Platelet-derived endothelial cell growth factor was previously identified as the sole angiogenic activity present in platelets; it is now known to be thymidine phosphorylase (TP). Intense interest has recently centered on the angiogenic process, largely as a result of the realization that disregulated blood vessel growth plays a critical role in several disease states, including (inter alia) cancer (tumor angiogenesis), diabetic retinopathy, psoriasis, rheumatoid arthritis, and hyperproliferation of the vasa vasorum in atherosclerosis (1). Platelet-derived endothelial cell growth factor was described as a mitogenic and angiogenic factor present in platelets (2).Platelet-derived endothelial cell growth factor is now known to be thymidine phosphorylase (TP) (3) and the effects of TP on cellular uptake of [methyl-3H]thymidine when it is added exogenously to cells arise from its effect on the availability of thymidine in the extracellular culture medium (4-6). Several years prior to the isolation of the so-called plateletderived endothelial growth factor and demonstration of its angiogenic activity, TP had been identified as an enzyme whose level was significantly elevated in the plasma of cancer patients relative to that in healthy volunteers (7) and in the plasma of xenografted mice relative to that of controls (8) and expressed at a high level in tumors (9, 10). We have found (11) that expression of TP shows a strong correlation with ovarian malignancy and ovarian tumor blood flow.We report here that TP is angiogenic in the rat sponge model (12) and in a freeze-injured skin graft model (13). Expression of TP strongly correlated with malignancy in breast tumors, and while expression of TP had no effect on breast carcinoma cell growth in vitro, it greatly enhanced tumor growth in vivo. MATERIALS AND METHODSCell Isolation and Culture. Bovine aortic endothelial cells were isolated as described (14) and maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% (vol/vol) fetal calf serum. Low-passage MCF-7 cells (passage 53) were a gift from Marc Lippman (Georgetown University, Washington, DC).Antibodies to TP. Rabbit anti-TP antisera and mouse anti-TP monoclonal antibodies were raised against recombinant TP expressed in Escherichia coli (4).Site-Directed Mutagenesis and Protein Expression. Three site-directed mutants of TP were constructed by a two-step PCR (15). Recombinant proteins were expressed in E. coli using the expression vector pET-14b (ams Biotechnology, Witney, U.K.) and purified by metal chelate affinity chromatography. By gel filtration, recombinant TP was dimeric with a molecular mass of 100 kDa. Concentrations of pure TP were calculated by using a molecular mass of 100 kDa.Rat Sponge Angiogenesis Assay. Sterile circular polyether sponge discs with central cannula were implanted subcutaneously in male Wistar rats (180-200 g) after induction of neuroleptanalgesia by Hypnorm (12). Four sponges were used in each experimental group. Protein in 50 ,ul of PBS was injected daily into...

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Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China. Due to its worldwide use, potential impact on healthcare and opportunities for new drug development, TCM is also of great international interest. Recently, a new era for modernisation of TCM was launched with the successful completion of the Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (GP-TCM) project, the European Union’s Seventh Framework Programme (FP7) coordination action on TCM research. This 3.5-year project that involved inputs from over 200 scientists resulted in the production of 20 editorials and in-depth reviews on different aspects of TCM that were published in a special issue of Journal of Ethnopharmacology (2012; volume 140, issue 3). In this narrative review, we aim to summarise the findings of the FP7 GP-TCM project and highlight the relevance of TCM to modern medicine within a historical and international context. Advances in TCM research since the 1950s can be characterised into three phases: Phase I (1950s-1970s) was fundamental for developing TCM higher education, research and hospital networks in China; Phase II (1980s-2000s) was critical for developing legal, economic and scientific foundations and international networks for TCM; and Phase III (2011 onwards) is concentrating on consolidating the scientific basis and clinical practice of TCM through interdisciplinary, interregional and intersectoral collaborations. Taking into account the quality and safety requirements newly imposed by a globalised market, we especially highlight the scientific evidence behind TCM, update the most important milestones and pitfalls, and propose integrity, integration and innovation as key principles for further modernisation of TCM. These principles will serve as foundations for further research and development of TCM, and for its future integration into tomorrow’s medicine.

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In this study, women with dysmenorrhea of at least 6 months' duration were recruited to a randomized, double-blind, controlled trial, which compared the effectiveness of conservative surgical treatment with treatment with presacral neurectomy. One hundred twenty-six women with a diagnosis of dysmenorrhea caused by endometriosis who had been unresponsive to medical treatment formed the study subjects. A preoperative evaluation established a baseline for frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain. Similar measurements were made at 6 and 12 months. Pain severity was rated using a 100-point visual analog scale with 100 being the most severe pain. Patients were randomized to 1 of 2 treatment groups. Group A (n ϭ 63) received electrocautery ablation or excision of visible pelvic endometriotic lesions, enucleation of endometriomas, and lysis of pelvic adhesions. Group B (n ϭ 63) underwent presacral neurectomy after conservative treatment. Presacral neurectomy was performed after retraction of the sigmoid colon and vasopressin infiltration of the sacral promontory area. The presacral area was exposed and underlying tissue layers cauterized. At the periosteum, a semilunar piece of retroperitoneal tissue was dissected. Neurectomy was confirmed with pathologic examination of this tissue for evidence of nerve fiber presence. The 2 treatment groups were similar in demographic and clinical data. All laparoscopies were successfully completed with no surgical complications in either group. The length of surgery was significantly greater for those in group B (mean 123 minutes vs. 110 minutes; P Յ.05), but otherwise all operative parameters were similar. Short-term complications were minimal in both groups. No patient in group A had long-term complications. In group B, 21 and 9 women, at the 6-and 12-month visits, respectively, reported constipation. Medical therapy was successful in 15 of the 21 women at 6 months. Three patients reported urinary urgency at both the 6-and 12-month follow up. At the 6-month and 12-month visits, 83.2% and 85.6%, respectively, of the patients in group B reported either no dysmenorrhea or only light discomfort and were considered cured. In comparison, 60.3% and 57% of the women in group A were cured at 6 and 12 months, respectively (P Յ.05 for both). At each stage of endometriosis, and in women with deep rectovaginal septum endometriosis, the cure rate in group B was significantly higher compared with those in group A. Women in group A who had deep rectovaginal septum endometriosis were less likely to be cured compared with all stages of endometriosis in the same group. The severity of dysmenorrhea and dyspareunia was significantly improved at the 6-and 12-month visit in group B compared with group A, but the frequency of symptoms was similar in both groups after treatment. ABSTRACTTwo hundred nulliparous women were enrolled in a prospective observational study to investigate the influence of childbirth on pelvic organ mobility. The mobility of the urethra, bladder, c...