INTRODUCTIONNovel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished.

MATERIALS AND METHODSA working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified.

RESULTSThe NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of <30 mLs/min. Meticulous consideration of risk versus benefits should be exercised before starting a patient on a NOAC. In patients presenting with bleeding, risk stratification of the severity of bleeding as well as identification of the source of bleeding should be performed. In life-threatening bleeds, recombinant activated factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required.

CONCLUSIONNOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

Administration, Oral ; Anticoagulants ; therapeutic use ; Benzimidazoles ; Consensus ; Dabigatran ; Hemorrhage ; prevention & control ; Humans ; Singapore ; Thiophenes

OBJECTIVETo evaluate the effects of amlodipine-based antihypertensive combination regimen on blood pressure control and impact on cardiovascular events.

METHODSFrom Oct. 2007 to Oct. 2008, a total of 13 542 hypertensive patients from 180 centers in China were included in this multi-centre randomized, controlled, blind-endpoint assessment clinical trial. Inclusion criteria were: essential hypertension, 50 - 79 years of age with at least one cardiovascular risk factor and signed consent forms. Patients were randomly assigned to receive low-dose amlodipine + diuretics (group A) or low-dose amlodipine + telmisartan (group T). The primary endpoints are composite of non-fatal stroke/myocardial infarction and cardiovascular death. All patients will be followed-up for 4 years.

RESULTSThe characteristics of patients between the two groups were similar: mean age (61.5 +/- 7.7) Yrs with 19% history of cerebrovascular diseases, 12% coronary diseases, 18% diabetes, 42% dyslipidemia, mean initial blood pressure 157/93 mm Hg. After 8-week treatment, mean blood pressure in group A and B were reduced to (133.0 +/- 11.0)/(81.0 +/- 7.6) mm Hg, (132.9 +/- 11.6)/(80.6 +/- 7.9) mm Hg respectively. Blood pressure control rates reached 72.1% and 72.6% in group A and T, respectively.

CONCLUSIONAmlodipine-based antihypertensive combination regimens achieved satisfactory blood pressure control rate in patients with essential hypertension in this patient cohort.

Aged ; Amlodipine ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Benzimidazoles ; administration & dosage ; Benzoates ; administration & dosage ; Blood Pressure ; Drug Therapy, Combination ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Middle Aged

A case of Fasciola gigantica-induced biliary obstruction and cholestasis is reported in Turkey. The patient was a 37- year-old woman, and suffered from icterus, ascites, and pain in her right upper abdominal region. A total of 7 living adult flukes were recovered during endoscopic retrograde cholangiopancreatography (ERCP). A single dose of triclabendazole was administered to treat possible remaining worms. She was living in a village of southeast of Anatolia region and had sheeps and cows. She had the history of eating lettuce, mallow, dill, and parsley without washing. This is the first case of fascioliasis which was treated via endoscopic biliary extraction during ERCP in Turkey.
Adult ; Animals ; Anthelmintics/administration & dosage ; Benzimidazoles/administration & dosage ; Cholangiopancreatography, Endoscopic Retrograde ; Fasciola/isolation & purification/*physiology ; Fascioliasis/drug therapy/*parasitology/radiography ; Female ; Humans ; Turkey

OBJECTIVETo observe the blood lowering effect of telmisartan and amlodipine taking on the morning or at bedtime in hypertensive patients.

METHODSA total of 108 individuals with hypertension (grade 2 or above) were randomized to receive telmisartan and amlodipine in one of the following four therapeutic schemes: Group A (26 cases): both medications taken on the morning; Group B (28 cases): both medication taken at bedtime; Group C (27 cases): telmisartan on the morning and amlodipine at bedtime; or Group D (27 cases): amlodipine on the morning and telmisartan at bedtime. ABPM was performed before and after 8 weeks treatment.

RESULTSBP was significantly reduced in 4 groups and the value of 24 hours SBP/DBP decline for each group after treatment was 29.94/16.32, 31.37/18.35, 29.49/17.30 and 25.80/15.51 mm Hg (1 mm Hg = 0.133 kPa) respectively (P < 0.05 vs. baseline). SI (smooth index) of 24 hours SBP/DBP was 1.79/1.34, 2.07/1.54, 1.70/1.43 and 1.55/1.32 respectively (P > 0.05). The night-time BP decline and the distributive difference of dipper, non-dipper, extreme dipper and reverse dipper pattern were similar among groups at both baseline and after various treatment regimens (all P > 0.05) . Morning blood pressure surge (MBPS) after treatment in group B declined more significantly than other groups (P < 0.05).

CONCLUSIONTelmisartan/amlodipine administered either on the morning or at bedtime can effectively reduce blood pressure. The efficacy of BP lowering is independent of the drug taking time. There is a trend both in better BP lowering and less BP variability when two medications are administered at bedtime.

Adult ; Aged ; Amlodipine ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Benzimidazoles ; administration & dosage ; Benzoates ; administration & dosage ; Blood Pressure Monitoring, Ambulatory ; Drug Administration Schedule ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged

Studies were conducted under pot conditions to determine the comparative efficacy of carbofuran at 1 mg a.i./kg soil, bavistin at 1 mg a.i./kg soil, neem (Azadirachta indica) seed powder at 50 mg/kg soil, green mould (Trichoderma harzianum) at 50.0 ml/kg soil, rhizobacteria (Pseudomonas fluorescens) at 50.0 ml/kg soil against root-knot nematode, Meloidogyne incognita-wilt fungus, Fusarium oxysporum disease complex on green gram, Vigna radiata cv ML-1108. All the treatments significantly improved the growth of the plants as compared to untreated inoculated plants. Analysis of data showed that carbofuran and A. indica seed powder increased plant growth and yield significantly more in comparison to bavistin and P. fluorescens. Carbofuran was highly effective against nematode, bavistin against fungus, A. indica seed powder against both the pathogens and both the bioagents were moderately effective against both the pathogens.
Animals ; Benzimidazoles ; administration & dosage ; Carbamates ; administration & dosage ; Carbofuran ; administration & dosage ; Fusarium ; drug effects ; pathogenicity ; Glycerides ; administration & dosage ; Pest Control ; methods ; Phaseolus ; drug effects ; microbiology ; parasitology ; Plant Diseases ; microbiology ; parasitology ; Terpenes ; administration & dosage ; Tylenchoidea ; drug effects ; microbiology ; pathogenicity

Adult ; Animals ; Anthelmintics ; administration & dosage ; Antibodies, Helminth ; blood ; Benzimidazoles ; administration & dosage ; Fasciola hepatica ; drug effects ; immunology ; Fascioliasis ; blood ; diagnosis ; drug therapy ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Tomography, X-Ray Computed ; methods ; Treatment Outcome

BACKGROUNDCongestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin converting-enzyme inhibitor (ACEI) is the cornerstone in its treatment. However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin II (Ang II) by alternative pathways. The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang II type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI).

METHODSCongestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery. The experiment protocol included sham-operated rats (Sham), MI-control rats (MI-control), MI rats treated with ramipril 3 mg/kg (MI-ramipril) or TCV116 2 mg/kg (MI-TCV116) per day, half dosage (MI-1/2R&T) or full dosage (MI-R&T) combination of the two. At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as beta myosin heavy chain (betaMHC), B-type natriuretic peptide (BNP), transforming growth factor-beta1 (TGF-beta1), collagen I and III were quantified with reverse transcription polymerase chain reaction (RT-PCR) in the surviving septum myocardium, and survival rates were calculated.

RESULTSThere were no significant differences in MI sizes (%) among each MI related experimental groups (33 +/- 13, 34 +/- 14, 33 +/- 13, 35 +/- 13 and 33 +/- 14 for MI-control, MI-ramipril, MI-TCV116, MI-1/2R&T and MI-R&T, respectively, no statistical significance for all). Compared with sham-operated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly impaired (P < 0.01), and in terms of spontaneous deaths survival rate shortened (P < 0.05). Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P < 0.01); while their hemodynamic parameters were significantly improved (P < 0.05 or P < 0.01), and in terms of spontaneous deaths survival rate prolonged (P < 0.05). Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of betaMHC, BNP mRNA expressions (P < 0.05 vs monotherapy); while LVEDP was further lowered (P < 0.05 vs monotherapy). However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatments.

CONCLUSIONSThe results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI.

Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Animals ; Benzimidazoles ; administration & dosage ; Biphenyl Compounds ; administration & dosage ; Blood Pressure ; drug effects ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; pathology ; physiopathology ; Male ; Myocardial Infarction ; complications ; Myocardium ; pathology ; Ramipril ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; drug effects ; Tetrazoles ; administration & dosage ; Ventricular Function, Left ; drug effects

AIMTo study the chiral inversion of dextropantoprazole in human.

METHODSThree healthy Chinese male volunteers after an oral dose of 40 mg dextropantoprazole. An HPLC method was developed and used to determine the total plasma concentrations of each enantiomer. The ratios of the enantiomers in plasma samples were measured on a Chiral-AGP column. The plasma concentration of each enantiomer was then calculated using the ratios of enantiomers and total concentrations of the two enantiomers previously measured.

RESULTSThe AUC0-t of levopantoprazole was only 1.5% of the total AUC0-t of enantiomers.

CONCLUSIONThe chiral inversion from dextropantoprazole to levopantoprazole does not occur in the three healthy Chinese male volunteers after an oral dose of 40 mg dextropantoprazol.

2-Pyridinylmethylsulfinylbenzimidazoles ; Administration, Oral ; Adult ; Anti-Ulcer Agents ; blood ; chemistry ; pharmacokinetics ; Area Under Curve ; Benzimidazoles ; blood ; chemistry ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Humans ; Male ; Omeprazole ; analogs & derivatives ; blood ; chemistry ; pharmacokinetics ; Stereoisomerism ; Sulfoxides ; blood ; chemistry ; pharmacokinetics

OBJECTIVETo observe the effect of Shenshuaining Granule (SG) combined telmisartan on serum creatinine (SCr) levels and urinary albumin contents in diabetic nephropathy (DN) patients, and to explore its efficacy.

METHODSTotally 204 DN patients were recruited, and further assigned to 3 groups, i.e., the early DN group, the clinical stage of DN with normal renal function group, the clinical stage of DN with insufficient renal function group. Patients in the same group were randomly allocated to the telmisartan treatment group, the SG treatment group, and the combination of SG and telmisartan treatment group, 68 in each group. Patients in the telmisartan treatment group took telmisartan tablet, 80 mg per day, once daily. Those in the SG treatment group took SG, 5 g each time, 3 times per day. Those in the combination of SG and telmisartan treatment group took telmisartan tablet (80 mg per day, once daily) and SG (5 g each time, 3 times per day). The therapeutic course for all was 3 successive months. SCr levels, serum urea nitrogen (BUN),24 h urine microalbumin (24 h U-MA) were detected before and after treatment. Results In three different treatment groups, 24 h U-MA decreased after treatment in the telmisartan treatment group; SCr and BUN decreased after treatment in the SG treatment group; and 24 h U-MA, SCr and BUN decreased after treatment in the combination of SG and telmisartan treatment group (P<0.05). In the clinical stage of DN with insufficient renal function group, SCr obviously increased after treatment in the telmisartan treatment group (P <0. 05). In the 3 DN stages, SCr and 24 h U-MA obviously decreased in the combination of SG and telmisartan treatment group, when compared with the telmisartan treatment group and the SG treatment group (P<0.05). Compared with the telmisartan treatment group, SCr and BUN obviously decreased in the SG treatment group, but 24 h U-MA quantitation obviously increased (P<0.05). BUN obviously decreased in the combination of SG and telmisartan treatment group (P<0. 05).

CONCLUSIONThe combination of SG and telmisartan could decrease urinary albumin, and stabilize SCr levels.

Adult ; Albumins ; metabolism ; Antihypertensive Agents ; therapeutic use ; Benzimidazoles ; therapeutic use ; Benzoates ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Tablets

OBJECTIVETo investigate the long-term effects of TCV116 (candesartan cilexetil) on cardiac function changes after myocardial infarction.

METHODSMyocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in rats. One week after the surgical performance,the surviving rats were randomly assigned to the following treatment groups: (1) MI rats with no therapy; (2) MI rats treated with TCV116 2 mg/kg per day; (3) Sham-operated control and (4) Sham-operated rats treated with TCV116 2 mg/kg per day. At 22 weeks, left ventricular function and cardiac histomorphometric parameters were measured, mRNA expression of cardiac genes such as beta myosin heavy chain, B-type natriuretic peptide, transforming growth factor beta1, collagen I and III quantified, and survival rates calculated.

RESULTSTreatment with TCV116 significantly improved LV function, suppressed mRNA expression of cardiac genes,and extended the survival period compared with MI rats with no therapy (P<0.05).

CONCLUSIONTreatment with long-term angiotensin II type 1 receptor blocker may improve LV function and prolong the survival of rats after MI.

Angiotensin II Type 2 Receptor Blockers ; Animals ; Benzimidazoles ; administration & dosage ; pharmacology ; Biphenyl Compounds ; administration & dosage ; pharmacology ; Heart Failure ; drug therapy ; etiology ; physiopathology ; Male ; Myocardial Infarction ; complications ; Myocardium ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 2 ; administration & dosage ; Tetrazoles ; administration & dosage ; pharmacology ; Ventricular Function, Left ; drug effects ; Ventricular Myosins ; metabolism ; Ventricular Remodeling ; drug effects