the necessary knowledge in costuming and swordplay have died off. But the jidaigeki still persist... more the necessary knowledge in costuming and swordplay have died off. But the jidaigeki still persists. In the age of "Cool Japan," when Japan seems to be represented by games, anime, and manga, stories about the pre-1868 past as well as past films themselves-continue to complicate our notions about Japan and cinema, and the connections between the two.
Drug delivery and translational research, Dec 13, 2016
Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and re... more Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and retina carries ocular risks, a high patient treatment burden, and compliance barriers that can lead to suboptimal treatment. Here we introduce a device that produces sustained release of ranibizumab in the vitreous cavity over the course of several months. Composed of twin nanoporous polymer thin films surrounding a ranibizumab reservoir, these devices provide release of ranibizumab over 16 weeks in vitro and 12 weeks in vivo, without exhausting the initial drug payload. Following implantation in vivo, devices were well-tolerated and showed no sign of immune response. This platform presents a potential solution to the challenge of delivering protein therapeutics to the vitreous and retina for sustained periods of time.
We created implantable intraocular devices capable of constant and continuous rapamycin release o... more We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. Microporous PCL thi...
Background-Experimental studies have shown that the standard dose of R or R+UVA as solo treatment... more Background-Experimental studies have shown that the standard dose of R or R+UVA as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R+UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. Methods-The log of either polyhexamethylene biguanide (PHMB) or chlorhexidine minimal cysticidal concentration (MCC) in solutions containing riboflavin (concentrations 0.1 %; 0.05% and 0.025 %) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm 2 for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P-value associated with treatment. Results-Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agents concentrations ≥ 200 µg/mL for Acanthamoeba castellanii samples and ≥ 100 µg/mL for Acanthamoeba polyphaga samples. There was no statistical evidence that R+UVA treatment was associated with MCC (P = 0.82). Conclusion-R+UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro.
To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vit... more To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vitreous to small- and large-solute diffusion. Vitreous from freshly excised porcine eyes was treated for 30 minutes with control or 0.01%, 0.1%, or 1% methylglyoxal (MG) solution. The efficacy of the glycation regimen was verified by measuring nonenzymatic cross-link density by fluorescence in the vitreous samples. Resistance to collagenase digestion as well as Nε-(carboxyethyl) lysine (CEL) content were also measured. The permeability coefficient for fluorescein and fluorescein isothiocyanate (FITC)-IgG diffusion through 3 mL of the vitreous samples was determined by using a custom permeability tester. Vitreous cross-linking with MG treatment was confirmed by increased fluorescence, increased CEL concentration, and increased resistance to collagenase digestion. Vitreous glycation resulted in a statistically significant decrease in the permeability coefficient for fluorescein diffusion whe...
Americans frequently give the impression of being at once more royalist than the English and more... more Americans frequently give the impression of being at once more royalist than the English and more republican than the French. Indeed, if the American public adulates the House of Windsor to an extant which sometimes startles the more phlegmatic (and often more critical) English, this same public regards any and all resurgence of authoritarianism in France with greater fear and suspicion than many a Frenchman.' The crisis of May, 1958, is a good case in point. It would not be too much to say that the fall of the Fourth Republic aroused more emotion in the United States than in France! 2 Commenting on the French Republic is like commenting on the future of the canoeist caught in the hurtling current and about to go over the falls. One is tempted to close his eyes and turn away until the hoarse howl of the other spectators confirms his fears.3 The number and caliber of editorials on the fall of the Fourth Republic indicate that American newspapers generally ignored the advice of the Los Angeles Times. One thing is certain: the magnitude of the crisis engendered by the events of May 13 was fully appreciated by the press from the very start. 'There is serious concern throughout the Free World today for the future of democratic rule in France'.4 4 'Like a ship without a rudder, France is heading into a hurricane.5 5 'The term political crisis in France has almost lost any meaning. But this seems to be the real thing'. 'The long awaited test of France's loyalty to its republican regime has finally arrived'.' 7 'The most serious French crisis since the circling of the Maginot Line by Hitler's Panzer divisions'. 'Pflimlin and the Assembly will either save the French Republic or see it go down in civil wary These commentaries * The documentation of this article consists entirely of the editorials of some twenty American dailies concerning the French political crisis of 1958. These newspapers were selected with the double aim of obtaining at once a geographical cross section and a sampling of the various shades of political opinion. This type of material was chosen because it is more flavorful and much more representative of American public opinion than the releases of the wire services and the articles of foreign correspondents reporting fi-om Paris and Algeria. The author wishes to thank the personnel of the Newspaper Division, Philadelphia Public Library, for its help in gathering this material.
the necessary knowledge in costuming and swordplay have died off. But the jidaigeki still persist... more the necessary knowledge in costuming and swordplay have died off. But the jidaigeki still persists. In the age of "Cool Japan," when Japan seems to be represented by games, anime, and manga, stories about the pre-1868 past as well as past films themselves-continue to complicate our notions about Japan and cinema, and the connections between the two.
Drug delivery and translational research, Dec 13, 2016
Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and re... more Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and retina carries ocular risks, a high patient treatment burden, and compliance barriers that can lead to suboptimal treatment. Here we introduce a device that produces sustained release of ranibizumab in the vitreous cavity over the course of several months. Composed of twin nanoporous polymer thin films surrounding a ranibizumab reservoir, these devices provide release of ranibizumab over 16 weeks in vitro and 12 weeks in vivo, without exhausting the initial drug payload. Following implantation in vivo, devices were well-tolerated and showed no sign of immune response. This platform presents a potential solution to the challenge of delivering protein therapeutics to the vitreous and retina for sustained periods of time.
We created implantable intraocular devices capable of constant and continuous rapamycin release o... more We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years. Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films. In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin. Microporous PCL thi...
Background-Experimental studies have shown that the standard dose of R or R+UVA as solo treatment... more Background-Experimental studies have shown that the standard dose of R or R+UVA as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R+UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. Methods-The log of either polyhexamethylene biguanide (PHMB) or chlorhexidine minimal cysticidal concentration (MCC) in solutions containing riboflavin (concentrations 0.1 %; 0.05% and 0.025 %) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm 2 for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P-value associated with treatment. Results-Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agents concentrations ≥ 200 µg/mL for Acanthamoeba castellanii samples and ≥ 100 µg/mL for Acanthamoeba polyphaga samples. There was no statistical evidence that R+UVA treatment was associated with MCC (P = 0.82). Conclusion-R+UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro.
To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vit... more To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vitreous to small- and large-solute diffusion. Vitreous from freshly excised porcine eyes was treated for 30 minutes with control or 0.01%, 0.1%, or 1% methylglyoxal (MG) solution. The efficacy of the glycation regimen was verified by measuring nonenzymatic cross-link density by fluorescence in the vitreous samples. Resistance to collagenase digestion as well as Nε-(carboxyethyl) lysine (CEL) content were also measured. The permeability coefficient for fluorescein and fluorescein isothiocyanate (FITC)-IgG diffusion through 3 mL of the vitreous samples was determined by using a custom permeability tester. Vitreous cross-linking with MG treatment was confirmed by increased fluorescence, increased CEL concentration, and increased resistance to collagenase digestion. Vitreous glycation resulted in a statistically significant decrease in the permeability coefficient for fluorescein diffusion whe...
Americans frequently give the impression of being at once more royalist than the English and more... more Americans frequently give the impression of being at once more royalist than the English and more republican than the French. Indeed, if the American public adulates the House of Windsor to an extant which sometimes startles the more phlegmatic (and often more critical) English, this same public regards any and all resurgence of authoritarianism in France with greater fear and suspicion than many a Frenchman.' The crisis of May, 1958, is a good case in point. It would not be too much to say that the fall of the Fourth Republic aroused more emotion in the United States than in France! 2 Commenting on the French Republic is like commenting on the future of the canoeist caught in the hurtling current and about to go over the falls. One is tempted to close his eyes and turn away until the hoarse howl of the other spectators confirms his fears.3 The number and caliber of editorials on the fall of the Fourth Republic indicate that American newspapers generally ignored the advice of the Los Angeles Times. One thing is certain: the magnitude of the crisis engendered by the events of May 13 was fully appreciated by the press from the very start. 'There is serious concern throughout the Free World today for the future of democratic rule in France'.4 4 'Like a ship without a rudder, France is heading into a hurricane.5 5 'The term political crisis in France has almost lost any meaning. But this seems to be the real thing'. 'The long awaited test of France's loyalty to its republican regime has finally arrived'.' 7 'The most serious French crisis since the circling of the Maginot Line by Hitler's Panzer divisions'. 'Pflimlin and the Assembly will either save the French Republic or see it go down in civil wary These commentaries * The documentation of this article consists entirely of the editorials of some twenty American dailies concerning the French political crisis of 1958. These newspapers were selected with the double aim of obtaining at once a geographical cross section and a sampling of the various shades of political opinion. This type of material was chosen because it is more flavorful and much more representative of American public opinion than the releases of the wire services and the articles of foreign correspondents reporting fi-om Paris and Algeria. The author wishes to thank the personnel of the Newspaper Division, Philadelphia Public Library, for its help in gathering this material.
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