Mutagenicity Tests ; methods ; Tobacco Smoke Pollution ; adverse effects

OBJECTIVETo investigate the effects and mechanisms of high glucose on the phenotype transformation of rat vascular smooth muscle cells (VSMCs).

METHODSVSMCs ere isolated from rat thoracic aorta and the 3rd-5th VSMCs were incubated with normal glucose (5.5 mmol/L), high glucose (25 mmol/L), or high glucose (25 mmol/L) + P38 inhibitor (25 mmol/L +SB203580) for another 24 hours. Then the gene expression of osteopontin (OPN), alpha smooth-actin (alpha-SMA), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9(MMP-9) were assayed by real time RT-PCR, the protein expression of P38 were assayed by Western blot.

RESULTS(1) High glucose promoted the phenotype transformation of VSMCs and up-regulated the expression of MMP-2 and MMP-9. (2) High glucose promoted the phosphorylation of P38. (3) SB203580, the inhibitor of P38/MAPK signal pathway, inhibited the effects of high glucose on phenotype transformation and expression of MMP-2 and MMP-9.

CONCLUSIONHigh glucose may promote phenotype transformation of VSMCs via the signal pathway of P38/MAPK.

Actins ; metabolism ; Animals ; Aorta, Thoracic ; cytology ; Blotting, Western ; Cells, Cultured ; Glucose ; pharmacology ; Imidazoles ; pharmacology ; MAP Kinase Signaling System ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; metabolism ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Osteopontin ; metabolism ; Phenotype ; Pyridines ; pharmacology ; Rats ; p38 Mitogen-Activated Protein Kinases ; metabolism

Acute Disease ; Humans ; Insecticides ; poisoning ; Male ; Occupational Exposure ; adverse effects ; Poisoning ; etiology ; prevention & control

Adult ; Amphotericin B ; therapeutic use ; Cryptococcosis ; diagnostic imaging ; pathology ; therapy ; Female ; Humans ; Lung Diseases, Fungal ; diagnostic imaging ; pathology ; therapy ; Male ; Middle Aged ; Radiography, Thoracic

Objective To explore acute toxicity of succimer on mice.Methods Twenty Kunming mice(10 males and 10 females) weighting approximately (21.2?2.3)g were acclimatized for 3 days prior to dosing,then were divided into control group and experiment group with 10 mice in each group according to body weight.Fasted for 12 hours,the mice in experiment group received intragastric administration of 160mg DMSA in deionized water in 24 hours,and the control group received the same volume of deionized water,and then they were observed for 7 days.Blood was collected into heparinized-tubes by removal of eyeball.All mice were sacrificed and brain,heart,liver and kidney were removed and washed with normal saline.The activity or amount of BUN,Scr,AST,ALT,SOD, GSH-PX and MDA were analyzed.Results (1)Given 160rag DMSA in 24 hours,gastrointestinal symptoms were main side effects.During the observation,experiment group lost weight due to the decrease of food-intake ,and some mice had slight hydroabdomen.(2)High dose of DMSA caused a significant inhibition of GSH-PX(P0.05).The hepatic cell was damaged accord- ing to the significant raise of MDA in liver(P0.05),which was related to acute toxicity on liver.Conclusion Succimer could inhibit the antioxidarrt systems and could do damage to liver and kidney.

BACKGROUNDThe equations for estimating glomerular filtration rate (GFR) based on creatinine have been found to have limitations and have not been generalizable across all populations. Equations based on cystatin C provide an alternative method to estimate GFR. Whether the equation based on cystatin C alone or combined creatinine would improve GFR estimates has not been validated among Chinese patients with chronic kidney disease (CKD) and diabetes. The aim of this study was to compare the performance of the modification of diet in renal disease (MDRD) equation based on creatinine with the five cystatin C-based formulae for estimation of GFR in patients with CKD and diabetes.

METHODSA total of 166 patients with CKD and 91 patients with type 2 diabetes were enrolled in this study. Cystatin C was measured by using the particle-enhanced immunonephelometric method and estimated formulae proposed by five different investigator teams (Stevens, Ma, Rule, Macisaac and Perkins). The plasma clearance of (99m)Tc-DTPA was determined as measured GFR (mGFR).

RESULTSFor CKD patients, the bias and accuracy for the Ma and Macisaac equations were superior compared with the MDRD, and the mean results for the Ma formula were closer to mGFR than the other equations in CKD stages 2 - 5. The differences between Macisaac and mGFR in CKD stages 2 - 4 were significantly less than those in CKD stage 1 or 5. Stevens and Rule's formulae revealed a similar bias and accuracy compared with the MDRD equation. The MDRD formula had a higher accuracy in CKD stages 3 - 5 as compared with the results in other stages. For diabetic patients, the mean results between Macisaac and mGFR were closer than those of other equations in mGFR >or= 90 mlxmin(-1)x1.73 m(-2) stage. In GFR 60 - 89 mlxmin(-1)x1.73 m(-2) stage, the MDRD formula showed the smallest difference compared with other equations. All equations overestimated GFR in the cases with GFR < 60 mlxmin(-1)x1.73 m(-2) stages. The MDRD formula had a greater accuracy within 50% of mGFR than the equations based on cystatin C in diabetic patients. Perkins formula showed a large positive bias and low accuracy, therefore it may not be suitable for assessing GFR in patients with CKD and diabetes.

CONCLUSIONSThe formulae for estimating GFR based on cystatin C or creatinine have different trends and accuracies in patients with CKD and diabetes, especially in patients with various GFR levels. The equations based on cystatin C provide less accurate results than MDRD formulae, at least in the diabetic patients. Therefore, whether the formulae based on cystatin C are superior to MDRD formula requires further investigation in large diverse populations.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chronic Disease ; Creatinine ; blood ; Cystatin C ; blood ; Diabetes Mellitus ; physiopathology ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; physiopathology ; Male ; Middle Aged

Design space approach is applied in this study to enhance the robustness of first ethanol precipitation process of Codonopsis Radix (Dangshen) by optimizing parameters. Total flavonoid recovery, dry matter removal, and pigment removal were defined as the process critical quality attributes (CQAs). Plackett-Burman designed experiments were carried out to find the critical process parameters (CPPs). Dry matter content of concentrated extract (DMCE), mass ratio of ethanol to concentrated extract (E/C ratio) and concentration of ethanol (CEA) were identified as the CPPs. Box-Behnken designed experiments were performed to establish the quantitative models between CPPs and CQAs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of Dangshen can be guaranteed by operating within the design space parameters. Recommended normal operation space are as follows: dry matter content of concentrated extract of 45.0% - 48.0%, E/C ratio of 2.48-2.80 g x g(-1), and the concentration of ethanol of 92.0% - 92.7%.
Chemical Precipitation ; Chemistry, Pharmaceutical ; methods ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification

Ligustrazine, one of the major effective components of the Chinese traditional medicinal herb Ligusticum Chuanxiong Hort, has been reported plenty of biological activities, such as protect cardiovascular and cerebrovascular, neuroprotection and anti-tumor, et al. Because of its remarkable effects, studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades are mainly derived from four primary intermediates (TMP-COOH, TMP-OH, TMP-NH2, HO-TMP-OH). To explore the neuroprotection activitiy of ligustrazine intermediates, six ligustrazine intermediates (2, 5, 8, 11, 12, 13) were synthesized and their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells were studied. The target compounds were prepared via different chemical methods, including oxidation, substitution, esterification and amidation without changing the structure nucleus of ligustrazine. Compared with TMP (EC50 = 56.03 micromol x L(-1)), four compounds (2, 5, 12 and 13) exhibited higher activity (EC50 < 50 micromol x L(-1)) respectively, of which, compound 2 displayed the highest protective effect against the damaged PC12 cells (EC50 = 32.86 micromol x L(-1)), but target compounds 8 and 11 appeared lower activity (EC50 > 70 micromol x L(-1)). By structure-activity relationships analysis, the introduction of carboxyl, amino to the side chain of ligustrazine and appropriately increase the proportion of ligustrazine may contribute to enhance its neuroprotective activity, which provides a reference for the design, synthesis and activity screening of relevant series of ligustrazine derivatives in the future.
Animals ; Cell Differentiation ; drug effects ; Chemistry Techniques, Synthetic ; Cobalt ; toxicity ; Drugs, Chinese Herbal ; chemistry ; Neuroprotective Agents ; chemical synthesis ; chemistry ; pharmacology ; Neurotoxins ; toxicity ; PC12 Cells ; Pyrazines ; chemical synthesis ; chemistry ; pharmacology ; Rats

OBJECTIVETo develop an HPLC method to determine the contents of danshensu, hydroxysafflor yellow A, rosmarinic acid, lithospermic acid, salvianolic acid B in the water extract of mixed Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos simultaneously.

METHODThe separation were carried out at 30 degrees C on a ZORBAX Eclipse Plus C18 column (4.6 mm x 100 mm, 1.8 microm) with formic acid-500 mmol x L(-1) ammonium formate-water solution (0.5:10:90) as mobile phase A and acetonitrile-formic acid solution (100: 0.5) as mobile phase B in gradient mode at a flow rate of 0.5 mL x min(-1). Detection wavelengths were 280 nm for danshensu, rosmarinic acid, lithospermic acid, salvianolic acid B, and 380 nm for hydroxysafflor yellow A.

RESULTThe 5 components were separated well with a good linearity (R2 > 0.999 3) in the range of the test concentration. The average recoveries of danshensu, hydroxysafflor yellow A, rosmarinic acid, lithospermic acid, and salvianolic acid B were 99.1%, 102%, 102%, 98.5% and 101%, respectively.

CONCLUSIONThis method is simple, accurate, and repeatable.

Benzofurans ; analysis ; Chalcone ; analogs & derivatives ; analysis ; Chromatography, High Pressure Liquid ; methods ; Cinnamates ; analysis ; Depsides ; analysis ; Lactates ; analysis ; Quinones ; analysis ; Rhizome ; chemistry ; Salvia miltiorrhiza ; chemistry

Objective To study the bone biomechanics of the rabbit osteoporosis models induced by dexamethasone sodium phosphate injection (DX) using a combined treatment modality of 99Tc-MDP and GuKangLing.Methods Rabbits were intramuscularly injected with DX (2 mg/kg) twice a week for 6 weeks.The animal osteoporosis model group (Group C) and normal group (Group A) were compared to confirm the model was available.Another control group (Group B),the osteoporosis control group (Group D) were set for the comparison at the end of the experiment.The 99Tc-MDP therapy group (Group E),GuKangLing therapy group (Group F) and 99Tc-MDP plus GuKangLing therapy group (Group G) were included in the study.The treatment lasted for 16 weeks.The bone biomechanics,cytopathology bone histomorphology,bone mineral density (BMD),X-ray,CT,bone scintigraphy and serum bone alkaline phosphatase (BALP)and P (bone gla protein) were chosen as the markers or methods to evaluate the treatment results (excellent,effective and invalid).The analysis of variance (ANOVA) and t-test were used for group comparison analysis.Results Cytopathology result indicated that there was no bone trabecula destruction in Group A.However,there was distinct bone destruction in Group C.The bone biomechanics (left femur head (265.914 ±52.773) N,L4(369.671 ±94.919) N),BMD(left femur (0.238 ±0.016) g/cm2,L4(0.236 ±0.016) g/cm2)and bone histomorphology ( (66.230 ± 10.848) ％ ) in Group C reduced clearly as compared with Group A ((405.343±55.410) N,(750.870±53.718) N,(0.294±0.017) g/cm2,(0.302±0.023) g/cm2,( 131.500 ± 21.846) ％ ) ( t ≥4.550,all P ＜ 0.01 ).Radionuclide bone scan also showed that the uptake of tracers was higher by the main arthrosis in Group C than that in Group A.Vertebra was not clearly visualized on bone scan image.There were significant differences between Group A and Group C in serum BALP and P ((45.000±7.303) vs (12.485 ±1.512) U/L,(0.168±0.018) vs (0.115 ±0.017) μg/L,t =4.126,5.476,both P ＜ 0.01 ),which indicated that the animal osteoporosis model was available.The pathological results showed an improved recovery of bone structure and trabecular in Groups E and G,but a worse recovery in Group F.Biomechanics result in Groups E and G (left femur head (386.457 ±77.077) N and (432.771 ± 17.525) N,L4(649.550 ± 126.859) N and (655.443 ±76.555) N) improved apparently,which were similar to Group B.The radiotracer uptake in Group F was lower than that in group D.The bone biomechanics,bone histomorphology,BMD,serum BALP and P after the treatment showed significant differences in Groups E,F and G (F:8.556 - 31.608,all P＜0.01 ),and the bone biomechanics result in Group G was a little better than that in Group E (t =2.625,P ＜ 0.05 ).The results of Group G and E were considered as excellent,and Group F was considered as effective.Conclusions The treatment of 99Tc-MDP combined with GuKangLing could improve the bone biomechanics of rabbit osteoporosis models and may be a potential method to increase the bone strength for resisting external force.