The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
Administration, Oral ; Adolescent ; Adult ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Antihypertensive Agents ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Cross-Over Studies ; Drug Liberation ; Humans ; Hydrochlorothiazide ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Male ; Tablets ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Valsartan ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Young Adult

Objective:To investigate the variations in ocular biometry and its influencing factors in adult Tibetans of Lhasa.Methods:A cross-sectional study was adopted.A total of 100 consecutive adult Tibetans (100 eyes) with cataract, who were treated in Tibet Autonomous Region People's Hospital from March 2017 to July 2017 were enrolled, including 51 males and 49 females, with an average age of (63.38±12.80) years.The subjects were divided into two groups, with 57 subjects (57 eyes) older than 60 years in the elder group and 43 subjects (43 eyes) younger than 60 years in the youth group.Corneal curvature, corneal astigmatism, anterior chamber depth and axial length of subjects were measured and compared with those of Beijing population which were used as standardized data of Han Chinese.The differences in ocular parameters associated with age and gender were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Tibet Autonomous Region People's Hospital (No.ME-TBHP-21-KJ-005).Written informed consent was obtained from each subject prior to any examination.Results:The mean corneal curvature, corneal astigmatism, anterior chamber depth and axial length of the 100 Tibetans were (43.68±1.62)D, 0.750 (0.375, 1.000)D, (3.05±0.41)mm, (23.07±0.86)mm, respectively.The axial length of Tibetan was shorter than that of Beijing Han people and the difference was significant ( t=2.65, P<0.01).Corneal astigmatism of the elder group was higher than that of youth group and the difference was significant ( t=2.11, P<0.05).There were no significant differences in corneal curvature, anterior chamber depth and axial length between the elder group and youth group (all at P>0.05).The anterior chamber depth and axial length of males were much longer than those of females, and the differences were significant ( t=2.71, 2.25; both at P<0.05). Conclusions:In adult Tibetan population, the axial length is short, and the anterior chamber is deep.The corneal astigmatism increases with age and there is a gender difference in axial length and anterior chamber depth.

The study is to develop a method to determine 3 batches leaves of Nauclea officinalis and stems of N. officinalis by HPLC. The differences between strictosamide contents and fingerprints was compared, then chromatographic peak of fingerprints was validated with the assistance of LC-MS. The strictosamide contents in stems of N. officinalis were higher than leaves of N. officinalis. The main chemical composition in leaves of N. officinalis and stems of N. officinalis were alkaloid which revealed by LC-MS. There are 7 chemical compositions were same between them, but the chemical composition in leaves of N. officinalis is more than stems of N. officinalis. This provides a scientific basis for the development of the potential medicinal value of leaves of N. officinalis and the sustainable utilization of N. officinalis.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Molecular Structure ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rubiaceae ; chemistry ; Spectrometry, Mass, Electrospray Ionization

ObjectiveTo observe the activity and safety of a novel combination therapy for patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL).MethodsSix consecutive patients with recurrent or refractory aggressive NHL were treated with B-VIP regimen,boanmycin (5 mg/m2 on Days 1,4,8,12 and 15),vincristine (1.4 mg/m2 on Days 1,8 and 15),ifosfamide (1.2 g/m2 on Days 1,2,3 and 15,16,17) and prednisone (50 mg on Days 1 to 10),every 21 days.All the patients had received ≥5 cycles (average 8.3 cycles) of previous chemotherapy.ResultsSix patients (100 ％) were evaluable for response.The overall objective response rate was 66.7 ％ (4 patients),including 1 case complete (CR) and 3 cases partial responses.Myelosuppression was the most frequent serious complication of this regimen.ConclusionIn the current study,B-VIP was a highly active and safe combination therapy for patients with refractory disease with a poor prognosis or for patients with multiply recurrent aggressive NHL.

AIMThe anti-gastric ulcer constituents from the roots of Crepis napifera (Franch) Babc (Compositae) were studied.

METHODSSolvent partition, Si gel and Rp-18 column chromatography, crystallization and spectral methods were used to extract, isolate and identify two compounds. The activity of compound 1 was tested on the rat stomach by determining the effect on aspirin-induced gastric lesions and on histamine-stimulated gastric acid secretion.

RESULTSTwo sesquiterpene lactone glycosides, taraxinic acid-1'-O-beta-D-glucopyranoside (1) and 11,13-dihydro-taraxinic acid-1'-O-beta-D-glucopyranoside (2) were obtained. Compound 1 at the dose of 80 mg.kg-1 p.o. inhibited significantly the development of aspirin-induced gastric lesions in the rat and at an i.v. dose of 70 mg.kg-1 did not affect histamine-stimulated gastric acid secretion in the lumen-perfused rat stomach.

CONCLUSIONCompound 1 is the active component of the plant which protects gastric mucosa and exhibits anti-gastric ulcer action.

Animals ; Anti-Ulcer Agents ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Aspirin ; Crepis ; chemistry ; Disease Models, Animal ; Female ; Gastric Acid ; secretion ; Gastric Mucosa ; secretion ; Male ; Molecular Conformation ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sesquiterpenes ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Stomach Ulcer ; chemically induced ; drug therapy

OBJECTIVETo observe effects of ginsenoside-Rb (G-Rb) on total cholesterol, lipoprotein cholesterol metabolism and anti-oxidation in experimental hyperlipidemia rats.

METHODHyperlipidemia rats were respectively given G-Rb 50, 100, 200 mg x kg(-1) x d(-1) ig for twelve days. Total cholesterol, lipoprotein cholesterol and lipid peroxidation (LPO) contents, prostacycline (PGI2), thromboxane (TXA2), superoxide dismutase (SOD) and blood viscosity were measured. Fat accumulation in liver was also observed.

RESULTTriglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) in serum, TXA2 in plasma, LPO in serum and liver, and blood viscosity were decreased significantly. High density lipoprotein cholesterol (HDLc) in serum, PGI2 in plasma and SOD in serum and liver were significantly increased by G-Rb (100, 200 mg x kg(-1)) in experimental hyperlipidemia rats. In addition, G-Rb could decrease TC/HDL-c, LDLc/HDL-c ratio, increase PGI2/TXA2 ratio and inhibit fat accumulation in liver.

CONCLUSIONG-Rb could have anti-arteriosclerosis effect by improving cholesterol and lipoprotein-cholesterol metabolism, suppressing lipid peroxidation, increasing anti-oxidase activity and PGI2/TXA2 ratio.

Animals ; Antioxidants ; pharmacology ; Female ; Ginsenosides ; pharmacology ; Hyperlipidemias ; metabolism ; Lipid Peroxides ; metabolism ; Liver ; metabolism ; Male ; Rats ; Rats, Wistar

This paper is aimed to develop rapid, sensitive and convenient HPLC-MS/MS methods for the quantification of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma. According to the different natures of the compounds, two sets of liquid chromatography and ionization modes were used for determination the concentration of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma, separately. Following protein precipitation with methanol, the levosimendan and internal standard (rosuvastatin) were separated on a Capcell MG III C18 column (35 mm x 2.0 mm ID, 3 microm) with the mobile phase consisted of methanol-15 mmol x L(-1) ammonium acetate-formic acid (55: 45: 0.02, v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in the negative ion mode. Its metabolites OR-1855, OR-1896 and internal standard doxofylline were extracted from plasma by liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Zorbax Extend C18 column (150 mm x 4.6 mm ID, 5 microm) with the mobile phase consisted of methanol-15 mmol x L(-1) ammonium acetate-formic acid (65 :35 :0.1, v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated at the positive ion mode. The linear concentration ranges of the calibration curves for levosimendan and OR-1855 and OR-1896 were 0.10-50.0 ng x mL(-1), 0.20-100 ng x mL(-1), 0.20-100 ng x mL(-1), respectively. The lower limits of quantification of levosimendan and OR-1855 and OR-1896 were 0.10 ng x mL(-1), 0.20 ng x mL(-1), 0.20 ng x mL(-1), respectively. The methods proved to be sensitive, simple and rapid, and suitable for the pharmacokinetic study of levosimendan injection.
Acetamides ; blood ; Cardiotonic Agents ; blood ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Humans ; Hydrazones ; blood ; metabolism ; Male ; Pyridazines ; blood ; metabolism ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods

OBJECTIVETo assess the bacterial profile and pattern of antibiotic resistance of urinary tract infections (UTIs) pathogens and to determine its clinical impact on management.

METHODSMidstream urine samples were submitted for culture from 1998 to 2002, and 798 isolates were obtained for antimicrobial susceptibility testing including amikacin (AMK), ampicillin (AMP), cefzolin (CFZ), cefuroxime (CXM), ceftriaxone (CRO), ceftaxime (CTX), ceftazidime (CAZ), nalidixoc acid (NAL), ciprofloxacin (CIP), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NIT) for Gram-negative bacteria and oxcillin (OXA), ampicillin (AMP), cefzolin (CFZ), ciprofloxacin (CIP), gentamicin (Gen), vancomycin (VAN), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NIT) for Gram-positive cocci. beta-lactamases and ESBLs were tested when needed.

RESULTSEnterobacteriaceae was the most frequently isolated pathogen. Among all the isolates, Escherichia coli accounted for 66.0%, followed by Enterococcus (6.5%), Klebsiella spp. (6.0%), Staphylococcus (5.4%). High resistance rates to CIP (56.0%), SXT (67.0%) and AMP (78.9%) were observed among the E. coli. CIP-resistant E. coli strains are being isolated with increasing frequency. From 1998 to 2002 the incidence of CIP-resistant increased steadily from 46.6% to 59.4%. A higher resistance rate to NAL was apparent. In contrast, NIT displayed a resistance rate of 8.9%, and AMK 4.9%. The ESBLs positive rate was 12.9% among the E. coli and 33.3% among the Klebsiella spp. respectively. A high resistance rate to CIP was also observed among the Staphylococcus (38.1%), Enterococcus (61.5%) and Streptococcus (85.0%), and the beta-lactamases positive rate was 95.2% among the Staphylococcus, but a lower resistance rate to NIT among Staphylococcus (2.4%) and Enterococcus (11.5%).

CONCLUSIONSResistance rates among common uropathogens continue to evolve and appear to be increasing to many commonly used agents especially to quinolones. Continued surveillance of resistance rates among uropathogens is needed to ensure appropriate recommendations for the treatment of the infections. Currently, the most appropriate agent for the empirical management of UTIs seems to be nitrofurantoin.

Ciprofloxacin ; therapeutic use ; Drug Resistance, Bacterial ; Humans ; Microbial Sensitivity Tests ; Nitrofurantoin ; therapeutic use ; Urinary Tract Infections ; drug therapy ; microbiology

OBJECTIVETo observe the protective effect of compound acanthopanax senticosus injection (CASI) on myocardial ischemia-reperfusion arrhythmia in rats.

METHODThe myocardial ischemia-reperfusion model was induced by 30 min coronary occulusion and 60 min reperfusion in openchest anesthetized rats. The changes of arrhythmia with electrocardiogram lead II, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the contents of malondialdehyde (MDA) and Ca2+ in myocardium were determined.

RESULTIn rats treated by CASI (in a dosage of 25, 50 and 100 mg x kg(-1) femoral vein infusion at 30 min after coronary occulusion), the incidence of myocardial ischemia-reperfusion ventricular arrhythmias, for instance the ventricular tachycardia (VT) and ventricular fibrillation (Vf), was effectively prevented, the appearing time of arrhythmia was delayed and the duration of arrhythmia was shortened, while the elevated ST segment lowered as well. At the same time, the contents of myocardial Ca2+ and MDA were decreased significantly as well as the activities of myocardial SOD and GSH-Px increased markedly.

CONCLUSIONCASI is of protective effect on myocardial ischemia-reperfusion arrhythmia, which may be related to scavenging the oxygen free radicals and Ca2+ overload formed during reperfusion.

Animals ; Anti-Arrhythmia Agents ; isolation & purification ; pharmacology ; Arrhythmias, Cardiac ; drug therapy ; etiology ; physiopathology ; Calcium ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Electrocardiography ; Eleutherococcus ; chemistry ; Female ; Ginsenosides ; isolation & purification ; pharmacology ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; complications ; Myocardium ; metabolism ; pathology ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Saponins ; isolation & purification ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the protective effect of Acanthopanax senticosus saponins (ASS) on myocardial ischemia-reperfusion injury in rats.

METHODThe myocardial ischemia-reperfusion model was induced by 30 min left anterior descending coronary occlusion and 120 min reperfusion in rats. The changes of myocardial infarct size (MIS), the serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) activity, the serum lipid peroxidation (LPO) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and plasma endothelin (ET), angiotensin II (Ang II), prostacycline (PGI2) and thromboxane A2 (TXA2) levels and myocardial free fatty acid (FFA) content of infarct and noninfarct area were determined.

RESULTIn rats treated by ASS (in a dosage of 25, 50 and 100 mg x kg(-1) i.v. at 30 min after coronary occulusion), the MIS was significantly reduced, the serum CK and LDH activity, the plasma ET, Ang II and TXA2 level and myocardial FFA content declined, while plasma PGI2 level and PGI2/TXA2 was increased signficantly. In addition, serum LPO content declined, SOD and GSH-Px activity were increased markedly.

CONCLUSIONASS has protective effect on myocardial ischemia-reperfusion injury, which may be due to its function of improving free radicals and myocardial metabolism, decreasing plasma ET, Ang II and TXA2 levels and increasing plasma PGI2 level and PGI2/TXA2 ratio etc.

Animals ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Eleutherococcus ; chemistry ; Female ; Male ; Myocardial Reperfusion Injury ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Saponins ; isolation & purification ; pharmacology