Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

健血升白冲剂对小鼠造血功能的影响

目的：研究健血升白冲剂对小鼠血液系统的影响。方法：以骨髓细胞计数，白细胞计数和血象为指标，观察健血升白冲剂对正常小鼠和化学及放射损伤小鼠的影响。结果：健血升白冲剂明显增加正常小鼠白细胞计数（Ｐ＜００１），显著改善环磷酰胺诱导小鼠白细胞和骨髓细胞的减少作用（分别为Ｐ＜００５，Ｐ＜００１），并能显著增加６０Ｃｏ放射损伤小鼠骨髓细胞（Ｐ＜００１）和白细胞（Ｐ＜００１）。结论：健血升白冲剂对化学及放射损伤小鼠血液系统有明显的保护及改善作用。是一个有开发价值的药物。     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Ridge number density: A new parameter for in vivo bone structure analysis

An advanced analysis of the mechanical properties of bone should include information about the microarchitecture of cancellous bone in addition to its density. It has recently been shown that high-resolution quantitative computed tomography and magnetic resonance imaging have the potential to assess such information in a noninvasive way in patients. Both techniques, however, lack sufficient spatial resolution to image the individual trabeculae with true precision. In this work, a new parameter, Ridge number density (RND), is introduced. RND is a measure for the trabecular number, which can be extracted directly from high-resolution three-dimensional (3D) images of patients. We applied the RND technique to a test group of nine healthy, postmenopausal women measured repetitively with a high-resolution 3D peripheral quantitative computed tomography (3D-pQCT) system with 165 × 165 × 165 μm³ voxel size. Simultaneously with the RND determination, the trabecular bone density (TBD) was also assessed in the same volume of interest. The examination site was the distal radius. The intersubject variability of the measured test group was 10.5% for RND and 26.3% for TBD. The root mean square error between first and second examinations (midterm reproducibility) was 1.6% and 1.1%, respectively. RND is determined independently from TBD and pertains to the structure of the cancellous bone. As such, it might add crucial information in cases where bone mass or bone density measurements alone give ambigous results.     

Relationship Among MRTA, DXA, and QUS

Dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) are the accepted modalities for the evaluation of fracture risk in the clinical setting. However, neither method provides a direct measurement of bone mechanics. In this study, we investigated a prototype device, known as a mechanical response tissue analyzer (MRTA), which provides direct mechanical measurements of mechanical properties of bone. A total of 56 healthy volunteers (20 men and 36 women) between the ages of 18 and 83 were recruited. The MRTA was used to measure the cross-sectional bending stiffness (EI) of the ulna bone. Axial speed of sound (SOS) at the ulna bone was determined by QUS; bone mineral content (BMC) and bone mineral density (BMD) were determined by DXA. Correlations, regression analysis, and analyses of variance (ANOVAs) were used to compare the three modalities. These analyses revealed that although there are strong linear relationships among the data collected by the various technologies, the bone properties reflected by MRTA are not fully explained by DXA and QUS. We conclude that the total information conveyed by MRTA measurements is unique. Further research is needed to delineate the different qualities of bone strength that are captured by MRTA, but not by DXA or QUS.     

Value of digital volume tomography in patients with conductive hearing loss

Digital volume tomography (DVT) is an extension of panoramic tomography. With this diagnostic technique, characterized by high resolution, a narrow section width (0.125 mm) and three-dimensional display, small pathological processes can be well visualized. Twenty-five patients with the history of a progressive hearing loss were examined with DVT (Accu-I-tomo, Morita, Japan). The results were compared with pre- and intraoperative findings to evaluate the diagnostic value of DVT in cases of erosion of the ossicular chain. With high resolution and artifact-free demonstration of the middle ear and the ossicular chain, it was possible to define its continuity preoperatively by DVT in all 25 cases. An intact ossicular chain was found by DVT in 13 cases and was later confirmed by surgery. The predicted erosion of the ossicles was verified in 12 patients, and a tympanoplasty type III was performed. Digital volume tomography is an excellent technique to examine the middle ear cleft and inner ear, and expands the application of diagnostic possibilities in the lateral skull base. Therefore, improvement in preoperative diagnosis is achieved along with more accurate planning of the surgical procedure. Digital volume tomography delivers a small radiation dose with a high resolution and a low purchase price for the equipment.     

Occurrence and Distribution of Bone Tumors in Beagle Dogs Exposed to 90Sr

Radiation-induced bone tumors in beagle dogs exposed to ⁹⁰Sr have been evaluated in terms of their incidence, time of appearance, occurrence as multiple tumors, anatomic distribution, and the influence of sex on their development. Among dogs fed ⁹⁰Sr during skeletal development, the incidence of bone tumors was dose dependent. Tumors thus appeared in 10 of 19 dogs receiving average skeletal doses of 130 Gy, 15 of 60 receiving 97 Gy, 5 of 61 receiving 61 Gy, 2 of 65 receiving 26 Gy, and 1 of 40 receiving 1.3 Gy. No tumors appeared among 66 dogs who received 8 Gy, 78 who received 0.3 Gy, and 80 non-irradiated controls, all of which have been observed for life. Among dogs given a single intravenous injection of ⁹⁰Sr in early adulthood, tumor production was somewhat higher than among ⁹⁰Sr-fed dogs at the same radiation dose: bone tumors were present in 6 of 25 dogs who received 62 Gy and 1 of 20 dogs who received 7.5 Gy. Bone tumors appeared sooner and were more often multiple in animals receiving the higher doses. Long bones were the sites of most of the tumors appearing after the highest dose level. Bones of the head, particularly the mandible, were the predominant site of tumors in the next highest dose level group.     

Bone disease in primary biliary cirrhosis: Lack of association with distal renal tubular acidosis

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.