Search PubMed⌕ Search

Biomedical subjects

Yao Wang

Publications and source records attributed to Yao Wang.

At least 37 records · Page 2Linked to original sources
PubMed2005

Deletion of iNOS gene impairs mouse fracture healing.

Nitric oxide (NO) is a signaling molecule synthesized from l-arginine by nitric oxide synthases (NOSs). NOS isoforms are either constitutive (endothelial NOS [eNOS] and neuronal NOS [nNOS]) or inducible NOS (iNOS). Previously, our group has reported that NO is expressed during and modulates fracture healing. In this study, we evaluated the specific contribution of iNOS to fracture healing by using iNOS gene therapy in iNOS-deficient mice. Twelve-week-old female wild-type mice and iNOS-KO mice had a right femoral midshaft osteotomy fixed with an intramedullary 0.5-mm-diameter needle. A gelatine sponge was implanted across the fracture site. The gelatine sponge received either Ad5-CMViNOS (in iNOS-deficient mice; n=16) or Ad5-CMVempty (in wild-type mice; n=15, and iNOS-deficient mice; n=15) at a dose of 10(7) pfu. Mice were sacrificed at day 14, and their right and left hind limbs were harvested. Cross-sectional area (CSA) was determined by measuring the callus diameter across the mediolateral and anteroposterior plane using a vernier caliper. Specimens were loaded to failure torsionally in a biaxial INSTRON testing system, and maximum torque, torsional stiffness, and maximal and total energy were determined. Deletion of the iNOS gene decreased the total and maximum energy absorption of the healing femoral fracture by 30% and by 70% (P<0.01), respectively, in comparison to the wild-type mice. This reduction in energy absorption was reversed by iNOScDNA administration via adenovirus vector. Furthermore, iNOScDNA caused an increase in torsional failure by 20% (P=0.01) in comparison to iNOS(-/-) mice that did not receive the iNOScDNA. There were no significant differences in the biomechanical properties of intact femora. These data indicate that iNOS is important in mouse fracture healing. However, the clinical utility of NOS gene therapy to enhance fracture healing will need further evaluation.

Animals↗
PubMed2005

Coded excitation for synthetic aperture ultrasound imaging.

Peak acoustic power limits the signal-to-noise ratio (SNR) of real-time ultrasound images. For most conventional scan formats, however, the average power is well below heating limits. This means the SNR can be significantly increased using coded excitation. A coded system transmits a broadband, temporally elongated excitation pulse with a finite time-bandwidth product. The received signal must be decoded to produce an imaging pulse with improved SNR resulting from the higher average power in the elongated excitation. Decoding can produce significant range side lobes, however, greatly reducing image quality. All practical coding designs, therefore, represent a trade-off between SNR gain and range side lobes. A specific coding scheme appropriate for synthetic aperture imaging is presented. A 14.5 dB SNR improvement with acceptable range side lobes is demonstrated on a forward-looking imaging system appropriate for intravascular applications.

Algorithms↗
PubMed2005

Inhibition of urokinase receptor gene expression and cell invasion by anti-uPAR DNAzymes in osteosarcoma cells.

The urokinase-type plasminogen activator (uPA) receptor (uPAR) has been implicated in signal transduction and biological processes including cancer metastasis, angiogenesis, cell migration, and wound healing. It is a specific cell surface receptor for its ligand uPA, which catalyzes the formation of plasmin from plasminogen, thereby activating the proteolytic cascade that contributes to the breakdown of extracellular matrix, a key step in cancer metastasis. We have synthesized three different DNA enzymes (Dz372, Dz483 and Dz720) targeting uPAR mRNA at three separate purine (A or G)-pyrimidine (U or C) junctions. Two of these DNAzymes, Dz483 and Dz720, cleaved uPAR transcript in vitro with high efficacy and specificity at a molar ratio (uPAR to Dz) as low as 1 : 0.2. When analyzed over 2 h with a 200-fold molar excess of DNAzymes to uPAR transcript, Dz720 and Dz483 were able to decrease uPAR transcript in vitro by approximately 93% and approximately 84%, respectively. They also showed an ability to cleave uPAR mRNA in the human osteosarcoma cell line Saos-2 after transfection. The DNAzyme Dz720 decreased uPAR mRNA within 4 h of transfection, and inhibited uPAR protein concentrations by 55% in Saos-2 cells. The decrease in uPAR mRNA and protein concentrations caused by Dz720 significantly suppressed Saos-2 cell invasion as assessed by an in vitro Matrigel assay. The use of DNAzyme methodology adds a new potential clinical agent for decreasing uPAR mRNA expression and inhibiting cancer invasion and metastasis.

Cell Line, Tumor↗
PubMed2005

Tetracycline at subcytotoxic levels inhibits matrix metalloproteinase-2 and -9 but does not remove the smear layer.

BACKGROUND: The antibacterial and anticollagenolytic properties of tetracycline (TCN) are valuable in periodontal therapy, and TCN treatment can remove the smear layer following root instrumentation. However, recent reports pointing to cytotoxic effects of several acids prompted this study to define TCN concentrations that are anticollagenolytic and remove the smear layer, but have low cytotoxicity. METHODS: Human gingival (hGF) and periodontal ligament (hPDL) cells were treated short- (3 minutes) or long-term (24 hours) with TCN to determine concentrations yielding 50% (TD(50)) and 90% (TD(10)) cell survival. Activity assays measured TCN concentrations with half-maximal inhibition (IC(50)) of matrix metalloproteinase- 2 and -9 (MMP-2 and -9). Finally, we analyzed the effects of TCN with high (75 mg/ml) or low (1 mg/ml) cytotoxicity on the smear layer by scanning electron microscopy (SEM). RESULTS: The TD(50) for TCN after short-term treatment was 4 mg/ml for both hGF and hPDL. Ninety percent of the cells survived 0.2 mg/ml. With long-term treatment, the TD(50) for hGF and hPDL was 70 and 30 microg/ml, respectively, and the TD(10) was 20 and 5 microg/ml. HGF and hPDL recovered from the 3-minute treatment with 1 mg/ml, but not from concentrations exceeding 3 and 9 mg/ml, respectively. The IC(50) was 25 microg/ml for both MMP-2 and MMP-9. Whereas 75 mg/ml TCN removed the smear layer, 1 mg/ml TCN had no effects. CONCLUSIONS: Tetracycline has significant cytotoxicity on periodontal cells. Since non-cytotoxic concentrations of TCN inhibited MMP-2 and -9 but had no effects on the smear layer, TCN is not recommended for root surface treatment.

Anti-Bacterial Agents↗
PubMed2005

[Experimental studies on the treatment of colon cancer by cytosine deaminase gene and 5-fluorocytosine].

OBJECTIVE: To investigate the effect of cytosine deaminase (CD) gene plus 5-fluorocytosine (5-Fc) on the growth of human colon cancer xenograftin nude mice. METHODS: Retroviral vector expressing CD gene was transfected into human colon cancer SW1116 cells. Expression of the transfected CD gene in SW1116 (SWCD(2)) was confirmed by RT-PCR. The cytotoxicity of 5-Fc on SW1116 was determined by MTT assay in vitro. In vivo, the CD gene expression vector was injected intratumorally and 5-Fc was given by ip injections. RESULTS: In vitro, SWCD(2) cells were killed by 5-Fc with an IC(50) of 66 micromol/L while the nontrasfected SW1116 cells needed an IC(50) of 16 000 micromol/L to be killed. The growth of SWCD(2) xenografts was significantly inhibited by systemic administration of 5-Fc. CONCLUSION: CD gene/5-Fc system is a potential gene therapy strategy for human colon cancer.

Animals↗
PubMed2005

[Inhibition of proliferation of human lens epithelial cell line HLE-B3 by adenovirus-mediated transfer of antisense c-myc gene].

OBJECTIVE: To investigate the effects of adenovirus-mediated transfer of antisense c-myc gene on proliferation and survival of human lens epithelial cell. METHODS: Immortalized human lens epithelial cell line (HLE-B3) was infected by replication-deficient adenovirus of antisense c-myc gene (Ad-AS-myc). The expression of c-myc mRNA and protein was detected by RT-PCR and Western blotting respectively. Cell proliferation was analyzed by cell growth curve and MTT colorimetric assay, cell death and cell cycle of HLE-B3 were examined by flow cytometry. RESULTS: More than 80% of HLE-B3 cells were infected successfully after 48 hours incubation with Ad-AS-myc adenovirus. The expression of c-myc mRNA and protein was decreased. Ad-AS-myc suppressed the growth rate, enhanced the cell death (18.33% after 48 hours and 26.93% after 96 hours transduction). The proportions of G1 phase cells were increased to (60.50 +/- 7.59)% after 48 hours and (81.90 +/- 8.60)% after 96 hours transduction, while the proportions of S phase cells were decreased to (28.40 +/- 3.38)% after 48 hours and (16.75 +/- 8.97)% after 96 hours infection. CONCLUSIONS: Adenovirus-mediated antisense c-myc may inhibit proliferation and induce apoptosis of HLE-B3.

Adenoviruses, Human↗
PubMed2005

[Isolation and functional analysis of tobacco MARs].

Two new MAR segments (M14 and M17) were cloned from tobacco genome. Both of the sequences contained several typical consensus sequences of MARs, which were different from the original MAR sequence, such as 90%AT-box, A-box, T-box, the base unpairing regions (BUR), autonomously replicating sequences (ARS), the consensus sequence for topoisomerase II, MAR recognition sequence (MRS), origin of replication (ORI), curved DNA motifs and ATATTT et al. To investigate the effects of these two sequences on gene expression in transgenic plants, 3 plant expression vectors were constructed with uidA gene coding beta-glucuronidase (GUS) which were flanked on one side and on both sides by the MARs we obtained. These plant expression vectors with one or two MARs were transformed into tobaccos via Agrobacterium-mediated transformation method, with the plant expression vector pCAMBIA2301 without MAR and wild type tobacco as controls. GUS histochemical staining results showed that the uidA gene expressed stably in transgenic tobaccos. Quantitative detection of GUS activity showed that the MARs could increase GUS expression levels in vivo in contrast to the controls, wherever they were flanked on one side or both sides of uidA gene. The vector ligated with MARs in the same direction on both sides of uidA could increase the GUS expression level much better than both vectors which just ligated with single MARs on one side. The former one increased the average GUS activity for 3.14 folds, but 1.56 and 2.43 folds for the latter two vectors with single MARs respectively contrasting to the pCAMBIA2301 control. But the expression differences among individual transformants were still obvious. Therefore, it was concluded that the DNA sequences we obtained in this experiment were two novel MARs and could enhance gene expression in vivo. In the meanwhile, although the numbers of the MARs typical motifs in M14 were more than in M17, especially the 90% AT box which had been considered to be the highest correlative motif with binding strength in vitro, the enhancement of gene expression was lower yet, which implied no correlation between improvement of gene expression and binding strength between MARs and nuclear matrix in vitro.

Cloning, Molecular↗
PubMed2004

[Impact of lowering the cut-point for impaired fasting glucose on the distribution of impaired glucose regulation subcategories in Chinese adult population].

OBJECTIVE: To evaluate the impact of lowering of cut-point value for impaired fasting glucose (IFG) from 6.1 mmol/L to 5.6 mmol/L. by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, US, on the prevalence rates of different impaired glucose regulation (IGR) subcategories in Chinese adults, and to explore the ability of the new cut-point to diagnose IGR. METHODS: The data of 15 564 persons undergoing standard 75 g oral glucose tolerance test (OGTT) in the National Diabetes Mellitus Survey (1994) in Chinese adults (>or= 25 years) were reanalyzed. The prevalence of isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG and IGT (IFG/IGT) were calculated by the new criteria of 5.6 mmol/L <or= fasting plasma glucose (FPG) < 7.0 mmol/L and old criteria of 6.1 mmol/L <or= FPG < 7.0 mmol/L. The sensitivity and specificity of different FPG to diagnosis of IGR were analyzed with the value of blood sugar 2 hour after OGTT as 7.8 mmol/L <or= PG2 h < 11.1 mmol/L as the gold standard. Receiver operator characteristic curve (ROC) was used to determine the best FPG cut-point value for diagnosing IGR. RESULTS: (1) The prevalence of I-IFG, I-IGT, and IFG/IGT were 8.71%, 12.08% and 5.95% when classified by the old criteria, and 21.25%, 6.89% and 11.13% by the new criteria respectively. (2) ROC analysis showed an optimum FPG cut-point to diagnose IGR of 5.6 mmol/L, which yielded a sensitivity of 61.9% and specificity of 63.9%. CONCLUSION: The decrease of the lower cut-point value for IFG from 6.1 mmol/L to 5.6 mmol/L is associated with a 1.2 time increase of IFG prevalence among Chinese adults. From the viewpoint of minimizing the discrepancy between IFG and IGT, it may be suitable to lower the IFG cut-point value.

Adult↗
PubMed2004

A predictive pharmacophore model of human melanocortin-4 receptor as derived from the solution structures of cyclic peptides.

Using nuclear magnetic resonance (NMR) spectroscopy, we have determined the solution structures for a series of potent agonists for the human melanocortin-4 receptor (hMC4R), based on the cyclic peptide MT-II [Ac-Nle-cyclo-(Asp-Lys) (Asp-His-(D)Phe-Arg-Trp-Lys)-NH2]. Members of this series were designed to improve selectivity for MC4R versus the other melanocortin receptors, and to reduce the flexibility of the side chains. The most selective and rigid analog [penta-cyclo(D-K)-Asp-Apc-(D)Phe-Arg-(2S,3S)-beta-methylTrp-Lys-NH2] was found to be a full agonist of hMC4R with an EC50 of 11nM against hMC4R, and to exhibit 65-fold selectivity against hMC1R. This compound represents the most constrained hMC4R peptide agonist described to date. A beta-turn structure was conserved among all of the cyclic peptides studied. The rigidity of the analogs allowed an exceptionally well-defined pharmacophore model to be derived. This model was used to perform a virtual screen using a library of 1000 drug-like compounds, to which a small set of known potent ligands had been intentionally added. The utility of the model was validated by its ability to identify the known ligands from among this large library.

Humans↗
PubMed2004

Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector.

Attempts to generate reliable and versatile vectors for gene therapy and biomedical research that express multiple genes have met with limited success. Here we used Picornavirus 'self-cleaving' 2A peptides, or 2A-like sequences from other viruses, to generate multicistronic retroviral vectors with efficient translation of four cistrons. Using the T-cell receptor:CD3 complex as a test system, we show that a single 2A peptide-linked retroviral vector can be used to generate all four CD3 proteins (CD3epsilon, gamma, delta, zeta), and restore T-cell development and function in CD3-deficient mice. We also show complete 2A peptide-mediated 'cleavage' and stoichiometric production of two fluorescent proteins using a fluorescence resonance energy transfer-based system in multiple cell types including blood, thymus, spleen, bone marrow and early stem cell progenitors.

Amino Acid Sequence↗
PubMed2004

Clinical significance of urokinase-type plasminogen activator receptor (uPAR) expression in cancer.

The involvement of the urokinase-type plasminogen activator (uPA) system in particular has been extensively studied in the pathogenesis of cancer. The molecular role of the uPA receptor (uPAR) is well characterized with its participation in cell migration and extracellular matrix (ECM) degradation. Over-expression of uPAR in cancer has been demonstrated in many studies and is considered an attractive target for anticancer agents. We and others have down-regulated uPAR expression in an attempt to inhibit cancer metastasis based on its molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored protein is not only bound to the cell surface but also has a soluble form, suPAR. There is now accumulated clinical and experimental evidence supporting the significant role of uPAR and its soluble counterpart in a number of solid cancers. The expression of uPAR can be associated with tumor cells or stromal cells or both. Differences observed in the expression of uPAR using immunohistochemistry (IHC) are likely explained by the use of different antibodies and techniques rather than true cellular differences and are reviewed here. This review summarizes the clinical relevance of uPAR and its soluble form in the prognosis and diagnosis of different cancers.

Female↗
PubMed2004

Contributions of the MMP-2 collagen binding domain to gelatin cleavage. Substrate binding via the collagen binding domain is required for hydrolysis of gelatin but not short peptides.

Two matrix metalloproteinases, MMP-2 and MMP-9, contain each three fibronectin type II-like modules, which form their collagen binding domains (CBDs). The contributions of CBD substrate interactions to the catalytic activities of these gelatinases have attracted special interest. Recombinant (r) CBDs retain collagen binding properties and deletions of CBDs in these MMPs reduce activities on collagen and elastin. We have characterized further the requirement of the CBD for MMP-2 cleavage of gelatin. The analyses used intact rMMP-2 and rCBD to eliminate any confounding effects that might result from structural perturbations in rMMP-2 induced by deletion of the approximately 20 kDa internal CBD. In protein-protein binding assays, 2% DMSO disrupted gelatin interactions of both rCBD and rMMP-2. At this concentration, DMSO also reduced the gelatinolytic activity by approximately 70%, pointing to a central role of CBD-substrate interactions during MMP-2 cleavage of gelatin. Subsequently, soluble rCBD was determined to competitively inhibit gelatin binding of unmodified rMMP-2 to gelatin by 73% and to reduce the MMP-2 degradation of gelatin by 70-80%. The residual gelatin cleavage that was not inhibited even by molar excess rCBD could be accounted for by degradation of short substrate molecules. Indeed, rCBD inhibited rMMP-2 cleavage of an 11 amino acid collagen-like peptide substrate (NFF-1) by less than 10%. These observations were confirmed with enzyme extracts from experimental tumors in mice. In the presence of rCBD, approximately 65% of the MMP-derived gelatinolytic activity was eliminated. Together, these results demonstrate that the CBD is absolutely required for MMP-2 cleavage of full-length collagen alpha-chains, but not for short protein fragments such as those generated by hydrolysis of gelatin.

Animals↗
PubMed2004

[Long-term effects of TCV116 on cardiac function changes after myocardial infarction].

OBJECTIVE: To investigate the long-term effects of TCV116 (candesartan cilexetil) on cardiac function changes after myocardial infarction. METHODS: Myocardial 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. RESULTS: Treatment 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). CONCLUSION: Treatment 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↗
PubMed2003

Effect of nitric oxide on cytotoxicity of Taxol: enhanced Taxol transcellular permeability.

The present studies were aimed at testing the hypothesis that nitric oxide (NO) may enhance Taxol-induced cytotoxicity in carcinoma cells by increasing influx of Taxol into intracellular compartments. Prostate carcinoma cells (PC-3, LNCaP) and neuroblastoma cells (SKNDZ, CHP212) were used to investigate both transmembrane permeability and cytotoxicity of Taxol in the presence and absence of S-nitrosocaptopril (CapNO), a nitric oxide donating compound. The order of permeability rate of Taxol across the four cell lines was SKNDZ>LNCaP>PC-3>CHP212. Pretreatment of the cell lines with CapNO (100 microM) enhanced permeability of Taxol across prostate PC-3 and LNCaP cells, but not neuroblastoma SKNDZ and CHP212 cells. Taxol inhibited cell growth at nanomolar levels with IC(50)s of 0.21, 17.4, 96.4 and 842.9 nM corresponding to SKNDZ, PC-3, LNCaP and CHP212 cells, respectively. However, CapNO inhibited proliferation of the four cell lines at millimolar levels with IC(50)s ranging from 0.3 to 1.1 mM. Enhancing effect of CapNO (100 microM) on Taxol cytotoxicity were found in PC-3 and LNCaP cells, but not in SKNDZ and CHP212. The findings suggest that the cytotoxic potency of Taxol is mainly dependent upon the cell membrane permeabilization to Taxol, and the enhancing effect of CapNO on Taxol-induced cytotoxicity is primarily mediated via the increased influx of Taxol by NO into intracellular compartments, while NO-induced cytotoxicity cannot be excluded.

Biological Transport↗
PubMed2003

Possible mechanisms underlying the protective effects of SY-21, an extract of a traditional Chinese herb, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampus.

We examined the neuroprotective actions of SY-21, a potent ingredient of a traditional Chinese herb, histologically. Transient brain ischemia (15 min) was induced by four-vessel occlusion in Sprague-Dawley rats. Administration of SY-21 20 min before or 6 h after brain ischemia significantly increased the number of surviving hippocampal CA1 pyramidal cells in rats subjected to transient brain ischemia followed by 5 days of reperfusion. Neuronal cell death resulting from ischemic events is associated with abnormal activation of the NMDA receptors. Tyrosine phosphorylation of the NMDA receptor subunit NR2A by Src or Fyn has been implicated in the up-regulation of NMDA receptor activity. In order to investigate the possible mechanism of the neuroprotective action of SY-21, we examined the effects of SY-21 on the ischemia/reperfusion-induced increases in tyrosine phosphorylation of the NMDA receptor subunit 2A (NR2A) and on the interactions involving NR2A, PSD-95 and Src/Fyn. We found that the increase in the tyrosine phosphorylation of NR2A induced by brain ischemia/reperfusion is suppressed by SY-21 administered 15 min before, or instantly after, brain ischemia. Also, SY-21 attenuated the increased interactions involving NR2A, PSD-95, Fyn and Src. These results demonstrate that SY-21 has a prominent neuroprotective action against brain ischemic insult, and the mechanism may involve the regulation of the tyrosine phosphorylation of NR2A by changing the above interactions.

Animals↗
PubMed2003

Synthesis of naturally occurring pyridine alkaloids via palladium-catalyzed coupling/migration chemistry.

The palladium-catalyzed cross-coupling of 3-iodopyridine, long-chain terminal dienes, and benzylic amines or tosylamides provides a novel route to key intermediates for the synthesis of the naturally occurring, biologically active pyridine alkaloids theonelladins C and D, niphatesine C, and xestamine D. This process involves (1) oxidative addition of the heterocyclic iodide to Pd(0), (2) carbopalladation of the least hindered carbon-carbon double bond of the diene, (3) palladium migration, and (4) pi-allylpalladium displacement by the nitrogen nucleophile with simultaneous regeneration of the Pd catalyst. Subsequent hydrogenation and deprotection affords good yields of the natural products. The Pd-catalyzed coupling of 3-iodopyridine and 2-methyl-11-dodecen-1-ol provides a convenient synthesis of a long-chain aldehyde by an analogous palladium migration process, which is easily converted to the pyridine alkaloid ikimine A.

Alkaloids↗
PubMed2003

Carbendazim: disposition, cellular permeability, metabolite identification, and pharmacokinetic comparison with its nanoparticle.

The purpose of this study was to systematically evaluate the pharmacokinetic profiles of carbendazim, a novel anticancer drug. Carbendazim reached the highest concentrations in stomach and small intestine by 1 h after oral administration (500 mg/kg) to tumor-bearing nude mice. Four hours later, carbendazim in the large intestine reached maximum concentrations, probably because of pH-induced precipitation of the drug in the large intestine. The highest concentrations of carbendazim in well-perfused tissues, solid tumor, and blood ranged from 63 to 164 microg/g by 4 h. The percentage of carbendazim distributed to solid tumor by 4 h was higher than most well-perfused tissues. Carbendazim concentrations in blood were similar to, or somewhat lower than, those in tumor and other tissues. By 24 h post-dosing, carbendazim concentrations in tissues and blood declined to almost basal levels. The total percentage of administered carbendazim eliminated in urine was 25.7%, and in feces 16.6% within 24 h. Carbendazim exhibited fast permeation across Caco-2 and HT-29 carcinoma cell lines with corresponding permeability coefficients 7.74-8.06 x 10(-5) and 6.8-8.42 x 10(-5) (cm/s). The overall plasma protein binding of carbendazim (0.2-125 microg/mL) assessed by ultrafiltration ranged from 60 to 74%. Comparative pharmacokinetics was conducted in rats by high-pressure liquid chromatography to evaluate the relative bioavailability of carbendazim versus its nanoparticle formulation. Carbendazim and its nanoparticle reached T(max) at 2.01 and 1.57 h, respectively. The relative bioavailability of nanoparticle carbendazim versus regular carbendazim was 166%. High-pressure liquid chromatography analysis of the rat serum obtained at 20 h after oral dosing revealed a carbendazim metabolite, which was identified by mass spectroscopy analysis as 2-aminobenzimidazole, a hydrolyzed product of carbendazim. Incubation of carbendazim with human and rat liver microsomes produced a metabolite identified by mass spectrometry as 5(6)- or 4(7)-hydroxyl carbendazim. The comprehensive pharmacokinetic information is important to the current clinical investigation of carbendazim.

Animals↗