Endovascular Treatment of Internal Iliac Artery Stenosis in Patients with Buttock Claudication

Aim

To assess the technical feasibility and clinical outcome of percutaneous transluminal angioplasty (PTA) with and without stent placement for treatment of buttock claudication caused by internal iliac artery (IIA) stenosis.

Methods

Between September 2001 and July 2011, thirty-four patients with buttock claudication underwent endovascular treatment. After angiographic lesion evaluation PTA with or without stent placement was performed. Technical success was recorded. Clinical outcome post-treatment was assessed at three months post-intervention and was classified as: 1) complete relief of symptoms, 2) partial relief, or 3) no relief of symptoms. Complications during follow-up were recorded.

Results

Forty-four lesions in 34 symptomatic patients were treated with PTA. Eight lesions were treated with additional stent placement. Technical success was achieved in 40/44 lesions (91%). Three procedure-related minor complications occurred, i.e. asymptomatic conservatively treated intimal dissections. After a median of 2.9 months, patients experienced no relief of symptoms in 7/34 cases (21%), partial relief in 14/34 cases (41%), and complete relief in 13/34 cases (38%). Six patients required a reintervention during follow-up.

Conclusion

Endovascular treatment of IIA stenosis has a high technical success rate and a low complication rate. Complete or partial relief of symptoms is achieved in the majority (79%) of patients.     

血管内支架介入成形术对老年缺血性脑血管病患者的神经功能、动脉血流速度及预后的影响

摘要 目的：探讨血管内支架介入成形术对老年缺血性脑血管病（ICVD）患者的神经功能、动脉血流速度及预后的影响。方法：选取2018年3月~2019年4月期间我院收治的117例老年ICVD患者作为研究对象,根据随机数字表法分为对照组（n=58）和研究组（n=59）,其中对照组患者予以保守药物治疗,研究组患者予以血管内支架介入成形术治疗,比较两组患者疗效、神经功能、动脉血流速度、预后及并发症情况。结果：研究组治疗6个月后的临床总有效率为91.53%（54/59）,高于对照组的72.41%（42/58）（P<0.05）。两组患者治疗后1个月、治疗后3个月、治疗后6个月美国国立卫生研究院卒中量表（NIHSS）评分均下降（P<0.05）,且研究组低于对照组（P<0.05）。两组患者治疗后6个月大脑中动脉、基底动脉、颈内动脉血流速度均升高（P<0.05）,且研究组高于对照组（P<0.05）。两组患者治疗后1个月、治疗后3个月、治疗后6个月改良Rankin量表（mRS）评分呈下降趋势（P<0.05）,且研究组低于对照组（P<0.05）。两组患者并发症发生率对比未见统计学差异（χ²=2.261,P=0.133）。结论：老年ICVD患者经血管内支架介入成形术治疗后的疗效显著,可有效改善患者神经功能、动脉血流速度及预后,且不增加并发症发生率,具有较高的临床应用价值。     

Characterization of the Inhibition of Vein Graft Intimal Hyperplasia by a Biodegradable Vascular Stent

Characterization of biodegradable stent vein graft thickening. Polydioxanone vascular sutures (PDSs) were used in a biodegradable arteriovenous bypass model. Twenty-four rabbits underwent carotid interposition bypass via ipsilateral jugular vein. One half received the stent (PDS group) and the remaining half a simple vein graft (controls). Group subsets received external stent removal or sham-control exploration at 4 and 12 weeks. At 4 and 12 weeks, the PDS group had significantly less medial and intimal thickening than the control group (P < 0.05), and there were fewer proliferating smooth muscle cells and extra cellular matrix formation than the control group at every interval. At 12 weeks, partial stent degradation occurred without deleterious effects. Furthermore proliferating cell nuclear antigen (PCNA), angiotensin type 1 receptor (AT1R), and transforming growth factor beta 1 (TGF-β1) levels were significantly lower than the control group. The external stent inhibited medial and intimal hyperplasia, an effect that remains after the material has completely degraded. This PDS stent is feasible option for vein grafts.     

阔筋膜与涤纶布修补术对胸壁肿瘤切除后胸壁缺损的临床疗效

目的:探讨阔筋膜修补术与涤纶布修补术对胸壁肿瘤切除后胸壁缺损的临床疗效观察。方法:选取我院胸外科收治的早期胸壁肿瘤患者81例,随机分为阔筋膜组40例行阔筋膜修补术,涤纶布组41例行涤纶布修补术。比较两组患者术后镇痛药用量、肺部体征、引流量、CRP、白细胞及临床康复情况。结果:治疗后与阔筋膜组比较,涤纶布组患者术后镇痛药量、呼吸受限时间及胸膜粘连发生率均较低,(P0.05)。与治疗前比较,两组患者白细胞水平均升高(P0.05),C反应蛋白水平均降低,(P0.05)。与阔筋膜组相比较,涤纶组白细胞水平,C反应蛋白水平均较低(P0.05),涤纶布组治疗后SPO2水平恢复正常的天数缩短(P0.05)。与阔筋膜组比较,涤纶布组患者术后发热天数,引流天数及住院天数均较少,(P0.05)。结论:涤纶布修补术较传统阔筋膜修补术临床疗效优越,且患者痛苦小,术后恢复快,对临床具有指导意义。     

自体髂骨移植用于后路椎弓根钉棒系统矫形内固定术治疗脊柱侧凸的临床效果及对预后的影响

目的:探讨自体髂骨移植用于后路椎弓根钉棒系统矫形内固定术治疗脊柱侧凸的临床效果及对患者预后的影响。方法:选取2014年4月至2017年4月90例在我院及山西医科大学进行手术治疗的退行性脊柱侧凸患者作为研究对象,按照随机法将患者分为两组,各组45例患者。对照组采用后路椎弓根钉棒系统矫形内固定术,观察组采用后路椎弓根钉棒系统矫形内固定结合自体髂骨移植术。比较两组患者围手术期情况,术前、术后7天及术后12个月腰椎后凸角度、Cobb角、JOA评分、ODI评分的变化及术后并发症发生情况。结果:两组患者手术时间、术中出血量、体温恢复时间、WBC恢复正常时间、引流管置管时间比较差异无统计学意义(P0.05)。两组患者术后腰椎前凸角度、Cobb角较手术前明显改善(P0.05);术后12个月,观察组患者腰椎前凸角度高于对照组,Cobb角显著低于对照组(P0.05)。两组患者术后JOA评分高于手术前,ODI评分低于手术前(P0.05);观察组患者术后12个月JOA评分高于对照组,ODI评分低于对照组(P0.05)。观察组患者并发症发生率显著低于对照组(P0.05)。结论:自体髂骨移植应用于后路椎弓根钉棒系统矫形内固定术治疗退行性脊柱侧弯效果较好,不仅可纠正脊柱侧弯,同时可减轻患者疼痛感及不适感,安全性较高。     

Neuropsychological Sequelae of Carotid Angioplasty with Stent Placement: Correlation with Ischemic Lesions in Diffusion Weighted Imaging

Background and Purpose

Few studies investigated the neuropsychological outcome after carotid angioplasty with stent placement (CAS), yielding partially inconsistent results. The present investigation evaluated the effect of CAS in patients with high-grade stenosis and assessed the predictive value of ischemic lesion number for postinterventional cognitive deterioration.

Methods

22 patients were tested neuropsychologically before and six weeks after CAS. Cerebral ischemic changes were assessed with diffusion weighted imaging (DWI) prior to and after angioplasty.

Results

Pre- to postinterventional cognitive performance improved significantly in terms of verbal memory (t = −2.30; p<0.05), whereas significant deterioration was noted regarding verbal memory span (t = 2.31; p<0.05). 8 (36%) persons conformed to the criteria of cognitive improvement. 6 patients (27%) were postinterventionally classified as having deficits. Analysis yielded no statistically significant correlations between lesion quantity and cognitive change.

Conclusion

Both improvement and deterioration of cognitive functioning was observed in our collective of patients, leaving the neuropsychological outcome after percutaneous transluminal angioplasty unpredictable in individual cases. The presence of acute ischemic lesions on DWI was found to be not tightly associated with cognitive dysfunction after CAS.     

Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

Background

The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect.

Methods

In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model.

Results

Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation.

Conclusion

This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields.     

冠心病三支病变置入Firebird2术后3年的随访研究

目的:通过对冠心病三支病变患者置入Firebird 2支架术后3年的随访,探讨Firebird 2支架的性能。方法:收集2009年1月~2012年12月在解放军总医院住院行冠脉造影确诊为冠心病且首次置入Firebird 2支架患者的临床资料,按术后随访时间不同分为术后3年组(70例)与术后1年组(69例),比较两组的临床资料及术后MACE的结果。结果:术后3年组再发心绞痛的比例显著高于术后1年组(33.8 vs 18.2)%,差异有统计学意义(P0.05)。而两组间性别、年龄、体重指数、SYNTAX积分、LVEF、优势血管(右)、既往史、诊断、NYHA心功能分级,MACE、再次血运重建、总死亡、非致死性心肌梗死及造影复查比例,支架总数及前降支、回旋支和右冠置入支架数比较均无统计学差异(P0.05)。结论:冠心病三支病变置入Firebird 2术后3年主要心血管不良事件的发生情况与术后1年相当,但还需大规模、多中心继续随访研究。     

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke

Background

Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever.

Methods

We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months.

Results

Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months.

Conclusion

Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.     

覆膜支架腔内修复术与药物保守治疗对Stanford B型主动脉夹层动脉瘤患者肝肾功能、炎性因子以及预后的影响

目的:比较覆膜支架腔内修复术与药物保守治疗对Standford B型主动脉夹层动脉瘤的疗效及对患者肝肾功能、炎性因子及预后的影响。方法:选择2012年1月～2014年8月我院收治的Standford B型主动脉夹层动脉瘤患者68例,按照随机数字表法分为对照组与研究组,各34例。对照组入院后采取药物保守治疗,研究组应用覆膜支架腔内修复术治疗。观察两组住院期间死亡率、再次手术或介入率以及治疗前、治疗2周后肝肾功能、血清炎性因子变化。所有患者随访36个月,比较两组患者预后情况。结果:研究组再次手术或介入率为2.94%,低于对照组的22.58%(P0.05)。治疗2周后,研究组丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Cr)、胱抑素C、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、γ-干扰素(INF-γ)、C反应蛋白(CRP)水平较治疗前降低(P0.05),且研究组低于对照组(P0.05)。两组患者均随访36个月,随访12个月时两组患者生存率分别为100.00%和80.65%,随访36个月时两组患者生存率分别为91.18%和29.03%,经Log Rank分析显示,两组生存率比较差异有统计学意义(P0.05)。结论:覆膜支架腔内修复术治疗Standford B型主动脉夹层动脉瘤的疗效确切,能够改善患者肝肾功能,降低炎症反应,患者近中期随访生存率较高,其效果优于保守治疗。     

Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

Objective

Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs.

Methods

In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41⁺, endothelium-derived MPs (EMPs) as CD144⁺, CD62E⁺ and CD31⁺/CD41^-, leukocyte-derived MPs as CD45⁺, and erythrocyte-derived MPs as CD235⁺.

Results

In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41⁺: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144⁺: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E⁺: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P<0.05), but not different between RCAs and SVG-RCAs.

Conclusion

Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs.

Trial Registration

ClinicalTrials.gov NCT01430884     

导管接触性溶栓同期球囊扩张+支架治疗血栓性髂静脉压迫综合征的疗效

摘要 目的：为提高治疗效率,本研究对髂静脉压迫综合征合并下肢深静脉血栓患者的导管接触溶栓同期球囊扩张+支架治疗方案和分期治疗方案进行比较。方法：以65例髂静脉压迫综合征合并下肢深静脉血栓患者为研究对象,根据治疗方法分为研究组和对照组,研究组32例,进行导管接触溶栓同期球囊扩张+支架治疗,对照组33例,进行导管接触溶栓分期球囊扩张+支架治疗。以治疗前后患者大腿围、小腿围、血管通畅评分,手术指标（住院时间、住院次数、溶栓时间及穿刺次数）,并发症（血栓复发、出血以及肺栓塞）及深静脉血栓后遗症为指标,考察两组疗效。结果：两组患者大腿围、小腿围和静脉畅通评分在治疗前均无显著差异（P＞0.05）,经过治疗,两组大腿围、小腿围和静脉畅通评分均显著改善（P＜0.05）,但两组间各项指标无显著差异（P＞0.05）。研究组患者住院时间、住院次数、溶栓时间及穿刺次数均显著低于对照组（P＜0.05）。研究组血栓复发0例,对照组血栓复发4例,有显著差异（P＜0.05）;研究组出血1例,肺栓塞0例,对照组出血2例,肺栓塞0例,两组出血和肺栓塞情况比较,无显著差异（P＞0.05）。研究组PTS发生率为6.25 %,显著低于对照组的18.18 %（P＜0.05）。结论：导管接触溶栓同期球囊扩张+支架治疗方案对髂静脉压迫综合征合并下肢深静脉血栓有良好的疗效。     

The Recombination Protein RAD52 Cooperates with the Excision Repair Protein OGG1 for the Repair of Oxidative Lesions in Mammalian Cells

Oxidized bases are common types of DNA modifications. Their accumulation in the genome is linked to aging and degenerative diseases. These modifications are commonly repaired by the base excision repair (BER) pathway. Oxoguanine DNA glycosylase (OGG1) initiates BER of oxidized purine bases. A small number of protein interactions have been identified for OGG1, while very few appear to have functional consequences. We report here that OGG1 interacts with the recombination protein RAD52 in vitro and in vivo. This interaction has reciprocal functional consequences as OGG1 inhibits RAD52 catalytic activities and RAD52 stimulates OGG1 incision activity, likely increasing its turnover rate. RAD52 colocalizes with OGG1 after oxidative stress to cultured cells, but not after the direct induction of double-strand breaks by ionizing radiation. Human cells depleted of RAD52 via small interfering RNA knockdown, and mouse cells lacking the protein via gene knockout showed increased sensitivity to oxidative stress. Moreover, cells depleted of RAD52 show higher accumulation of oxidized bases in their genome than cells with normal levels of RAD52. Our results indicate that RAD52 cooperates with OGG1 to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. Our observations suggest a coordinated action between these proteins that may be relevant when oxidative lesions positioned close to strand breaks impose a hindrance to RAD52 catalytic activities.Oxidative DNA damage is generated at high levels in mammalian cells, even in cells not exposed to exogenous sources of reactive oxygen species. Several kinds of DNA modifications are formed upon oxidative stress (8). The most prevalent modifications, quantitatively, are single-strand breaks and oxidized bases. Clustered DNA damage, when two or more modifications are closely positioned in opposite strands, is detectable after gamma irradiation and has recently been shown to be generated by normal oxidative metabolism (3, 35). One unique aspect of such clustered lesions is that they can be converted into double-strand breaks (DSB) if a DNA glycosylase removes the two opposite bases and an apurinic/apyrimidinic (AP)-endonuclease cleaves the resulting abasic sites. Thus, although quantitatively minor, DSB are possible outcomes of oxidative DNA damage.Oxidized DNA bases are repaired primarily by the base excision repair pathway (BER) (22, 39). BER is initiated by a lesion-specific DNA N-glycosylase that recognizes and excises the damaged base. Eight-hydroxyguanine (8-oxoG) is one of the most abundant oxidized bases detected in cellular DNA. This adduct is easily bypassed by replicative polymerases; however, it can direct the misincorporation of adenine opposite 8-oxoG, thus leading to G·C-to-T·A transversion mutations (31). 8-oxoG accumulation has been causally associated with carcinogenesis and aging in several experimental models (1, 12). In eukaryotes, oxoguanine DNA glycosylase (OGG1) is the major 8-oxoG DNA glycosylase. OGG1 possesses an associated AP-lyase activity, such that it removes 8-oxoG and cleaves the DNA backbone. Human cells express two distinct OGG1 isoforms, α and β, which share the first 316 amino acids but differ significantly in their C termini (25). While OGG1-α is a bone fide DNA glycosylase (5) and localizes both to nuclei and mitochondria, OGG1-β localizes exclusively to mitochondria. We recently showed that the recombinant OGG1-β protein has no DNA glycosylase activity (13). The high degree of conservation of repair pathways for 8-oxoG, from bacteria to humans, along with epidemiological data correlating OGG1 polymorphisms and activity with predisposition to some cancers (11, 27, 33) attest to the biological importance of the repair of 8-oxoGs and other oxidative DNA lesions.Until recently, distinct classes of DNA lesions were believed to be metabolized by different and independent repair pathways. However, experimental evidence indicates that these pathways can interact and that there is a considerable degree of overlap in their substrate specificity and in the proteins that participate in each pathway. Experiments using yeast strains lacking one or more distinct DNA repair genes suggest that DSB repair pathways may play a role in repair of oxidative DNA damage. Swanson et al. showed that while yeast cells lacking ntg1 and ntg2 (homologues of Escherichia coli endonuclease III, a DNA glycosylase specific for pyrimidine lesions formed by oxidation) and apn1 (the major yeast abasic site endonuclease) are not overtly sensitive to oxidative stress, the additional disruption of the rad52 gene significantly increases sensitivity to H₂O₂ and menadione (36). Similarly, yeast cells expressing decreased levels of frataxin, which leads to elevated oxidative stress, show accumulation of oxidative damage in nuclear DNA only in a rad52 mutant background (18). RAD52 is a member of the RAD51 epistatic group. These proteins are believed to be involved in the early steps of homologous recombination, contributing to homology search and strand invasion; disruption of the corresponding genes renders cells deficient in DSB repair and hyper-recombinogenic (19).These results suggested a possible role for RAD52 in the repair of oxidative DNA damage. Moreover, an in vitro screening of protein partners that interact physically with OGG1-β performed in our lab (unpublished data) showed that human RAD52 strongly interacted with this glycosylase, again suggesting a possible function for RAD52 in the oxidative DNA damage response. Thus, we investigated whether RAD52 plays a role in the repair of oxidative DNA damage in human cells. We show here that human RAD52 physically interacts with both OGG1-α and -β, in vitro and in cell extracts. We also show that OGG1-α and -β inhibit RAD52 enzymatic activities. Conversely, RAD52 stimulates OGG1-α 8-oxoG incision activity. RAD52 colocalizes with OGG1-α in cells, and this colocalization increases after oxidative stress. Moreover, lower RAD52 expression, via gene knockdown (KD) or disruption of the RAD52 gene, render cells sensitive to oxidative stress. Based on our results, we discuss a model in which OGG1 and RAD52 cooperate to repair 8-oxoG lesions.     

GO System,a DNA Repair Pathway to Cope with Oxidative Damage

Molecular Biology - The GO system is part of the DNA base excision repair pathway and is required for the error-free repair of 8-oxoguanine (oxoG), one of the most common oxidative DNA lesions. Due...     

Arterial Wall Stiffness and the Risk of Atherosclerosis in Egyptian Patients with Overt and Subclinical Hypothyroidism

Objective: Hypothyroidism is associated with an increased risk of atherosclerosis. Pulse wave velocity (PWV) is an index of arterial wall stiffness widely used for noninvasive assessment of early atherosclerosis. We assessed PWV in Egyptian patients with hypothyroidism.Methods: The study included 100 Egyptian females aged 18 to 55 years. They were classified into three groups: group I, 40 women with overt hypothyroidism; group II, 40 women with subclinical hypothyroidism; and group III, 20 euthyroid women as a control group. The three groups were age matched. Doppler ultrasonography was used to calculate the heart-femoral PWV.Results: PWV was significantly higher in women with overt and subclinical hypothyroidism as compared with the control group (9.55 ± 1.81 m/s and 9.30 ± 1.28 m/s, respectively vs. 7.82 ± 2.14 m/s; P<.001 and <.01, respectively). There was a positive correlation between thyroid-stimulating hormone (TSH) and PWV in women with overt hypothyroidism and in those with subclinical hypothyroidism (P<.05 for both). Multivariate regression analysis showed that age and diastolic blood pressure were independent determinants of PWV in women with overt and subclinical hypothyroidism (P<.01 for all). TSH was also an independent determinant of PWV in both groups (P<.05 for both).Conclusion: PWV is significantly higher in Egyptian women with overt and subclinical hypothyroidism as compared with normal control subjects. This denotes early increase in arterial wall stiffness in patients with hypothyroidism, even in the subclinical phase. The positive correlation between PWV and TSH in both groups of patients suggests that the risk of atherosclerosis is proportionate to the severity of hypothyroidism.Abbreviations: ABI = ankle/brachial index; baPWV = brachial-ankle pulse wave velocity; BP = blood pressure; CIMT = carotid intima-media thickness; ECG = electrocardiogram; FT4 = free thyroxine; HDL = high-density lipoprotein; hfPWV = heart-femoral pulse wave velocity; LDL = low-density lipoprotein; PTT = pulse transit time; PWV = pulse wave velocity; SCH = subclinical hypothyroidism; TSH = thyroid-stimulating hormone     

Defective Repair of Oxidative Base Lesions by the DNA Glycosylase Nth1 Associates with Multiple Telomere Defects

Telomeres are chromosome end structures and are essential for maintenance of genome stability. Highly repetitive telomere sequences appear to be susceptible to oxidative stress-induced damage. Oxidation may therefore have a severe impact on telomere integrity and function. A wide spectrum of oxidative pyrimidine-derivatives has been reported, including thymine glycol (Tg), that are primarily removed by a DNA glycosylase, Endonuclease III-like protein 1 (Nth1). Here, we investigate the effect of Nth1 deficiency on telomere integrity in mice. Nth1 null (Nth1^−/−) mouse tissues and primary MEFs harbor higher levels of Endonuclease III-sensitive DNA lesions at telomeric repeats, in comparison to a non-telomeric locus. Furthermore, oxidative DNA damage induced by acute exposure to an oxidant is repaired slowly at telomeres in Nth1^−/− MEFs. Although telomere length is not affected in the hematopoietic tissues of Nth1^−/− adult mice, telomeres suffer from attrition and increased recombination and DNA damage foci formation in Nth1^−/− bone marrow cells that are stimulated ex vivo in the presence of 20% oxygen. Nth1 deficiency also enhances telomere fragility in mice. Lastly, in a telomerase null background, Nth1^−/− bone marrow cells undergo severe telomere loss at some chromosome ends and cell apoptosis upon replicative stress. These results suggest that Nth1 plays an important role in telomere maintenance and base repair against oxidative stress-induced base modifications. The fact that telomerase deficiency can exacerbate telomere shortening in Nth1 deficient mouse cells supports that base excision repair cooperates with telomerase to maintain telomere integrity.     

Behaviour of a New Composite Mesh for the Repair of Full-Thickness Abdominal Wall Defects in a Rabbit Model

Introduction

Composite biomaterials designed for the repair of abdominal wall defects are composed of a mesh component and a laminar barrier in contact with the visceral peritoneum. This study assesses the behaviour of a new composite mesh by comparing it with two latest-generation composites currently used in clinical practice.

Methods

Defects (7x5cm) created in the anterior abdominal wall of New Zealand White rabbits were repaired using a polypropylene mesh and the composites: Physiomesh^TM; Ventralight^TM and a new composite mesh with a three-dimensional macroporous polyester structure and an oxidized collagen/chitosan barrier. Animals were sacrificed on days 14 and 90 postimplant. Specimens were processed to determine host tissue incorporation, gene/protein expression of neo-collagens (RT-PCR/immunofluorescence), macrophage response (RAM-11-immunolabelling) and biomechanical resistance. On postoperative days 7/14, each animal was examined laparoscopically to quantify adhesions between the visceral peritoneum and implant.

Results

The new composite mesh showed the lowest incidence of seroma in the short term. At each time point, the mesh surface covered with adhesions was greater in controls than composites. By day 14, the implants were fully infiltrated by a loose connective tissue that became denser over time. At 90 days, the peritoneal mesh surface was lined with a stable mesothelium. The new composite mesh induced more rapid tissue maturation than Physiomesh^TM, giving rise to a neoformed tissue containing more type I collagen. In Ventralight^TM the macrophage reaction was intense and significantly greater than the other composites at both follow-up times. Tensile strengths were similar for each biomaterial.

Conclusions

All composites showed optimal peritoneal behaviour, inducing good peritoneal regeneration and scarce postoperative adhesion formation. A greater foreign body reaction was observed for Ventralight^TM. All composites induced good collagen deposition accompanied by optimal tensile strength. The three-dimensional macroporous structure of the new composite mesh may promote rapid tissue regeneration within the mesh.     

Gap-Repair方式建立一种基于pBR322-Red的新型重组工程系统

应用Gap—Repair新技术,以pBR322为载体,在λ噬菌体Red重组酶的作用下,通过同源重组直接从大肠杆菌DY330染色体上亚克隆了长度为6．7kb的包含Red重组酶基因的λ噬菌体左向操纵子基因序列。建立了一种能够随意在不同细菌宿主中转移的基于pBR322-Red的重组工程系统。为了验证pBR322-Red的生物功能,以大肠杆菌染色体上的galk基因为靶标,用Red介导的单链DNA重组技术敲入T→G单碱基突变,使galk基因内编码第145位氨基酸的密码子由TAT转变成TAG,产生了一个琥珀突变。确定了pBR322-Red系统的重组功能。