1.Pharmacological therapy in age-related macular degeneration (AMD)
Yan-Hong, ZOU ; George C.Y.CHIOU
International Eye Science 2005;5(1):8-18
· Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals aged over 65 in the United States and other industrialized nations. Till now, we have limited choices of treatment for this kind of disease. Treatment available can be grouped into two major categories: physical and pharmacological therapies. The former received extensive attention with little success whereas the latter attract new attention with great hope of success. The pharmacological therapies indude photodynamic therapy (PDT), steroids, vascular endothelial growth factor (VEGF) inhibitors, extracellular matrix (ECM) modifiers, gene therapy, nutrition supplements, choroidal blood flow facilitators and the like. PDT treatment is the only available effective treatment for certain forms of neovascular AMD. Anecortave acetate,as a synthetic derivative of cortisol, might stabilize vision in patients with predominantly classic subfoveal choroidal neovascularization (CNV) for up to 6mo through subtenon juxtascleral depot application. Intravitreous injection of VEGF aptamer stabilized or improved vision in 87.5% of patients with subfoveal CNV 3mo after treatment. Malfunction of choroidal blood flow is found in early stage of AMD. Elevation of intravascular pressure is the crucial hemodynamic factor in age-related macular degeneration, resulting in a decrease of the blood flow of choriocapillaries. Chain reactions are triggered which lead to retinal pigment epithelium (RPE) degeneration,Bruch's membrane breakdown, CNV formation, AMD and blindness in the end. Therefore, specific drugs that can increase the choroidal blood flow could be very useful to prevent the AMD from developing and worsening. Although most of them are still in the experimental stage,it is hopeful to find a way to treat AMD at the early stage and to prevent the disease to be triggered and developed.
3.The effect of D-Timolol and L-Timolol on rat experimental choroidal neovascularization vivo and endothelial cells in vitro
Xin-Rong, XU ; Yan-Hong, ZOU ; George C. Y. CHIOU
International Eye Science 2005;5(5):831-835
·AIM: Impairment of choroidal perfusion was found in AMD patients. We postulated that vasoactive agents,which can reduce choroidal blood flow resistance, might prevent the development of choroidal neovascularization (CNV). D-Timolol and L-Timolol are hypotensive agents used in cardiovascular and glaucoma therapy. Their effects on laser-induced experimental CNV rat model and human umbilical vein endothelial cells (HUVEC) were thus evaluated.·METHODS: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. D-Timolol and L-Timolol were given once daily through intraperitoneal injection after laser treatment for 4wk. Fluorescein angiography was performed on 2wk and 4wk. HUVEC were tested by proliferation assay and adhesion assay with D-Timolol and L-Timolol at different concentrations.· RESULTS: D-Timolol reduced the fluorescein leakage to 83% of the control group in laser-induced rat's CNV model at a dosage of 15mg/(kg·d). L-Timolol had no effect on CNV formation even at a higher dosage of 20mg/(kg·d). D-Timolol inhibited the endothelial cells proliferation significantly by 300mg/L. L-Timolol also significantly inhibited the cell proliferation at 1 000mg/L. But at a lower dose such as 300mg/L, no significant inhibitory effect was found. Both drugs showed no effect on cell adhesion function in cell culture experiments.· CONCLUSION: D-Timolol was found to prevent CNV development in laser-induced model in vivo and inhibit vascular endothelial cells proliferation in vitro. L-Timolol had no effect on cell proliferation at the same dose, and neither on rat CNV model. The results indicate these two isomers have different functions on rat's CNV prevention and on HUVEC cell proliferation.
4.Study on Pharmacokinetics of Ferulic Acid in Ordinary Guipi Pills and Ultramicro Guipi Pills in Rabbits
Hui GUI ; Hong YAN ; Long ZOU ; Dongwen LIU ; Guangxian CAI
China Pharmacy 2005;0(23):-
OBJECTIVE: To study the pharmacokinetic parameter and the relative bioavailability of ferulic acid in ordinary Guipi pills and ultramicro Guipi pills in rabbit.METHODS: HPLC-MS/MS was used to identify the concentration of ferulic acid in the blood sample.RESULTS: Plasma concentration of ferulic acid in ordinary pills was different from that in ultramicro pills.The main pharmacokinetic parameters of ferulic acid in ordinary pills vs.that in ultramicro pills were as follows:t1/2a:(17.59?2.57) min vs.(23.51?4.49) min;t1/2?:(300.91?38.74) min vs.(167.17?45.66) min;tmax: (9.61?1.69) min vs.(12.33?2.27) min;Cmax:(58.92?8.42) ng?mL-1 vs.(112.35?31.29) ng?mL-1;AUC: (5 851.67?895.49) ng?min-1?mL-1 vs.(8 586.13?1 497.62) ng?min-1?mL-1.There were significant difference in Cmax and AUC between ordinary pills and ultramicro pills.CONCLUSION: The application of super fine crushing technique in the preparation of Guipi pills could improve the bioavailability of Guipi pills.
5.The effect of dexamethasone on the proliferation and osteogenic differentiation of human marrow stromal cells in vitro
Feng-Hong YUAN ; Yao-Hong ZOU ; Kai-Yan GAO ; Ke-Jia YU ;
Chinese Journal of Rheumatology 2003;0(08):-
Objective To observe the effect of dexamethasone(Dex)on the proliferation and os- teogenic differentiation of human marrow stromal cells(MSCs)in vitro.Methods The primary human MSCs were isolated and cultured by Ficoll seperation culture in vitro.In subcultures,human MSCs were respectively treated with dexamethasone 10~(-9),10~(-8) and 10~(-7) mol/L.The proliferation of human MSCs was measured using MTF method;cytoplasmic alkaline phosphatase(ALP)activity was measured;the osteogenic marker osteopontin (OPN)mRNA were examined by reverse transcriptase polymerase chain reaction(RT-PCR).Results The op- tical density values in cultures treated with dexamethasone 10~(-8) and 10~(-7) mol/L for 8 days were significantly lower than those in the controls(P<0.05).Treatment of cells with Dex for 12 days led to a significant increase in cytoplasmic ALP activity(P<0.05)in a dose-dependent manner.Dex induced OPN mRNA.Conclusion Dex inhibits the proliferation of human MSCs and dexamethasone 10~(-7) mol/L leads to a strong decrease in cell number.Dex induces human MSCs differentiate to osteoblastic cells.
6.Solitary fibrous tumor of pleura associated with episodic hypoglycemia: report of a case.
Zong-kai ZOU ; Wen-qiao WU ; Hai-yan SU ; Hong-wu SHEN
Chinese Journal of Pathology 2007;36(1):67-67
Antigens, CD34
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metabolism
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Female
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Humans
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Hypoglycemia
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etiology
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Immunohistochemistry
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Middle Aged
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Pleura
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metabolism
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pathology
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surgery
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Solitary Fibrous Tumor, Pleural
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complications
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metabolism
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surgery
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Treatment Outcome
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Vimentin
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metabolism
7.Research on correlation between odor and chemical compounds of Lonicera japonica.
Lian PENG ; Shuo LI ; Yong-hong YAN ; Hui-qin ZOU ; Xiao-yun YANG ; Jia-hui LI
China Journal of Chinese Materia Medica 2014;39(22):4383-4388
This study aims to investigate the relationship between odor and contents of the chemical compounds in Lonicera japonica, including chlorogenic acid, galuteolin and polyphenols. High performance liquid chromatography (HPLC) was applied to determine the contents of chlorogenic acid and galuteolin in L. japonica. The ponptent of polyphenols was determined by UV-Vis Spectrophotometry. Electronic nose was used to extract and measure the odor of L. japonica. Then SPSS 17.0 software was employed for data processing. There is a significant positive correlation between the comprehensive index value of aroma and the contents of chlorogenic acid and polyphenols. The regression equations have been established. However, the relationship between the comprehensive index value and the content of galuteolin is not obvious. This is proof that the odor of L. japonica has close connection with the chemical compounds. Therefore, this research offered a new method for initially determine or predict the content of the chemical composition in L. japonica,
Chlorogenic Acid
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chemistry
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Chromatography, High Pressure Liquid
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methods
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Electronic Nose
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Lonicera
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chemistry
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Odorants
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analysis
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Polyphenols
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chemistry
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Smell
8.Review: plant polyphenols modulate lipid metabolism and related molecular mechanism.
Yan-li DAI ; Yu-xiao ZOU ; Fan LIU ; Hong-zhi LI
China Journal of Chinese Materia Medica 2015;40(21):4136-4141
Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms.
Animals
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Humans
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Lipid Metabolism
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drug effects
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Metabolic Diseases
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drug therapy
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metabolism
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Polyphenols
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pharmacology
9.In vitro targeting effect of lactoferrin modified PEGylated liposomes for hepatoma cells.
Min-yan WEI ; Qi ZOU ; Chuan-bin WU ; Yue-hong XU
Acta Pharmaceutica Sinica 2015;50(10):1272-1279
A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma.
Asialoglycoprotein Receptor
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metabolism
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Carcinoma, Hepatocellular
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pathology
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Coumarins
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Drug Delivery Systems
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Endocytosis
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Hep G2 Cells
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drug effects
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Humans
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Lactoferrin
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pharmacology
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Liposomes
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Liver Neoplasms
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pathology
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Particle Size
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Phosphatidylethanolamines
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Polyethylene Glycols
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Thiazoles
10.Effects of cardiac remodeling on atrial arrhythmogenesis in aged rabbit left atrium
Teng WANG ; Yuting CHEN ; Hong CAO ; Yan HUANG ; Tao LIU ; Qiang ZOU
Chinese Journal of Pathophysiology 2017;33(2):244-250
AIM: To investigate the effects of myocardial remodeling of aged left atrium (LA) on atrial ar-rhythmogenesis in rabbits .METHODS:The male New Zealand rabbits were divided into young LA and aged LA groups . By observing the changes of monophasic action potential ( MAP) and burst-pacing in LA of the rabbits in vivo, the main cardioelectrophysiological parameters such as resting membrane potential ( RMP) , action potential amplitude ( APA) , ma-ximum rise veloctiy of action potential (dv/dtmax), plateau potential and action potential duration at 30%, 50%and 90%( APD30 , APD50 and APD90 ) , as well as the inducibility and duration of atrial arrhythmias were recorded .L-type calcium current (ICa,L) was analyzed via whole-cell patch-clamp technique in enzymatically dissociated single rabbit LA myocytes . The myocardial collagen content was quantified after Masson staining , and the ultrastructure of the LA cells was observed under scanning electron microscope .The expression of Cav 1.2 in LA tissue of the 2 groups was detected by Western blot . RESULTS:Compared with young LA group , dv/dtmax and plateau potential were significantly decreased , APD30 and APD50 were shortened, and APD90 was notably prolongated in aged LA group (P<0.01).The inducibility or duration of atrial arrhythmias was severely increased or prolongated in aged LA group (P<0.01).With voltage clamp model, the den-sity of ICa,L in aged LA group was significantly decreased , and current-voltage curve was notably moved upward compared with young LA group.When the clamp potential was +20 mV, the density of ICa,L was notably modified from (11.72 ± 1.39) pA/pF in young LA group to (6.08 ±0.98) pA/pF in aged LA group ( P<0.01).Compared with young LA group, the protein level of collagen was significantly increased (P<0.01), and the arrange of atrial myocytes was irregular in LA of rabbits in aged LA group .The atrial myocytes of the LA wall in aged LA group exhibited abnormal ultrastructural alterations , such as karyopyknosis , irregular and swelling mitochondria with the presence of vacuoles , and mild and severe sarcomere degeneration .Compared with those in LA tissues of young rabbits , the expression levels of Cav 1.2 in the LA tis-sues of aged rabbits were severely reduced (P<0.01), and had a significant positive correlation with the reduction of ICa,L (r=0.83, P<0.01).CONCLUSION:The pathophysiological characteristics of aged LA are significantly altered , and might contribute to vulnerability and susceptibility of occurrence of atrial fibillation in aged rabbits .The mechanisms might completely attribute to the notable reduction of ICa,L , abnormal alterations of ultrastructures and obvious decrease in the ex-pression of Cav1.2 in the aged LA of aged rabbits .