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551.
Hawkes M Opoka RO Namasopo S Miller C Conroy AL Serghides L Kim H Thampi N Liles WC John CC Kain KC 《Medical hypotheses》2011,77(3):437-444
We hypothesize that supplemental inhaled nitric oxide (iNO) will improve outcomes in children with severe malaria receiving standard antimalarial therapy. The rationale for the hypothesized efficacy of iNO rests on: (1) biological plausibility, based on known actions of NO in modulating endothelial activation; (2) pre-clinical efficacy data from animal models of experimental cerebral malaria; and (3) a human trial of the NO precursor l-arginine, which improved endothelial function in adults with severe malaria. iNO is an attractive new candidate for the adjunctive treatment of severe malaria, given its proven therapeutic efficacy in animal studies, track record of safety in clinical practice and numerous clinical trials, inexpensive manufacturing costs, and ease of administration in settings with limited healthcare infrastructure. We plan to test this hypothesis in a randomized controlled trial (ClinicalTrials.gov Identifier: NCT01255215). 相似文献
552.
de Claro RA Zhu X Tang J Morgan-Stevenson V Schwartz BR Iwata A Liles WC Raines EW Harlan JM 《The American journal of pathology》2011,178(6):2931-2937
The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr(-/-)). Bone marrow from Fas(-/-) mice was used to reconstitute irradiated Ldlr(-/-) mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr(-/-) mice reconstituted with Fas(-/-) hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas(-/-) bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr(-/-) mice. 相似文献
553.
Background Emergency colectomy is well accepted for treating complicated right-sided colonic diverticulitis. However, the role of colectomy
for uncomplicated diverticulitis is not well defined. The aim of this study was to evaluate the short-term and long-term surgical
outcome of uncomplicated right-sided diverticulitis in our locality.
Patients and Methods Retrospective chart review of patients operated for right-sided diverticulitis over a 20-year period was conducted. Recurrent
attacks of right-sided diverticulitis, re-operation rate and re-hospitalisation rate were the long-term parameters of interest.
An updated telephone interview was carried out for all surviving patients.
Results Seventy-four patients (35 males and 39 females), median age 35.5 (range 16–70) years, were operated for uncomplicated diverticulitis.
Thirty patients underwent colectomy, whereas the others underwent appendectomy with diverticulectomy (n = 8) or appendectomy
alone (n = 36). All short-term parameters were less favourable for the colectomy group, including higher complication rate,
slower return of gastrointestinal function, higher requirement of parenteral analgesic and longer hospital stay. Without colectomy,
only 2 patients developed recurrent diverticulitis necessitating hospitalisation, both of whom resolved on conservative treatment.
On the other hand, 1 patient required re-operation after colectomy because of intestinal obstruction. The overall re-hospitalisation
rate was comparable between the colectomy and the non-colectomy group (16.7% vs. 13.6%).
Conclusions Emergency colectomy can eradicate suspicious lesions and eliminate risk of recurrent diverticulitis but at the expense of
higher morbidity rates. As the natural course of uncomplicated right-sided colonic diverticulitis is usually benign, conservative
treatment with minimal surgery may be a better therapeutic option. 相似文献
554.
Liles JT Dabisch PA Hude KE Pradhan L Varner KJ Porter JR Hicks AR Corll C Baber SR Kadowitz PJ 《The Journal of pharmacology and experimental therapeutics》2006,316(1):95-105
The mechanism of the pressor response to ephedrine is controversial. In the present study. i.v. injections of ephedrine increased systemic and pulmonary arterial pressure, and i.a. injections decreased hindlimb blood flow in a dose-related manner. Responses to ephedrine were inhibited by alpha-receptor blocking agents and were not attenuated by blockade of the norepinephrine reuptake transporter (NET) or by catecholamine depletion using reserpine or a combination of reserpine and alpha-methyl-p-tyrosine, whereas responses to tyramine and amphetamine were inhibited by these treatments. The magnitude of the pressor response to ephedrine was similar in anesthetized and conscious rats. Tachyphylaxis developed to pressor responses to ephedrine and amphetamine with sequential injections; however, ephedrine tachyphylaxis differed in that subsequent responses to alpha-receptor agonists were attenuated. These results suggest that the systemic and pulmonary pressor and hindlimb vasoconstrictor responses to ephedrine are mediated by direct action on alpha-adrenergic receptors and that the release of norepinephrine from adrenergic terminals plays no significant role. These results provide support for the hypothesis that responses to ephedrine are directly mediated in the intact rat, whereas responses to amphetamine are mediated in a large part by the release of norepinephrine from adrenergic terminals. 相似文献
555.
Because of the potential value of evoked potential methods in evaluating striatal organization, a study was made to examine the reliability of evoked potentials in demonstrating the fine topographic details of the corticostriatal projection in comparison with the autoradiographic fiber-tracing method. The present data indicate a close relation between the distribution of striatal evoked potentials to electrical stimulation of a specific site in the motor cortex and the distribution of axon terminals emanating from that same cortical site in the same animal. 相似文献
556.
目的 :探索以新型生物可降解材料聚羟基丁酸酯 羟基戊酸酯共聚物 (PHBV)为载体的地西泮药物中长期缓释微球制备工艺 ;方法 :以溶剂蒸发法制备微球 ,用扫描电镜SEM观察微球表面及内部横断面形态结构 ;结果 :微球的平均粒径为 3 0 .5μm ,平均载药量 (1 8.66± 0 .2 3 ) % ,包封率 (80 .85± 1 .0 1 ) %。体外释放第一天呈突释效应 ,而后药物释放基本符合零级动力学过程 .其释放曲线方程为 Q =2 0 .55 2 .3 99t,r=0 .9569;结论 :开发与研制PHBV为载体的中长期缓释微球具有较好应用前景。 相似文献
557.
558.
Mohammed Asker MSc Jean-Philippe Krieger PhD Amber Liles MSc Ian C. Tinsley PhD Tito Borner PhD Ivana Maric MSc Sarah Doebley BSc C. Daniel Furst MSc Stina Börchers MSc Francesco Longo PhD Yashaswini R. Bhat BS Bart C. De Jonghe PhD Matthew R. Hayes PhD Robert P. Doyle PhD Karolina P. Skibicka PhD 《Diabetes, obesity & metabolism》2023,25(3):856-877