1.Significance of Serum Transferrin Receptors and Iron Overload in Children with Hemoglobin H Disease
hui-hong, DOU ; gui-fang, LONG
Journal of Applied Clinical Pediatrics 2006;0(15):-
Objective To measure the levels of serum transferrin receptors (sTfR) and serum ferritin (SF) in children with hemoglobin H disease for investigation the iron metabolism(sideropenic or iron overload) and to guide the proper intervention.To get a best index of judging the iron overload in HbH children by analysis of the values of sTfR and sTfR/lgSF.Methods Peripheral blood specimens were obtained from 50 cases of HbH children and 30 cases of healthy normal controls,the levels of sTfR and SF were examined by enzyme linked immunosorbent assays(ELISA).The diagnosis efficiency of sTfR and sTfR/lgSF in HbH children′s iron metabolism was judged by receiver operator cha-racteristic (ROC) curve analysis.Results The level of sTfR in HbH group was (6.74?1.02) mg?L-1,which was significantly lower than that in healthy control group[(8.09?0.67) mg?L-1](P
2.Study on the rhythm of urine iodine level of children aged 8-10 in Chongqing city
Ting, ZHANG ; Ge, LI ; Bang-zhong, XIAO ; Wen-fang, LIAO ; Xin-shu, LI ; Gui-wang, DOU
Chinese Journal of Endemiology 2010;29(3):313-315
Objective To undemtand the rhythm of urinary iodine level of children aged 8-10 in Chongqing city.Methods In April 2008,using the stratified random sampling method,we sampled 60 children aged 8-10 in a lodging primary school in Chongqing(20 per age group,half male and half female),the urine samples were collected in the morning and at 10:00,12:30,16:00,iodine in urine was detected by method of Ce and arsenic catalytic speetrophotometry(WS/T 107-2006).The difference of the urinary iodine level was compared by age,sex and time of day.Results The median urinary iodine of 60 children was 265.07μg/L on the overall.Irrespective of the stratification factors,excluding morning urinary iodine(366.75μg/L)and urinary iodine at 10:00(338.30 μg/L),the urinary iodine between 12:30(235.15μg/L)and 16:00(251.50μg/L)was not significant(all P>0.05),statistically significant differences(all P<0.05)were found between any two.The urinary iodine of 8-year-old group at different times of the day was significantly different(all P<0.05),except between morning urinary iodine (298.90 μg/L)and at 10:00,16:00(279.00,286.59 μg/L),between urinary iodine at 10:00 and 16:00(all P>0.05).The 9-year-old group's urinary iodine were not significantly different between morning urine(366.15μg/L)and 10:00(368.10 μg/L),and between 12:30(244.00 μg/L)and 16:00(186.30 μg/L,all P>0.05),significant differences were faund at other times of the day(all P<0.05).The 10-year-old group of urinary iodine changed very little before 12:30 (382.85,449.60,337.00 μg/L, all P > 0.05 ), followed by rapid decline to 16: 00 (269.35 μg/L), and compared with the morning urine and 10:00, there was significant difference(all P < 0.05).Regardless boys or girls, the urinary iodine at different times qf the day was significantly different (all P < 0.05),except between morning urinary iodine(337.32,309.28 μg/L) and at 10:00(316.15,288.27 μg/L), between urinary iodine at 12:30(251.18,211.45 μg/L) and 16:00(235.02,211.45 μg/L, all P > 0.05). Conclusions The change of urinary iodine level in children aged 8 - 10 was not obvious before noon, changes can be seen in the afternoon.Urinary iodine level before 10:00 is indicative.
3.The effects of balloon dilatation on swallowing dysfunction in patients with dysphagia
Wei-Hong QIU ; Zu-Lin DOU ; Gui-Fang WAN ; Jia-Xuan LIN ; Jie-Xin LIN ;
Chinese Journal of Physical Medicine and Rehabilitation 2003;0(12):-
Objective To study the effect of balloon dilatation therapy on dysphagia caused by cricopharyn- geal achalasia.Methods Ten cases of dysphagia were diagnosed as cricopharyngeal achalasia by videofluoroscopic swallowing study(VFSS).A 14~* urethral catheter was inserted into the esophagus and an amount of water was injec- ted into the balloon of the urethral catheter to make it turgid.Then the catheter was pulled upwards and passed through the stricture of esophagus to dilatate the cricopbarygeus muscle.Meanwhile,low frequency electrical stimula- tion was used and combined with functional training of the organs related to deglutition and ingestion.The results be- fore and after the treatment were evaluated.Results After 19.7 times of dilatation therapy,the content of water in- jected into the balloon was increased from 2.65?0.91 ml to 8.20?0.92 ml.Cricopharyngeal achalasia was alle- viated significantly(P
4.Expression of transforming growth factor β1/Smad4 signal pathway in rats with nonalcoholic fatty liver disease
Hao PAN ; Aixia DOU ; Weihua CHEN ; Kun ZHOU ; Ting CHEN ; Changqing ZHU ; Xi GUI ; Jingyuan FANG ; Mingde ZENG ; Lungen LU
Chinese Journal of Digestion 2009;29(5):317-321
Objective To investigate the expression of transforming growth factor β1,transforming growth factor beta receptor(TBR)Ⅰ,TβR Ⅱ,Smad4 and C-Jun in rats with nonalcoholic fatty liver disease(NAFLD)and to find out the mechanisms of liver fibrosis in patients with NAFLD.Methods A total of 18 male SD rats were randomly divided into normal control group(n=9)and model group(n=9).The rats in control group were fed with normal diet,and those in model group were fed with fat-rich diet(consisted of 10%lard oil+2%cholesterol).An rats were sacrificed at the 20th week.The levels of TGFβ1,TβR Ⅰ and TβR Ⅱ mRNA were examined by RT-PCR.The expressions of TGFβ1 and Smad4 in liver tissue were detected by immunohistochemistry.The expression of C-Jun protein was detected by Western blotting.Results The NAFLD model was successfully established.The immunohistochemistry examination revealed that TGFβ1 and Smad4 were expressed weekly in control group,but strongly expressed in model group.RT-PCR showed that A values of TGFβ1,TβR Ⅰ and TβR Ⅱ mRNA were 0.46±0.12,5.z4±2.70 and 3.35±1.95,respectively,in model group,which were higher than those in control group(0.21±0.09,1.36±0.77 and 0.52±0.19,all P values<0.01).The Western blotting results demonstrated that the expression of C-Jun protein in model group(0.93±0.41)was higher than that in control group (0.32±0.25,P=0.001).Conclusion TGFβ1/Smad4 signal pathway might be involved in the development of hepatic fibrosis in NAFLD.Blocking TGFβ1/Smad4 signal pathway will be helpful in treatment of NAFLD.
5.In vitro metabolism of forscolin isolated from Coleus forskohlii.
Man ZHANG ; Zhi-Yun MENG ; Xiao-Xia ZHU ; Gui-Fang DOU
Acta Pharmaceutica Sinica 2013;48(3):383-389
This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.
Animals
;
Chromatography, High Pressure Liquid
;
Coleus
;
chemistry
;
Colforsin
;
blood
;
isolation & purification
;
metabolism
;
Cytochrome P-450 CYP3A
;
metabolism
;
Dogs
;
Humans
;
Macaca
;
Metabolic Clearance Rate
;
Microsomes, Liver
;
metabolism
;
Plants, Medicinal
;
chemistry
;
Rats
;
Tandem Mass Spectrometry
6.Recent advances in research on granulocyte colony-stimulating factor--review.
Jing-Min YU ; Zhi-Yun MENG ; Gui-Fang DOU
Journal of Experimental Hematology 2008;16(2):452-456
Granulocyte colony-stimulating factor (G-CSF) is a kind of hematopoietic growth factor which is produced by monocytes, fibroblasts and endothelial cells. G-CSF acts on neutrophilic progenitor cells by binding to specific cell surface receptors, thereby stimulates proliferation, differentiation, commitment, and selected end-cell functional activation including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing and the increased expression of some functions associated with cell surface antigens. G-CSF is effective and safe for treatment of neutropenia. In this paper, structure of G-CSF and its mechanism, recent status of research on G-CSF, pharmacokinetics, clinical application, adverse effects and prospect of G-CSF are mainly reviewed.
Granulocyte Colony-Stimulating Factor
;
pharmacokinetics
;
pharmacology
;
therapeutic use
;
Hematopoiesis
;
drug effects
;
Humans
7.Rapid pharmacokinetics screening of drug candidates in vitro and in vivo.
Xiao-na DONG ; Xiao-xia ZHU ; Zhi-yun MENG ; Jiang-lin LIU ; Ying-lin CAO ; Gui-fang DOU
Acta Pharmaceutica Sinica 2009;44(11):1309-1312
The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.
Animals
;
Chromatography, Liquid
;
methods
;
Drug Evaluation, Preclinical
;
methods
;
Female
;
High-Throughput Screening Assays
;
methods
;
Male
;
Microsomes, Liver
;
metabolism
;
Pharmaceutical Preparations
;
administration & dosage
;
blood
;
metabolism
;
Pharmacokinetics
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Spectrometry, Mass, Electrospray Ionization
;
methods
8.Metabolism, Distribution and Excretion of Recombinant Human Thrombopoietin in Mice
Xiu-Wen LIU ; Zhong-Ming TANG ; Hai-Feng SONG ; Gui-Fang DOU
Journal of Experimental Hematology 2001;9(4):318-322
The metabolism, distribution and excretion profiles of recombinant human thrombopoietin (rhTPO) in mice were studied by means of (125)I-labeled rhTPO ((125)I-rhTPO) combined with size exclusive high performance liquid chromatography (SHPLC) or trichloroacetic acid (TCA) precipitation analysis. (125)I-rhTPO was prepared by iodogen method. Purification was performed on Sephacryl S-200 HR gel. Radioactive-purity of (125)I-rhTPO identified by SHPLC was (96.9 +/- 1.5)% (n = 3). The proliferation effect of TPO dependent cell line (TD-3) and the increase of peripheral platelet counts in mouse by (125)I-rhTPO demonstrated that (125)I-labeled protein maintained the biological activities of TPO both in vitro and in vivo. SHPLC analysis of serum and urine samples taken after sc 1 micro g/mouse (345 kBq/mouse) of (125)I-rhTPO revealed that there were two lower molecular weight (125)I-degradation metabolites ((125)I-MI and (125)I-MII) other than parent molecule. (125)I-MI was mainly found in urine, and (125)I-MII was detected both in serum and in urine. The maximal concentration of (125)I-rhTPO was reached at 2 hours after injection. The terminal half-life was 10.8 hours, which was much longer than those of other peptides. TCA precipitable radioactivity in tissue showed that the radioactivity in bone marrow was rather high. The highest level was found in urinary system. Levels in adrenals, lymph nodes, and fat were near to that in serum. Lowest was found in brain. The main excretion route was urinary system and (98 +/- 5.6)% of (125)I-rhTPO was excreted within 72 hours after dosing.
9.LC-MSn analysis of metabolites of 1,2-bis (1,2-benzisoselenazolone-3(2H)-ketone)-ethane, a novel anti-cancer agent in rat.
Hai-Yan ZHOU ; Zhi-Yun MENG ; Gui-Fang DOU ; Jin-Lan MA ; Ya-Qing LOU ; Guo-Liang ZHANG
Acta Pharmaceutica Sinica 2010;45(5):627-631
This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.
Administration, Oral
;
Animals
;
Antineoplastic Agents
;
administration & dosage
;
blood
;
metabolism
;
urine
;
Bile
;
metabolism
;
Bridged Bicyclo Compounds, Heterocyclic
;
administration & dosage
;
blood
;
metabolism
;
urine
;
Chromatography, Liquid
;
Feces
;
chemistry
;
Male
;
Organoselenium Compounds
;
administration & dosage
;
blood
;
metabolism
;
urine
;
Rats
;
Rats, Sprague-Dawley
;
Spectrometry, Mass, Electrospray Ionization
10.Lidamycin metabolism in vitro.
Yan-qing WEN ; Zhi-yun MENG ; Shu-zhen CHEN ; Xiao-xia ZHU ; Gui-fang DOU
Acta Pharmaceutica Sinica 2011;46(9):1132-1136
This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.
Aminoglycosides
;
blood
;
metabolism
;
Animals
;
Antibiotics, Antineoplastic
;
blood
;
metabolism
;
Chromatography, High Pressure Liquid
;
Cytochrome P-450 CYP1A2
;
metabolism
;
Cytochrome P-450 Enzyme System
;
metabolism
;
Dogs
;
Enediynes
;
blood
;
metabolism
;
Enzyme Activation
;
Humans
;
Macaca
;
Microsomes, Liver
;
metabolism
;
Rats
;
Tandem Mass Spectrometry