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In memoriam: Michael G. Humphreys-Beher 纪念:迈克尔·g·汉弗莱斯·贝赫
I. Ambudkar, E. Kousvelari
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引用次数: 8
Biocompatibility of dental casting alloys. 牙科铸造合金的生物相容性。
W. Geurtsen
Most cast dental restorations are made from alloys or commercially pure titanium (cpTi). Many orthodontic appliances are also fabricated from metallic materials. It has been documented in vitro and in vivo that metallic dental devices release metal ions, mainly due to corrosion. Those metallic components may be locally and systemically distributed and could play a role in the etiology of oral and systemic pathological conditions. The quality and quantity of the released cations depend upon the type of alloy and various corrosion parameters. No general correlation has been observed between alloy nobility and corrosion. However, it has been documented that some Ni-based alloys, such as beryllium-containing Ni alloys, exhibit increased corrosion, specifically at low pH. Further, microparticles are abraded from metallic restorations due to wear. In sufficient quantities, released metal ions-particularly Cu, Ni, Be, and abraded microparticles-can also induce inflammation of the adjacent periodontal tissues and the oral mucosa. While there is also some in vitro evidence that the immune response can be altered by various metal ions, the role of these ions in oral inflammatory diseases such as gingivitis and periodontitis is unknown. Allergic reactions due to metallic dental restorations have been documented. Ni has especially been identified as being highly allergenic. Interestingly, from 34% to 65.5% of the patients who are allergic to Ni are also allergic to Pd. Further, Pd allergy always occurrs with Ni sensitivity. In contrast, no study has been published which supports the hypothesis that dental metallic materials are mutagenic/genotoxic or might be a carcinogenic hazard to man. Taken together, very contradictory data have been documented regarding the local and systemic effects of dental casting alloys and metallic ions released from them. Therefore, it is of critical importance to elucidate the release of cations from metallic dental restorations in the oral environment and to determine the biological interactions of released metal components with oral and systemic tissues.
大多数铸造牙修复体是由合金或商业纯钛(cpTi)制成的。许多正畸器具也由金属材料制成。在体外和体内都有文献记载,金属牙科装置释放金属离子,主要是由于腐蚀。这些金属成分可能在局部和全身分布,并可能在口腔和全身病理状况的病因学中发挥作用。释放阳离子的质量和数量取决于合金的类型和各种腐蚀参数。合金的高贵性和腐蚀之间没有普遍的联系。然而,有文献表明,一些镍基合金,如含铍的镍合金,特别是在低ph下,表现出更强的腐蚀。此外,由于磨损,金属修复体中的微粒被磨损。如果释放的金属离子足够多,特别是Cu、Ni、Be和磨损的微粒,也会引起邻近牙周组织和口腔黏膜的炎症。虽然也有一些体外证据表明,免疫反应可以被各种金属离子改变,但这些离子在牙龈炎和牙周炎等口腔炎症性疾病中的作用尚不清楚。金属牙修复体引起的过敏反应已有文献记载。镍尤其被认为具有高度过敏性。有趣的是,对Ni过敏的患者中有34% ~ 65.5%也对Pd过敏。此外,Pd过敏总是与Ni敏感同时发生。相比之下,没有发表任何研究支持牙科金属材料具有诱变/遗传毒性或可能对人类有致癌危害的假设。综上所述,关于牙科铸造合金及其释放的金属离子对局部和全身的影响,已经记录了非常矛盾的数据。因此,阐明金属牙修复体在口腔环境中阳离子的释放,并确定释放的金属成分与口腔和全身组织的生物相互作用是至关重要的。
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引用次数: 252
Cell cycle dysregulation in oral cancer. 口腔癌细胞周期失调。
R. Todd, P. Hinds, K. Munger, A. Rustgi, O. Opitz, Y. Suliman, David T. W. Wong
The dysregulation of the molecular events governing cell cycle control is emerging as a central theme of oral carcinogenesis. Regulatory pathways responding to extracellular signaling or intracellular stress and DNA damage converge on the cell cycle apparatus. Abrogation of mitogenic and anti-mitogenic response regulatory proteins, such as the retinoblastoma tumor suppressor protein (pRB), cyclin D1, cyclin-dependent kinase (CDK) 6, and CDK inhibitors (p21(WAF1/CIP1), p27(KIP1), and p16(INK4a)), occur frequently in human oral cancers. Cellular responses to metabolic stress or genomic damage through p53 and related pathways that block cell cycle progression are also altered during oral carcinogenesis. In addition, new pathways and cell cycle regulatory proteins, such as p12(DOC-1), are being discovered. The multistep process of oral carcinogenesis likely involves functional alteration of cell cycle regulatory members combined with escape from cellular senescence and apoptotic signaling pathways. Detailing the molecular alterations and understanding the functional consequences of the dysregulation of the cell cycle apparatus in the malignant oral keratinocyte will uncover novel diagnostic and therapeutic approaches.
控制细胞周期的分子事件的失调正在成为口腔癌发生的一个中心主题。响应细胞外信号或细胞内应激和DNA损伤的调控途径集中在细胞周期装置上。有丝分裂和抗有丝分裂反应调节蛋白的缺失,如视网膜母细胞瘤肿瘤抑制蛋白(pRB)、细胞周期蛋白D1、细胞周期蛋白依赖性激酶(CDK) 6和CDK抑制剂(p21(WAF1/CIP1)、p27(KIP1)和p16(INK4a)),在人类口腔癌中经常发生。在口腔癌发生过程中,细胞对代谢应激或基因组损伤的反应(通过p53和相关途径阻断细胞周期进程)也发生了改变。此外,新的途径和细胞周期调节蛋白,如p12(DOC-1),正在被发现。口腔癌发生的多步骤过程可能涉及细胞周期调控成员的功能改变,以及细胞衰老和凋亡信号通路的逃逸。详细了解恶性口腔角化细胞中细胞周期装置失调的分子改变和功能后果,将发现新的诊断和治疗方法。
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引用次数: 140
Reflex control of human jaw muscles. 人类颚肌的反射控制。
K. Türker
The aim of this review is to discuss what is known about the reflex control of the human masticatory system and to propose a method for standardized investigation. Literature regarding the current knowledge of activation of jaw muscles, receptors involved in the feedback control, and reflex pathways is discussed. The reflexes are discussed under the headings of the stimulation conditions. This was deliberately done to remind the reader that under each stimulation condition, several receptor systems are activated, and that it is not yet possible to stimulate only one afferent system in isolation in human mastication experiments. To achieve a method for uniform investigation, we need to set a method for stimulation of the afferent pathway under study with minimal simultaneous activation of other receptor systems. This stimulation should also be done in an efficient and reproducible way. To substantiate our conviction to standardize the stimulus type and parameters, we discuss the advantages and disadvantages of mechanical and electrical stimuli. For mechanical stimulus to be delivered in a reproducible way, the following precautions are suggested: The stimulus delivery system (often a probe attached to a vibrator) should be brought into secure contact with the area of stimulation. To minimize the slack between the probe, the area to be stimulated should be taken up by the application of pre-load, and the delivered force should be recorded in series. Electrical stimulus has advantages in that it can be delivered in a reproducible way, though its physiological relevance can be questioned. It is also necessary to standardize the method for recording and analyzing the responses of the motoneurons to the stimulation. For that, a new technique is introduced, and its advantages over the currently used methods are discussed. The new method can illustrate the synaptic potential that is induced in the motoneurons without the errors that are unavoidable in the current techniques. We believe that once stimulation, recording, and analysis methods are standardized, it will be possible to bring out the real "wiring diagram" that operates in conscious human subjects.
这篇综述的目的是讨论什么是已知的反射控制的人类咀嚼系统,并提出一个标准化的研究方法。文献关于目前的知识,下颌肌肉的激活,参与反馈控制的受体,和反射途径进行了讨论。在刺激条件的标题下讨论反射。这样做是为了提醒读者,在每种刺激条件下,有几个受体系统被激活,在人类咀嚼实验中,还不可能单独刺激一个传入系统。为了获得一种统一的研究方法,我们需要设定一种方法,在最小程度上同时激活其他受体系统的情况下刺激所研究的传入通路。这种刺激也应该以有效和可重复的方式进行。为了证实我们对刺激类型和参数标准化的信念,我们讨论了机械刺激和电刺激的优缺点。为了以可重复的方式传递机械刺激,建议以下注意事项:刺激传递系统(通常是连接到振动器的探针)应与刺激区域安全接触。为了尽量减少探针之间的松弛,应通过施加预载荷来占用受刺激的区域,并应连续记录所传递的力。电刺激的优势在于它可以以可重复的方式传递,尽管其生理相关性可能受到质疑。同时,有必要规范运动神经元对刺激反应的记录和分析方法。为此,介绍了一种新技术,并讨论了其相对于现有方法的优点。新方法可以显示运动神经元的突触电位,而不存在目前技术中不可避免的误差。我们相信,一旦刺激、记录和分析方法标准化,就有可能在有意识的人类实验对象身上找到真正的“接线图”。
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引用次数: 144
Destructive periodontitis lesions are determined by the nature of the lymphocytic response. 破坏性牙周炎病变是由淋巴细胞反应的性质决定的。
E. Gemmell, K. Yamazaki, G. Seymour
It is now 35 years since Brandtzaeg and Kraus (1965) published their seminal work entitled "Autoimmunity and periodontal disease". Initially, this work led to the concept that destructive periodontitis was a localized hypersensitivity reaction involving immune complex formation within the tissues. In 1970, Ivanyi and Lehner highlighted a possible role for cell-mediated immunity, which stimulated a flurry of activity centered on the role of lymphokines such as osteoclast-activating factor (OAF), macrophage-activating factor (MAF), macrophage migration inhibition factor (MIF), and myriad others. In the late 1970s and early 1980s, attention focused on the role of polymorphonuclear neutrophils, and it was thought that periodontal destruction occurred as a series of acute exacerbations. As well, at this stage doubt was being cast on the concept that there was a neutrophil chemotactic defect in periodontitis patients. Once it was realized that neutrophils were primarily protective and that severe periodontal destruction occurred in the absence of these cells, attention swung back to the role of lymphocytes and in particular the regulatory role of T-cells. By this time in the early 1990s, while the roles of interleukin (IL)-1, prostaglandin (PG) E(2), and metalloproteinases as the destructive mediators in periodontal disease were largely understood, the control and regulation of these cytokines remained controversial. With the widespread acceptance of the Th1/Th2 paradigm, the regulatory role of T-cells became the main focus of attention. Two apparently conflicting theories have emerged. One is based on direct observations of human lesions, while the other is based on animal model experiments and the inability to demonstrate IL-4 mRNA in gingival extracts. As part of the "Controversy" series, this review is intended to stimulate debate and hence may appear in some places provocative. In this context, this review will present the case that destructive periodontitis is due to the nature of the lymphocytic infiltrate and is not due to periodic acute exacerbations, nor is it due to the so-called virulence factors of putative periodontal pathogens.
距Brandtzaeg和Kraus(1965)发表他们的开创性著作《自身免疫与牙周病》已经过去35年了。最初,这项工作导致破坏性牙周炎是一种局部超敏反应,涉及组织内免疫复合物的形成。1970年,Ivanyi和Lehner强调了细胞介导免疫的可能作用,它刺激了一系列以淋巴因子(如破骨细胞激活因子(OAF)、巨噬细胞激活因子(MAF)、巨噬细胞迁移抑制因子(MIF)等)的作用为中心的活动。在20世纪70年代末和80年代初,注意力集中在多形核中性粒细胞的作用上,人们认为牙周破坏是一系列急性加重。同样,在这个阶段,人们对牙周炎患者是否存在中性粒细胞趋化缺陷的概念产生了怀疑。一旦认识到中性粒细胞的主要保护作用和严重的牙周破坏发生在缺乏这些细胞,注意力又回到淋巴细胞的作用,特别是t细胞的调节作用。到20世纪90年代初,虽然白细胞介素(IL)-1、前列腺素(PG) E(2)和金属蛋白酶作为牙周病的破坏性介质的作用已经得到了很大程度的了解,但这些细胞因子的控制和调节仍然存在争议。随着Th1/Th2范式的广泛接受,t细胞的调控作用成为人们关注的主要焦点。出现了两种明显相互矛盾的理论。一种是基于对人类病变的直接观察,而另一种是基于动物模型实验,无法证明牙龈提取物中含有IL-4 mRNA。作为“争议”系列的一部分,本评论旨在激发辩论,因此可能在某些地方出现挑衅性。在这种情况下,这篇综述将提出的情况下,破坏性牙周炎是由于淋巴细胞浸润的性质,而不是由于周期性急性加重,也不是由于所谓的毒力因素假定的牙周病原体。
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引用次数: 222
Gene expression profiling by DNA microarray technology. DNA微阵列技术的基因表达谱分析。
K. Iida, I. Nishimura
Methods in molecular and genetic biology have provided important clues to elucidate the complex mechanisms of oral and craniofacial development and pathogenesis of diseases. It has become increasingly clear that a biological phenotype is a result of multiple factors involving a large number of regulatory genes, while a single nucleotide mutation can cause various degrees of oral and craniofacial abnormalities. These oral and craniofacial problems often present a challenge to the molecular screening process. Recent advances in microarray-based technologies allow for large-scale gene expression analysis in a single experiment, which have been applied to genome-wide assays, mutational analysis, drug discovery, developmental biology, and molecular analysis of various diseases. This review introduces the basic principle and some modifications of techniques and materials used in microarray technology, as well as currently available microarray data analysis strategies. Microarray technology can be applied to the soon-to-be-available human genome database and will be a powerful research tool for those inquiring into specific problems associated with oral and craniofacial biology.
分子生物学和遗传生物学的方法为阐明口腔和颅面发育的复杂机制和疾病的发病机制提供了重要线索。越来越清楚的是,生物学表型是涉及大量调控基因的多因素的结果,而单个核苷酸突变可引起不同程度的口腔和颅面异常。这些口腔和颅面问题经常对分子筛选过程提出挑战。基于微阵列技术的最新进展允许在单个实验中进行大规模基因表达分析,这已应用于全基因组分析,突变分析,药物发现,发育生物学和各种疾病的分子分析。本文介绍了微阵列技术的基本原理和一些技术和材料的改进,以及目前可用的微阵列数据分析策略。微阵列技术可以应用于即将可用的人类基因组数据库,并将成为那些探究与口腔和颅面生物学相关的特定问题的强大研究工具。
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引用次数: 45
Cementum and periodontal wound healing and regeneration. 牙骨质和牙周伤口愈合和再生。
Wojciech J Grzesik, A S Narayanan

The extracellular matrix (ECM) of cementum resembles other mineralized tissues in composition; however, its physiology is unique, and it contains molecules that have not been detected in other tissues. Cementum components influence the activities of periodontal cells, and they manifest selectivity toward some periodontal cell types over others. In light of emerging evidence that the ECM determines how cells respond to environmental stimuli, we hypothesize that the local environment of the cementum matrix plays a pivotal role in maintaining the homeostasis of cementum under healthy conditions. The structural integrity and biochemical composition of the cementum matrix are severely compromised in periodontal disease, and the provisional matrix generated during periodontal healing is different from that of cementum. We propose that, for new cementum and attachment formation during periodontal regeneration, the local environment must be conducive for the recruitment and function of cementum-forming cells, and that the wound matrix is favorable for repair rather than regeneration. How cementum components may regulate and participate in cementum regeneration, possible new regenerative therapies using these principles, and models of cementoblastic cells are discussed.

牙骨质的细胞外基质(ECM)在组成上与其他矿化组织相似;然而,它的生理机能是独特的,它含有在其他组织中未被检测到的分子。牙骨质成分影响牙周细胞的活性,并对某些类型的牙周细胞表现出选择性。鉴于新出现的证据表明外基质决定细胞如何对环境刺激作出反应,我们假设骨水泥基质的局部环境在健康条件下维持骨水泥的稳态中起着关键作用。牙周疾病导致牙骨质基质的结构完整性和生化成分严重受损,牙周愈合过程中产生的临时基质与牙骨质不同。我们认为,在牙周再生过程中,为了形成新的牙骨质和附着体,局部环境必须有利于牙骨质形成细胞的招募和功能,伤口基质有利于修复而不是再生。讨论了骨水泥成分如何调节和参与骨水泥再生,利用这些原理的可能的新再生疗法以及成骨水泥细胞的模型。
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引用次数: 280
Supragingival calculus: formation and control. 牙上牙结石:形成与控制。
Ye Jin, Hak-Kong Yip

Dental calculus is composed of inorganic components and organic matrix. Brushite, dicalcium phosphate dihydrate, octacalcium phosphate, hydroxyapatite, and whitlockite form the mineral part of dental calculus. Salivary proteins selectively adsorb on the tooth surface to form an acquired pellicle. It is followed by the adherence of various oral micro-organisms. Fimbriae, flagella, and some other surface proteins are essential for microbial adherence. Microbial co-aggregation and co-adhesion enable some micro-organisms, which are incapable of adhering, to adhere to the pellicle-coated tooth surface. Once organisms attach to the tooth surface, new genes could be expressed so that mature dental plaque can form and biofilm bacteria assume increased resistance to antimicrobial agents. Supersaturation of saliva and plaque fluid with respect to calcium phosphates is the driving force for plaque mineralization. Both salivary flow rate and plaque pH appear to influence the saturation degree of calcium phosphates. Acidic phospholipids and specific proteolipids present in cell membranes play a key role in microbial mineralization. The roles of crystal growth inhibitors, promoters, and organic acids in calculus formation are discussed. Application of biofilm culture systems in plaque mineralization is concisely reviewed. Anti-calculus agents used--centering on triclosan plus polyvinyl methyl ether/maleic acid copolymer, pyrophosphate plus polyvinyl methyl ether/maleic acid copolymer, and zinc ion-in commercial dentifrices are also discussed in this paper.

牙结石由无机成分和有机基质组成。刷石、二水磷酸二钙、磷酸八钙、羟基磷灰石和白钨矿构成牙石的矿物部分。唾液蛋白选择性地吸附在牙齿表面形成获得性外膜。其次是各种口腔微生物的粘附。菌毛、鞭毛和其他一些表面蛋白质对于微生物的粘附是必不可少的。微生物的共同聚集和共同粘附使一些不能粘附的微生物能够粘附在被膜包裹的牙齿表面。一旦生物附着在牙齿表面,新的基因就会表达出来,这样成熟的牙菌斑就会形成,生物膜细菌对抗菌剂的抵抗力就会增强。唾液和斑块液与磷酸钙的过饱和是斑块矿化的驱动力。唾液流速和斑块pH值似乎都影响磷酸钙的饱和度。细胞膜中存在的酸性磷脂和特异性蛋白脂在微生物矿化中起关键作用。讨论了晶体生长抑制剂、促进剂和有机酸在结石形成中的作用。简要综述了生物膜培养系统在牙菌斑矿化中的应用。以三氯生加聚乙烯醇甲基醚/马来酸共聚物、焦磷酸盐加聚乙烯醇甲基醚/马来酸共聚物和锌离子为中心,讨论了商品牙膏中常用的防牙石剂。
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引用次数: 176
Immunodominant antigens in periodontal disease: a real or illusive concept? 免疫优势抗原在牙周病:一个真实的还是虚幻的概念?
M. Podmore, J. Ebersole, Denis F. Kinane
The humoral arm of the immune system provides protection from many medically significant pathogens. The antigenic epitopes of the pathogens which induce these responses, and the subsequent characteristics of the host response, have been extensively documented in the medical literature, and in many cases have resulted in the development and implementation of effective vaccines or diagnostic tests. There is a substantial body of literature on the humoral immune response in periodontal disease, which is targeted at micro-organisms present within periodontal pockets. However, the significance and specificity of the immune response in periodontal disease have proved difficult to elucidate, due to the large number of potential pathogens in the plaque biofilm and the apparent commensal nature of many of these opportunistic pathogens. This review addresses our current knowledge of the approaches and strategies which have been used to elucidate and examine the concept of immunodominant antigens in medical infections and, more recently, periodontal disease. An identification/understanding of the immunodominant antigens would be informative with respect to: (i) the relative importance of the implicated pathogens, (ii) new approaches to immunological diagnosis, (iii) specific bacterial virulence determinants, (iv) natural protective responses, and (v) the selection of potential vaccine candidate antigens. We conclude that immunodominance of antigens in periodontal disease may be relevant to our understanding of periodontal disease pathogenesis, but due to the complexity and diversity of the 'pathogenic microbial ecology', it is currently an enigmatic topic requiring a multidisciplinary approach linking clinical, microbiological, and immunological investigations. We also conclude, after assessing the literature available on the topic of immunodominance, that it is a term that, if used, must be clearly defined and understood, since it is often used loosely, leading to a general misinterpretation by readers of oral and medical literature.
免疫系统的体液部分提供了对许多医学上重要病原体的保护。引起这些反应的病原体的抗原表位以及宿主反应的后续特征已在医学文献中广泛记录,并在许多情况下导致开发和实施有效的疫苗或诊断测试。有大量的文献关于牙周病的体液免疫反应,这是针对微生物存在于牙周袋。然而,由于牙菌斑生物膜中有大量潜在的病原体,并且许多这些机会性病原体具有明显的共生性质,因此很难阐明牙周病免疫反应的意义和特异性。这篇综述阐述了我们目前所知的用于阐明和检查医学感染和最近牙周病中免疫显性抗原概念的方法和策略。识别/了解免疫优势抗原将有助于以下方面:(i)所涉病原体的相对重要性,(ii)免疫学诊断的新方法,(iii)特定细菌毒力决定因素,(iv)自然保护反应,以及(v)潜在疫苗候选抗原的选择。我们得出结论,牙周病中抗原的免疫优势可能与我们对牙周病发病机制的理解有关,但由于“致病微生物生态学”的复杂性和多样性,它目前是一个谜题,需要将临床、微生物学和免疫学研究结合起来的多学科方法。在评估了有关免疫优势的现有文献后,我们还得出结论,如果使用这个术语,必须明确定义和理解,因为它经常被松散地使用,导致口腔和医学文献的读者普遍误解。
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引用次数: 22
Morphology and physiology of masticatory muscle motor units. 咀嚼肌运动单元的形态学和生理学。
T. Eijden, S. Turkawski
Motor unit territories in masticatory muscles appear to be smaller than territories in limb muscles, and this would suggest a more localized organization of motor control in masticatory muscles. Motor unit cross-sectional areas show a wide range of values, which explains the large variability of motor unit force output. The proportion of motor unit muscle fibers containing more than one myosin heavy-chain (MHC) isoform is considerably larger in masticatory muscles than in limb and trunk muscles. This explains the continuous range of contraction speeds found in masticatory muscle motor units. Hence, in masticatory muscles, a finer gradation of force and contraction speeds is possible than in limb and in trunk muscles. The proportion of slow-type motor units is relatively large in deep and anterior masticatory muscle regions, whereas more fast-type units are more common in the superficial and posterior muscle regions. Muscle portions with a high proportion of slow-type motor units are better equipped for a finer control of muscle force and a larger resistance to fatigue during chewing and biting than muscle portions with a high proportion of fast units. For the force modulation, masticatory muscles rely mostly on recruitment gradation at low force levels and on rate gradation at high force levels. Henneman's principle of an orderly recruitment of motor units has also been reported for various masticatory muscles. The presence of localized motor unit territories and task-specific motor unit activity facilitates differential control of separate muscle portions. This gives the masticatory muscles the capacity of producing a large diversity of mechanical actions. In this review, the properties of masticatory muscle motor units are discussed.
咀嚼肌的运动单元区域似乎比肢体肌肉的区域小,这可能表明咀嚼肌的运动控制组织更局部。运动单元横截面积显示的值范围很广,这解释了运动单元力输出的大变异性。咀嚼肌中含有多于一种肌球蛋白重链(MHC)亚型的运动单位肌纤维的比例比四肢和躯干肌肉大得多。这解释了咀嚼肌运动单元收缩速度的连续范围。因此,咀嚼肌的力和收缩速度可能比四肢和躯干肌肉更精细。慢速型运动单元在咀嚼肌深层和前区所占比例较大,而快速型运动单元在咀嚼肌浅部和后区所占比例较多。拥有高比例慢速运动单元的肌肉部位,在咀嚼和咬咬过程中,能够更好地控制肌肉力量,并且比拥有高比例快速运动单元的肌肉部位具有更大的抗疲劳能力。咀嚼肌的力调节主要依靠低力水平时的招募梯度和高力水平时的速率梯度。Henneman的运动单元有序募集原则也被报道用于各种咀嚼肌。局部运动单元区域和特定任务运动单元活动的存在促进了对不同肌肉部分的差异控制。这赋予了咀嚼肌产生多种机械动作的能力。本文就咀嚼肌运动单元的特性作一综述。
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引用次数: 105
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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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