OBJECTIVETo observe the effect of activation of aldehyde dehydrogenase 2 (ALDH2) by ethanol on the expression of c-Jun N-terminal kinase (JNK) in the kidney of diabetic rats.

METHODSEightheen healthy male SD rats were randomly divided into 3 groups (n = 6): normal control group, diabetes group and ethanol + diabetes group. After 8 weeks, 24 h urine samples from rats were collected to detect urinary protein content. The kidney was isolated and the ratio of kidney weight/body weight (index of kidney weight) was detected. The levels of fasting blood glucose, glycosylated hemoglobin serum urea nitrogen and serum creatinine were measured. Morphological changes of renal tissue were observed by optical microscope. The protein expressions of ALDH2 and JNK in renal tissue were detected by Western blot.

RESULTSCompared with the normal control rats, the levels of fasting blood glucose, glycosylated hemoglobin, serum urea nitrogen, serum creatinine and the index of kidney weight were increased markedly in diabetic rats. The expression of ALDH2 protein was decreased, while p-JNK, JNK protein expressions and the ratio of p-JNK/JNK were increased. The morphological observation was shown that the amount of glomerular mesangial matrix were increased, basement membrane were thickened and capillary lumen were narrowed. However,in ethanol + diabetes group, renal function was improved and the damage of renal structure was attenuated. The expression of ALDH2 protein was increased, while p-JNK, JNK and the ratio of p-JNK/JNK were decreased.

CONCLUSIONEnhanced ALDH2 expression can protect kidney in diabetic rats, which may be relevant with inhibitting the activity of JNK pathway.

Aldehyde Dehydrogenase ; metabolism ; physiology ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Diabetes Mellitus, Experimental ; enzymology ; Ethanol ; pharmacology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Kidney ; enzymology ; Male ; Mitochondrial Proteins ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo compare the effects of TCM therapeutic principles of tonifying Shen (TS), benefiting Qi (BQ), invigorating Pi (IP) and activating blood circulation (ABC) herbs in regulating the gene expression in senescence related cell cycle.

METHODSDrug sera containing TCM herbs of the above-mentioned principles were used to treat the aged human diploid fibroblast cell line 2BS. The effect of TCM on the senescence related cell cycle and its related gene expression (P16INK4, Cyclin D1 and PCNA) were examined by means of cell proliferative doublings, flow cytometry, RT-PCR and Western blot analysis.

RESULTSTCM herbs of TS and BQ could improve the cell cycle, down-regulate the P16 and Cyclin D1 mRNA/protein expression, up-regulate PCNA mRNA/protein expression, while TCM herbs of IP and ABC showed insignificant effect on these indexes.

CONCLUSIONTCM herbs of TS and BQ have effect in improving cell cycle, it may be achieved through promoting the P16 pathway of gene expression.

Aging ; genetics ; Animals ; Cell Cycle ; drug effects ; Cells, Cultured ; Cellular Senescence ; genetics ; Cyclin D1 ; biosynthesis ; genetics ; Cyclin-Dependent Kinase Inhibitor p16 ; biosynthesis ; genetics ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Fibroblasts ; cytology ; Gene Expression Regulation ; Lung ; cytology ; Male ; Medicine, Chinese Traditional ; Proliferating Cell Nuclear Antigen ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: We wanted to report our experience of metallic stent placement after insufficient balloon dilation in graft hemodialysis patients. MATERIALS AND METHODS: Twenty-three patients (13 loop grafts in the forearm and 10 straight grafts in the upper arm) underwent metallic stent placement due to insufficient flow after urokinase thrombolysis and balloon dilation. The indications for metallic stent deployment included 1) recoil and/or kinked venous stenosis in 21 patients (venous anastomosis: 17 patients, peripheral outflow vein: four patients); and 2) major vascular rupture in two patients. Metallic stents 8-10mm in diameter and 40-80 mm in length were used. Of them, eight stents were deployed across the elbow crease. Access patency was determined by clinical follow-up and the overall rates were calculated by Kaplan-Meier survival analysis. RESULTS: No procedure-related complications (stent fracture or central migration) were encountered except for a delayed Wallstent shortening/migration at the venous anastomosis, which resulted in early access failure. The overall primary and secondary patency rates (+/- standard error) of all the vascular accesses in our 23 patients at 3, 6, 12 and 24 months were 69% +/- 9 and 88% +/- 6, 41% +/- 10 and 88% +/- 6, 30% +/- 10 and 77% +/- 10, and 12% +/- 8 and 61% +/- 13, respectively. For the forearm and upper-arm grafts, the primary and secondary patency rates were 51% +/- 16 and 86% +/- 13 vs 45% +/- 15 and 73%+/-13 at 6 months, and 25% +/- 15 and 71% +/- 17 vs 23% +/- 17 and 73% +/- 13 at 12 months (p = .346 and .224), respectively. CONCLUSION: Metallic stent placement is a safe and effective means for treating peripheral venous lesions in dialysis graft patients after insufficient balloon dilation. No statistically difference in the patency rates between the forearm and upper-arm patient groups was seen.
Vascular Patency ; Treatment Failure ; Stents ; Renal Dialysis ; Polytetrafluoroethylene ; Middle Aged ; Metals ; Male ; Humans ; Graft Occlusion, Vascular/*therapy ; Forearm ; Female ; *Arteriovenous Shunt, Surgical ; *Angioplasty, Balloon ; Aged, 80 and over ; Aged

OBJECTIVETo investigate the relationship between plasma cytochrome P450 3A4 (CYP3A4) 894C>T gene polymorphism and the risk of recurrence of adverse cardiac events after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS).

METHODSA total of 275 patients with ACS received standard dual antiplatelet therapy and PCI. Platelet aggregation rate (PAR) was detected in each patient before and 7 days after administration of the anti-platelet drugs. Single nucleotide polymorphism of CYP3A4 gene 894C>T was detected with PCR and microarray technique. The number of coronary artery lesions was determined by PCI and the Gensini score was calculated. The patients were followed up for 3-12 months after discharge.

RESULTSNo significant difference was found in CYP3A4 gene polymorphism between patients with clopidogrel resistance (CR group) and those without CR (NCR group) (P>0.05). Multivariate logistic regression analysis showed that CYP3A4 gene 894C>T polymorphism was not correlated with CR in patients with ACS (OR 1.359, P>0.05). During the follow-up, the incidence of cardiovascular events was significantly higher in CR group than in NCR group (P<0.05), but this difference was not related to the mutation type of 894C>T locus of CYP3A4 gene.

CONCLUSIONThe CYP3A4 gene 894C>T polymorphism is not associated with the effect of anti-platelet therapy and the risk of cardiovascular event in patients with ACS following PCI.

Acute Coronary Syndrome ; therapy ; Alleles ; Blood Platelets ; Cytochrome P-450 CYP3A ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Function Tests ; Polymorphism, Single Nucleotide ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/R) injury in diabetic rats.

METHODSNormal male SD rats were divided into normal, diabetes and ethanol (the agonist of ALDH2) + diabetes groups. In the latter two groups, diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ. Four weeks after the modeling, myocardial I/R was mimicked ex vivo, and lactate dehydrogenase (LDH) content in the coronary flow was determined. The activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bcl-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR.

RESULTSIn diabetic group, LDH release and caspase-3 activity were increased, while ALDH2 activity and Bcl-2/Bax mRNA expression were decreased as compared to those in normal control group. Compared with the diabetic group, ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity, increased ALDH2 activity and Bcl-2/Bax mRNA expression.

CONCLUSIONIn diabetic rats, enhanced ALDH2 expression can offer mycardial protection possibly in relation to suppress cell apoptosis.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; complications ; enzymology ; Ethanol ; pharmacology ; Male ; Mitochondrial Proteins ; agonists ; metabolism ; Myocardial Ischemia ; enzymology ; etiology ; Myocardial Reperfusion Injury ; enzymology ; pathology ; prevention & control ; Myocardium ; enzymology ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/ R) injury in diabetic rats.

METHODSDiabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups (n = 8). After 8 weeks, myocardial ischemia/reperfusion model was mimicked in vitro. The ventricular dynamical parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. The fasting blood glucose and glycosylated hemoglobin (HbA1c) level were determined by automatic biochemistry analyzer. The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot.

RESULTSIn contrast to I/R in normal rat, in diabetic rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/- dp/dtmax) and left ventricular work (RPP) were decreased, left ventricular end diastolic pressure (LVEDP) and LDH release were increased, and ALDH2 mRNA and protein expressions were decreased; compared with I/R in diabetic rat, ALDH2 agonist ethanol significantly promoted the recovery of LVDP, +/- dp/dtmax, RPP, reduced HbA1c level, LVEDP and LDH released, ALDH2 mRNA and protein expressions were increased.

CONCLUSIONIn diabetic rat, the expression of ALDH2 was decreased when heart was subjected to I/R. Enhanced mitochondrial ALDH2 expression in diabetic rat could play cardiac protective role.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects of simvastatin on vascular endothelial cell apoptosis and Bcl-2 protein expression in the aorta in a rat model of atherosclerosis.

METHODSThirty-six rats were randomized into control group (n=10), atherosclerosis model group (n=13) and simvastatin intervention group (n=13). In the latter two groups, rat models of atherosclerosis were established by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6 weeks, and the control rats were fed with regular diet. In the intervention group, the rats were further fed with high-fat diet with daily simvastatin treatment for 4 weeks. After the treatments, the pathological changes and plaque in the thoracic aorta were observed, and the expression of Bcl-2 protein was detected with immunohistochemistry. TUNEL assay was used to determine the apoptosis index (AI) of the vascular endothelial cells.

RESULTSCompared with that in the control group, Bcl-2 protein expression in the aorta of atherosclerotic rats was significantly decreased (P<0.05); simvastatin treatment obviously increased the expression of Bcl-2 protein in atherosclerotic rats (P<0.05) to a level similar to that in the control group. The AI was the highest in the model group (P<0.05) and comparable between the control and simvastatin treatment group.

CONCLUSIONThe therapeutic effect of simvastatin against atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.

OBJECTIVE：To investigate the role of clinical pharmacists in the diagnosis and treatment of liposome-induced hand-food syndrome （HFS），and to provide reference for rational use of liposome preparation in clinic. METHODS ：One case of elderly female patient with breast cancer ，admitted to our hospital suffered from HFS （grade 2）after treated with Doxorubicin hydrochloride liposome ；after successful therapy ，the patient had skin symptoms （grade 3）again due to Paclitaxel liposome ，and clinical pharmacist judged the recurrence of HFS. For symptomatic treatment ，stopping the treatment and external use of hormone was suggested ，and whole-process pharmaceutical care was provided. The pathogenesis ，differential diagnosis ，risk factors and therapeutic drugs of HFS were summarized based on literature review and 2 case reports in the database. RESULTS ：The physicians adopted the suggestion of clinical pharmacists ；the patient ’s symptoms improved significantly on the third day and disappeared after 1 week. Combined with literature analysis and 2 case reports ，doxorubicin liposome metabolized more slowly than non liposomes in palms and soles of feet ，resulting in accumulation of doxorubicin in sweat duct and stratum corneum ，aggravating skin damage and leading to HFS. Sequential paclitaxel in liposome form may also lead to the accumulation in eccrine duct ，further caused skin damage and induced HFS. CONCLUSIONS ：Clinical pharmacists actively participate in the diagnosis and treatment of ADR ， which is conducive to the rehabilitation of patients. At same time ，combination or sequential of Paclitaxel liposome with PLD should be avoided ，as it can lead to ADR as HFS.

OBJECTIVE: To investigate the effects and mechanisms of irbesartan on myocardial injury in diabetic rats, and to analyze the changes of Notch1 signaling pathway in it. METHODS: Thirty rats were randomly divided into four groups:normal control group (CON, =6), high calorie group (HC, =6) and diabetes mellitus group (DM, =9), irbesartan + diabetes group (Ir + DM, =9). After modeling 8 weeks later, the body weight ratio and left ventricular weight index were measured and the serum levels of triglyceride (TG) and total cholesterol (TC) were measured by automatic biochemical analyzer. The changes of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium of rats were determined by the kit and the expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 assaciated X protein (Bax) protein in myocardium were detected by immunohistochemistry. The expressions of Notch1, Hes-1 and jagged-1 in myocardium of rats were detected by Western blot. RESULTS: Compared with CON group, the levels of heart weight/body weight (H/B), left ventricular weight index(LVWI) and fasting blood glucose(FBG) in HC group were not significantly changed, while the levels of blood lipids, MDA and Bax were increased significantly, and the expressions of SOD, Bcl-2 and Notch1, Hes-1 and Jagged-1 were decreased. Compared with HC group, the levels of H/B, LVWI, FBG, MDA and Bax in DM group were increased significantly, and the levels of SOD, Bcl-2 and Notch1, Hes-1 and Jagged-1 were decreased. The expression of H/B, LVWI, Notch1, Hes-1 and Jagged-1 in Ir+DM group were increased, but there was no significant difference between the other indexes. The H/B and LVWI in Ir + DM group were significantly lower than those in DM group, the levels of blood lipid and blood glucose did not change significantly, but the incidence of oxidative stress and apoptosis was reduced. While Notch1, Hes-1, Jagged -1 protein expressions were increased. CONCLUSIONS Diabetes can induce myocardial injury, and irbesartan has myocardial protective effects through activation of Notch1.
Animals ; Diabetes Mellitus, Experimental ; Irbesartan ; Myocardium ; Rats ; Rats, Sprague-Dawley ; Receptor, Notch1 ; Signal Transduction