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Biomedical subjects

J B Zhu

Publications and source records attributed to J B Zhu.

At least 19 recordsLinked to original sources

Development of a sensitive and rapid liquid chromatography/tandem mass spectrometry method for the determination of apomorphine in canine plasma.

A sensitive, rapid and specific quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of apomorphine (APO) in canine plasma. The analytes were prepared using one-step liquid-liquid extraction, and analyzed on a Waters Symmetry C(18) column interfaced with triple quadrupole tandem mass spectrometer. A mixture of methanol/0.1% formic acid in water (70: 30, v/v) was employed as the isocratic mobile phase. Positive electrospray ionization was utilized as the ionization source. The analyte and clenbuterol (internal standard) were both detected using multiple reaction monitoring (MRM) mode. The limit of detection (LOD) obtained was 0.03 ng/mL. The assay was linear over the concentration range of 0.1-100 ng/mL, and provided good precision (RSD) and good accuracy (RE). The analyte was stable by using antioxidants throughout the whole study. The experimental results show that LC/MS/MS is a rapid and sensitive method to analyze APO in plasma. Finally, the proposed method was successfully applied to a pharmacokinetic study of APO after intranasal administration of 0.5 mg apomorphine to 10 healthy beagle dogs.

Administration, Intranasal↗

Phylogenetic analysis of the S7 gene does not segregate Chinese strains of bluetongue virus into a single topotype.

Bluetongue virus (BTV) infection of ruminants is endemic throughout tropical and subtropical regions of the world. The S7 gene segments of prototype Chinese strains of BTV serotypes 1, 2, 3, 4, 12, 15, and 16 were sequenced and compared to the same genes of prototype strains of BTV from the US, Australia, and South Africa. The S7 genes and predicted VP7 proteins of the Chinese viruses were relatively conserved, with the notable exception of serotype 15. Furthermore, phylogenetic analysis of the S7 genes did not predict geographic origin of the various strains of BTV.

Animals↗

[Preparation of sterically stabilized liposomes containing all-trans retinoic acid].

AIM: To prepare sterically stabilized liposomes containing all-trans retinoic acid, and to study its physicochemical properties. METHODS: The microstructure, the particle size and its distribution was determined by DSC, 1HNMR and 90 Plus Particle Size Analyzer and a TEM photo was taken. RESULTS: The size of conventional liposomes and sterically stabilized liposomes were about 0.35 and 0.42 micron. The sterically stabilized structure can be confirmed by TEM photo. CONCLUSION: The stericallly stabilized liposomes containing all-trans retinoic acid can be prepared by combination of film-casting and freeze-drying.

Drug Carriers↗

Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.

The objective of the present study was to investigate the specific drug targeting of anticarcinogenic drugs, such as camptothecin (CA), after intravenous (i.v.) injection by incorporation into solid lipid nanoparticles (SLN). A CA loaded SLN suspension consisted of 0.1% (w/w) camptothecin, 2.0% (w/w) stearic acid, 1.5% (w/w) soybean lecithin and 0.5% (w/w) polyoxyethylene-polyoxypropylene copolymer (Poloxamer 188) was prepared by high pressure homogenization. In vitro drug release was investigated in pH 7.4 phosphate-buffered saline at 37 degrees C. The concentrations of camptothecin in various organs were determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after i.v. administration of CA-SLN and a camptothecin control solution (CA-Sol). The results showed that the CA-SLN had an average diameter 196.8 nm with a Zeta potential of -69.3 mV and in vitro drug release was achieved for up to a week. In tested organs, the AUC/dose and the mean residence times (MRT) of CA-SLN were much higher than those of CA-Sol, especially in brain, heart and reticuloendothelial cells containing organs. The brain AUC ratio of CA-SLN to CA-Sol was the highest among the tested organs. These results indicate that SLN are a promising sustained release and drug targeting system for lipophilic antitumour drugs, and may also allow a reduction in dosage and a decrease in systemic toxicity.

Animals↗

Studies on drug release kinetics from ibuprofen-carbomer hydrophilic matrix tablets: influence of co-excipients on release rate of the drug.

Controlled-release (CR) matrix tablets of ibuprofen (IBF) and Carbopol(R) 934P, and blended mixture of Carbopol(R) 934P and 971P resins, at different drug to polymers ratios, were prepared by the direct compression method. The investigation focuses on the influence of the proportion of the matrix material, and several co-excipients (lactose, microcrystalline cellulose (MCC), and starch) on the mechanism and release rate of the drug from the tablets. In vitro drug release in pH 7.2 phosphate buffer solution appears to occur both by diffusion and a swelling-controlled mechanism, exhibiting either anomalous or Case II type transport. The release process could be described by plotting the fraction released versus time and fitting data to the simple exponential model: Mt/Minfinity=ktn. The release kinetics were modified when the blended mixtures of Carbopol(R) 934P and 971P resins were used as the matrix materials. In general, all of the co-excipients, used in this study, enhanced the release rate of IBF. However, lactose demonstrated slower and more linear release behavior as compared to microcrystalline cellulose or starch. The dissolution T50 and T90 values for the three co-excipients were in the order of lactose>microcrystalline cellulose>starch.

Acrylic Resins↗

Ibuprofen release kinetics from controlled-release tablets granulated with aqueous polymeric dispersion of ethylcellulose II: influence of several parameters and coexcipients.

The objective of this study was to investigate the mechanism of ibuprofen (IBF) release from tablets prepared by wet granulation method, using Surelease as a granulating agent. The influence of certain parameters such as the levels of Surelease solids content (SSC), pH of dissolution media, selected dissolution method, and agitation speed on the release profiles of IBF was investigated. The effect of partial replacement of lactose (primary excipient) by various coexcipients such as microcrystalline cellulose, starch, polyvinylpyrrolidone (PVP), sodium alginate, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethyl cellulose (CMC-Na) was also studied. Tablets prepared with surelease as a granulating agent were non-disintegrating and exhibited prolonged release rates as compared to control tablets. The release of IBF from the tablets appears to occur either via water-filled pores or by diffusion through membrane, depending on the levels of SSC. At higher SSC levels pH independent release profiles for IBF were achieved. Dissolution method and agitation speed exhibited no significant effect on the release profiles. All the coexcipients studied enhanced the release rates, irrespective of whether the coexcipients were water-soluble or water-insoluble.

Anti-Inflammatory Agents, Non-Steroidal↗

Progesterone receptor immunoreactivity at the maternofetal interface of first trimester pregnancy: a study of the trophoblast population.

The aim of our study was to localize oestrogen receptor (ER) and progesterone receptor (PR) in the trophoblast population at the maternofetal interface in early pregnancy. Rat monoclonal antibodies to human ER and PR were used to study 44 cases of chorionic villi and 82 cases of decidua using an immunocytochemical method. The PR-immunoreactive products were localized in the nuclei of syncytiotrophoblast and cytotrophoblast cells of the villi. Specific staining was also present in the cytoplasm. Villous stroma and vessels were stained occasionally. Using cytokeratin staining in an adjacent section or double staining with PR and cytokeratin, the distribution of invading trophoblast cells and their PR expression were examined. In decidual stroma, a type of interstitial cell was identified which simultaneously expressed cytokeratin and PR in the cytoplasm, indicating that the invading trophoblast cells may express PR. All extravillous populations at the interface were positive for PR, including the syncytial lining of the decidual surface, the cytotrophoblast column, the cytotrophoblast shell and the interstitial trophoblast. The immunoreactivity of PR was also localized in the nuclei of vascular endothelial cells, whereas Factor VIII was localized in the cytoplasm of the same cells, thus confirming their endothelial nature. In contrast to PR, little ER could be detected in the trophoblast cell population using anti-ER antibody D75 in our study.

Adult↗

Immunocytochemical colocalization of progesterone receptor and prolactin in individual stromal cells of human decidua.

Progesterone stimulates decidual PRL production. However, decidualized tissue, in which a high level of PRL is present, features a relatively low level of progesterone receptor (PR) expression. The discrepancy has to be explored at the individual cell level. The present study employed a double labeling method to colocalize PR and PRL in human decidua to examine the correlation between these two proteins. In frozen sections, decidual stroma presented two kinds of cell, which differed in PRL staining. Decidualized cells were positively stained with PRL in cytoplasm and displayed a large cell size and a clear cell outline. Nondecidualized cells showed no specific PRL staining and no clear cell boundary. In decidual stroma, PR staining was exclusively localized in the nuclei, with variations in intensity. When double staining with PR and PRL was performed, these two types of cells demonstrated diverse staining patterns. The PRL-producing cells exhibited weak PR staining, whereas PRL-negative cells evidenced stronger PR staining. In RU 486-treated samples, decidual stroma became less stained with PRL, compared with the control, and fewer cells displayed typical morphology of decidualization, whereas PR staining in the tissue became more extensive and intensive. Double labeling disclosed that the cells with enhanced PR staining were coupled to weaker PRL immunoreaction. Our data suggested an inverse relationship between PRL and PR in individual stromal cells in vivo, which could be reversed by antiprogestin treatment. A possible autocrine mechanism controlling this phenomenon was proposed and deserves further study.

Cell Nucleus↗

Evidence that the nodulation regulatory gene nodD3 of Rhizobium meliloti is transcribed from two separate promoters.

The Bgl II fragment carried in plasmid pMH903, which covers the nodD3 region of Rhizobium meliloti, has been sequenced. By using both S1 nuclease mapping and primer extension, two transcription start sites were demonstrated in the sequence. After the first transcription start site, there were two open reading frames (ORF) followed by the nodD3 coding sequence which was also preceded by the second promoter. The nodD3 gene under the first promoter mediated high, constitutive expression of nodC-lacZ fusion, and the gene under the second promoter required the product of nodD1 and alfalfa (Medicago sativa) seed exudate for the activation of fusion. Nodulation experiments showed that the nodD3 gene under either promoter was functional in eliciting nodules on alfalfa. The deletion of part of the two ORFs after the first promoter or deletion of the second promoter did not block the constitutive expression of nodC-lacZ fusion, whereas the deletion of the first promoter region or a polar insertion mutation between the two promoters did cause nodD3 to activate nodC only in the presence of the inducer. It indicates that nodD3 can be transcribed from the first promoter as well as from a separate second promoter.

Amino Acid Sequence↗

[Pharmacokinetics and pharmacodynamics of diltiazem floating tablets].

Floating tablet is a new type of delayed-action preparations. The present study was aimed at pharmacokinetic and hemodynamic effects of diltiazem floating tablet in 8 healthy volunteers. Each subject received po 90 mg diltiazem floating and normal tablets in a crossover design. For floating tablets the T1/2 (6.4 +/- 4.4 h) and Cmax (56 +/- 23 ng.ml-1) were longer and lower than those of normal tablets (2.3 +/- 1.1 h and 96 +/- 30 ng.ml-1, P < 0.01), respectively. AUC of the 2 forms were similar, suggesting that they had same bioavailability. Diltiazem lowered the blood pressure of the subjects. Although there was no significant difference between the 2 formulations in maximal decreases of systolic and diastolic blood pressures, the duration of hypotension was longer with floating tablets than that with normal ones. There was a positive correlation between diltiazem concentration and its hypotensive action. Thus, administration of floating tablets twice a day may be effective in controlling the blood pressure of hypertensive patients.

Adult↗

[Development of rapid-dissolution armillarisin-A tablet and study on its choleretic action in rats].

For increasing the choleretic action of armillarision-A, a new formulation of rapid-dissolution tablet (A) was developed. The effect of A, a marketed amillarisin-A tablet (B) and a armillarisin-A Na sterile power (C) on rats biliation in vivo were investigated. The dissolution rates of A and B were also determined. The results demonstrate that the choleretic action of A is equal to C but superior to B, and the dissolution rate of A is higher than B. Moreover, the armillarisin-A dissolved percentage of A in vitro at time t was well correlated with the biliation net accumulative amount in vivo at time 3t.

Animals↗

Studies on heterologous expression of Rhizobium meliloti nifA gene and oxygen sensitivity of its product.

When the R. meliloti (Rm) nifA'-lacZ fusion-carrying plasmids were introduced into the strains of Agrobacterium tumefaciens, R. trifolii and R. astragalus, beta-galactosidase activity was demonstrated. However, activity was not induced by microaerobiosis. Furthermore, R. meliloti nifA'-lacZ fusion was also not expressed in the nodule bacteroids of R. trifolii and R. astragalus. We speculate that some factor(s) important for the induction of Rm nifA presumed to be the fixLJ regulatory system would not be operative in these bacteria. Experiments using R. meliloti nifH'-lacZ/K. Pneumoniae nifH'-lacZ fusion and the constitutive Rm nifA system to test the nifA-dependent expression of nifH'-lacZ under aerobic and microaerobic conditions in E. coli were performed. The inhibition of the Rm nifA activation of nifH'-lacZ expression in the bacteria grown in the aerobic condition was shown. Assays on the Rm nifA-m RNA produced by the constitutive Rm nifA in E. coli under aerobic and microaerobic conditions with the cloned nifA as a probe for dot blot hybridization showed a marked decrease of Rm nifA mRNA when the bacteria were grown under aeration.

Aerobiosis↗

[Studies on the bioavailability of nitrendipine tablet].

The problem of nitrendipine tablets manufactured in China is its low bioavailability. To solve this, a new tablet formulation was developed by using milling method to increase its relative bioavailability. The commercially available conventional tablet A (Nanjing factory) and C (a Hebei factory) and the new tablet formulation D were compared with the reference tablet B (Bayer Company, West Germany) in vitro and in vivo. The determination of nitrendipine in vivo was carried out by GC-MS. The pharmacokinetic parameters of nitrendipine in vivo were estimated by using the nonlinear least square computer program on the basis of the compartment model (zero order dissolution, first order absorption). The bioavailability of A, C and D relative to B was 31.8%, 72.2% and 138.9% respectively. The new tablet formulation D is superior to the imported tablet B in both the extent and rate of absorption.

Biological Availability↗

Evaluation of a clinical scintillation camera with pulse tail extrapolation electronics.

The performance of a new scintillation camera, designed for high event rate capability, was evaluated. The system consisted of a 400 mm field-of-view Nal(T1) camera with 61 photomultiplier tubes and modified General Electric Starport electronics. A significant feature of the system was circuitry for performing pulse tail extrapolation and separation of individual pulses involved in pulse pile-up events. System deadtime, flood field uniformity, energy resolution, linearity, spatial resolution, and bar phantom image quality were evaluated for count rates up to 200 kcps in a 20% photopeak window. Our results indicate that this camera design does not compromise image quality at normal clinical count rates and at higher event rates can provide better image quality and increased sensitivity over many Anger cameras currently employed in nuclear medicine.

Evaluation Studies as Topic↗

Evaluation of the renal tubulo-toxic effect of gossypol by urinary protein analysis with SDS-polyacrylamide gel electrophoresis.

The present study assessed the urinary protein with SDS-PAGE technique and by using gentamicin as a positive control for a comparative study to evaluate the renal toxic effect of gossypol. Results indicated that gentamicin could induce proteinuria by alteration of glomerular permeability to cause over-filtration of high molecular weight proteins, damage the brush border (BB) membrane of proximal renal tubules and impair tubular reabsorption function. Gossypol could also induce proteinuria in certain cases of guinea pigs but not at all in gossypol-treated rats. However, an increase in low molecular weight protein bands (M.W. range 20-30 kd) in urinary electrophoregram of gossypol-treated rats were detectable.

Animals↗

A study on furosemide disposition in man.

Furosemide disposition in man was studied. Six male young healthy volunteers were given 20 mg furosemide by bolus intravenous injection and 10, 20, 30 and 40 mg furosemide (solution) orally. The serum drug concentration was determined by high performance liquid chromatography and the urinary excretion was determined spectrophotometrically after diazotization. The experimental data from serum and urine samples were simultaneously subjected to computer analysis. On the basis of the results, it was demonstrated that disposition of furosemide in man can be described by a two-compartment open model with the following average parameters: t1/2 alpha = 0.237 +/- 0.069 h, t1/2 beta = 1.29 +/- 0.20 h and Vss = 8.46 +/- 2.171. After oral administration of furosemide solution, the drug was rapidly absorbed from the gastrointestinal tract with a first-order absorption rate constant ka of 2.33 +/- 0.93 h-1 but there was a lag time of about 6.45 min for drug resolution and entering the absorption site. The oral relative bioavailability was estimated as 83 +/- 14%, which was higher than reported values. The elimination of furosemide was very rapid and was mainly via the renal route. The systemic clearance (CLs) and renal clearance (CLr), following bolus intravenous dosing were 7.60 +/- 2.29 and 6.44 +/- 1.81 l/h, respectively. The oral route did not influence CLs and CLr on the whole, but the nonrenal clearance ratio (CRnr) after oral dosing (15.7 +/- 4.8%) was significantly higher than that after intravenous administration (11.2 +/- 4.0%), which can be explained by a first-pass effect of the liver-portal system.

Administration, Oral↗

The diuretic effect of furosemide in relation to its disposition in man.

Experiments concerning the diuretic effect and disposition of furosemide were performed in nine healthy male volunteers. During the test period, each of subject was given 50 ml of water every half an hour. Under this experimental condition, interesting phenomena, such as almost identical duration of diuretic effect independent of given dose and the so-called clockwise hysteresis of the concentration-effect curve were observed. These phenomena revealed that the body water regulation system had intervened in the pharmacodynamics of furosemide. Based on experimental results, a model and a new equation are presented, which describe the quantitative relationship of the drug disposition, the diuretic response and the body water regulatory function.

Administration, Oral↗