1.Bone marrow mesenchymal stem cells suppress E coli-induced bacterial prostatitis in rats.
Guang-wei HAN ; Cheng-cheng LIU ; Wen-hong GAO ; Dong CUI ; Shan-hong YI
National Journal of Andrology 2015;21(4):294-299
OBJECTIVETo investigate the inhibitory effect of bone marrow mesenchymal stem cells (BMSCs) on E coliinduced prostatitis in rats.
METHODSBMSCs were isolated, cultured and amplified by the attached choice method. Fifty SD rats were randomized into five groups of equal number: normal control, acute bacterial prostatitis (ABP) , chronic bacterial prostatitis (CBP), ABP + BMSCs, and CBP + BMSCs, and the animals in the latter four groups were injected with E. coli into both sides of the prostate under ultrasound guidance for 1 - 14 days to induce ABP and for 4 - 12 weeks to induce CBP. The control rats were injected with the same amount of PBS. Two weeks after injection of BMSCs into the prostates, pathomorphological changes in the prostate were observed under the light microscope and the mRNA and protein levels of IL-1β and TNF-α determined by RT-PCR and ELISA, respectively, followed by statistical analysis with SPSS 18.0.
RESULTSHistopathological evaluation showed typical pathological inflammatory changes in the prostates of the rats in the ABP and CBP groups, including glandular structural changes, interstitial edema, inflammatory cell infiltration, and fibrous hyperplasia, which were all remarkably relieved after treated with BMSCs. The mRNA and protein levels of IL-β ([0.829 ± 0.121] and [271.75 ± 90.59] pg/ml) and TNF-α ([0.913 ± 0. 094] and [105.78 ± 19. 05] pg/ml) in the ABP and those of IL-1β ([0. 975 ± 0. 114] and [265. 31 ± 71. 34] pg/ml) and TNF-α ([0. 886 ± 0. 084] and [107. 45 ± 26. 11 ] pg/ml) in the CBP groups were significantly higher than those in the control rats ([0. 342 ± 0.087] and [45.76 17. 99] pg/ml, P <0. 05); ([0.247 ± 0.054] and ([19.42 ± 7. 75] pg/ml, P <0. 01) as well as than those in the ABP + BMSCs ([0. 433 ± 0. 072] and [51. 34 ± 22. 13] pg/ml, P < 0. 05 ) ; ( [0. 313 ± 0. 076] and [28. 38 ± 8. 78] pg/ml, P < 0. 01) and the CBP + BMSCs group ([0.396 ± 0.064] and [56.37 ± 21.22] pg/ml, P <0.05); ([0.417 ± 0.068] and [29.21 ± 10.22] pg/ml, P <0.01).
CONCLUSIONInjection of BMSCs can reduce E coli-induced prostatic inflammation reaction, which.may be associated with its reduction of inflammatory cell infiltration and the expressions of IL-1β and TNF-α in the prostate tissue.
Acute Disease ; Animals ; Bone Marrow Cells ; physiology ; Chronic Disease ; Escherichia coli Infections ; therapy ; Humans ; Interleukin-1beta ; genetics ; Male ; Mesenchymal Stromal Cells ; physiology ; Prostate ; metabolism ; Prostatitis ; metabolism ; microbiology ; therapy ; RNA, Messenger ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; metabolism
2.CT-guided percutaneous biopsy for transplanted liver
Bin GAO ; Ke-Wu HE ; Xiu-Shan ZHANG ; Gang WEN ; Hui-Min CHAO ; Yong-Cui HUANG ;
Journal of Interventional Radiology 2006;0(12):-
Objective To study the technique and clinical significance of percutaneous biopsy of transplanted liver guided by CT.Methods 19 transplanted liver were undergone 25 times of percutaneous biopsy and the pathomorphologic changes were demonstrated by HE staining.Results The successful rate of the percutaneous biopsy was 100% for all the 25 times of this procedure,including acute rejection on 9 episodes,preservation perfusion retrauma in 6,bile duct strictures in 4,drug-induced injury in 4,chronic rejection in 1 and acute hepatic necrosis in 1.Conclusions CT-guided percutaneous biopsy is an important method for diagnosing transplanted liver injury and providing great value for distinguishment of the causes for transplanted liver injury.(J Intervent Radiol,2007,16:855-857)
3.Efficacy and feasibility of radiofrequency ablation for decompensated cirrhotic patients with hepatocellular carcinoma.
Jin-yu WU ; Wei YANG ; Ming CUI ; Shan-shan YIN ; Wen GAO ; Wei WU ; Kun YAN ; Min-hua CHEN
Chinese Medical Journal 2010;123(15):1967-1972
BACKGROUNDMost HCC patients with decompensation of liver function lost the chance of surgical and/or interventional treatment. The aim of this study was to evaluate feasibility and outcome of radiofrequency ablation (RFA) in treating hepatocellular carcinoma (HCC) patients with poor liver function (Child-Pugh class C), who are not suitable for surgery or hepatic artery chemo-embolization.
METHODSThirteen HCC patients (the number of tumors was 17) with liver function of Child-Pugh C (scores: 10.2 +/- 0.4) were included in the study. Among the patients, 8 were male and 5 were female with the average age of (61.6 +/- 10.9) years old. The average size of HCC was (3.8 +/- 1.0) cm. Two patients were recurrent HCC and 30.8% of the patients had multiple tumors (2 - 3 tumors). All the patients were treated with RFA.
RESULTSThere were 22 RFA sessions (1 - 4 sessions per patient) in all, average ablations per tumor at first session was 3.1. One week after RFA, the liver enzymes elevated in 9 patients (69.2%), in 7 of them, the liver enzyme returned to pre-RFA level in 1 - 3 months. One month after RFA, the Child-Pugh grading was 10.3 +/- 0.8 (Child-Pugh C), while that of pre-RFA was 10.2 +/- 0.4 (Child-Pugh C), with no significant difference. Computer tomography (CT) one month after RFA showed that the tumor necrosis rate was 88.2% (15/17). Five patients had 2 - 4 repeated RFA due to HCC recurrence. During the follow-up of 2- 69 months in this group, survival rate of one year was 53.8%, two years was 30.8%, and three year was 15.4%. The incidence of RFA-related complications was 13.6% (3/22 sessions), including 1 case of GI hemorrhage and 1 sub-capsular hemorrhage of the liver. One patient with HCC over 5 cm who had fever and liver abscess after RFA, and was dead 2 months later due to liver function failure.
CONCLUSIONSMinimal invasive RFA provides possible treatment modality for HCC patients with poor liver function, who are not candidates for surgical and/or interventional therapy. For large HCC, due to the required extended treatment region, special attention should be paid to the possibility of acute liver failure.
Adult ; Aged ; Carcinoma, Hepatocellular ; therapy ; Catheter Ablation ; methods ; Female ; Humans ; Liver Cirrhosis ; therapy ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Treatment Outcome
4.Effect of extracted ZG from gardenia on Hep-2 cell membrane post infected with parainfluenza virus type 1 (PIV-1).
Shan-Shan GUO ; Yang HUANG ; Ye ZHAO ; Ying-Jie GAO ; Wen-Feng GONG ; Xiao-Lan CUI
Chinese Journal of Virology 2007;23(5):384-388
In order to study the anti-viral mechanism of extracted ZG from Gardenia, the effect of extracted ZG on Hep-2 cell membrane potential, Na -K+-ATPase activity and membrane fluidity post infected with parainfluenza virus type 1 (PIV-1) was observed. Acetylcholine which was fluorescent labeled with DiBAC4 (3) was taken as positive control to observe the changes of membrane potential and was measured by flow cytometer. The phosphorus determination method and spectrophotometer were used to measure the Na+-K+-ATPase activity of Hep-2 cell membrane post PIV-1 infection. Hep-2 cell membrane phospholipids was labeled with fluorescent NBD-C6-HPC and membrane fluidity was measured by confocal laser scanning microscope. The results demonstated that after PIV-1 infection the Hep-2 cell membrane potential decreased significantly and the membrane was in the state of hyperpolarization, Na+-K+-ATPase activity increased and membrane fluidity decreased significantly. There was no apparent interferring effect of extracted ZG on the changes of membrane potential and Na+-K+-ATPase activity post PIV-1 infection, while membrane fluidity was improved significantly. Acetylcholine improved the state of hyperpolarization. The changes of membrane potential, Na -K+-ATPase activity and membrane fluidity might be the biomechanism of PIV-1 infectoin. The extracted ZG improved membrane fluidity to prevent from PIV-1 infection by protecting the cell membrane, which was probably the mechanism of anti-PIV-1 activity of the extracted ZG, but ZG probably had nothing to do with membrane potential and Na+-K+-ATPase activity.
Acetylcholine
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pharmacology
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Antiviral Agents
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pharmacology
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Cell Line, Tumor
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Cell Membrane
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drug effects
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Gardenia
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chemistry
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Humans
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Membrane Fluidity
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drug effects
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Membrane Potentials
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drug effects
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Parainfluenza Virus 1, Human
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drug effects
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Plant Extracts
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pharmacology
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Sodium-Potassium-Exchanging ATPase
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metabolism
5.A novel dipeptidyl peptidase IV inhibitors developed through scaffold hopping and drug splicing strategy.
Shan-Chun WANG ; Li-Li ZENG ; Yu-Yang DING ; Shao-Gao ZENG ; Hong-Rui SONG ; Wen-Hui HU ; Hui XIE
Acta Pharmaceutica Sinica 2014;49(1):61-67
Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.
Dipeptidyl-Peptidase IV Inhibitors
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chemical synthesis
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chemistry
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Drug Design
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Drug Discovery
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methods
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Humans
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Hypoglycemic Agents
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chemical synthesis
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chemistry
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Linagliptin
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chemical synthesis
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chemistry
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Molecular Structure
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Piperidines
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chemical synthesis
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chemistry
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Structure-Activity Relationship
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Uracil
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analogs & derivatives
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chemical synthesis
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chemistry
6.Clinical effectiveness and safety of domestic 125I plaque irradiation for experimental choroidal melanoma
Jin-qiong, ZHOU ; Wen-bin, WEI ; Bin, LI ; Wen-li, YANG ; Fei, GAO ; Liao-qing, LI ; Cheng-xun, YANG ; Shan-yu, CAI
Chinese Journal of Experimental Ophthalmology 2012;30(8):692-698
Background Choroidal melanoma (CM)is the most common primary intraocular tumor,and brachytherapy is one of the most common therapeutic modality in the treatment of the tumor.However,this irradiation approach has not been evaluated in China. Objective The present study was to analyze the effectiveness and safety of domestic 125I plaque irradiation in the treatment of CM. Methods Forty New Zealand albino rabbits were randomized into 5 groups with 8 rabbits 8 eyes (right eyes) in each group.CM models were established in 16 of 40 New Zealand albino rabbits by implanting the rat B16F10 melanoma cell fragments into the suprachoroidal space of right eyes.After 3 weeks,domestic 125I plaque was fixed at the location of CM in the irradiation group 1,and 8 rabbits with CM served as model control group.The clinical effectiveness of 125I plaque for CM was evaluated based on the fundus examination with indirect ophthalmoscopy,B scan ultrasonography,fundus photographs and color Dopplerimaging.Regarding the safety study,domestic 125I plaque was fixed on the normal right cycs of normal rabbits,while the plaques without 125I seeds were used as the sham group.No intervene was performed in the rabbits of blank group.The number of CD4+,CD8+ T cells in peripheral blood was detected by flow cytometry before plaques implanted and on 3,7,15 and 30 days after the plaque was removed.The animals were sacrificed and the eyes were obtained for histology examination.The use of the experimental animals complied with Statement of ARVO. Results After implantation of B16F10 melanoma cell fragments,CM grew steadily and rapidly with the similar size between irradiation group 1 and model control group ( P =0.550).One week after administration of the treatment,tumor size was(0.31±0.07 )cm in irradiation group 1 and (0.85±0.18 )em in the model control group,with the significant difference between them( P=0.001 ).Two week after application of 125I plaque,the size of tumor was smaller than that before irradiation (P=0.007 ).Histologically,the tumors were mostly limited beneath the pigment epithelial layer with less neovascularization,fibrosis in the tumor was found in some area in the irradiation group when compared with model control group.No significant differences were found in the proportions of CD4+,CD8+ T cells and CD4+/CD8+ at different time points in the irradiation groups of normal eyes and sham group (Fgroup =0.770,8.110,2.230; P=0.380,0.060,0.140; Ftime =0.770,3.220,4.230; P =0.550,0.170,0.004 ).Chronic inflammatory cells infiltration cornea,subconjunctival epithelial and selera surface,but sclera had no necrosis and organization.Conclusions These results suggest that domestic 125I plaque irradiation is effective for the treatment of CM,and has limited side effects on normal rabbits.
7.Characterization and identification of alkaloids in Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex based on UHPLC-IM-Q-TOF-MS.
Shan-Shan WEN ; Ping LI ; Wen GAO
China Journal of Chinese Materia Medica 2023;48(12):3294-3307
A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.
Chromatography, High Pressure Liquid
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Algorithms
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Alkaloids
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Isoquinolines
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Quinolines
8.Advances in metabolic reprogramming in heart failure
Lei HUANG ; Wen-Wen LI ; Pei-Wen WENG ; Shan GAO
Chinese Pharmacological Bulletin 2024;40(8):1418-1423
Adenosine triphosphate(ATP)production in cardio-myocytes in healthy heart depends primarily on the oxidative phosphorylation of fatty acids and,to a lesser extent,on the oxi-dation or glycolysis of glucose.Patients with heart failure devel-op severe disturbances in energy metabolism,including disturb-ances in substrate uptake and utilization,oxidative phosphoryla-tion,and ATP shuttling,resulting in inadequate cardiac energy supply.By intervening in energy metabolism pathways,cardiac efficiency can be increased,energy production deficits can be reduced,and cardiac function can be improved in patients with heart failure.We hence have reviewed and outlined the mecha-nisms and therapeutic implications of metabolic changes during heart failure.
9.Relevant low toxicities with rhG-CSF mobilized and cryopreserved autologous peripheral blood stem cell return infusions in children.
Jian-Wen WANG ; Suo-Qin TANG ; Shan-Gen LÜ ; Chong-Rong RAN ; Guang YANG ; Ying LIU ; Xiao-Ning GAO
Journal of Experimental Hematology 2007;15(2):404-407
The purpose of this study was to evaluate the safety of cryopreserved and thawed peripheral blood stem cell (PBSC) fractionated return infusions in children. 35 children patients with malignant tumors (13 acute leukaemias, 15 neuroblastomas and 7 malignant lymphomas) received fractionated return infusions of cryopreserved stem cells after undergoing high-dose chemotherapy without or with total body irradiation. The toxicities of 70 return infusions were evaluated. All patients were mobilized by chemotherapy plus recombination human granulocyte colony-stimulating factor (rhG-CSF), and then PBSCs were collected by a separator CS-3000 plus or COBE spectra-4. The grafts were cryopreserved in 10% dimethyl sulfoxide (DMSD) and stored in liquid nitrogen. There were totally 70 PBSC transfusions. The total volume of PBSCs transfused: 190 - 420 ml (265 +/- 73 ml or 13.7 +/- 4.2 ml/kg) with a mean of (4.43 +/- 1.91) x 10(8)/kg of PBSCs, and 0.94 +/- 0.18 g/kg of DMSO. The single dose: 90 - 300 ml (132 +/- 37 ml or 6.6 +/- 5.2 ml/kg) with a mean of 0.68 +/- 0.12 g/kg of DMSO. Symptoms occurring during the infusions were recorded. All patients were monitored for 24 hours after infusion. Pulse, blood pressure, body temperature, and respiratory rate were recorded every 15 minutes. At four hours before and 8 hours after infusion, urinalysis was performed. Serum potassium, sodium, creatinine, total bilirubin, aspartate amino transferase (AST), and alanine amino transferase (ALT) levels were examined within 24 hours before and after the first infusion. The results showed that the toxicities observed included hemoglobinuria in 54 return infusions (77.1%), headache in 28 (40.0%), nausea in 24 (34.3%), vomiting in 17 (24.3%), and abdominal pain in 8 (11.4%). Patients who received a graft > 200 ml tended to have a higher frequency of hemoglobinuria, headache, nausea, vomiting, or abdominal pain (P<0.01), and they disappeared quickly, too. Total bilirubin increased after the first return infusion (P<0.01), and there was a significant correlation between the volume of infusion and the degree of total bilirubin increase (r=0.8977, P<0.01). No renal failure or shock occurred. It is concluded that transient hemoglobinuria, headache, nausea, vomiting, and abdominal pain are common toxicities associated with PBSC autograft, and these toxicities are related with a single volume of PBSCs transfused. Total bilirubin increase is correlated with the volume of infusion. In a word, the toxicity is less frequent and lower severe in children with fractionated infusions of cryopreserved peripheral blood stem cell.
Acute Disease
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Adolescent
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Child
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Child, Preschool
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Cryopreservation
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Female
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Granulocyte Colony-Stimulating Factor
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therapeutic use
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Headache
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etiology
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Hematopoietic Stem Cell Mobilization
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methods
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Hemoglobinuria
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etiology
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Humans
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Leukemia
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therapy
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Lymphoma
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therapy
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Male
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Nausea
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etiology
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Neoplasms
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therapy
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Neuroblastoma
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therapy
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Peripheral Blood Stem Cell Transplantation
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adverse effects
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methods
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Recombinant Proteins
10.Effects of chronic cadmium loading on the testis and endocrine function of reproduction in male rats.
Long CHEN ; Wen-Hua REN ; Shan-Liang ZHU ; Wei GAO ; Juan ZHOU ; Ying-Zi JIANG ; Yu GU
Acta Physiologica Sinica 2002;54(3):258-262
Sixty healthy Sprague-Dawley male rats were used and divided randomly into control group (group C), cadmium loading group with medium dose (group M) and cadmium loading group with high dose (group H). Groups C, M and H were orally dosed daily with 0, 5 and 10 mg/kg of cadmium for over 6 weeks. Effects of cadmium loading on testis and endocrine function of reproduction in male rats were studied. The results showed that the zinc content decreased slightly in testis and plasma, and the cadmium concentration increased significantly in the testis of groups M and H; while the plasma levels of cadmium and zinc had no obvious difference as compared with those of group C; daily sperm production in the testis of group H decreased markedly during week 3 of cadmium loading, and was significantly lower in groups M and H as compared to that in group C during week 6; alkaline phosphatase (ALP) in group H and lactate dehydrogenase-X (LDH-X) in groups M and H were markedly lower compared to those of group C; plasma testosterone (T) level in both cadmium loading groups decreased and was low or significantly lower than that in group C; follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels had no apparent difference between the three groups. It is suggested that the gradual accumulation of cadmium in testis tissue induced by chronic cadmium loading results in changes in some enzyme activity, a decrease in sperm production, and defect of endocrine function activity in the testis.
Alkaline Phosphatase
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drug effects
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Animals
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Cadmium
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blood
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Cadmium Chloride
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administration & dosage
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toxicity
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Follicle Stimulating Hormone
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blood
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Isoenzymes
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drug effects
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L-Lactate Dehydrogenase
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drug effects
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Luteinizing Hormone
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blood
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Male
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Reproduction
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drug effects
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Spermatogenesis
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drug effects
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Testis
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enzymology
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pathology
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Testosterone
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blood