.9986, respectively. The calculated detection limits (S/N=3) were 0.79μM for caffeine and 0.45μM for paracetamol. The effects of some interfering substances in the determination of caffeine and paracetamol were also studied and their interferences were found to be negligible which proved the selectivity of the modified electrode. The method was successfully applied for the quantitative determination of caffeine and paracetamol in Coca-Cola, Pepsi-Cola and tea samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electrical stimulation promotes nerve cell differentiation on polypyrrole/poly (2-methoxy-5 aniline sulfonic acid) composites.

Science.gov (United States)

Liu, Xiao; Gilmore, Kerry J; Moulton, Simon E; Wallace, Gordon G

2009-12-01

The purpose of this work was to investigate for the first time the potential biomedical applications of novel polypyrrole (PPy) composites incorporating a large polyelectrolyte dopant, poly (2-methoxy-5 aniline sulfonic acid) (PMAS). The physical and electrochemical properties were characterized. The PPy/PMAS composites were found to be smooth and hydrophilic and have low electrical impedance. We demonstrate that PPy/PMAS supports nerve cell (PC12) differentiation, and that clinically relevant 250 Hz biphasic current pulses delivered via PPy/PMAS films significantly promote nerve cell differentiation in the presence of nerve growth factor (NGF). The capacity of PPy/PMAS composites to support and enhance nerve cell differentiation via electrical stimulation renders them valuable for medical implants for neurological applications.

Asiatic Acid (AA) Sensitizes Multidrug-Resistant Human Lung Adenocarcinoma A549/DDP Cells to Cisplatin (DDP) via Downregulation of P-Glycoprotein (MDR1) and Its Targets.

Science.gov (United States)

Cheng, Qilai; Liao, Meixiang; Hu, Haibo; Li, Hongliang; Wu, Longhuo

2018-01-01

P-glycoprotein (P-gp, i.e., MDR1) is associated with the phenotype of multidrug resistance (MDR) and causes chemotherapy failure in the management of cancers. Searching for effective MDR modulators and combining them with anticancer drugs is a promising strategy against MDR. Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, may have an antitumor activity. The present study assessed the reversing effect of AA on MDR and possible molecular mechanisms of AA action in MDR1-overexpressing cisplatin (DDP)-resistant lung cancer cells, A549/DDP. Human lung adenocarcinoma A549/DDP cells were either exposed to different concentrations of AA or treated with DDP, and their viability was measured by the MTT assay. A Rhodamine 123 efflux assay, immunofluorescent staining, ATPase assay, reverse-transcription PCR (RT-PCR), and western blot analysis were conducted to elucidate the mechanisms of action of AA on MDR. Our results showed that AA significantly enhanced the cytotoxicity of DDP toward A549/DDP cells but not its parental A549 cells. Furthermore, AA strongly inhibited P-gp expression by blocking MDR1 gene transcription and increased the intracellular accumulation of the P-gp substrate Rhodamine 123 in A549/DDP cells. Nuclear factor (NF)-kB (p65) activity, IkB degradation, and NF-kB/p65 nuclear translocation were markedly inhibited by pretreatment with AA. Additionally, AA inhibited the MAPK-ERK pathway, as indicated by decreased phosphorylation of ERK1 and -2, AKT, p38, and JNK, thus resulting in reduced activity of the Y-box binding protein 1 (YB1) via blockage of its nuclear translocation. AA reversed P-gp-mediated MDR by inhibition of P-gp expression. This effect was likely related to downregulation of YB1, and this effect was mediated by the NF-kB and MAPK-ERK pathways. AA may be useful as an MDR reversal agent for combination therapy in clinical trials. © 2018 The Author(s). Published by S. Karger AG, Basel.

Glycoprotein 90K Promotes E-Cadherin Degradation in a Cell Density-Dependent Manner via Dissociation of E-Cadherin–p120-Catenin Complex

Directory of Open Access Journals (Sweden)

So-Yeon Park

2017-12-01

Full Text Available Glycoprotein 90K (also known as LGALS3BP or Mac-2BP is a tumor-associated protein, and high 90K levels are associated with poor prognosis in some cancers. To clarify the role of 90K as an indicator for poor prognosis and metastasis in epithelial cancers, the present study investigated the effect of 90K on an adherens junctional protein, E-cadherin, which is frequently absent or downregulated in human epithelial cancers. Treatment of certain cancer cells with 90K significantly reduced E-cadherin levels in a cell-population-dependent manner, and these cells showed decreases in cell adhesion and increases in invasive cell motility. Mechanistically, 90K-induced E-cadherin downregulation occurred via ubiquitination-mediated proteasomal degradation. 90K interacted with the E-cadherin–p120-catenin complex and induced its dissociation, altering the phosphorylation status of p120-catenin, whereas it did not associate with β-catenin. In subconfluent cells, 90K decreased membrane-localized p120-catenin and the membrane fraction of the p120-catenin. Particularly, 90K-induced E-cadherin downregulation was diminished in p120-catenin knocked-down cells. Taken together, 90K upregulation promotes the dissociation of the E-cadherin–p120-catenin complex, leading to E-cadherin proteasomal degradation, and thereby destabilizing adherens junctions in less confluent tumor cells. Our results provide a potential mechanism to explain the poor prognosis of cancer patients with high serum 90K levels.

Evodiamine synergizes with doxorubicin in the treatment of chemoresistant human breast cancer without inhibiting P-glycoprotein.

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Shengpeng Wang

Full Text Available Drug resistance is one of the main hurdles for the successful treatment of breast cancer. The synchronous targeting of apoptosis resistance and survival signal transduction pathways may be a promising approach to overcome drug resistance. In this study, we determined that evodiamine (EVO, a major constituent of the Chinese herbal medicine Evodiae Fructus, could induce apoptosis of doxorubicin (DOX-sensitive MCF-7 and DOX-resistant MCF-7/ADR cells in a caspase-dependent manner, as confirmed by significant increases of cleaved poly(ADP-ribose polymerase (PARP, caspase-7/9, and caspase activities. Notably, the reversed phenomenon of apoptosis resistance by EVO might be attributed to its ability to inhibit the Ras/MEK/ERK pathway and the expression of inhibitors of apoptosis (IAPs. Furthermore, our results indicated that EVO enhanced the apoptotic action of DOX by inhibiting the Ras/MEK/ERK cascade and the expression of IAPs without inhibiting the expression and activity of P-glycoprotein (P-gp. Taken together, our data indicate that EVO, a natural product, may be useful applied alone or in combination with DOX for the treatment of resistant breast cancer.

Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein.

Science.gov (United States)

von Moltke, Lisa L; Weemhoff, James L; Perloff, Michael D; Hesse, Leah M; Harmatz, Jerold S; Roth-Schechter, Barbara F; Greenblatt, David J

2002-12-01

The influence of high concentrations of zolpidem (100 microM, corresponding to approximately 200 times maximum therapeutic concentrations) on the activity of six human Cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Zolpidem produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. Transport of rhodamine 123, presumed to be mediated mainly by the energy-dependent efflux transport protein P-glycoprotein, was studied in a cell culture system using a human intestinal cell line. High concentrations of zolpidem (100 microM), exceeding the usual therapeutic range by more than 100-fold, produced only modest impairment of rhodamine 123 transport. The findings indicate that zolpidem is very unlikely to cause clinical drug interactions attributable to impairment of CYP activity or P-gp mediated transport. Copyright 2002 John Wiley & Sons, Ltd.

Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

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Bankstahl, Jens P; Kuntner, Claudia; Abrahim, Aiman; Karch, Rudolf; Stanek, Johann; Wanek, Thomas; Wadsak, Wolfgang; Kletter, Kurt; Müller, Markus; Löscher, Wolfgang; Langer, Oliver

2008-08-01

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.

Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation.

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Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna; Iliuk, Anton; Tao, W Andy

2016-11-30

Glycoproteins have vast structural diversity that plays an important role in many biological processes and have great potential as disease biomarkers. Here, we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase glycoprotein array (polyGPA), to capture and profile glycoproteomes specifically, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture preoxidized glycans on glycoproteins from complex protein samples such as biofluids. The captured glycoproteins were subsequently detected using the same validated antibodies as in RPPA. We demonstrated the outstanding specificity, sensitivity, and quantitative capabilities of polyGPA by capturing and detecting purified as well as endogenous α-1-acid glycoprotein (AGP) in human plasma. We further applied quantitative N-glycoproteomics and the strategy to validate a panel of glycoproteins identified as potential biomarkers for bladder cancer by analyzing urine glycoproteins from bladder cancer patients or matched healthy individuals.

Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer blood-retinal barrier

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Yue-Hong Zhang

2017-07-01

Full Text Available AIM: To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp in mitochondria of D407 cells. METHODS: D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123 alone and in the presence of P-gp inhibitor (Tariquidar using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. RESULTS: P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. CONCLUSION: H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

(R-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

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Lammertsma Adriaan A

2011-01-01

Full Text Available Abstract Background Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp expression and functionality at an early stage after induction of status epilepticus by kainate. Methods (R-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles as well as by population mixed effects modelling (NONMEM. Results All data analysis approaches indicated only modest differences in brain distribution of (R-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. Conclusions P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

(R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

International Nuclear Information System (INIS)

Syvänen, Stina; Luurtsema, Gert; Molthoff, Carla FM; Windhorst, Albert D; Huisman, Marc C; Lammertsma, Adriaan A; Voskuyl, Rob A; Lange, Elizabeth C de

2011-01-01

Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate. (R)-[ 11 C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[ 11 C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R)-[ 11 C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM). All data analysis approaches indicated only modest differences in brain distribution of (R)-[ 11 C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate

Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

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Dong, Guang-Hui; Wang, Jing; Zhang, Ying-Hua; Liu, Miao-Miao; Wang, Da; Zheng, Li; Jin, Yi-He

2012-01-01

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. -- Highlights: ► PFOS immunotoxicity is caused by induction of apoptosis via the p53 activation. ► PFOS exposure can induce down regulation of Bcl-xl. ► Mitochondria are involved in PFOS-induced apoptosis. ► PFOS exposure can cause the release of cytochrome c and activation of caspase-3.

Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

Energy Technology Data Exchange (ETDEWEB)

Dong, Guang-Hui, E-mail: ghdong@mail.cmu.edu.cn [School of Public Health, China Medical University, Shenyang 110001 (China); Wang, Jing [Department of Biostatistics, School of Public Health, Saint Louis University, Saint Louis, MO 63104 (United States); Zhang, Ying-Hua; Liu, Miao-Miao; Wang, Da [School of Public Health, China Medical University, Shenyang 110001 (China); Zheng, Li [Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Jin, Yi-He [School of Public Health, China Medical University, Shenyang 110001 (China); School of Environmental Science and Technology, Dalian University of Technology, Key Laboratory of Industrial Ecology and Environmental Engineering, Ministry of Education, Dalian 116024 (China)

2012-10-15

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. -- Highlights: ► PFOS immunotoxicity is caused by induction of apoptosis via the p53 activation. ► PFOS exposure can induce down regulation of Bcl-xl. ► Mitochondria are involved in PFOS-induced apoptosis. ► PFOS exposure can cause the release of cytochrome c and activation of caspase-3.

Radiation-induced apoptosis in different pH environments in vitro

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Lee, Hyung-Sik; Park, Heon J.; Lyons, John C.; Griffin, Robert J.; Auger, Elizabeth A.; Song, Chang W.

1997-01-01

Purpose: The effect of environmental pH on the radiation-induced apoptosis in tumor cells in vitro was investigated. Methods and Materials: Mammary adenocarcinoma cells of A/J mice (SCK cells) were irradiated with γ-rays using a 137 Cs irradiator and incubated in media of different pHs. After incubation at 37 deg. C for 24-120 h the extent of apoptosis was determined using agarose gel electrophoresis, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, flow cytometry, and release of 3 H from 3 H-thymidine labeled cells. The clonogenicity of the cells irradiated in different pH medium was determined, and the progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Results: Irradiation with 2-12 Gy of γ-rays induced apoptosis in SCK cells in pH 7.5 medium within 48 h as judged from the results of four different assays mentioned. Radiation-induced apoptosis declined as the medium pH was lowered from 7.5 to 6.4. Specifically, the radiation-induced degradation of DNA including the early DNA breaks, as determined with the TUNEL method, progressively declined as the medium pH was lowered so that little DNA fragmentation occurred 48 h after irradiation with 12 Gy in pH 6.6 medium. When the cells were irradiated and incubated for 48 h in pH 6.6 medium and the medium was replaced with pH 7.5 medium, DNA fragmentation promptly occurred. DNA fragmentation also occurred even in pH 6.6 medium when the cells were irradiated and maintained in pH 7.5 medium for 8 h or longer post-irradiation before incubation in pH 6.6 medium. The radiation-induced G 2 arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Conclusion: Radiation-induced apoptosis in SCK cells in vitro is reversibly suppressed in an acidic environment. Taking the results of four different assays together, it was concluded that early step(s) in the apoptotic pathway, probably the DNA break or upstream of DNA break, is