RANKL is a marker and mediator of local and systemic bone loss in two rat models of inflammatory arthritis.

RANKL is an essential mediator of bone erosions, but the role of RANKL in systemic bone loss had not been studied in arthritis. RANKL protein was increased in rat joint extracts and serum at the earliest stages of arthritis. Osteoprotegerin (OPG) treatment reversed local and systemic bone loss, suggesting that RANKL is both a marker and mediator of bone loss in arthritis. INTRODUCTION: RANKL is well established as an essential mediator of bone erosions in inflammatory arthritis, but the role of RANKL in systemic bone loss in arthritis had not been studied. We hypothesized that serum RANKL could serve as both a mediator and as a novel biomarker for local and systemic bone loss in arthritis. We challenged this hypothesis in two established rat models of inflammatory arthritis. We sought to determine whether serum RANKL was elevated early in disease progression and whether RANKL suppression could prevent both local and systemic bone loss in these models. MATERIALS AND METHODS: Detailed time-course studies were conducted in animals with collagen-induced (CIA) or adjuvant-induced (AIA) arthritis to evaluate the onset and progression of inflammation (paw swelling), bone erosions, osteoclast numbers, and RANKL protein levels in arthritic joints and in serum. Additional CIA and AIA rats (n=8/group) received placebo (PBS) or recombinant OPG (3 mg/kg three times weekly) for 10 days beginning 4 days after disease onset (first macroscopic evidence of hind paw erythema and edema) to assess the role of RANKL in local and systemic bone loss. RESULTS: RANKL protein was significantly elevated in the joints and serum of CIA and AIA rats within 1-2 days of disease onset. Increased RANKL levels were associated with local (hind paw) and systemic (vertebral) osteopenia in both models. The RANKL inhibitor OPG prevented local and systemic osteopenia in both models of established disease. CONCLUSIONS: RANKL protein is significantly increased both locally and systemically during the earliest stages of inflammatory arthritis in rats, suggesting that serum RANKL might have prognostic value for bone erosions and systemic osteopenia in this condition. RANKL inhibition through OPG prevented local and systemic bone loss in these arthritis models, suggesting that RANKL inhibition is a promising new approach for treating bone loss in arthritis.     

论发展高效囊式抗荷系统

综述了国内外发展抗荷装备的状况，明确了高效囊式抗荷系统是当今的发展趋势，提出加速这方面的研究，以提高囊式抗荷装备的性能，实现抗荷装备通用化、系列化的建议。     

Transpulmonary disposition of prilocaine, mepivacaine, and bupivacaine in humans in the course of epidural anaesthesia

The pulmonary first-pass kinetics of the amide-linked local anaesthetics prilocaine, mepivacaine and bupivacaine were studied in 33 patients after a single epidural injection. Drug concentrations were monitored before and after lung passage, i.e. in samples withdrawn simultaneously from mixed venous and arterial blood. In most cases, maximum plasma concentrations were observed 10 min after injection (range 2 to 30 min). Two min after injection the local anaesthetics were distinctly extracted by the lung (prilocaine 40%, mepivacaine 20%, and bupivacaine 12%). Prilocaine was retained by the lung more effectively than bupivacaine and mepivacaine. However, a transpulmonary concentration gradient could be observed only for a short time, i.e. maximum 15 min. Altogether, in the case of accidental fast absorption, e.g. inadvertent intravenous injection, arterial peak concentrations of these drugs will be attenuated by passage of the lung. However, the lung will not substantially lower the risk of toxicity by amide-linked local anaesthetics during normal conditions of regional anaesthesia where slow absorption occurs.     

Assessment of Thymic Activity in Human Immunodeficiency Virus-Negative and -Positive Adolescents by Real-Time PCR Quantitation of T-Cell Receptor Rearrangement Excision Circles

Circular DNA molecules known as T-cell receptor rearrangement excision circles (TREC) arise during T-cell development and are present in cells that have recently emigrated from the thymus. In cross-sectional studies, the number of peripheral blood lymphocytes bearing TREC decreases with age, consistent with an anatomically demonstrated loss of thymic epithelial tissue. TREC numbers increase following hematopoietic stem cell transplantation and during therapy for human immunodeficiency virus (HIV) infection. Quantitation of TREC has therefore been proposed as a parameter of thymic activity. In this study, we used real-time PCR to quantify TREC in peripheral blood samples obtained longitudinally from HIV-seronegative adolescents. TREC values in peripheral blood T cells were very stable throughout adolescence, once thought to be a time of rapid involution of the thymus. In addition, in a cross-sectional analysis, we examined TREC values in a cohort of HIV-positive adolescents and found evidence of ongoing thymopoiesis in perinatally infected individuals, despite lifelong infection. These data demonstrate the utility of TREC assessment in adolescents and that HIV infection does not uniformly result in accelerated thymic involution in childhood.     

人皮移植于裸小鼠体上的实验模型

本文报道了人皮移植到裸鼠背部的实验模型.通过肉眼及组织学检查,人皮片可活存3个月之久.在皮片移植约1个月后,此模型可用于皮肤药理学和皮肤毒理学的研究.文中简要地讨论了皮片厚度、皮肤创面的固定及包扎和皮片的保护等有关技术问题.     

Plasmatocyte depletion in larvae of Manduca sexta following injection of bacteria

Injection of bacteria and bacterial cell walls into larvae of the tobacco hornworm elicits a rapid, specific depletion of plasmatocytes from circulation. Plasmatocyte depletion in response to injection of bacteria is dose dependent with a threshold for response between 10(3)-10(4) bacteria per insect and a maximal depletion at greater than 10(7) bacteria per insect. Injection of saline, latex beads that are phagocytized, or fragments of peptidoglycan that elicit antibacterial protein synthesis do not affect plasmatocyte abundance.     

星形胶质细胞瘤MRI信号变化病理基础探讨（附102例分析）

星形胶质细胞瘤是脑内最常见的一类肿瘤（占１７％），根据生物学特征分为Ⅰ－Ⅳ级，其ＭＲＩ信号变化各有侧重。作者收集１９８８－１９９３年间经ＭＲＩ诊断及手术病理证实的１０２例星形胶质瘤，对其ＭＲＩ特征及其信号强度变化的病理基础进行探讨。结果显示ＭＲＩ信号变化与肿瘤的良恶性及肿瘤内囊变、出血、坏死等病理改变所占比例密切相关。