[The in vitro transport mechanism of bentysrepinine: a novel anti-hepatitis B virus drug candidate].

Bentysrepinine (Y101), a derivative of phenylalanine dipeptide, is a novel drug candidate for the treatment of hepatitis B virus (HBV) infection. Our previous preclinical pharmacokinetic study showed that its in vivo absorption and distribution characteristics were probably related to transmembrane transport after Y101 was administered intragastically in rats. In this study, Caco-2 and MDCK-MDR1 cell models were used to investigate interactions between Y101 and P-gp through the apparent permeation coefficient (P(app)) and efflux ratio (RE); the results showed that Y101 was a substrate of P-gp. In addition, gene-transfected cell models, HEK293-h OATP1B1, HEK293-h OATP2B1 and CHO-PEPT1 were used to evaluate the affinity to OATP1B1, OATP2B1 and PEPT1. The results suggest that Y101 has a weak inhibitory effect on OATP1B1 and OATP2B1, and Y101 may not be substrates of OATP1B1, OATP2B1 or PEPT1. The above results can be used to explain the in vivo absorption and distribution characteristics, and to provide a scientific basis for the further development of Y101.

[The in vitro inhibition and induction of cytochrome P450 activities by bentysrepinine: a novel candidate of anti-hepatitis B virus drug].

Bentysrepinine (Y101), a derivative of phenyalanine dipeptide, has a novel mechanism in the treatment of hepatitis B virus (HBV) infection with a good anti-HBV effect. In the present study, a fluorometric-based high throughput method using cytochrome P450 (CYP) screening kit was adopted to evaluate in vitro inhibition potential of Y101 on CYP isoenzymes by calculating remaining enzyme activities and inhibitory potential (IC(50) values) using the determined values of fluorescence intensity. The result showed that Y101 exhibited little activity in the inhibition of CYP1A2, CYP3A4, CYP2C9, CYP2C19 and CYP2D6 (IC(50) > 100 µmol·L(-1)). Y101 was used to treat human primary hepotocytes for 72 h, and the enzyme activities of CYP1A2, CYP2B6 and CYP3A4 were determined with a cocktail of probe substrates for the three CYP isoforms. The metabolites were simultaneously determined using a LC-MS/MS method. Y101 had no activity in the induction of CYP1A2, CYP2B6 and CYP3A4 on the basis of the following results: 1 The ratio of enzyme activities between test and control groups were all below than 1 (varied from 0.662 to 0.928); 2 The induction potential of Y101 were lower than forty percent compared with that of positive groups. The above results suggest that Y101 has little activity in the regulation of metabolic drug-drug interactions based on the CYP isoform changes following co-administration of drugs.

The Targeted-liposome Delivery System of Antitumor Drugs.

The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy. Considering further application for clinical use, the great challenges of the liposome-based delivery system were also proposed as follows: 1) prepare stealth liposome with steric stabilization and further enhance the therapeutic effects and safety; 2) explore more safe clinical targets and complementary or different types of targeting liposome; 3) thirdly, more investment is needed on the research of pharmacokinetics of the elements such as the ligands (antibody), PEG and lipids of liposome delivery system as well as safety evaluation. Considering the complex process of the liposomal encapsulation drugs in vivo, the author inferred that there are maybe different forms of the encapsulation drug to be internalized by the tumor tissues at the same time and space, although there are little reports on it.

Mycoplasma pneumoniae infection in hospitalized adult patients with community-acquired pneumonia in China.

INTRODUCTION: This study aimed to investigate the prevalence, clinical and radiographic features, and antibiotic responses of Mycoplasma pneumoniae (M. pneumoniae) infections in hospitalized adults with community-acquired pneumonia (CAP) in China. METHODOLOGY: Serum specimens collected from 189 CAP patients in both acute phase and convalescence were tested for IgG, IgA, and IgM mixed antibodies specific to M. pneumoniae. The clinical and radiographic characteristics and efficacy of three antibiotic regimens were compared between patients with M. pneumoniae infection and those without. RESULTS: Among 189 CAP patients, 88 (46.6%) were positive for M. pneumoniae infection. Compared to the negative patients, patients with M. pneumoniae infection were significantly younger, had higher rates of dry cough, and had white blood cell counts of <1010/L, but had less purulent sputum. Radiography further showed more centrilobular nodules, ground-glass opacities, tree-in-bud patterns and thickened bronchovascular bundles, but less pleural effusion and larger tracts of real opacities in patients with M. pneumoniae infections. Among the three regimens used, patients with moxifloxacin required significantly shorter fever abatement, treatment, and hospitalization times than those with azithromycin plus ceftriaxone and ceftriaxone only. CONCLUSIONS: M. pneumoniae infection was present in almost half of the CAP population in east China, with some distinct clinical and radiographic features. Moxifloxacin was an effective antibiotic for this infection.

[Effects of applying selenium on selenium allocation, grain yield, and grain quality of two maize cultivars].

A pot experiment with conventional maize cultivar ZD958 and glutinous maize cultivar JN218 was conducted to study the effects of applying different concentrations (0, 10, 25 and 50 mg x kg(-1)) of selenium (Se) on the Se allocation in plant organs, grain yield, and its quality. At low concentrations (< or = 10 mg x kg(-1)), Se stimulated maize growth, and increased biomass accumulation and grain yield significantly. At high concentrations (> 25 mg x kg(-1)), Se inhibited maize growth, and decreased dry mass accumulation, grain yield, and its quality. The Se concentration in plant organs was in the order of root > leaf > stalk > sheath. The Se concentrations in plant organs had a positive correlation with the Se concentration in soil. Comparing with ZD958, JN218 could accumulate more Se in natural low-Se environment, but enrich lesser Se in the environment with 10 mg x kg(-1) of Se. Taking the Se accumulation amount in grain and aboveground vegetative organs as the standard for evaluation, JN218 was more available planted on natural low-Se (0.25 mg x kg(-1)) soil or high-Se (25 mg x kg(-1)) soil, while ZD958 was appropriate planted on Se-rich (10 mg x kg(-1)) soil or Se-polluted (50 mg x kg(-1)) soil.

[Effects of arsenic on maize growth, antioxidant system, and ion distribution].

A greenhouse sand culture experiment was conducted to study the effects of arsenic (As) on the biomass accumulation, photosynthetic pigments, antioxidant system, and the absorption and distribution of As and mineral ions in maize Zhengdan 958. At lower concentrations (<2 mg As x L(-1)), As stimulated the growth of maize seedlings, and increased the plant height, taproot length, and biomass accumulation significantly; at higher concentrations (>4 mg As x L(-1)), As inhibited the seedlings growth severely. At 2 mg As x L(-1), the chlorophyll a, b, and a+b contents reached their peaks; but with increasing As concentration, the chlorophyll contents decreased gradually. At 10 mg As x L(-1), the destruction of chloroplast structure and the dissolution of thylakoid membrane were observed by electron microscopy. With increasing As concentration, the activities of antioxidant enzymes SOD, POD, and CAT in root increased, and those in leaf reached the maximum at 8 mg As x L(-1). The sensibility of the enzymes in leaf to As stress was in the order of POD >CAT>SOD. Correlation analysis showed that the contents of MDA, soluble sugar, and soluble protein were positively correlated with As concentration. High concentration As inhibited the absorption of P, K, Ca, Fe and other elements obviously. And comparing with shoot, root was more sensitive to As stress. The growth indices of root could be more available to be used as the indicators of plant arsenic toxicity.

[The expression of the early growth responsive gene-1 in acute pulmonary embolism of rats].

AIM: To investigate the dynamic changes of Egr-1 expression in the lungs of acute pulmonary embolism of rats by infusion of autoblood thrombs. METHODS: The model of pulmonary embolism by infusion of autoblood thrombs in the pulmonary artery of rats was established and the mean pulmonary arterial pressure was continuously monitored by computer, and the results were evaluated by lung perfusion scan and pathological changes. Expression of Egr-1 proteinum and mRNA were measured by immunohistochemistry and reverse transcription polymerase chain reaction. RESULTS: The mPAP of rats was increased significantly after infusion of autoblood thrombs at the half hour, and reached high level at the second hour, then remained the high level to four hours compared with group control at the same time point (P < 0.01). ECT image was showed significantly filling defect after infusion of autoblood thrombs at the first hour. The infused thromb was witnessed by hematoxylin and eosin stain. In the tracheal epithelium cells, alveolar epithelium cells and vascular smooth muscle cells of embolism rats, Egr-1 protein expression was increased significantly after embolization at the second hour compared with group control at the same time point (P<0.01), and was decreased slowly at the fourth hour. Egr-1 mRNA expression was showed the similar changes. CONCLUSION: Expression of Egr-1 was low level in group control, but increased significantly after infusion of autoblood thromb at the second hour in the specificity of cells, suggesting that Egr-1 expression might be an important link of pathological changes in the acute pulmonary embolism.

[Induction, purification and antifungal activity of beta-1, 3-glucanase from wheat leaves].

Treatment with mercuric chloride (0.01%), salicylic acid (10.0 mg/mL) or riboflavin (1 mmol/L) induced the beta-1, 3-glucanase activity in all the three wheat varieties i.e. 331, Kangdao 680 and Lumai 23 tested, with the strongest inductive effect on variety 331 by treatment with mercuric chloride (0.01%) for 24 h. From leaves of variety 331 treated with mercuric chloride (0.01%) for 24 h, a kind of beta-1, 3-glucanase was purified by fractional precipitation with ammonium sulphate, Phenyl-Sepharose chromatography (Phenyl-Sepharose Fast Flow), ion-exchange chromatography (DEAE-Sepharose Fast Flow) and gel-filtration chromatography (Sephacryl S-100). Through SDS-PAGE and gel filtration, the molecular weight of the purified beta-1, 3-glucanase was determined to be about 52.0-53.6 kD. The purified beta-1, 3-glucanase showed antifungal activity against both Alternaria longipes and Rhizoctonia cerealis on tested plates, and inhibited the germ tube elongation and spore germination of Verticillium dahliae and Fusarium omysporum f.sp cucumerinum.

catena-Poly[[di-mu-chloro-bis[(triphenylphosphine)silver(I)]]-mu-2-aminopyrimidine-kappa 2N1:N3].

In the title supramolecular complex, [Ag(2)Cl(2)(C(4)H(5)N(3))(C(18)H(15)P)(2)](n), a one-dimensional chain is formed by dimeric [Ag(2)Cl(2)(PPh(3))(2)] units bridged by 2-aminopyrimidine moieties. The Ag atoms are four-coordinate, with an AgCl(2)NP core. A crystallographic inversion centre is located in the centre of the Ag(2)Cl(2) chelate ring, while the crystallographic twofold axis bisects the 2-aminopyrimidine ligand.