Long Telomeres in Blood Leukocytes Are Associated with a High Risk of Ascending Aortic Aneurysm

Ascending aortic aneurysm is a connective tissue disorder. Even though multiple novel gene mutations have been identified, risk profiling and diagnosis before rupture still represent a challenge. There are studies demonstrating shorter telomere lengths in the blood leukocytes of abdominal aortic aneurysm patients. The aim of this study was to measure whether relative telomere lengths are changed in the blood leukocytes of ascending aortic aneurysm patients. We also studied the expression of telomerase in aortic tissue samples of ascending aortic aneurysms. Relative lengths of leukocyte telomeres were determined from blood samples of patients with ascending aortic aneurysms and compared with healthy controls. Telomerase expression, both at the level of mRNA and protein, was quantified from the aortic tissue samples. Mean relative telomere length was significantly longer in ascending aortic aneurysm blood samples compared with controls (T/S ratio 0.87 vs. 0.61, p<0.001). Expressions of telomerase mRNA and protein were elevated in the aortic aneurysm samples (p<0.05 and p<0.01). Our study reveals a significant difference in the mean length of blood leukocyte telomeres in ascending aortic aneurysm and controls. Furthermore, expression of telomerase, the main compensating factor for telomere loss, is elevated at both the mRNA and protein level in the samples of aneurysmal aorta. Further studies will be needed to confirm if this change in telomere length can serve as a tool for assessing the risk of ascending aortic aneurysm.     

Changes in inflammatory response after endovascular treatment for type B aortic dissection

This present study aims to investigate the changes in the inflammatory markers after elective endovascular treatment of Type B aortic dissection with aneurysm, as related to different anatomical features of the dissection flap in the paravisceral perfusion. Consecutive patients with type B aortic dissections with elective endovascular stent graft repair were recruited and categorized into different groups. Serial plasma levels of cytokines (Interleukin-1β, -6, -8, -10, TNF-α), chemokines (MCP-1), and serum creatinine were monitored at pre-, peri- and post-operative stages. The length of stent graft employed in each surgery was retrieved and correlated with the change of all studied biochemical parameters. A control group of aortic dissected patients with conventional medication management was recruited for comparing the baseline biochemical parameters. In total, 22 endovascular treated and 16 aortic dissected patients with surveillance were recruited. The endovascular treated patients had comparable baseline levels as the non-surgical patients. There was no immediate or thirty day-mortality, and none of the surgical patients developed post-operative mesenteric ischaemia or clinically significant renal impairment. All surgical patients had detectable pro-inflammatory mediators, but none of the them showed any statistical significant surge in the peri-operative period except IL-1β and IL-6. Similar results were obtained when categorized into different groups. IL-1β and IL-6 showed maximal levels within hours of the endovascular procedure (range, 3.93 to 27.3 higher than baseline; p?=?0.001), but returned to baseline 1 day post-operatively. The change of IL-1β and IL-6 at the stent graft deployment was statistically greater in longer stent graft (p>0.05). No significant changes were observed in the serum creatinine levels. In conclusion, elective endovascular repair of type B aortic dissection associated with insignificant changes in inflammatory mediators and creatinine. All levels fell toward basal levels post-operatively suggesting that thoracic endovascular aortic repair is rather less aggressive with insignificant inflammatory modulation.     

Effect of major surgery on the release of interferon gamma by peripheral blood mononuclear cells: an investigation at the single cell level using the reverse haemolytic plaque assay.

The release of interferon gamma (IFN-gamma) by peripheral blood mononuclear cells from patients undergoing abdominal aortic aneurysm repair was measured using the reverse haemolytic plaque assay. The plasma of these patients was also assayed for interferon gamma using enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells from the surgical patients released significantly more IFN-gamma by 9 hours after incision than that released prior to surgery (P less than 0.001). This change persisted up to 9 days after surgery. Plasma IFN-gamma was not detectable using either of two different ELISA techniques. The increased secretion of IFN-gamma by peripheral blood mononuclear cells following major surgery may be a beneficial component of the host's immune response to injury.     

Blood phagocyte activation during open heart surgery with cardiopulmonary bypass

Open heart surgery with a cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response which significantly contributes to adverse postoperative complications. The purpose of this study was to characterize the activation of blood phagocytes during open heart surgery with CPB. Blood samples were collected during and up to 24 h after surgery. The production of reactive oxygen species (ROS) in whole blood, the expression of surface molecules by blood phagocytes and complement activity in the plasma were determined. A cDNA microarray analysis of leukocyte RNA profile of genes was performed related to the inflammatory response. Activation of the complement was already observed at the beginning of CPB. This was followed by an increase in the neutrophil number and in both spontaneous and opsonized zymosan-activated ROS production after the onset of reperfusion. The activation of blood phagocytes was affirmed by changes in surface receptors involved in the adhesion and migration of leukocytes (CD11b, CD62L and CD31). Gene arrays also confirmed the activation of leukocytes 4 h after reperfusion. In conclusion, open heart surgery with a cardiopulmonary bypass was found to be associated with a rapid and pronounced activation of blood phagocytes and complement activation which was partly independent at the onset of CPB.     

腔内修复术与传统开腹手术对腹主动脉瘤的治疗效果对比

目的:探讨腔内修复术与传统开腹手术在腹主动脉瘤患者治疗中的效果。方法:收集我院就诊或住院治疗的40例腹主动脉瘤患者,根据手术方式不同,将所选研究对象分为OR组和EVAR组,每组20例。OR组患者行传统开腹手术,EVAR组患者行腔内修复术。观察并比较两组患者术中出血量、输血量、手术时间、住院天数以及并发症的发生率。结果:与OR组患者相比,EVAR组患者手术出血量、输血量较少,手术时间、住院天数、ICU住院天数较短,患者围手术期的并发症发生率较低,但患者的远期并发症发生率较高(P0.05)。结论:腔内修复术与传统开腹手术相比,在手术的出血量以及患者的恢复时间等方面具有较为明显的优点,但远期的并发症发生率较高,对临床有指导意义。     

Altered expression profiles of clock genes hPer1 and hPer2 in peripheral blood mononuclear cells of cancer patients undergoing surgery

Patients undergoing surgery often develop symptoms of circadian rhythm disorders such as insomnia or delirium. However, the effect of surgery on the biological clock remains unknown. The present study examines the expression of clock genes in peripheral blood mononuclear cells (PBMCs) and measures plasma hormone concentrations in patients with esophageal cancer and early gastric cancer who underwent surgery. Six blood samples per day were collected from 9 patients with esophageal cancer before and after esophagectomy and from 9 patients with early gastric cancer before and after laparoscopy-assisted distal gastrectomy (LADG). The expression profiles of hPer1 and hPer2 mRNAs in PBMCs were determined by real-time RT-PCR. Plasma melatonin and cortisol concentrations were measured by radioimmunoassay. Plasma melatonin levels decreased in both groups throughout the day and plasma cortisol levels changed after surgery. The acrophase of clock gene expression was altered after surgery as follows: hPer1, from 6:19+/-1:50 to 13:59+/-0:59 (p=0.0003) and from 7:47+/-1:27 to 12:33+/-1:30 (p=0.0043) and hPer2, from 5:01+/-2:59 to 19:30+/-2:15 (p<0.0001) and from 6:49+/-1:59 to 13:39+/-3:06 (p=0.0171) in patients with esophageal and early gastric cancer, respectively. The post-operative phase change of hPer2 was more prominent after esophagectomy than after LADG. Our results suggest that surgical stress affects the peripheral clock as well as endogenous hormones in humans.     

Progression of apoptic signaling from mesenteric ischemia–reperfusion injury to lungs: correlation in the level of ER chaperones expression

Multiple organ dysfunction syndrome (MODS) is characterized by the development of probably reversible, progressive dysfunction of vital systems in two or more organs, directly undamaged by surgery or other trauma. The organs which have the most common potential dysfunction are lungs, liver, kidneys, heart and gastrointestinal tract. The small intestine is the source of production of proinflammatory mediators leading and contributing to multiorgan failure. The endoplasmic reticulum (ER), after ischemia and post-ischemic reperfusion, is significantly involved in the activation of enterocyte apoptosis. The purpose of this study was to determine the stage of apoptosis in the lungs, initiated through inflammatory response from the small intestine. We analyzed changes in mRNA levels of pro-apoptotic genes Gadd153 (Chop) and anti-apoptotic genes Grp78 (Bip) in the small intestine wall and lung parenchyma. During experimental procedure the rats underwent 60 min of ischemia, caused by complete occlusion of the mesenteric arteria cranialis, with subsequent reperfusion and evaluation after 1 h, 24 h and 30 days (from R1, R24 to R30, respectively, each group n = 8). The gene expression levels were measured using RT-PCR followed by electrophoresis and visualization under UV. In the lungs we detected significantly lower level of expression Grp78 by 45 ± 6.9%. This suggests that ischemic attack and subsequent reperfusion did not promote ER stress in the lungs through induction of Gadd153 expression in the small intestine. There is still no effective approach to the treatment of affected ischemic intestine tissue, to stop the processes with could eventually lead to MODS. Therefore it is necessary to study changes in the damaged tissue at the molecular level and try to suggest possible therapeutic defined routes to the protection of tissue.     

胰十二指肠切除术后肠黏膜屏障损伤与肠道细菌移位的临床研究（英文）

目的：探讨胰十二指肠切除手术后肠道细菌移位（BT）与术后全身炎症反应综合征（SIRS）关系。方法：40例择期行胰十二指肠切除手术患者,于术前和术后1、3、5天采集外周血,进行血浆D-乳酸,全血细菌DNA检测.全血DNA提取后进行PCR扩增,采用靶基因为大肠杆菌特异性β半乳糖苷酶基因和16SrRNA基因。观察患者术后10天以监测SIRS情况。结果：术前PCR检测全血细菌DNA均为阴性,术后共有13例阳性。术后出现全身炎症反应综合征（SIRS）的患者PCR阳性率为85.7%（12/14）,无SIRS组为3.8%（1/26（）P〈0.01）。PCR阳性组SIRS发生率为93.2%（12/13）,阴性组为7.4%（2/27）（P〈0.01）.PCR阳性的患者外周血血浆D-乳酸浓度较PCR阴性者明显升高（P〈0.01）,有SIRS的患者外周血血浆D-乳酸浓度较无SIRS患者明显升高（P〈0.01）。结论：胰十二指肠切除术后肠黏膜屏障损伤与BT关系密切,术后SIRS和与BT密切相关。PCR技术对术后SIRS有较好的早期预警价值。     

No influence of surgical stress on postoperative leptin gene expression in different adipose tissues and soluble leptin receptor plasma levels

As part of the postsurgical stress response, plasma leptin levels increase in-between 12 h postoperatively. OBJECTIVE: To study the kinetics of leptin gene expression in different adipose tissues before and after severe surgical trauma in children and adults. METHODS: In 22 adults and 23 children with cardiac and 19 adult patients with abdominal surgery, we measured plasma leptin concentrations preoperatively, 4 and 10-17 h postoperatively and quantified leptin mRNA expression by TaqMan real-time PCR in adipose tissue taken at the beginning and the end of surgery from subcutaneous, intrathoracic, omental and mesenteric fat. Plasma-soluble leptin receptor levels were measured in 23 children after cardiosurgery. RESULTS: Plasma leptin levels doubled between 4 and 10-17 h postoperatively in adults (p < 0.001) as well as in children (p = 0.0002) with cardiac surgery. After abdominal surgery, 10-17 h postoperatively, plasma leptin concentrations increased significantly (p < 0.05). During the operation, leptin gene expression did not change in neither of the patient groups. Plasma-soluble leptin receptor levels decreased immediately after the onset of surgery and remained unchanged thereafter. CONCLUSIONS: Leptin gene expression is not up-regulated during surgery. The measured increase in plasma leptin after surgery does not result from elevated levels of soluble leptin receptor but may follow an up-regulation of leptin gene expression later after the operation due to postsurgical metabolic changes.     

Abdominal Aortic Aneurysms

Aneurysms are common in our increasingly elderly population, and are a major threat to life and limb. Until the advent of vascular reconstructive techniques, aneurysm patients were subject to an overwhelming risk of death from exsanguination. The first successful repair of an abdominal aortic aneurysm using an interposed arterial homograft was reported by Dubost in 1952. A milestone in the evolution of vascular surgery, this event and subsequent diagnostic, operative and prosthetic graft refinements have permitted patients with an unruptured abdominal aortic aneurysm to enjoy a better prognosis than patients with almost any other form of major systemic illness.     

The pharmacokinetics of cefazolin in patients undergoing elective & semi-elective abdominal aortic aneurysm open repair surgery

Background

Surgical site infections are common, so effective antibiotic concentrations at the sites of infection are required. Surgery can lead to physiological changes influencing the pharmacokinetics of antibiotics. The aim of the study is to evaluate contemporary peri-operative prophylactic dosing of cefazolin by determining plasma and subcutaneous interstitial fluid concentrations in patients undergoing elective of semi-elective abdominal aortic aneurysm (AAA) open repair surgery.

Methods/Design

This is an observational pharmacokinetic study of patients undergoing AAA open repair surgery at the Royal Brisbane and Women's Hospital. All patients will be administered 2-g cefazolin by intravenous injection within 30-minutes of the procedure. Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration by cefazolin. Participants will be administered indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes occurring during surgery. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters and the effect of peri-operative physiological changes on cefazolin disposition.

Discussion

The study will describe cefazolin levels in plasma and the interstitial fluid of tissues during AAA open repair surgery. The effect of physiological changes to the patient mediated by surgery will also be determined. The results of this study will guide clinicians and pharmacists to effectively dose cefazolin in order to maximize the concentration of antibiotics in the tissues which are the most common site of surgical site infections.     

Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis

Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation and by increasing VEGF and leukocyte infiltration into the lung.     

胰十二指肠切除术后肠黏膜屏障损伤与肠道细菌移位的临床研究

目的:探讨胰十二指肠切除手术后肠道细菌移位(BT)与术后全身炎症反应综合征(SIRS)关系。方法:40例择期行胰十二指肠切除手术患者,于术前和术后1、3、5天采集外周血,进行血浆D-乳酸,全血细菌DNA检测.全血DNA提取后进行PCR扩增,采用靶基因为大肠杆菌特异性β半乳糖苷酶基因和16SrRNA基因。观察患者术后10天以监测SIRS情况。结果:术前PCR检测全血细菌DNA均为阴性,术后共有13例阳性。术后出现全身炎症反应综合征(SIRS)的患者PCR阳性率为85.7%(12/14),无SIRS组为3.8%(1/26()P<0.01)。PCR阳性组SIRS发生率为93.2%(12/13),阴性组为7.4%(2/27)(P<0.01).PCR阳性的患者外周血血浆D-乳酸浓度较PCR阴性者明显升高(P<0.01),有SIRS的患者外周血血浆D-乳酸浓度较无SIRS患者明显升高(P<0.01)。结论:胰十二指肠切除术后肠黏膜屏障损伤与BT关系密切,术后SIRS和与BT密切相关。PCR技术对术后SIRS有较好的早期预警价值。     

Upregulation of DNA repair genes in active cirrhosis associated with hepatocellular carcinoma

Phenotypic changes in injured livers involve complex network of genes whose interplays may lead to fibrosis and cirrhosis, a major risk of hepatocellular carcinoma. Gene expression profiles in fibrotic livers were analyzed by using cDNA microarray, hierarchical clustering and gene ontology. Analyses of a major cluster of upregulated genes in cirrhosis identified a new set of genes involved in DNA repair and damage. The upregulation of DNA repair genes was confirmed by real-time quantitative polymerase chain reaction and associated with necroinflammatory activity (P<0.001). Increased DNA repair activity in cirrhosis with inflammatory activity may reflect increased DNA damages as a consequence of chronic liver injury.     

Upregulation of the high mobility group AT-hook 2 gene in acute aortic dissection is potentially associated with endothelial-mesenchymal transition

The high mobility group AT-hook 2 (HMGA2) gene is proposed to regulate the genes involved in the epithelial-mesenchymal transition (EMT). One form of EMT is endothelial-mesenchymal transition (EndMT). We analyzed the expression profile of the HMGA2 gene in different human aortic diseases. Aortic specimens were collected from 51 patients, including 19 with acute aortic dissection, 26 with aortic aneurysm, two with Marfan syndrome and four aortic valves. Quantitative real-time polymerase chain reaction was carried out for HMGA2 and immunohistochemical analyses were performed for HMGA2, SNAI1, Vimentin, CD34, MKI-67 and TGFB1. The expression of let-7d microRNA, which is assumed to play a role in the regulation of HMGA2, was also quantified. The level of HMGA2 gene expression was significantly higher in acute aortic dissection compared with all the other samples (193.1 vs. 8.1 fold normalized to calibrator, P<0.001). The immunohistochemical investigation showed that HMGA2, SNAI1, and Vimentin proteins were mainly detected in the endothelial cells of the vasa vasorum. The HMGA2 gene is upregulated in acute aortic dissection. This is the first report describing a link between HMGA2 and acute aortic dissection. The HMGA2, SNAI1 and Vimentin proteins were mainly detected in the endothelium of the vasa vasorum. It seems that HMGA2 overexpression in acute aortic dissection occurs in a let-7d-independent manner and is associated with EndMT of the vasa vasorum.     

Acute Phase Response of Selenium Status and Glutathione Peroxidase Activity in Blood Plasma Before and After Total Knee Arthroplasty Surgery

Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p?相似文献   

Ultrasound screening for clinically occult abdominal aortic aneurysm.

In a review of the records of 74 patients who had undergone repair of an abdominal aortic aneurysm at a community hospital between 1977 and 1983 we found that the aneurysm had been undiagnosed before rupture in 35%; these patients had an operative death rate of 50%, whereas elective repair carried a death rate of 4%. The characteristic patient was an obese man over the age of 55 years with hypertension, coronary artery disease, cerebrovascular disease or peripheral vascular disease. Ultrasound examination was performed in 45 patients with these characteristics, and six aneurysms were diagnosed. Either surgery or computed tomography confirmed the diagnosis. The rate of false-negative results was estimated by review of the charts of 100 men over the age of 55 years who had undergone abdominal ultrasonography for other indications: no undetected aneurysms were discovered over 3 years of follow-up. Routine screening in this high-risk group would improve the rate of diagnosis of this potentially fatal condition before rupture and offer the patient the lower mortality rate associated with elective surgery.