The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Jason Y. Chang - One of the best experts on this subject based on the ideXlab platform.
-
Methylmercury causes oxidative stress and cytotoxicity in microglia: attenuation by 15-deoxy-delta 12, 14-Prostaglandin J2.
Journal of Neuroimmunology, 2006Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Methylmercury (MeHg) causes severe neurological disorders in the central nervous system. This study focused on the effects of MeHg on microglia, macrophage-like cells that reside in the CNS important in neuro-immune interactions. The murine N9 microglial cell line was used in this set of study. MeHg caused reactive oxygen species generation, mitochondrial depolarization and aconitase inactivation, all of which were signs of cellular oxidative stress. MeHg greatly increased microglial IL-6 secretion despite the fact that it severely inhibited protein synthesis. The concentration that caused 50% cell death in 24 h was approximately 9 microM. Pretreatment of microglia with the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 attenuated MeHg induced cell death. The saving effect did not appear to be mediated through activation of peroxisome proliferator activated receptors (PPAR) since other agonists of these receptors did not prevent MeHg induced microglial death.
-
Methylmercury causes oxidative stress and cytotoxicity in microglia: Attenuation by 15-deoxy-delta 12, 14-Prostaglandin J2
Journal of Neuroimmunology, 2005Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Abstract Methylmercury (MeHg) causes severe neurological disorders in the central nervous system. This study focused on the effects of MeHg on microglia, macrophage-like cells that reside in the CNS important in neuro-immune interactions. The murine N9 microglial cell line was used in this set of study. MeHg caused reactive oxygen species generation, mitochondrial depolarization and aconitase inactivation, all of which were signs of cellular oxidative stress. MeHg greatly increased microglial IL-6 secretion despite the fact that it severely inhibited protein synthesis. The concentration that caused 50% cell death in 24 h was ∼9 μM. Pretreatment of microglia with the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 attenuated MeHg induced cell death. The saving effect did not appear to be mediated through activation of peroxisome proliferator activated receptors (PPAR) since other agonists of these receptors did not prevent MeHg induced microglial death.
-
15-deoxy-delta 12, 14-Prostaglandin J_2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress
BMC Pharmacology, 2004Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Background With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H_2O_2. We also demonstrated that the cytotoxicity caused by H_2O_2 could be prevented by the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J_2 (15d-PGJ_2). Results Further characterization of the experimental system indicated that the half-life of H_2O_2 in cultures was ~1 hour. At a fixed H_2O_2 concentration, the cytotoxicity was dependent on the volume of H_2O_2 solution used in the culture, such that higher volume caused more cytotoxicity. Most cells were committed to die if the culture was treated for 2 hours with a cytotoxic concentration of H_2O_2. The Prostaglandin Derivative, 15d-PGJ_2, could prevent oxidative damage caused by t-butyl hydroperoxide, in addition to H_2O_2. Further studies indicated that both H_2O_2 and tBH caused an increase in reactive oxygen species and depolarization of mitochondrial membrane potential. Pretreatment of cells with 1 μM 15d-PGJ_2 led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential. Conclusion This agent may be used in the future as a pharmacological tool for preventing cellular damage caused by oxidative stress.
-
15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress.
BMC Pharmacology, 2004Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Background With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H2O2. We also demonstrated that the cytotoxicity caused by H2O2 could be prevented by the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 (15d-PGJ2).
-
Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ_2
BMC Ophthalmology, 2003Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Background The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H_2O_2) induced oxidative stress on retinal pigment epithelium were characterized in this study. Methods The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. Results The treatment of retinal pigment epithelial cells with H_2O_2 caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the Prostaglandin Derivative, 15d-PGJ_2 and by the protein kinase inhibitor, AG126. Conclusion 15d-PGJ_2 and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases.
Tarun K. Garg - One of the best experts on this subject based on the ideXlab platform.
-
Methylmercury causes oxidative stress and cytotoxicity in microglia: attenuation by 15-deoxy-delta 12, 14-Prostaglandin J2.
Journal of Neuroimmunology, 2006Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Methylmercury (MeHg) causes severe neurological disorders in the central nervous system. This study focused on the effects of MeHg on microglia, macrophage-like cells that reside in the CNS important in neuro-immune interactions. The murine N9 microglial cell line was used in this set of study. MeHg caused reactive oxygen species generation, mitochondrial depolarization and aconitase inactivation, all of which were signs of cellular oxidative stress. MeHg greatly increased microglial IL-6 secretion despite the fact that it severely inhibited protein synthesis. The concentration that caused 50% cell death in 24 h was approximately 9 microM. Pretreatment of microglia with the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 attenuated MeHg induced cell death. The saving effect did not appear to be mediated through activation of peroxisome proliferator activated receptors (PPAR) since other agonists of these receptors did not prevent MeHg induced microglial death.
-
Methylmercury causes oxidative stress and cytotoxicity in microglia: Attenuation by 15-deoxy-delta 12, 14-Prostaglandin J2
Journal of Neuroimmunology, 2005Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Abstract Methylmercury (MeHg) causes severe neurological disorders in the central nervous system. This study focused on the effects of MeHg on microglia, macrophage-like cells that reside in the CNS important in neuro-immune interactions. The murine N9 microglial cell line was used in this set of study. MeHg caused reactive oxygen species generation, mitochondrial depolarization and aconitase inactivation, all of which were signs of cellular oxidative stress. MeHg greatly increased microglial IL-6 secretion despite the fact that it severely inhibited protein synthesis. The concentration that caused 50% cell death in 24 h was ∼9 μM. Pretreatment of microglia with the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 attenuated MeHg induced cell death. The saving effect did not appear to be mediated through activation of peroxisome proliferator activated receptors (PPAR) since other agonists of these receptors did not prevent MeHg induced microglial death.
-
15-deoxy-delta 12, 14-Prostaglandin J_2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress
BMC Pharmacology, 2004Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Background With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H_2O_2. We also demonstrated that the cytotoxicity caused by H_2O_2 could be prevented by the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J_2 (15d-PGJ_2). Results Further characterization of the experimental system indicated that the half-life of H_2O_2 in cultures was ~1 hour. At a fixed H_2O_2 concentration, the cytotoxicity was dependent on the volume of H_2O_2 solution used in the culture, such that higher volume caused more cytotoxicity. Most cells were committed to die if the culture was treated for 2 hours with a cytotoxic concentration of H_2O_2. The Prostaglandin Derivative, 15d-PGJ_2, could prevent oxidative damage caused by t-butyl hydroperoxide, in addition to H_2O_2. Further studies indicated that both H_2O_2 and tBH caused an increase in reactive oxygen species and depolarization of mitochondrial membrane potential. Pretreatment of cells with 1 μM 15d-PGJ_2 led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential. Conclusion This agent may be used in the future as a pharmacological tool for preventing cellular damage caused by oxidative stress.
-
15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress.
BMC Pharmacology, 2004Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Background With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H2O2. We also demonstrated that the cytotoxicity caused by H2O2 could be prevented by the Prostaglandin Derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 (15d-PGJ2).
-
Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ_2
BMC Ophthalmology, 2003Co-Authors: Tarun K. Garg, Jason Y. ChangAbstract:Background The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H_2O_2) induced oxidative stress on retinal pigment epithelium were characterized in this study. Methods The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. Results The treatment of retinal pigment epithelial cells with H_2O_2 caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the Prostaglandin Derivative, 15d-PGJ_2 and by the protein kinase inhibitor, AG126. Conclusion 15d-PGJ_2 and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases.
Shiro Takahashi - One of the best experts on this subject based on the ideXlab platform.
-
radioimmunoassay and gas chromatography mass spectrometry for a novel antiglaucoma medication of a Prostaglandin Derivative s 1033 in plasma
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Goro Kominami, Masahiro Nakamura, Minoru Mizobuchi, Kyoko Ueki, Tomoko Kuroda, Akira Yamauchi, Shiro TakahashiAbstract:Abstract A radioimmunoassay (RIA) and a gas chromatographic/mass spectrometric (GC/MS) method for a new antiglaucoma medicament, the Prostaglandin Derivative sodium (5 Z ,9 α ,11 α ,13 E )-9,11-dihydroxyprosta-5,13-dienoate (S-1033), in human and rabbit plasma were investigated. For a competitive RIA, antisera from rabbit and radioiodine-labeled S-1033 were prepared by immunizing a conjugate of S-1033 with bovine serum albumin and by the Bolton and Hunter method, respectively. Pretreatment by C 18 solid-phase extraction (SPE) for rabbit plasma sample and further purification by high-performance liquid chromatography (HPLC) for human plasma samples followed by the RIA (SPE/RIA and HPLC/RIA, respectively) were developed. The assay recoveries of SPE/RIA and HPLC/RIA were both excellent and the limits of quantitation were 320 and 10 pg ml −1 , respectively. GC/MS for plasma samples after solid-phase extraction and thin-layer chromatographic purification was also developed using deuterium-labeled S-1033 as internal standard. The limit of quantitation was 100 pg ml −1 in human or rabbit plasma. Rabbit plasma samples after administration of this drug were measured by SPE/RIA and GC/MS and the assay results from both methods agreed well. The SPE/RIA, HPLC/RIA and GC/MS assay methods were suitable for measuring samples from preclinical studies, clincial studies and cross-validation, respectively.
-
Radioimmunoassay and gas chromatography/mass spectrometry for a novel antiglaucoma medication of a Prostaglandin Derivative, S-1033, in plasma
Journal of pharmaceutical and biomedical analysis, 1996Co-Authors: Goro Kominami, Masahiro Nakamura, Minoru Mizobuchi, Kyoko Ueki, Tomoko Kuroda, Akira Yamauchi, Shiro TakahashiAbstract:Abstract A radioimmunoassay (RIA) and a gas chromatographic/mass spectrometric (GC/MS) method for a new antiglaucoma medicament, the Prostaglandin Derivative sodium (5 Z ,9 α ,11 α ,13 E )-9,11-dihydroxyprosta-5,13-dienoate (S-1033), in human and rabbit plasma were investigated. For a competitive RIA, antisera from rabbit and radioiodine-labeled S-1033 were prepared by immunizing a conjugate of S-1033 with bovine serum albumin and by the Bolton and Hunter method, respectively. Pretreatment by C 18 solid-phase extraction (SPE) for rabbit plasma sample and further purification by high-performance liquid chromatography (HPLC) for human plasma samples followed by the RIA (SPE/RIA and HPLC/RIA, respectively) were developed. The assay recoveries of SPE/RIA and HPLC/RIA were both excellent and the limits of quantitation were 320 and 10 pg ml −1 , respectively. GC/MS for plasma samples after solid-phase extraction and thin-layer chromatographic purification was also developed using deuterium-labeled S-1033 as internal standard. The limit of quantitation was 100 pg ml −1 in human or rabbit plasma. Rabbit plasma samples after administration of this drug were measured by SPE/RIA and GC/MS and the assay results from both methods agreed well. The SPE/RIA, HPLC/RIA and GC/MS assay methods were suitable for measuring samples from preclinical studies, clincial studies and cross-validation, respectively.
Subbu S Venkatraman - One of the best experts on this subject based on the ideXlab platform.
-
sustained drug release in nanomedicine a long acting nanocarrier based formulation for glaucoma
ACS Nano, 2014Co-Authors: Jayaganesh V Natarajan, Anastasia Darwitan, Veluchamy A Barathi, Marcus Ang, Hla Myint Htoon, Freddy Yin Chiang Boey, K C Tam, Tina T Wong, Subbu S VenkatramanAbstract:Therapeutic nanomedicine has concentrated mostly on anticancer therapy by making use of the nanosize for targeted therapy. Such nanocarriers are not expected to have sustained release of the bioactive molecule beyond a few days. There are other conditions where patients can benefit from sustained duration of action following a single instillation, but achieving this has been difficult in nanosized carriers. An important prerequisite for sustained delivery over several months is to have sufficiently high drug loading, without disruption or changes to the shape of the nanocarriers. Here we report on successful development of a drug-encapsulated nanocarrier for reducing intraocular pressure in a diseased nonhuman primate model and explain why it has been possible to achieve sustained action in vivo. The drug is a Prostaglandin Derivative, latanoprost, while the carrier is a nanosized unilamellar vesicle. The mechanistic details of this unique drug–nanocarrier combination were elucidated by isothermal titrati...
-
Sustained Drug Release in Nanomedicine: A Long-Acting Nanocarrier-Based Formulation for Glaucoma
2014Co-Authors: Jayaganesh V Natarajan, Anastasia Darwitan, Veluchamy A Barathi, Marcus Ang, Hla Myint Htoon, K C Tam, Tina T Wong, Freddy Boey, Subbu S VenkatramanAbstract:Therapeutic nanomedicine has concentrated mostly on anticancer therapy by making use of the nanosize for targeted therapy. Such nanocarriers are not expected to have sustained release of the bioactive molecule beyond a few days. There are other conditions where patients can benefit from sustained duration of action following a single instillation, but achieving this has been difficult in nanosized carriers. An important prerequisite for sustained delivery over several months is to have sufficiently high drug loading, without disruption or changes to the shape of the nanocarriers. Here we report on successful development of a drug-encapsulated nanocarrier for reducing intraocular pressure in a diseased nonhuman primate model and explain why it has been possible to achieve sustained action in vivo. The drug is a Prostaglandin Derivative, latanoprost, while the carrier is a nanosized unilamellar vesicle. The mechanistic details of this unique drug–nanocarrier combination were elucidated by isothermal titration calorimetry. We show, using Cryo-TEM and dynamic light scattering, that the spherical shape of the liposomes is conserved even at the highest loading of latanoprost and that specific molecular interactions between the drug and the lipid are the reasons behind improved stability and sustained release. The in vivo results clearly attest to sustained efficacy of lowering the intraocular pressure for 120 days, making this an excellent candidate to be the first truly sustained-release nanomedicine product. The mechanistic details we have uncovered should enable development of similar systems for other conditions where sustained release from nanocarriers is desired
Anna Sparatore - One of the best experts on this subject based on the ideXlab platform.
-
New Prostaglandin Derivative for glaucoma treatment.
Bioorganic & medicinal chemistry letters, 2009Co-Authors: Elena Perrino, Caterina Uliva, Cecilia Lanzi, Piero Del Soldato, Emanuela Masini, Anna SparatoreAbstract:A hydrogen sulphide-releasing Derivative of latanoprost acid (ACS 67) was synthesized and tested in vivo to evaluate its activity on reduction of intraocular pressure and tolerability. Glutathione (GSH) and cGMP content were also measured in the aqueous humour. The increased reduction of intraocular pressure, with a marked increase of GSH and cGMP and the related potential neuroprotective properties, make this compound interesting for the treatment of glaucoma. This is the first time that an application of a hydrogen sulphide-releasing molecule is reported for the treatment of ocular diseases.
