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ABSTRACT: Abstract Purpose: To investigate the varied effects of sperminated pullulans (SP) with different amino residues on cornea permeability and its local toxicity. Methods: Three groups of rabbits were used: control, low-amino residue content SP (SP-L), and high-amino residue content SP (SP-H). The in vitro and in vivo spreading assays were combined with high performance liquid chromatography (HPLC) to measure the concentration of puerarin in the external medium or aqueous humor when 0% SP, 0.2% SP-L, and 0.2% SP-H were included. The toxicity of SP was determined by corneal hydration values, Draize score, aqueous humor protein concentration, corneal endothelial evaluation, as well as light microscopy and electron microscopy. Results: The application of 0.2% SP-L and 0.2% SP-H to the cornea in vitro increased puerarin apparent permeability coefficient by 1.96-fold (P<0.05) and 2.95-fold (P<0.01), respectively. SP-H showed stronger effect than SP-L (P<0.05). For the in vivo assay, those were 1.81-fold (P<0.05) and 3.71-fold (P<0.01), respectively. With the SP application, the corneal hydration values were <83% and Draize scores were <4, with no apparent changes in histological observations. Conclusion: SP is one potential adjuvant promoting puerarin permeability to the cornea, and the high-content amino residue SP showed stronger effect, without ocular toxicity.
Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 06/2012; 28(5):497-501. · 1.46 Impact Factor
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ABSTRACT: To assess how safe and effective it is to use menthol as a permeability enhancer in ophthalmic drug delivery systems.
In this study, the effect of menthol on permeability of dexamethasone disodium phosphate in the cornea and sclera was investigated in vitro. Application of topical drops and subconjunctival injection of dexamethasone disodium phosphate with or without 0.1% menthol was administered to rabbit eyes, and the drug concentration was detected in aqueous humor, cornea, vitreous, and retinochoroidal tissues. The safety of menthol was assessed on the basis of corneal hydration level, Draize test, electroretinography (ERG), and histological examination.
0.05% and 0.1% menthol significantly enhanced the penetration of dexamethasone in the cornea, but did not change the dexamethasone penetration in sclera in vitro. When topical drops of dexamethasone containing 0.1% menthol were administered, a significantly increased concentration of dexamethasone in the cornea and aqueous humor tissues was reported, but dexamethasone concentrations remained unaffected in the retina-choroid tissues. On the other hand, increased drug concentration in aqueous humor, cornea, vitreous and retinochoroidal tissues was achieved through subconjunctival injection. No signs of irritation were observed when menthol was administered at concentrations ranging from 0.025%-0.1%; moreover, no substantial toxic reactions were observed in corneal hydration level, electrophysiological, or histological examinations after the addition of 0.1% menthol.
Menthol may improve the ocular penetration of a drug in a transcorneal and transscleral drug delivery system without causing toxic reactions.
Albrecht von Graæes Archiv für Ophthalmologie 05/2011; 249(10):1503-10. · 2.17 Impact Factor
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ABSTRACT: The purpose of this study is to investigate the distribution and expression of the tight junction membrane proteins, claudin-5 and occludin, in rat blood-optic nerve barrier after borneol treatment. Seventy-two female Wistar rats were randomly divided into the borneol gastric lavage group and the equal volume solvent gastric lavage control group. The bilateral optic nerve from the retrobulbar region to the optic chiasma was collected from the rats in the two groups before gastric lavage and at 30 min, 1, 2, 4, and 8 h after gastric lavage. The distribution and expression of claudin-5 and occludin were detected using immunofluorescence staining, Western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Results showed that claudin-5 translocated from the cell membrane to the cytoplasm at 30 min following initiation of borneol treatment, and this translocation peaked at 1 h. During this period of time, a small amount of occludin also translocated from the cell membrane to the cytoplasm. Four hours after initiation of treatment, claudin-5 and occludin levels in the cytoplasm began to decrease and were restored to their normal pattern 8 h after initiation of treatment. There were no significant differences in the levels of claudin-5 or occludin before or after treatment in either group. It was concluded that claudin-5 and occludin translocate within cells of the rat blood-optic nerve barrier after borneol treatment, and this translocation was reversible. Claudin-5 may play a potential role in permeability of the blood-optic nerve barrier following borneol treatment.
Molecular Biology Reports 02/2011; 38(2):913-20. · 2.93 Impact Factor
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ABSTRACT: The process of brain death can induce acute lung injury in donors and aggravate ischemia-reperfusion injury in grafts. Carbon monoxide (CO) and biliverdin (BV) have been shown to attenuate ischemia-reperfusion injury. We therefore examined if the administration of both CO and BV provide enhanced cytoprotection against lung graft injury from brain-dead (BD) rat donors.
Brain death was induced in all donors, after which they were observed for 1.5 hours and then underwent lung transplantation. The recipients were ventilated with 40% oxygen (control group), ventilated with 250 ppm CO in 40% oxygen (CO group), treated with BV (35 mg/kg) intraperitoneally (BV group), or treated with CO and BV conjointly (COBV group) before transplantation (n = 8 each group). The recipients were sacrificed 2 hours after lung transplantation by exsanguination. Serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay.
CO and/or BV treatment attenuated partial pressure of arterial oxygen (Pao(2))/fraction of inspired oxygen (Fio(2)) aggravation in the recipients after reperfusion, reduced the wet weight/dry weight ratio, decreased the lung injury score, inhibited the activity of myeloperoxidase in grafts, and decreased serum levels of IL-8 and TNF-α compared with the control group (p < 0.05). The COBV group had significantly decreased malonaldehyde levels and increased superoxide dismutase levels in lung grafts compared with the CO group (p < 0.05). The static pressure-volume curve of the lungs was ameliorated in the CO group, BV group, and COBV group compared with the control group (p < 0.05).
CO and BV exert protective effects through anti-inflammatory and anti-oxidant mechanisms, and dual treatment provided enhanced cytoprotection against lung graft injury from BD rat donors.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2011; 30(4):460-6. · 3.54 Impact Factor
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ABSTRACT: Brain death (BD) induces acute lung injury and makes donor lungs unfit for transplantation. Carbon monoxide (CO) inhalation at 50-500 ppm exerts anti-inflammatory and anti-apoptosis effects in several lung injury models. We examined whether CO inhalation would show favorable effects on lung injury in BD rats. BD rats inhaled 250 ppm CO for two hours. Inhalation decreased the severity of lung injury, as checked by histological examination. CO treatment reversed aggravation in PaO(2)/FiO(2), base excess and pH of BD rats. CO inhalation downregulated the pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6), and inhibited activity of myeloperoxidase in lung tissue. Inhalation significantly decreased cell apoptosis of lungs, and inhibited mRNA expression of intercellular adhesion molecule-1 and caspase-3 in the lungs. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of extracellular signal-regulated kinase expression in the lungs. In conclusion, CO exerts potent protective effects on lungs from BD rats, exhibiting anti-inflammatory and anti-apoptosis functions by modulating the mitogen-activated protein kinase signal transduction.
Experimental Biology and Medicine 10/2010; 235(10):1236-43. · 2.64 Impact Factor
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ABSTRACT: To determine whether Tauroursodeoxycholic acid (TUDCA) can penetrate the blood-ocular barrier after orally administration of Fel Ursi.
56 rabbits were divided into two groups, 48 rabbits were used in experimental group, and other 8 rabbits were served as control. 100 mg/ml Fel Ursi were a fused into rabbits stomach. 2 ml blood from vein of auris-edge, aqueous humor from left eye and vitreous sample from right eye were obtained at 0.5, 1.0, 2.0, 4.0, 6.0 and 8.0 h after Fel Ursi administration. Concentration of TUDCA from all of samples was determined by HPLC.
TUDCA Concentrations were (999.1 +/- 17.2) - (1300.6 +/- 78.2) microg/ml, (12.7 +/- 1.4) - (47.8 +/- 4.7) microg/ml, and (10.8 +/- 2.9) - (57.9 +/- 7.9) microg/ml in blood, aqueous humor and vitreous respectively. There was no significant differences in the concentration of TUDCA in samples of aqueous humor and vitreous (P > 0.05). However the concentration of TUDCA in rabbit blood was much higher compared with that in aqueous humor and vitreous (P < 0.01).
Fel Ursi can reach intraocular tissue through penetrating blood-aqueous barrier and blood-vitreous barrier after orally application.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 12/2006; 42(11):1023-5.
