Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model / Potencial regenerativo do fator básico de crescimento de fibroblastos contido em microesferas biodegradáveis de hidrogel de gelatina aplicadas após lesão de prega vocal: efeito inicial no reparo tecidual em modelo de coelho

Abstract Introduction Postoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging. Objective The goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor. Methods Videoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement. Results The presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection. Conclusion A prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.

Resumo Introdução A disfonia pós-operatória é causada principalmente por cicatrizes nas pregas vocais. Tem sido relatado que o manejo cuidadoso da cirurgia das pregas vocais reduz o risco de formação de cicatriz. No entanto, a depender da lesão da prega vocal, o tratamento da disfonia pós-operatória pode ser desafiador. Objetivo Desenvolver uma nova abordagem regenerativa profilática para o tratamento de pregas vocais lesionadas após a cirurgia, com microesferas biodegradáveis de hidrogel de gelatina como sistema de administração de medicamentos para o Fator Básico de Crescimento de Fibroblastos (bFGF). Método A cirurgia laríngea videoendoscópica foi feita para criar lesão nas pregas vocais em 14 coelhos. Imediatamente após esse procedimento, microesferas biodegradáveis de hidrogel de gelatina com bFGF foram injetadas na prega vocal. Duas semanas após a injeção, as laringes foram excisadas para avaliação da histologia das pregas vocais e do movimento da mucosa. Resultados A presença de função vibratória deficiente foi confirmada nas pregas vocais lesionadas. A histologia e a análise de imagem digital demonstraram que as pregas vocais lesionadas injetadas com microesferas de hidrogel de gelatina com bFGF apresentaram menor formação de cicatriz, em comparação com as pregas vocais lesionadas injetadas apenas com microesferas de hidrogel de gelatina ou aquelas sem injeção. Conclusão Uma injeção profilática de microesferas biodegradáveis de hidrogel de gelatina com bFGF demonstra um potencial regenerativo para pregas vocais lesionadas em um modelo de coelho.

The curative effects of twinlight laser treatment on chronic periodontitis / 实用口腔医学杂志

Objective:To observe the effects of Er ∶YAG(erbium:yttrium-aluminum-garnet) laser combined with diode laser in the treatment of chronic periodontitis.Methods:30 patients with chronic periodontitis patients were treated by mechanical scaling and root planning(SRP),pure Er ∶ YAG laser(ERT),diode + Er ∶ YAG + diode laser therapy(TPT) respectively.In the treatment VAS pain score was recorded.Probing deepth (PD),clinical attachment level (CAL) and bleeding on probing (BOP) were examined,IL-1 β,TNF-α and b-FGF in GCF,Porphyromonas gingivalis(Pg) in subgingiva plaqure were measured before and after treatment.Data were analyzed by SPSS 21.0 software.Results:6 weeks,12 weeks after treatment PD,BOP and CAL in TPT group were lower than those in ERT and SRP groups(P ＜0.05),TGF-β and b-FGF in TPT group were higher,IL-1β and TNF-α were lower than those in ERT and SRP groups (P ＜ 0.05).The content of Pg relative to total bacteria in TPT group were lower than that in ERT and SRP groups (P ＜ 0.05),VAS value in twinlight laser group was significantly lower than hand instruments group(P ＜ 0.05).Conclusion:The twinlight laser is effective in the treatment of periodontitis.

Study on the effect of low level laser in the treatment of periodontal disease / 国际生物医学工程杂志

Objective The purpose of this study was to explore the efficacy of low level laser treatment (LLLT) combined with initial periodontal therapy in treating chronic periodontits.Methods Eighteen patients with chronic periodontitis were randomly treated in a spit-mouth design with combination of laser (808 nm,80 mW) treatment with scaling and root planing (experimental) or with scaling and root planing alone (contol) after OHI and supragingival cleaning.Clinical parameters of sulcus bleeding index (SBI),periodontal probing depth (PD) and clinical attachment loss (CAL) of both sides were recorded and gingival crevicular fluid samples were collected at baseline and 1,4,12 weeks after the treatment.GCF samples were analyzed for b-FGF,IL-1β,IL-8 level using ELISA assay.Results For the change of SBI and PD,only SBI in the experimental group experienced significant reduction (P＜0.05) at 1 week compared with baseline (P＜0.05),and the reduction in both groups were statistically significant (P＜0.05) at 4 weeks.The same situation occurred while both experimental groups made more significant difference (P＜0.01) at 12 weeks.The reduction of SBI was obvious in both groups when the PD was more than 6 mm.For CAL,the experimental group showed signs of improvement (P＜0.05) at 4 weeks; both groups indicated improvement (P＜0.05),while the experimental was more significant (P＜0.01) at 12 weeks.For the levels of b-FGF,it showed steady rise after treatment in experimental group,while it went up to the baseline after falling in control group.At 12 weeks,there were statistical significance of differences between two groups (P＜0.05).The changes of IL-1β and IL-8,in the experimental group showed better results than that in control group,while the difference between two groups was not significant (P＞0.05).Conclusion LLLI can accelerate the healing of periodontal tissue by reducing the SBI,decreasing the PD,improving the CAL and increasing levels of b-FGF in the GCF of the patients.

Inhibitory effects of pioglitazone on alkaline burninduced corneal neovascularization in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of pioglitazone on corneal neovascularization(CNV)induced by alkali burnin rats and on expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF).METHODS: CNV was induced by alkaline burn in rats which were then administered pioglitazone subconjunctivally.Corneal angiogenesis was evaluated and observed with a slit lamp microscope and the VEGF and b-FGF level were determined by immunohistochemistry and Western blot at different intervals.RESULTS: The CNV of the rats was shown two days after alkaline burn, and reached its highest level in 7-10 days. The mean values of the area and length of neovascularization and the VEGF and b-FGF levels in the pioglitazone-treated group were significantly lower than those in the control group at various time.CONCLUSTON: Local application of pioglitazone could remarkably inhibit CNV, probably by means of downregulation of VEGF and b-FGF expression.

Influence of Mahong Decoction on Serum VEGF and b-FGF of Rat Model of Bronchus Asthma Airway Remolding / 中国中医药信息杂志

Objective To investigate the effect of Mahong decoction on serum VEGF and b-FGF of rat model bronchus asthma airway remolding. Method Forty SD rats randomly divided into four groups: blank group, asthma group, hormone group, Chinese medicine group. The asthmatic model was established by sensitization and challenge with ovalbumin, and the rats in the hormone group and Chinese medicine group conferred hormone and Chinese medicine before the challenge. ELISA was used to measure the level of serum VEGF and b-FGF. Results The serum VEGF and b-FGF in asthma group was higher than in other groups (P0.05). Conclusion Mahong decoction may control the level of serum VEGF and b-FGF of rat model of bronchus asthma airway remolding, which has the similar result with hormone.

In vitro Neural Cell Differentiation of Genetically Modified Human Embryonic Stem Cells Expressing Tyrosine Hydroxylase / 대한불임학회지

OBJECTIVE: This study was to examine in vitro neural cell differentiation pattern of the genetically modified human embryonic stem cells expressing tyrosine hydroxylase (TH). MATERIALS AND METHODS: Human embryonic stem (hES, MB03) cell was transfected with cDNAs cording for TH. Successful transfection was confirmed by western immunoblotting. Newly transfected cell line (TH#2/MB03) was induced to differentiate by two neurogenic factors retinoic acid (RA) and b-FGF. Exp. I) Upon differentiation using RA, embryoid bodies (EB, for 4 days) derived from TH#2/MB03 cells were exposed to RA (10-6 M)/AA (5x10-2 mM) for 4 days, and were allowed to differentiate in N2 medium for 7, 14 or 21 days. Exp. II) When b-FGF was used, neuronal precursor cells were expanded at the presence of b-FGF (10 ng/ml) for 6 days followed by a final differentiation in N2 medium for 7, 14 or 21 days. Neuron differentiation was examined by indirect immunocytochemistry using neuron markers (NF160 & NF200). RESULTS: After 7 days in N2 medium, approximately 80% and 20% of the RA or b-FGF induced Th#2/MB03 cells were immunoreactive to anti-NF160 and anti-NF200 antibodies, respectively. As differentiation continued, NF200 in RA treated cells significantly increased to 73.0% on 14 days compared to that in b-FGF treated cells (53.0%, p<0.05), while the proportion of cells expressing NF160 was similarly decreased between two groups. However, throughout the differentiation, expression of TH was maintained (~90%). HPLC analyses indicated the increased levels of L-DOPA in RA treated genetically modified hES cells with longer differentiation time. CONCLUSION: These results suggested that a genetically modified hES cells (TH#2/MB03) could be efficiently differentiated in vitro into mature neurons by RA induction method.

Expression of b-FGF in Different Type of Herniated Nucleus Pulposus / 대한정형외과학회잡지

PURPOSE: To clarify b-FGF expression in different types of herniated nucleus pulposus (HNP) as angiogenesis marker, and to identify the novel vasculature in avascular nucleus pulposus. MATERIALS AND METHODS: Twenty-seven disc specimens removed surgically from patients who underwent discectomy for L4-5 HNP. The control disc specimens were obtained from five patients who underwent surgery for spine fracture or idiopathic scoliosis. According to MRI and operative findings, HNP was classified into 3 groups; protruded, extruded and sequestrated. The study involved; 7 protruded cases, 10 extruded cases and 10 sequestrated cases. Specimens were analyzed by western quantitative comparisons were performed upon the different bands. H-E stain and immunohistochemistry of CD 34 were performed to identify vessels in the avascular nucleus pulposus. RESULTS: The expression of b-FGF was not significantly increased in the protruded disc (p>0.05), but was significantly increased in the extruded disc as compared with the protruded disc (p<0.05) and in the sequestrated disc in compared with the extruded disc (p<0.05). Immunohistochemical study revealed novel vasculature at the periphery of the sequestrated disc. CONCLUSION: It is possible to confirm that sequestrated HNP is exposed to more vigorous regression via new vessel infiltration into the avascular nucleus pulposus tissue.

Expressions of VEGF, b-FGF,NOS_2 and NOS_3 in human non-small cell lung cancer and the relationship between them and tumor angiogenesis and lymph node metastasis / 中国癌症杂志

Purpose:To investigate the expression and distribution of VEGF, b FGF, NOS 2 and NOS 3 in human non small cell lung cancer (NSCLC),and to evaluate the relationship between their expression and tumor angiogenesis and lymph node metastasis.Methods:The expression of VEGF, b FGF, NOS 2, NOS 3 and IMVD in 95 patients with NSCLC were examined using immunohistochemical methods (SP), and the relationship between them and many clinicopathological parameters was analyzed.Results:The positive expression of VEGF and b FGF was associated with intratumor microvessel density(IMVD), TNM stage and lymph node metastases of NSCLC, respectively( P

Clinical Correlation of VEGF, TGF-beta1, and b-FGF Expression in Patients with Hepatocellular Carcinoma

PURPOSE: Angiogensis plays an important role in the proliferation and metastasis of solid tumors. Hepatocellular carcinoma (HCC) is the second most prevalent tumor in Korean males and is known to be a typical hypervascular tumor with frequent invasion of the portal vein. This study was designed to evaluate the expression of VEGF, TGF-beta1, b-FGF in HCC and to determine whether these angiogenic growth factors are related to clinicopathologic factors as well as prognosis. METHODS: The medical records of 30 patients who were diagnosed as HCC and treated with hepatic resection between January 1994 and December 1998 at Soonchunhyang University Chunan Hospital were selected according to the condition of the paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum alpha-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in the portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus (HBV) infection, and Edmonson-Steiner (E-S) grade were investigated. The immunopathologic expression of TGF-beta1, b-FGF, and VEGF was examined and compared with survival using Kaplan-Meier estimate and cox propositional hazard model. RESULTS: Thirty patients (24 males, 6 females) were included in the study, with mean age of 50.6 years. The mean size of the tumor was 5.2 cm. All patients were followed up for7 to 63 months. Child's classification A and B were 23 (76.7%) and 7 (23.3%) cases, respectively. The immunopathologic expression of VEGF, b-FGF, and TGF-beta1 were 56.7%, 33.3%, and 33.3%, respectively. VEGF was significantly related to tumor size and TNM classification (P0.05). alpha-fetoprotien (risk=6.33), Child classification (risk=7.65), and E-S grade (risk=1.94) remained as significant independent prognostic factors of survival (P<0.05). CONCLUSION: Our data suggests that the expression of angiogenic factors in HCC cells may be a potential prognostic factor for survival and is associated with the clinicopathologic factors of HCC.

Study on anti-angiogenesis effect of clarithromycin on angiogenesis induced by b-FGF / 第二军医大学学报

Objective:To study the inhibitory effect of clarithromycin on angiogenesis induced by b-FGF. Methods:TheMatrigel implant assay was used. Matrigel (500?l) containing b-FGF and heparin were injected subcutaneously into the ab-domen of mice and were harvested 5 d later. The amount of hemoglobin and micro-vascular area present in the implant weremeasured and cotnpared. The mice were given either CAM (study group) or the same volume of glucose (vehicle group) oncea day by gastric intubation. Treatmen started 3 d before Matrigel implant and continued until the end of study. Results:Clar-ithromycin reduced hemoglobin content and micro-vascular area in Matrigel implant at high dosage(≥40 mg/(kg?d). Con-clusion:These data demonstrate that clarithromycin is a potent inhibitor of angiogenesis and may has possible therapeutic value in controlling pathologic angiogenesis.