Both aspirin and angiotensin converting enzyme (ACE) inhibitors are often used concomitantly in patients with cardiovascular disease. The safety of the combination has been questioned. The potential antagonistic interactions between ACE inhibitors and aspirin has become the focus of both increasing research and intense debate, with conflicting conclusions having been reported in the literature. We reviewed systematically available literature on the interactions between ACE inhibitors and aspirin in hypertension, acute myocardial infarction and congestive heart failure and found that further trials are needed to shed light on the effects and mechanism of interaction between these drugs.

AIM: To observe the effects of interactions between captopril and aspirin on injured myocardial cells from neonate rats and its mechanism. METHODS: The injury model of cultured neonatal rat myocardial cells was developed. The activity of lactate dehydrogenase (LDH) and the level of nitric oxide (NO) were measured by LDH kits and Griess reagent respectively, the intracellular free calcium concentrations were measured with Fura-2/AM. RESULTS: Both captopril and aspirin could reduce obviously the activity of LDH and increase the level of NO in medium, but their combination produced significant antagonistic interactions. Captopril reduced obviously the intracellular free calcium concentrations in the injury model, but aspirin alone or in combination with captopril significantly increased it. CONCLUSION: Captopril and aspirin combination produced significant antagonistic interactions, the effects may be related to its actions of reducing the production of NO and increasing the intracellular free calcium concentrations.

Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Pancreatic Neoplasms ; diagnosis ; Solitary Fibrous Tumors ; diagnosis

OBJECTIVETo investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts.

METHODSThe pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n = 20 each): normol control group, control sham group, DAC group, Los group (DAC + Los, 5 mg/kg), Sim group (DAC + Sim, 2 mg/kg), Los + Sim group (DAC + Los + Sim, Los 5 mg/kg, Sim 2 mg/kg). Water, Los or Sim drug was administrated by gavage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR.

RESULTSCollagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P < 0.01) which could be significantly reduced by Los and Sim (P < 0.05), especially in DAC + Los + Sim group (P < 0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P < 0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P < 0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P > 0.05).

CONCLUSIONUpregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sim and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.

Animals ; Gene Expression Regulation ; Heart Failure ; metabolism ; Losartan ; pharmacology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

BACKGROUNDRecent studies have suggested that p38 mitogen-activated protein kinases (MAPK) signalling pathway plays an important role in hepatic fibrosis. This study explored the antifibrotic effect of oxymatrine on tetrachloromethane induced liver fibrosis in rats and its modulation on the p38 MAPK signalling pathway.

METHODSOne hundred and twenty healthy male Sprague-Dawley rats were randomly assigned to six groups: normal (n = 20), induced fibrosis (n = 20), colchicine (n = 20) and three treatment groups of oxymatrine (n = 20 x 3). We obesrved changes in deposition of collagen, hyaluronic acid (HA), laminin (LN), collagen type IV (CIV), procollagen III (PCIII) and hydroxyproline (Hyp), a-smooth muscle actin (alpha-SMA) and phosphor-p38 (pp38).

RESULTSThe relative indicators of changes in histopathology, HA, LN, CIV, PCIII, Hyp, alpha-SMA and pp38 were raised significantly in the induced fibrosis group (P < 0.01 vs normal group). The semiquantitative hepatic fibrosis staging scores of middle dose group and high dose group were decreased (P < 0.05 and P < 0.01 respectively vs the induced fibrosis group), as was the average area of collagen in rats' liver, the concentrations of serum HA, LN, CIV, PCIII and liver tissue homogenate Hyp. The gene expression of alpha-SMA mRNA was considerably decreased in the treated animals, as was the protein espression of pp38 protein.

CONCLUSIONSOxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats in ways which relate to modulating the fibrogenic signal transduction via p38 MAPK signalling pathway.

Actins ; metabolism ; Alkaloids ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Carbon Tetrachloride ; Collagen ; metabolism ; Collagen Type IV ; metabolism ; Hyaluronic Acid ; metabolism ; Hydroxyproline ; metabolism ; Laminin ; metabolism ; Liver Cirrhosis ; chemically induced ; drug therapy ; metabolism ; Male ; Procollagen ; metabolism ; Quinolizines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo evaluate the feasibility and clinical effect of transperitoneal laparoscopic enucleation of renal angiomyolipoma (RAML) without obstruction of renal pedicle.

METHODSTen patients with renal angioleiomyoma (tumor diameter < 4 cm) were operated by transperitoneal laparoscopy without obstruction of renal pedicle. The operating time, blood loss, hospital stay after operation, intraoperative and postoperative complications and the operative effect were observed.

RESULTSAll the 10 patients underwent the operation successfully. The average operating time was 90 min, average blood loss was 80 ml, the average hospital stay after operation was 7 d. No intraoperative or postoperative complications occurred. Follow-up period was 3-19 months and no tumor metastasized or occurred again.

CONCLUSIONThis mininvasive procedure is a more precise and complete method than before, which can minimize the blood loss and make patients recover quickly, so it is well worth clinical applying.

Adult ; Angiomyolipoma ; surgery ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; surgery ; Laparoscopy ; Male ; Middle Aged ; Nephrectomy ; methods ; Treatment Outcome

OBJECTIVETo compare the effect between lumbar backwards flexion manipulation and rotating manipulation for treating lumbar intervertebral disc herniation.

METHODSTwo hundred and nine patients of lumbar intervertebral disc herniation, male 131, female 78, the age from 20 to 79 years old, 58 cases of all these patients age above 50. According to diagnosis the ladder of the 92 cases bulging type, 69 hernia type, 48 cases free type. The patients were randomly divided into treatment group (107 cases) and control group (102 cases). All the patients were treated with the three-dimensional computer-controlled traction therapeutic apparatus, with continued traction for 30 minutes. After traction, lumbar backwards flexion manipulation and rotating manipulation were respectively adopted in treatment group and control group (on alternate days one time, 3 times as a course of treatment). The symptoms and signs (including back pain and discomfort, lower limb pain and numbness, powerless urination and defecation, numbness in perineum, straight-leg raising degree, ability of lower extremity walking, work and live) of patients were observed after treatment.

RESULTSAll the patients were followed up from 1 to 6 months with an average of 3.2 months. After treatment, the symptoms and signs of patients have markedly improved (P < 0.01), but the lower back pain and discomfort, lower limb walking ability in treatment group were better than control group (P < 0.05). According therapeutic criteria, the effect of treatment group was better than of control group (P < 0.01). In cases with bulging type, 47 in treatment group and 45 in control group, the effect of treatment group was better than of control group (P < 0.05); in cases with hernia type, 35 in treatment group and 34 in control group, there was no significantly difference in effect between two groups (P > 0.05); in cases of free type, 25 in treatment group and 23 in control group, there was no significantly difference in effect between two groups (P > 0.05).

CONCLUSIONThe global effect of lumbar backwards flexion manipulation was satisfactory than rotating manipulation for treating lumbar intervertebral disc herniation. But rotating manipulation suited to free type.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Displacement ; surgery ; therapy ; Lumbar Vertebrae ; pathology ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Treatment Outcome

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.
Animals ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; HEK293 Cells ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lactates ; pharmacology ; Organic Anion Transporters ; metabolism ; Rats ; Rosuvastatin Calcium ; pharmacology ; Solute Carrier Organic Anion Transporter Family Member 1b1

BACKGROUNDYupingfeng, a traditional Chinese complex prescription, has been used efficaciously in China for the cure and prevention of inflammatory diseases related to immunodeficiency such as allergic rhinitis and chronic bronchitis. However, the active components of this prescription remain unclear. The present study focused on investigating the antiinflammatory and immunoregulatory effects of the glucosidic extract from Yupingfeng.

METHODSWe tested animal models for ear swelling induced by dimethylbenzene in mice; palm swelling induced by carregeenin and granuloma induced by cotton pellet in rats; level of haemolysin, antibody generation by the splenic cells, delayed hypersensitivity and T cell subsets in spleen of immunosuppressed mice.

RESULTSGlucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg significantly inhibited mice's ear swelling induced by dimethylbenzene. Similarly glucosidic extract of 16 mg/kg, 32 mg/kg and 64 mg/kg inhibited rats' palm swelling induced by carregeenin and granuloma induced by cotton pellet. Glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg improved the IgM level in serum and level of haemolysin in splenocytes in mice immunosuppressed by cyclophosphamide. Delayed hypersensitivity in mice suppressed by cyclophosphamide was enhanced by glucosidic extract of 24 mg/kg, 48 mg/kg and 96 mg/kg. These results suggested that Yupingfeng could recover humoral and cellular immune function in mice with immunosuppression. Glucosidic extract of 48 mg/kg and 96 mg/kg significantly resisted the immunosuppressive mice ear swelling and maintained it at nearly normal level. The enhanced, delayed hypersensitivity actions of glucosidic extract, suppressed by cyclophosphamide, might be brought about by inducing TH cell and regulating T lymphocytes subset.

CONCLUSIONSThe glucosidic extract from Yupingfeng has antiinflammatory and immunoregulation action, suggesting that these glucosides are the principal active components of the traditional Chinese prescription Yupingfeng.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Carrageenan ; toxicity ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Glucosides ; therapeutic use ; Granuloma ; chemically induced ; drug therapy ; Guinea Pigs ; Immunosuppressive Agents ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Otitis ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Xylenes ; toxicity