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The biochemistry and physiology of metallic fluoride: action, mechanism, and implications. 金属氟化物的生物化学和生理学:作用、机制和意义。
Liang Li

Fluoride is a well-known G protein activator. Activation of heterotrimeric GTP-binding proteins by fluoride requires trace amounts of Al3+ or Be2+ ions. AlFx mimics a gamma-phosphate at its transition state in a Galpha protein and is therefore able to inhibit its GTPase activity. AlFx also forms complexes with small GTP-binding proteins in the presence of their GTPase-activating proteins (GAP). As phosphate analogs, AlFx or BeFx affect the activity of a variety of phosphoryl transfer enzymes. Most of these enzymes are fundamentally important in cell signal transduction or energy metabolism. Al3+ and F- tend to form stable complexes in aqueous solution. The exact structure and concentration of AlFx depend on the pH and the amount of F- and Al3+ in the solution. Humans are exposed to both F and Al. It is possible that Al-F complexes may be formed in vivo, or formed in vitro prior to their intake by humans. Al-F complexes may play physiological or pathological roles in bone biology, fluorosis, neurotoxicity, and oral diseases such as dental caries and periodontal disease. The aim of this review is to discuss the basic chemical, biochemical, and toxicological properties of metallic fluoride, to explore its potential physiological and clinical implications.

氟化物是一种众所周知的G蛋白活化剂。氟激活异三聚体gtp结合蛋白需要微量的Al3+或Be2+离子。AlFx模仿α -磷酸在α - pha蛋白中的过渡状态,因此能够抑制其GTPase活性。在gtpase激活蛋白(GAP)存在的情况下,AlFx也与小的gtp结合蛋白形成复合物。作为磷酸类似物,AlFx或BeFx影响多种磷酸基转移酶的活性。这些酶在细胞信号转导或能量代谢中起着重要的作用。Al3+和F-在水溶液中倾向于形成稳定的配合物。AlFx的确切结构和浓度取决于溶液中的pH值和F-和Al3+的量。人类同时暴露于氟和铝。在人类摄入氟和铝之前,可能在体内或体外形成氟和铝复合物。Al-F复合物可能在骨生物学、氟中毒、神经毒性和口腔疾病(如龋齿和牙周病)中发挥生理或病理作用。本文旨在讨论金属氟化物的基本化学、生化和毒理学特性,探讨其潜在的生理和临床意义。
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引用次数: 137
Yeasts in apical periodontitis. 根尖牙周炎中的酵母菌。
T M T Waltimo, B H Sen, J H Meurman, D Ørstavik, M P P Haapasalo

Microbiological reports of apical periodontitis have revealed that yeasts can be isolated from approximately 5-20% of infected root canals. They occur either in pure cultures or together with bacteria. Almost all isolated yeasts belong to the genus Candida, and the predominant species is C. albicans. Pheno- and genotypic profiles of C. albicans isolates show heterogeneity comparable with those of isolates from other oral sites. C. albicans expresses several virulence factors that are capable of infecting the dentin-pulp complex, including dentinal tubules. This causes, consequentially, an inflammatory response around the root apex, which suggests a pathogenic role for this organism in apical periodontitis. Yeasts are particularly associated with persistent root canal infections that do not respond favorably to conservative root canal therapy. This may be due to the resistance of all oral Candida species against a commonly used topical medicament, calcium hydroxide. However, other antimicrobial agents may offer alternative therapeutic approaches and improve the treatment of these persistent cases of apical periodontitis.

根尖牙周炎的微生物学报告显示,酵母菌可以从大约5-20%的感染根管中分离出来。它们要么发生在纯培养物中,要么与细菌一起发生。几乎所有分离的酵母菌都属于念珠菌属,优势种是白色念珠菌。白色念珠菌分离株的表型和基因型表现出与其他口腔部位分离株相当的异质性。白色念珠菌表达几种能够感染牙本质-牙髓复合体的毒力因子,包括牙本质小管。这必然会引起根尖周围的炎症反应,这表明这种微生物在根尖牙周炎中的致病作用。酵母菌与持续性根管感染特别相关,这种感染对保守的根管治疗反应不佳。这可能是由于所有口腔念珠菌对一种常用的外用药物氢氧化钙具有耐药性。然而,其他抗菌药物可能提供替代治疗方法,并改善这些持续性根尖牙周炎病例的治疗。
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引用次数: 91
Neurobiological mechanisms involved in sleep bruxism. 睡眠磨牙症的神经生物学机制。
G J Lavigne, T Kato, A Kolta, B J Sessle

Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

据报道,8%的成年人患有睡眠磨牙症(SB),主要与有节奏的咀嚼肌活动(RMMA)有关,其特征是颚肌重复收缩(频率为1hz的3次或更多)。SB的后果可能包括牙齿破坏、下颚疼痛、头痛或下颌活动受限,以及磨牙声,扰乱床伴的睡眠。SB可能是大多数正常人睡眠时发生的咀嚼肌活动的一种极端表现,因为60%的正常睡眠者在没有研磨声的情况下观察到RMMA。SB的病理生理学正在变得越来越清晰,并且有大量的证据概述了与咀嚼、吞咽和呼吸有关的节律性下颌运动(RJM)的神经生理学和神经化学。睡眠文献提供了大量证据,描述了从睡眠开始到以快速眼动(REM)睡眠为特征的肌张力下降的机制。一些脑干结构(如网状口桥、尾桥、细胞旁桥)和神经化学物质(如血清素、多巴胺、γ -氨基丁酸[GABA]、去甲肾上腺素)参与了RJM的发生和睡眠时肌肉张力的调节。目前尚不清楚为什么在正常受试者中有高比例的人在睡眠期间出现RMMA,以及为什么在SB患者中这种活动的频率和幅度是正常人的三倍。同样不清楚的是,为什么睡眠时的RMMA以开颌肌和闭颌肌共同激活为特征,而不是咀嚼时的开颌肌和闭颌肌交替活动模式。本综述的最后一部分提出,睡眠期间的RMMA具有润滑上消化道和增加气道通畅的作用。这篇综述最后概述了未来研究的问题。
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引用次数: 514
Lipoxins in chronic inflammation. 慢性炎症中的脂质。
Alpdogan Kantarci, Thomas E Van Dyke
The discovery of endogenous molecules involved in counterregulation of inflammatory responses that may lead to tissue injury provides an opportunity to explore new therapeutic approaches based on manipulation of new pathways. Natural counterregulatory pathways may reduce the possibility of unwanted toxic side-effects. Lipoxins are trihydroxytetraene-containing eicosanoids that are generated within the vascular lumen during platelet-leukocyte interactions and at mucosal surfaces via leukocyte-epithelial cell interactions. During cell-cell interactions, transcellular biosynthetic pathways are the major lipoxin biosynthetic routes, and thus, in humans, lipoxins are formed in vivo during multicellular responses, such as inflammation and asthma. This branch of the eicosanoid cascade generates specific tetraene-containing products that serve as "stop signals" for neutrophils that regulate key steps in leukocyte trafficking and prevent neutrophil-mediated tissue injury. These novel anti-inflammatory lipid mediators also appear to facilitate the resolution of the acute inflammatory response. In this review, recent findings and new concepts pertaining to the generation of lipoxins and their impact on the resolution of acute inflammation, and organ protection from leukocyte-mediated injury, are presented. The parallels and possible associations with periodontal diseases are discussed.
内源性分子参与炎症反应的反调节,可能导致组织损伤的发现提供了一个机会,探索新的治疗方法基于操作新的途径。天然的反调控途径可以减少不必要的毒副作用的可能性。脂毒素是一种含三羟基四烯的类二十烷化合物,在血小板-白细胞相互作用时在血管腔内产生,在粘膜表面通过白细胞-上皮细胞相互作用产生。在细胞-细胞相互作用过程中,跨细胞生物合成途径是主要的脂肪素生物合成途径,因此,在人类中,脂肪素是在体内多细胞反应中形成的,如炎症和哮喘。这个类二十烷级联的分支产生特定的含四烯的产物,作为中性粒细胞的“停止信号”,调节白细胞运输的关键步骤,防止中性粒细胞介导的组织损伤。这些新型抗炎脂质介质似乎也有助于急性炎症反应的解决。在这篇综述中,最近的发现和新的概念有关脂毒素的产生及其影响的急性炎症的解决,和器官保护从白细胞介导的损伤,介绍。讨论了牙周病的相似之处和可能的联系。
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引用次数: 71
Oral sequelae of head and neck radiotherapy. 头颈部放射治疗的口腔后遗症。
A Vissink, J Jansma, F K L Spijkervet, F R Burlage, R P Coppes

In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.

除了抗肿瘤作用外,电离辐射还会对位于辐射入口的正常组织造成损伤。头颈部放射治疗的口腔并发症是放射对唾液腺、口腔黏膜、骨、牙列、咀嚼肌肉组织和颞下颌关节等有害影响的结果。放射治疗的临床后果包括粘膜炎、唾液分泌不足、味觉丧失、放射性骨坏死、放射性龋齿和牙关。粘膜炎和味觉丧失是可逆的,通常在辐照后早期消退,而唾液分泌不足通常是不可逆的。此外,患放射性龋齿和放射性骨坏死的风险是一种终身威胁。所有这些后果都给患者造成了沉重的负担,并对放疗期间和放疗后的生活质量产生了巨大的影响。在这篇综述中,讨论了辐射引起的健康口腔组织的变化及其临床后果。
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引用次数: 515
Molecular recognition at the protein-hydroxyapatite interface. 蛋白质-羟基磷灰石界面的分子识别。
Patrick S Stayton, Gary P Drobny, Wendy J Shaw, Joanna R Long, Michele Gilbert

Proteins found in mineralized tissues act as nature's crystal engineers, where they play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (bones/teeth) and calcium oxalate (kidney stones). Despite their importance in hard-tissue formation and remodeling, and in pathological processes such as stone formation and arterial calcification, there is little known of the protein structure-function relationships that govern hard-tissue engineering. Here we review early studies that have utilized solid-state NMR (ssNMR) techniques to provide in situ secondary-structure determination of statherin and statherin peptides on their biologically relevant hydroxyapatite (HAP) surfaces. In addition to direct structural study, molecular dynamics studies have provided considerable insight into the protein-binding footprint on hydroxyapatite. The molecular insight provided by these studies has also led to the design of biomimetic fusion peptides that utilize nature's crystal-recognition mechanism to display accessible and dynamic bioactive sequences from the HAP surface. These peptides selectively engage adhesion receptors and direct specific outside-in signaling pathway activation in osteoblast-like cells.

在矿化组织中发现的蛋白质就像自然界的晶体工程师,它们在促进或抑制羟基磷灰石(骨骼/牙齿)和草酸钙(肾结石)等矿物质的生长方面起着关键作用。尽管它们在硬组织形成和重塑以及结石形成和动脉钙化等病理过程中很重要,但对控制硬组织工程的蛋白质结构-功能关系知之甚少。在此,我们回顾了利用固态核磁共振(ssNMR)技术在其生物相关的羟基磷灰石(HAP)表面上原位测定石蜡蛋白和石蜡蛋白肽二级结构的早期研究。除了直接的结构研究外,分子动力学研究为羟基磷灰石上的蛋白质结合足迹提供了相当大的见解。这些研究提供的分子洞察力也导致了仿生融合肽的设计,利用自然界的晶体识别机制,从HAP表面显示可接近的动态生物活性序列。这些多肽选择性地参与粘附受体,并在成骨细胞样细胞中直接特异性的外-内信号通路激活。
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引用次数: 117
Chronic hyperplastic candidosis/candidiasis (candidal leukoplakia). 慢性增生性念珠菌病/念珠菌病(念珠菌白斑)。
M A M Sitheeque, L P Samaranayake

Chronic hyperplastic candidosis/candidiasis (CHC; syn. candidal leukoplakia) is a variant of oral candidosis that typically presents as a white patch on the commissures of the oral mucosa. The major etiologic agent of the disease is the oral fungal pathogen Candida predominantly belonging to Candida albicans, although other systemic co-factors, such as vitamin deficiency and generalized immune suppression, may play a contributory role. Clinically, the lesions are symptomless and regress after appropriate antifungal therapy and correction of underlying nutritional or other deficiencies. If the lesions are untreated, a minor proportion may demonstrate dysplasia and develop into carcinomas. This review outlines the demographic features, etiopathogenesis, immunological features, histopathology, and the role of Candida in the disease process. In the final part of the review, newer molecular biological aspects of the disease are considered together with the management protocols that are currently available, and directions for future research.

慢性增生性念珠菌病/念珠菌病;念珠菌性白斑是口腔念珠菌病的一种变种,通常表现为口腔粘膜交界处的白色斑块。该疾病的主要病因是口腔真菌病原体念珠菌,主要属于白色念珠菌,尽管其他全身辅助因素,如维生素缺乏和全身免疫抑制,可能起一定作用。临床上,在适当的抗真菌治疗和纠正潜在的营养或其他缺陷后,病变无症状并消退。如果病变未经治疗,一小部分可能表现为发育不良并发展成癌。本文综述了该疾病的人口学特征、发病机制、免疫学特征、组织病理学以及念珠菌在该疾病过程中的作用。在回顾的最后一部分,新的分子生物学方面的疾病是考虑与目前可用的管理方案,以及未来的研究方向。
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引用次数: 186
Ultrasound stimulation of maxillofacial bone healing. 超声刺激颌面骨愈合。
J Schortinghuis, B Stegenga, G M Raghoebar, L G M de Bont

A substantial part of the maxillofacial surgery practice deals with maxillofacial bone healing. In the past decades, low-intensity ultrasound treatment has been shown to reduce the healing time of fresh fractures of the extremities up to 38%, and to heal delayed and non-unions up to 90% and 83%, respectively. Based on the assumption that the process of bone healing in the bones of the extremities and maxillofacial skeleton is essentially the same, the potential of ultrasound to stimulate maxillofacial bone healing was investigated. Although limited evidence is available to support the susceptibility of maxillofacial bone to the ultrasound signal, ultrasound may be of value in the treatment of delayed unions, in callus maturation after distraction, and in the treatment of osteoradionecrosis.

颌面外科实践的一个重要部分涉及颌面骨愈合。在过去的几十年里,低强度超声治疗已被证明可将四肢新骨折的愈合时间缩短38%,延迟愈合和不愈合分别缩短90%和83%。基于四肢骨骼和颌面骨骼的骨愈合过程基本相同的假设,研究了超声刺激颌面骨愈合的潜力。虽然支持颌面骨对超声信号敏感性的证据有限,但超声在治疗延迟愈合、牵张后骨痂成熟和治疗放射性骨坏死方面可能有价值。
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引用次数: 53
Paracoccidioidomycosis of the mouth: an emerging deep mycosis. 口腔副球孢子菌病:一种正在出现的深部真菌病。
Oslei Paes Almeida, Jorge Jacks, Crispian Scully

Oral fungal infections (mycoses) have come into particular prominence since the advent of infection with Human Immunodeficiency Virus (HIV), and recognition of the Acquired Immune Deficiency Syndrome (AIDS), as well as the phenomenal increase in world travel with increased exposure to infections endemic in the tropics. Paracoccidioidomycosis is a rare mycosis worldwide but common in Brazil and some other areas in Latin America. It can be life-threatening and can manifest with a spectrum of clinical presentations, including frequent oral lesions. This paper reviews the more recent information on Paracoccidioidomycosis, emphasizing those areas most relevant in dental science.

自从人类免疫缺陷病毒(HIV)感染、获得性免疫缺陷综合征(艾滋病)的认识以及世界旅行的显著增加(热带地区感染地方病的增加)出现以来,口腔真菌感染(真菌病)变得特别突出。副球孢子菌病在世界范围内是一种罕见的真菌病,但在巴西和拉丁美洲的一些其他地区很常见。它可能危及生命,并可能表现为一系列临床表现,包括频繁的口腔病变。本文综述了近年来关于副球孢子菌病的研究进展,重点介绍了与口腔科学最相关的研究领域。
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引用次数: 45
Update on burning mouth syndrome: overview and patient management. 灼口综合征最新进展:概述和患者管理。
A Scala, L Checchi, M Montevecchi, I Marini, M A Giamberardino

Burning Mouth Syndrome (BMS) is a chronic pain syndrome that mainly affects middle-aged/old women with hormonal changes or psychological disorders. This condition is probably of multifactorial origin, often idiopathic, and its etiopathogenesis remains largely enigmatic. The present paper discusses several aspects of BMS, updates current knowledge, and provides guidelines for patient management. There is no consensus on the diagnosis and classification of BMS. The etiopathogenesis seems to be complex and in a large number of patients probably involves interactions among local, systemic, and/or psychogenic factors. In the remaining cases, new interesting associations have recently emerged between BMS and either peripheral nerve damage or dopaminergic system disorders, emphasizing the neuropathic background in BMS. Based on these recent data, we have introduced the concepts of "primary" (idiopathic) and "secondary" (resulting from identified precipitating factors) BMS, since this allows for a more systematic approach to patient management. The latter starts with a differential diagnosis based on the exclusion of both other orofacial chronic pain conditions and painful oral diseases exhibiting muco-sal lesions. However, the occurrence of overlapping/overwhelming oral mucosal pathologies, such as infections, may cause difficulties in the diagnosis ("complicated BMS"). BMS treatment is still unsatisfactory, and there is no definitive cure. As a result, a multidisciplinary approach is required to bring the condition under better control. Importantly, BMS patients should be offered regular follow-up during the symptomatic periods and psychological support for alleviating the psychogenic component of the pain. More research is necessary to confirm the association between BMS and systemic disorders, as well as to investigate possible pathogenic mechanisms involving potential nerve damage. If this goal is to be achieved, a uniform definition of BMS and strict criteria for its classification are mandatory.

灼口综合征(BMS)是一种以激素变化或心理障碍为主的中老年妇女慢性疼痛综合征。这种情况可能是多因素的,通常是特发性的,其发病机制在很大程度上仍然是谜。本文讨论了BMS的几个方面,更新了现有的知识,并为患者管理提供了指导。BMS的诊断和分类尚无共识。其发病机制似乎很复杂,在许多患者中可能涉及局部、全身和/或心理因素之间的相互作用。在其余病例中,最近出现了新的有趣的BMS与周围神经损伤或多巴胺能系统障碍之间的联系,强调了BMS的神经病变背景。基于这些最近的数据,我们引入了“原发性”(特发性)和“继发性”(由确定的诱发因素引起)BMS的概念,因为这允许更系统的患者管理方法。后者首先在排除其他口腔面部慢性疼痛条件和表现粘膜病变的口腔疼痛疾病的基础上进行鉴别诊断。然而,出现重叠/压倒性的口腔黏膜病理,如感染,可能会给诊断带来困难(“复杂的BMS”)。BMS的治疗仍然不令人满意,并且没有明确的治愈方法。因此,需要多学科的方法来更好地控制病情。重要的是,BMS患者应在症状期接受定期随访,并提供心理支持,以减轻疼痛的心因性成分。需要更多的研究来证实BMS与全身性疾病之间的联系,并调查可能涉及潜在神经损伤的致病机制。要实现这一目标,必须对BMS进行统一的定义,并对其进行严格的分类标准。
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引用次数: 537
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Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists
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