Table of Content

Volume 17 Issue 12
26 December 2012

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Effects of genistein on the growth of ovarian cancer cell SKOV3 by regulating miR-27a and target gene expression

XU Lin-lin, SUN Qing-min, LUO Xuan, ZHAI Su-lan, LI Ping, ZHAO Xiao-mei, WANG Xue-rong

2012, 17(12):  1321-1326. 

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AIM: To investigate the effects of genistein on the growth of ovarian cancer cell SKOV3 and potential mechanism. METHODS: The expression of the miR-27a in formalin-fixed paraffin-embedded (FFPE) ovarian cancer tissues and benign ovarian tissues were examined by RT-PCR. SKOV3 cells were treated with different concentration of genistein. Then the SRB assays were performed to assess the growth inhibition of genistein to ovarian cancer cells. RT-PCR and Western blot were used to test expression of miR-27a and Sprouty2 respectively. RESULTS: The expression levels of miR-27a in FFPE ovarian cancer tissues were significantly higher than those seen in benign ovarian tissues. Genistein could markedly decrease human ovarian cancer cell growth in time- and dose- dependent manner and downregulate the expression of miR-27a, which was accompanied by significantly increased expression of Sprouty2. CONCLUSION: Genistein has an inhibitory effect on the growth of ovarian cancer cells, which was due to the downregulation of miR-27a expression.

Therapeutic effects of benthiacthiactzine against circulatory failure induced by methomyl

WANG Ru-huan, SHI Yong-ping, JIN Xin, LONG Chao-liang, CUI Wen-yu, ZHANG Yan-fang, PAN Zhi-yuan, WANG Hai

2012, 17(12):  1327-1332. 

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AIM: To investigate the therapeutic effects of benthiactzine against circulatory failure induced by methomyl in rats. METHODS: Thirty-six healthy SD male rats, were divided into four groups randomly: methomyl poisoning rats treated with benthiactzine or atropine by i.m.Rats were treated with methomyl (i.p) to induce circulatory failure in which the mean blood pressure (MBP) dropped to 40-45 mm Hg as an index, then treated with benthiactzine or atropine. The changes of peripheral blood pressure,cardiac function and Electrocardiographic were observed before and circulatory failure. RESULTS: In circulatory failure rats induced by methomyl, the peripheral blood pressure, HR, and cardiac systolic function parameters were decreased significantly (P<0.01), while cardiac diastolic function parameters were increased dramatically (P<0.01). The electrocardiogram of circulatory failure rats showed bradycardia, nodal rhythm and sharp T wave. After treated with benthiactzine 0.25-1.0 mg/kg or atropine 1.0 mg/kg, the peripheral blood pressure was increased markedly in 1 min (P<0.05 and P<0.01 respectively) and remained stable during 60 minutes experimental period. After treated 0.5-2 min, all hemodynamic parameters were improved significantly (P<0.05,P<0.01). The electrocardiogram was ameliorated in 1 min and restored to normal level in 3 min.CONCLUSION: Treated with benthiactzine, methomyl poisoning rats can get away from circulatory failure in a short time. Benthiactzine can be a favourable medicine against circulatory failure induced by methomyl.

Construction of eukaryotic plasmid of pFLAG-AMPKα2 and the effect on cardiomyocytes subjected to anoxia-reoxygenation injury

LIU Dan, ZHONG Bin, WAN Qing, ZENG Shu, WU Xiao-mu, HE Ming

2012, 17(12):  1333-1338. 

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AIM: To construct eukaryotic plasmid pFLAG-AMPKα2, and explore the effect on cardiomyocytes subjected to anoxia/reoxygenation (A/R) injury. METHODS: Total mRNA was extracted from H9c2 cells, and cDNA was formed by reverse transcription. The AMPKα2 coding sequence was amplified by polymerase chain reaction (PCR) and cloned into pFLAG-CMV-4. The plasmid was transfected into H9c2 cells and AMPKα protein was detected by Western blot. A/R injury model was established, cell viability was detected by MTT assay, LDH activity was analyzed with an automatic biochemical analyzer. The percentage of apoptosis, and intracellular ROS were measured by flow cytometry. SOD and GSH-Px were measured by a colorimetric method.RESULTS: AMPKα2 was successfully constructed into pFLAG-CMV-4 the expression vector. The length of the fragment identified by restriction enzyme digestion was 1700 bp. AMPKα2 protein was significant increase after transfecting with pFLAG-AMPKα2. After anoxia/reoxygenation in H9c2 cells, LDH activity, ROS production, and apoptosis were remarkably increased, while cell viability, activities of SOD and GSH-Px were decreased compared with control group (P<0.01). However, the overexpression of AMPKα2 with transfecting pFLAG-AMPKα2 could reverse above index and then protect against A/R injury. CONCLUSION: Recombinant plasmid pFLAG-AMPKα2 could protect H9c2 cells against A/R injury and the mechanism involving improvement of oxidative stress.

Distribution and drug resistance of pathogens causing nosocomial infections in 2012

YANG Hui-zhi, JIA Heng-min, ZHANG Li-li

2012, 17(12):  1338-1342. 

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AIM: To investigate the distribution and drug resistance of pathogens causing nosocomial infections, and consequently guide rational use of antibiotics. METHODS: A retrospective study was performed to investigate the distribution and drug resistance of gram-negative bacterial isolated from our hospital during January 2012 to June 2012, and the WHONET 5.4 software was used to analyze the data based on the guideline of CLSI 2011 version. RESULTS: 2791 bacterial strains were isolated, the most common pathogens identified were Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus lactis, the detection rate were 18.99%,15.84%,11.03%,8.53%,7.45%, respectively; Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii have higher drug-resistant rate, in which Acinetobacter baumannii is more likely to resistant to antibiotics. CONCLUSION: In order to restrict antibiotic resistance, appropriate use of antibiotics must be strengthened.

Protective effects of matrine on Neurons and Astrocytes in focal ischemia induced by pMCAO in mouse

CHENG Li-yan, SHEN Jia, SHEN Tao-ye, SHI Hong

2012, 17(12):  1343-1348. 

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AIM: To investigate the protective effects of matrine on neurons and astrocytes in focal ischemia induced by permanent middle cerebral artery occlusion (pMCAO) in mouse and explore the possible mechanism. METHODS: MTT and LDH assays were used to assess the protective effects of matrine in primary culture of neurons and astrocytes injured by oxygen and glucose deprivation (OGD). The improvement effects of matrine in 10 min, 1 h, 3 h and 6 h on focal ischemia induced by pMCAO in mouse were evaluated by neuroethology and staining images. The expression of IκBα, IKK, p-IKK and NF-κB in ischemic region 24 h after pMCAO were evaluated by Western blot. RESULTS: Matrine at 50 μmol/L increased the survival rates of neurons and astrocytes and decreased the LDH leakage in astrocytes injured by OGD. In intact animals, matrine (37.5 mg/kg) improved the neuroethology of pMCAO mouse, the time window may be within 1 h after onset of the ischemia; matrine (37.5 mg/kg) significantly reduce infarction volumes of pMCAO mouse and the expression of IκBα, IKK and NF-κB in ischemic area.CONCLUSION: The present findings suggest that matrine, administrated 1 h after ischemia, has protective effects on neurons and astrocytes, possibly via inhibition of NF-κB signaling pathway.

Experimental study on ectopic osteogenesis by implants of gelatin sponge combined with recombinant human bone morphogenetic protein-7

WANG Guo-dong, LI Ping, HAN Jin-xiang, WANG Shi-li, LIU Li-na

2012, 17(12):  1349-1354. 

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AIM: To investigate the ectopic osteogenetic capacity of gelatin sponge contained with recombinant human bone morphogenetic protein-7 (rhBMP-7) by animal experiment and evaluate the biologic activity of rhBMP-7 expressed in Escherichia coli. METHODS: KM mice were divided into two groups randomly. Gelatin sponge contained with rhBMP-7 were implanted into intramuscular spatium of mice as experimental group, while gelatin sponge were implanted as control group. The mice were sacrificed and the tissue samples were harvested at 1st, 2nd, 3rd and 4th week after implantation. Tissue response was observed by HE staining. The contents of proteins and calcium were measured and the activities of alkaline phosphatase (ALP) were detected. RESULTS: HE staining showed that some cells similar to osteocytes and calcific tissues were formed in the group of gelatin sponge contained with rhBMP-7 after implantation at 2nd, 3rd and 4th week. The contents of proteins and calcium and the activities of ALP in experimental group were significantly higher than those in the control group which implanted with gelatin sponge at 2nd, 3rd and 4th week.CONCLUSION: The gelatin sponge combined with rhBMP-7 could induce ectopic osteogenesis more effectively and it is a good biomaterial which could be used to detect the biological activity of rhBMP-7.

Effect and mechanism of platelet inhibitor from Agkistrodon halys venom on artery thrombosis

HUANG Lu, ZHANG Gen-bao, MIN Zhi-xue, MA Kai-ran, ZHENG Ru-qi, SUN Yao, WU Juan

2012, 17(12):  1355-1360. 

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AIM: To explore the effect and mechanism of platelet inhibitor from Agkistrodon halys venom (AHV-PI) on artery thrombosis in rabbits. METHODS: Twenty-four New Zealand rabbits were randomly divided into normal control, artery thrombosis model, positive control (sodium ozagrel at dose of 5 mg/kg) and AHV-PI (0.1 mg/kg) experiment groups (n=6 for each). The model of rabbits carotid artery thrombosis was induced by infiltering 70% FeCl₃. Thrombelastogram was obtained by thromboelastography instrument. The experiment of platelet aggregation was determined by the turbidimetric method. The content of GMP-140 and TXB₂ in plasma were determined by ELISA. The structural changes of the artery thrombosis and platelet were observed under microscope and transmission electron microscope respectively. RESULTS: Compared with model group, R and K were significantly prolonged in AHV-PI experiment group. The alpha angle, MA, CI and the indices of platelet aggregation were decreased (P<0.01 and P<0.05). The levels of GMP-140 and TXB₂ in plasma were decreased (P<0.01). Artery thrombosis histological observation showed that thrombosis in AHV-PI experiment group were not found. Platelet electron microscope showed that the platelet morphology and ultrastructure approach normal control group. AHV-PI can inhibit producing pseudopods process and increase in the number of theαgranules associated with enhanced intensities of their electron densities compared with model group. CONCLUSION: AHV-PI can inhibit platelet aggregation and provent the information of artery thrombosis. The mechanism may be attributed to protecting platelet ultrastructure and reducing the release of platelet lipid metabolism and particulate contents.

Protection of gastrodin on PC12 cell injury induced by glutamate via inhibition of cell apoptosis

WU Hai-yun, JIANG Gen-ling, LI Qing-lin

2012, 17(12):  1361-1367. 

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AIM: To study the protection and the molecular mechanisms of gastrodin on PC12 cells injury induced by glutamate. METHODS: The injury model was established by treating PC12 cells with glutamate in vitro and the cell activity was analyzed by MTT assay. Cell apoptosis morphological changes were detected by AO/EB staining with fluorescence microscope. The flow cytometry (FCM) was used to evaluate the level of intracellular reactive oxygen species (ROS) and to examine cell apoptosis rate via Annexin V-FITC/PI double staining. The expression of caspase-3 protein was determined by Western blot methods. RESULTS: It was indicated that gastrodin can apparently inhibit PC12 cell apoptosis induced by glutamate , it presented a dose-response relationship of the dosage 0.1-10 μmol/L. Gastrodin can also reduce ROS level, drop the expression of cleaved caspase-3 protein and decrease cell apoptosis rate, and gastrodin of 0.1-10 μmol/L presented a dose-response relationship. CONCLUSION: Gastrodin has a protective effect on apoptosis of PC12 cell within a certain dosage range, the protective mechanism of gastrodin on PC12 cell injury induced by glutamate may be related to gastrodin reducing the releasing of ROS, preventing occurrence of oxidative damage and thereby inhibiting caspase-3 pathway-dependent apoptosis in PC12 cell.

Effects of mannitol on the function in isolated hearts of rats

CHEN Min, ZHANG Ming-sheng, WANG Yan, LIANG Yue-qin

2012, 17(12):  1368-1372. 

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AIM: To observe the effects of mannitol in isolated rat hearts. METHODS: The langendorff system was used to evaluate the function of rat hearts treated with mannitol (20 mmol/L, 40 mmol/L and 60 mmol/L respectively). Following a stabilization period of 30 min, the isolated hearts were subjected to continuous perfusion for a further 60 min with vehicle or increasing concentration of mannitol. Heart functional indexes including left ventricular develop pressure (LVDP), rate-pressure product (RPP), maximal rate of pressure increased (+dpp/dt_max), maximal rate of pressure decreased (-dp/dt_max), left ventricular end diastolic pressure (LVEDP) and coronary flow were recorded.RESULTS: LVDP,+dp/dt_max and RPP were increased significantly in hearts perfused with 20 mmol/L mannitol in a time dependent manner. However, when the hearts perfused with 40 mmol/L or 60 mmol/L mannitol, time used for reaching the maximum LVDP,+dp/dt_max and RPP by 40 mmol/L and 60 mmol/L mannitol was shorter in hearts treated with 20 mmol/L mannitol. More, the results demonstrated that heart treated with 60 mmol/L mannitol could significantly increase the LVDEP and decrease the -dp/dt_max. CONCLUSION: Mannitol could affect left ventricular contraction function in a time and concentration dependent manner. Ventricular diastolic function was weakened by perfusing the high concentration of mannitol.

Determination and pharmacokinetics of S-Adenosylmethionine in rats plasma by HPLC-UV

ZHU Li-li, ZHANG Li-jiu, FANG Hai-ming, YAO Ting-ting, YANG Jiao, WANG Jia-jia, XIA Quan

2012, 17(12):  1372-1377. 

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AIM: To establish an HPLC-UV assay for determining plasma concentration of S-Adenosylmethionine (SAMe) and to study its pharmacokinetics in rats. METHODS: The chromatographic conditions were as follows: a Kromasil C₁₈ column (4.6 mm×200 mm , 5 μm) ,a flow rate of 0.6 mL/min for the mobile phase of methanol/0.3% trifluoroacetic acid (V/V) (dissolve 1% phosphate buffer) (2∶98) , an isocratic elution mode was carried out at column temperature (30 ℃) and the UV detection at the wavelength of 260 nm. 140 mg/kg SAMe was administrated by intravenous and plasma concentration were determined by HPLC-UV assay. RESULTS: SAMe was successfully separated. The calibration curve showed a good linear regression within the range of 10-2000 μg/mL. The regression equation was Y=30241X+256204, r=0.9991. The precision of intra-assay and inter-assay were 2.6%, 3.6%, 3.9% and 6.3%, 4.9%, 7.9%, respectively. The average extraction recovery was 107%, 101%, 98.3%, respectively. The pharmacokinetic parameter were AUC_(0-t) (569.52±174.87) mg·L^-1·h,t_1/2 (2.03±0.96) h, CL (0.21±0.13) L·h^-1·kg^-1, V_d (0.53±0.31) L/kg, respectively.CONCLUSION: This method was proved to be simple and efficient with excellent specificity, sensitivity, precision, recovery and can be applied to pharmacokinetic investigation of SAMe.

Pharmacokinetic and absolute bioavailability study of Guanfu Base A hydrochloride in Beagle dogs

SUN Jian-guo, XIAO Ya-nang, PENG Ying, ZHANG Xue-yuan, WU Hui, YU Guang-wei, LIU Jing-han, WU Ming-shu, A Ji-ye, WANG Guang-ji

2012, 17(12):  1378-1383. 

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AIM: An LC-MS method was developed and validated for the analysis of Guanfu Base A in dog plasma to support the pharmacokinetic study. METHODS: Blood was withdrawn at different times and absolute bioavailability was studied by LC-MS at dosage of 4 mg/kg in 6 beagle dogs. RESULTS: The pharmacokinetic of Guanfu Base A in Beagle dogs fits best to two compartment model with AUC_{0-48 h}, C_max, t_max and half life t_1/2 of (17623.9±7006.4) ng·mL^-1·h, (1988±972)ng/mL, (0.8±0.7) h, and (11.2±1.6) h, respectively. Compared with i.v administration, the absolute bioavailability of Guanfu Base A was(99.0±11.2)%, with absorption rate (K₀₁)at (7.563±4.612)/h.CONCLUSION: After oral administration, GFA can be rapidly and completely absorbed by Beagle dogs, which suggested that oral administration of Guanfu Base A could be a substitute way for anti-arrhythmic treatment.

Synergistic combination of topotecan and low-intensity ultrasound to enhance HepG2 cell apoptosis

QIU Ri-xiang, WANG Yan-li, CHEN Yang-di, LIN YAN, YANG Feng, CHEN Zhi-yi

2012, 17(12):  1384-1388. 

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AIM: To study the combined effects of low-intensity pulsed ultrasound (LIPUS) and topotecan (TOP) on cell apoptosis induction of HepG2 cells and the mechanisms involved. METHODS: Human liver cancer HepG2 cells were used for the experiments. Experiments were conducted in 4 groups: non-treated, TOP treated, ultrasound treated, and combined (TOP+LIPUS). The viability was evaluated by trypan blue dye exclusion test and apoptosis and incorporation of TOP was assessed by flow cytometry. Involvement of sonoporation in molecular incorporation was evaluated using FITC-dextran. RESULTS: Synergistic enhancement in cell killing and additive enhancement in induction of apoptosis were observed at and above 0.8W/cm². Incorporation of TOP was increased 12.88% in combined group (vs. TOP) at 1.0W/cm². Increasing in incorporation of the TOP by cavitation and ultrasound were the mechanisms of enhancements. CONCLUSION: Combination of TOP and LIPUS can enhance the effect of apoptosis induction, and cavitation is the main mechanism for their synergistic.

Expressions and its prognostic value research of MMP-14 and cathepsin-D in esophageal squamous cell carcinoma

WU Xu-hui, WU Gong-zhi, PENG Cong-xiong, ZHOU Yao-hong, WU Yi-zhi, HU Ding-zhong

2012, 17(12):  1387-1390. 

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AIM: To detect the expressions of MMP-14 and cathepsin D(Cath-D), and investigate their significance on different clinical characteristic in esophageal squamous cell carcinonma, for providing help to clinical work. METHODS: The study included 95 cases of esophageal squamous cell carcinoma as observation group, 70 cases of normal esophageal tissue as control group. We detected the expressions of MMP-14 and Cath-D by IHC methods in two groups. RESULTS: The positive rate of MMP-14 and Cath-D were higher in the observation group than in control group. The positive rate of MMP-14 and Cath-D were correlated with tumor diameter, differentiation and Ki67 expressions. There was positive correlationship between MMP-14 and Cath-D in esophageal squamous cell carcinoma. The expressions of MMP-14 and Cath-D were correlated with prognosis in esophageal squamous cell carcinoma. CONCLUSION: The high-expressions of MMP-14 and Cath-D may promote the occurrence and development in esophageal squamous cell carcinoma. The joint detection of MMP-14 and Cath-D may be helpful to predict the prognosis of esophageal squamous cell carcinoma.

Influence of the curative effect of salmeterol/fluticasone and bi-level positive airway pressure on severe chronic obstructive pulmonary disease with respiratory failure

TONG Ya-ling, LI Qian-bing, XU Jian-lin, CHEN Jun

2012, 17(12):  1392-1397. 

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AIM: To observe the curative effect of inhaling Salmeterol (50 microg)/ fluticasion (500 microg) and bi-level positive airway pressure for severe chronic obstructive pulmonary disease (COPD) with respiratory failure cases on lung function, anxiety and depression, quality of life and the times of acute exacerbation of COPD. METHODS: 48 severe COPD with respiratory failure cases were randomly divided into two groups. The therapy group received inhaling. Salmeterol/fluticasion and bi-level positive airway pressure including routine treatment.At the same time,the comparative group were given bi-level positive airway pressure including routine treatment.The arterial blood gas, lung function,six minutes walking distance (6MWD),the scores of SGRQ and SAS and the times of acute exacerbation of COPD were observed before the treatment,and 7 days,3 months,6 months after the treatment. RESULTS: The arterial blood gas, lung function,six minutes walking distance(6MWD), the scores of SGRQ and SAS and reduce the frequence of exacerbations of COPD of the treatment group and the end of 6 months.The significant differences were seen between the treatment group and the comparative group. The therapy group had better curative effect than the comparative group. CONCLUSION: The treatment of severe COPD with Respiratory failure cases inhaling. Salmeterol/fluticasion and bi-level positive airway pressure were effective.

Double blinded randomized and controlled study on premenstrual syndrome by Mifepristone

ZHOU Chun-hui, YANG Bai-lan, YANG Zhang-li, LONG Wen-xiang

2012, 17(12):  1398-1400. 

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AIM: To evaluate the efficacy and safety of Mifepristone in treating patients with premenstrual syndrome(PMS). METHODS: 80 subjects diagnosed with PMS were participated in the study. The study was designed as randomized double blind placebo controlled trial. The experimental group was treated with Mifepristone for 3 months, while controlled with placebo. And a 3-month follow up for effectiveness and safety would be taken and experimental.RESULTS: The total effective rates of experimental and controlled were 92.5% and 45% respectively, and the total clinical effect rates of 3-month follow up were 90% and 37.5% respectively, comparisons of the two indices were significantly different(P<0.05). As for safety, there was no significant difference.CONCLUSION: Mifepristone can improve the PMS. And its effect is obvious, with more safety less side effects in treating PMS.

Clinical effect comparison on gynecological preoperative bowel cleansing with mannitol solution and magnesium sulfate solution

WANG Jing-xia, WANG Xin-mei, LI Qing-yan

2012, 17(12):  1401-1403. 

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AIM: To compare the clinical effect on gynecological preoperative bowel cleansing with mannitol solution and magnesium sulfate solution,in order to guide clinical drugs of choice. METHODS: The prepare hysterectomy medical records 106 cases were chosed,which was randomly divided into oral the mannitol solution group (n=53) and oral magnesium sulfate group (n=53). The intestinal cleanliness, number of bowel movements,exhaust time and related adverse reactions were compared.RESULTS: There was no statistical significance in the intestinal cleanliness, number of bowel movements,exhaust time in the two groups (P>0.05); there was no statistical significance in the nausea, vomiting, stomach pain, bloating, abdominal pain, anal stimulation,dizziness,headache in the two groups (P>0.05). CONCLUSION: There was no significant difference in the clinical effect and the related adverse reactions in the two groups.Mannitol solution and magnesium sulfate solution can be used in clinic,but magnesium sulfate solution is bitter in taste. Mannitol solution is easy to use, easy to store, and good taste, and can be widely used for bowel preparation before gynecologic surgery.

Observation on IL-8 level change and the curative effect of combined ribavirin with Tangreqing injection for hand-foot-mouth disease in younger children

CUI Ling

2012, 17(12):  1404-1406. 

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AIM: To observe the serum interleukin-8(IL-8) level variation and the curative effects of combined ribavirin with Tangreqing injection in treatment of hand-foot-mouth disease(HFMD) of younger children. METHODS: Eighty-four younger children with HFMD were randomly assigned to groups of control (n=42) and treatment (n=42). The control group were managed with conventional ribavirin injection and the treatment group were administered with combined ribavirin with Tangreqing injection besides conventional symptomatic treatment for the two groups. Venous blood was taken, five days after the treatment, from the two groups for determination of the serum IL-8 level. RESULTS: Lower serum level of IL-8 and better therapeutic effects were seen in the treatment group as compared with the controls, and the difference was significant(P<0.05).CONCLUSION: Combined ribavirin with Tangreqing injection for child HFMD has better therapeutic effects than single dosage of ribavirin injection, may be related with reducing the serum IL-8 level.

Transmission of inflammatory signals along the [brain gut] advances and intervention strategies

KANG An, ZHENG Xiao, WEN Hong-mei, WANG Xiao-long

2012, 17(12):  1407-1412. 

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Accumulating evidence reveals a close linkage between the central nervous system disorders and the peripheral diseases. It is believed that the “brain-gut axis” mediated inflammatory signal transmission is an important pathway to link the brain disorders and peripheral inflammation.In this review, we discusse the potential mechanisms involved in the inflammatory signal transmission along the “brain-gut axis” and its influence on the subsequently developed neuropsychiatric disorders especially major depression. Also the potential strategies to intervene the inflammatory signal transmission along the “brain-gut axis” for the prevention and treatment of brain disorders are discussed in this paper.

Reversal of the anticoagulant effect of dabigatran etexilate

TAN Sheng-lan, ZHOU Xin-min, PENG Juan, ZHANG Wei, LIU Zhao-qian, ZHOU Hong-hao, LI Zhi

2012, 17(12):  1413-1418. 

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Dabigatran etexilate is a new oral anticoagulant that acts as a direct thrombin inhibitor. Dabigatran etexilate generally shows good efficacy and safty, however, bleeding is the most common side effect which is slightly lower than or similar to that of warfarin or enoxaparin. In certain clinical situations including major bleeding and requirement of surgery or invasive procedure, clinicians will have to reverse the anticoagulant effect of dabigatran etexilate emergently. So far no antidote for dabigatran etexilate has been established.The management of bleeding resulting from dabigatran etexilate should be individualized based on the location and severity of the hemorrhage. Tests including thrombin clotting time (TT) and ecarin clotting time (ECT) will be helpful to determine the reversal of the anticoagulant effect of dabigatran etexilate.

Research progress of intracellular activity of antibiotics and its celluar pharmacokinetics evaluation

WANG Yao-yao, ZHOU Fang, ZHANG Jing-wei, SONG Da-wei, LI Song-lu, ZHA Wei-bin, WU Xiao-lan, WANG Guang-ji

2012, 17(12):  1419-1426. 

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Intracellular bacteria are protected from the attack of the immune system as well as from the action of the antibiotics present in the extracellular milieu, besides, antibiotics usually poorly act on intracellular bacteria. This is one of the main causes for recurrence and reinfection of infectious diseases. Thus, classical pharmacokinetic studies based on plasma drug concentrations may not be sufficient to predict activity of antibiotics in vivo, and there is a pressing need to expand pharmacokinetics to the new age of cellular pharmacokinetics. This review aims to present and summary the current knowledge of cellular pharmacokinetics of antibiotics including the PK/PD parameters governing the intracellular activity of antibiotics, and to discuss strategies for optimizing this activity.

Research advancement of heartleaf houttuynia herb on antibacterial action

LI Juan, SHAO Hui, ZHONG Zheng-ling, CHU Ji-ru, XIE Hai-tang

2012, 17(12):  1427-1432. 

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Heartleaf houttuynia herb has many pharmacologic actions especially antibacterial action. This review describes the research advancement of heartleaf houttuynia herb on antibacterial action from three aspects including the whole antibacterial action evaluation, special antibacterial action, and the trouble in clinic and the study direction. This paper provides a review for the next research.

Research on the pharmacokinetics of prodrugs

ZHU Yin-ci, SUN Jian-guo, PENG Ying, WANG Guang-ji

2012, 17(12):  1433-1440. 

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Prodrugs are chemicals with little or no pharmacological activity, which can be changed to therapeutically active metabolite after undergoing biotransformation in vivo. The design of prodrugs has become an important way to overcome the shortcomings of drugs such as poor solubility, low bioavailability, short elimination half-life, devoid of ideal targets and so on. However, there still lacks criteria to evaluate pharmacokinetic properties of prodrugs. This paper reviews the pharmacokinetic profiles of various types of prodrugs in recent years, and proposes full evaluation from absorption, distribution, metabolism and excretion perspectives.