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67. The degradation of platelet-activating factor in the plasma of a patient with familial high density lipoprotein deficiency (Tangier disease)

Author

PH Pritchard, CC Yeung, and A Chonn

Subjects
Male, medicine.medical_specialty, PAF acetylhydrolase, Immunology, Lipoproteins, VLDL, Biochemistry, Phospholipases A, chemistry.chemical_compound, Phospholipase A2, Tangier disease, Internal medicine, medicine, Humans, Platelet, Platelet Activating Factor, Tangier Disease, biology, Platelet-activating factor, Catabolism, Cell Biology, Hematology, Hypolipoproteinemias, medicine.disease, Lipoproteins, LDL, Phospholipases A2, Phenotype, Endocrinology, chemistry, Low-density lipoprotein, 1-Alkyl-2-acetylglycerophosphocholine Esterase, biology.protein, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, Lipoprotein
Abstract

Platelet Activating Factor (PAF) (1-O-alkyl-2-acetyl sn-glycerol 3- phosphocholine) has been characterized by its ability to aggregate platelets at low concentrations and its profound hypotensive effects. There is evidence that the rate of catabolism of this compound in the plasma regulates its concentration. In humans, we and others have shown that a PAF acetylhydrolase is associated with low density lipoprotein (LDL). The LDL particle in the plasma of patients with Tangier disease is quite different from normal as its lipid core appears to be enriched with triacylglycerol. Thus, we have studied the potential of this abnormal lipoprotein to degrade PAF. The assay for PAF acetylhydrolase was based on the release of 3H from PAF that was labelled in the acetate moiety of the sn-2 position. Tangier disease plasma had approximately 3.3-fold higher PAF acetylhydrolase activity (208 +/- 9 nmol/min/mL) than controls (63 +/- 18 nmol/min/mL). This increase was brought about by an increase in the Vmax (400 +/- 40, Tangier disease; 54 +/- 5, controls) and Km for PAF (120 +/- 20 mumol/L, Tangier disease; 28 +/- 4 mumol/L, controls). The activity appears to be a specific acetylhydrolase rather than a phospholipase A2 as preincubation of the substrate with 0 to 100 mumol/L phosphatidylcholine did not affect the amount of [3H] acetate released. The role of PAF, and its degradation by LDL-bound PAF acetylhydrolase in the phenotypic expression of this patient with Tangier disease, is not known. However, this is the first patient so far described who has an increased ability to degrade PAF in the plasma.

Published
1985
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69. Large unilamellar liposomes with low uptake into the reticuloendothelial system

Author

Allen, T.M. and Chonn, A.

Abstract

Particulate drug carriers, including liposomes, are rapidly removed from blood by cells of the reticuloendothelial system (RES) with resulting adverse effects on this important host defense system. In order to overcome this and other major disadvantages of liposomes, we have altered liposome composition in an effort to achieve prolonged circulation half‐lives. Gangliosides and sphingomyelin act synergistically to dramatically diminish the rate and extent of uptake of liposomes by macrophages in vivo. The significantly extended circulation times achieved by these modified large unilamellar liposomes overcome an important barrier to the targeting of particulate drug carriers to specific tissues in vivo.

Published
1987
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70. Ganglioside GM1 and Hydrophilic Polymers Increase Liposome Circulation Times by Inhibiting the Association of Blood Proteins

Author

Chonn, Arcadio and Cullis, Pieter

Abstract

Several agents have been shown to prolong the circulation lifetime of liposomes. These agents, such as ganglioside GM1 or phosphatidylethanolamine-derivatives of monomethoxypolyethyleneglycols, provide insight into the mechanism(s) by which liposomes are cleared from the circulation. It is suggested here that the primary mechanism by which these molecules alter the biodistribution of liposomes in vivo involves an inhibition of the association of blood proteins to liposomes, resulting in a diminished rate of clearance of liposomes from the circulation.

Published
1992
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71. Beta 2 glycoprotein I is a major protein associated with very rapidly cleared liposomes in vivo, suggesting a significant role in the immune clearance of "non-self" particles.

Author

Chonn, A, Semple, S C, and Cullis, P R

Abstract

Liposomes recovered from the blood of liposome-treated CD1 mice were previously reported to have a complex protein profile associated with their membranes (Chonn, A., Semple, S.C., and Cullis, P.R. (1992) J. Biol. Chem. 267, 18759-18765). In this study, we have further characterized and identified the major proteins associated with very rapidly cleared large unilamellar vesicles. These liposomes contained phosphatidylcholine, cholesterol, and anionic phospholipids (phosphatidylserine, phosphatidic acid, or cardiolipin) that dramatically enhance the clearance rate of liposomes from the circulation. These anionic phospholipids are normally found exclusively in the interior of cells but become expressed when cells undergo apoptosis or programmed cell death, and thus, they are believed to be markers of cell senescence. Analysis of the proteins associated with these liposomes by SDS-polyacrylamide gel electrophoresis revealed that two of the major proteins associated with the liposome membranes are proteins with electrophoretic mobilities corresponding to M(r) of 66,000 and 50,000-55,000. The 66-kDa protein was identified to be serum albumin by immunoblot analysis. Using various biochemical and immunological methods, we have identified the 50-55-kDa protein as the murine equivalent of human beta 2-glycoprotein I. beta 2-glycoprotein I has a strong affinity for phosphatidylserine, phosphatidic acid, and cardiolipin inasmuch as the levels of beta 2-glycoprotein I associated with these anionic liposomes approach or even exceed those of serum albumin, which is present in serum at a concentration 200-fold greater than beta 2-glycoprotein I. Further, we demonstrate that the amount of beta 2-glycoprotein I associated with liposomes, as quantitated by an enzyme-linked immunosorbent assay, is correlated with their clearance rates; moreover, the circulation residency time of cardiolipin-containing liposomes is extended in mice pretreated with anti-beta 2-glycoprotein I antibodies. These findings strongly suggest that beta 2-glycoprotein I plays a primary role in mediating the clearance of liposomes and, by extension, senescent cells and foreign particles.

Published
1995

72. Large unilamellar liposomes with low uptake into the reticuloendothelial system

Author

A. Chonn and Theresa M. Allen

Subjects
Sphingomyelin, Biophysics, Biology, Endocytosis, Biochemistry, Dosage form, Structural Biology, In vivo, Gangliosides, Genetics, Tissue Distribution, Molecular Biology, Mononuclear Phagocyte System, Liposome, Ganglioside, Cell Biology, Mononuclear phagocyte system, Sialic acid, Sphingomyelins, Cholesterol, Delayed-Action Preparations, Reticuloendothelial system, Liposomes, Phosphatidylcholines, Drug carrier
Abstract

Particulate drug carriers, including liposomes, are rapidly removed from blood by cells of the reticuloendothelial system (RES) with resulting adverse effects on this important host defense system. In order to overcome this and other major disadvantages of liposomes, we have altered liposome composition in an effort to achieve prolonged circulation half-lives. Gangliosides and sphingomyelin act synergistically to dramatically diminish the rate and extent of uptake of liposomes by macrophages in vivo. The significantly extended circulation times achieved by these modified large unilamellar liposomes overcome an important barrier to the targeting of particulate drug carriers to specific tissues in vivo.

Published
1987

73. Relaciones entre los valores, la personalidad y las actitudes hacia la piratería en Lima Metropolitana

Author

Chonn Ching, Violeta and Chonn Ching, Violeta

Abstract

Esta tesis analiza las relaciones entre los valores de Schwartz, los cinco factores de personalidad y las actitudes hacia la piratería en consumidores de películas piratas de la ciudad de Lima. Para tal fin, se desarrolló un estudio descriptivo-correlacional en una muestra de 153 participantes. Los resultados muestran que tanto el valor de Conservación como el factor de Conciencia se relacionan de manera directa y significativa con una visión más crítica o negativa hacia la piratería además de reportar un menor nivel de consumo de ella. Mediante estas relaciones se encontró que la piratería es un fenómeno legitimado, tolerado e instaurado en la sociedad peruana a pesar de haber una conciencia de ser un acto informal y de sus implicancias. Adicionalmente, se encontró que las variables demográficas no resultan significativas en el nivel de consumo de piratería., This thesis analyzes the relationship between Schwartz´s values, the big five factors of personality, and the attitudes toward piracy in consumers of pirated movies in the city of Lima. To this end, a sample of 153 participants was part of a descriptive-correlational research. The results show that both the value of Conservation and the factor of Consciousness are related in a direct and significant way with a more critical or negative vision toward piracy and a lower rate of pirated product consumption. This study shows that piracy is considered a legitimate phenomenon; it is tolerated and is embedded in the Peruvian society in spite of being an illegal act. Additionally, it is found that there were demographic variables that are not significant when measuring consumption of pirated goods.

74. Estrategias de innovación en e-commerce y su relación con la supervivencia en el sector de calzado en Lima Metropolitana dentro del contexto de la pandemia

Author

Chonn Li, Michelle Wu, Ramirez Matos, Nicole Alessandra, Chonn Li, Michelle Wu, and Ramirez Matos, Nicole Alessandra

Abstract

La presente investigación tiene como objetivo principal analizar las estrategias de innovación en e-commerce, utilizadas por MYPES en el sector calzado en Lima Metropolitana dentro del contexto de la pandemia. Dicho objetivo se sustenta en la importancia que tienen las MYPES para la economía y cadena productiva nacional, pero son quienes menos invierten en innovación, factor importante para sobrevivir en la pandemia. En ese sentido, surge la necesidad de estudiar el fenómeno de la gestión de la innovación, enfocado en e-commerce, mediante el estudio de casos, los cuales fueron seleccionados de manera conjunta con CITECCAL. De esta forma, se investiga cuáles fueron las nuevas estrategias digitales de comercialización que usaron las MYPES del sector calzado durante la pandemia por el cambio de canal de comunicación y venta. Cabe destacar que es de vital importancia el rol que juega la tecnología y cómo incide en el accionar de las organizaciones, especialmente las del sector calzado, quienes fueron uno de los más golpeados durante pandemia. Después de los hallazgos obtenidos, se concluye que los tres casos de estudio aplicaron estrategias digitales relacionadas a la comercialización, en las que el uso de la tecnología fue primordial para sobrevivir durante la pandemia. Sin embargo, a partir de la información recogida por expertos, algunos innovaron en producto, implementando una nueva línea de negocio y otros no fueron capaces de adaptarse a este nuevo contexto y no llegaron a digitalizarse de manera correcta, por lo que no sobrevivieron a las adversidades.

75. Relaciones entre los valores, la personalidad y las actitudes hacia la piratería en Lima Metropolitana

Author

Chonn Ching, Violeta and Chonn Ching, Violeta

Abstract

Esta tesis analiza las relaciones entre los valores de Schwartz, los cinco factores de personalidad y las actitudes hacia la piratería en consumidores de películas piratas de la ciudad de Lima. Para tal fin, se desarrolló un estudio descriptivo-correlacional en una muestra de 153 participantes. Los resultados muestran que tanto el valor de Conservación como el factor de Conciencia se relacionan de manera directa y significativa con una visión más crítica o negativa hacia la piratería además de reportar un menor nivel de consumo de ella. Mediante estas relaciones se encontró que la piratería es un fenómeno legitimado, tolerado e instaurado en la sociedad peruana a pesar de haber una conciencia de ser un acto informal y de sus implicancias. Adicionalmente, se encontró que las variables demográficas no resultan significativas en el nivel de consumo de piratería., This thesis analyzes the relationship between Schwartz´s values, the big five factors of personality, and the attitudes toward piracy in consumers of pirated movies in the city of Lima. To this end, a sample of 153 participants was part of a descriptive-correlational research. The results show that both the value of Conservation and the factor of Consciousness are related in a direct and significant way with a more critical or negative vision toward piracy and a lower rate of pirated product consumption. This study shows that piracy is considered a legitimate phenomenon; it is tolerated and is embedded in the Peruvian society in spite of being an illegal act. Additionally, it is found that there were demographic variables that are not significant when measuring consumption of pirated goods., Tesis

76. Relaciones entre los valores, la personalidad y las actitudes hacia la piratería en Lima Metropolitana

Author

Chonn Ching, Violeta and Chonn Ching, Violeta

Abstract

Esta tesis analiza las relaciones entre los valores de Schwartz, los cinco factores de personalidad y las actitudes hacia la piratería en consumidores de películas piratas de la ciudad de Lima. Para tal fin, se desarrolló un estudio descriptivo-correlacional en una muestra de 153 participantes. Los resultados muestran que tanto el valor de Conservación como el factor de Conciencia se relacionan de manera directa y significativa con una visión más crítica o negativa hacia la piratería además de reportar un menor nivel de consumo de ella. Mediante estas relaciones se encontró que la piratería es un fenómeno legitimado, tolerado e instaurado en la sociedad peruana a pesar de haber una conciencia de ser un acto informal y de sus implicancias. Adicionalmente, se encontró que las variables demográficas no resultan significativas en el nivel de consumo de piratería., This thesis analyzes the relationship between Schwartz´s values, the big five factors of personality, and the attitudes toward piracy in consumers of pirated movies in the city of Lima. To this end, a sample of 153 participants was part of a descriptive-correlational research. The results show that both the value of Conservation and the factor of Consciousness are related in a direct and significant way with a more critical or negative vision toward piracy and a lower rate of pirated product consumption. This study shows that piracy is considered a legitimate phenomenon; it is tolerated and is embedded in the Peruvian society in spite of being an illegal act. Additionally, it is found that there were demographic variables that are not significant when measuring consumption of pirated goods.

79. Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo.

Author

Cullis PR, Chonn A, and Semple SC

Abstract

Liposomes and lipid-based drug delivery systems have been used extensively over the last decade to improve the pharmacological and therapeutic activity of a wide variety of drugs. More recently, this class of carrier systems has been used for the delivery of relatively large DNA and RNA-based drugs, including plasmids, antisense oligonucleotides and ribozymes. Despite recent successes in prolonging the circulation times of liposomes, virtually all lipid compositions studied to date are removed from the plasma compartment within 24h after administration by the cells and tissues of the reticuloendothelial system (RES). Plasma proteins have long been thought to play a critical role in this process but only a few efforts were made to evaluate the relevant importance of plasma protein-liposome interactions in the clearance process. Strategies to increase the bioavailability of liposomal drugs have included altering lipid compositions and charge, increasing lipid doses, and incorporating surface coatings. All of these modifications can influence membrane-protein interactions. In this article, we will focus on our experiences with liposome-blood protein interactions and how alterations in the chemical and physical properties of the carrier system influence the interactions with blood proteins and circulation times.

Published
1998
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80. Recent advances in liposome technologies and their applications for systemic gene delivery.

Author

Cullis PR and Chonn A

Abstract

The recent clinical successes experienced by liposomal drug delivery systems stem from the ability to produce well-defined liposomes that can be composed of a wide variety of lipids, have high drug-trapping efficiencies and have a narrow size distribution, averaging less than 100 nm in diameter. Agents that prolong the circulation lifetime of liposomes, enhance the delivery of liposomal drugs to specific target cells, or enhance the ability of liposomes to deliver drugs intracellularly can be incorporated to further increase the therapeutic activity. The physical and chemical requirements for optimum liposome drug delivery systems will likely apply to lipid-based gene delivery systems. As a result, the development of liposomal delivery systems for systemic gene delivery should follow similar strategies.

Published
1998
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81. Condensation of plasmid DNA with polylysine improves liposome-mediated gene transfer into established and primary muscle cells.

Author

Vitiello L, Chonn A, Wasserman JD, Duff C, and Worton RG

Subjects
Animals, Cells, Cultured, DNA ultrastructure, Drug Delivery Systems, Humans, Liposomes, Mice, Polylysine, Rats, DNA genetics, Gene Transfer Techniques, Muscle, Skeletal, Plasmids genetics
Abstract

Cationic liposomes provide a means to introduce genes into cells both ex vivo and in vivo. In the past few years their use has been described in several tissues, e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially available poly-cationic liposome formulation in delivering a reporter gene into cultured myogenic cell lines from mouse and rat, and primary fetal human myoblasts. We also examined the effect of serum on liposome-mediated transfection and designed a new procedure to enhance transfection efficiency, based on the pre-condensation of plasmid DNA with polylysine. Polylysine pre-condensation was particularly effective when transfecting the cells in the presence of serum, a finding that could be significant for in vivo transfections.

Published
1996

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