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31.
32.
Sarah A. Taylor Jacqueline Benedetti David Schuller Stephen P. Richman Goronwy O. Broun Alexander Hantel 《Investigational new drugs》1993,11(2-3):227-229
Summary Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with piroxantrone 150 mg/m2 intravenously every 21 days. There were no objective responses. The 95% upper confidence bound for response is 15%. Primary toxicity was hematologic. 相似文献
33.
Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real-time measurement in vivo 总被引:6,自引:3,他引:3
Nicholas Dale Alexander V. Gourine Enrique Llaudet David Bulmer Teresa Thomas† K. Michael Spyer 《The Journal of physiology》2002,544(1):149-160
We have measured the release of adenosine and inosine from the dorsal surface of the brainstem and from within the nucleus tractus solitarii (NTS) during the defence response evoked by hypothalamic stimulation in the anaesthetised rat. At the surface of the brainstem, only release of inosine was detected on hypothalamic defence area stimulation. This inosine signal was greatly reduced by addition of the ecto-5'-nucleotidase inhibitor α,β-methylene ADP (200 μM), suggesting that the inosine arose from adenosine that was produced in the extracellular space by the prior release of ATP. By placing a microelectrode biosensor into the NTS under stereotaxic control we have recorded release of adenosine within this nucleus. By contrast to the brainstem surface, a fast increase in adenosine, accompanied only by a much smaller change in inosine levels, was seen following stimulation of the hypothalamic defence area. The release of adenosine following hypothalamic stimulation was mainly confined to a narrow region of the NTS some 500 μm in length around the level of the obex. Interestingly the release of adenosine was depletable: when the defence reaction was evoked at short time intervals, much less adenosine was released on the second stimulus. Our novel techniques have given unprecedented real-time measurement and localisation of adenosine release in vivo and demonstrate that adenosine is released at the right time and in sufficient quantities to contribute to the cardiovascular components of the defence reaction. 相似文献
34.
Georgios K Glantzounis Henryk J Salacinski Wenxuan Yang Brian R Davidson Alexander M Seifalian 《Liver transplantation》2005,11(9):1031-1047
Oxidative stress is an important factor in many pathological conditions such as inflammation, cancer, ageing and organ response to ischemia-reperfusion. Humans have developed a complex antioxidant system to eliminate or attenuate oxidative stress. Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and hemorrhagic shock with subsequent fluid resuscitation, leading to significant morbidity and mortality. It is characterized by significant oxidative stress but accompanied with depletion of endogenous antioxidants. This review has 2 aims: firstly, to highlight the clinical significance of liver ischemia-reperfusion injury, the underlying mechanisms and the main pathways by which the antioxidants function, and secondly, to describe the new developments that are ongoing in antioxidant therapy and to present the experimental and clinical evidence about the role of antioxidants in modulating hepatic ischemia-reperfusion injury. 相似文献
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36.
Andreas G Schatzlein Bernd H Zinselmeyer Adurrahim Elouzi Christine Dufes Ya Tsz A Chim Clive J Roberts Martyn C Davies Avril Munro Alexander I Gray Ijeoma F Uchegbu 《Journal of controlled release》2005,101(1-3):247-258
Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration. 相似文献
37.
Simultaneous angiographic late stent thrombosis in two different coronary vessels after withdrawal of the combined anti-platelet therapy 总被引:2,自引:2,他引:0
38.
Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E2) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis
remain unknown. E2 regulate adipocyte differentiation in subcutaneous and visceral fat through interaction with other nuclear receptors. This
interaction has not been assessed in bone marrow adipocytes in vivo. In this study, we compared two groups of animals, young
and old, after either oophorectomy (OVX) or oophorectomy plus E2 (OVX + E2) replacement. We found that absence of E2 was associated with higher levels of PPARγ and lower levels of Sirt1 most significantly in the old group. In addition, old
mice responded better to E2 replacement in terms of reducing adipogenesis and PPARγ expression as well as increasing levels of Sirt1 expression. Our
findings represent a new understanding of the role of E2 in age-related bone loss, which could be mediated through the regulation of Sirt1 expression within the bone marrow. In addition,
this evidence suggests that old individuals may show a better response to E2 administration in terms of reverting the high levels of marrow fat seen in age-related bone loss. 相似文献
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