Mechanisms of angiogenesis in gliomas

Gliomas are the most frequent primary tumors of the central nervous system in adults. Glioblastoma muhiforme, the most aggressive form of astrocytic tumors, displays a rapid progression that is accompanied by particular poor prognosis of patients. Intense angiogenesis is a distinguishing pathologic characteristic of these tumors and in fact, glioblastomas are of the most highly vascularized malignant tumors. For this reason, research and therapy strategies have focused on derstanding the mechanisms leading to the origin of tumor angiogenic blood vessels in order to develop new approaches that effectively block angiogenesis and cause tumor regression.     

去氢甲基睾丸素的合成工艺研究

目的 :研究蛋白同化激素去氢甲基睾丸素的合成工艺。方法 :以去氢表雄酮醋酸酯为原料 ,经格氏反应 ,水解 ,沃氏氧化 ,DDQ脱氢等四步反应制得。结果 :该合成路线不仅收率高 ,产品纯 ,而且无需过柱分离。结论 :该工艺路线适合工业化生产。     

The impact of heart health promotion on coronary heart disease lifestyle risk factors in schoolchildren: lessons learnt from a community-based project

A community health promotion project called Action Heart was undertaken in two electoral wards in Rotherham to try to change lifestyles of people. Schools were included within the project.Coronary heart disease lifestyle risk factors were measured at baseline and after a three year period in the intervention area and a similar control area. Lifestyle factors in schoolchildren were measured separately from adults using a different instrument.The post intervention survey of adults and economic evaluation demonstrated that Action Heart had achieved cost-effective estimated health gains. In the schoolchildren however, a mixture of positive and negative risk factor changes in both areas was demonstrated. Significant changes in lifestyle risk factors in schoolchildren were not elicited using this approach.The possible reasons for the lack of impact on lifestyle risk factors in schoolchildren are examined and the implications for further work explored.     

COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer

Extensive documentation has validated the role of UV irradiation as a tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase). One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to UVB irradiation results in increased production of prostaglandin E2 (PGE2). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were irradiated on sun- protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy. RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at approximately 12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.      

交流示波极谱滴定法测定盐酸环丙沙星及其制剂的含量

目的：采用交流示波极谱滴定法测定了盐酸环丙沙星及其制剂的含量。方法：在ｐＨ５．０－５．５的醋酸－醋酸钠缓冲液溶液中，环丙沙星与四苯硼钠定量反应形成１：１沉淀。过量的四苯硼钠用醋酸亚铊标准溶液回滴至示波极谱图上四苯硼钠切口消失。结果：该法平均回收率为９９．１８％，ＲＳＤ为０．４９％。结论：本法简便，快速，结果准确，可靠。     

马陆的抗炎药理研究初报

目的：实验研究开发具有抗炎效果好，来源丰富的动物药资源。方法：以马陆为研究对象，采用耳肿胀法、足跖肿胀法及测定其炎性渗出物含量等方法。结果：各项指标表明，马陆对实验动物的抗炎作用达到显著或极显著的效果。结论：马陆资源丰富，又有较强的抗炎作用，因此具有进一步研究开发的价值。     

Activation of iGluR5 kainate receptors inhibits neurogenic dural vasodilatation in an animal model of trigeminovascular activation

Background and purpose:

Migraine is a disabling neurological disorder involving activation, or the perception of activation, of trigeminovascular afferents containing calcitonin gene-related peptide (CGRP). Released CGRP from peripheral trigeminal afferents causes dilatation of dural blood vessel, and this is used to measure trigeminal nerve activation. Kainate receptors with the GluR5 subunit (iGluR5, ionotropic glutamate receptor) are present in the trigeminal ganglion and may be involved in nociception. We investigated the possible involvement of prejunctional iGluR5 kainate receptors on CGRP release from trigeminal afferents.

Experimental approach:

We used neurogenic dural vasodilatation, which involves reproducible vasodilatation in response to CGRP release after electrical stimulation of the dura mater surrounding the middle meningeal artery. The effects of the specific iGluR5 receptor antagonist UBP 302 and agonist (S)-(-)-5-iodowillardiine were investigated on neurogenic and CGRP-induced dural vasodilatation in rats, by using intravital microscopy.

Key results:

Administration of 10 and 20 mg·kg⁻¹ of iodowillardiine inhibited electrically induced dural vessel dilatation, an effect blocked by pretreatment with 50 mg·kg⁻¹ UBP 302. Administration of the iGluR5 receptor antagonist UBP 302 alone had no significant effect. CGRP (1 mg·kg⁻¹)-induced dural vasodilatation was not inhibited by the iGluR5 receptor agonist iodowillardiine.

Conclusions and implications:

This study demonstrates that activation of the iGluR5 kainate receptors with the selective agonist iodowillardiine is able to inhibit neurogenic dural vasodilatation probably by inhibition of prejunctional release of CGRP from trigeminal afferents. Taken together with recent clinical studies the data reinforce CGRP mechanisms in primary headaches and demonstrate a novel role for kainate receptor modulation of trigeminovascular activation.     

Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

Background and purpose

Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice.

Experimental approach

Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10–400 mg kg⁻¹). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests.

Key results

Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A₁ adenosine-receptor antagonist, DPCPX, but not the selective A_2A adenosine-receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg⁻¹. Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid.

Conclusions and implications

Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans.