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BACKGROUND:The clinical manifestation of acute radiation skin injury is recurrent necrotic ulcers,and its pathogenesis is still not fully understood.The establishment of a suitable animal model will have important clinical implications for the study of its pathogenesis,prevention and treatment. OBJECTIVE:To establish a model of acute β-ray radiation skin injury and to investigate the mechanism of injury. METHODS:Sixty-nine Sprague-Dawley rats were randomly divided into 30,45,60 Gy 32P-β-ray groups(n=21 per group)and control group(n=6).A single local irradiation of the back of the rats was performed using 32P radionuclide.The control group was operated in the same way as the irradiated groups except that it was not irradiated.The body mass and skin appearance of the rats were measured at 7,15,30,45,and 60 days after irradiation.Three rats from each group were selected at each observation time point.The skin injury was observed by hematoxylin-eosin staining,Masson staining,transmission electron microscopy,and TUNEL assay.P53,Bcl-2 and Bax protein levels in the skin were measured by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION:There was no accidental death after irradiation,and the body mass of rats showed a gradual increase.The rats showed different degrees of epidermal necrosis,inflammatory cell infiltration,reduction of hair follicles and appendages,and collagen fibrillation,which were evident at 60 and 45 Gy.The levels of serum inflammatory factors,interleukin-6 and tumor necrosis factor-α,were significantly increased in a dose-dependent manner.Under the electron microscope,there are varying degrees of mitochondrial reduction,vacuolization and nuclear pyknosis in the cells.The degree of cell apoptosis showed a certain dose-dependence.Immunohistochemistry and western blot results showed an increase in the expression of P53 and Bax proteins and a decrease in the expression of Bcl-2 protein in the skin after irradiation.There were significant differences between the 60 Gy group and the 45 Gy and 30 Gy groups(P＜0.05).To conclude,irradiation with 60 Gy and 45 Gy 32P radionuclide on the back of rats could successfully establish a practically pre-clinical animal model,and the mechanism is related to the up-regulation of P53 and Bax and the down-regulation of Bcl-2.This model can provide a reference for the establishment of animal models for the study of the mechanism of radiation skin injury and its prevention and treatment.
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Objective To establish a benign esophageal stricture model and observe the effect of 32P radioactive isotopes on benign esophageal stricture scarring with intracavitary irradiation so as to provide experimental evidence for inhibiting scar hyperplasia and preventing esophageal restenosis after endoscopic dilation for benign esophageal stricture.Methods Benign esophageal stricture models were established in 18 healthy adult rabbits by annular incision and anastomosis.Then the rabbits were randomly divided into control group,hormone group and irradiation group,with six rabbits in each group.On day 2 after surgery,we measured inner diameter of the anastomotic stoma;then the control group received saline intervention,the hormone group was given dexamethasone,and the irradiation group was given 32P radioactive isotopes.The rabbits were observed for two weeks for their general condition and weight.After the intervention,we measured inner diameter of the anastomotic stoma.Liver functions (ALT and AST) were tested again before modeling and after intervention.Then the rabbits were put to death and had tissue in the esophageal stricture area removed for pathological examination and esophageal HE staining.We determined hydroxyproline (HYP) content of esophageal tissue around the anastomotic stoma.Restlts Benign esophageal stricture model was established successfully.After 2 weeks,the rabbits' appetite was obviously diminished in control group and relatively poor in hormone group;obviously improved in irradiation group.The rabbits' weight increased in radiation group compared with the other two groups (P＜0.05).The esophageal inner diameter in irradiation group widened obviously compared with the other two groups (P ＜ 0.05).In irradiation group,the number of fibroblasts decreased obviously,collagen fiber and granulation tissue were not obvious;HYP content was lower than that in the other two groups,and was close to that in a normal esophagus (P＞0.05).ALT and AST did not differ before and after intervention in all groups (P＞0.05).Conclusion ① We can establish benign esophageal stricture model successfully through the surgery.② 32Pradioactive isotopes radiation therapy can be used to prevent early scar formation in esophageal benign stricture,and is superior to dexamethasone therapy.
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Objective To investigate the value of single photon emission computed tomography (CT) imaging and transmis‐sion CT imaging (microSPECT‐CT ) bremsstrahlung imaging for the solid tumor mesenchymal implantaion of 32 P‐chromic phos‐phate‐paclitaxel‐poly‐L‐lactic acid (32 P‐CP‐PSP‐PLLA) sustained release seeds and to investigate the 32 P in vivo biodistribution and degradation sustained release churacteristics .Methods The animal model of prostate cancer subcutaneously transplanted tumor was established .32 P‐CP‐PSP‐PLLA sustained‐release seeds were intratumorally implanted by the mediation of microSPECT‐CT brems‐strahlung imaging and the 32 P distribution in bearing tumor mouse was verified by the imaging and biological distrubtion tests .The ultrastructural changes of 32 P seeds were observed by the scanning electron microscope .Results The MicroSPECT/CT brems‐strahlung imaging could effectively guide the intratumoral implantation operation of the 32 P sustained‐release seeds with clear visu‐alization .Partial sustained‐release 32 P was remained in the tumor tissues with little distribution in important organs of spleen and liver ,which was proved by the biodistribution results .The particle surface and inside micropores and tunnels formation ,their pro‐gressive increase ,fusion and connection were found by the electronic microscope after the 32 P sustained‐release seeds intratumoral implantation .Conclusion The MicroSPECT/CT bremsstrahlung imaging can effectively monitor the 32 P sustained‐release seeds and their in vivo biodistribution and lays a foundation for the sustained‐release seeds prostatic targeted implantation .
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Objective To study the therapeutic and toxic effects of 32 P-chromic phosphate-poly (L-lactic) acid (32p-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma.Methods Twenty four nude mice bearing tumors were injected with 0,9.3,18.5 and 37.0 M Bq 32p-CP-PLLA microparticle,respectively.The relative tumor growth rates were observed every day,and white blood cells,platelets and body weight were measured.At 14 d after administration,the tumors were removed,histological examination and immunohistochemical analysis were performed.Results The relative tumor growth rates of each treatment group was lower than 40％.Histological examination showed the degenerative necrosis at the site nearby the mircoparticle.Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast,the expression of bax in treated group were higher than those in control group.The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43,0.47 ± 0.13,1.10 ± 0.32,2.19 ± 0.57 for 0,9.3,18.5 and 37.0 MBq 32 P-CP-PLLA microparticle,respectively ( t =2.36 - 2.77,P ＜ 0.05).MVD were 31.2 ± 2.3,23.8 ± 1.5,14.8 ±0.8,11.0 ± 1.2,respectively.Dose dependence was observed in both HE and IHC staining after 14 d treatment ( t =2.30 - 2.57,P ＜ 0.05 ).Conclusions Intratumoral injection of 32p-CP-PLLA microparticle might be a safe,easy and effective radionuclide interventional therapy for pancreatic carcinoma.
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Objective To evaluate the therapeutic effect of 32P application and interventional therapy in skin hemangioma, and to sum up the role of nursing in the process of the treatment. Methods 734 cases of skin hemangiorna were involved in the study. Personalized treatment strategy and nursing measures were implemented according to different kinds of skin hernangioma, 32p application device was made with the dose of 1 Gy per square centimeter every day, and the total dose of interventional therapy was from 6.8μCi to 10.0μCi per square centimeter according to the site of lesions and the patients' age. The treatment interva] was about one and a haft month or two months. The specific nursing measures were as follows: effective communication should be undertaken to remove the concerns of patients before therapy. Meanwhile, the lesions should be taken a picture by a digital camera before and after therapy. Thus, the effect could be evaluated objectively. In addition, the follow-up by telephone also was done in the study. Results the cure rate and the effective rate of 32P in the treatment of skin hemangioma were 78.88% and 94.14% respectively.The treatment effect was the best in hemangioma simplex among different kinds of skin hemangioma. The treatment effect had a negative correlation with the age of the patients. Selective nursing reduced incidence of complication. Conclusions There's a satisfactory effect of 32p application and interventional therapy in the treatment of skin hemangioma. Meanwhile, nursing plays an important role in the treatment.
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Objective To explore the toxicity and safety of 32P-CP-PLLA seeds interstitial implantation. Methods 30 beagle dogs were randomly divided into 10 groups according to different drugs (32P-CP-PLLA and 32P-CP),different doses (185, 370 and 740 MBq) and different sites (gluteus and liver). At different time-points after surgery, the weights of dogs were measured. The blood routine and blood biochemical indexes,PC Ⅲ ,HA,CG,PCⅣ and LN were examined. ECT imaging was performed and histology was observed dynamically. Blood, urine and faeces were measured continuously for 12 weeks and 30 days, respectively. Results ECT imaging demonstrated in seed groups and 32P-CP muscle groups radioactivity concentrated continuously in the area of implantation, without liver imaging. 471.67 MBq/m2 of 32 P-CP was injected in liver,while the absorbed dose was 31 Gy,without significant liver damage. When the dose was 794. 28 MBq/m2 , the absorbed dose was 56 Gy,with strong liver and systemic toxicity. But implanting seeds at the same or higher dose, the absorbed dose was 89.83-178.68 Gy in the area of implantation, and the rest liver was 1.09-2. 18 Gy,without liver damage. Dogs in liver group died at 23, 29 and 45 d, respectively, and the inspections of liver fibrosis were higher than the means of the other groups.Blood routine and blood biochemistry indexes between the other groups showed no significant differences.Effective half-life of 32P-CP-PLLA was 11.78 d, while that of 32P-CP was 6. 82 d in liver, and 8. 73 d in gluteus. Mild to moderate injury were found in liver group at 4 weeks. Moderate to serious injury were found. Liver cell necrosis and proliferation were found at 4-6 weeks in other liver groups. In muscle groups,only cellular edema was found in muscle groups at 2 week. The radioactivity count rate in blood for seed groups showed slowly jagged decreasing over time, and decreased exponentially for 32PCP groups. The radioactivity count rate in urine and faeces were multi-peak descending in seed groups. Conclusions 32P-CP-PLLA seeds have the advantages of suitable target location, degradable, non-migration and easy to protection, and it could be used in treatment for different blood supply types of solid tumors. Liver of beagle dog could endure the dose from 32 P-CP-PLLA seed twice as 32P-CP lethal dose.
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Objective To explore the possibility and safety of ~(32)P-colloidal chromic phosphate interstitial injection.Methods Ten Beagle dogs were randomly divided into 5 groups (n ＝ 2) according to different doses (185 and 370 MBq) ,different sites (gluteus maximus and liver) and cold colloid as a control group.At different time-points after surgery,the weights of dogs were measured,and the blood and blood biochemical inspections were examined.ECT imaging was performed and histomorphology was observed dynamically.The radioactive counts of body surface for 90 days,blood for 12 weeks and urine and feces for 30 days were measured continuously.Measured data were expressed by mean ±standard error ((x) ±s) and SPSS 13.0 software was used for statistical analysis.Results ECT imaging demonstrated that the whole liver imaging was obtained although the radioactive distribution was uneven in liver groups,and the radioactivity concentrated continuously in the area of injection,but no liver imaging in muscle groups.Dogs in group 4 lost weight progressively and reduced by 2.7 kg till 45 d after operation.While the mean weight increments in the other groups were 3.0,1.6,0.8 and 3.1 kg in order.In group 4,PLT and RBC reduced obviously.Dogs died at 23 or 45 d.AST and ALT were elevated sharply before death.In the other groups,blood and blood biochemistry inspection showed there were no significant statistical differences.The highest radioactive counts after operation were obtained from the injection spot,while the urinary bladder and the spleen were followed.The peak of blood cpm in liver groups presented at 5 min.Peak values were 0.5 × 10~7/min and 1.0 × 10~7/min,respectively.The blood cpm in the muscle groups was always maintained at 3 × l0~5/min.Histology study showed the hyperemia dropsy changes in muscle groups and 185 MBq liver group in 4 weeks,while after 8 weeks the organizational structure restored normally.There were partial liver cells necrosis in 4 weeks,and the massive liver cells balloon type changes in 6 weeks,as well as obvious hyperemia dropsy and the hepatic lobe structure unclear in 370 MBq liver group.For the radioactive counts of urine and excrement,the peak appeared at 13 and 12 d respectively,and the peak values were (42.0 ±3.3) × 10~4 and (29.6 ±4.5) ×10~4 /min in muscle groups,respectively ;while the peak appeared at 5 and 9 d,respectively and the peak values were (49.0 ± 10.2) × 10~4 and (28.5 ± 7.1) × 10~4 /min in liver groups,respectively.Cumulative excretion ratios in urine and excrement were 36.58% and 10.62% in muscle groups,respectively and 23.48% and 8.76% in liver groups till 30 d,respectively.The liver absorbed doses were 30.6 and 55.6 Gy in liver groups,while those were 2.3 and 6.5 Gy in muscle groups.The maximus absorbed doses of gluteus were 53.4 and 98.1 Gy in muscle groups.Conclusions When ~(32)P- colloidal chromic phosphate of 794.39 MBq/m~2 was injected into the liver of Beagle,the liver absorbed dose was 56 Gy,which could be lethal dose for its strong liver toxicity and systemic side effects.Injection of 463.98-772.93 MBq/m~2 in muscle of Beagle could be safe.~(32) P-colloidal chromic phosphate interstitial injection is secure to treat the solid tumors with poor and middle blood supply which could be reached by puncture.
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Objective To investigate the effects of intratumoral implantation of ~(32)P-CP-PLLA seeds on the normal canine liver tissue and to exolore the metabolism of ~(32)P-CP-PLLA seeds implanted in the liver of experimental dogs.Methods Twelve beagles were enrolled in this study.The dogs were randomly and equally divided into four groups:group A(185 MBq),group B(370 MBq),group C(740 MBq)and group D(0 MBq).By using laparotomy procedure ~(32)P-CP-PLLA seeds were implanted into dog's liver.CT scan was performed before operation as well as before the dog was sacrificed.All dogs were sacrificed three months after the implantation.Before the procedure and 1,2,4,8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted.One dog from group B and group C was selected respectively and was fed in a metabolic cage.Within one month after the procedure the cpm in feces and in urine was determined every 24 hours.One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1,2,4,8 and 12 weeks after the implantation,and SPECT imaging was also performed at the same time.Pathologic study,both macroscopic and microscopic(including optical and electronic microscopy)was made to observe the liver damage after the dog was sacrificed.The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean±standard deviation((x)±s).Results Two months after the procedure,serological examination found that the serum alkaline phosphatase(BKP)in both group Band group C was significantly higher than that in other groups,the difference was statistically significant (P ＜0.05),and the BKP levels returned to normal in three months.The postoperative 30-day inspection of the urine showed that the radioactive particles slowly released into the body and eliminated from the body with the urine and feces,mainly through the renal excretion.The 30-day cumulative percentage of eliminated radioactive dose in the urine and in the feces was 6.34% and 11.64% respectively.No sign of particle displacement was found on SPECT imaging.On autopsy three months after the implantation,the size of the radioactive seeds became smaller and fragile.With the radioactive dose used increasing,the area of liver damage at the site of seed implantation became bigger,which was demonstrated on CT scan,macroscopic exam and pathologic study.The local damaged focus of the liver caused by ~(32)P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally.Conclusion The implantation of ~(32)P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general adverse effects.The implanted seeds can slowly release the radioactive dose and will not immigrate to other organs in the body.Besides,the seeds possess excellent stability,targeted orientation and safety.
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Objective To explore and evaluate the effect of 32P and pinyangmycin injected in combination for the treatment of maxillofacial hemangioma. Methods The patients were randomly divided into three groups. The first group of patients was treated with 32P; 100 patients were enrolled in this group, of which 37 were male and 63 female. 32P dosage between 0.37 and 0. 74 MBq per cm3 was prepared together with 0.5 ml of 2 %lidocaine, and appropriate normal saline, and then the mixture was injected into hemangioma every two weeks. The second group was given pinyangmycin, and the third group received both 32P and pinyangmycin. The second group included 30 male and 60 female, and the third group 64 male and 136 female. The dose and frequency were given as the same to the first group. Results 88.5 % of patients were cured using both 32P and pinyangmycin, and the cure rate was 77.0 % and 71.7 % with either 32P or pinyangmycin. Conclusion These results prove that 32P and pinyangmycin injected in combination for the treatment of maxillofacial hemangioma is more effective than either 32P or pinyangmycin alone, and furthermore, the method is easy, safe and has less complications.
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Objective To evaluate the efficacy of radiosynovectomy with 32P colloid in haemophilic synovitis of adolescents. MethodsRadiosynovectomy with 32P colloid was primary performed on 26 male haemophilic patients(26 joints),whose average age was 16 years(11 to 21 years).The average dose of 32P colloid was 2.1 mCi(1.0 to 3.0 mCi). Results After 6-month interval,haemarthrosis was reduced by no less than 30% in 23 patients,with a total efficacy of 88.5%.The mean frequency of haemarthrosis was reduced from 1.9 per month of presynovectomy to 0.3 per month of postsynovectomy(P
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Objective To study the influence on the tumor after percutaneous intra-tumor injection of ~(32)P-GMS in liver cancer as well as its suitable dose.Methods 24 New Zealand rabbits were used to establish the animal model of VX-2 liver cancer,and divided into A,B,C and D groups with individually 37,74,111 and 148 MBq of ~(32)P-GMS being injected,respectively;and then pathological changes of tumor were observed by light and electron microscope respectively.Result The dose of ~(32)P-GMS was obviously correlated with the radioactivity damage of tumor cells.In the A and B groups,the tumor cells were not observed to disappear completely after injection of ~(32)P-GMS,but in C group,tumor cells were almost completely disappeared and surrounded by a lot of connective tissue.Although the tumor cells were found to disappear completely in D group,normal liver tissues were also involved.Conclusion Percutaneous intra-tumor injection of ~(32)P-GMS with suitable dose that may induce the tumor tissue to be maximally damaged and may also provide some significances to prevent the tumor metastasis.
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Objective To explore if strand breaks of DNA in human early chorionic villus cells in uterus were induced by diagnostic ultrasound and to evaluate the method used for detection of single-stranded breaks and doublestranded breaks in human DNA. Methods 60 normal pregnant women aged 20-30, who underwent artificial abortion during 6-8 weeks of gestation, were randomly divided into 2 experimental groups: All 30 cases were exposed to diagnostic ultrasound in uterus for 10 minutes, and 24 hours later chorionic villi were extracted; the other 30 cases were taken as the control group. Single-stranded DNA and double-stranded DNA in villus cells in all cases were isolated by the alkaline unwinding combined with hydroxylapatite chromatography, and were quantitatively detected using32 P-labeled Alu probe for dot-blotting hybridization. Results There was no significant difference in quantity and percentage in single-stranded DNA and double-stranded DNA between 2 groups (P＞0.05). 32 P-Alu probe could only hybridize with human DNA, and could detect DNA isolated from as few as 2.5 × 103 chorionic villus cells and 0.45 ng DNA in human leukocytes. Conclusion The results suggested that there were no DNA strand damages in human chorionic villus cells when the uterus was exposed to diagnostic ultrasound for 10 minutes. The method, 32P-Alu probe for dot-blotting hybridization, was even more specific, sensitive and accurate than conventional approaches.
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Objective To compare the therapeutic effect of the combination of ~(99m)Tc-methnetium methylene diphosphunate and colloidal chromic,phosphate ~(32)p with the monotherapies in rats with adjuvant arthritis(AA).Methods In this study,50 Sprague-Dawley rats were randomly divided into five groups with 10 rats in each:normal control group(arthritis induced and treated with the same volume of normal saline via the same administration route),AA control group(arthritis induced with adjuvant and treated with normal sa- line),~(32)p colloid group(arthritis induced with adjuvant and treated with single intra-articular injection of col- luidal chromic phosphate ~(32)p 0.74 MBq and intra-peritoneal injection of normal saline every other clay),~(99m)Tc- MDP group(arthritis induced with adjuvant and treated with intra-peritoneal injection of ~(99m)Tc-MDP 2.5?10~(-3)?g/kg every other day and single intra-articular injection of normal saline),combination group(arthritis in- duced with adjuvant and treated with the combination of the two drugs).The diameter of the left hind ankle, serum levels of turnout necrosis factor(TNF)and interleukin-1?(IL-1?),and the pathological changes of an- kle joints were tested at different time points.Results The diameter of the left hind ankle at week 4 was smaller in the combination group than that of the ~(32)p colloid treatment alone group [(7.11?0.34)mm vs(7.57?0.29)mm,P
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Objective To evaluate the efficiency of injection of colloidal chromic phosphate 32 P cavity in rats with rheumatoid arthritis.Methods Collagen induced arthritis (CIA) was produced in Sprague Dawley rats.After one week immune,the right post ankle was given colloidal chromic phosphate 32 P intra articular injection.Severity of arthritis was observed by the left to right diameter of the right post ankle joint,the volume of right post paw and the arthritic index.Results The group treated with colloidal chromic phosphate 32 P intra articular injection developed milder arthritis compared with control CIA group after 6 weeks.The left to right diameter of the right post ankle joint was (3 96?0 05) mm of the colloidal chromic phosphate 32 P intra articular treated group compared with (4 11?0 08) mm of the control CIA group ( P
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Twenty-three joints in 14 cases of chronic synovitis were treated with intra-articular injection of 32 p-chromic phosphate, including 19 knee joints, one elbow joint with rheumatoid arthritis and 3 knee joints with degenerative arthritis that was recractory to medical treatment. Results of 23 joints evaluated at end of one year were excellent in 43.5$, good in 30.5%, .fair in 13% and poor in 13%. There was a good correlation between the radiographic stage of the joints and the response to treatment. Patients in stage 1 and 2 were more likely to have good to excellent response. Cur study shows that radiation synovectomy is a simple, safe and effective treatment than other managements for chronic synovitis
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DNA in the livers of rats was isolated 24 h af-ter oral administration of benzidine, Congo red andEvan's blue, DNA adducts in the livers of ratswere investigated by a ~(32)P-postlabeling assay. Thelevel of DNA adducts in the livers of rats after oraladministration of benzidine, congo red andEvan'blue were 18. 17, 1. 03 and 1. 74?mol/kgDNA respectively. The results showed that themetabolites of the benzidine derivative azo dyes canform adducts with DNA in the livers of rats.These DNA adducts probably are one of the rea-sons that the incidence of the bladder cancer rosein the people group who are only exposed to benzi-dine derivative azo dyes.
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Objective To study the effects of basic fibroblast growth factor(bFGF) on protein kinase B(PKB) activity. Methods The cytosol and membrane activity of PKB at the indicated time periods was determined by [?-()~(32)P]ATP incorporation assay. Results Both membrane and cytosol activity of PKB in HEK293 cell treated with bFGF(75??g/L) reached to the peak at 10?min.Wortmannin efficiently inhibited the activity of PKB in HEK293 cell.Conclusion bFGF rapidly stimulats both membrane and cytosol activity of PKB via P13K in HEK293 cell.