Objective:To evaluate the 5-year sa fety and efficacy of adjunctive 0.005%latanoprost once daily.Methods:Pa-tients with primary open-angle or exfoliation glaucoma who completed a 3-year,open-label,uncontrolled,prospec...Objective:To evaluate the 5-year sa fety and efficacy of adjunctive 0.005%latanoprost once daily.Methods:Pa-tients with primary open-angle or exfoliation glaucoma who completed a 3-year,open-label,uncontrolled,prospective trial could enter a 2-year extension phase.High-resolution color photographs of irides were tak en at baseline and at 14subsequent visits.Photographs were assessed for change in iris pigmentation compared with baseline.Intraocular pressures and adverse events were re corded.Main Outcome Measure:Development and progression of increased iris pigmentation over 5years.Results:Of the 519original patients,380enrolled in the extension phase with approx-imately 89%having an eye color known to be susceptible to color change.After 5years,most p atients had no in-crease in iris pigmentation,but certain colored irides ex-hibited notably greater susceptibi lity than others.For those whose irides did change,onset occur red during the first 8months in 74%and during the first 24months in 94%.No patient developed an increase in pig mentation after month36;the rate of progression decrease d over time.Adverse event profiles were similar for pati ents with and without increased pigmentation.The overall mean intraocular pressure reduction from baseline of25%was sustained with no need for change in intraocular pre ssure-lowering treat-ment in 70%of the eyes.Conclusion:L atanoprost therapy is safe and well tolerated for long-term treatment of open-angle glaucoma.展开更多
Treatment options for Alzheimer＇s disease （AD） are limited because of the inability of drugs to cross the blood-brain barrier （BBB）. A promising strategy to overcome this obstacle is the use of nanoparticles （NP...Treatment options for Alzheimer＇s disease （AD） are limited because of the inability of drugs to cross the blood-brain barrier （BBB）. A promising strategy to overcome this obstacle is the use of nanoparticles （NPs）. Previously, we showed that intraperitoneal administration of liposomes functionalized with phosphatidic acid and an ApoE-derived peptide （mApoE-PA-LIP） reduces brain beta-amyloid （A） burden and ameliorates impaired memory in AD mice. Here, we investigated lung administration as an alternative, non-invasive NP delivery route for reaching the brain. Our results show that mApoE-PA-LIP were able to cross the pulmonary epithelium （[C]-PA permeability = 6.5 ＋ 2.0 × 10^4 cm/min） in vitro and reach the brain （up to 0.6 μg PA/g brain） following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreased total brain Aβ （-60%; p 〈 0.05） compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of NPs designed for AD therapy.展开更多
BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopam...BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.展开更多
文摘Objective:To evaluate the 5-year sa fety and efficacy of adjunctive 0.005%latanoprost once daily.Methods:Pa-tients with primary open-angle or exfoliation glaucoma who completed a 3-year,open-label,uncontrolled,prospective trial could enter a 2-year extension phase.High-resolution color photographs of irides were tak en at baseline and at 14subsequent visits.Photographs were assessed for change in iris pigmentation compared with baseline.Intraocular pressures and adverse events were re corded.Main Outcome Measure:Development and progression of increased iris pigmentation over 5years.Results:Of the 519original patients,380enrolled in the extension phase with approx-imately 89%having an eye color known to be susceptible to color change.After 5years,most p atients had no in-crease in iris pigmentation,but certain colored irides ex-hibited notably greater susceptibi lity than others.For those whose irides did change,onset occur red during the first 8months in 74%and during the first 24months in 94%.No patient developed an increase in pig mentation after month36;the rate of progression decrease d over time.Adverse event profiles were similar for pati ents with and without increased pigmentation.The overall mean intraocular pressure reduction from baseline of25%was sustained with no need for change in intraocular pre ssure-lowering treat-ment in 70%of the eyes.Conclusion:L atanoprost therapy is safe and well tolerated for long-term treatment of open-angle glaucoma.
文摘Treatment options for Alzheimer＇s disease （AD） are limited because of the inability of drugs to cross the blood-brain barrier （BBB）. A promising strategy to overcome this obstacle is the use of nanoparticles （NPs）. Previously, we showed that intraperitoneal administration of liposomes functionalized with phosphatidic acid and an ApoE-derived peptide （mApoE-PA-LIP） reduces brain beta-amyloid （A） burden and ameliorates impaired memory in AD mice. Here, we investigated lung administration as an alternative, non-invasive NP delivery route for reaching the brain. Our results show that mApoE-PA-LIP were able to cross the pulmonary epithelium （[C]-PA permeability = 6.5 ＋ 2.0 × 10^4 cm/min） in vitro and reach the brain （up to 0.6 μg PA/g brain） following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreased total brain Aβ （-60%; p 〈 0.05） compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of NPs designed for AD therapy.
文摘BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.
