Atherosclerosis ; Humans ; Urotensins

Arrhythmias, Cardiac ; Brugada Syndrome ; Cardiac Conduction System Disease ; Coma ; etiology ; Electrocardiography ; Female ; Heart Conduction System ; abnormalities ; Humans ; Organophosphate Poisoning ; complications ; diagnosis

OBJECTIVETo investigate the efficacy and safety of bisoprolol/hydrochlorothiazide (Lodoz) in patients with mild and moderate essential hypertension.

METHODSAfter 2 weeks of placebo run-in period, 90 hypertensive patients with sitting diastolic blood pressure (DBP) between 95 and 109 mm Hg (1 mm Hg = 0.133 kPa) and systolic blood pressure (SBP) below 180 mm Hg were treated by Lodoz (2.5 mg/6.25 mg/day) for 4 weeks. If DBP > 90 mm Hg at 4 weeks, Lodoz (5 mg/6.25 mg/day) was given for another 8 weeks. Clinic systolic and diastolic blood pressure measurements and ambulatory blood pressure monitoring (ABPM) were performed at the end of placebo run-in period and at 4 and 8 weeks.

RESULTSAfter 4 or 8 weeks treatment with Lodoz, clinic systolic and diastolic blood pressure, the 24-hour mean, daytime and nocturnal blood pressures reduced significantly compared to placebo run-in period [SBP and DBP reduced (14.89 +/- 10.99)/(10.37 +/- 7.35) mm Hg (4 weeks) and (19.40 +/- 10.55)/(13.31 +/- 7.77) mm Hg (8 weeks)] respectively (P < 0.05). The total efficacy rate is 59.3% for Lodoz 2.5 mg/6.25 mg and 69.8% for Lodoz 5 mg/6.25 mg. The trough: peak ratio for SBP and DBP were 91.5% and 94.4% with Lodoz 2.5 mg/6.25 mg, and 79.9% and 80.5% with Lodoz 5 mg/6.25 mg. The smoothness index (SI) for SBP and DBP were 9.07 and 6.48 with Lodoz 2.5 mg/6.25 mg, and 4.17 and 4.47 with Lodoz 5 mg/6.25 mg, respectively. Few side effects were observed during treatment including mild headache and dizziness and slightly increased serum urea acid.

CONCLUSIONLodoz (2.5 mg/6.25 mg and 5 mg/6.25 mg) can effectively reduce the 24 hours blood pressure in patients with mild to moderate essential hypertension.

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Bisoprolol ; therapeutic use ; Drug Combinations ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; Male ; Middle Aged ; Single-Blind Method ; Treatment Outcome

OBJECTIVETo compare the safety and efficacy of midazolam and estazolam in hypertensive patients with chronic insomnia.

METHODSIn this multicentre, open labeled, randomized clinical trial, 217 adult (18 - 75 years) hypertensive patients (BP range 140 mm Hg or= 3 times/week for more than 1 month) were randomly divided into midazolam (7.5 - 15 mg before sleep, n = 113) or estazolam group (1 - 2 mg before sleep, n = 104). Patients took medication according to own need. Sleep diary should be completed within 15 minutes after getting up next morning. Follow-up analysis was performed in patients completed 8 sleep diaries or received midazolam or estazolam for 1 month. Patients' sleep diaries were evaluated, blood pressure and heart rate before and after therapy were measured and adverse events were recorded.

RESULTS(1) Blood pressure was equipotent reduced after both treatments (-11.8/7.3 mm Hg for midazolam group, and -9.1/5.6 mm Hg for estazolam group, all P < 0.05 vs. before treatment). (2) The total sleep score was also significantly decreased in both groups after medication (P < 0.01) and midazolam was significantly superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness, but there were no differences in dream frequency and total sleep time. (3) The adverse reactions such as dizziness, headache and nausea was similar in midazolam (3%) and estazolam group (7%, P > 0.05).

CONCLUSIONSIt is safe to take midazolam or estazolam for hypertensive patients with chronic insomnia and both drugs reduced blood pressure. Midazolam is superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness.

Aged ; Estazolam ; therapeutic use ; Female ; Humans ; Hypertension ; complications ; Hypnotics and Sedatives ; therapeutic use ; Male ; Midazolam ; therapeutic use ; Middle Aged ; Sleep Initiation and Maintenance Disorders ; drug therapy ; etiology

OBJECTIVETo investigate the role and significance of P38-MAPK in the pathological process of hypoxic hypercapnia pulmonary hypertension in rats, and the protection of panax notoginoside (PNS).

METHODS(1) To set up rat pathological model of hypoxic hypercapnia pulmonary hypertension: seventy two male SD rats (200 280 g) were randomly divided into six groups (n = 12), which were normal group (N group), hypoxic hypercapnia for 3-day group (H3d), hypoxic hypercapnia for 1-week group(H1w), hypoxic hypercapnia for 2-week group (H2w), hypoxic hypercapnia for 4-week group (H4w) and PNS-injected group (Hp). The rats of PNS -injected group were injected PNS before being placed in the chamber (50 mg/(kg x d), ip), and other groups were injected normal sodium (2 ml/kg, ip). (2) The shapes of pulmonary artery were detected by HE staining. (3) Western blot was used to study the protein expression of p38-MAPK. The expression of p38-MAPK in lung tissue and pulmonary blood vessel was investigated by immunohistochemistry.

RESULTS(1) The ratio of vessel wall area/total area (WA/ TA) in H1w, H2w, H4w and Hp group was higher than that of N group (P < 0.05), but that of H3d group did not change obviously (P > 0. 05 vs N group). The ratio of WA/TA in Hp group was obviously lower than that of H4w, group (P < 0.05). (2) The levels of P-p38 protein was markedly ascended in H3d group (0.225 +/- 0.071) compared with N group (0.012 +/- 0.006), and expression of P-p38 protein was significantly positive in H1w, H2w, H4w groups. (P < 0.05). (3) As P-p38 protein in pulmonary arterial tunica intima and tunica media, sterile expression in N group (0.099 +/- 0.015) and H3d group (0.107 +/- 0.013) contrasted to H4w group (0.124 +/- 0.025, P < 0.05), then tended to rise in H2w, H4w group (P < 0.05). (4) In pulmonary tissue, the levels of P-p38 protein in PNS-injected group were lower 53.02% (P < 0.05) than those in H4w group. In pulmonary arterial tunica intima and tunica media the levels of P-p38 protein in PNS-injected group were lower 87.33% (P < 0.05) than those in H4w group.

CONCLUSIONp38-MAPK as a signal transduction may play an important role in the development of hypoxia induced pulmonary hypertension. The effect of PNS on reducing pulmonary hypertension and improving pulmonary vascular wall remodeling may be related to its inhibiting expression of p38 MAPK.

Animals ; Ginsenosides ; pharmacology ; therapeutic use ; Hypertension, Pulmonary ; drug therapy ; metabolism ; physiopathology ; Hypoxia ; metabolism ; physiopathology ; MAP Kinase Signaling System ; drug effects ; Male ; Panax notoginseng ; Phytotherapy ; Pulmonary Artery ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice.

METHODSGrowth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot.

RESULTSThe inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05).

CONCLUSIONSIntraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Brucea ; Cell Line, Tumor ; Cisplatin ; Female ; Fruit ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Ovarian Neoplasms ; Plant Oils ; pharmacology

OBJECTIVETo evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).

METHODSTwenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA).

RESULTSLeft ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01).

CONCLUSIONSGarlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

Allyl Compounds ; pharmacology ; therapeutic use ; Animals ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Contrast Media ; Disease Models, Animal ; Disulfides ; pharmacology ; therapeutic use ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; complications ; diagnostic imaging ; drug therapy ; pathology ; Myocardial Reperfusion ; No-Reflow Phenomenon ; complications ; diagnostic imaging ; drug therapy ; pathology ; Swine ; Swine, Miniature ; Thiazoles ; metabolism ; Ultrasonography

Tussilago farfara contained the chemical constitutents including terpenes, flavonoids, and alkanoids. It has been used for the relief of coughs and as an expectorant, blood pressure raiser, platelet activating factor inhibitor and anti-inflammatory agents. This paper reviewed the phytochemical and pharmacological research progress in T. farfara, including the chemical ingredients, the pharmaceutical activities and the security evaluation aiming at its toxicity. The problems at present and the reseach direction for the future on T. farfara have been put forward.
Alkaloids ; chemistry ; pharmacology ; toxicity ; Animals ; Drug Evaluation, Preclinical ; methods ; trends ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; toxicity ; Flavonoids ; chemistry ; pharmacology ; toxicity ; Molecular Structure ; Plants, Medicinal ; chemistry ; Terpenes ; chemistry ; pharmacology ; toxicity ; Tussilago ; chemistry

OBJECTIVETo investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow.

METHODSHUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively.

RESULTSMMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol.

CONCLUSIONFosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.

Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; Fosinopril ; pharmacology ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Metoprolol ; pharmacology ; RNA, Messenger ; metabolism ; Stress, Mechanical ; Umbilical Veins ; cytology

OBJECTIVETo investigate the effects of ox-LDL, ACEI and ARB on expressions and activities of TF and TFPI in VSMC.

METHODS(1) Rabbit VSMC was cultured by explant-attached method in vitro. (2) The effects of ox-LDL and valsartan on TF and TFPI expressions were analyzed by immunohistochemistry and immunofluorescence. Laser scanning confocal microscopy were applied to analyze the effects of ox-LDL and valsartan on TF expression. The effects of ox-LDL, valsartan and captopril on TF and TFPI antigen expressions were analyzed by ELISA. Chromogenic substrate method was used to determine the effects of ox-LDL, valsartan and captopril on TF activity. The effects of ox-LDL and valsartan on TF mRNA expression were analyzed by RT-PCR.

RESULTS(1) ox-LDL could upregulate TF antigen, activity and TF expression at mRNA level and downregulate TFPI antigen. (2) Valsartan and captopril could reduce TF antigen and activity in VSMC treated by ox-LDL, and valsartan reduce it in a dose-dependent manner. Valsartan could also attenuate TF expression at mRNA level in VSMC treated by ox-LDL. (3) Using ELISA, valsartan and captopril could also enhance TFPI antigen in VSMC treated by ox-LDL.

CONCLUSIONOur study showed upregulated TF and downregulated TFPI expression and activity by ox-LDL and these effects could be reversed by ACEI and ARB indicating a new insight on the antiatherosclerotic effects of ACEI and ARB.

Animals ; Captopril ; pharmacology ; Cells, Cultured ; Endothelium, Vascular ; cytology ; metabolism ; Male ; Proton-Translocating ATPases ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; Rabbits ; Tetrazoles ; pharmacology ; Thromboplastin ; biosynthesis ; genetics ; Valine ; analogs & derivatives ; pharmacology ; Valsartan