The formation of advanced glycosylation end products (AGEs) is enhanced in diabetes mellitus, closely associated with diabetic vascular complication. In this review, biochemical properties and structures of AGEs,AGEs receptors and binding proteins ,pathogenic properties of AGEs,deposition and turnover of AGEs, inhibitors of AGEs were summarized.

This study was designed to investigate the effects of calcium antagonists and glucosylated LDL on intracellular lipid metabolism . The human serum LDL was isolated by density gradient ultracentri-fugation and glucosylated by incubation with glucose. The content of intracellular cholsterol was determined by enzymatic method which is simple, convenient and satisfactory. It was found that the contents of cholesterol in cultured human fibroblasts incubated with verapamil and(or)glucosylated LDL were higher than those incubat- ed with control LDL or without verapamil. The results suggested that calcium antagonists and glucosylation of LDL might affect in-tracellular lipid metabolism and play a role in atherosclerosis.

There is overwhelming evidence for an involvement of reactive oxygen species(ROS) in the pathogenesis of atherosclerosis(AS) in diabetes mellitus(DM). For many years, knowledge on the contribution to diabetic complications and vascular disease induced by advanced glycation end-products(AGEs)has been rising. During the development of atherosclerosis, AGEs and ROS might have interaction. In this article, we provided four angles of view to discuss the role of ROS in the pathogenesis of atherosclerosis: the chemistry of ROS, the effect of vascular targets of ROS on activity of AGEs, the role of ROS in the pathogenesis of atherogenesis by AGEs, the same effect of ROS and AGEs-transcriptional regulation. [

Clinical internship is a key step for training qualified clinician. This article narrates the measures that the hospital have taken to improve administration of clinical internship and teaching quality on the aspect of clinical intern training, examination and quality control.

Objective To investigate the effects of rosiglitazone on the proliferation,connective tissue growth factor and Smad expression in cultured cardiac fibroblasts induced by advanced glycosylation end-products (AGEs).Methods After being treated with various amounts of rosiglitazone,the cultured neonatal rat cardiac fibroblasts were incubated with AGEs.The status of cardiac fibroblasts proliferation and cell cycle were detected by 3-(4,5-dimethyhhiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTI) assay and flow cytometry.Furthermore,ELISA technique was applied to identify the level of TGF-β1.The protein expressions of CTGF and Smad in cardiac fibroblasts of neonatal SD rats were detected with Western blotting.Results The exposure of cardiac fibroblasts to AGEs at doses of 0-200 mg/L induced a dose-dependent increase in cell proliferation.At the concentration of rosiglitazooe (0.1,1,and 10 μmol/L),the cell proliferation was reduced compared with 200 mg/L AGEs group by O.823±0.072,0.785±0.060,0.601±0.081 vs 0.981±0.049,respectively (P < 0.05).The increased levels of TGF-β1 in supematants of cultured cardiac fibroblasts stimulated by AGEs were inhibited by rosiglitazone at the concentrations of 0.1,1,10μmol/L by 257.77±9.09,230.29±6.56,200.84±10.26 vs 300.68±8.56,respectively (vs 200 mg/L AGEs,P<0.01).Western blot indicated that pretreatment with rosiglitazone (0.1,1,and 10 μmol/L) inhibited CTGF protein production in a dose-dependent by 0.769±0.108,0.590±0.095,0.534±0.115 vs 1.021±0.113,respectively (vs 200 mg/L AGEs,P<0.01).It was also demonstrated that pretreatment with rosiglitazone (1 and 10 μmol/L) inhibited Smad2 protein production by 0.424±0.059,0.396±O.080 vs 0.572±0.073,respectively (vs 200 mg/L AGEs,P < 0.05 or P < 0.01).Meanwhile pretreatment with rosiglitazone (1 and 10 μmol/L) inhibited Smad4 protein production by 0.580±0.063,0.556±0.051 vs 0.672±0.059,respectively (vs 200 mg/L AGEs,P < 0.05 or P < 0.01).Conclusions The findings suggest that AGEs promote the proliferation of cardiac fibroblasts and stimulate the protein production of Smad and CTGF of cardiac fibroblasts.Rosiglitazone inhibits the above reaction.These results indicate that CTGF/Smad pathway may play an important role in the protective effect of rosiglitazone on myocardial fibrosis.

Objective To investigate induction effect of AGE on oxidative stress and type Ⅰ ,Ⅲcollagen synthesis in rat cardiac fibroblasts and interference effect of RGZ during the course. Methods Incubate rat cardiac fibroblasts with AGE of different concentration ,add RGZ to interfere for 48 h ,and then collect supernatant fluid .Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by SOD kit and MDA kit separately ,and type Ⅰ ,Ⅲ collagen contents were measured by ELISA. Results When incubating cardiac fibroblasts with RGZ and 200 mg/L AGE together for 48 h , with the rise of RGZ concentration(0.1 ,1 and 10 mol/L) ,SOD activity in the supernatant fluid of cultured cardiac fibroblasts gradually increased [(21.564 ± 1.614) ,(22.323 ± 1.260) ,(23.661 ± 1.562) vs (19.320 ± 0.896) nU/ml ,P<0.05 or P<0.01] ,MDA content gradually decreased [(1.325 ± 0.048) ,(1.279 ± 0.032) ,(1.229 ± 0.045 ) vs (1.629 ± 0.043 ) nmol/ml ,P< 0.01 ] and type Ⅰ ,Ⅲ collagen Contents gradually decreased [(79.17 ± 3.25) ,(60.42 ± 3.58) ,(42.71 ± 5.11) vs (85.54 ± 2.28) ng/ml ,P<0.01 ;(37.52 ± 3.43) ,(27.09 ± 4.75) ,(20.81 ± 3.26) vs (40.75 ± 2.70) ng/ml ,P<0.01] as compared with 200 mg/L AGE group. Conclusion AGE can induce oxidative stress in cardiac fibroblasts and increase type Ⅰ ,Ⅲ collagen contents .RGZ can inhibit oxidative stress in cardiac fibroblasts and synthesis and secretion of type Ⅰ ,Ⅲ collagen induced by AGE. This finding indicates that RGZ may play an important role in the prevention of diabetic myocardial fibrosis.

Objective To observe the effect of advanced glycosylation end products(AGEs) on gene expression of connective tissue growth factor(CTGF) in NIH Swiss mouse embryo fibroblasts(NIH/3T3),and to assess the intervention actions of aminoguanidine(AG) and puerarin(Pue) on CTGF mRNA expression in NIH/3T3.Methods AGEs were synthesized by coincubation of BSA with glucose.The AGEs content was measured by fluorescence spectroscopy.NIH/3T3 cells were treated with AGEs(prepared with 20,50,80 mmol?L-1 glucose) for 24 h.The NIH/3T3 cells were treated with AGEs(prepared with 50 mmol?L-1 glucose) for 0,6,12,24 and 48 h.The intervention actions of AG and Pue with different concentration(0.25,0.5,1.0 and 1.5 g?L-1) were evaluated.The CTGF mRNA expression in NIH/3T3 was determined by RT-PCR.Results Compared with BSA control,the CTGF mRNA expression levels in NIH/3T3 were increased by treatment with AGEs(prepared with 20,50,80 mmol?L-1 glucose) for 24 h(P

Objective To study the effects of puerarin on advanced glycation end products (AGEs) and expression of monocyte chemoattractant protein-1 (MCP-1) in diabetic rats. Methods The rats were randomly divided into normal control rats (CON rats), diabetic rats (DM rats), diabetic rats treated with aminoguanidine (AG rats), and diabetic rats treated with puerarin (PU rats). The diabetic rat model was induced by streptozotocin. The serum levels of AGEs and MCP-1 were quantified by fluorescence spectroscopy and ELISA respectively. Tissue sections with PAS staining and electronic microscopy were used for observation of the pathologic changes in renal tissues. Immunohistochemistry was applied to detect the expression of MCP-1 protein in renal cortex. Results Serum levels of AGEs and MCP-1 in DM rats were higher than those in PU rats and AG rats (both P

In order to investigate the action of calcium antagonists on metabolism of intracellular macromolecules, The authors observed the effects of verapamil on the incor-poration of 〔 3H 〕 TdR, 〔 3H 〕 UR and 〔 3H 〕 Leu into human fibroblasts. The inhibitory effects on DNA and RNA synthesis were concentration dependent, ID50 was l2.3mg/L and 22mg/L, respectively. The inhibitory effect on the synthesis of protein was weak.

An intensive practice scheme,integrating clinical practicing education with continuing medieal education after graduation was introduced to Provide a new mode of teaching activities and management of clinical practice.