Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation.

High-frequency whole body vibrations can be osteogenic, but their efficacy appears limited to skeletal segments that are weight bearing and thus subject to the induced load. To determine the anabolic component of this signal, we investigated whether low-level oscillatory displacements, in the absence of weight bearing, are anabolic to skeletal tissue. A loading apparatus, developed to shake specific segments of the murine skeleton without the direct application of deformations to the tissue, was used to subject the left tibia of eight anesthesized adult female C57BL/6J mice to small (0.3 g or 0.6 g) 45 Hz sinusoidal accelerations for 10 min/day, while the right tibia served as an internal control. Video and strain analysis revealed that motions of the apparatus and tibia were well coupled, inducing dynamic cortical deformations of less than three microstrain. After 3 weeks, trabecular metaphyseal bone formation rates and the percentage of mineralizing surfaces (MS/BS) were 88% and 64% greater (p < 0.05) in tibiae accelerated at 0.3 g than in their contralateral controls. At 0.6 g, bone formation rates and mineral apposition rates were 66% and 22% greater (p < 0.05) in accelerated tibiae. Changes in bone morphology were evident only in the epiphysis, where stimulated tibiae displayed significantly greater cortical area (+8%) and thickness (+8%). These results suggest that tiny acceleratory motions--independent of direct loading of the matrix--can influence bone formation and bone morphology. If confirmed by clinical studies, the unique nature of the signal may ultimately facilitate the stimulation of skeletal regions that are prone to osteoporosis even in patients that are suffering from confinement to wheelchairs, bed rest, or space travel.     

Laser trabecular ablation (LTA).

As part of a pilot study for glaucoma surgery, the use of 3 infrared solid state lasers with 4 fiber optic delivery systems to ablate human trabecular meshwork was investigated. Laser trabecular ablation (LTA) was attempted with the Erbium:YAG (2.94 microns), Erbium:YSGG (2.79 microns), and Holmium:YSGG (2.1 microns) lasers. Laser energy was delivered as a single pulse (250 microseconds) by tissue fiber optic contact with low hydroxyl-fused silica (200 and 500 microns), zirconium fluoride (250 microns), or sapphire (250 microns) fiber optics. Total energy required and thermal effects decreased as laser wavelength increased. LTA was best achieved at 2.94 microns (4 mJ total energy; energy densities = 8.2-12.7 J/cm2; pulse length 250 microseconds) with average thermal damage zones of 5.3-10.3 +/- 1.3-2.4 microns (means +/- SDs) to contiguous structures. This finding has potential applications in the surgical treatment of open-angle and congenital glaucoma and may minimize failure rates seen in other types of surgery on the trabecular meshwork where disrupted trabecular meshwork is not removed.     

非穿透性小梁切除术联合人羊膜植入临床观察

目的：观察非穿透性小梁切除术联合人羊膜植入的临床效果。方法：对18例（30眼）中、晚期开角型青光眼进行非穿透性小梁切除术联合人羊膜植入，术后观察视力、视野、眼压及滤过泡形成情况。结果：术后随访3－9月，视力、视野稳定，眼压≤20mmHg(1mmHg=0.133kPa)，滤过泡形成良好，并发症少。结论：非穿透性小梁切除术 联合人羊膜植入治疗开角型青光眼，能有效降低眼压，形成功能性滤过泡和并发症少等优点，是治疗开角型青光眼较理想的方法。     

Inhibitory Effect of Tissue Transglutaminase （tTG） Antisense Oligodeoxynucleotides on tTG Expression in Cultured Bovine Trabecular Meshwork Cells

To study the effect of tTG fully phosphorothioated antisense oligodeoxynucleotides （tTG-ASDON） on tTG expression in cultured bovine trabecular meshwork cells （BTMCs） in vitro and explore a new treatment alternative for primary open angle glaucoma （POAG）, the ASDON1 and ASDON2 complementary to the protein codogram region of tTG were designed, synthesized and phosphorothioated according to the secondary structure of tTG. The ASDON1 and ASDON2 were embedded in Lipofectamine and transfected into BTMCs. The untreated group served as negative controls. The expression of tTG in the mRNA and protein level were measured by semi-quantitative RT-PCR and immunohistochemical technique-Supervision method respectively. Our results showed that both the mRNA and the protein of tTG with tTG-ASDON1 and tTCr-ASDON2 were significantly decreased as compared with that of the controls （P〈0.05）. On the other hand, no significant difference was found between the ASDON1 group and the ASDON2 group. It is concluded that the expression of tTG mRNA and protein in cultured BTMC are down-regulated by tTG- ASDON. As a result, tTG-ASDON may be used for the treatment of POAG through the inhibitory effect on the expression of tTG.     

维拉帕米对牛眼小梁细胞增殖和吞噬功能的影响

目的　研究维拉帕米对牛眼小梁细胞 (BTMC)增殖和吞噬功能的影响。方法　采用MTT和3 H TDR实验检测 0 0 0 0 1、0 0 0 0 5、0 0 0 1、0 0 0 5、0 0 1、0 0 5、0 1mg/ml 7种质量浓度的维拉帕米对BTMC增殖功能的影响。以乳胶微粒为标记 ,定量检测等于和低于 0 0 1mg/ml维拉帕米对BTMC吞噬功能的影响。结果　低于 0 0 1mg/ml维拉帕米对BTMC增殖功能无抑制作用 (P >0 0 5 ) ,等于或高于 0 0 1mg/ml的维拉帕米可浓度依赖性地抑制BTMC增殖功能 (P <0 0 5 ) ,其IC50 分别为 0 0 3 2 3mg/ml(MTT)和 0 0 2 5 9mg/ml( 3 H TDR)。 0 0 0 1、0 0 0 5、0 0 1mg/ml维拉帕米可浓度依赖性地促进BTMC的吞噬功能 (P <0 0 5 )。结论　临床应用的 0 12 5 %维拉帕米滴眼剂在房水中的质量浓度为 ( 160 7± 2 72 )ng/ml ,该质量浓度范围不抑制BTMC增殖。选用等于和低于 0 0 1mg/ml作为后续实验的质量浓度。维拉帕米还可通过促进小梁细胞的吞噬功能 ,减少房水外流阻力 ,有望在发病学环节上治疗原发性开角型青光眼     

丝裂霉素C对体外培养牛眼小梁细胞毒性的研究

向第3～4代牛眼小梁细胞（bovinetrabecularmeshworkcell，BTMcell）体外培养液内加入不同浓度的丝裂霉素C（MitomycinC，MMC），通过光镜、电镜等观察该药对细胞的形态、结构及吞噬功能的影响.发现MMC可以引起细胞皱缩变形，超微结构中出现线粒体及科面内质网扩张、核固缩或核碎裂等，细胞吞噬微球的数目也有所减少。苔盼蓝染色结果显示MMC不影响小梁细胞存活的浓度为1×10(-7)g／L，半数致死量为1×10(-4)～1×10(-3)g／L。MMC的临床应用是否会对小梁细胞造成损伤值得进一步研究。     

Recent origin of low trabecular bone density in modern humans

Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations.Obligate bipedalism—a defining feature of humans that distinguishes us from our closest living relatives, the African apes—has transformed the human skeleton. Among these unique features are long lower limbs with large joint surfaces. These large joint surfaces help distribute loads over a larger surface area and thus are better at resisting the high forces incurred during locomotion on two limbs instead of four (1–5). Early African Homo erectus at 1.8–1.5 Ma had enlarged lower limb joint surfaces (1, 3) and a larger stature (6) and body mass (7, 8) than many earlier hominins, and this pattern often is considered to reflect the emergence of a more modern human-like body plan (1, 3, 5, 6, 9; but also see ref. 7).Recent modern human (Holocene Homo sapiens) skeletons also appear to be gracile as compared with earlier hominins (10–14). Here, “gracilization” refers to the reduction in strength and bone mass relative to body mass inferred from osseous tissue and overall bone size and has been studied mainly using diaphyseal cortical bone cross-sections (10–16). Although the relationship between mechanical loading during life and bone strength is likely to be complex (17), there is much evidence that increased mechanical loading leads to increases in relative bone strength (18). Thus, diaphyseal skeletal gracilization in recent modern humans relative to earlier hominins generally has been attributed to a decrease in daily physical activity via technological and cultural innovations (6, 10, 13–15, 19–22).There also is evidence that increased activity level and mechanical loading increases trabecular bone mineral density within limb bones (ref. 23 and references therein). However, although there currently is extensive literature on the variation and evolution of long bone shaft strength in humans and fossil hominins (10, 15, 16, 24–27), there has been comparatively less research on trabecular bone (28–30) because of the technical challenges in quantifying its structure: limited access to high-resolution CT (microCT), problems with preservation and/or imaging of fine trabecular structures, particularly in fossils, and intensive processing time. A few studies examining individual limb elements have reported low trabecular density, as measured by volumetric density (the trabecular bone fraction, TBF, or bone volume relative to total volume), in recent modern human epiphyses. The recent modern human arm (humerus) and hand (metacarpals) have low TBF (31, 32) and mineral density (33) compared with chimpanzees and orangutans. This finding might be expected, because humans rarely use their upper limbs for locomotion and therefore do not habitually expose their upper limb bones to the high loads of body-weight support. Indeed, recent modern human upper limb bones have relatively low diaphyseal strengths compared with the lower limbs (34). However, recent modern humans also have low TBF in the calcaneus (35) and metatarsals (36) compared with great apes, despite the increased proportionate loading and full body-weight support incurred during bipedal locomotion.To our knowledge, this study is the first to examine how trabecular density varies throughout the human appendicular skeleton, how that variation compares with other primates, and how trabecular density evolved in the hominin lineage. We test the hypotheses that (i) recent modern humans have lower TBF throughout the upper and lower limbs compared with that of other primates and (ii) the reduction in TBF first occurred in African Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in recent modern humans. This study is the first, to our knowledge, to evaluate TBF in upper and lower limb joints in fossil hominins from late Pliocene Australopithecus to recent Homo.To assess whether low trabecular density is a systemic phenomenon throughout the human skeleton, we examined trabecular density in seven epiphyseal elements throughout the upper limb (humeral head, proximal ulna, distal radius, metacarpal heads) and lower limb (femoral head, distal tibia, and metatarsal heads) (Tables S1 and S2). We measured trabecular density in a 2D image as the ratio of bone pixels/total pixels (i.e., the TBF) within a defined region of interest (ROI) for each epiphysis (Fig. S1). We first compared TBF across extant primate (baboon, orangutan, chimpanzee, and recent modern human) limb epiphyses (Table S2). We also compared TBF in late Pliocene and Pleistocene hominins (n = 42) within the context of changes in body form in early Homo at 1.8 Ma and throughout the Pleistocene (Table S2).

Table 1.

Sample size of taxa studied

Gracility of the modern Homo sapiens skeleton is the result of decreased biomechanical loading

The postcranial skeleton of modern Homo sapiens is relatively gracile compared with other hominoids and earlier hominins. This gracility predisposes contemporary humans to osteoporosis and increased fracture risk. Explanations for this gracility include reduced levels of physical activity, the dissipation of load through enlarged joint surfaces, and selection for systemic physiological characteristics that differentiate modern humans from other primates. This study considered the skeletal remains of four behaviorally diverse recent human populations and a large sample of extant primates to assess variation in trabecular bone structure in the human hip joint. Proximal femur trabecular bone structure was quantified from microCT data for 229 individuals from 31 extant primate taxa and 59 individuals from four distinct archaeological human populations representing sedentary agriculturalists and mobile foragers. Analyses of mass-corrected trabecular bone variables reveal that the forager populations had significantly higher bone volume fraction, thicker trabeculae, and consequently lower relative bone surface area compared with the two agriculturalist groups. There were no significant differences between the agriculturalist and forager populations for trabecular spacing, number, or degree of anisotropy. These results reveal a correspondence between human behavior and bone structure in the proximal femur, indicating that more highly mobile human populations have trabecular bone structure similar to what would be expected for wild nonhuman primates of the same body mass. These results strongly emphasize the importance of physical activity and exercise for bone health and the attenuation of age-related bone loss.Compared with other hominoids and extinct hominin species, more recent humans possess relatively gracile postcranial skeletons (1–9). One of the consequences of this gracility in contemporary humans is an increased fracture risk associated with age-related bone loss and osteoporosis [hip fractures alone are projected to reach 6.26 million per year globally by 2050 (10)] (11–15). The etiology of this relative gracility remains uncertain, and this uncertainty hinders the development of strategies for mitigating fracture risk and morbidity. The progressive gracilization of the Homo postcranial skeleton was originally detected in cortical bone structure (1, 2), but has now been demonstrated in the trabecular bone microstructure of joints (12, 14, 16–19), where osteoporotic fracture risk is highest (20). Most notably, in an analysis of thoracic vertebral bodies, Cotter et al. (12) found that young adult humans have significantly lower trabecular bone volume fraction (BV/TV) and thinner vertebral shells than similarly sized apes. Griffin et al. (16) also found significantly lower BV/TV in the human first and second metatarsal heads compared with hominoid primates. The results of these studies are corroborated by work on the hominoid calcaneus (17), the anthropoid proximal femur (18), and several other clinical studies of femoral head trabecular bone architecture in contemporary adult humans (21–24). The results of these studies suggest that relative trabecular bone volume in the axial skeleton and lower limbs is significantly lower in modern humans compared with quadrupeds, despite the legs and vertebral column bearing a higher proportion of body mass and peak substrate reaction forces during bipedal locomotion (25–27). The high positive correlation between BV/TV and bone material properties (28–32) suggests that trabecular bone in the human lower limb and vertebral column is less stiff than in other primates. Ongoing debates aimed at enhancing our understanding of bone adaptation, skeletal health, and the prevention and treatment of osteoporosis would be greatly enhanced by the determination of the primary factors underlying the relatively gracile skeleton of living humans.Several explanations for the skeletal gracility of recent modern humans have been offered. The most common explanation is that living populations are simply less physically active compared with extinct hominins or closely related contemporary wild apes (1–6). This hypothesis suggests that a shift in subsistence patterns away from hunting and gathering, combined with an increased reliance on technology, led to reductions in overall physical activity levels and mobility in more recent hominins (cf. 2). In contrast, some (12, 13) attribute lower trabecular bone volume in humans to the mechanical consequences of the larger vertebral cross-sectional areas and larger joint surface areas required of an obligate biped. The crux of this argument is that larger joint surfaces distribute loads across a greater area, thereby reducing strain in the underlying trabecular tissue and leading to lower bone volume. Cotter et al. (12) have suggested that even if human activity levels were equal to those of wild apes, this loading would still be insufficient to illicit comparable trabecular bone growth. Alternatively, it has been suggested that the low bone-volume fraction observed in human thoracic vertebrae and the first and second metatarsals are the result of systemic physiological differences between humans and apes (14, 16). These studies do not suggest the mechanism or the function of this systemic gracility, but one potential explanation may be selection for increased tissue economy in hominins (5, 33–35).The aim of this study is to assess explanations for the trabecular bone gracility found in contemporary populations by evaluating the skeletal structure of human groups with divergent behavioral patterns within the broader context of primate biology. The impact of this research is twofold: (i) the samples and methods (imaging of trabecular bone microstructure using microCT) allow us to address questions inaccessible to research focused on living participants, yet inform on prevention and treatment in the 21st century; and (ii) these novel analyses allow us to evaluate the efficacy of quantifying trabecular bone structure for the purpose of differentiating activity and mobility patterns among prehistoric hominins. For this assessment, trabecular bone architecture of the proximal femur is compared among human foragers, village agriculturalists, and a large sample of extant primates. One of three outcomes is possible: (i) trabecular bone architecture does not separate Homo sapiens from the general nonhuman primate pattern, indicating a high level of canalization in primates for specific trabecular architectural features; (ii) trabecular bone architecture separates all H. sapiens from the nonhuman primate allometric pattern, indicating that trabecular bone structure in humans is largely driven by postcranial joint size or a genetic predisposition to maintaining a relatively gracile skeleton; or (iii) trabecular bone architecture separates agriculturalists and foragers, indicating structural differences among the groups, highlighting the influence of biomechanical loading or other osteogenic factors on trabecular bone composition.     

Evaluation of MRI resolution affecting trabecular bone parameters: Determination of acceptable resolution

The objective of this study is to evaluate the effect of MR image resolution on trabecular bone parameters and to determine the acceptable resolution that can be accurately analyzed to assess structural parameters. Ten distal femoral condyle specimens of 1 × 1 × 1 cm³ were scanned with a 4.7‐T Bruker BioSpec MRI scanner using a three‐dimensional fast large‐angle spin‐echo sequence with various iso‐cubic voxels sizes (65, 130, 160, 196, 230, and 260 μm). Otsu thresholding was applied to identify voxels containing bone. Conventional bone parameters, structural bone parameters, and skeleton‐based local trabecular thickness (slTB.Th) were evaluated. The Bland–Altman method and correlation indicated that the conventional and structural bone parameters were preserved with an iso‐cubic voxel size up to 230 μm (r > 0.932 and r > 0.843, respectively). In addition, slTB.Th derived from the highest resolution images (65 μm iso‐cubic voxel size), correlated well (r > 0.833) with the values computed from lower resolution images, up to 230 μm, which is twice typical human trabecular thickness range (100–150 μm). The outcome of this study suggests that the various bone parameters were well preserved up to 230 μm images. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

层间巩膜瓣切除联合小梁巩膜条转移治疗青光眼疗效观察

目的探讨层间巩膜瓣切除联合小梁巩膜条转移治疗青光眼的疗效。方法收集2010年5月至2011年2月在我院眼科住院治疗的青光眼患者42例(51眼),分为治疗组(21例26眼)与对照组(21例25眼)。治疗组采用层间巩膜瓣切除联合小梁巩膜条转移术,对照组采用常规小梁切除术。术后观察两组视力、眼压、滤过泡情况及并发症。采用SPSS17.0软件进行统计学处理。结果术后两组视力均较术前有所改善,治疗组改善更为明显。治疗组手术后眼压明显下降,至随访12个月时眼压为(14.46±1.92)mmHg(1kPa=7.5mmHg)。对照组手术后眼压亦明显下降,至随访12个月时眼压为(19.27±1.76)mm-Hg,差异有统计学意义(P<0.05)。术后12个月治疗组功能性滤过泡发生率所占比例为88.5%,对照组为60.0%,差异有统计学意义(P<0.05)。治疗组26眼中7眼出现浅前房,对照组仅3眼术后出现浅前房。治疗组Ⅰ级前房积血3眼,对照组Ⅰ级前房积血3眼,术后3～5d可完全吸收。治疗组5眼出现低眼压,对照组3眼出现低眼压,术后8d内眼压缓慢回升。结论层间巩膜瓣切除联合小梁巩膜条转移操作相对简单,手术安全,远期降眼压效果明显,值得临床推广应用。