3.Preparation of two poor water soluble drugs - nanoporous ZnO solid dispersions and the mechanism of drug dissolution improvement.
Bei GAO ; Changshan SUN ; Zhuangzhi ZHI ; Yan WANG ; Di CHANG ; Siling WANG ; Tongying JIANG
Acta Pharmaceutica Sinica 2011;46(11):1399-407
Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.
4.Role of various concentrations of glucose and insulin on expression of transforming growth factor-?_1 in HK2 cells
Zhi-Min MIAO ; Rui-Xia SUN ; Zheng-Ju FU ; Chang-Gui LI ;
Chinese Journal of Endocrinology and Metabolism 2001;0(05):-
HK-2 cells were cultured with various concentrations of glucose and insulin for 12,24,48,72 h.Transforming growth factor-?_1(TGF-?_1) protein in supematant was measured by ELISA,while TGF-?_1 mRNA expression was assessed by RT-PCR.Data showed that high concentration of glucose and insulin up-regulated the expression of TGF-?_1 in HK-2 cells through different pathways.
5.Over-articular external fixator combined with limited internal fixation for the treatment of high-energy Pilon fractures.
Da-Cheng LIU ; Xiao-Ning YANG ; Chang-Zhi HUANG ; Yi-Gong SUN ; Xing-Ming DAI
China Journal of Orthopaedics and Traumatology 2014;27(4):331-334
OBJECTIVETo study clinical effects of the over-articular external fixator combined with limited internal fixation for the treatment of Pilon fractures caused by high energy.
METHODSFrom September 2003 to April 2011, 36 patients with Pilon fractures caused by high energy were treated with the over-articular external fixator combined with limited internal fixator. There were 25 males and 11 females, ranging in age from 16 to 72 years old,with an average of 38 years old. The diagnoses of all patients were determined by conventional X-ray examination or three-dimensional spiral CT examination. The AOFAS scoring criteria was used to evaluate the therapeutic effects. The patients with comminuted fractures were treated with screw or Kirschner wire fixation without uncovering periost so as to enhance stability between fracture end and bone blocks,followed by the fixation with over-articular external fixators.
RESULTSAll the patients were followed up, and the duration ranged from 4 to 27 months, with an average of 13 months. Thirty-two patients got wound healing at the first stage. And the bone union duration ranged from 2 to 6 months, with a mean of 3 months. According to the AOFAS ankle-hindfoot subjective scoring standard, 13 patients got an excellent result, 20 good and 3 fair, with an score of 88.2 +/- 3.6. Twelve patients had infections at pinhole, 5 patients had pinhole pain. One patient had the fixator broken induced by over loading, who was cured after treatment. There were no complications such as nerve or vascular injuries, or osteomyelitis.
CONCLUSIONThe over-articular external fixation combined with limited internal fixation for the treatment of Pilon fractures caused by high energy is an ideal method, which has such advantages as reliable fixation, simple operation, coincidence with principles of biomechanical fixation, and benefit for fracture healing.
Adolescent ; Adult ; Aged ; Ankle Injuries ; diagnostic imaging ; surgery ; Ankle Joint ; diagnostic imaging ; surgery ; External Fixators ; Female ; Fracture Fixation ; Fracture Fixation, Internal ; Humans ; Internal Fixators ; Male ; Middle Aged ; Radiography ; Treatment Outcome ; Young Adult
6.Characteristics and significance of IGF-1 and IGFBP2 gene expressions in ankle cartilage of patients with Kashin-Beck disease
Ming CHEN ; Bo YANG ; Yanhai CHANG ; Zhengming SUN ; Xiaoqing WANG ; Zhi YI ; Ming LING ; Xiong GUO
Chinese Journal of Endemiology 2021;40(3):179-185
Objective:To investigate the characteristics and significance of insulin-like growth factor 1(IGF- 1) and insulin-like growth factor binding protein 2 (IGFBP2) expressions in ankle cartilage of patients with Kashin-Beck disease (KBD).Methods:In this case-control study, 10 KBD patients who were hospitalized in the Department of Orthopedics of Shaanxi Provincial People's Hospital from January 2010 to December 2016 were selected as KBD group, and 10 patients with ankle fracture caused by trauma but without talus injury during the same period were selected as control group, the cartilage tissues of the two groups were collected. IGF-1, IGFBP2 positive cells, the mRNA and protein expressions of IGF-1, IGFBP2 in the cartilage tissues were detected by immunohistochemistry, real-time fluorescent quantitative PCR and Western blotting, respectively. According to the expressions of IGF-1 and IGFBP2 in ankle cartilage of KBD patients, a patient with amputation caused by trauma was selected in Shaanxi Provincial People's Hospital, and ankle joint cartilage was taken to prepare chondrocytes for in vitro cell verification experiments. The chondrocyte were divided into control group (0 ng/ml T-2 toxin), T-2 treatment group (20 ng/ml T-2 toxin) and T-2+ IGFBP2 silenced group (20 ng/ml T-2 toxin+ 50 nmol/L IGFBP2 siRNA), the MTT method and dimethyl methylene blue staining were used to detect the activity of chondrocyte and the secretion of sulfated glycosaminoglycan (sGAG). Results:In the control group and the KBD group, the number of IGF-1[(47.26 ± 8.97), (68.15 ± 7.42) cells] and IGFBP2 positive cells [(27.56 ± 5.40), (71.85 ± 7.62) cells] in the cartilage tissues were significantly different ( t = 4.487, 9.402, P < 0.01). Compared with the control group, the IGF-1, IGFBP2 mRNA and protein expression levels in KBD group were significantly higher, the differences were significantly different ( t = 3.340, 20.700, 4.684, 8.699, P < 0.05 or < 0.01). In cell experiment, the chondrocyte activitives and sGAG contents of the control group, T-2 treatment group, and T-2+ IGFBP2 silenced group were significantly different ( F = 226.70, 80.66, P < 0.01); among them, the cell activitives and sGAG contents of the T-2 treatment group and T-2+ IGFBP2 silenced group were lower than those of control group ( P < 0.05), and the T-2+ IGFBP2 silenced group were higher than those of the T-2 treatment group ( P < 0.05). Conclusions:The expressions of IGF-1 and IGFBP2 in the ankle cartilage of KBD patients are significantly higher. Silencing IGFBP2 gene can reduce the inhibitory effect of T-2 toxin on chondrocyte activity and the secretion of sGAG.
7.Comparison of Osteogenic Potential in vivo between Autologous Bone Marrow Mesenchymal Stem Cell Implanting and Fibrin Sealant Combined with Recombined Human Bone Morphogenetic Protein-2 Grafting
Yuli CHANG ; Tiansheng SUN ; Zhi LIU ; Chaoqun YE ; Zhaozhong YU ; Zhicheng ZHANG ; Dajiang REN
Chinese Journal of Rehabilitation Theory and Practice 2009;15(1):44-47
Objective To investigate the osteogenic potential for size-critical bone defect of fibrin sealant combined with recombined human bone morphogenetic protein-2 (rhBMP-2) grafting and varied autologous bone marrow mesenchymal stem cells (BMSCs) implanting in vivo. Methods BMSCs were cultured and induced with osteogenic supplement (OS) medium. BMSCs with and without OS induction were collected and percutaneously autologous injected respectively into the 15 mm bone defect of experimental rabbit model. The grafts were BMSCs, osteo-induced BMSCs, BMSCs and osteo-induced BMSCs, BMP combined with fibrin sealant, 0.9% NaCl solution. Osteogenesis at the defect area was assessed with regular radiography, histology and biomechanics. Results The FS/BMP group and the BMSCs+osteo-induced BMSCs group achieved complete bone healing with medullary cavity united, with the most new bone formation and the maximal load among those groups. Conclusion The osteogenic potential of both osteo-induced BMSCs combined with BMSCs and FS/BMP are similar, which are superior to that of BMSCs or osteo-induced BMSCs along.
8.Preparation of two poor water soluble drugs - nanoporous ZnO solid dispersions and the mechanism of drug dissolution improvement.
Bei GAO ; Chang-shan SUN ; Zhuang-zhi ZHI ; Yan WANG ; Di CHANG ; Si-ling WANG ; Tong-ying JIANG
Acta Pharmaceutica Sinica 2011;46(11):1399-1407
Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.
Anti-Inflammatory Agents, Non-Steroidal
;
administration & dosage
;
chemistry
;
Calorimetry, Differential Scanning
;
Drug Carriers
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Indomethacin
;
administration & dosage
;
chemistry
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Microscopy, Electron, Scanning
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Nanostructures
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Phosphodiesterase 3 Inhibitors
;
administration & dosage
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chemistry
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Solubility
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Spectroscopy, Fourier Transform Infrared
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Tetrazoles
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administration & dosage
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chemistry
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X-Ray Diffraction
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Zinc Oxide
;
chemistry
9.The underground part growth distribution pattern of Glycyrrhiza uralensis and its effects on glycyrrhizinic acid content.
Zhi-rong SUN ; Wen-quan WANG ; Chang-hua MA ; Min-bin SUN ; Yong-hong YAN ; Chang-li LIU
China Journal of Chinese Materia Medica 2004;29(4):305-309
OBJECTIVETo ascertain the relationship between glycyrrhizinic acid content and the underground part growth character of Glycyrrhiza uralensis and provide the theoretical evidence for wild resources protection and artificial cultivation method of G. uralensis.
METHODThrough the analytical investigation on the underground part of G. uralensis and analysis of glycyrrhizinic acid content in different organs, parts, ages, and diameter medicinal materials, the systematic study on the relationship between glycyrrhizinic acid content and the underground part growth character of glycyrrhiza uralensis was carried out.
RESULTThe underground part of a G. uralensis seedling consisted of seed root, random root, horizontal underground stem, vertical underground stem and assimilating root. The glycyrrhizinic acid content in horizontal underground stem with the age below two years old or in random root with the diameter below 0.5 cm was low. The difference of glycyrrhizinic acid content among horizontal underground stem, random root and vertical underground stem was obvious, but the difference between horizontal underground stem and random root was not obvious.
CONCLUSIONThe horizontal underground stem was of G. uralnesis acts as a link that can connect random root, vertical underground and stem assimilating root, so that the whole underground part constructs one huge underground net system. The glycyrrhizinic acid accumulation is a effected by organ type, growth age, root diameter and grow position, and the distribution pattern of random root and vertical underground stem has influence on glycyrrhizinic acid distribution in horizontal underground stem.
Glycyrrhiza uralensis ; chemistry ; growth & development ; Glycyrrhizic Acid ; analysis ; Plant Roots ; chemistry ; growth & development ; Plants, Medicinal ; chemistry ; growth & development ; Seedlings ; chemistry ; growth & development ; Time Factors
10.Screening of specific binding peptide targeting blood vessel of human esophageal cancer in vivo in mice.
Min ZHI ; Kai-chun WU ; Zhi-ming HAO ; Chang-cun GUO ; Jia-yin YAO
Chinese Medical Journal 2011;124(4):581-585
BACKGROUNDCancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer.
METHODSThe phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced. During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues. Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and VIII-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test.
RESULTSThe number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P < 0.01 in tumor and spleen, P < 0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or VIII-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by analyzing the homology of these peptide sequences. The staining distribution of phage with the sequence of PNPNNST was similar to that of the blood vessel marker factor VIII-related antigen staining. After sequencing, each phage with the selected peptide of PNPNNST with 1.0 × 10(11) pfu/ml was injected intravenously into mice. The homing ability to tumor vessel of these 9 kinds of peptides in the xenograft was higher than control tissues (lung and spleen).
CONCLUSIONNine peptides obtained from in vivo screening homed to the blood vessel of human esophageal cancer, and the two motifs of YSXNXW and PXNXXN are the possible biochemical recognition units binding to vascular endothelial cells of esophageal cancer.
Animals ; Antineoplastic Agents ; therapeutic use ; Endothelial Cells ; drug effects ; Esophageal Neoplasms ; blood supply ; drug therapy ; metabolism ; Humans ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Peptide Library ; Peptides ; therapeutic use