Detection of Helicobacter pylori in oral aphthous ulcers

A causative role for Helicobacter pylori (H. pylori) in the pathogenesis of oral mucosal ulcerations has been suggested previously. We have adopted the polymerase chain reaction (PCR) as a rapid and sensitive means to detect H. pylori in swabs of recurrent oral aphthous ulcers and in samples of other oral sites. Of the oral aphthous ulcer samples, 32 (71.8%) were found to be positive, while the saliva and plaque samples (most of them taken from the patients with aphthous ulcers) were consistently negative for H. pylori DNA, as detected by the PCR assay. Only two of the swab samples from the tongue (collected at the time of concurrent, H. pylori-positive oral aphthous ulcers) were found to be positive. The data suggest that H. pylori may be associated frequently with recurrent oral aphthous ulcers, and are consistent with previous studies indicating that saliva and plaque are not likely sources of contamination with this microorganism. There was no apparent correlation with HIV status (infection with human immunodeficiency virus). The possible pathogenic significance of Helicobacter pylori in oral ulcerations is discussed.     

Smecta 治疗口腔粘膜复发性阿弗它溃疡的临床探讨

目的 :初步探讨思密达在治疗口腔粘膜复发性阿弗它溃疡中的作用。方法 :选择临床病例共 118例 ,随机分成二组 ,即思密达治疗组 6 0例 ,锡类散治疗组 5 8例进行比较。结果 :二组比较 ,思密达治疗组总有效率为 96 .7% ,而锡类散治疗组的总有效率为 79% ,两者在统计学上有显著性差异 (P(0 .0 1)。结论 :思密达在治疗口腔粘膜复发性阿弗它溃疡中是值得提倡的理想药物。     

Oral nicorandil-induced lesions are not aphthous ulcers

OBJECTIVES: (i) To accurately define these lesions determining whether oral nicorandil-induced lesions are aphthous ulcers; (ii) To determine clinical characteristics of oral nicorandil-induced lesions. MATERIALS AND METHODS: Two slide conferences were held. A total of 60 dermatologists assigned diagnosis and clinical criteria to 11 photographs of oral nicorandil-induced lesions. Two slides were randomly selected and duplicated to be used as control. The panel of slides included independent lesions and photographs of different lesions of the same patient. Statistical analysis used chi2-test, estimation of the percentage interobserver agreement, and kappa-values. RESULTS: The diagnosis of non-aphthous ulcer (71.8%) was significantly held in comparison with the diagnosis of oral aphthous ulcer (28.2%; P<0.001). To differentiate aphthous ulcer from non-aphthous ulcer, physicians significantly used three clinical criteria. The diagnosis of non-aphthous ulcer were significantly associated with the absence of yellow-based ulceration (P<0.001), with the linear shape (P=0.006) and the absence of inflammatory halo (P=0.003). CONCLUSION: Oral nicorandil-induced lesions are not aphthous ulcers. We propose that at this stage of our knowledge, oral nicorandil-induced ulcer is the most suitable terminology.     

Preliminary evidence for an association of Epstein-Barr virus with pre-ulcerative oral lesions in patients with recurrent aphthous ulcers or Behiçet's disease

In this study we used the polymerase chain reaction (PCR), slot blot and Southern blot hybridization, direct sequencing and in situ hybridization (ISH) to show the possible presence of EBV-DNA in pre-ulcerative oral aphthous lesions of patients with recurrent aphthous ulcers (RAU) or Behet's disease (BD). For this purpose, formalin-fixed biopsy specimens were obtained from 13 pre-ulcerative oral aphthous lesions of nine RAU and four BD patients. Five specimens of normal oral mucosa (NOM) from five normal control subjects and 10 specimens of oral erosive or ulcerative lesions from 10 patients with erosive lichen planus (ELP) were also included. EBV-DNA was detected by PCR in 5 of the 13 (38.5%) pre-ulcerative oral aphthous lesions, two from RAU patients and three from BD patients. However, no EBV-DNA was demonstrated in five NOM specimens from normal control subjects and in 10 specimens of oral lesions from ELP patients. EBV-DNA was also demonstrated in patients'peripheral blood lymphocytes and/ or plasma, suggesting that the lymphocytes may be the reservoir of latent EBV infection and there is EBV shedding in the plasma. EBV-DNA was detected by ISH in only one PCR-positive case; the reaction product was found to deposit on the nuclei of some of the epithelial cells and lymphocytes. By immunohistochemistry, expression of Epstein-Barr nuclear antigen and EBV/C3d receptors was also noted in some of the epithelial cells and lymphocytes in this ISH-positive case. Therefore, we suggest that the epithelial cells of pre-ulcerative oral aphthous lesions may be infected by EBV through EBV-infected lymphocytes; also, the cytotoxic T lymphocyte-induced lysis of the EBV-infected epithelial cells, but not the virus-induced cytolysis, may be the main mechanism causing oral ulcer formation. Our data provide preliminary evidence for an association of EBV with pre-ulcerative oral aphthous lesions in RAU and BD patients.     

Human cytomegalovirus as a potential etiologic agent in recurrent aphthous ulcers and Behçet's disease

In a preliminary study on anti-human cytomegalovirus (HCMV) antibody (Ab) by ELISA. the serum anti-HCMV/IgG Ab concentrations in 22 patients with recurrent aphthous ulcers (RAU) in the remission stage were found to be significantly higher than in 22 control subjects (121±42 vs 100±27, P<0.05) and in 39 patients with RAU in the active stage (121±42 vs 88±45, P<0.01). Therefore, the potential of HCMV as an etiologic agent in RAU was proposed and studies using the polymerase chain reaction (PCR) and in situ hybridization (ISH) have been performed to investigate the possible presence of HCMV DNA in pre-ulcerative oral aphthous lesions in patients with RAU or Behçet's disease (BD) of the mucocutaneous type. For this purpose, formalin-fixed biopsy specimens were obtained from 13 pre-ulcerative oral aphthous lesions, 2 samples of normal oral mucosa and 1 ileal mucosal lesion from 9 RAU patients and 4 BD patients. Five specimens of normal oral mucosa from 5 normal control subjects and 12 specimens of oral erosive or ulcerative lesions from 12 patients with erosive lichen planus (ELP) were also included. By PCR, HCMV DNA was detected in 5 of the 13 (38.5%) pre-ulcerative oral aphthous lesions. 3 from RAU patients and 2 from BD patients. The ileal mucosa specimen was also HCMV DNA-positive, whereas HCMV DNA was not demonstrated in any of the 7 specimens of normal oral mucosa from RAU patients and normal control subjects; 12 specimens of oral lesions from ELP patients were similarly negative. ISH did not detect HCMV DNA in any of the biopsy specimens from RAU patients and control subjects. Our findings suggest that HCMV may be an etiologic agent in some cases of RAU and BD.     

免疫方法建立复发性口腔溃疡动物模型

目的 :利用试验家兔口腔黏膜蛋白注射方法 ,建立复发性口腔溃疡动物模型 ,为研究人类RAU的发病机制及治疗提供理论基础。方法 :应用从试验家兔提取的口腔黏膜蛋白及沉淀物 ,分别作为抗原免疫家兔。将上述抗原注入家兔脊柱二侧皮内 ,2周注射一次 ,观察家兔口腔溃疡的发病情况及愈合情况。检测试验家兔血清中抗口腔黏膜抗体并做溃疡的组织病理学检查。结果 :以口腔黏膜蛋白作为抗原的实验家兔都发生了RAU ,血清中抗口腔黏膜抗体阳性。以口腔黏膜蛋白作为抗原组与以沉淀物作为抗原组引发实验家兔RAU有显著统计学差异(p <0 .0 1)。结论 :利用兔口腔黏膜蛋白作为抗原 ,可引起实验家兔发生RAU ,其临床表现及组织学检查均与人类RAU相似 ,表明此动物模型可作为研究人类RAU的模型。也提示了人类RAU的发生可能与自身免疫有关。     

Smokeless tobacco use prevents aphthous stomatitis.

Aphthous stomatitis is a common, recurrent, painful ulcerative condition of the oral mucosa. Cigarette smoking has been reported to protect against aphthous ulcers. To determine whether smokeless tobacco use also protects against aphthous ulcers, we examined the oral mucosa in 1456 professional baseball players, about half of whom were smokeless tobacco (ST) users. After controlling for the confounding effects of age, race, cigarette smoking, alcohol consumption, and dental hygiene practices, ST use was found to significantly reduce the risk of aphthous ulcers among these healthy young men (odds ratio = 0.4; p = 0.04). It has been suggested that cigarette smoking prevents aphthous ulcers by causing increased keratinization of the oral mucosa, and ST may protect by the same mechanism. Alternatively, a component of tobacco that is systemically absorbed might be responsible for protecting against aphthous ulcers. If the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor.     

Immunoglobulin-bearing lymphocytes and polymorphonuclear leucocytes in recurrent aphthous ulcers in man.

Direct immunofluorescent techniques were used to study the number of immunoglobulin-bearing lymphocytes and polymorphonuclear leucocytes in specimens of mucosal lesions from 10 patients with recurrent aphthous ulcers. The proportion of immunoglobulin-coated cells in the peripheral blood of the 10 patients was also studied. Ten normal healthy controls were included. IgM-, IgD- and IgE-bearing lymphocytes and polymorphonuclear leucocytes were found in sections adjacent to the mucosal lesions. IgE-bearing peripheral blood lymphocytes were slightly but significantly increased in patients with recurrent aphthous ulcers. The recruitment of immunoglobulin-bearing lymphocytes and polymorphonuclear leucocytes into the lamina propria and their migration into the stratum spinosum of mucosa may be involved in the pathogenesis of these ulcers.     

Molecular identification of bacteria on the tongue dorsum of subjects with and without halitosis

Aim:  Compare the microbial profiles on the tongue dorsum in patients with halitosis and control subjects in a UK population using culture-independent techniques.
Materials and methods:  Halitosis patients were screened according to our recently developed recruitment protocol. Scrapings from the tongue dorsum were obtained for 12 control subjects and 20 halitosis patients. Bacteria were identified by PCR amplification, cloning and sequencing of 16S rRNA genes.
Results:  The predominant species found in the control samples were Lysobacter -type species, Streptococcus salivarius , Veillonella dispar , unidentified oral bacterium, Actinomyces odontolyticus , Atopobium parvulum and Veillonella atypica . In the halitosis samples, Lysobacter -type species, S. salivarius , Prevotella melaninogenica , unidentified oral bacterium, Prevotella veroralis and Prevotella pallens were the most commonly found species. For the control samples, 13–16 (4.7–5.8%) of 276 clones represented uncultured species, whereas in the halitosis samples, this proportion increased to 6.5–9.6% (36–53 of 553 clones). In the control samples, 22 (8.0%) of 276 clones represented potentially novel phylotypes, and in the halitosis samples, this figure was 39 (7.1%) of 553 clones.
Conclusions:  The microflora associated with the tongue dorsum is complex in both the control and halitosis groups, but several key species predominate in both groups.     

Induction of adhesion molecule expression on blood vessels and keratinocytes in recurrent oral ulceration

Adhesion molecules are known to play a crucial role in the recruitment of inflammatory cells to sites of inflammation. In this study endothelial cell and keratinocyte adhesion molecule expression in recurrent oral ulcers (ROU) ( n =13) was compared with that found in normal oral mucosa (NOM) ( n =11) and experimentally induced ulcers (EIU) ( n =5) by using immunohistochemistry. Significantly greater expression of both vascular cell adhesion molecule-1 (VCAM-1) and E-selectin was demonstrated on vasculature in ROU compared with that found in both NOM and EIU. Induction of keratinocyte intercellular adhesion molecule-1 (ICAM-1) was also a prominent feature of ROU. The expression of VCAM-1 and E-selectin on blood vessels in ROU is likely to be important in the accumulation of lymphocytes that characterise early aphthous lesions. The induction of keratinocyte ICAM-1 may facilitate lymphocyte invasion of the epithelium in ROU, which may ultimately result in ulcer formation.     

Innervation of recurrent aphthous ulcers

Specimens from nonkeratinized oral mucosa were obtained from diseased and clinically healthy mucosa from 7 patients with minor recurrent aphthous ulcers. The innervation of the specimens was visualized using antibodies to neuron-specific intermediate cytoskeletal neurofilament fiber, the cytoplasmic protein gene product 9.5 and a 38 kDa integral membrane protein of synaptic vesicles applied in avidin-biotin-peroxidase staining. Mapping with these 3 antibodies revealed dense and basically similar pattern of innervation in the specimens of the clinically healthy oral mucosa. In recurrent aphthous ulcers, all 3 general markers disclosed peripheral nerve fibers also in the lesions, apart from the necrotic area, among the inflammatory cells without signs of retraction from the diseased area. Synaptophysin staining suggested that these peripheral nerve fibers in the inflammatory areas still contained synaptic vesicles. Accordingly, they were shown to contain substance P and calcitonin gene-related peptide, which are known to be relased upon stimulation of the nerve and can exert potent paracrine actions, possibly on the local inflammatory cells as suggested by a close spatial relationship between neuropeptide-containing nerves and inflammatory cells.     

Delayed contact sensitivity on the lips and oral mucosa due to propolis-case report

We report a rare case of a patient who was referred to the Department of Oral medicine in Zagreb, Croatia. The patient was 20 years old, otherwise healthy and not taking any medication. She presented with irregular erosions partially covered with pseudomembranes that involved both lips and retrocomissural mucosa. Discrete erosion was also noticed on her lower lingual gingiva in the area 42. She reported a propolis solution self-medication for treatment of recurrent aphthous ulcers. After ten days of propolis application, lip and oral lesions developed. Patch test to propolis was proven. We highlight the fact that some folk medicine medications, such as propolis, although being known for many decades to be helpful in various conditions, in some individuals might lead to unwanted side-effects due to its antigenic potential. Additionally, every colleague, during the differential diagnosis of the oral lesions must bear in mind unwanted reactions to folk medicine products.     

表皮生长因子受体蛋白和基因在口腔复发性阿弗他溃疡中表达的变化及意义

目的　观察表皮生长因子受体 (EGFR)在口腔复发性阿弗他溃疡 (RAU)组织中蛋白和基因表达变化。方法　用免疫组化和RT PCR技术检测EGFR在RAU中表达的变化。结果　RAU组织中EGFR的mRNA表达明显下降 (P <0 .0 5 )。EGFR在正常黏膜和RAU中表达水平较低 ,阳性表达位于细胞膜、胞质 ,正常黏膜中表达主要位于基底细胞层中。在RAU中该蛋白表达水平明显降低 (P <0 .0 5 )。结论　RAU中的EGFR表达受抑 ,这可能与RAU的发病机制有着密切的联系     

Immunolocalization of tumor necrosis factor-α expressing cells in recurrent aphthous ulcer lesions (RAU)

Tumor necrosis factor (TNF)-alpha is a pro-inflammatory cytokine and crucial mediator in many aspects of immunity. Although several studies have shown that recurrent aphthous ulcers (RAU) can be prevented by treatment that prevents the synthesis of endogenous TNF-alpha little is known about the location and distribution of TNF-alpha-expressing cells at disease sites. The aim of the present work is, therefore, to investigate TNF-alpha and its cellular distribution in RAU lesions compared with those in induced oral traumatic ulcers (TUs). Twelve biopsies of RAU lesions of oral mucosa were obtained from 12 patients with RAU. They were compared to a control group consisting of ten samples of induced TUs. All samples were analyzed for TNF-alpha expression by using monoclonal mouse anti-human TNF-alpha antibody in avidin-biotin-peroxidase complex (ABC) staining. Results were quantified by a semi-automatic VIDAS image analysis system. TNF-alpha immunoreactivity was contained mainly in monocyte/macrophages and lymphocytes within the mononuclear inflammatory infiltrates. TNF-alpha was often seen in mast cells and vascular endothelial cells in connective tissue lateral to the inflammatory infiltrates. Interestingly, 32%-60% of the mononuclear cells were found to be TNF-alpha immunoreactive in RAU lesions. TNF-alpha containing cells were more numerous in aphthae (188+/-46 cells/0.2 mm2) compared with controls (52+/-14 cells/0.2 mm2, P<0.001). These findings suggest that RAU lesions are characterized by high expression of TNF-alpha. Because such expression occurred in the mononuclear inflammatory cells, mast cells and vascular endothelial cells, TNF-alpha, which is a major inflammatory mediator, may contribute to the activation and recruitment of leukocytes that are found in RAU lesions.     

梅毒在口腔黏膜表现的临床分析——附8例报告

目的:分析梅毒在口腔黏膜的临床表现。方法:总结8例以口腔梅黏膜病损为首发症状的梅毒患者的临床特征,并结合相关文献进行临床分析。结果:8例梅毒患者中7例表现为梅毒黏膜斑,好发部位为下唇;3例表现为梅毒性黏膜炎。1例在一期梅毒时期被误诊为复发性口疮。1例儿童因父母双方均为梅毒患者而间接感染结论:梅毒在口腔的首发症状以梅毒黏膜斑最为常见。口腔医生应掌握梅毒的口腔病损,并及时对患者家属进行梅毒筛查,以免误诊,漏诊。     

康复新液治疗复发性阿弗他溃疡近期疗效观察

目的：探讨康复新液治疗复发性阿弗他溃疡（RAU）的近期疗效。方法：86例RAU病例随机分为2组,实验组用康复新液治疗,对照组用本院制剂口腔溃疡软膏局部涂抹,根据中华口腔医学会口腔黏膜病专业委员会制定的“RAU疗效评价试行标准”评价其疗效。结果：实验组和对照组的溃疡持续时间和疼痛指数及疗效的差异性均有统计学意义。结论：康复新液对RAU的治疗效果较口腔溃疡软膏佳,可以作为临床上治疗RAU的首选药物。     

Leukocyte migration inhibition in recurrent aphthous ulceration

Leukocyte inhibitory factor (LIF) production in response to streptococcal antigens and oral mucosa was examined as a possible pathogenic mechanism in recurrent aphthous ulceration (RAU). Mononuclear cells from RAU patients and controls were stimulated with antigens prepared from two species of streptococci and from oral mucosa. Candida albicans and foreskin were tested as control antigens. There-were some statistically significant differences in leukocyte migration inhibition between patients and controls with some concentrations of Streptococcus sanguis (ATCC 10556) and C. albicans , and a trend toward low migration indices with oral mucosa. However, the roughly equal numbers of patients and controls responding positively to each antigen and the large background variation suggest a lack of biological significance. LIF production did not increase consistently in the early stages and did not correlate with ulcer development in patients studied sequentially. We conclude that LIF production (at least in response to the antigens tested) plays no pathogenic role in RAU. Our data do not support the hypothesis that a specific cell-mediated sensitivity to streptococcal antigens is involved in RAU.     

Helicobacter pylori DNA in recurrent aphthous stomatitis

BACKGROUND: Considering not only the fact that recurrent aphthous stomatitis (RAS) and stomach ulcers are immunologically mediated ulcers associated with Helicobacter pylori, but also the recent evidence that anaemia can be associated with both diseases, and the discovery of H. pylori in the oral mucosa led us to hypothesize that this bacteria may be related to RAS pathogenesis. METHODS: Thirty-six consecutive subjects affected by minor and major forms of RAS and 48 healthy volunteers were included in the present study. The nested polymerase chain reaction (PCR) technique was used to detect the presence of H. pylori in the oral lesion, the normal contralateral mucosa of patients affected by RAS and the oral mucosa of control subjects. The chi2- and Fisher's tests were used for statistical analysis. RESULTS: No association between RAS lesions and H. pylori was observed. However, 14 out of 36 (38.9%) of the patients with RAS were found to show the presence of H. pylori DNA in the lesion and/or contralateral mucosa. Sixteen out of 48 (33.3%) of the patients without RAS (control subjects) were positive (P > 0.05). CONCLUSION: The present study does not give support to the assumption that H. pylori could be involved in RAS development.     

Effect of a mouth rinse containing amyloglucosidase and glucose oxidase on recurrent aphthous ulcers in children and adolescents.

Recurrent aphthous ulcers are one of the most common painful diseases affecting the oral mucosa in children and adults. The aetiology is poorly understood and the treatment thus has for years mostly been symptomatic. However, there has been some promising methods in decreasing the frequency of aphthous ulcer episodes. One of these is the use of a dentifrice containing the combination of the enzymes amyloglucosidase and glucose oxidase (Zendium). The aim of this investigation was, in a pre-study and a double-blind, crossover study, to report if a mouth rinse containing the same enzymes was effective against aphthous ulcers. Thirty-six children and adolescents 7 to 19 years of age took part in the pre-study and thirty-three children and adolescents 7 to 19 years of age took part in the double-blind, crossover study. In both tests the mouth rinses with enzymes resulted in a significant reduction in the number of new aphthous ulcers and pain. In the double-blind, crossover test the 33 children experienced 60 episodes of new ulcers during a 6-month period, including a 3-month period with enzyme rinsings, compared to 221 episodes when rinsing with placebo solution. 55% of the children were completely free from ulcers during the enzyme solution rinsing period followed by a 3-month recovery period compared to 0% when rinsing with placebo. The study confirms earlier studies. Daily rinsing with the enzyme solution can be a recommended treatment to children and adolescents with recurrent aphthous ulcers.     

HIV感染者和AIDS患者口腔非特异性溃疡

目的:口腔非特异性(NOS)溃疡是一类与H IV感染有关的口腔病变,其临床表现不同于常见口腔溃疡。通过对NOS口腔溃疡临床特征的分析,为临床医师提供鉴别诊断。方法:回顾性分析72例H IV/AIDS患者,NOS口腔溃疡有3例,探讨其临床特征并与复发性阿弗他溃疡、单纯疱疹性口炎进行比较,探讨其发病机制。结果:NOS口腔溃疡的好发部位为软腭、口咽及舌腭弓处,常为1~2个,病程较长,CD4 细胞明显减少,多伴发白色念珠菌感染。结论:NOS口腔溃疡的发病部位、病程与预后较为特殊,与AIDS的病程进展有一定的联系。