Electrodeposition of Pt-Pb nanoparticles (PtPbNPs) to multi-walled carbon nanotubes (MWCNTs) resu... more Electrodeposition of Pt-Pb nanoparticles (PtPbNPs) to multi-walled carbon nanotubes (MWCNTs) resulted in a stable PtPbNP/MWCNT nanocomposite with high electrocatalytic activity to glucose oxidation in either neutral or alkaline medium. More importantly, the nanocomposite electrode with a slight modification exhibited high sensitivity, high selectivity, and low detection limit in amperometric glucose sensing at physiological neutral pH (poised at a negative potential). At +0.30 V in neutral solution, the nanocomposite electrode exhibited linearity up to 11 mM of glucose with a sensitivity of 17.8 microA cm(-2) mM(-1) and a detection limit of 1.8 microM (S/N=3). Electroactive ascorbic acid (0.1 mM), uric acid (0.1 mM) and fructose (0.3 mM) invoked only 23%, 14% and 9%, respectively, of the current response obtained for 3 mM glucose. At -0.15 V in neutral solution, the electrode responded linearly to glucose up to 5 mM with a detection limit of 0.16 mM (S/N=3) and detection sensitivity of approximately 18 microA cm(-2) mM(-1). At this negative potential, ascorbic acid, uric acid, and fructose were not electroactive, therefore, not interfering with glucose sensing. Modification of the nanocomposite electrode with Nafion coating followed by electrodeposition of a second layer of PtPbNPs on the Nafion coated PtPbNP/MWCNT nanocomposite produced a glucose sensor (poised at -0.15 V) with a lower detection limit (7.0 microM at S/N=3) and comparable sensitivity, selectivity and linearity compared to the PtPbNP/MWCNT nanocomposite. The Nafion coating lowered the detection limit by reducing the background noise, while the second layer of PtPbNPs restored the sensitivity to the level before Nafion coating.
ABSTRACT We report the design and fabrication of a novel single cell electroporation biochip feat... more ABSTRACT We report the design and fabrication of a novel single cell electroporation biochip featuring high aspect ratio nickel micro-electrodes with smooth side walls between which individual cells are attached. The biochip is fabricated using Proton Beam Writing (PBW), a new direct write lithographic technique capable of fabricating high quality high-aspect-ratio nano and microstructures. By applying electrical impulses across the biochip electrodes, SYTOX® Green nucleic acid stain is incorporated into mouse neuroblastoma (N2a) cells and observed via green fluorescence when the stain binds with DNA inside the cell nucleus. Three parameters; electric field strength, pulse duration, and numbers of pulses have been investigated for the single cell electroporation process. The results indicate high transfection rates as well as cell viability of 82.1 and 86.7% respectively. This single cell electroporation system may represent a promising method for the introduction of a wide variety of fluorophores, nanoparticles, quantum dots, DNAs and proteins into cells.
We have proposed that the translocation/activation of protein kinase C (PKC) in synergism with a ... more We have proposed that the translocation/activation of protein kinase C (PKC) in synergism with a Ca2+-mediated event plays an essential role in hippocampal long-term potentiation (LTP). In a previous study, we saw no effect of PKC-activating phorbol esters alone on baseline responseS, although it has been reported by others to enhance synaptic transmission. To resolve this discrepancy, we investigated the dose-response to phorbol esters of both baseline and potentiated granule cell responses elicited with perforant path stimulation. It was confirmed that iontophoretic ejection of phorbol ester to the dentate hilus, which alone had no effect on baseline responses, prolonged the persistence of potentiation produced by 2 trains of 400 Hz stimulation. These data support the proposed synergistic model in which the effects of phorbol ester and high frequency stimulation together produce a long-lasting potentiation of synaptic activation. A similar synergism was observed with ejection of a lower dose of phorbol ester into the perforant path synaptic zone in the molecular layer. Higher doses delivered to the synaptic zone without 400 Hz stimulation were sufficient to enhance baseline synaptic responses, but these doses inhibited the initial potentiation induced with 2 trains of 400 Hz stimulation delivered immediately after ejection. There was at times a slowly developing enhancement observed after the initial blockade. Thus, induction of a persistent synaptic enhancement was observed without initial potentiation. Measurement of PKC activity in membrane and cytosol indicated that PKC activation is only associated with the persistence phase of LTP. In contrast, there was no change in PKC subcellular distribution associated with the blockade of initial potentiation by higher doses of PDBu.
Gold clusters have been electrodeposited on a boron-doped diamond (BDD) electrode by scanning the... more Gold clusters have been electrodeposited on a boron-doped diamond (BDD) electrode by scanning the potential from 0.7 V to 0.0 V (vs. 3 M KCl-Ag/AgCl reference) in a solution of 0.5 mM KAuCl 4 and 1.0 M KCl. The cluster-modified diamond (Au/ BDD) electrode has been used to investigate the oxidative properties of dopamine (DA) and ascorbate (AA). The modified diamond electrode shows a higher activity for DA oxidation than AA; the oxidation potential of DA shifted to a less-positive potential (0.11 V) than that of AA, which oxidized at 0.26 V, and DA possesses a much higher peak current than that of AA. The reversibility of the electrode reaction with DA is significantly improved at the Au/BDD electrode, which results in a large increase in the square-wave voltammetric peak current, with a detection limit of 0.1 lM in the presence of a large excess of AA. The Au/BDD electrode shows excellent sensitivity and good selectivity for DA detection. A self-assembled monolayer (SAM) of mercaptoacetic acid on the Au clusters was used to provide an antifouling effect as the negative CO 2 ± groups repulse negative ascorbate and attract positive dopamine in pH 7.4 buffer. After pre-absorption, the SAM/Au/BDD electrode could detect 1.0 nM DA in a linear range from 10 nM to 10 lM in the presence of 10 ±4 M AA.
Differential mechanisms underlying the modulation of delayed-rectifier K ϩ channel in mouse neoco... more Differential mechanisms underlying the modulation of delayed-rectifier K ϩ channel in mouse neocortical neurons by nitric oxide.
Publisher Summary This chapter describes the procedure for the preparation of protein kinase C is... more Publisher Summary This chapter describes the procedure for the preparation of protein kinase C isozymes and substrates from rat brain. The potential importance of protein kinase C (PKC) in the regulation of nervous functions has been well recognized. Both the short-term responses associated with neurotransmitter release, modulation of ion channels, regulation of receptor functions, and cellular metabolism as well as long-term responses that are involved in the enhancement of synaptic plasticity and control of growth and differentiation have been linked to the action of PKC. PKC α, β, γ, and ɛ are copurified from the rat brain extract during the early stage of purification, and the resolution of each isozyme is achieved at the final step by hydroxylapatite column chromatography. Fractions containing the major PKC α, β, and γ and those also containing PKC ɛ are concentrated separately in Amicon cells and exchanged with buffer B by repetitive dilution and concentration. The cofactor requirements of the PKC-catalyzed reaction depend on the substrates used in the assay. With histone H1 as a substrate, PKC α, β, and γ are stimulated by Ca2+, PS, and DAG or phorbol ester, PKC δ and ɛ are stimulated by PS and DAG, and PKC ζ is stimulated by PS alone. Significant variations in the cofactor requirement are related to the interactions among the various components in the assay. Identification of these PKC substrates during purification is based on the apparent Mr on SDS-PAGE, immunoreactivities toward specific antibodies, and elution profiles on the C4 reversed-phase column. It should be noted that these proteins are frequently eluted from the C4 column as cluster of peaks of the same Mr. Calmodulin, which binds neuromodulin, neurogranin, and MARCKS at a domain adjacent to the PKC phosphorylation site(s), exerts its inhibitory effect by hindering the access of the kinase to the substrates.
Journal of Pharmacology and Experimental Therapeutics, Jun 30, 2006
Dose-limiting diarrhea and myelosuppression compromise the success of irinotecan (7-ethyl-10-[4-[... more Dose-limiting diarrhea and myelosuppression compromise the success of irinotecan (7-ethyl-10-[4-[1-piperidino]-1-piperidino]carbonyloxycamptothecin) (CPT-11)-based chemotherapy. A recent pilot study indicates that thalidomide attenuates the toxicity of CPT-11 in cancer patients. This study aimed to investigate whether coadministered thalidomide modulated the toxicities of CPT-11 and the underlying mechanisms using several in vivo and in vitro models. Diarrhea, intestinal lesions, cytokine expression, and intestinal epithelial apoptosis were monitored. Coadministered thalidomide (100 mg/kg i.p. for 8 days) significantly attenuated body weight loss, myelosuppression, diarrhea, and intestinal histological lesions caused by CPT-11 (60 mg/kg i.v. for 4 days). This was accompanied by inhibition of tumor necrosis factor-alpha, interleukins 1 and 6 and interferon-gamma, and intestinal epithelial apoptosis. Coadministered thalidomide also significantly increased the systemic exposure of CPT-11 but decreased that of SN-38 (7-ethyl-10-hydroxycampothecin). It significantly reduced the biliary excretion and cecal exposure of CPT-11, SN-38, and SN-38 glucuronide. Thalidomide hydrolytic products inhibited hydrolysis of CPT-11 in rat liver microsomes but not in primary rat hepatocytes. In addition, thalidomide and its major hydrolytic products, such as phthaloyl glutamic acid (PGA), increased the intracellular accumulation of CPT-11 and SN-38 in primary rat hepatocytes. They also significantly decreased the transport of CPT-11 and SN-38 in Caco-2 and parental MDCKII cells. Thalidomide and PGA also significantly inhibited P-glycoprotein (PgP/MDR1), multidrug resistance-associated protein (MRP1)- and MRP2-mediated CPT-11 and SN-38 transport in MDCKII cells. These results provide insights into the pharmacodynamic and pharmacokinetic mechanisms for the protective effects of thalidomide against CPT-11-induced intestinal toxicity.
... LI Zheng-qiang 1* * , LI Xiao-yuan1 , SHEU Fwu-shan2, CHEN Dong-ming 1 and YU Nai-teng 1 ( 1 ... more ... LI Zheng-qiang 1* * , LI Xiao-yuan1 , SHEU Fwu-shan2, CHEN Dong-ming 1 and YU Nai-teng 1 ( 1 Department of Chemistry, 2 Department of Biochemistry, H ong K ong University of Science & T echnology, H ong K ong ) (Received April 4, 1997) ...
Iron-phthalocyanines (FePc) are functionalized at multi-walled carbon nanotubes (MWNTs) to remark... more Iron-phthalocyanines (FePc) are functionalized at multi-walled carbon nanotubes (MWNTs) to remarkably improve the sensitivity toward hydrogen peroxide. We constructed a highly sensitive and selective glucose sensor on FePc-MWNTs electrode based on the immobilization of glucose oxidase (GOD) on poly-o-aminophenol (POAP)electropolymerized electrode surface. SEM images indicate that GOD enzymes trapped in POAP film tend to deposit primarily on the curved tips and evenly disperse along the sidewalls. The resulting GOD @ POAP/FePc-MWNTs biosensor exhibits excellent performance for glucose with a rapid response (less than 8 s), a wide linear range (up to 4.0 Â 10 À3 M), low detection limits (2.0 Â 10 À7 M with a signal-to-noise of 3), a highly reproducible response (RSD of 2.6%), and long-term stability (120 days). Such characteristics may be attributed to the catalytic activity of FePc and carbon nanotube, permselectivity of POAP film, as well as the large surface area of carbon nanotube materials.
Microchim Acta (2008) 162: 235243 DOI 10.1007/s00604-007-0882-0 Printed in The Netherlands ... E... more Microchim Acta (2008) 162: 235243 DOI 10.1007/s00604-007-0882-0 Printed in The Netherlands ... Electrocatalytic oxidation of methanol on a platinum modified carbon nanotube electrode ... Ying Wen1,2, Jian-Shan Ye3,4, Wei-De Zhang3, Fwu-Shan Sheu4, Guo Qin Xu2
Previous correlative and interventive work from this laboratory has suggested that activation of ... more Previous correlative and interventive work from this laboratory has suggested that activation of protein kinase C (PKC) is important for the maintenance of the hippocampal long-term potentiation (LTP) response. One such study demonstrated that application of the cis- unsaturated fatty acid, oleate, a newly discovered PKC activator, could prolong the time course of LTP. The present study explored the mechanism of cis-unsaturated fatty acid action on LTP produced by perforant path stimulation. First, neither oleate application nor high- frequency stimulation alone produced a persistent change in synaptic transmission, while the 2 in conjunction did so. This suggests that oleate acts synergistically with the consequences of this stimulation to produce an enhancement of the LTP response. Second, oleate enhancement of LTP was more potent when applied in the perforant path synaptic terminal zone than in the dentate hilus, implying that the site of oleate action is at the synapse (where PK...
Platinum nanoparticles were electrochemically deposited onto highly oriented pyrolitic graphite (... more Platinum nanoparticles were electrochemically deposited onto highly oriented pyrolitic graphite (HOPG) from H2PtCl6 solutions and observed by tapping mode atomic force microscopy. Spontaneous Pt deposition, which resulted in a wide particle size distribution, would occur on HOPG at open-circuit potential but could be suppressed by using anodic bias of the substrate before and after deposition. Nanoparticles with a narrow size distribution could be obtained when spontaneous reduction was avoided. Pt nucleated both at step edges and on terraces, with a preference for the former. The density of Pt nanoparticles on HOPG was 109–1010cm−2. Increasing the deposition overpotential or adding HCl as supporting electrolyte resulted in more uniform particles and less aggregation. These findings confirm previous results obtained by our group using only electrochemical methods [G. Lu, G. Zangari, J. Phys. Chem. B 109 (2005) 7998].
Carbon nanotubes (CNTs) have emerged as promising drug delivery systems particularly for cancer t... more Carbon nanotubes (CNTs) have emerged as promising drug delivery systems particularly for cancer therapy, due to their abilities to overcome some of the challenges faced by cancer treatment, namely non-specificity, poor permeability into tumour tissues, and poor stability of anticancer drugs. Encapsulation of anticancer agents inside CNTs provides protection from external deactivating agents. However, the open ends of the CNTs leave the encapsulated drugs exposed to the environment and eventually their uncontrolled release before reaching the desired target. In this study, we report the successful encapsulation of cisplatin, a FDA-approved chemotherapeutic drug, into multi-walled carbon nanotubes and the capping at the ends with functionalised gold nanoparticles to achieve a "carbon nanotube bottle" structure. In this proof-ofconcept study, these caps did not prevent the encapsulation of drug in the inner space of CNTs; on the contrary, we achieved higher drug loading inside the nanotubes in comparison with data reported in literature. In addition, we demonstrated that encapsulated cisplatin could be delivered in living cells under physiological conditions to exert its pharmacological action.
Recent evidence has implicated activation of the N-methyl-D-aspartate (NMDA) class of glutamate r... more Recent evidence has implicated activation of the N-methyl-D-aspartate (NMDA) class of glutamate receptor in the initiation of hippocampal long-term potentiation (LTP), an electrophysiological model of information storage in the brain. A separate line of evidence has suggested that activation of protein kinase C (PKC) and the consequent phosphorylation of its substrates is necessary for the maintenance of the LTP response. To determine if PKC activation is a consequence of NMDA receptor activation during LTP, we applied the NMDA receptor antagonist drug, Dt,-aminophosphonovalerate (APV) both immediately prior to and following high frequency stimulation, resulting in successful and unsuccessful blockade of LTP initiation, respectively. We then measured the phosphorylation of a PKC substrate (protein F1) in hippocampal tissue dissected from these animals. Only successful blockade of LTP initiation by prior application of APV was seen to block the LTP-associated increase in protein F1 phosphorylation measured in vitro (P < 0.001 by ANOVA). This suggests that NMDA receptor-mediated initiation triggers maintenance processes that are, at least in part, mediated by protein F1 phosphorylation. These data provide the first evidence linking two mechanisms associated with LTP, NMDA receptor activation and PKC substrate phosphorylation.
Electrodeposition of Pt-Pb nanoparticles (PtPbNPs) to multi-walled carbon nanotubes (MWCNTs) resu... more Electrodeposition of Pt-Pb nanoparticles (PtPbNPs) to multi-walled carbon nanotubes (MWCNTs) resulted in a stable PtPbNP/MWCNT nanocomposite with high electrocatalytic activity to glucose oxidation in either neutral or alkaline medium. More importantly, the nanocomposite electrode with a slight modification exhibited high sensitivity, high selectivity, and low detection limit in amperometric glucose sensing at physiological neutral pH (poised at a negative potential). At +0.30 V in neutral solution, the nanocomposite electrode exhibited linearity up to 11 mM of glucose with a sensitivity of 17.8 microA cm(-2) mM(-1) and a detection limit of 1.8 microM (S/N=3). Electroactive ascorbic acid (0.1 mM), uric acid (0.1 mM) and fructose (0.3 mM) invoked only 23%, 14% and 9%, respectively, of the current response obtained for 3 mM glucose. At -0.15 V in neutral solution, the electrode responded linearly to glucose up to 5 mM with a detection limit of 0.16 mM (S/N=3) and detection sensitivity of approximately 18 microA cm(-2) mM(-1). At this negative potential, ascorbic acid, uric acid, and fructose were not electroactive, therefore, not interfering with glucose sensing. Modification of the nanocomposite electrode with Nafion coating followed by electrodeposition of a second layer of PtPbNPs on the Nafion coated PtPbNP/MWCNT nanocomposite produced a glucose sensor (poised at -0.15 V) with a lower detection limit (7.0 microM at S/N=3) and comparable sensitivity, selectivity and linearity compared to the PtPbNP/MWCNT nanocomposite. The Nafion coating lowered the detection limit by reducing the background noise, while the second layer of PtPbNPs restored the sensitivity to the level before Nafion coating.
ABSTRACT We report the design and fabrication of a novel single cell electroporation biochip feat... more ABSTRACT We report the design and fabrication of a novel single cell electroporation biochip featuring high aspect ratio nickel micro-electrodes with smooth side walls between which individual cells are attached. The biochip is fabricated using Proton Beam Writing (PBW), a new direct write lithographic technique capable of fabricating high quality high-aspect-ratio nano and microstructures. By applying electrical impulses across the biochip electrodes, SYTOX® Green nucleic acid stain is incorporated into mouse neuroblastoma (N2a) cells and observed via green fluorescence when the stain binds with DNA inside the cell nucleus. Three parameters; electric field strength, pulse duration, and numbers of pulses have been investigated for the single cell electroporation process. The results indicate high transfection rates as well as cell viability of 82.1 and 86.7% respectively. This single cell electroporation system may represent a promising method for the introduction of a wide variety of fluorophores, nanoparticles, quantum dots, DNAs and proteins into cells.
We have proposed that the translocation/activation of protein kinase C (PKC) in synergism with a ... more We have proposed that the translocation/activation of protein kinase C (PKC) in synergism with a Ca2+-mediated event plays an essential role in hippocampal long-term potentiation (LTP). In a previous study, we saw no effect of PKC-activating phorbol esters alone on baseline responseS, although it has been reported by others to enhance synaptic transmission. To resolve this discrepancy, we investigated the dose-response to phorbol esters of both baseline and potentiated granule cell responses elicited with perforant path stimulation. It was confirmed that iontophoretic ejection of phorbol ester to the dentate hilus, which alone had no effect on baseline responses, prolonged the persistence of potentiation produced by 2 trains of 400 Hz stimulation. These data support the proposed synergistic model in which the effects of phorbol ester and high frequency stimulation together produce a long-lasting potentiation of synaptic activation. A similar synergism was observed with ejection of a lower dose of phorbol ester into the perforant path synaptic zone in the molecular layer. Higher doses delivered to the synaptic zone without 400 Hz stimulation were sufficient to enhance baseline synaptic responses, but these doses inhibited the initial potentiation induced with 2 trains of 400 Hz stimulation delivered immediately after ejection. There was at times a slowly developing enhancement observed after the initial blockade. Thus, induction of a persistent synaptic enhancement was observed without initial potentiation. Measurement of PKC activity in membrane and cytosol indicated that PKC activation is only associated with the persistence phase of LTP. In contrast, there was no change in PKC subcellular distribution associated with the blockade of initial potentiation by higher doses of PDBu.
Gold clusters have been electrodeposited on a boron-doped diamond (BDD) electrode by scanning the... more Gold clusters have been electrodeposited on a boron-doped diamond (BDD) electrode by scanning the potential from 0.7 V to 0.0 V (vs. 3 M KCl-Ag/AgCl reference) in a solution of 0.5 mM KAuCl 4 and 1.0 M KCl. The cluster-modified diamond (Au/ BDD) electrode has been used to investigate the oxidative properties of dopamine (DA) and ascorbate (AA). The modified diamond electrode shows a higher activity for DA oxidation than AA; the oxidation potential of DA shifted to a less-positive potential (0.11 V) than that of AA, which oxidized at 0.26 V, and DA possesses a much higher peak current than that of AA. The reversibility of the electrode reaction with DA is significantly improved at the Au/BDD electrode, which results in a large increase in the square-wave voltammetric peak current, with a detection limit of 0.1 lM in the presence of a large excess of AA. The Au/BDD electrode shows excellent sensitivity and good selectivity for DA detection. A self-assembled monolayer (SAM) of mercaptoacetic acid on the Au clusters was used to provide an antifouling effect as the negative CO 2 ± groups repulse negative ascorbate and attract positive dopamine in pH 7.4 buffer. After pre-absorption, the SAM/Au/BDD electrode could detect 1.0 nM DA in a linear range from 10 nM to 10 lM in the presence of 10 ±4 M AA.
Differential mechanisms underlying the modulation of delayed-rectifier K ϩ channel in mouse neoco... more Differential mechanisms underlying the modulation of delayed-rectifier K ϩ channel in mouse neocortical neurons by nitric oxide.
Publisher Summary This chapter describes the procedure for the preparation of protein kinase C is... more Publisher Summary This chapter describes the procedure for the preparation of protein kinase C isozymes and substrates from rat brain. The potential importance of protein kinase C (PKC) in the regulation of nervous functions has been well recognized. Both the short-term responses associated with neurotransmitter release, modulation of ion channels, regulation of receptor functions, and cellular metabolism as well as long-term responses that are involved in the enhancement of synaptic plasticity and control of growth and differentiation have been linked to the action of PKC. PKC α, β, γ, and ɛ are copurified from the rat brain extract during the early stage of purification, and the resolution of each isozyme is achieved at the final step by hydroxylapatite column chromatography. Fractions containing the major PKC α, β, and γ and those also containing PKC ɛ are concentrated separately in Amicon cells and exchanged with buffer B by repetitive dilution and concentration. The cofactor requirements of the PKC-catalyzed reaction depend on the substrates used in the assay. With histone H1 as a substrate, PKC α, β, and γ are stimulated by Ca2+, PS, and DAG or phorbol ester, PKC δ and ɛ are stimulated by PS and DAG, and PKC ζ is stimulated by PS alone. Significant variations in the cofactor requirement are related to the interactions among the various components in the assay. Identification of these PKC substrates during purification is based on the apparent Mr on SDS-PAGE, immunoreactivities toward specific antibodies, and elution profiles on the C4 reversed-phase column. It should be noted that these proteins are frequently eluted from the C4 column as cluster of peaks of the same Mr. Calmodulin, which binds neuromodulin, neurogranin, and MARCKS at a domain adjacent to the PKC phosphorylation site(s), exerts its inhibitory effect by hindering the access of the kinase to the substrates.
Journal of Pharmacology and Experimental Therapeutics, Jun 30, 2006
Dose-limiting diarrhea and myelosuppression compromise the success of irinotecan (7-ethyl-10-[4-[... more Dose-limiting diarrhea and myelosuppression compromise the success of irinotecan (7-ethyl-10-[4-[1-piperidino]-1-piperidino]carbonyloxycamptothecin) (CPT-11)-based chemotherapy. A recent pilot study indicates that thalidomide attenuates the toxicity of CPT-11 in cancer patients. This study aimed to investigate whether coadministered thalidomide modulated the toxicities of CPT-11 and the underlying mechanisms using several in vivo and in vitro models. Diarrhea, intestinal lesions, cytokine expression, and intestinal epithelial apoptosis were monitored. Coadministered thalidomide (100 mg/kg i.p. for 8 days) significantly attenuated body weight loss, myelosuppression, diarrhea, and intestinal histological lesions caused by CPT-11 (60 mg/kg i.v. for 4 days). This was accompanied by inhibition of tumor necrosis factor-alpha, interleukins 1 and 6 and interferon-gamma, and intestinal epithelial apoptosis. Coadministered thalidomide also significantly increased the systemic exposure of CPT-11 but decreased that of SN-38 (7-ethyl-10-hydroxycampothecin). It significantly reduced the biliary excretion and cecal exposure of CPT-11, SN-38, and SN-38 glucuronide. Thalidomide hydrolytic products inhibited hydrolysis of CPT-11 in rat liver microsomes but not in primary rat hepatocytes. In addition, thalidomide and its major hydrolytic products, such as phthaloyl glutamic acid (PGA), increased the intracellular accumulation of CPT-11 and SN-38 in primary rat hepatocytes. They also significantly decreased the transport of CPT-11 and SN-38 in Caco-2 and parental MDCKII cells. Thalidomide and PGA also significantly inhibited P-glycoprotein (PgP/MDR1), multidrug resistance-associated protein (MRP1)- and MRP2-mediated CPT-11 and SN-38 transport in MDCKII cells. These results provide insights into the pharmacodynamic and pharmacokinetic mechanisms for the protective effects of thalidomide against CPT-11-induced intestinal toxicity.
... LI Zheng-qiang 1* * , LI Xiao-yuan1 , SHEU Fwu-shan2, CHEN Dong-ming 1 and YU Nai-teng 1 ( 1 ... more ... LI Zheng-qiang 1* * , LI Xiao-yuan1 , SHEU Fwu-shan2, CHEN Dong-ming 1 and YU Nai-teng 1 ( 1 Department of Chemistry, 2 Department of Biochemistry, H ong K ong University of Science & T echnology, H ong K ong ) (Received April 4, 1997) ...
Iron-phthalocyanines (FePc) are functionalized at multi-walled carbon nanotubes (MWNTs) to remark... more Iron-phthalocyanines (FePc) are functionalized at multi-walled carbon nanotubes (MWNTs) to remarkably improve the sensitivity toward hydrogen peroxide. We constructed a highly sensitive and selective glucose sensor on FePc-MWNTs electrode based on the immobilization of glucose oxidase (GOD) on poly-o-aminophenol (POAP)electropolymerized electrode surface. SEM images indicate that GOD enzymes trapped in POAP film tend to deposit primarily on the curved tips and evenly disperse along the sidewalls. The resulting GOD @ POAP/FePc-MWNTs biosensor exhibits excellent performance for glucose with a rapid response (less than 8 s), a wide linear range (up to 4.0 Â 10 À3 M), low detection limits (2.0 Â 10 À7 M with a signal-to-noise of 3), a highly reproducible response (RSD of 2.6%), and long-term stability (120 days). Such characteristics may be attributed to the catalytic activity of FePc and carbon nanotube, permselectivity of POAP film, as well as the large surface area of carbon nanotube materials.
Microchim Acta (2008) 162: 235243 DOI 10.1007/s00604-007-0882-0 Printed in The Netherlands ... E... more Microchim Acta (2008) 162: 235243 DOI 10.1007/s00604-007-0882-0 Printed in The Netherlands ... Electrocatalytic oxidation of methanol on a platinum modified carbon nanotube electrode ... Ying Wen1,2, Jian-Shan Ye3,4, Wei-De Zhang3, Fwu-Shan Sheu4, Guo Qin Xu2
Previous correlative and interventive work from this laboratory has suggested that activation of ... more Previous correlative and interventive work from this laboratory has suggested that activation of protein kinase C (PKC) is important for the maintenance of the hippocampal long-term potentiation (LTP) response. One such study demonstrated that application of the cis- unsaturated fatty acid, oleate, a newly discovered PKC activator, could prolong the time course of LTP. The present study explored the mechanism of cis-unsaturated fatty acid action on LTP produced by perforant path stimulation. First, neither oleate application nor high- frequency stimulation alone produced a persistent change in synaptic transmission, while the 2 in conjunction did so. This suggests that oleate acts synergistically with the consequences of this stimulation to produce an enhancement of the LTP response. Second, oleate enhancement of LTP was more potent when applied in the perforant path synaptic terminal zone than in the dentate hilus, implying that the site of oleate action is at the synapse (where PK...
Platinum nanoparticles were electrochemically deposited onto highly oriented pyrolitic graphite (... more Platinum nanoparticles were electrochemically deposited onto highly oriented pyrolitic graphite (HOPG) from H2PtCl6 solutions and observed by tapping mode atomic force microscopy. Spontaneous Pt deposition, which resulted in a wide particle size distribution, would occur on HOPG at open-circuit potential but could be suppressed by using anodic bias of the substrate before and after deposition. Nanoparticles with a narrow size distribution could be obtained when spontaneous reduction was avoided. Pt nucleated both at step edges and on terraces, with a preference for the former. The density of Pt nanoparticles on HOPG was 109–1010cm−2. Increasing the deposition overpotential or adding HCl as supporting electrolyte resulted in more uniform particles and less aggregation. These findings confirm previous results obtained by our group using only electrochemical methods [G. Lu, G. Zangari, J. Phys. Chem. B 109 (2005) 7998].
Carbon nanotubes (CNTs) have emerged as promising drug delivery systems particularly for cancer t... more Carbon nanotubes (CNTs) have emerged as promising drug delivery systems particularly for cancer therapy, due to their abilities to overcome some of the challenges faced by cancer treatment, namely non-specificity, poor permeability into tumour tissues, and poor stability of anticancer drugs. Encapsulation of anticancer agents inside CNTs provides protection from external deactivating agents. However, the open ends of the CNTs leave the encapsulated drugs exposed to the environment and eventually their uncontrolled release before reaching the desired target. In this study, we report the successful encapsulation of cisplatin, a FDA-approved chemotherapeutic drug, into multi-walled carbon nanotubes and the capping at the ends with functionalised gold nanoparticles to achieve a "carbon nanotube bottle" structure. In this proof-ofconcept study, these caps did not prevent the encapsulation of drug in the inner space of CNTs; on the contrary, we achieved higher drug loading inside the nanotubes in comparison with data reported in literature. In addition, we demonstrated that encapsulated cisplatin could be delivered in living cells under physiological conditions to exert its pharmacological action.
Recent evidence has implicated activation of the N-methyl-D-aspartate (NMDA) class of glutamate r... more Recent evidence has implicated activation of the N-methyl-D-aspartate (NMDA) class of glutamate receptor in the initiation of hippocampal long-term potentiation (LTP), an electrophysiological model of information storage in the brain. A separate line of evidence has suggested that activation of protein kinase C (PKC) and the consequent phosphorylation of its substrates is necessary for the maintenance of the LTP response. To determine if PKC activation is a consequence of NMDA receptor activation during LTP, we applied the NMDA receptor antagonist drug, Dt,-aminophosphonovalerate (APV) both immediately prior to and following high frequency stimulation, resulting in successful and unsuccessful blockade of LTP initiation, respectively. We then measured the phosphorylation of a PKC substrate (protein F1) in hippocampal tissue dissected from these animals. Only successful blockade of LTP initiation by prior application of APV was seen to block the LTP-associated increase in protein F1 phosphorylation measured in vitro (P < 0.001 by ANOVA). This suggests that NMDA receptor-mediated initiation triggers maintenance processes that are, at least in part, mediated by protein F1 phosphorylation. These data provide the first evidence linking two mechanisms associated with LTP, NMDA receptor activation and PKC substrate phosphorylation.
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