Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the m...Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.展开更多
To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the...To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the medicine group treated with BHD, the control group with dexamethasone liquid, and the blank group with distilled water. Oral administration was given for 14 consecutive days, once daily. Model of arterial thrombosis was established in the animals 2 hours after final medication, the blood content of PAF, dry weight (DW) and occlusion time (OT) of thrombus, and dry weight of thrombus/body weight (TW/BW) ratio were observed. Results indicated that BHD could markedly lower the arterial blood content of PAF after thrombosis, increase the OT of thrombus, reduce the dry weight of thrombus and the TW/BW ratio (P展开更多
AIM: To observe the pharmacokinetics and pharmacodynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS: The CYP2C19 genotype status of Chinese Han healthy vol...AIM: To observe the pharmacokinetics and pharmacodynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS: The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS: The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION: In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.展开更多
Orphanin FQ(OFQ) or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperre...Orphanin FQ(OFQ) or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure (MABP) in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats (250~300 g body weight, 2. 5~3 months old) were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ (0. 5 mg/kg) induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI(60 μg/kg), 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.展开更多
To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wa...To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity (PWV) was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.展开更多
We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bil...We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m^2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 μg/L. The area under the curve of paclitaxel was 4398.6 μg·h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.展开更多
In order to investigate the mechanisms of acute cerebral ischemia, and to look for effective drugs on cerebral resuscitation, we made a model of acute complete global brain ischemia, reperfusion and resuscitation on r...In order to investigate the mechanisms of acute cerebral ischemia, and to look for effective drugs on cerebral resuscitation, we made a model of acute complete global brain ischemia, reperfusion and resuscitation on rats according to Garavilla's method.Our results showed that the event of cerebral ischemia and reperfusion injury could resuh in the increase of total brain calcium content, and anisodamine has the same reducing brain calcium contents as diltiazem's, while improving neurological outcome and alleviating injury to neurons.展开更多
AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with no- tably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10...AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with no- tably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10 times upper limit of normal range (ULN) were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS: A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury (n = 46, 35.7%), DILl (n = 25, 19.4%) and malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury (14.5 5.6 ULN vs 32.5 :I: 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case was classified as definite, 19 (76%) cases were clas- sified as probable and 5 (20%) as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge, 10 (40%) patients were recovered and the other 15 (60%) were improved. The improved patients tended to have a higher peak ALT (808 + 348 U/L vs 623 + 118 U/L, P = 0.016) and shorter treatment duration before discharge (8 + 6 d vs 28 ~ 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%) cases. Twenty-four (96%) cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs (e.g., glycyr- rhizinate), antioxidants (e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin), polyene phospha- tidyl choline and herbal extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio (OR) 32.7, 95%CI (2.8-374.1),CONCLUSION: DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.展开更多
Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and m...Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.展开更多
A 63-year-old man was admitted to our observation unit with atypical angina found to be non-adherent with his an- ti-hypertensive medication regimen for one month. His medical history was notable for hypertension for ...A 63-year-old man was admitted to our observation unit with atypical angina found to be non-adherent with his an- ti-hypertensive medication regimen for one month. His medical history was notable for hypertension for ten years and current tobacco smoking. He was hypertensive with otherwise, stable vital signs. Cardiac auscultation revealed normal S1 and $2 without a murmur.展开更多
A new high-performance liquid chromatography (HPLC) method for the quantitative determination of sitagliptin in rat plasma was developed and validated for pharmacokinetics study. The plasma was spiked with the inter...A new high-performance liquid chromatography (HPLC) method for the quantitative determination of sitagliptin in rat plasma was developed and validated for pharmacokinetics study. The plasma was spiked with the internal standard (hydrocortisone, IS), treated with sodium hydroxide, and extracted with ethyl acetate. The extracted analyte was injected into an Agilent Zorbax Extend-C18 column (250 mm×4.6 mm, 4 μm) maintained at 30℃ and monitored at 267 nm. The mobile phase consisting of methanol-water (60:40, v/v, containing 10 mM Tris and 10 mM triethylamine) was titrated to pH 9.0 using 1 mol/L hydrochloric acid. The flow rate was 1.0 mL/min. The method showed high specificity. Calibration curves of the peak area ratio of each analyte/IS versus sitagliptin concentration were linear in the range of 0.75-100.0μg/mL (r〉0.9957). The lower limit of quantification (LLOQ) was 0.75 μg/mL. The intra-day and inter-day coefficient of variation was lower than 10%. The accuracy (relative recovery) at three levels was 105.3% (0.75 μg/mL), 99.8% (10.0 μg/mL) and 99.0% (100.0 μg/mL). The extraction recovery was 81.5%, 82.4% and 84.5% at the concentrations of 0.75, 10.0 and 100.0 μg/mL, respectively. The short-term, long-term, freeze-thaw storage stability of plasma samples and the stability of standard solutions were satisfactory. This HPLC method is suitable for determining the concentration of sitagliptin in rat plasma and it was applied to determine the concentration-time profiles of sitagliptin in rat plasma following oral administration of sitagliptin.展开更多
Hypertension is associated with at least 7.6 million annual deaths worldwide.While pharmacotherapy may provide good control for blood pressure,it sometimes induces adverse effects.Meanwhile,acupuncture has been used f...Hypertension is associated with at least 7.6 million annual deaths worldwide.While pharmacotherapy may provide good control for blood pressure,it sometimes induces adverse effects.Meanwhile,acupuncture has been used for the treatment of cardiovascular diseases,such as hypertension,coronary artery disease,and stroke,but its mechanisms of actions remain poorly understood.The efficacy of acupuncture depends on multiple constituent elements including acupoints,manipulation skills,and implementation programs,which are termed as acupuncture prescription.This review summarized the previous information of experimental use of acupuncture on animals including species,hypertension models,acupoints selection,acupoint location,stimulation protocols,and evaluation of effectiveness to provide useful guidance for researchers when performing acupuncture in animal experiments.展开更多
OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were g...OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.展开更多
A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarit...A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME CI8 column with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (acetonitrile) at a flow rate of 0.3 mL/min. Multiple reaction monitoring (MRM) was used with an electrospray ionization source (ESI) in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 ~g/mL for paeoniflorin and 0.000l to 0.05 ~tg/mL for astragaloside IV. The accuracy (RE) was within the range of-3.5% to 6.3%, and the intra- and inter-day precisions (RSD) were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction (HGWD) was successfully completed through this method. The method develooed in this studv will fill a gap in oharmacokinetic studies of HGWD.展开更多
OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the mechani...OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the mechanisms.METHODS:In the IAI group,CMCC was injected into the Zusanli acupoint(ST 36) immediately after 30-min stimulation by electro-acupuncture(EA) at the acupoints,and into the femoral vein and skeletal muscle in IVI and IMI groups,respectively.Intra-gastric pressure was detected.The plasma concentration of CMCC was measured at various times.RESULTS:The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups.In the IAI group,this effect was significantly stronger than that in the IMI group at 2 min and 15 min,but not significantly different between the two groups at 5 min and 30 min.Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min,but higher than that in the IMI group.The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5,15 and 30 min,indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group.There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups.CONCLUSION:The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI,which correlated with the blood concentration of CMCC.展开更多
A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol c...A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-Cjg column (3.5 pm, 2.1 mmx 100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3->352.9 for isochlorogenic acid B and m/z 227.1-143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5-2500 ng/mL (r^2= 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.展开更多
Objective: To observe the anti inflammatory effect of cerivastatin in a mouse model of vascular injury and its cholesterol lowering effect. Methods: We developed a mouse model of vascular remodeling induced by polyeth...Objective: To observe the anti inflammatory effect of cerivastatin in a mouse model of vascular injury and its cholesterol lowering effect. Methods: We developed a mouse model of vascular remodeling induced by polyethylene cuff placement and determined the anti inflammatory effects of cerivastatin in wild mice. Cerivastatin was given by Alzet micro osmotic minipumps implanted intraperitoneally at the same time as cuff placement at doses of 0.1 mg/kg, 0.5 mg/kg and 1 mg/kg per day, respectively for 2 weeks after cuff placement. The insufficient doses of Cerivastatin to lower serum cholesterol and systolic blood pressure through the neointimal formation and BrdU index were investigated in mouse femoral injury artery induced by cuff placement. Results: There was a little change in serum cholesterol by the treatment with cerivastatin, the cross sectional area of intima of injured femoral artery was significantly increased, the neointima formation was significantly increased by the cuff induced vascular injury at day 14. The neointimal formation and BrdU index were inhibited in the 1 mg/kg cerivastatin, but not in the 0.1 mg/kg and 0.5 mg/kg cerivastatin. Furthermore, 1 mg/kg of cerivastatin significantly inhibited the expression of tumor necrosis factor α (TNF α) and interleukin 1β (IL 1β) without lowering serum cholesterol. Conclusions: These results suggest that cerivastatin can inhibit vascular inflammation and the proliferation of vascular smooth muscle cells (VSMCs) through its lipid lowering independent action. Such effects of cerivastatin may be an important mechanism, by which it prevents the development of atherosclerotic lesions.展开更多
Objective: To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation. Methods: 108 Wistar rats weighing (200 g±30 g) were randomly divided into a sham shock (S...Objective: To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation. Methods: 108 Wistar rats weighing (200 g±30 g) were randomly divided into a sham shock (SS) group (n=36), a hemorrhagic shock resuscitation (HS) group (n=36) and a hemorrhagic shock cisapride treated (HSC) group (n=36). Sampling at 1, 2 and 4 hours after resuscitation was done and 6 samples for each observation item were taken. The gastric blood flow volume was measured by isotope label biological microglobulin. Gastric pHi, gastric emptying, MDA and Na+-K+-ATPase of gastric mucosa were measured. Results: In the HSC group, the relative residual rate of gastric pigment decreased significantly, the gastric blood flow volume elevated; gastric pHi increased significantly at 2 hours; the level of mucosal MDA decreased at 4 hours, the activity of Na+-K+-ATPase increased and the lactic acid level in the portal vein decreased significantly compared to the HS group. Conclusions: After hemorrhagic shock resuscitation, cisapride contained the following functions,1) promoting gastric emptying, 2) increasing the blood flow of gastric blood flow volume and gastric pHi, 3) depressing the lactic acid concentration of the portal vein and improving MDA volume and Na+-K+ -ATPase activity of gastric mucosa. It suggests that after comple menting effective circulating blood volume for hemorrhagic shock resuscitation, early use of cisapride for gastric motility is helpful for an improvement of lasting ischemia and hypoxia in stomach.展开更多
文摘Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.
文摘To explore the effect of Buyang Huanwu Decoction (BHD) on platelet activating factor (PAF) content in arterial blood pre- and post-arterial thrombosis in rats, male Wistar rats were randomly divided into 3 groups, the medicine group treated with BHD, the control group with dexamethasone liquid, and the blank group with distilled water. Oral administration was given for 14 consecutive days, once daily. Model of arterial thrombosis was established in the animals 2 hours after final medication, the blood content of PAF, dry weight (DW) and occlusion time (OT) of thrombus, and dry weight of thrombus/body weight (TW/BW) ratio were observed. Results indicated that BHD could markedly lower the arterial blood content of PAF after thrombosis, increase the OT of thrombus, reduce the dry weight of thrombus and the TW/BW ratio (P
基金Natural Science Foundation of Anhui Education Department, No. 2003kj199
文摘AIM: To observe the pharmacokinetics and pharmacodynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS: The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS: The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION: In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.
文摘Orphanin FQ(OFQ) or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure (MABP) in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats (250~300 g body weight, 2. 5~3 months old) were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ (0. 5 mg/kg) induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI(60 μg/kg), 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.
文摘To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity (PWV) was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.
文摘We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m^2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 μg/L. The area under the curve of paclitaxel was 4398.6 μg·h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.
文摘In order to investigate the mechanisms of acute cerebral ischemia, and to look for effective drugs on cerebral resuscitation, we made a model of acute complete global brain ischemia, reperfusion and resuscitation on rats according to Garavilla's method.Our results showed that the event of cerebral ischemia and reperfusion injury could resuh in the increase of total brain calcium content, and anisodamine has the same reducing brain calcium contents as diltiazem's, while improving neurological outcome and alleviating injury to neurons.
基金Supported by Zhejiang Provincial Bureau of Education,No.200908690Zhejiang Provincial Bureau of Health,No.2012KYA090
文摘AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with no- tably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10 times upper limit of normal range (ULN) were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS: A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury (n = 46, 35.7%), DILl (n = 25, 19.4%) and malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury (14.5 5.6 ULN vs 32.5 :I: 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case was classified as definite, 19 (76%) cases were clas- sified as probable and 5 (20%) as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge, 10 (40%) patients were recovered and the other 15 (60%) were improved. The improved patients tended to have a higher peak ALT (808 + 348 U/L vs 623 + 118 U/L, P = 0.016) and shorter treatment duration before discharge (8 + 6 d vs 28 ~ 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%) cases. Twenty-four (96%) cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs (e.g., glycyr- rhizinate), antioxidants (e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin), polyene phospha- tidyl choline and herbal extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio (OR) 32.7, 95%CI (2.8-374.1),CONCLUSION: DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.
基金This work were supported by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201303), the National Natural Science Foundation of China (No. 81470429, No.81270285), and The capital health research and development of special (No 2011-2006-14).
文摘Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.
文摘A 63-year-old man was admitted to our observation unit with atypical angina found to be non-adherent with his an- ti-hypertensive medication regimen for one month. His medical history was notable for hypertension for ten years and current tobacco smoking. He was hypertensive with otherwise, stable vital signs. Cardiac auscultation revealed normal S1 and $2 without a murmur.
基金National Integrity Innovational Technology Platform of New Drug and Research and Development (Grant No. 2009ZX09301-010)National Fund for Talent Training in Basic Science
文摘A new high-performance liquid chromatography (HPLC) method for the quantitative determination of sitagliptin in rat plasma was developed and validated for pharmacokinetics study. The plasma was spiked with the internal standard (hydrocortisone, IS), treated with sodium hydroxide, and extracted with ethyl acetate. The extracted analyte was injected into an Agilent Zorbax Extend-C18 column (250 mm×4.6 mm, 4 μm) maintained at 30℃ and monitored at 267 nm. The mobile phase consisting of methanol-water (60:40, v/v, containing 10 mM Tris and 10 mM triethylamine) was titrated to pH 9.0 using 1 mol/L hydrochloric acid. The flow rate was 1.0 mL/min. The method showed high specificity. Calibration curves of the peak area ratio of each analyte/IS versus sitagliptin concentration were linear in the range of 0.75-100.0μg/mL (r〉0.9957). The lower limit of quantification (LLOQ) was 0.75 μg/mL. The intra-day and inter-day coefficient of variation was lower than 10%. The accuracy (relative recovery) at three levels was 105.3% (0.75 μg/mL), 99.8% (10.0 μg/mL) and 99.0% (100.0 μg/mL). The extraction recovery was 81.5%, 82.4% and 84.5% at the concentrations of 0.75, 10.0 and 100.0 μg/mL, respectively. The short-term, long-term, freeze-thaw storage stability of plasma samples and the stability of standard solutions were satisfactory. This HPLC method is suitable for determining the concentration of sitagliptin in rat plasma and it was applied to determine the concentration-time profiles of sitagliptin in rat plasma following oral administration of sitagliptin.
基金the National Basic Research Program of China:the Epigenetic Regulatory Mechanism of the Specificity of Acupoints(973 Program,No.2012CB518501)the National Natural Science Foundation of China:the Regulatory Mechanism of AS-Neuron Crosstalk With Energy for Promoting Synaptic Plasticity in Hippocampus Treated by Acupuncture(No.81202743)+1 种基金Deacetylation Modification in Personalized Medicine for Acupuncture-Based Weight-Loss(No.81303019)Mechanistic Study of STAT5-miR-193b Pathway in Obesity and Weight Loss by Acupuncture(No.81273838)
文摘Hypertension is associated with at least 7.6 million annual deaths worldwide.While pharmacotherapy may provide good control for blood pressure,it sometimes induces adverse effects.Meanwhile,acupuncture has been used for the treatment of cardiovascular diseases,such as hypertension,coronary artery disease,and stroke,but its mechanisms of actions remain poorly understood.The efficacy of acupuncture depends on multiple constituent elements including acupoints,manipulation skills,and implementation programs,which are termed as acupuncture prescription.This review summarized the previous information of experimental use of acupuncture on animals including species,hypertension models,acupoints selection,acupoint location,stimulation protocols,and evaluation of effectiveness to provide useful guidance for researchers when performing acupuncture in animal experiments.
基金Supported by the National Natural Sciences Foundation of China(A Study on the Anti-gout Effects and Related Mechanisms of Tibetan Medicine Rupeng15 Powder,No.81160410)
文摘OBJECTIVE: To evaluate the influence of the Tibetan medicine Ru Peng15 powder(RPP15) on uric acid levels, and explore its possible mechanisms of action in hyperuricemic animal models.METHODS: Hyperuricemic mice were generated by orally administering yeast extract paste twice daily(30 g/kg) for 8 days, to mimic human hyperuricemia induced by high-protein diets. Hyperuricemic rats were generated by intraperitoneal injection of 250 mg/kg potassium oxonate to each animal 1 h before the last oral administration of test compounds, which raised the serum uric acid level by inhibiting the decomposition of uric acid. Levels of uric acid and creatinine in serum and urine were detected by the phosphotungstic acid and picric acid methods respectively, and the activity of xanthine oxidase(XOD) was assayed using a commercial test kit.RESULTS: RPP15(0.4, 0.8, 1.2 g/kg) significantly decreased the level of serum uric acid in healthy rats(P < 0.05). Furthermore, hyperuricemic rats treated with RPP15(0.4, 0.8, 1.2 g/kg) had lower serum uric acid levels(P < 0.05), accompanied by lower urine uric acid(P < 0.05). For the hyperuricemic mice, the levels of uric acid in the serum decreased significantly(P < 0.05) and the activity of XOD in the liver was restored to normal levels after treatment with RPP15(P < 0.05).CONCLUSION: RPP15(0.4, 0.8, 1.2 g/kg) demonstrated an anti-hyperuricemic effect on both healthy and hyperuricemic animals, and the mechanism is most likely associated with inhibiting the activity of XOD.
文摘A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV, This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME CI8 column with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (acetonitrile) at a flow rate of 0.3 mL/min. Multiple reaction monitoring (MRM) was used with an electrospray ionization source (ESI) in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 ~g/mL for paeoniflorin and 0.000l to 0.05 ~tg/mL for astragaloside IV. The accuracy (RE) was within the range of-3.5% to 6.3%, and the intra- and inter-day precisions (RSD) were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction (HGWD) was successfully completed through this method. The method develooed in this studv will fill a gap in oharmacokinetic studies of HGWD.
基金Supported by Beijing Natural Science Foundation Grant(grant number 7072053)the National Basic Research Pro-gram of China (973 Program) of China Grant(2006CB504506)+1 种基金the National Natural Science Foundationof China (NSFC) Grants (30873295 and 30801485)the Business fees of China academy of Chinese Medical Sciences for independent Topics of Basic Researchers (ZZ2007001)
文摘OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the mechanisms.METHODS:In the IAI group,CMCC was injected into the Zusanli acupoint(ST 36) immediately after 30-min stimulation by electro-acupuncture(EA) at the acupoints,and into the femoral vein and skeletal muscle in IVI and IMI groups,respectively.Intra-gastric pressure was detected.The plasma concentration of CMCC was measured at various times.RESULTS:The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups.In the IAI group,this effect was significantly stronger than that in the IMI group at 2 min and 15 min,but not significantly different between the two groups at 5 min and 30 min.Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min,but higher than that in the IMI group.The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5,15 and 30 min,indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group.There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups.CONCLUSION:The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI,which correlated with the blood concentration of CMCC.
基金Chinese Academy of Medical Sciences(Grant No.CAMS-2017-I2M-1-011)
文摘A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-Cjg column (3.5 pm, 2.1 mmx 100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3->352.9 for isochlorogenic acid B and m/z 227.1-143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5-2500 ng/mL (r^2= 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.
文摘Objective: To observe the anti inflammatory effect of cerivastatin in a mouse model of vascular injury and its cholesterol lowering effect. Methods: We developed a mouse model of vascular remodeling induced by polyethylene cuff placement and determined the anti inflammatory effects of cerivastatin in wild mice. Cerivastatin was given by Alzet micro osmotic minipumps implanted intraperitoneally at the same time as cuff placement at doses of 0.1 mg/kg, 0.5 mg/kg and 1 mg/kg per day, respectively for 2 weeks after cuff placement. The insufficient doses of Cerivastatin to lower serum cholesterol and systolic blood pressure through the neointimal formation and BrdU index were investigated in mouse femoral injury artery induced by cuff placement. Results: There was a little change in serum cholesterol by the treatment with cerivastatin, the cross sectional area of intima of injured femoral artery was significantly increased, the neointima formation was significantly increased by the cuff induced vascular injury at day 14. The neointimal formation and BrdU index were inhibited in the 1 mg/kg cerivastatin, but not in the 0.1 mg/kg and 0.5 mg/kg cerivastatin. Furthermore, 1 mg/kg of cerivastatin significantly inhibited the expression of tumor necrosis factor α (TNF α) and interleukin 1β (IL 1β) without lowering serum cholesterol. Conclusions: These results suggest that cerivastatin can inhibit vascular inflammation and the proliferation of vascular smooth muscle cells (VSMCs) through its lipid lowering independent action. Such effects of cerivastatin may be an important mechanism, by which it prevents the development of atherosclerotic lesions.
文摘Objective: To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation. Methods: 108 Wistar rats weighing (200 g±30 g) were randomly divided into a sham shock (SS) group (n=36), a hemorrhagic shock resuscitation (HS) group (n=36) and a hemorrhagic shock cisapride treated (HSC) group (n=36). Sampling at 1, 2 and 4 hours after resuscitation was done and 6 samples for each observation item were taken. The gastric blood flow volume was measured by isotope label biological microglobulin. Gastric pHi, gastric emptying, MDA and Na+-K+-ATPase of gastric mucosa were measured. Results: In the HSC group, the relative residual rate of gastric pigment decreased significantly, the gastric blood flow volume elevated; gastric pHi increased significantly at 2 hours; the level of mucosal MDA decreased at 4 hours, the activity of Na+-K+-ATPase increased and the lactic acid level in the portal vein decreased significantly compared to the HS group. Conclusions: After hemorrhagic shock resuscitation, cisapride contained the following functions,1) promoting gastric emptying, 2) increasing the blood flow of gastric blood flow volume and gastric pHi, 3) depressing the lactic acid concentration of the portal vein and improving MDA volume and Na+-K+ -ATPase activity of gastric mucosa. It suggests that after comple menting effective circulating blood volume for hemorrhagic shock resuscitation, early use of cisapride for gastric motility is helpful for an improvement of lasting ischemia and hypoxia in stomach.