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Mitochondria are dynamic organelles that continuously divide and fuse. In recent years, in addition to the studies related to mitochondrial metabolism, the unique dynamics of mitochondria have gradually attracted researchers' attention. A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells. Mitochondrial fission proteins (mitochondrial fission protein 1, FIS1) mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission. They are important proteins in the process of mitochondrial fusion and fission. However, few studies have revealed the expression and role of FIS1 in human cervical cancer. In this study, the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared. The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues (P<0. 01). Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions. Subsequently, HeLa cells with overexpressed FIS1 were investigated for their proliferation, migration, mitochondrial fission and ROS levels. The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability, enhanced mitochondrial fission and higher ROS levels. In conclusion, the expression of FIS1 in human cervical cancer cells was attenuated, while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells. Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.
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OBJECTIVE@#MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer.@*METHODS@#Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors.@*RESULTS@#99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR.@*CONCLUSION@#99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.
Subject(s)
Animals , Female , Humans , Mice , Breast Neoplasms/diagnostic imaging , Cell Line, Tumor , MicroRNAs/analysis , Oligonucleotides, Antisense , Oligopeptides , Radiopharmaceuticals , Succinimides , Technetium , Tissue DistributionABSTRACT
Objective To construct the eukaryotic expression vector of pyruvate kinase M1 (PKM1) gene labeled with pXJ-40-myc and detect its biological activity in ocular B16 melanoma cells.Methods Ocular B16 melanoma ceils were randomly divided into experimental and control group,and the experimental group was transfected with pXJ-40-myc-PKM1 plasmid and the control group was transfected with pXJ-40-myc plasmid.Then PKM1 gene was amplified by PCR with human liver cDNA library as the template.The recombinant plasmid pXJ-40-myc-PKM1 was identified by bacteria PCR and double enzyme digestion,followed by transfection of pXJ40-myc-PKM1 and pXJ-40-myc plasmid into B16 melanoma cells,and finally,the expression of PKM1 protein was verified by the Western blot,while wound healing assay was used to detect the effects of PKM1 on the migration of ocular melanoma ceils.Results The length of PKM1 gene was 1800bp,which was consistent with the expected size.Compared with the control group,the result of bacteria PCR was positive.The length of double enzyme digestion was 4000 bp and 1800 bp respectively.Western blot results showed that recombinant plasmld pXJ-40-myc-PKM1 was successfully expressed in ocular B16 melanoma cells.Compared with the control group,wound healing assay showed that recombinant plasmid could inhibit the migration of ocular B16 melanoma cells.Conclusion The eukaryotic expression vector of pXJ-40-myc-PKM1 is successfully constructed,which can suppress the migration of ocular B16 melanoma cells.
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Objective To construct the eukaryotic expression vector of LDHA with Flag label and detect its effects on the growth of human choroidal melanoma (CM) MUM-2B cells.Methods CM cells line MUM-2B subcultured by the Military Academy of Sciences were divided into two groups:experimental group and control group.The experimental group was transiently transfected with Flag-LDHA plasmid,and the control group was transiently transfected with Flag plasmid.Using the Flag-LDHA with GST label as a template,the LDHA gene was amplified by polymerase chain reaction (PCR),which then was inserted into eukaryotic expression vector of Flag,and the recombinant plasmid Flag-LDHA was identified by bacterial liquid PCR,double enzyme digestion and sequencing,both which were transiently transfected into human CM MUM-2B cells after successful identification,and finally,its expression was determined by Western blot.The biology behaviors of melanoma cell line MUM-2B transfected with Flag-LDHA and Flag plasmid were analyzed by counting Kit-8 (CCK8) assays.Results The coding region sequence of LDHA gene of approximately 1000 bp was harvested from PCR amplification,which was successfully cloned into the Flag vector.Compared with the control group,the PCR result of the bacterial liquid in the experimental group was positive.The double enzyme digestion results showed that eukaryotic expression vector of Flag with a length of about 4000 bp Flag vector and a 1000 bp LDHA gene band.And the sequencing results indicated that the inserted sequence was completely in consonance with the coding sequence of the LDHA gene.Western blot results showed the successful expression of recombinant plasmid Flag-LDHA in MUM-2B melanoma cells.CCK8 assays demonstrated that Flag-LDHA recombinant plasmid could promote the growth of melanoma cell line MUM-2B.Conclusion The eukaryotic expression vector of Flag-LDHA was successfully constructed,which can promote the growth of melanoma cell line MUM-2B.This will lay the foundation for studying the function of LDHA in the initiation and progression of human CM.
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Objective To investigate the phenotype of a boy with osteogenesis imperfecta(OI)and detect the path-ogenic gene mutation in his family.Methods The clinical data of a uygur ethnic boy was investigated in detail, who suffered from early onset repeated fragile fractures.Bone turnover biomarkers, bone mineral density(BMD) and bone morphology were evaluated.The pathogenic mutations in this patient were investigated by targeted next-generation sequencing and subsequently confirmed by Sanger sequencing.Results Serum β-cross linked C-te-lopeptide of type Ⅰcollagen was elevated.Radiological assessment revealed a generalized osteoporosis in thoraco-lumbar spine,slender long bone with thin cortices.The pathogenic mutations in TMEM38B were detected as follow:a homozygous mutation c.507G>A transition in exon 4,which would generate a new downstream termination codon (p.W169X).His parents were heterozygous carriers of the mutation.Conclusions Mutation in TMEM38B is iden-tified for the first time in a uygur ethnic boy with extremely rare autosomal recessive OI type XIV.The clinical and genetic findings expands our understanding of rare OI induced by TMEM38B mutation.
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Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women.Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose (70 mg per two weeks) or standard dose (70 mg weekly) of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density (BMD), serum cross-linked C-telopeptide of type I collagen (β-CTX), and total alkaline phosphatase (ALP) were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed.Results rs10925503 polymorphism of GGPPS gene was correlated to serum β-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype (all P<0.05). No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly (P<0.01), and without obvious differences between the low dose and standard dose groups (all P>0.05). However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels (all P>0.05).Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.
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Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet.
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1,2,3,4,6-penta-O-galloyl-D-glucose (PGG) is one of the main active compounds of Guizhi Fuling capsule. Molecularly imprinted polymers (MIP) have high affinity toward template molecules synthesized by molecularly imprinted technology for its specific combined sites, which can overcome the shortcoming of traditional separation methods, such as complex operation, low efficiency, using large quantity of solvent and environmental pollution. In this paper, surface molecularly imprinted polymer (SMIP) was prepared by surface imprinting with PGG as the template molecule. Its adsorption capacity was measured by the scatchard equation. The separation of PGG from Guizhi Fuling capsule at preparatived scale was achieved with molecularly imprinted polymer as stationary phase and the purity was 90.2% by HPLC. This method can be used to prepare PGG from Guizhi Fuling capsule with large capacity and is easy to operate. It provides a new method for efficient separation and purification for other natural products.
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Adsorption , Capsules , Chemistry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Hydrolyzable Tannins , Chemistry , Molecular Imprinting , Polymers , ChemistryABSTRACT
In this study, the active components and potential molecular .mechanism of Guizhi Fuling formula in treatment on dysmenorrhea, pelvic inflammation, and hysteromyoma were investigated using network pharmacological methods. Sterols and pentacyclic triterpenes, with high moleculal network degree, revealed promising effects on anti-inflammatory, analgesic, anti-tumor, and immune-regulation, according to D-T network analysis. On the other hand, the targets with high degree were involved in inflammatory, coagulation, angiopoiesis, smooth muscle contraction, and cell reproduction, which showed the novel function in anti-dysmenorrhea, pelvic inflammation, and hysteromyoma. Furthermore, the formula was indicated to play a key role in smooth muscle proliferation, inhibition of new vessels, circulation improvement, reduction of hormone secretion, alleviation of smooth muscle, block of arachidonic acid metabolism, and inflammation in uterus. Thus, the main mechanism of Guizhi Fuling formula was summarized. In conclusion, Guizhi Fuling formula was proven to alleviated dysmenorrhea, pelvic inflammation, and hysteromyoma by acting on multiple targets through several bioactive compounds, regulating 21 biological pathways.
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Female , Humans , Drugs, Chinese Herbal , Therapeutic Uses , Dysmenorrhea , Drug Therapy , Genetics , Metabolism , Gene Regulatory Networks , Leiomyoma , Drug Therapy , Genetics , Metabolism , Pelvic Inflammatory Disease , Drug Therapy , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To compare the effect of reinforcing Shen method (RSM) and activating blood method (ABM) in treating osteoarthritis (OA) at the molecular level.</p><p><b>METHODS</b>The physical and chemical characteristics of components from respective recipes of RSM and ABM, and network features of component-target interaction network were analyzed by computer simulation methods including chemical space, molecular docking, and biological network, etc.</p><p><b>RESULTS</b>The chemical components of RSM and ABM were scarcely scattered with larger overlapping. Among established networks, the distribution of network features was partially similar in RSM and ABM. The average target number correlated with each component was 1.86 in RSM and 2.11 in ABM respectively. Each average target number was respectively correlated with 4.46 compounds and 3.93 compounds, reflecting multi-component and multi-target actions.</p><p><b>CONCLUSION</b>Computer simulation could intuitively trace out similarities and differences of two different methods and their interaction with targets, which revealed that the compatibility of RSM and ABM could have broader protein targets and potential synergism at the molecular level.</p>
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Humans , Computer Simulation , Drugs, Chinese Herbal , Therapeutic Uses , Osteoarthritis , Drug Therapy , Phytotherapy , MethodsABSTRACT
<p><b>OBJECTIVE</b>To explore the material basis of Caulis sinomenii (CS) in treating osteoarthritis (OA), and to give a pharmacodynamic illustration for the multi-targeting therapeutics of CS.</p><p><b>METHODS</b>The computational methods, consisting of molecular docking and biological network were carried out to search the database targeting twelve important OA related enzymes: ASAMTS4, ASAMTS5, MMP-1, MMP-3, MMP-13, MMP-8, MMP-2, COX-2, COX-1, IL-1beta, TNF-alpha, iNOS, and map the ligand-target interaction networks about molecules from CS and DrugBank. After that, an aggregate analysis was performed to analyze the mechanisms of compositions in CS.</p><p><b>RESULTS</b>Totally 14 had good interaction in all molecules in database with two or more than two of the OA correlated enzymes, and 6 molecules had interaction with four or more enzymes. Moreover, both herb ligand-target interaction network and drug ligand-target interaction network were similar in the interaction profiles and network features, which revealed multi-drugs effects in CS.</p><p><b>CONCLUSIONS</b>There were a lot of multi-target molecules in CS, providing pharmacodynamic illustrations for the multi-target therapeutics of Chinese medicine. Meanwhile, they supplied certain reference and inspiration for finding out new drugs for OA therapy.</p>
Subject(s)
Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Molecular Docking Simulation , Osteoarthritis , Drug Therapy , Phytotherapy , SinomeniumABSTRACT
<p><b>OBJECTIVE</b>To study the polypharmacological mechanism of herbal pair Chuanxiong Rhizome-Paeonia Albifora Pall (HP CXR-PAP) on the treatment for osteoarthritis (OA).</p><p><b>METHODS</b>Chemical space was used to discuss the similarities and differences between the molecule sets of HP CXR-PAP and drugs. Docking protocol was used to study the interaction between HP CXR-PAP and OA target enzymes. The similarities and differences of HP CXR-PAP and drugs in target spaces were elucidated by network features.</p><p><b>RESULTS</b>The plots between the molecule sets of HP CXR-PAP and drugs in chemical space had the majority in the same region, and compounds from HP CXR-PAP covered a much larger additional region of space than drug molecules, which denoted the diverse structural properties in the molecule set of HP CXR-PAP. The molecules in HP CXR-PAP had the properties of promiscuous drugs and combination drug, and both HP CXR-PAP ligand-target interaction network and drug ligand-target interaction network were similar in the interaction profiles and network features, which revealed the effects of multicomponent and multitarget.</p><p><b>CONCLUSION</b>The clue of potential synergism was obtained in curing OA disease by Chinese medicine, which revealed the advantages of Chinese medicine for targeting osteoarthritis disease.</p>
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Humans , Drug Combinations , Drug Synergism , Drug Therapy, Combination , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Ligands , Models, Molecular , Molecular Targeted Therapy , Osteoarthritis , Drug Therapy , Principal Component AnalysisABSTRACT
<p><b>OBJECTIVE</b>To investigate whether progesterone receptor B (PRB) can be sumoylated by SUMO-2/3 and the effect of sumoylation on PRB transcriptional activity.</p><p><b>METHODS</b>SUMO-2/3 cDNA was amplified from MCF-7 cDNA and cloned into the eukaryotic expression vector pcDNA3-FLAG. The plasmid pXJ40-myc-PRB was cotransfected with pcDNA3FLAG-SUMO2, pcDNA3FLAG-SUMO3 or the mock control into 293T cells, and PRB sumoylation was detected by immunoprecipitation and Western blotting. The effect of PRB sumoylation on its transcriptional activity was determined using reporter luciferase assay.</p><p><b>RESULTS</b>pcDNA3FLAG-SUMO2 and pcDNA3FLAG-SUMO3 vectors were successfully constructed. SUMO-2/3 could bind covalently to PRB and increase its transcriptional dependent on the presence of progesterone.</p><p><b>CONCLUSION</b>PRB can be sumoylated by SUMO-2/3 and its function is regulated by this modification.</p>
Subject(s)
Animals , Humans , Cell Line , Plasmids , Genetics , Receptors, Progesterone , Genetics , Metabolism , Small Ubiquitin-Related Modifier Proteins , Genetics , Metabolism , Transcription, Genetic , Transfection , Ubiquitination , Ubiquitins , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the pharmacological properties of Tougu Xiaotong Granule (TGXTG) in preventing and treating knee osteoarthritis (KOA) at the molecular level.</p><p><b>METHODS</b>The computational methods, including principal component analysis, molecular docking, target-ligand space distribution, and the predictions of absorption, distribution, metabolism, excretion and toxicity (ADMET), were introduced to characterize the molecules in TGXTG.</p><p><b>RESULTS</b>The structural properties of molecules in TGXTG were more: diverse than those of the drug/drug-like molecules, and TGXTG could interact with significant target enzymes related to KOA. In addition, the cluster of effective components was preliminarily identified by the target-ligand space distributions. As to the results of ADMET properties, some of them were unsatisfactory, and were merely regarded as references here.</p><p><b>CONCLUSION</b>Based on this computational pharmacology study, TGXTG is a broad-spectrum recipe inhibiting many important target enzymes, which could effectively postpone the degeneration of spectrum cartilage by coordinately inhibiting the biological effects of cytokines, matrix metallopeptidase 3, and oxygen free radicals. radicals.</p>
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Animals , Anti-Inflammatory Agents , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Osteoarthritis, Knee , Drug TherapyABSTRACT
Correct data without noise is the basis for obtaining useful information and knowledge. The database system of Chinese materia medica is the application of database technology in the field of Chinese materia medica. Its establishment is based on the analysis, processing and supplementary of much irregular raw data during studying Chinese materia medica information. This paper reviewed several key problems in the data processing of Chinese materia medica based on the information system of Chinese herbal medicine that we are constructing.
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Database Management Systems , Drugs, Chinese Herbal , Medicine, Chinese TraditionalABSTRACT
The rapid development of computer technology, molecular pharmacology and molecular biology extremely promoted the extensive and successful application of virtual screening technique (VST) in pharmaceutical exploitation. Based on plentiful literature and their own previous work, the authors elaborated the principles, methodology and strategy of VST systematically, gave a retrospection on the application of VST in the field of TCM in the last several years, and supposed that along with deepening of understanding, VST would play a greater role in TCM.
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Computational Biology , Computer Simulation , Drug Design , Drugs, Chinese Herbal , Chemistry , Medicine, Chinese Traditional , Methods , Software , Structure-Activity Relationship , Technology, Pharmaceutical , MethodsABSTRACT
<p><b>OBJECTIVE</b>To investigate the flavonoids of Oxytropisfalcata.</p><p><b>METHOD</b>Compounds were isolated by column chromatography using silica gel, Sephadex LH -20 and ODS as the adsorbents. Their structures were elucidated by NMR and MS spectroscopic data.</p><p><b>RESULT</b>Eight compounds were isolated and elucidated as 2', 4'-dihydroxy-4-methoxy chalcone (1), 2', 4'-dihydroxy chalcone (2), 5,7-dihydroxy-4'-methoxy flavonol (3), 7-hydroxy-4'-methoxy flavanones (4), 3', 7-dihydroxy-2',4'-dimethoxy isoflavan (5), 2'-hydroxy-4'-methoxy chalcone (6), 2'-methoxy-4'-hydroxy chalcone (7), 2',4'-dihydroxy dihydrochalcone (8).</p><p><b>CONCLUSION</b>All compounds were obtained from O. falcata for the first time.</p>
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Chalcones , Chemistry , Flavonoids , Chemistry , Oxytropis , Chemistry , Plants, Medicinal , ChemistryABSTRACT
To study the molecule recognition capability of corilagin-molecularly imprinted polymer (MIP) by the high performance liquid chromatography (HPLC), the molecularly imprinted polymer was synthesized by using corilagin as the template. Chromatographic performance of corilagin was investigated in different mobile phases. The MIP was investigated for the recognition of corilagin and its derivatives and other compounds in the same mobile phase. The MIP exhibited very high affinity for corilagin in the mobile phase of acetonitrile. The K' value will be reduced when the content of polar solvent increased in the mobile phase. The MIP has good selectivity in the mobile phase of acetonitrile-methanol (95:5), but it has no affinity for corilagin's derivatives. The corilagin-MIP has good selectivity for corilagin and it can be used in extracting corilagin and its analogs from herbs.
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Acetonitriles , Chromatography, High Pressure Liquid , Methods , Glucosides , Hydrolyzable Tannins , Polymers , ChemistryABSTRACT
<p><b>OBJECTIVE</b>Determine the content of ursolic acid of Liuwei Dihuangwan.</p><p><b>METHOD</b>Using NIR with PLS, PCA-BPANN and WT-BPANN.</p><p><b>RESULT</b>The predication recovery were 100.7%, 100.6%, 100.1%, and the RSD were 5.42%, 6.49%, 6.52% respectively.</p><p><b>CONCLUSION</b>NIR can be used in the determination of ursolic acid, which set up the foundation of on-line control of traditional Chinese medicine.</p>
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Cornus , Chemistry , Drug Combinations , Drugs, Chinese Herbal , Chemistry , Plants, Medicinal , Chemistry , Quality Control , Spectroscopy, Near-Infrared , TriterpenesABSTRACT
<p><b>AIM</b>To establish an HPLC-fluorescence method for determination of loratadine in human plasma and evaluate its relative bioavailability.</p><p><b>METHODS</b>An Alltech-C18 column and a mobile phase of acetonitrile-water-glacial acetic acid-triethylamine (90:100:6:0.15) were used. The fluorescence detector was set at Ex 274 nm, Em 450 nm. The flow rate was 1 mL.min-1.</p><p><b>RESULTS</b>The calibration curve was linear over a concentration range of 0.2-30 micrograms.L-1. The limit of quantification was 0.2 microgram.L-1. The average method recoveries varied from 96% to 98%. The results showed AUC, Tmax, Cmax and T1/2 beta between the testing tablets, testing capsules and reference tablets had no significant difference (P > 0.05). Relative bioavailabilities were 107% +/- 17% and 100% +/- 14% respectively.</p><p><b>CONCLUSION</b>The three formulations were bioequivalent.</p>