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101.
目的:观察6-羟基多巴胺帕金森病大鼠模型的氧化应激反应及其可能的机制。方法:实验于2005-06/12在上海中医药大学科研实验中心完成。实验分组:Wistar雄性大鼠18只,随机分为正常对照组、假手术组、模型组,每组6只。实验干预:采用6-羟基多巴胺(溶于0.2g/L抗坏血酸的生理盐水中)注射于脑右侧黑质,10d后以腹腔注射阿朴吗啡0.5mg/kg诱发大鼠向一侧旋转,记录开始旋转至30min内的旋转圈数,以平均每分钟旋转圈数超过7次者为合格的帕金森病模型。假手术组6只大鼠只注射含0.2g/L抗坏血酸的等量生理盐水,其余条件与造模组手术相同。正常对照组6只大鼠只进行大鼠固定,不进行任何处理。在旋转诱发实验完成后,动物每天自由饮水与进食,共45d。实验评估:应用化学比色法测定大鼠中脑黑质纹状体部位活性氧、丙二醛、谷胱甘肽含量,谷胱甘肽过氧化物酶、超氧化物歧化酶的活性。结果:18只大鼠均进入结果分析。①活性氧含量:模型组明显高于正常对照组和假手术组[(451.13±73.42),(135.62±53.46),(161.15±61.16)U/mg,P<0.01]。②谷胱甘肽含量:模型组明显低于正常对照组和假手术组[(4.26±0.75),(7.03±1.39),(7.03±1.42)mg/g,P<0.05]。③谷胱甘肽过氧化物酶活性:模型组明显低于正常对照组和假手术组[(3.05±0.38),(3.96±0.39),(3.77±0.38)NU/g,P<0.01]。④超氧化物歧化酶活性:模型组明显低于正常对照组和假手术组[(137.74±4.65),(190.77±8.47),(199.73±8.23)NU/mg,P<0.01]。⑤丙二醛含量:模型组明显高于正常对照组和假手术组[(10.90±2.17),(4.18±2.88),(4.52±2.45)μmol/g,P<0.01]。结论:帕金森病模型大鼠的氧化反应被激活,处于氧化应激状态,氧化应激反应增强可能是帕金森病的发病机制之一。 相似文献
102.
R Castillo ; G Escolar ; J Monteagudo ; J Aznar-Salatti ; JC Reverter ; A Ordinas 《Transfusion》1997,37(8):785-790
BACKGROUND: A defective hemostatic effect of plasma concentrate infusion in patients with severe von Willebrand disease (vWD) has been ascribed to the absence of platelet von Willebrand factor (vWF) STUDY DESIGN AND METHODS: The role of platelet vWF in hemostasis of severe vWD was investigated. A plateletpheresis unit (4-5 × 10(11) platelets) from a normal compatible donor was transfused before any cryoprecipitate infusion to three type 3 vWD patients and to one patient with severe type 1 vWD with low levels of platelet vWF who required replacement therapy for bleeding episodes. Autologous platelets were transfused to one of the patients with type 3 vWD. RESULTS: Partial corrections of bleeding times (14-17 min vs. baseline>30 min) were observed in all patients after the transfusion of normal platelets. During cryoprecipitate infusion, bleeding times were normalized (<6 min), and bleeding episodes stopped when plasma levels of vWF activity ranged from 14 to 18 U per dL. Platelet interactions with the subendothelium increased in parallel with the correction of bleeding times. These results indicate that if approximately 20 percent of the total number of platelets have normal vWF antigen and if plasma vWF levels are at least 14 U per dL, then bleeding times will normalize and mucosal hemorrhages will stop. Transfusion of autologous platelets in one patient with type 3 vWD did not modify bleeding times or platelet adhesion on the subendothelium. CONCLUSION: The hemostatic effect of normal platelets in type 3 vWD seems to be related to the platelet vWF in the transfused platelets. 相似文献
103.
个性化颅骨成形术中植入材料类型与颅骨缺损面积的关系 总被引:2,自引:0,他引:2
目的:分析个性化颅骨成形术中,植入材料类型与颅骨缺损面积的关系。
方法:选择解放军总医院第二附属医院神经外科2002-03/2005-01和河北省三河市医院神经外科2003-09/2005-04收治的资料齐全的计算机辅助设计颅骨成形术患者75例,分为嵌入性材料(骨水泥、硅橡胶)组40例,根据颅骨缺损面积又分为大面积(≥36cm2)组17例和小面积(〈36cm2)组23例;覆盖性材料(钛网)组35例,大面积组14例和小面积组21例。采用头颅CT超薄扫描(层厚1.5mm),三维重建,模拟缺损颅骨补片,应用激光快速成形技术,制作缺损颅骨及颅骨补片模型,患者认可后,根据患者的病情应用硅橡胶、骨水泥、钛网作为植入材料,进行手术植入。术后1周观察并发症:头痛、积液、松动。
结果:75例患者的补片与颅骨完整适配,塑形满意,术中无需修整,平均手术时间45min,83%(63/75)患者感到基本或完全恢复了原有容貌。手术并发症:嵌入性材料组头痛4例,积液10例,松动2例,共16例,其中大面积组13例,小面积组3例;覆盖性材料组头痛1例,积液2例,松动0例,共3例次,其中大面积组2例,小面积组1例。应用精确概率分析,两材料组之间手术并发症差异显著,两材料组颅骨缺损面积之间手术并发症差异显著,嵌入性材料大面积组与覆盖性材料大面积组之间手术并发症差异显著,嵌入性材料小面积组与覆盖性材料小面积组之间手术并发症无显著性差异。
结论:个性化设计的颅骨修补材料,能够最大限度的恢复患者外形,缩短手术时间,大面积的颅骨缺损应用钛网修补,小面积的应用钛网和嵌入性材料修补。根据患者颅骨缺损面积,选择不同植入材料,可以提高手术疗效,减少术后并发症。 相似文献
104.
S Resino D Micheloud P Miralles JM Bellón A Vargas P Catalán E Álvarez J Cosín R Lorente JC López MA Muñoz-Fernández J Berenguer 《HIV medicine》2010,11(1):64-73
Background
Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F≥3) in HIV/hepatitis C virus (HCV)‐coinfected patients.Methods
We carried out a cross‐sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM‐3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase‐1 and hyaluronic acid.Results
In the EG, the area under the receiver operating characteristic curve (AUC‐ROC) of HGM‐3 for identification of F≥3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC‐ROC of the HGM‐2, FIB‐4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM‐3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM‐3 >0.570 in the EG for F≥3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F≥3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG.Conclusions
HGM‐3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV‐coinfected patients. 相似文献105.
Vita W Jongen Thijs Reyniers Zorah MH Ypma Maarten F Schim van der Loeff Udi Davidovich Hanne ML Zimmermann Liza Coyer Mark AM van den Elshout Henry JC de Vries Kristien Wouters Tom Smekens Bea Vuylsteke Maria Prins Marie Laga Elske Hoornenborg 《Journal of the International AIDS Society》2021,24(8)
IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered. 相似文献
106.
JC McGrath 《British journal of pharmacology》2009,157(4):491-493
In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new therapeutic targets. The themed section includes three reviews on the pathophysiology of the endothelium and the drug targets that this presents, four research papers and three commentaries on research.This themed section also forms the nucleus of an online Virtual Issue that collects in one place further reviews and research papers on the topic of the ‘Endothelium’ that BJP and our sister journal BJCP have published in the past year, and that should help researchers and students to find the latest work in this field.To view the entire Endothelium Themed Section and the Endothelium Virtual Issue, please visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009British Journal of Pharmacology (2009) 157, 491–493; doi:10.1111/j.1476-5381.2009.00366.xThis article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009Thirty years ago Robert F Furchgott found that a substance was released from vascular endothelium that caused relaxation of the smooth muscle in the vascular wall (Furchgott and Zawadzki, 1980), a discovery for which, a decade ago, he was awarded the Nobel Prize (Furchgott, 1999). This remarkable finding was, from my recollection anyway, the most exciting aspect of the second Symposium on Mechanisms of Vasodilatation, held at Wilrijk, Belgium in July 1980 (Vanhoutte and Leusen, 1981) and has been, one suspects, a major part of the reason that this series is now celebrating its 10th occurrence at Matsushima, Miyagi, Japan, in June 2009 (it is planned to publish work arising from this event in Circulation Journal).Thirty years on, the endothelium continues to yield information on pathophysiological mechanisms that provides many therapeutic targets for drug discovery and new explanations for drug action. A special Endothelium Themed Section in this issue of BJP collates three new reviews on the pathophysiology of the endothelium and the drug targets that this presents (Esposito and Cuzzocrea, 2009; Grgic et al., 2009; Versari et al., 2009), four research papers (de Andrade et al., 2009; Andrews et al., 2009; McKenzie et al., 2009; Orie et al., 2009) and three commentaries on research papers that discuss the significance and draw out controversies from their new findings (Martin, 2009, commenting on Andrews et al., 2009; Tammaro, 2009, commenting on Orie et al., 2009; Miller and Wadsworth, 2009, commenting on Wenzl et al., 2009 that was published in an earlier issue).These Endothelium reviews and two others already published (Félétou, 2009; Félétou et al., 2009) follow up symposia held at the Meeting of the Federation of European Pharmacological Societies (EPHAR) in Manchester, UK, in July 2008, and show the continuing importance of this field. To reflect this and provide access to our extensive portfolio of endothelial papers, we have collated this section with other recent reviews, commentaries and original articles from BJP and from our sister journal BJCP, in a Virtual Issue on Endothelium, available at: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 (see http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009)
Open in a separate windowThemed Section: Endothelium in PharmacologyEndothelium in pharmacology: 30 years on: J. C. McGrathRole of nitroso radicals as drug targets in circulatory shock: E. Esposito & S. CuzzocreaEndothelial Ca2+-activated K+ channels in normal and impaired EDHF–dilator responses – relevance to cardiovascular pathologies and drug discovery: I. Grgic, B. P. Kaistha, J. Hoyer & R. KöhlerEndothelium-dependent contractions and endothelial dysfunction in human hypertension: D. Versari, E. Daghini, A. Virdis, L. Ghiadoni & S. TaddeiNitroxyl anion – the universal signalling partner of endogenously produced nitric oxide?: W. MartinA role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries: K. L. Andrews, J. C. Irvine, M. Tare, J. Apostolopoulos, J. L. Favaloro, C. R. Triggle & B. K. Kemp-HarperVascular KATP channels: dephosphorylation and deactivation: P. TammaroCa2+/calcineurin regulation of cloned vascular KATP channels: crosstalk with the protein kinase A pathway: N. N. Orie, A. M. Thomas, B. A. Perrino, A. Tinker & L. H. ClappUnderstanding organic nitrates – a vein hope?: M. R. Miller & R. M. WadsworthIncreased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia: C. R. de Andrade, P. F. Leite, A. C. Montezano, D. A. Casolari, A. Yogi, R. C. Tostes, R. Haddad, M. N. Eberlin, F. R. M. Laurindo, H. P. de Souza, F. M. A. Corrêa & A. M. de OliveiraMechanisms of U46619-induced contraction of rat pulmonary arteries in the presence and absence of the endothelium: C. McKenzie, A. MacDonald & A. M. ShawThis issue is available online at http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 相似文献
107.
Background and purpose:
Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro- and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin-resistant JCR : LA-cp rat that exhibits micro- and macrovascular disease with ischaemic myocardial lesions and renal disease.Experimental approach:
Obese male rats were treated with irbesartan (30 mg·kg−1·day−1, incorporated into chow) from 12 to 25 weeks of age.Key results:
Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA-cp rats was marginally improved, at the expense of increased plasma insulin levels (∼50%). Fasting plasma triglycerides were marginally reduced (∼25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium-dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%).Conclusions and implications:
Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end-stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease. 相似文献108.
Introduction
Major blood loss can often be life-threatening and is most commonly encountered in the settings of surgery and trauma. Patients receiving anticoagulant therapy are also at increased risk of bleeding. We investigated the use of a prothrombin complex concentrate (PCC; Beriplex P/N, CSL Behring, Marburg, Germany) to treat severe bleeding in a variety of settings: cardiac surgery, warfarin therapy and other surgery.Methods
Thirty consecutive patients who had received PCC were identified from blood transfusion records. For cardiac surgery and warfarin reversal, PCC was administered in accordance with hospital protocols. PCC was administered to cardiac and other surgical patients responding poorly to recognized blood products, whereas it was administered first-line to patients with life-threatening bleeds and requiring warfarin reversal, in accordance with British Committee for Standards in Haematology guidelines. We conducted a retrospective analysis of patient records in order to ascertain PCC dose, use of other blood products and response to PCC (clotting screen results before and after PCC administration, haemostasis achievement, and survival).Results
Six patients (20%) were excluded because of inadequate documentation (n = 5) or acquired haemophilia (n = 1). Therefore, 24 patients were included in the analysis: coronary artery bypass graft (n = 5), mitral/aortic valve replacement (n = 2), other surgery (n = 9) and warfarin reversal (n = 8). Most patients (83.3%) received no more than 1500 IU of Beriplex P/N 500. Considerable reduction in administration of other blood products was seen during the 24 hours after PCC administration. Partial or complete haemostasis was achieved in 14 out of 18 cases (77.8%). In total, 12 out of 24 patients (50%) died during the study; two-thirds of the deaths were considered unrelated to bleeding. No thrombotic complications or adverse drug reactions were observed.Conclusion
This study emphasizes the value of PCC in reversing the effects of oral anticoagulant therapy in bleeding patients. It also demonstrates the potential value of PCC in controlling bleeding in patients undergoing cardiac and other surgical procedures. The use of PCC in bleeding patients without hereditary or anticoagulation-related coagulopathy is novel, and further investigation is warranted. In the future, it may be possible to use PCC as a substitute for fresh frozen plasma in this setting; adequate documentation is crucial for all blood products. 相似文献109.
Richter GM; Noeldge G; Palmaz JC; Roessle M; Slegerstetter V; Franke M; Gerok W; Wenz W; Farthman E 《Radiology》1990,174(3):1027
110.