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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的炎性疾病.患者进食刺激性食物时口内疼痛,口腔黏膜苍白僵硬,触摸有条索感,舌运动、张口受限,以致咀嚼、吞咽困难,有的甚至发生癌变,严重影响患者的生存质量和身心健康.复杂的发病机制导致该病至今尚无满意的治疗方法.本文介绍了目前主要的治疗方法,包括药物治疗、物理治疗和手术治疗等,主张根据病变发展的阶段,采用多种方法联合治疗.     

Auto-fluorescence spectra of oral submucous fibrosis

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic oral mucosal disease characterized by progressive deposition of collagen in the subepithelial connective tissue and epithelial atrophy. Previous studies have shown that at 330-nm excitation, the 380- and 460-nm emission peaks of the auto-fluorescence spectra for oral mucosal tissues reflect the collagen content in the subepithelial connective tissue and the nicotinamide adenine dinucleotide phosphate (NADH) content in the epithelial cells, respectively. Therefore, at 330-nm excitation OSF mucosa may have a higher 380-nm emission peak and a lower 460-nm emission peak than the normal oral mucosa (NOM). METHODS: To test the above hypothesis, we measured the in vivo auto-fluorescence spectra of 59 OSF mucosal sites and compared the measured spectra with auto-fluorescence spectra obtained from 15 NOM samples from 15 healthy volunteers, five samples of friction hyperkeratosis (histologic diagnosis, hyperkeratosis and acanthosis) on OSF buccal mucosa (FHOSF), and 29 samples of oral leukoplakia (histologic diagnosis, hyperkeratosis and acanthosis) on OSF buccal mucosa (OLOSF). RESULTS: We found that the spectrum of the OSF mucosa had a significantly higher 380-nm emission peak and a significantly lower 460-nm emission peak than the spectra of NOM, FHOSF, and OLOSF samples. When the mean (+/-SD) fluorescence intensities at 380 +/- 15 nm (I380 +/- 15 nm) and 460 +/- 15 nm (I460 +/- 15 nm) emission peaks and the mean ratio of I460 +/- 15 nm/I380 +/- 15 nm were compared between groups, we found that OSF group had a significantly higher mean value of I380 +/- 15 nm, a significantly lower mean value of I460 +/- 15 nm, and a significantly lower mean ratio of I460 +/- 15 nm/I380 +/- 15 nm than the NOM, FHOSF, and OLOSF groups (P < 0.001). However, no significant differences in the mean values of I380 +/- 15 nm, I460 +/- 15 nm, and ratio of I460 +/- 15 nm/I380 +/- 15 nm were found between NOM and FHOSF or OLOSF samples as well as between FHOSF and OLOSF samples (P > 0.05). CONCLUSION: Because OSF mucosa has a very unique pattern of auto-fluorescence spectrum, we conclude that auto-fluorescence spectroscopy is a good method for real-time diagnosis of OSF.     

Molecular pathogenesis of oral submucous fibrosis – a collagen metabolic disorder

Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is characterized by a generalized submucosal fibrosis. The pathogenesis of the disease is not well established. Epidemiological evidences strongly indicate the association of the betel quid (BQ) habit and OSF. Various findings indicate the disease to be a consequence of disturbances in the homeostatic equilibrium between synthesis and degradation of extracellular matrix (ECM), wherein collagen forms a major component, thus can be considered as a collagen-metabolic disorder. Transforming growth factor-beta (TGF-beta) is a potent stimulator of production and deposition of the ECM. The objectives of this review are to highlight the molecular events involved in the overproduction of insoluble collagen and decreased degradation of collagen occurring via exposure to BQ and stimulation of the TGF-beta pathway, and elucidate the cell signaling that is involved in the etiopathogenesis of the disease process.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的口腔黏膜病。本文对OSF的病名来由、病因、发病机制和病变的性质进行了系统的描述。     

Immunohistochemical distribution of collagens type I, III, IV and VI, of undulin and of tenascin in oral fibrous hyperplasia

The distribution of collagens type I, IV and VI, of procollagen type III, of undulin and of tenascin was studied in 10 lesions which were clinically and histologically diagnosed as localized oral fibrous hyperplasias. The immunohistochemical distribution of these proteins was similar to that observed for normal oral mucosa. Undulin showed a pattern of parallel fibers throughout. Collagen type VI was pronounced in the subepithelial connective tissue, whereas the collagen fiber bundles were equally reactive for collagens type I and III. Tenascin was observed close to the subepithelial basement membrane and in proximity to collagen fiber bundles in the upper connective tissue. The present findings indicate that oral fibrous hyperplasias that are probably caused by inflammation or chronic irritation show the differentiated and ordered pattern of extracellular matrix proteins characteristic of normal oral mucosa.     

口腔黏膜下纤维性变的药物治疗进展

由于口腔黏膜下纤维性变(OSF)发病机制复杂,目前尚缺乏特效治疗手段,主要治疗方式仍为药物治疗.本文回顾介绍了近年来国内外临床上治疗OSF的药物种类,并主张根据疾病的病程选择不同的药物治疗.     

HLA-antigens in oral submucous fibrosis

HLA–typing was carried out on 122 areca nut chewers who attended hospitals for complaints unrelated to the habit. The subjects were South Africans of Indian extraction. The study did not include haplotypes. Palpable fibrous bands in the mouth indicated oral submucous fibrosis. The subjects were divided into 4 groups based on specific oral symptoms and signs. Groups A and B were without fibrous bands. Group A (47 subjects) included those with one or no symptoms while group B (28 subjects) suffered from 2 to 7 oral symptoms. Group C (17 subjects) had oral symptoms and represented early or mild oral submucous fibrosis and exhibited at least one discrete palpable fibrous hand. Group D (30 subjects) were classic oral submucous fibrosis cases with multiple bands. The high occurrence of oral submucous fibrosis in this study group (39%) is similar to the occurrence in comparable age groups reported earlier–n South Africa and is conceivably due to the higher age range of the subjects and their relatively long exposure to the area nut. We were unable to demonstrate a specific pattern of HLA–antigen frequencies in chewers with or without the disease. Furthermore, there were no differences between the study population and the controls. It is concluded that there is not necessarily a HLA–associated susceptibility in oral submucous fibrosis.     

The fibroblast population in oral submucous fibrosis

The purpose of the investigation was to compare the morphology of fibroblasts cultured from healthy oral mucosa and mucosa of patients with oral submucous fibrosis (OSF) and to collate the occurrence of cell types of similar morphology. Cells cultured from biopsy specimens from the buccal mucosa of six subjects who did not chew the areca nut and six patients with OSF who chewed areca nut were grown according to standard techniques. Ninety cells per cell line were recorded daily for 8 days, classified into types F1, F2 and F3 according to their morphology, and the results statistically analyzed. We found that there was a relative increase of F3 cells in relation to Fl cells in OSF resulting in the ratio of F3 to F1 cells being significantly larger in OSF than the ratio in the controls. As it has been reported that F3 cells m rat connective tissues produce significantly more collagen types I and III than F1 cells, we concluded that a change of fibroblast population has occurred in OSF and that this relative increase of F3 cells in humans, which could be committed to the production of large quantities of collagen, can be an explanation for the excessive collagen formation in OSF.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性且具有癌变倾向的疾病,主要发生于印度、巴基斯坦等东南亚国家以及我国湖南、台湾两省。OSF病因不明,咀嚼槟榔是其最主要的致病因素,且咀嚼槟榔的频率越高、年限越长,越易患OSF。所有OSF患者都有咀嚼槟榔史,咀嚼槟榔还与口腔白斑、口腔癌发病高度相关。此外,OSF的发生还与遗传因素、免疫反应、胶原相关性基因,营养缺乏等有关。本文就OSF致病因素做一简单介绍。     

HLA typing in Taiwanese patients with oral submucous fibrosis

BACKGROUND: A significant association of certain human leukocyte antigens (HLA) and haplotypic pairs with oral submucous fibrosis (OSF) has been reported. However, controversial result of no HLA association with OSF has also been reported. In this study, the phenotype and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 in 135 Taiwanese OSF patients were calculated and compared with those in 540 healthy control Taiwanese. METHODS: The analysis of HLA-A, -B, and -C antigens, and of HLA-DRB1 and -DQB1 alleles in OSF patients and healthy control subjects, was performed by serologic typing and DNA typing using polymerase chain reaction with sequence-specific primers (PCR-SSP), respectively. RESULTS: We found that the phenotype frequency of HLA-B76 (3.0%) in OSF patients was significantly greater than that (0%) in healthy control subjects (corrected P (Pc) = 0.000). In addition, the haplotype frequencies of HLA-B48/Cw7 (3.0%), -B51/Cw7 (6.7%), and -B62/Cw7 (8.2%) in OSF patients were significantly greater than the corresponding haplotype frequencies (0, 0.7, and 1.9%, respectively) in healthy control subjects (Pc = 0.000). The relative risk (RR) values of haplotypes B51/Cw7 (9.57) and B62/Cw7 (4.7) were greater than the RR values of phenotypes B51 (1.81), B62 (2.31), and Cw7 (1.91) in OSF patients. In addition, the etiologic fraction (EF) value of haplotype B51/Cw7 (0.63) was higher than the EF values of phenotypes B51 (0.2) and Cw7 (0.59). CONCLUSIONS: We conclude that some Taiwanese areca quid (AQ) chewers with particular HLA phenotypes and haplotypes are prone to have OSF. In addition, some particular HLA haplotypes may play more important roles than the individual HLA phenotypes for the genetic susceptibility to OSF. However, the significantly increased HLA phenotype B76 and three of the common HLA haplotypes detected are present in only about 20% of incident cases of OSF.     

Role of chewing and smoking habits in the etiology of oral submucous fibrosis (OSF): a case-control study

Oral submucous fibrosis (OSF), a premalignant and crippling condition of the oral mucous membrane, was studied to identify its relationship to various chewing and smoking habits. Two hundred and thirty-six consecutive cases of OSF were compared with 221 control subjects matched for age, sex and socio-economic conditions. It was found that chewing of areca nut/quid or pan masala (acommercial preparation of areca nuts, lime, catechu and undisclosed colouring, flavouring and sweetening agents) was directly related to OSF. Also, pan masala was chewed by a comparatively younger age group and was associated with OSF changes earlier than areca nut/quid chewing. However, chewing or smoking tobacco with various other chewing habits did not increase the risk of developing OSF. It was also found that frequency of chewing rather than the total duration of the habit was directly correlated to OSF.     

High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis.

BACKGROUND: Previous study has shown a high incidence of autoantibodies including antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies in a small group of 26 patients with oral submucous fibrosis (OSF). The reasons why some of the OSF patients have high titers of autoantibodies in serum have not been completely explained and no further study on autoantibodies in OSF patients has been done in a large group of patients. METHODS: In this study, we determined the serum levels of ANA, SMA, GPCA, and TMA in a large group of 109 male Taiwanese patients with OSF by an indirect immunofluorescence technique (for ANA, SMA, and GPCA), and by a semiquantitative microtiter particle agglutination test (for TMA). The presence of serum autoantibodies in OSF patients was further correlated with patients' oral habits and the severity of OSF measured by maximum mouth opening (MMO) and sites of involvement. RESULTS: We found that the frequencies of presence of serum ANA (23.9%), SMA (23.9%), and GPCA (14.7%) in OSF patients were significantly higher than those (9.2, 7.3, and 5.5%, respectively) in healthy control subjects (P < 0.01, P < 0.005, and P < 0.05, respectively). Although the frequency of presence of TMA (5.5%) in OSF patients was also greater than that (2.8%) in healthy control subjects, the difference was not significant (P > 0.05). The presence of serum GPCA in OSF patients was significantly associated with daily areca quid (AQ) consumption (P < 0.05). The presence of serum ANA in OSF patients associated with daily AQ consumption was of borderline statistical significance (P = 0.066). However, no significant correlations were demonstrated between the presence of serum autoantibodies in OSF patients and other variables of oral habits, MMO, and sites of involvement. CONCLUSION: In this study, all the 109 OSF patients had AQ chewing habit and 73.4% of the OSF patients swallowed the 'juice' of AQ during the chewing process. The presence of serum GPCA and ANA in OSF patients was associated with daily consumption of AQs. AQ chewing caused mucosal microtrauma, and ulcerations facilitated the diffusion of genotoxic and cytotoxic AQ ingredients into the oral and gastric tissues. Altered autoantigens released from AQ ingredients-damaged cells may induce autoantibody production. Higher frequencies of specific HLA-DR antigens in OSF patients may also help autoantibody production. Therefore, we conclude that the high incidence of autoantibodies in OSF patients may be due to AQ chewing habit, toxic AQ ingredients, and genetic susceptibility of the OSF patients.     

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口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种慢性、隐匿性、具有癌变倾向的口腔黏膜疾病。其主要临床表现为口腔黏膜纤维化、进食刺激性食物时口内疼痛,严重者可致张口和进食困难。目前,OSF的诊断手段主要包括临床检查和病理诊断。本文旨在结合笔者的临床经验和最新的相关文献,评述OSF诊断方法的研究进展,如分子生物学方法在OSF诊断中的应用、OSF合并症的诊断等。     

Growth of oral and skin fibroblasts from patients with oral submucous fibrosis

The purpose of the investigation was to evaluate and compare the proliferation (growth) of mouth fibroblasts and skin fibroblasts from patients with oral submucous fibrosis (OSF). Material comprised fibroblasts from fibrous bands situated in the buccal mucosa and from the inner aspect of the forearm of 8 patients with classic features of OSF as well as fibroblasts from 6 buccal mucosa and 8 skin biopsy specimens from healthy non-areca nut chewing individuals. Cells were cultured for 8 days according to standard techniques. Their growth was monitored daily, under optimal conditions as well as exposure to concentrations of arecoline. The data were analyzed using regression analysis, analysis of variance and the Kruskal-Wallis test. We found no statistically significant differences between the proliferation patterns of oral and skin fibroblasts from patients or between those from patients and controls. The reaction of the cells exposed to concentrations of arecoline was similar; at low concentrations (0.1–10 μg/ml) normal growth was maintained, while 100 μg/ml inhibited growth. It is concluded that fibroblasts from mouths affected by OSF have proliferation patterns which fall within normal parameters, that the excessive collagen formation in established OSF is not due to increased fibroblast proliferation and that arecoline does not stimulate fibroblast proliferation.     

Regional variations in oral submucous fibrosis in India

Regional variations in the characteristics of submucous fibrosis were studied in two districts in India. In Pune district this condition involved soft palate, uvula and retromolar areas significantly more often than in Ernakulam district. The tongue, floor of the mouth and the hard palate were not involved in Pune. The age of the patients in Pune district was lower than in Ernakulam district. Associated oral cancer, leukoplakia and petechiae were observed solely among patients in Ernakulam. The most important etiologic factor for submucous fibrosis is the chewing of areca nut, and in both areas studied all patients chewed areca nut. In Pune, cured areca nut without other ingredients was chewed by 66% and in Ernakulam, raw areca nut was chewed as an ingredient of pan with tobacco by 100%. Thus in Ernakulam, the juice and the quid were mostly spat out, whereas in Pune they were swallowed. The regional variations in the characteristics of submucous fibrosis could be related to the differences in the areca nut chewing habit between the two areas.     

口腔黏膜下纤维化中VEGF mRNA的表达研究

目的:研究口腔黏膜下纤维化(oral submucous fibrosis,OSF)患者早、中、晚期组中血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达,探讨VEGF与OSF微血管病变发生发展的关系.方法:选取OSF患者30例,其中早、中、晚期组各10例,5例健康志愿者为对照组.每例研究对象取其1:3腔黏膜,运用逆转录聚合酶链反应(RT-PCR)方法,研究OSF患者早、中、晚期组中VEGF mRNA的表达水平.结果:VEGF mRNA在OSF早、中期的表达均较正常口腔黏膜高(P＜0.05):VEGF mRNA在OSF早期的表达均明显高于中、晚期(P＜0.05),其中中期的表达与晚期相比差异无显著性(P＞0.05).结论:VEGF对OSF微血管病变的影响主要在黏膜下层,各种调控因素在基因转录水平导致VEGF的高表达可能是OSF局部组织缺血的代偿.     

口腔黏膜下纤维性变组织中Smad7蛋白的表达研究

目的检测Smad7蛋白在口腔黏膜下纤维性变(OSF)组织中的表达及分布,探讨其在OSF发病机制中的作用。方法采用免疫组化抗生蛋白链菌素生物素复合体法(strept Avidin-Biotin complex,SABC),用Smad7兔抗人多克隆抗体检测20例OSF病变组织及10例正常口腔黏膜组织中的Smad7蛋白的表达及分布。结果Smad7在OSF病变组织中为弱阳性表达,在正常口腔黏膜组织中为阴性表达,差别具有显著意义(P<0.05)。结论Smad7蛋白在OSF病变组织中弱阳性表达,在OSF发病机制中有重要作用。     

43例口腔黏膜下纤维性变血液流变学的研究

目的 了解口腔黏膜下纤维性变(oral subumcous fibrosis,OSF)患者血液流变方面的情况变化。方法 采用常规的血液流变学检测方法 ,对OSF患者的血液流变结果与正常值进行观察分析。结果 43例OSF患者的血液流变学40例出现异常。结论 提示OSF患者需做血液流变检查和在治疗时应作降脂、降粘的综合处理。?     

Treatment of oral submucous fibrosis by collagenase: effects on oral opening and eating function

OBJECTIVE: Patients with oral submucous fibrosis (OSF) suffer from the limitation of the oral opening. The aim of this study was to develop a simple and rapid method to improve the opening of the oral cavity and determine its effect on the incidence of developing oral carcinoma. METHODS: We first induced an OSF-like lesion in rabbits which histopathologically resembles OSF in betel nut chewers and evaluated the effects of exogenous collagenase on these lesions. We then applied the collagenase treatment regimen to patients with OSF. RESULTS: Endogenous collagenase activities in normal oral mucosa of patients exhibited 3- to 5-fold higher levels than that of OSF tissues. The collagenase treatment not only resulted in a significant improvement of oral opening, but patients also experienced a striking reduction in hypersensitivity to spices, sour, cold, and heat which helped restore eating function. Sub-mucosal fibrous proliferation, persistently good vascularization, and a mild increase in thickness of the sub-mucosal fibrous tissues were noticed 10 months after collagenase treatment. Within the 2-year follow-up period none of the treated patients developed an oral squamous cell carcinoma. CONCLUSION: A reduced content of functional collagenase observed in OSF mucosa of patients might be one mechanism responsible for collagen accumulation. Intervention of OSF by collagenase treatment at the early stage may reduce the incidence of developing oral carcinoma.