OBJECTIVE: To observe whether bFGF could cross the blood-labyrinth barrier (BLB) after intra-abdominal injection and to establish an experimental basis for its clinical applications. METHOD: Thirty guinea pigs were divided into three groups. Animals in group 1 were administered o I-bFGF, while animals in group 2 and 3 were administered 125 and saline, respectively, via intra-abdominal injection. The both cochlea, blood, liver, brain, thyroid gland and kidney were collected and weighted. A radioimmunoassay analyzer was employed to measure counts per minute (CPM) of each sample, and autoradiography was performed on both cochlea. RESULT: The CPM value of organ samples in the 125I group was higher than that in other groups, and radioactive grain was observed in cochlear samples of this group. In the 125I-bFGF group, blood demonstrated the highest CPM value, while cochlea and brain demonstrated the lowest CPM value, with no radioactive grain observed in cochlear samples. CONCLUSION bFGF has some difficulties in getting across BLB, so the way of bFGF application in clinics need further study.
Animals ; Autoradiography ; Cochlea ; cytology ; metabolism ; Fibroblast Growth Factor 2 ; administration & dosage ; Guinea Pigs ; Injections, Intraperitoneal ; Iodine Radioisotopes ; administration & dosage

OBJECTIVETo study the preparative method of controlled release microspheres incorporating basic fibroblast growth factor (bFGF) and the bioactivities of bFGF, which were released from bFGF microspheres, on the cultured Schwann cells.

METHODSbFGF was microcapsulated with the multiple emulsion encapsulative method using polylactic-co-glycolic acid (PLGA) as coating material. Its morphology, particle size distribution, drug loading, enveloping rate and in vitro release property were studied. The cultured Schwann cells were grouped according to the different ingredients being added to the culture medium of bFGF group or bFGF-PLGA group. Then the cytometry, cytoactivity detection and mitotic cycle analysis of Schwann cells were performed.

RESULTSThe morphology and the particle size distribution of the bFGF-PLGA microspheres were even and good. The drug loading and enveloping rate of microspheres were (27.18 x 10(-3))%+/-(0.51 x 10(-3))% and 66.43%+/-1.24%. The release property of microspheres in vitro was good and the overall release rate was 72.47% in 11 days. The in vitro cellular study showed that: at the first 2 days of plate culture, the cell number and viability of the bFGF group were statistically higher than the bFGF-PLGA group; at the 3rd and 4th days of plate culture, the cell number and viability of bFGF and bFGF-PLGA groups showed no difference; at the 6th and 8th days of the plate culture, the cell number and viability of the bFGF-PLGA group were statistically higher than the bFGF group. By flow cytometry examination, at the 2nd day of plate culture, the G2/M+S percentage of bFGF group was statistically higher than the bFGF-PLGA group, at the 4th and 8th days of plate culture, the G2/M+S percentage of the bFGF-PLGA group was statistically higher than the bFGF group.

CONCLUSIONSIt is practical to prepare the bFGF-PLGA microspheres with the multiple emulsion encapsulative method. bFGF-PLGA microspheres can preserve the bioactivities of bFGF effectively and promote the proliferation of Schwann cells in a long period because of the controlled release of bFGF from the microspheres.

Animals ; Delayed-Action Preparations ; Fibroblast Growth Factor 2 ; administration & dosage ; pharmacology ; In Vitro Techniques ; Microspheres ; Rabbits ; Schwann Cells

OBJECTIVETo study the effect of inhalation of glucocorticoid on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.

METHODSPulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin (group M, group B, group D). Group B inhaled glucocorticoid daily from the next day of received bleomycin. Group D intraperitoneal injection glucocorticoid daily from the next day of received bleomycin. Normal controls received normal saline both intratracheally. Five rats in each group were killed at 1, 4 week after intratracheal instillation. Histological changes of the lungs were evaluated by HE, Masson trichrome stain. Lung expression of bFGF proteins was assessed by immunohistochemistry and the level of bFGF protein in serum and BALF was further measured by ELISA.

RESULTSPulmonary fibrosis of group M was higher than that of group C, pulmonary fibrosis of group B, D was lower than that of group M at 1, 4 week. bFGF in group M was higher than that in group C, bFGF in group B, D was lower than that in group M in lung, serum and BALF on 1, 4 week.

CONCLUSIONInhalation of glucocorticosteroid alleviates bleomycin-induced pulmonary fibrosis in rats. The mechanism may be related to the changes that bFGF is degrade or prevent it step up.

Administration, Inhalation ; Animals ; Fibroblast Growth Factor 2 ; metabolism ; Glucocorticoids ; administration & dosage ; therapeutic use ; Male ; Pulmonary Fibrosis ; drug therapy ; metabolism ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the approach of basic fibroblast growth factor(bFGF) entering inner ear, as well as its the protective mechanism to inner ear and nerve tissue in pathological situation.

METHODS125I-bFGF was injected into guinea pigs body via the lateral ventricle and muscle under physical situation as well as pathological situation. Then the per minute gamma-radioactive in blood, liver, thyroid gland, brain, cochlear and perilymph fluid was counted, and the distribution and metabolism of bFGF in the inner ear and autoradiography of the cochlea were also observed.

RESULTSGamma-radioactive cpm of blood and liver increased significantly, while it did not change in brain, cochlea and perilymph after 125I-bFGF intramuscular injections. Gamma-radioactive cpm in blood, liver, brain, perilymph and cochlea had increased and autoradiography granules was found in the cochlea in 30 min after 125I-bFGF injected into CSF. In brain, perilymph and cochlea, a maximal value of gamma-radioactive cpm was obtained between 2 h and 4 h, while that in 8 h decreased significantly. Autoradiography granules still were seen in 8 h. gamma-radioactive cpm in 12 h was still higher than that in control group, but autoradiography granules can't be seen. The result in 24 h was similar to that in control group. The time course of cpm in the blood, cochlea and perilymph always parallel changed.

CONCLUSIONSbFGF has some difficulties in getting across blood-labyrinth barrier (BLB) and blood-brain barrier (BBB) under physical and pathological situation, such as acute anoxia, aminoglycoside-induced deafness. bFGF can reach inner ear, perilymph fluid, brain tissue and blood rapidly when it is injected into CSF and excreted slowly in those tissues. Permeability of BBB and BLB to bFGF is similar and has orientation.

Animals ; Autoradiography ; Blood-Brain Barrier ; metabolism ; Ear, Inner ; metabolism ; Fibroblast Growth Factor 2 ; administration & dosage ; pharmacokinetics ; Guinea Pigs ; Iodine Radioisotopes ; administration & dosage

OBJECTIVETo study the therapeutic effect of chitosan-coated basic fibroblast growth factor (bFGF) slow-releasing microspheres on the knee osteoarthritis in the rabbit.

METHODSFrom November 2008 to July 2009, 54 New Zealand rabbits were divided into 6 groups at random, which were the control group, the model group, the PBS-M group, the bFGF-S group, the 10-bFGF-M group and the 100-bFGF-M group, respectively. The model of knee osteoarthritis was induced by the injection of papain in the rabbit. Except the control and model groups, all the experimental groups were implanted 1 ml intervention solution at the third and sixth weeks, including the PBS microspheres, bFGF solution, 10 µg bFGF microspheres and 100 µg bFGF microspheres, respectively. The rabbits were sacrificed at the ninth week after operation, and then articular cartilage was conducted the morphological and histopathological evaluation.

RESULTSThe damage of articular cartilage in the model group was more serious than that in the control group, with statistical differences according to the Ink score (t = 8.22, P = 0.00) and Mankin score (t = 17.20, P = 0.00). The damage of articular cartilage in the PBS-M and bFGF-S groups were similar with that in the model group, according to the Ink score (t = 0.26, P = 0.79; t = 0.80, P = 0.45) and Mankin score (t = 1.51, P = 0.17; t = 0.56, P = 0.60). The Ink and Mankin scores in the 10-bFGF-M and 100-bFGF-M groups were better than that in the model group (Ink score: t = 3.58, P = 0.01; t = 6.82, P = 0.00; Mankin score: t = 3.41, P = 0.01; t = 5.00, P = 0.00), with the 100-bFGF-M group much better (t = 5.29, P = 0.00; t = 2.80, P = 0.02).

CONCLUSIONSThe bFGF slow-releasing microsphere can keep its effective intra-articular concentration, which may accelerate the synthesis of proteoglycan and inhibit its decomposition to reverse the damage of articular cartilage.

Animals ; Drug Carriers ; administration & dosage ; therapeutic use ; Fibroblast Growth Factor 2 ; administration & dosage ; therapeutic use ; Injections, Intra-Articular ; Microspheres ; Osteoarthritis, Knee ; therapy ; Rabbits

OBJECTIVE: To explore the synergistic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on the growth of bone tissue. METHODS: A total of 36 rabbits were randomly divided into 4 groups with 9 rabbits (18 sides of the anterior limb) in each group, including group A,B,C, and D. For all rabbits 1.0 cm bone defects was created in both sides of the radius. These bone defect regions were implanted with corresponding composites: group A with calcium phosphate cement (CPC) only, group B with CPC/bFGF, group C with CPC/VEGF while group D with both bFGF and VEGF. At the 3rd, 6th, and 12th week after the operation, 6 specimens from each group were randomly selected. The effects were partly assessed by X-ray film examination, bone mineral density (BMD) measurements, biomechanical test and histological observation. RESULTS: X-ray showed that at the 12th week the bone defects in group D were completely repaired with CPC generally degraded,whereas bone defects in group B and C were only basically repaired. BMD measurements showed that at the 12th week the BMD of group D was significantly higher than that of group B and C (P < 0.05). Biomechanical testing(at the 12th week) showed that the maximum bending load of group D was significantly higher than that of group B and C (P < 0.05). Histological observation indicated that at the 12th week, woven bone had become mature lamellar bone in group D. At the same time, the normal relation of cortical bone and marrow had resumed, and so had the normal structure of trabecula. However, the recanalization of bone marrow cavity could not be seen in group B and C. CONCLUSION These 3 kinds of composite: CPC/bFGF, CPC/VEGF and CPC/ bFGF+VEGF can promote the growth of bone tissue and speed up the repair of bone defects. The composite of CPC/bFGF+VEGF is better than the other two composites in promoting the growth of bone tissues, indicating that bFGF and VEGF have a synergistic effect on the growth of bone tissue.
Animals ; Bone Cements ; Calcium Phosphates ; administration & dosage ; Drug Synergism ; Female ; Fibroblast Growth Factor 2 ; administration & dosage ; Implants, Experimental ; Male ; Rabbits ; Radius ; injuries ; surgery ; Random Allocation ; Vascular Endothelial Growth Factor A ; administration & dosage

The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 microg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 microg/(kg.h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-alpha was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-alpha and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities.
Animals ; Brain ; drug effects ; pathology ; Brain Ischemia ; drug therapy ; pathology ; Fibroblast Growth Factor 2 ; administration & dosage ; Infusions, Intravenous ; Rabbits ; Reperfusion Injury ; drug therapy ; pathology ; Treatment Outcome

OBJECTIVETo investigate the clinical efficacy of regimen consisting of lenalidomide combined with chemotherapy for acute leukemia and its impact on vascular endothilial growth factor (vEGF) and basic fibroblast growth factor (bFGF), and to analyze the relationship lenalidomide with therapeutic efficacy of leukemia.

METHODSThe patients with newly diagnosed acute myeloid leukemia (except M3) from October 2013 to October 2014 in our hospital were randomly divided into 2 groups: chemotherapy+placebo (CP) group and lenalidomide+chemotherapy (LC) group. In addition, healthy persons were used as healthy controls (HC). The expression of VEGF and bFGF was detected by ELISA, and the therapeutic efficacy for AML patients was analyzed.

RESULTSThe therapeutic efficacy in LC group and CP group was 87.9% and 77.2% respectively. Before treatment, the VEGF level in LC and CP groups was obviously higher than that in HC group; after treatment, the VEGF level significanthy decreased, and the decreased degree in LC group was larger than that in CP group. Before treatment, the bFGF level in LC and CP groups was higher than that in HC group; after treatment, the bFGF level decreased, and decreased degree in LC group was larger than that in CP group.

CONCLUSIONThe lenalidomide combined with chemotherapy can significantly decrease the expression level of VEGF and bFGF, and enhance the remission rate of patients with AML.

Acute Disease ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Thalidomide ; administration & dosage ; analogs & derivatives ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo investigate the effect of topical propranolol gel on the levels of plasma vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF) and matrix metalloproteinases-9 (MMP-9) in proliferating infantile hemangiomas (IHs) of superficial type.

METHODS33 consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma VEGF, MMP-9 and bFGF by enzyme-linked immunosorbent assay (ELISA) in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants. The clinical efficacy in IHs was evaluated by Achauer system. Differences of plasma results between the healthy group and the IHs group pre-treatment were analyzed using Mann-Whitney U-test. Paired sample comparisons of any two time points of pre-treatment, 1 month and 3 months after treatment in IHs were evaluated by Wilcoxon signed-rank test.

RESULTSThe clinical efficiency of topical propranolol gel at 1, 3 months after application were 45.45%, 81.82% respectively. The levels of plasma VEGF and MMP-9 in patients pre- treatment were higher than those in healthy infants [(362.16 ± 27.29) pg/ml vs (85.63 ± 8.14) pg/ml, (1376.41 ± 42.15) pg/ml vs (687.27 ± 44.1) pg/ml, P < 0.05], but the level of bFGF did not show significant difference [(176.03 ± 13.60 ) pg/ml vs (235.94 ± 35.43 ) pg/ml, P > 0. 05 ]. The concentrations of VEGF and bFGF at 1, 3 months after treatment decreased obviously [(271.51 ± 18.59) pg/ml vs (362.16 ± 27.29 ) pg/ml, (135.85 ± 12.66) pg/ml vs (176.03 ± 13.60) pg/ml], 1 month after treatment vs pre-treatment, P < 0.05; (240.80 ± 19.89) pg/ml vs (362.16 ± 27.29) pg/ml, (107.31 ± 5.82) pg/ml vs (176.03 ± 13.60) pg/ml, 3 month after treatment vs pre-treatment, P < 0.05, whereas the levels of plasma MMP-9 declined slightly [(1321.18 ± 48.74) pg/ml vs (1376.41 ± 42.15 ) pg/ml, (1468.68 ± 32.78) pg/ml vs (1376.41 ± 42 2.15 ) pg/ml, P > 0.05 ].

CONCLUSIONSPropranolol gel may suppress the proliferation of superficial infantile bemangiomas by reducing VEGF and bFGF.

Administration, Topical ; Case-Control Studies ; Child ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factor 2 ; blood ; Gels ; Hemangioma ; blood ; drug therapy ; Humans ; Infant ; Matrix Metalloproteinase 9 ; blood ; Propranolol ; pharmacology ; Time Factors ; Vascular Endothelial Growth Factor A ; blood

To study the preparation method of bFGF microspheres and to investigate the bioactivities of bFGF, which were released from the bFGF microspheres, on the cultured schwann cells. bFGF was microcapsulated with the multiple emulsion encapsulative method using PLGA as coating material. Its morphology, particle size distribution, drug loading-embedding rate and in vitro release property were studied. The cultured schwann cells were grouped according to the different ingredients being added to the culture medium: bFGF group, bFGF-PLGA group. Then the number, the viability and the cell cycle of schwann cells were measured. The morphology and the particle size distribution of the bFGF-PLGA microspheres were even and good; the drug-loading and drug-embedding rate of microspheres were (27.18 x 10(-3)) % +/- (0.51 x 10(-3)) %, 66. 43% +/- 1.24%; the release property of microspheres in vitro was good and the overall release rate was 72. 47% in 11 days. The in vitro cellular study showed: 1, 2 days after plate culture, the cell number and cell viability of bFGF group was much better than that of bFGF-PLGA group; 3, 4 days after plate culture, the cell number and cell viability of bFGF group and bFGF-PLGA group were not different statistically; 6, 8 days after plate culture, the cell number and cell viability of bFGF-PLGA group was much better than that of bFGF group. Through the flow cytometry examination: 2 days after plate culture, the GJ/M+S percentage of bFGF group was higher than that of bFGF-PLGA group; 4, 8 days after plate culture, the G2/M+S percentage of bFGF-PLGA group was higher than that of bFGF group. So, it is practical to prepare the bFGF-PLGA microspheres with the multiple emulsion encapsulative method. bFGF-PLGA microspheres can preserve the bioactivities of bFGF effectively and promotes the proliferation of schwann cells in a long period because of the controlled release of bFGF from microspheres.
Cell Proliferation ; drug effects ; Cells, Cultured ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; Fibroblast Growth Factor 2 ; administration & dosage ; pharmacology ; Lactic Acid ; administration & dosage ; Microspheres ; Polyglycolic Acid ; administration & dosage ; Polymers ; Schwann Cells ; cytology