1.The interactions between natural products and OATP1B1.
Mei-zhi SHI ; Yu LIU ; Jia-lin BIAN ; Meng JIN ; Chun-shan GUI
Acta Pharmaceutica Sinica 2015;50(7):848-853
Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals
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Biological Products
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CHO Cells
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Cricetulus
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Drug Interactions
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Fatty Acids, Monounsaturated
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pharmacology
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Flavonoids
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pharmacology
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Indoles
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pharmacology
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Inhibitory Concentration 50
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Organic Anion Transporters
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genetics
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metabolism
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Rosuvastatin Calcium
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pharmacology
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Structure-Activity Relationship
2.Case-control study on therapeutic effects of ozone and triamcinolone acetonide on the treatment of meniscal injury.
Bing WANG ; Gui-Zhi DONG ; Yan-Xin JU ; Chun-Shan YAN
China Journal of Orthopaedics and Traumatology 2014;27(4):295-298
OBJECTIVETo compare the clinical therapeutic effects between ozone and triamcinolone acetonide for the treatment of mild meniscal injury.
METHODSFrom January 2008 to December 2012, 119 patients with meniscal injury diagnosed as type I or II by MRI were divided into three groups. In the triamcinolone acetonide (A) group, there were 38 males and 2 females, with an average age of (25.34 +/- 6.34) years old, ranging from 18 to 48 years old; 36 patients had single knee injuries, 4 patients had double knee injuries and 44 knees with joint effusion. In the ozone (B) group,there were 37 males and 2 females, with an average age of (26.98 +/- 7.20) years old, ranging from 19 to 50 years old; 33 patients had single knee injuries, 6 patiens had double knees injuries and 40 knees with joint effusion. In the combination of ozone and triamcinolone acetonide (C) group, there were 37 males and 3 females,with an average age of (26.44 +/- 6.38) years old, ranging from 18 to 47 years old; 33 patients had single knee injuries, 7 patients had double knees injuries and 39 knees with joint effusion. The patients were treated with injection of 3 mg triamcinolone acetonide alone, 30 ml (30 microg/ml) ozone alone, or both two drugs respectively in knee joint cavity. All the treatment methods were carried out weekly and 4 times injections were required for a treatment course. Knee joint function was evaluated by Lysholm scale and knee joint effusion was examined by MRI before and after treatment.
RESULTSThe scale of knee joint function was 35.68 +/- 4.15 and 65.55 +/- 7.66 in group A, 36.35 +/- 6.83 and 74.39 +/- 8.47 in group B, 36.62 +/- 6.03 and 95.47 +/- 4.78 in group C before and after treatment. Compared with that before treatment, the total scale of knee joint function improved after treatment in every group. The total scale of group C was better than that of the other groups after the treatment,but there was no significant difference between group A and group B. The effective rate of these drugson joint effusion was 68.18% in group A, 62.5% in group B and 87.18% in group C. The effect of co-injection on joint effusion in group C was significantly better than that of triamcinolone acetonide or ozone alone, but the difference between group A and group B was not significant.
CONCLUSIONOzone and triamcinolone acetonide are effective in the treatment of mild meniscal injury, which can relieve symptoms and promote the recovery of joint function. Campared with the single injection, the combination of ozone and triamcinolone acetonide is better.
Adult ; Case-Control Studies ; Female ; Humans ; Knee Injuries ; drug therapy ; Male ; Menisci, Tibial ; drug effects ; Middle Aged ; Ozone ; administration & dosage ; Triamcinolone Acetonide ; administration & dosage ; Young Adult
3.Effects of surveillance system and preventive measures on the control of severe acute respiratory syndrome in a university in Guangdong Province of China.
Qing-shan CHEN ; Sheng-yong WANG ; Chun-xia JING ; Guo-ning LIU ; Gui-bo CHI ; Xiao-mei DONG
Chinese Journal of Preventive Medicine 2003;37(4):240-242
OBJECTIVETo evaluate the influence of the surveillance system and preventive measurements on the control of severe acute respiratory syndrome (SARS) in a university in Guangdong Province.
METHODSA university with more than thirty thousand undergraduates, staff and their relatives was retrospectively studied, from which information regarding the status of epidemic, organization of leadership, disease control strategies and measures were collected and analyzed.
RESULTSThe construction of the surveillance system in such a model as "individual-dormitory/home-class/unite-faculty and institute-university" largely contributed to the achievement of the goals of low incidence, no secondary, no epidemic, and no death. A series of control measures benefited the early diagnosis, effective isolation, prevention, and treatment of SARS control.
CONCLUSIONSARS could be effectively controlled in university only if strict surveillance system is built up, and all-round preventions, including early isolation of both confirmed or suspected cases and close contacted persons, are carried out.
Adolescent ; Adult ; China ; Communicable Disease Control ; methods ; Female ; Humans ; Male ; Population Surveillance ; methods ; Severe Acute Respiratory Syndrome ; prevention & control ; Universities
4.Long-term efficacy of temozolomide in patients with glioblastoma
Ji-Wei WANG ; Bu-Dong CHEN ; Chun-Zhi ZHANG ; Shu-Peng SUN ; Gui-Jun QI ; Hou-Lu WEI ; Si-Quan LIANG ; Yu-Shan YANG ; Xin YAO
Chinese Journal of Neuromedicine 2012;11(1):57-60
Objective To determine the efficacy of temozolomide (TMZ) in treating patients with glioblastoma using carmustine (BCNU) as control, and examine the effect of O6-methylguanine-DNA methyltransferase (MGMT) expression on the prognosis of patients with glioblastoma. Methods Two hundred and eighty-three patients with pathologically confirmed glioblastoma,admitted to and received treatment without chemotherapeutics in our hospital from January 2004 to January 2009, were enrolled in our study; TMZ was used in 97 patients and BCNU in 186 patients.The glioma tissues were examined for MGMT protein expression by immunohistochemistry.All patients in these 2 groups were performed long-term follow-up for survival time of the patients, tumor response and drug safety. Results In patients of the TMZ treatment group,the median survival time was (19.2±0.6) months,the 2-year survival rate 31% (30/97),the 5-year survival rate 6.2% (6/97) and the objective response rate 75.26% (73/97); while in patients of the BCNU treatment group,the median survival time of was (15.6±0.6) months,the 2-year survival rate 14% (26/186),the 5-year survival rate 0.5% (1/186),and objective response rate 45.16% (84/186); the cumulative survival rate of patients received TMZ treatment was significantly higher than that of patients received BCNU treatment (P<0.05);the objective response rate between the 2 groups was obviously different (x2=24.753, P=0.000); the incidence of hypoleukocytosis in patients received TMZ treatment was significantly lower than that in patients received BCNU treatment (x2=15.681,P=0.000). Conclusion TMZ shows more efficient oobjective response as compared with BCNU, with less adverse reaction and better tolerability.Therefore,it is an ideal drug of postoperative adjuvant chemotherapy for malignant glioma.
5.Effects of Shengmai injection on testicular injury after torsion/detorsion in rats of different ages.
Yi-fu ZHOU ; Chun-chao NI ; Ting-ting ZHENG ; Nai-jing XU ; Yu WANG ; Jing-jing YU ; Jin-ping ZHANG ; Gui-shan GAO
National Journal of Andrology 2011;17(2):185-188
OBJECTIVETo investigate the different effects of Shengmai injection on testicular injury after testis torsion/detorsion in rats of different ages.
METHODSSixteen healthy male SD rats aged 3, 6 and 12 weeks were equally randomized into an experimental group (testicular torsion/detorsion plus Shengmai injection) and a control group (testicular torsion/detorsion plus saline). The rat models of testicular torsion were killed 24 h after surgery for the measurement of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis.
RESULTSCompared with the controls, the 3- and 6-week-old rats of the experimental group showed no significant changes in T-AOC, SOD activity and MDA content (P > 0.05), while the 12-week-old experimental rats exhibited a remarkable increase in SOD and T-AOC and an obvious decrease in MDA content (P < 0.05).
CONCLUSIONShengmai injection has a protective effect against acute ischemia-reperfusion testicular injury after torsion/detorsion in rats, but the effect varies with the age, more obvious in older ones.
Animals ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Malondialdehyde ; metabolism ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Spermatic Cord Torsion ; drug therapy ; metabolism ; Superoxide Dismutase ; metabolism ; Testis ; drug effects ; injuries ; metabolism
6.Using 1H-MRS to evaluate the effects of warm ischemia reperfusion injury on the regeneration of hepatic cells in orthotopic transplanted livers in rats.
Ya-qin ZHANG ; Hong SHAN ; Qing-cong KONG ; Jin WANG ; Xiao-chun MENG ; Qiang SUN ; Yang YANG ; Gui-hua CHEN ; Hai-fang XING
Chinese Journal of Hepatology 2008;16(4):274-278
OBJECTIVETo investigate the prognostic value of proton magnetic resonance spectroscopy (1H-MRS) in the study of warm ischemia reperfusion injury to the regeneration of hepatic cells of the livers following their orthotopic transplantation in rats.
METHODSA rat orthotopic liver transplantation (OLT) model with warm ischemia, the experimental group, was established and the same was done with a control group but without warm ischemia of the livers. They were studied at 6 time points (6 hours, 1, 3, 7, 14, and 30 days after OLT). All rats took axial T1 weighted and T2 weighted imaging scans and 1H MR spectroscopies.
RESULTSThe positive rate of proliferating cell nuclear antigen (PCNA) and the mean peak choline/water ratio in the experimental group were significantly higher than those in the control group and the peak choline /water ratio had a positive correlation with the positive rate of PCNA. Serum ALT and AST increased significantly after OLT, especially during the 6 hour to 3day period. The levels of ALT and AST were markedly higher in the experimental group compared to the control group.
CONCLUSIONWarm ischemia reperfusion injury of OLT has a significant effect on the regeneration of hepatic cells, and the choline peak of 1H-MRS can be used to evaluate the regeneration of hepatic cells non-invasively.
Animals ; Graft Survival ; Hepatocytes ; cytology ; Liver Regeneration ; Liver Transplantation ; Magnetic Resonance Spectroscopy ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; diagnosis ; Warm Ischemia
7.The status of child neglect among rural areas children aged 0 - 6 years in China.
Fei WANG ; Jian-ping PAN ; Song-jie ZHANG ; Hua ZHANG ; Wei-qing WANG ; Hui-shan WANG ; Tao XU ; Gui-xiang WANG ; Wei-ping XI ; Fang-biao TAO ; Rui QIN ; Gui-xiong GU ; Shu-hua SHI ; Jing ZHANG ; Qi-yun DU ; Zhao-hui ZHONG ; Feng JIAO ; Xiao-mei YANG ; Chun-hong CAO ; Min LI
Chinese Journal of Preventive Medicine 2012;46(1):22-27
OBJECTIVETo explore the status of child neglect among rural areas children aged 0 - 6 years in China.
METHODSA total of 7411 rural children aged 0 - 6 years old who were composed of two age groups (3315 children aged 0 - 2 years old and 4096 children aged 3 - 6 years old) were multistage stratified randomly sampled from 84 villages which were representative of 10 provinces of China, in accordance with sex and age in November 2010. To identify the child neglect based on the Neglect Norms for Children Aged 0 to 2 and 3 to 6 Years Old in Rural Areas of China, SPSS 13.0 was employed for analyzing neglect frequency and degree for every group of different age, sex and neglect type (including physical, emotional, educational, medical, safety and social neglects). χ(2) test and analysis of variance were also used.
RESULTSThe degree of child neglect for the children aged 0 - 2 years old was 45.01 ± 7.56, the neglect frequency was 54.9% (1819/3315); the degree of child neglect for the children aged 3 - 6 years old was 44.42 ± 7.57, the neglect frequency was 53.8% (2203/4096). The neglect frequency of children aged 0, 1, 2 years old were 58.5% (654/1117), 52.2% (597/1144), 53.9% (568/1054) (P < 0.05). For children aged 3 - 6 years old, the degrees of emotional and safety neglect for males (44.60 ± 7.86, 36.82 ± 9.03) were higher than females (44.03 ± 7.72, 36.25 ± 9.05) (P < 0.05); and the frequencies of emotional and social neglect for males (16.8% (349/2072), 28.3% (586/2072)) were also higher than females (14.1% (286/2024), 24.8% (503/2024)) (P < 0.05). All children of two age groups suffered neglect mainly on one of the six neglect types (incidences were 20.6% (683/3315) and 22.7% (931/4096)). For 0-2 age groups, the higher neglect frequencies happened in the single-parent family and the remarried family (62.5% (15/24) and 63.2% (12/19)), but for children aged 3 - 6 years old groups, it happened in the single-parent family (60.0%, 27/45).
CONCLUSIONDegree and frequency of child neglect among children aged 0 to 6 years old in the rural areas of China are high, and we should find out risk factors and provide efficient prevention measures.
Child Abuse ; prevention & control ; statistics & numerical data ; Child, Preschool ; China ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Male ; Rural Population ; Surveys and Questionnaires
8.Chemical constituents from cell suspension cultures of Cudrania tricuspidata.
Yun-Ze YIN ; Rui-Shan WANG ; Ri-Dao CHEN ; Li-Rui QIAO ; Lin YANG ; Chun-Mei WANG ; Jun-Gui DAI
China Journal of Chinese Materia Medica 2012;37(24):3734-3737
Ten compounds were isolated and purified from cell suspension cultures of Cudrania tricuspidata with silica-gel column chromatography, semi-preparative HPLC and Sephadex LH-20. On the base of their physicochemical properties and spectral data, their structures were identified as 1, 3, 5-trihydroxy4-(3, 3-dimethylallyl) xanthone (1), wighteone (2), 6-prenylapigenin (3), licoflavone C(4), cudraflavanone C(5), erythrivarone A (6), derrone (7), carthamidin (8), genistein (9) and aromadendrin (10). Among them, compounds 2-10 were flavonoids, and compound 1 was a xanthone which was isolated from the plant for the first time.
Cell Culture Techniques
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methods
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Chromatography, High Pressure Liquid
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Flavanones
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isolation & purification
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Flavones
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isolation & purification
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Flavonoids
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isolation & purification
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Genistein
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isolation & purification
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Moraceae
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chemistry
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cytology
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Plant Leaves
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chemistry
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cytology
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Plants, Medicinal
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chemistry
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Xanthones
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isolation & purification
9.Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China.
Yue-Yun LAI ; Xiao-Jun HUANG ; Zhen CAI ; Xiang-Shan CAO ; Fang-Ping CHEN ; Xie-Qun CHEN ; Bao-An CHEN ; Mei-Yun FANG ; Jia-Fu FENG ; Wei-Ling FU ; Hai-Ying GUO ; Ming HOU ; Jian HOU ; Yu HU ; Xiao-Tong HU ; Xiao-Mei HU ; Li-Qiang HUANG ; Jie JIN ; Jian-Yong LI ; Juan LI ; Wei LI ; Ying-Min LIANG ; Ting LIU ; Qi-Fa LIU ; Yan-Hui LIU ; Ping MAO ; Jian OUYANG ; Lu-Gui QIU ; Lin QIU ; Chun-Kui SHAO ; Bin SHI ; Yong-Ping SONG ; Zi-Min SUN ; Qi-Shan WANG ; Chun WANG ; Jian-Ming WANG ; Yun-Shan WANG ; Zhao WANG ; Jian-Bo WU ; Yin-Xia WU ; Rui-Xiang XIA ; Yong-Quan XUE ; Bao-Zhen YANG ; Guang YANG ; Zheng-Lin YANG ; Li YU ; Zhong YUAN ; Sheng ZHANG ; Yin ZHANG ; Hong-Guo ZHAO ; Li ZHAO ; Dao-Bin ZHOU ; Shan-Hua ZOU ; Yun-Feng ZHU
Chinese Medical Journal 2012;125(15):2663-2670
BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.
METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.
RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.
CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.
Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology
10.Therapy of Duchenne muscular dystrophy with umbilical cord blood stem cell transplantation.
Cheng ZHANG ; Hui-yu FENG ; Shao-liang HUANG ; Jian-pei FANG ; Lu-lu XIAO ; Xiao-li YAO ; Chun CHEN ; Xin YE ; Yin ZENG ; Xi-lin LU ; Jian-ming WEN ; Wei-xi ZHANG ; Zhong LI ; Shan-wei FENG ; Hong-gui XU ; Ke HUANG ; Dun-hua ZHOU ; Wei CHEN ; You-mei XIE ; Jing XI ; Meng ZHANG ; Yang LI ; Ying LIU
Chinese Journal of Medical Genetics 2005;22(4):399-405
OBJECTIVETo analyze a Duchenne muscular dystrophy(DMD) patient's muscular regeneration, dystrophin expression and locomotive variation before and after he underwent umbilical cord blood stem cell transplantation in order to assess the therapeutic effect.
METHODSA 12-year-old DMD boy who could not walk for 3 years was confirmed by gene analysis and dystrophin protein immune test on his muscle. He had no other chronic disease. By HLA matching, a piece of umbilical cord blood stem cell with 6 HLA sites matching to the boy was found in Guangdong Umbilical Cord Blood Bank. The number of the nucleated cells of the umbilical cord blood stem cell was 24.08x 10(8). After pretreatment for the DMD boy with busulfan, cyclophosphamide and rabbit anti-human thymocyte globulin, the allergenic cord blood stem cells were transplanted into him by intravenous injection. Cyclosporin A, methylprednisolone, MMF, prostaglandin E1 and ganciclovir were given after the transplantation. At the same time, Gran, the granulocytic cell stimulating factor, and gamma globulin were administered. The biochemistry profile including serum creatine kinase (CK), the reconstruction of blood making, the deletion exon of DMD gene, the regenerating muscles, the dystrophin protein expression, and the locomotive function of the DMD boy were tested regularly.
RESULTS(1) The white blood cells (WBC) of peripheral blood decreased gradually to zero after pretreatment. In a period of 15 days after transplantation, the neutrophil increased to 0.5x 10(9)/L; at 25 days, WBC increased to normal level. Blood platelet was more than 20x 10(9)/L at 22 days. The hemoglobin rose to 85-100 g/L. At 140 days, sternal puncture revealed the rapid growth of neutrophil, blood platelet and hemoglobin. (2)At 140 days, the blood type of the DMD boy transformed from type O to type AB (the donor's blood type being AB). There was no grafe versus host reaction. (3) At 18, 30, 43, 55, 74 and 233 days after transplantation, the PCR-short tandem repeat test of the boy's peripheral blood DNA showed that his genotype was completely the same as the donor's. The results of PCR-short tandem repeat tests of the bone marrow cells DNA by sternal puncture at 140, 183 and 235 days were the same as those of the blood DNA. (4) At 60 days, DMD gene analysis by PCR showed that the defected DMD gene (exon 19 deletion) had been corrected by the umbilical cord stem cells transplantation. (5) At 75 days, the biopsy of calf muscle showed there were myoblast cells and muscular tubes growing. The dystrophin expressions were weak, but a few of them were strong. DNA analysis showed that the donor's gene DNA accounted for 1%-13%. At 126 days, obviously increased dystrophin positive muscular fibers of the boy were found. The donor's fibers rose to 2.5%-25%. (6) The serum CK of the boy declined from 5735 U/L to 274 U/L. (7) At 100 days, physical examination revealed improvement in his arms and legs.
CONCLUSIONThe therapy of Duchenne muscular dystrophy with allogeneic umbilical cord blood hematopoietic stem cell transplantation may reset up the blood-making function, decrease the serum CK level, restore the dystrophin in muscles, and improve the locomotive function of the DMD boy. These data suggest that the allogeneic umbilical cord blood hematopoietic stem cell transplantation may benefit the DMD boys.
Alprostadil ; therapeutic use ; Busulfan ; therapeutic use ; Child ; Combined Modality Therapy ; Cord Blood Stem Cell Transplantation ; methods ; Cyclosporine ; therapeutic use ; Dystrophin ; genetics ; Ganciclovir ; therapeutic use ; Humans ; Male ; Methylprednisolone ; therapeutic use ; Muscular Dystrophy, Duchenne ; genetics ; therapy ; Polymerase Chain Reaction ; Treatment Outcome