注射型rhBMP-2骨修复材料对兔桡骨骨缺损修复的实验研究

探讨以纤维蛋白胶(fibrin sealant,FS)为载体,复合重组BMP-2(rhBMP-2)的注射型骨修复材料,修复兔桡骨节段性骨缺损的能力,为其临床应用提供实验依据。将实验动物分为:实验组(FS rhBMP-2)、对照组(FS)。于28只新西兰白兔右侧桡骨干处造成1.5cm缺损,然后严密缝合皮下组织及皮肤,将各组材料经正常皮肤注射骨缺损处,术后4、8、16、24周进行放射学、组织学和骨密度等方法检查,对其成骨效应进行研究。结果表明:实验组(FS rhBMP-2)骨缺损区在成骨活跃程度、骨密度和再生髓腔结构等方面均显著优于对照组(FS),使骨缺损得到了彻底修复(P<0.01);对照组不能产生骨性愈合。由此说明以纤维蛋白胶为载体复合rhBMP-2的注射型骨修复材料具有高效的骨修复能力。     

注射型rhBMP-2/PLGA/FS缓释微球载体系统用于兔桡骨骨缺损修复的实验研究

探讨注射型重组人骨形态发生蛋白-2/聚乳酸-羟基乙酸/纤维蛋白胶(rhBMP-2/PLGA/FS)缓释微球载体系统在修复兔桡骨节段性骨缺损中的作用。制作新西兰大白兔桡骨缺损模型,将其分为实验组(rhBMP-2/PLGA/FS),对照组(FS)和空白组(不作处理)。在缺损局部注入各组材料后,通过X射线观察各组动物的骨缺损修复情况;取兔桡骨损伤节段定量分析其骨密度值,评估其成骨质量;利用HE及Masson染色,观察骨组织形态及骨再生情况,评估其修复作用。结果表明:rhBMP-2/PLGA/FS缓释微球载体组在骨缺损修复、成骨质量及成骨能力方面均显著优于对照组和空白组,能够显著促进兔骨缺损修复,是一种较为理想、高效的骨组织工程材料。     

纤维蛋白胶复合骨形态发生蛋白2塑形Bio-oss修复下颌骨缺损

背景：Bio-oss的颗粒状结构通常应用于洞形缺损的充填性移植,对于三壁以上的缺损修复难以成形。 目的：评价Bio-oss以纤维蛋白胶复合骨形态发生蛋白2作为赋形材料后的成骨性能。 方法：拔除9条杂种犬双侧下颌第2,4前臼齿及第2臼齿,造成1 cm×1 cm的骨缺损区,将Bio-oss+纤维蛋白胶+骨形态发生蛋白2、Bio-oss+纤维蛋白胶及Bio-oss材料分别植入第2,4前臼齿及第2臼齿骨缺损区。 结果与结论：各组软组织均一期愈合。Bio-oss复合纤维蛋白胶后,骨粉结合紧密,不易剥离。术后4,8,12周时 Bio-oss+纤维蛋白胶+骨形态发生蛋白2组新生骨百分率均高于其他两组(P < 0.05)。表明纤维蛋白胶的加入可以解决Bio-oss成形困难的问题,骨形态发生蛋白2的加入可促进成骨效果。     

纳米羟基磷灰石/重组人骨形成蛋白-2复合人工骨的实验研究

目的：探讨纳米羟基磷灰石复合重组人骨形成蛋白-2人工骨（Nano-HA／rhBMP-2）的骨缺损修复能力，为临床骨缺损修复提供依据。方法：采用新西兰大白兔75只，单侧桡骨制备骨缺损动物模型，以Nano-HA／rhBMP-2复合人工骨植入骨缺损处进行修复作为实验组（A组），以Nano-HA人工骨（B组）及空白组（C组）作为对照组；术后4周、8周、12周分别行大体标本观察、X线、扫描电镜（SEM）、放射性核素骨扫描（ECT）及生物力学测试，综合评价Nano-HA／rhBMP-2复合人工骨对骨缺损的修复能力及对机体的影响。结果：Nano-HA／rhBMP-2复合人工骨、Nano-HA人工骨均可促进新骨形成，前者新骨形成量大，骨缺损修复能力明显优于后者，差异有统计学意义（P〈0．05）。结论：Nano-HA／rhBMP-2复合人工骨具有良好的骨缺损修复能力，可望成为一种理想的骨缺损修复材料。     

四种BMP载体修复骨缺损的形态学观察

目的：研究带血供肌瓣、带血供肌瓣复合纤维蛋白粘合剂（FS）、无血供肌瓣和同种异体脱钙骨（AAA）等四种BMP载体修复骨缺损的形态变化。方法：取新西兰大白兔32只,采用双前肢桡骨中下段12mm缺损实验模型,分别在3、6、9、12周观察带血供肌瓣、带血供肌瓣复合FS、无血供肌瓣和同种异体脱钙骨等4种载体修复骨缺损的大体解剖学、X线和组织学。结果：带血供肌瓣和FS作为BMP复合载体修复骨缺损3周时有大量的软骨细胞生成,呈弹性软骨样特征。6周时大量编织骨、骨小梁形成。9周时出现哈佛氏系统。肌纤维萎缩消失。12周时出现哈费氏骨板和少量的间骨板,哈佛氏管内表面衬有成骨细胞。该复合载体比同时期单用带血供肌瓣成熟程度好,相当于AAA骨载体的骨修复能力。无血供肌瓣复合BMP形成“壳”状新骨。结论：带血供肌瓣复合纤维蛋白粘合剂是BMP的良好载体。     

生长因子复合支架材料在即刻种植周围骨缺损中的作用

背景:研究发现神经生长因子在骨的愈合过程中发挥重要作用,但关于生长因子复合支架材料在犬即刻种植周围骨缺损中作用的研究不多。目的:分析神经生长因子复合支架材料在犬即刻种植周围骨缺损中的作用。方法:制备神经生长因子复合锶磷灰石支架材料,建立犬下颌骨缺损动物模型,将犬下颌骨缺损种植体分为实验组、阳性对照组和空白对照组,实验组植入神经生长因子复合锶磷灰石;阳性对照组植入锶磷灰石;空白对照组不植入任何材料。观察3组犬下颌骨种植体周围骨缺损的CT三维图像重建情况和苏木精-伊红染色情况。结果与结论:1空白对照组犬骨缺损中央没有新骨生成,周围有少量新生骨生成;阳性对照组和实验组犬骨缺损处骨小梁从中间向四周扩散形成骨修复;2实验组犬下颌骨种植体周围骨小梁的骨密度、数量、厚度、种植体-骨结合率均高于阳性对照组和空白对照组(P0.05),阳性对照组4项指标高于空白对照组(P0.05);实验组犬下颌骨种植体周围骨小梁分离度低于阳性对照组和空白对照组(P0.05),阳性对照组低于空白对照组(P0.05);3苏木精-伊红染色显示,实验组犬下颌骨种植体支架网孔中有大量新骨生成,骨小梁排列整齐,周围骨质和新生组织连接紧密;阳性对照组犬下颌骨可见新生类骨质和骨小梁,以及少量死骨碎片;空白对照组骨缺损处有部分新骨生成,骨小梁排列不整齐,周围骨质和新生组织连接不紧密;4结果表明,神经生长因子复合支架材料能够促进犬即刻种植周围骨缺损的骨生成,是一种比较好的骨修复材料。     

中空羟基磷灰石复合rhBMP-2修复骨缺损过程的再血管化研究

目的　探讨和观察中空羟基磷灰石复合rhBMP-2在骨缺损修复过程的再血管化。  方法　将48只成年的新西兰雄性大白兔制作成桡骨骨缺损模型,随机分3组,各组分别植入以下材料：中空HA/ rhBMP-2复合人工骨、单纯中空HA人工骨、单纯rhBMP-2。植入后于4、8、12、16周分别注射99mTc-MDP进行放射性核素骨显像并监测骨缺损修复过程中再血管化情况,同时进行大体、X线、组织学观察。  结果　术后各时间段,中空HA/ rhBMP-2复合人工骨组在X线及放射性核素聚集强度明显高于单纯中空HA人工骨组(P<0.05) ,表现为成骨代谢活跃及早期的再血管化能力。  结论　中空HA/ rhBMP-2复合人工骨具有良好的骨缺损修复能力,成骨活性持久,再血管化能力强,有望成为一种理想的骨缺损修复材料。     

骨髓基质干细胞复合纳米材料修复骨缺损的微循环研究

目的:了解骨髓基质干细胞(MSCs)复合纳米羟基磷灰石/聚乳酸(n-HA/PLA)构建组织工程骨修复骨缺损过程中,实验动物血液流变学和骨缺损修复区血流量的变化。方法:选择20只新西兰白兔,制作15mm长的桡骨节段性骨缺损模型,根据植入不同移植材料分为实验组和对照组,实验组于动物左侧桡骨缺损区植入组织工程骨,对照组植入n-HA/PLA,观察各组动物术后1h、7天、14天血液流变学指标和术后14天骨缺损修复区血流量的变化。结果:实验组与对照组比较,血液流变学指标和骨缺损修复区血流量差异显著。组织工程骨修复骨缺损,实验动物血液粘度降低,骨缺损修复区局部血流量增加。结论:与单纯n-HA/PLA材料比较,组织工程骨可促进骨缺损的修复。     

丝素蛋白/羟基磷灰石复合材料修复骨缺损的微循环研究

了解丝素蛋白(silk fibroin,SF)表面修饰的羟基磷灰石(hydroxyapatite,HA)修复骨缺损过程中,实验动物血液流变学和骨缺损修复区血流量的变化。选择20只新西兰白兔,制作15 mm长的桡骨节段性骨缺损模型,根据植入不同移植材料分为实验组和对照组,实验组于动物左侧桡骨缺损区植入MSCs复合SF表面修饰的HA培养制备的组织工程骨,对照组植入MSCs复合HA培养制备的组织工程骨,观察各组动物术后7、14 d血液流变学和术后14 d骨缺损修复区血流量的变化。实验组与对照组比较,血液流变学指标和骨缺损修复区血流量差异显著,实验动物全身血液粘度降低,骨缺损修复区的局部血流量增加。SF表面修饰对以HA为支架材料组织工程骨的修复作用有明显优化作用。     

快速成型聚乳酸-聚羟乙酸/磷酸三钙支架修复兔桡骨缺损

背景：理想的骨修复材料除必须具有生物相容性、可吸收性、利于血管化及迅速被新生组织替代的孔隙率,还需要有与骨组织相似三维结构。 目的：检验快速成型工艺制作的聚乳酸-聚羟乙酸/磷酸三钙支架复合骨形态发生蛋白修复兔桡骨缺损的效果。 方法：将乳酸乙醇酸共聚物溶于1,4-二氧六环中并混合粉末状磷酸三钙制备成液态的浆料,放入生物材料快速成形机TissFormTM制备出直径5 mm,长15 mm的圆柱形人工骨载体材料。按每个材料15 mg的标准,采用预湿、负压复合骨形态发生蛋白、冻干3步处理,制备出活性人工骨材料。健康新西兰大白兔20只,制备右前肢桡骨中上段15 mm骨缺损模型,实验组和对照组分别植入复合骨形态发生蛋白的活性人工骨和未复合骨形态发生蛋白的单纯支架。通过影像学、组织学、材料降解及骨密度评价修复兔桡骨缺损的效果。 结果与结论：12周时实验组骨缺损愈合,新生骨痂连接缺损断端并塑形,支架材料近于完全降解,各检测指标与对照组比较差异均有显著性意义,对照组骨缺损内未见新骨形成。结果表明复合骨形态发生蛋白的聚乳酸-聚羟乙酸/磷酸三钙支架可以很好的修复兔15 mm骨缺损,且降解速度与成骨速度匹配良好。     

Counterpointing the functional role of the forebrain and of the brainstem in the control of the sleep-waking system

This paper reviews the lifetime contributions of the author to the field of sleep-wakefulness (S-W), reinterprets results of the early studies, and suggests new conclusions and perspectives. Long-term cats with mesencephalic transection show behavioral/polygraphic rapid eye movement sleep (REMS), including the typical oculo-pupillary behavior, even when the section is performed in kittens prior to S-W maturation. REMS can be induced as a reflex. Typical non-rapid eye movement S (NREMS) is absent and full W/arousal is present only after a precollicular section. The isolated forebrain (IF) rostral to the transection exhibits all features of W/arousal and NREMS [with electroencephalographic (EEG) spindles and delta waves], arousal to olfactory stimuli, and including the appropriate oculo-pupillary behaviors. These features also mature normally after neonatal transection. REMS is absent from the IF. After deprivation there is NREMS pressure and rebound in the IF, but the decerebrate cat only shows pressure for REMS. Most IF reactions to pharmacologic agents are within expectations, except for the tolerance/withdrawal effects of long-term morphine use which are absent. In contrast, these effects are supported by the brainstem (i.e. seen in the decerebrate cat). In cats with ablation of the telencephalon, or diencephalic cats, delta waves are absent in the thalamus. EEG thalamic spindle waves are seen triggering S for only 4-5 days after ablation. Therefore, true NREMS is absent in chronic diencephalic cats although pre- and postsomniac behaviors persist. These animals are hyperactive and show a pronounced, permanent insomnia; however, a low dose of barbiturate triggers a dramatic REMS/atypical NREMS rebound. Cats without the thalamus (athalamic cats), initially show a dissociation between behavioral hyperactivity/insomnia and the neocortical EEG, which for 15-20 days exhibits only delta and slower oscillations. Fast, low-voltage W rhythms appear later on, first during REMS, but spindle waves and S postures are absent from the start, such that these cats also display only atypical NREMS. Athalamic cats also show barbiturate-sensitive insomnia. Cats with ablation of the frontal cortices or the caudate nuclei remain permanently hyperactive. They also show a mild, but significant hyposomnia, which is permanent in afrontal cats, but lasts for about a month in acaudates. The polygraphic/behavioral features of their S-W states remain normal. We conclude and propose that: (a) the control of the S-W system is highly complex and distributed, but is organized hierarchically in a well-defined rostro-caudal manner; the rostral-most or highest level (telencephalon), is the most functionally complex/adaptative and regulates the lower levels; the diencephalic/basal forebrain, or middle level, has a pivotal role in inducing switching between S and W and in coordinating the lowest (brainstem) and highest levels; (b) W can occur independently in both the forebrain and brainstem, but true NREMS- and REMS-generating mechanisms exist exclusively in the forebrain and brainstem, respectively; (c) forebrain and brainstem S-W processes can operate independently from each other and are preprogrammed at birth; this helps understanding normal and abnormal polygraphic/behavioral dissociations in humans and normal dissociations/splitting in aquatic mammals; (d) NREMS homeostasis is present in the IF, but only REMS pressure after deprivation persists in the decerebrate cat; (e) the thalamus engages in both NREMS and W; (f) insomnia in diencephalic cats is the result of an imbalance between antagonistic W- and S-promoting cellular groups in the ventral brain (normally modulated by the telencephalon); (g) the EEG waves, which are signature for each S-W state, appear to truly drive the concomitant behaviors, e.g. a hypothetical human IF could alternate between behavioral NREMS and W/arousal/awareness; (h) a role for REMS is to keep the individual sleeping at the end of the self-limiting NREMS periods. The need for accelerating research on telencephaling NREMS periods. The need for accelerating research on telencephalic S-W processes and downstream control of the lower S-W system levels is emphasized.     

Effects of the lesion of the postcommissural part of the septum on the behavior of the rat.

The effects of the lesion of the postcommissural part of the septum on behavior of the rat has been studied. Results may be summarized as follows. An increase in the exploratory behavior in the open field which decreases rapidly; a decrease in the number of defecations in this test and a decrease in time leaving a dark environment for exploration. In the shuttle box test, no facilitation of the acquisition, but a permanent and quite significant increase in the intertrial activity has been found. We conclude that the lesions tend to decrease the emotivity of the subjects. An interpretation on the basis of the species -- specific defensive reactions explains the transitory and permanent effects of the lesions on the spontaneous activity.     

The Beauty of the Network in the Brain and the Origin of the Mind in the Control of Behavior

Behavior is not adequately described as a stimulus-response process. It is initiated by the animal and is generated because of its expected outcome in the future. The outcome can be good or bad for the animal. The brain is in charge of the selection process. This is the basic function of the brain. Taking Drosophila as a study case, this paper discusses initiating activity, several examples of outcome expectations, trying out (the internal search for a suitable behavior), chaining of actions, and the functional roles of chance in action selection. It takes mental processes and states such as goals, intentions, feelings, memories, cognition, and attention as higher levels of behavioral control that have their origin in biological evolution.     

Adequate function of the cell: Interactions between the needs of the cell and the needs of the organism

The continuous maintenance of cell adequate function (cellular stress) is considered to be the main feature which characterizes the activity of a live cell. In accordance with the concept of cellular stress, the transition of the cell to the state of adequate funcitoning represents a dual commitment. The cell must function adequately to respond to the demands of the organism and to provide for its own needs. Thus, it is proposed that two systems exist for the regulation of the adequate function of the cell: one enabling the cell to respond to the demands of the organism, and the other providing for the needs of the cell itself. The hormonal system of the organism represents the first of these mechanisms, and I believe that another system exists for regulation of intracellular needs. Adequate function of the cell is determined by the regulative, controlling and defense mechanisms. The balance between the needs of the cell and of the organism should be a concern of physician, since it provides for the optimal function and health of the organism as a whole.     

On the development of the sympathetic chain and the adrenal medulla in the mouse

Summary The first visible primordia of the sympathetic chain appear in the anterior thoracic region and run caudally through 8 segments in an embryo of 11 gestation days. At 12 gestation days the trunk reaches from the base of the skull into the sacral region. During the following days the trunk develops into ganglia with interganglionic fibers.At 16 gestation days there is a well developed trunk with a cranial ganglion cervicale superior and a ganglion stellatum in the anterior part of the thoracic region. In the remaining sympathetic chain there are segmentally arranged ganglia but in this common pattern large differences are noticed.At the 13th gestation day the first signs of the adrenal medulla and the splanchnic plexus appear in the form of sympathoblasts ventral to the sympathetic chain. The migration of sympathoblasts into the primordia of the adrenal cortex goes on for 3 days while the migration to the splancnic plexus in the mesenchym ventral and lateral to the aorta goes on at least 2 more days.     

Anatomical relationship between the morphology of the styloid process of the ulna and the attachment of the radioulnar ligaments

The radioulnar ligaments are the major stabilizers of the distal radioulnar joint under dynamic loading; however, anatomical detail regarding their attachment on the middle and distal thirds of the styloid process of the ulna remains unclear. Because previous anatomical studies included only old cadavers, their anatomical findings might not reflect the morphological features of younger and healthy specimens. This study investigated the anatomical features of the distal ulna, particularly the styloid process, to determine the attachment of the radioulnar ligaments to the styloid process and verified their direction and attachment to the styloid process in younger and healthy donors using magnetic resonance imaging (MRI). We investigated the morphological features of the distal ulna of 12 cadaveric wrists using micro-computed tomography (micro-CT). We also visualized and measured the distribution of the cortical bone thickness. We histologically analyzed three specimens in the axial plane and macroscopically analyzed seven specimens to examine the attachment of the radioulnar ligaments to the styloid process. In addition, we evaluated five wrists from living volunteers using 3.0 Tesla MRI. The distal ulna has a ridge on the dorsoradial aspect of the styloid process that corresponds to the attachment of the radioulnar ligaments. Micro-CT images after data processing revealed that the cortical thickness of the dorsoradial quadrant was thicker than that of the other quadrant at the proximal slice of the styloid process (p < 0.01), and that of the dorsoulnar (p = 0.021) and ulnopalmar (p < 0.01) quadrants at the middle slice. Histological analyses showed that the radioulnar ligaments were attached to the middle and distal thirds of the styloid process via chondral-apophyseal entheses. The direction of the fiber was dorsal in the middle third of the styloid process and changed to palmar in the distal third of the styloid process. The direction and attachment of the radioulnar ligaments on the styloid process were confirmed using MRI for younger and healthy participants. The radioulnar ligaments were attached to the dorsoradial ridge of the styloid process, which was confirmed by cortical bone thickening, histology at the attachment sites, and in vivo MR imaging. The directions of the radioulnar ligaments sterically intersected, which would satisfy both slipping stability and rotational mobility. These anatomical findings may provide the basis for biomechanical consideration of distal radioulnar joint stabilization.     

指背腱膜滑动与近侧指间关节屈曲关系及临床意义

目的:探讨指背腱膜滑动距离与近侧指间关节(PIP)屈曲关系,为临床修复提供解剖学基础。方法:男性成人新鲜尸体标本10侧30指(示、中、环指各10指),切除手指皮肤,不破坏腱鞘、屈肌支持带、伸肌支持带、内在肌及外在肌,使肌腱保持正常的生理状态,分别测量各指中央束(CS)、侧束(LB)在PIP屈曲45°和90°时的滑动距离。结果:当PIP屈曲45°时,CS滑动距离为(2.7±0.4)mm,LB滑动距离为(2.8±0.6)mm;当PIP屈曲90°时,CS滑动距离为(4.3±0.7)mm,LB滑动距离为(4.8±0.6)mm。结论:指背腱膜滑动距离减少,严重影响手指的屈曲功能。对于指背腱膜的新鲜性损伤应予以精确修复;对于陈旧性损伤的修复应确保指背腱膜的正常滑动范围。     

PEComas: the past,the present and the future

The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones.     

On the musculature of the gastro-intestinal tract of the guinea-pig

Summary The small intestine, caecum, colon and part of the stomach of guinea-pigs were studied by light microscopy, using semithin sections of plastic embedded specimens. The muscular coat is thicker in the duodenum than in the rest of the small intestine. The ratio between longitudinal and circular muscle is 1:4.6 in the duodenum and it increases regularly along the small intestine, to reach 1:2 in the terminal ileum. In the caecum, shape and sectional area of the muscle tissue were analyzed along the full length of the taeniae. In the caecal circular muscle there is a characteristic change in the arrangement of the muscle bundles from the regions in the centre of the haustrations to the regions of the grooves between haustrations or to those lying beneath a taenia. The functional significance of the taeniae is discussed in terms of an arrangement allowing reduction of the lumen of the organ (which at the level of the grooves between haustrations acquires a triangular outline) more efficiently than if the longitudinal musculature were spread over the entire surface of the organ. Haustrations are present also on one side of the wall of the ascending colon where there is no longitudinal muscle layer. In the descending colon the structure of the wall is examined in different functional states, namely in the regions between fecal pellets (constricted regions) and in the regions around a fecal pellet (moderately distended regions). The musculature increases considerably in thickness in the constricted regions (both muscle layers being actively contracted), while the mucosa and submucosa are thrown into prominent longitudinal folds. These folds produce occlusion of the lumen when the circular muscle has shortened by about 50%.