Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

Radiation effects on the cosmetic outcomes of immediate and delayed autologous breast reconstruction: an argument about timing.

OBJECTIVE: To conduct a systematic review to gather the available evidence on the optimum timing of the radiotherapy in relation to autologous breast reconstruction. MATERIAL AND METHODS: The data was extracted from scientific databases, and a manual follow-up of references. The studies were selected which included at least 20 patients with any method of autologous breast reconstruction who were treated with adjuvant radiotherapy either before or after their reconstruction, and had addressed the effects of radiotherapy on the cosmetic outcome in their results. The principal outcome was cosmetic appearance. Secondary outcomes were immediate and delayed complications. RESULTS: We could not find any randomised controlled trial on this topic. Ten studies were included, most were retrospective, heterogeneous in terms of control groups, radiation doses, follow-up duration, and outcome measurements. Two studies included no control groups, and four studies compared the outcomes of patients with radiotherapy either before (n=3) or after (n=1) autologous breast reconstruction. The overall incidence of complications was increased in patients with radiotherapy in three out of these four studies. Only four studies directly compared the outcomes of patients who received radiotherapy before with patients who received radiotherapy after autologous breast reconstruction and two out of these reported worse outcomes associated with post-reconstruction radiotherapy. CONCLUSIONS: Despite the paucity of the published data, the current evidence suggests that the radiation has a deleterious effect on autologous flap reconstruction. Until better methods of radiation delivery can be devised to minimise the long term radiation sequelae in the irradiated tissue, delayed reconstruction seems to be a safe option in most of the cases. However, the findings from these studies should be interpreted with great caution before generalising from their results.     

Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.     

Effects of cerulenin on the endogenous fatty acid synthetic activity in squamous cell carcinoma of the oral cavity.

PURPOSES: Inhibition of cerulenin on the endogenous fatty acid synthetic activities of oral squamous cell carcinoma (OSCC) and normal oral mucosa was assayed. METHODS: Squamous cell carcinoma and normal oral mucosa were collected fresh from surgical specimens. The collected tissues were minced in RPMI 1640 and divided into 3 groups: cerulenin treated, dimethylsulfoxide treated, and control. The tissues were incubated in [1(2)-(14)C]acetic acid, sodium salt for the last 2.5 hours of the treatment at 37 degrees C in 5% CO(2). After labeling, total lipids were extracted and counted for (14)C by scintillation counting. RESULTS: Endogenous fatty acid synthetic activities of oral squamous cell caranoma in the cerulenin-treated group decreased by 19% at 1 hour, 64% at 2 hours, and 87% at 4 hours; remained nearly unchanged in the dimethylsulfoxide-treated group; and increased slightly in the control group. The oral mucosa tissues were only mildly affected by cerulenin in fatty acid synthesis. CONCLUSIONS: Cerulenin significantly inhibits fatty acid synthetic activity in squamous cell carcinoma and only mildly affected the oral mucosa, indicating that the fatty acid synthetic pathway may be exploited as a target for developing anticancer drugs.     

Chemical analysis of powder and set forms of Portland cement, gray ProRoot MTA, white ProRoot MTA, and gray MTA-Angelus.

OBJECTIVE: To evaluate the chemical composition and crystalline structures of Portland cement, gray ProRoot MTA (gray MTA), white ProRoot MTA (white MTA), and gray MTA-Angelus. STUDY DESIGN: X-ray diffraction analysis was used to identify and characterize crystalline phases, and energy dispersive x-ray spectrometer was used to determine the chemical composition of the test materials. Both powder form and set form were examined. RESULTS: The crystalline structure and chemical composition of gray and white MTA were similar except for the presence of iron in gray MTA. Both were composed mainly of bismuth oxide and calcium silicate oxide. Portland cement was composed mainly of calcium silicate oxide and did not contain bismuth oxide. Gray MTA-Angelus had a lower content of bismuth oxide than ProRoot MTA. There were no noticeable differences in the chemical composition and crystalline structures between the powder and set forms of any of the material tested. CONCLUSION: Portland cement differed from the MTA by the absence of bismuth ions and presence of potassium ions. Gray MTA contained a significant amount of iron when compared with white MTA. In addition, gray MTA-Angelus had a lower content of bismuth oxide than ProRoot MTA.     

自体腹白线片修补十二指肠溃疡穿孔(附13例报告)

目的探讨用游离自体腹白线片修补急性十二指肠溃疡穿孔的应用价值。方法从2006年1月至2006年7月对13例用自体腹白线片修补急性十二指肠溃疡穿孔的病人的临床资料和随访情况进行回顾性分析,其中2例穿孔大于2cm2,平均手术时间60分钟,平均失血量20ml,平均住院天数9±1天。结果游离自体腹白线片修补急性十二指肠溃疡穿孔13例均痊愈出院。随访15天至6个月,无手术并发症。结论本方法操作较简单、安全、效果好,其适应症广,是一种可行的新方法。     

垂体腺瘤的分子病因学研究进展

垂体腺瘤是发生于垂体前叶的良性肿瘤，约占中枢神经系统肿瘤的10％-20％，而无功能微腺瘤占到成人尸检的23％左右。生理上根据免疫组化将垂体腺瘤按功能分为有激素分泌活性腺瘤（functioning pituitary adenoma，FPA）和非激素分泌活性腺瘤（non—functioning pituitary adenoma，NFPA）两大类。[第一段]     

Future direction of nanomedicine in gastrointestinal cancer]

Cancer is one of the leading causes of death in human, and among various cancers, gastrointestinal cancers occupy more than 55%. Gastric cancer is the first leading cause of cancer-related mortality in the world and the number of pancreas and colon cancers are increasing remarkably during last two decades which will continue to increase in the future. Even though the clinical importance of gastrointestinal cancers is very high and endless efforts has been made to develop novel diagnostic and therapeutic methods to improve the patient's quality of life and survival, the realistic advance in the actual survival benefit of the cancer patients are still strongly required. Nanotechnology has the power to radically change the way of cancer diagnosis and treatment. Currently, there is a lot of researches on novel nanodevices capable of detecting cancer at its earliest stage, pinpointing its location within the body, and delivering anticancer drugs specifically to the malignant cells. Nanoscale devices can readily interact with biomolecules both on the cell surface and within the cell. In addition, nanoscale devices are already proven that they can deliver therapeutic agents to target cells even within specific organelles. Major areas in which nanomedicine is being developed in cancer include early detection and proteomics, imaging diagnostics and multifunctional therapeutics. Because nanotechnology would provide a technical power and tool that enable new diagnostics, therapeutics, and preventives to keep pace with today's explosion in knowledge in the future, it would be very useful to know the perspectives in the direction of nanotechnology as a major clinician responsible for the patients with gastrointestinal malignancies.