Objective To investigate the effect of TanshinoneⅡA (TSN) on the cell hypertrophy induced by angiotensinⅡ(AngⅡ) in the primary culture of neonatal rat cardiomyocytes. Method The effect of TSN on cardiomyocyte was evaluated by the 3-[4, 5-dimethylthiazol-2-yl] -3, 5-diphenylformazan (MTF) assay. As the index of eardiomyocyte hypertrophy, protein synthesis rate was measured by H-Leucine incorporation and the cell size was determined by phase contrast microscope. The proto-oncogene c-los mRNA and c-jun mRNA expression was assessed using reverse transcription polymerase chain reaction (RT-PCR). Results Exposure of the myocytes to TSN (5～80 mmol/L) for 24hours produced no cytotoxicity. Protein synthesis rate and proto-oneogene c-fos and c-Jun mRNA expression of eardinmyoeytes increased significantly after AngⅡtreatment, and TSN inhibited these effect of AngⅡ.Conclusions TSN can prevent the hypertrophy of eardiomyocytes induced by AngⅡ, which be attributable relate to the decreased expression of proto-oncogene c-los and c-jun mRNA by TSN.

Chromatography, Gas ; methods ; Ethanol ; blood ; Humans ; Methanol ; blood

Aged ; Female ; Humans ; Neurilemmoma ; Pharyngeal Neoplasms

Adult ; Calcinosis ; Humans ; Male ; Pharyngeal Diseases

To study the pharmacokinetics of ~(131)I-Metuximab injection (Licartin) combined with transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). MethodsLicartin (27.75 MBq/kg) and the mixture of anticancer drug and Lipiodol were sequentially administered with interval of 20 minutes to 15 patients with HCC via a transfemoral catheter.After the Licartin was administrated, the pharmacokinetic and biodistribution data were evaluated through venous blood samples,urine collections,and 4 γ-scintigraphies (SPECT) over 7 days. The pharmacokinetic parameters were determined from integration of the blood radioactivity-time curves using the SPSS 12.0 software. The tumor-no-tumor ratio (T/NT) was calculated by ROI. Absorbed doses in organ were estimated according to the medical internal radiation dose formalism. The biodistribution of licartin within patient's body at different time points was compared for various organs using analysis of variance for repeated measures, as well as the T/NT ratio. ResultsThe blood radioactivity-time curves followed the dynamics two-compartment model, with the major pharmacokinetic parameters including t_(1/2)α(1.96±1.65) h, and t_(1/2)α(19.07±5.91) h,and t_(1/2)β (57.09±10.92) h, and C_(max) 2.113×10~9min~(-1)·L~(-1), and AUC_(0-∞) 1.302×10~(11) h·min~(-1)·L~(-1), respectively. The accumulated urine radioactivity was 52.2% of administrated dosage during 144 h after administration. There were statistical significant difference of biodistribution of licartin and T/NT ratio between organs at different time points (F=6.583, P<0.01 and F=3.546, P<0.01). SPECT scans showed the significant accumulation of the radioconjugate in liver tumor and faint uptake in other organs for 14 days. Tumor-to-liver ratio decreased from 2.88±1.02 at 3 h to 1.64±0.40 at 168 h (n=7). Organ absorbed dose was (3.19±1.01) Gy in liver (n=12) and (0.55±0.09) Gy in red marrow (n=7). ConclusionLicartin combined with TACE for treatment of HCC is helpful to significantly accrete the radioconjugate in liver tumor, and protect normal organs from radiotoxictiy.

Absract: Objective To report the result of annual monitoring and analysis of nasopharyngeal virus in children with respiratory tract infections in Nanxiang, Shanghai District. Methods Nasopharyngeal secretions were collected from 4389 children with acute respiratory tract infection in outpatient department from January 2007 to September 2013, 9 common respiratory viruses were analyzed by Multiplex RT-PCR, including inlfuenza virus (FLU), parainlfuenza virus (PIV), respiratory syncytical virus (RSV) , adenovirus (ADV), human bocavirus(HBOV), human coronavirus(Cov), enterovirus(EV), human metapneumovirus(HMPV), and rhinovirus(HRV). The same analysis was done in 123 asymptomatic children during the same period. Results The positive rate of detected respiratory viruses in children with respiratory tract infections in nasopharyngeal secretions were 34.8% (1526/4389), including FLU 10.3% (453/4389), RSV 7.3% (320/4389), PIV 6.2%(274/4389), ADV 3.3%(146/4389), HBOV 2.7%(118/4389), EV 2.5%(110/4389), Cov 2.4%(105/4389), HRV 1.6%(72/4389), HMPV 1.5%(67/4389);two and more combined respiratory viral infection were found in 273 cases (6.2%). The virus detection
rate between age groups was signiifcantly different (χ2=41.91, P<0.001). The school-age group had the lowest positive rate of 23.4%and the positive rates in other three groups were all higher than 35.0%. The infant group had the higher positive rate of RSV and HRV. FLU detection rate in school-age group was 13.6%. Respiratory viruses in children with asthmatic disease has high detection rate. RSV infection rate was the highest 14.8%(30/204) in the asthmatic disease group, followed by HBOV 13.8% (28/204). In nasopharyngeal secretions of 123 asymptomatic children, virus-positive detection rate of 6.5% (8/123), which showed signiifcant difference from that in respiratory virus infection group (χ2=42.60, P<0.001). Conclusions In seven consecutive years of testing, the inlfuenza virus and respiratory syncytial virus play an important role in children with respiratory tract infections in this region. The detection rate of virus showed difference between different age groups and a higher detection rate of RSV in infants with respiratory tract infections was observed. The overall detection rate of virus was decreased with the increase of age excluding the inlfuenza virus.

OBJECTIVETo observe the effects of sodium tanshinone II A sulfonate (STS) on angiotensin II (Ang II)-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2).

METHODSIn the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling.

RESULTS(1) The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang II (1 micromol/L) for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang II and the syntheses of protein. (2) After pretreatment of myocardial cells with Ang II (1 micromol/L) for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses (2, 10, 50 micromol/L) for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang II in a dose-dependent manner. (3) After the myocardial cells were stimulated by Ang II (1 micromol/L), the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang II was blocked distinctly by STS.

CONCLUSIONSTS inhibited the myocardial cell hypertrophy induced by Ang II, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.

Angiotensin II ; pharmacology ; Animals ; Hypertrophy ; Leucine ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Myocytes, Cardiac ; drug effects ; enzymology ; pathology ; Phenanthrenes ; pharmacology ; Phosphorylation ; drug effects ; Protein Biosynthesis ; drug effects ; Protein Transport ; drug effects ; Rats ; Rats, Wistar ; Tritium

OBJECTIVETo explore the effects of Tanshinone II A (Tan II A) on the myocardial apoptosis in rats with heart failure and its mechanisms for regulating the miR- 133 levels.

METHODSThe heart failure rat model was established by thoracic aorta constriction (TAC). Tan II A Injection was applied for 12 successive weeks. Meanwhile, partial heart failure rats were subcutaneously implanted with osmotic pump of antagonist to observe its inhibition on the miR-133 level. Twelve weeks later, the hemodynamic conditions, the myocardial apoptosis (using TUENL method), myocardial pro-apoptotic genes (Bax and Caspase-3), and the expressions of anti-apoptosis genes (Bcl-2) (using Western blot and RT-PCR method) were analyzed.

RESULTSCompared with the sham-operation group, TAC operation could deteriorate the heart function (except the mean arterial pressure), elevate the myocardial apoptosis level, increase the protein and mRNA levels of Bax and Caspase-3, and down-regulate the protein and mRNA levels of miR-133 and Bcl-2. TAC rats treated by Tan II A could significantly improve all indices with statistical difference except the heart rate. Subcutaneously pumping of antagonist could partially abolish the anti-apoptosis effect of Tan II A.

CONCLUSIONTan II A could decrease the myocardial apoptosis level of heart failure rats, which was possibly realized by up-regulating the miR-133 level.

Animals ; Apoptosis ; drug effects ; Diterpenes, Abietane ; pharmacology ; Heart Failure ; metabolism ; Male ; MicroRNAs ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the impact of low-level lead exposure on neural cell adhesion molecule (NCAM) expression of primarily cultured hippocampal neurons.

METHODSWistar rats gestated at 18th day were anaesthetized and paunched to get the pups, the hippocampi of the pups were separated and the hippocampal neurons were primarily cultured. After co-cultivated with different dosage of PbCl(2), the NCAM expression of the neurons were tested with Western blotting at different culture time.

RESULTSNormally, the expression of NCAM at the 1st culture day was very low and its integral obsorbency density was 14; the climax expression time of NCAM of the cultured hippocampal neurons was 3rd to 5th cultured day, and their integral obsorbency density were 2 542 to 2 580; henceforth, the NCAM expression declined. NCAM expression was inhibited significantly by lead during the 2nd to 4th cultured day, and dose-response relationship was observed. The inhibition of lead weakened along with the cultured time prolonged, at 5th cultured day, it disappeared, and the NCAM expression of 10(-2), 10(-3) and 10(-4) mmol/L groups even exceeded the control groups. After that, the expression of NCAM in all groups began to decline, and the dose-response relationship of lead to the NCAM expression was observed again.

CONCLUSIONLow-level lead might significantly inhibit the NCAM expression of the primarily cultured Wistar rats' hippocampal neurons, and might delay the climax NCAM expression time.

Animals ; Animals, Newborn ; Cell Separation ; Cells, Cultured ; Dose-Response Relationship, Drug ; Female ; Hippocampus ; cytology ; drug effects ; metabolism ; Lead ; toxicity ; Neural Cell Adhesion Molecules ; biosynthesis ; genetics ; Neurons ; cytology ; Pregnancy ; Rats ; Rats, Wistar

Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.