The effect of a polyurethane coating incorporating both a thrombin inhibitor and nitric oxide on hemocompatibility in extracorporeal circulation

Nitric oxide (NO) releasing (NORel) materials have been extensively investigated to create localized increases in NO concentration by the proton driven diazeniumdiolate-containing polymer coatings and demonstrated to improve extracorporeal circulation (ECC) hemocompatibility. In this work, the NORel polymeric coating composed of a diazeniumdiolated dibutylhexanediamine (DBHD-N₂O₂)-containing hydrophobic Elast-eon™ (E2As) polyurethane was combined with a direct thrombin inhibitor, argatroban (AG), and evaluated in a 4 h rabbit thrombogenicity model without systemic anticoagulation. In addition, the immobilizing of argatroban to E2As polymer was achieved by either a polyethylene glycol-containing (PEGDI) or hexane methylene (HMDI) diisocyanate linker. The combined polymer film was coated on the inner walls of ECC circuits to yield significantly reduced ECC thrombus formation compared to argatroban alone ECC control after 4 h blood exposure (0.6 ± 0.1 AG/HMDI/NORel vs 1.7 ± 0.2 cm² AG/HMDI control). Platelet count (2.8 ± 0.3 AG/HMDI/NORel vs 1.9 ± 0.1 × 10⁸/ml AG/HMDI control) and plasma fibrinogen levels were preserved after 4 h blood exposure with both the NORel/argatroban combination and the AG/HMDI control group compared to baseline. Platelet function as measured by aggregometry remained near normal in both the AG/HMDI/NORel (63 ± 5%) and AG/HMDI control (58 ± 7%) groups after 3 h compared to baseline (77 ± 1%). Platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry also remained near baseline levels after 4 h on ECC to ex vivo collagen stimulation (16 ± 3 AG/HMDI/NORel vs 11 ± 2 MFI baseline). These results suggest that the combined AG/HMDI/NORel polymer coating preserves platelets in blood exposure to ECCs to a better degree than AG/PEGDI/NORel, NORel alone or AG alone. These combined antithrombin, NO-mediated antiplatelet effects were shown to improve thromboresistance of the AG/HMDI/NORel polymer-coated ECCs and move potential nonthrombogenic polymers closer to mimicking vascular endothelium.     

The mediation of platelet quiescence by NO-releasing polymers via cGMP-induced serine 239 phosphorylation of vasodilator-stimulated phosphoprotein

Nitric oxide (NO) releasing (NORel) materials have been shown to create localized increases in NO concentration by the release of NO from a diazeniumdiolate-containing or S-nitrosothiol-containing polymer coating and the improvement of extracorporeal circulation (ECC) hemocompatibility. However, the mechanism and, in particular, the platelet upregulation of the NO/cGMP signaling protein, vasodilator-stimulated phosphoprotein phosphorylated at serine 239 (P-VASP (ser 239)), for the improved ECC hemocompatibility via NO release still needs elucidation. In this work, two NORel polymeric coatings were evaluated in a 4 h rabbit thrombogenicity model and the anti-thrombotic mechanism investigated for rabbit platelet P-VASP upregulation. Polymer films containing 25 wt% diazeniumdiolated dibutylhexanediamine (DBHD) or 5 wt% S-nitroso-N-acetylpenicillamine (SNAP) coated on the inner walls of ECC circuits yielded significantly reduced ECC thrombus formation and maintained normal platelet aggregation compared to polymer controls after 4 h of blood exposure. Platelet P-VASP (ser 239), a useful tool to monitor NO/cGMP signaling, was upregulated after 4 h on ECC and markedly increased after ex vivo sodium nitroprusside (SNP) stimulation. Interestingly, in the rabbit platelet, NO did not upregulate the cAMP P-VASP phosphoprotein P-VASP (ser 157) as previously shown in human platelets. These results suggest that NORel polymers preserve rabbit platelet quiescence by sustaining a level of cGMP signaling as monitored by P-VASP (ser 239) upregulation. The upregulation of this NO-mediated platelet signaling mechanism in this rabbit thrombogenicity model indicates the potential for improved thromboresistance of any NORel-coated medical device.     

Thrombogenicity is not reduced when heparin and phospholipid bonded circuits are used in a rabbit model of extracorporeal circulation

In an effort to better mimic the thromboresistive nature of vascular endothelium, extracorporeal circuits bonded with heparin or phospholipids were developed. Using no systemic heparinization, these circuits were compared with standard poly(vinyl)chloride (PVC) (Tygon) in a rabbit model of extracorporeal circulation (ECC). Control circuits were run with and without systemic heparinization and used as comparison groups against the test circuits. Two New Zealand White rabbits were used per study: One was used as the platelet donor for 111Indium platelet labeling; the other animal was placed on bicaval ECC for 4 hours. Circuits (heparin coated n = 6, phospholipid coated n = 8, nonheparinized controls n = 14, heparinized controls n = 18) consisted of 1 m of tubing, two downsizing connectors, and two venous cannulae. ECC blood flow was at least 75 ml/min. Platelet and fibrinogen measurements were made hourly, and circuit dosimetry was performed at the end of the study or on circuit thrombosis. Thrombosis of the circuit occurred in one heparin coated, two phospholipid coated, and eight nonheparinized control circuits. None of the heparinized control circuits thrombosed. There was no significant difference between the groups with regard to platelet count or platelet adhesion. Test circuits exhibited preservation of fibrinogen levels. In this rabbit model of ECC, circuits coated with heparin or phospholipids appeared to preserve fibrinogen levels but did not reduce platelet adhesion or consumption.     

A method for evaluating the influence of porosity on the early reactions of blood with materials.

A method is presented for evaluating the influence of porosity on the early reactions of blood with polymer membranes of cellulose acetate and polyethersulfone with two different pore sizes, 0.1-0.2 microm and 0.8 microm. A system of two phases consisting of capillary blood and Dulbecco's phosphate buffered saline was constructed. Platelet adhesion and exposure of thrombospondin was examined by immunofluorescence. Platelet adhesion was higher on the membrane with 0.8 microm pore size. Leukocyte adhesion and viability was measured by fluorescein diacetate/propidium iodide staining, and the respiratory burst response to PMA and opsonized zymosan was measured by chemiluminescence. Leukocyte viability was higher on the membranes with 0.8 microm pore size and higher on the cellulose membrane for exposures upto 2 h. After 3 h the leukocyte viability was highest on the polyethersulfone membrane with a pore size of 0.8 microm. The respiratory burst response of membrane-adhering leukocytes could not be triggered by opsonized zymosan on any of the tested membranes. A response was seen after stimulation with PMA of cells adhering to the cellulose membrane with a pore size of 0.8 microm.     

人脐带间充质干细胞治疗老年心肌梗死的CD34＋细胞、Toll样受体2和Toll样受体4的表达水平分析

目的 探讨循环CD34＋细胞（CD34＋）、Toll样受体2（toll like receptor 2, TLR2）和Toll样受体4（toll like receptor 4, TLR4）表达水平对人脐带间充质干细胞治疗老年人陈旧性心肌梗死的影响.方法 采用流式细胞仪检测经皮冠状动脉介入治疗（PCI）＋支架植入术患者（对照组）和PCI＋支架植入术＋人脐带间充质干细胞移植术患者（实验组）循环CD34＋、TLR2和TLR4的表达水平与心肌梗死面积和左心室射血分数（LVEF）的关系.评估CD34＋、TLR2和TLR4对细胞心肌成形术早期预后的影响.结果 对照组行PCI＋支架植入治疗后8周梗死面积为（26.6±3.4）%、LVEF为（38.4±2.8）%;实验组行PCI＋支架植入术＋人脐带间充质干细胞移植治疗后8周梗死面积为（24.2±3.9）%、LVEF为（46.1±1.9）%,两组比较差异均具有统计学意义（P〈0.01）.对照组治疗后8周CD34＋为（0.9±0.2）×109/L,实验组治疗后8周CD34＋为（1.4±0.1）×109/L;对照组治疗后8周TLR2为（5.9±2.2）平均荧光强度（MFI）和TLR4为（3.7±1.8）MFI,PCI＋支架植入术＋人脐带间充质干细胞移植治疗后8周TLR2为（3.6±0.3）MFI和TLR4为（2.2±1.3）MFI.两组患者治疗后8周CD34＋、TLR2和TLR4水平之间有显著差异（P〈0.01）.结论 CD34＋、TLR2和TLR4表达水平变化与人脐带间充质干细胞移植患者心肌梗死面积的缩小和LVEF的改善相关.     

Delayed Recovery of Myocardial Blood Flow After Intracoronary Stem Cell Administration

The aim of the present study was to investigate the changes in absolute myocardial blood flow (AMF) after intracoronary injections of mesenchymal SC (MSC) and compared to controls in closed-chest reperfused acute myocardial infarction (AMI) in pigs. Male MSCs, transiently transfected with Luciferase (Luc-MSC) were delivered (9.7 ± 1.2 x 10(6)) intracoronary in the open infarct-related artery one-week post-AMI in female pigs (group MSC), while saline was injected with the same injection rate in controls (group C). The AMF was measured immediately after, and 3, 12 and 24 h post-intracoronary Luc-MSC or saline injections. In vitro bioluminescence images and quantitative real-time TaqMan PCR measurements were performed to quantify the sex-mismatched MSCs. No difference between the groups was observed regarding the weight, heart rate, blood pressure and global ejection fraction 1-week post-AMI. The baseline AMF were similar in the groups (61.3?±?15. vs 61.1?±?12.0 ml/min). AMF was decreased significantly immediately after intracoronary MSC delivery (42.0?±?12.4 vs 57.7?±?15.7 ml/min p?=?0.013), and remained low at 3 h (40.9?±?13.4 vs 55.8?±?4.9 ml/min, p?=?0.004), 12 h (43.0?±?3.7 vs 57.8?±?5.4 ml/min, p?=?0.001) with incomplete recovery at 24 h (47.2?±?5.5 vs 62.1?±?14.1 ml/min, p?=?0.038) as compared to controls, respectively. In vitro bioluminescence displayed transfected Luc-MSCs along the proximal and mid part of the LAD, with limited number (295?±?101 sry copied/million cardiac cells) of Y-chromosome-MSCs in the infarcted area. Intracoronary injection of SCs results in immediate decrease of AMF, with delayed recovery. The delivery of the SC into the injured myocardium might be hindered by the altered coronary pressure and flow conditions.     

氯沙坦联合丹参酮注射液治疗高血压肾损害的疗效

目的 探讨氯沙坦联合丹参酮注射液治疗高血压肾损害的临床疗效。方法 选取2018年1月~12月我院收治高血压肾损害患者60例作为研究对象,采用随机数字表法分为观察组和对照组,每组30例。对照组给予氯沙坦治疗,观察组在对照组基础上联合丹参酮注射液治疗,比较两组治疗前后血压变化情况、血肌酐变化情况、β微球蛋白以及24h尿蛋白情况进行对比。结果治疗前两组收缩压、舒张压、血肌酐比较,差异无统计学意义（P＞0.05）;治疗后,观察组收缩压、舒张压、血肌酐水平均低于对照组[（130.67±5.49）mmHg vs（138.16±7.13）mmHg]、[（81.19±2.12）mmHg vs（87.49±2.84）mmHg]、[（137.15±6.49）μmol/L vs（158.67±8.61）μmol/L],差异有统计学意义（P＜0.05）。治疗前两组β微球蛋白、24h尿蛋白比较,差异无统计学意义（P＞0.05）;治疗后,观察组β微球蛋白、24h尿蛋白均低于对照组[（0.54±0.42）μg/ml vs（0.86±0.69）μg/ml]、[（0.52±0.29）g/24h vs（0.89±0.35）g/24h],差异有统计学意义（P＜0.05）。结论 氯沙坦联合丹参酮注射液可有效降低患者血压、血肌酐水平、β微球蛋白、24h尿蛋白,优于单一氯沙坦治疗。     

人工气管组分材料的生物相容性动物实验

目的 对制作人工气管的相关组分材料进行生物相容性评价.方法 皮肤致敏实验:雄性豚鼠分5组(n=8),纳米碳纤维组、胶原蛋白-羟基磷灰石组、混合材料组、阳性对照组(甲醛)和阴性对照组(生理盐水),观察各组的材料浸渍液是否引起豚鼠皮肤过敏反应.热原实验:新西兰兔分4组(n=3),纳米碳纤维组、胶原蛋白-羟基磷灰石组、混合材料组和阴性对照组(生理盐水),观察各组的材料浸渍液是否含有热原物质.以及通过溶血实验观察各组的材料浸渍液对兔血细胞溶血率的影响.结果 本实验涉及的生物材料致敏率均为0,与阴性对照组的皮肤致敏反应差异均无统计学意义(P>0.05).各材料组动物注射材料浸渍液后体温升高分别为(0.3±0.2)、(0.2±0.1)、(0.3±0.2)℃,均在0.6℃以下,且升高总数均在1.4℃以下.各组浸渍液溶血率分别为(0.130 1±0.000 4)%、(0.200 4±0.000 4)%、(0.150 2±0.000 4)%,均<5%.结论 人工气管的组分材料均符合生物相容性评价实验的安全标准,可为建立进一步动物实验模型提供相关依据.     

Clinical efficacy of leukofiltration on cardiopulmonary bypass related inflammatory response: Fact or Foe?

Objective:  The powerful precept of preoperative risk assessment has been applied to compare the efficacy of leukofiltration techniques for high-risk cohorts with the documentation of broad indicators of systemic inflammation. Methods:  Forty high risk patients were prospectively assigned to four perfusion protocols; the first group (n=10): Polyethyleneoxide (PEO) based heparin bonded extracorporeal circuits (ECC) + Continuous Leukocyte filtration; the second group (n=10): uncoated ECC + leukofiltration; the third group (n=10): PEO based heparin bonded ECC without leukofiltration; and control (n=10). Blood samples were obtained at the following intervals: Baseline (T1), on cardiopulmonary bypass (CPB) (T2), Cross clamp (T3), off CPB (T4), Intensive care unit-24 h (ICU24) (T5), ICU48 (T6). Results:  Tumor Necrosis Factor-alpha levels were significantly lower in Group 1 at T3, T4 (p<0.05) vs. control. Procalcitonin levels were significantly lower in Group 1 at T5, T6 (p<0.05) vs. control. Creatinine kinase-MB levels in coronary sinus blood demonstrated well preserved myocardium in filtered+coated (Group1) and coated groups (Group3) (p<0.05). Matrix metallopeptidase- 9 and D-Dimer levels in filtered+coated group were significantly lower at T5 and T6 vs. control (p<0.05). Conclusion:  Leukocyte filtration on coated surfaces alleviated systemic inflammatory response with a better clinical outcome in high risk patients. Received 26 December 2007; returned for revision 12 July 2008; received from final revision 12 November 2008; accepted by M.Katari 16 November 2008     

原发性肝癌患者免疫原快速激活红细胞调控IL-8和球蛋白变化仿真实验研究

目的 研究原发性肝癌患者血浆中红细胞固有免疫反应与来自白细胞的IL-8和球蛋白之间规律变化的关系.方法 灭活癌细胞(S180株5×106/ml)或生理盐水(对照组)0.2 ml加到枸橼酸抗凝的0.2 ml全血细胞悬液(自然实验组)或白细胞悬液(白细胞分离实验组)和新鲜血浆0.3 ml中,混匀后放37℃温育1 h,测定反应液中IL-8和球蛋白含量.结果 原发性肝癌患者自然实验组IL-8含量(376.35 ±243.96)Pg/ml和球蛋白(7.86 ±2.01)g/L,明显高于正常人自然实验组的IL-8含量(11.36±6.93)Pg/ml和球蛋白含量(7.21 ±1.75)g/L,(P＜0.01),正常人自然实验组IL-8含量(11.36 ±6.93)pg/ml和球蛋白含量(7.21 ±1.75)g/L明显高于正常人自然对照组IL-8含量(4.98 ±4.35)pg/ml和球蛋白含量(5.38±1.61)g/L,(P＜0.05),正常人自然实验组IL-8的激活指数2.49 ±2.33明显高于原发性肝癌患者自然实验组IL-8的激活指数0.22 ±0.24,(P＜0.05).结论 红细胞能快速调控血浆中的IL-8和球蛋白含量,但原发性肝癌患者红细胞调控IL-8和球蛋白的能力明显低于正常人,在原发性肝癌患者系统血液固有免疫反应中,红细胞固有免疫反应活性与白细胞固有免疫反应活性之间的关系处于失衡状态.     

经尿道前列腺电切术后老年患者自控-靶控舒芬太尼镇痛的安全性和有效性

目的 研究经尿道前列腺电切(TURP)术后老年患者应用自控-靶控舒芬太尼镇痛的安全性和有效性。方法 选择择期行TURP老年患者60例，随机分成4组。Ⅰ组：自控-靶控镇痛(PCATCI)模式，设置舒芬太尼初始血浆靶浓度(Cp) 0.06μg/L，最低有效Cp 0.04μg/L。Ⅱ组：PCA-TCI模式，设置舒芬太尼初始Cp 0.08 μg/L，最低有效Cp 0.05μg/L。Ⅲ组：PCA-TCI模式，设置舒芬太尼初始Cp 0.10 μg/L，最低有效Cp 0.05μg/L。Ⅰ、Ⅱ、Ⅲ组药液配置相同：舒芬太尼（sufentanil）Ⅰ mg/L。Ⅳ组（对照）：吗啡硬膜外自控镇痛(PCEA)，药液0.06％吗啡+0.2％罗哌卡因，用负荷剂量+持续输注+PCA(LCp)模式。4组患者术后均待腰麻感觉阻滞平面下降至T10后开启镇痛装置，监测其启动前及启动后各时点的视觉模拟评分(VAS)、Ramsay镇静评分、术后运动恢复时间（改良Bromage评分）、舒芬太尼Cp、收缩压(SBP)、舒张压(DBP)、心率(HR)、脉搏血氧饱和度(SpO2)、呼吸频率(RR)和患者对该镇痛装置的综合满意度；记录按压次数(D1)与实际进入次数(D2)、肛门排气时间、不良反应及24h用药总量。结果4组患者均获得满意的镇痛效果。在相同时间点的Ramsay镇静评分4组间比较差异无统计学意义(P＞0.05)；在相同时间点的VAS评分和D1，D2值在Ⅱ、Ⅲ、Ⅳ组组间比较差异无统计学意义(P＞0.05),Ⅰ组1、2、4h时点VAS评分较高(P＜0.05)。所有患者24h内均有肛门排气，Ⅰ组为(16.5±3.9)h,Ⅱ组为( 16.2±3.8)h,Ⅲ组为(16.8±4.1)h，均较IV组的(19.1±2.5)h时间缩短(P＜0.05)。Ⅰ、Ⅱ组用药量相似[(36.7±5.1)μg和(37.8±4.7)μg,P＞0.05]，Ⅲ组用药量[(42.3±5.6) μg]比Ⅰ、Ⅱ组高(P＜0.05)。各组不良反应发生率相似(P＞0.05)。结论 舒芬太尼PCA-TCI用于老年患者TURP术后镇痛安全有效。其设置舒芬太尼初始Cp为0.08μg/L，最低有效Cp为0.05 μg,/L时，VAS评分较低，用药量较少，且有利于患者循环功能的稳定。     

Human plasma fibrinogen adsorption and platelet adhesion to polystyrene.

The purpose of this study was to further investigate the role of fibrinogen adsorbed from plasma in mediating platelet adhesion to polymeric biomaterials. Polystyrene was used as a model hydrophobic polymer; i.e., we expected that the role of fibrinogen in platelet adhesion to polystyrene would be representative of other hydrophobic polymers. Platelet adhesion was compared to both the amount and conformation of adsorbed fibrinogen. The strategy was to compare platelet adhesion to surfaces preadsorbed with normal, afibrinogenemic, and fibrinogen-replenished afibrinogenemic plasmas. Platelet adhesion was determined by the lactate dehydrogenase (LDH) method, which was found to be closely correlated with adhesion of 111In-labeled platelets. Fibrinogen adsorption from afibrinogenemic plasma to polystyrene (Immulon I(R)) was low and <10 ng/cm2. Platelet adhesion was absent on surfaces preadsorbed with afibrinogenemic plasma when the residual fibrinogen was low enough (<60 microg/mL). Platelet adhesion was restored on polystyrene preadsorbed with fibrinogen-replenished afibrinogenemic plasma. Addition of even small, subnormal concentrations of fibrinogen to afibrinogenemic plasma greatly increased platelet adhesion. In addition, surface-bound fibrinogen's ability to mediate platelet adhesion was different, depending on the plasma concentration from which fibrinogen was adsorbed. These differences correlated with changes in the binding of a monoclonal antibody that binds to the Aalpha chain RGDS (572-575), suggesting alteration in the conformation or orientation of the adsorbed fibrinogen. Platelet adhesion to polystyrene preadsorbed with blood plasma thus appears to be a strongly bivariate function of adsorbed fibrinogen, responsive to both low amounts and altered states of the adsorbed molecule.     

Time-related hemolysis in stored shed mediastinal blood after cardiopulmonary bypass

Reinfusion of mediastinal shed blood during cardiopulmonary bypass reportedly reduces the need for homologous blood transfusion. Although the fragility of blood components is thought to be amplified by shear stress during cardiopulmonary bypass and processing, the time-related deterioration of red blood cells (RBCs) in stored shed blood has not been studied extensively. In this study, we examined time-related hemolysis in shed blood stored at different temperatures. We examined processed shed blood collected from 15 patients (11 men and 4 women; mean age?±?standard deviation, 71?±?9?years) during cardiopulmonary bypass. The shed blood was collected and stored at 20°C (group A) or 4°C (group B). Stored blood collected by venipuncture at the end of the surgery was used as a control. Damage was assessed by measuring its free hemoglobin (Hb) levels, using a photometric assay. The free Hb levels in blood samples from each group were tested at 0, 3, 6, 12, 24, 36, and 48?h after surgery. The free Hb levels (g/dl) at 0, 12, and 24?h were 0.03?±?0.01, 0.05?±?0.02*, and 0.06?±?0.02* in group A; 0.03?±?0.02, 0.04?±?0.03, and 0.05?±?0.02* in group B; and 0.01?±?0.01, 0.01?±?0.01, and 0.01?±?0.01 in the control group (*p?<?0.05 vs. 0?h after surgery). The free Hb levels in stored shed blood significantly increased after 12?h in group A (20°C) and increased after 24?h in group B (4°C), whereas in drawn blood, they did not significantly increase over the first 24?h. Compared to storage at 20°C, storage at 4°C suppresses the increase in the free Hb levels.     

C-reactive protein enhances the respiratory burst of neutrophils-induced by antineutrophil cytoplasmic antibody

Serum C-reactive protein (CRP) was one of the useful biomarkers for evaluating the disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Cumulating studies proved that CRP was pathogenic in a variety of diseases. In the current study, the in vitro effects of CRP to prime neutrophils for ANCA-induced respiratory burst were investigated with flow cytometry. Without TNF-α in the reactive system, ANCA could only induce a slight level of respiratory burst of neutrophils. CRP could enhance the respiratory burst of neutrophils induced by ANCA against myeloperoxidse [mean fluorescence intensity (MFI, 68.45 ± 16.87 vs. 58.65 ± 15.09, P < 0.05) or by ANCA against proteinase 3 (MFI, 79.51 ± 15.90 vs. 61.73 ± 14.89, P < 0.05). Although CRP (50 μg/mL, incubating for 30 min) could not active neutrophils alone, after incubation with neutrophils for 10 min, CRP (50 μg/mL) could increase the expression of membrane proteinase 3 of neutrophils (MFI, 365.27 ± 143.50 vs. 235.32 ± 124.65, P < 0.05). Heat-treated CRP could not enhance the levels of neutrophils respiratory burst induced by ANCA or increase the expression of membrane proteinase 3 of neutrophils. So CRP can prime neutrophils and enhance the respiratory burst induced by ANCA and might be pathogenic in AAV.     

溃疡性结肠炎患者外周血Tim-4 mRNA表达水平的变化及意义

目的 探究溃疡性结肠炎患者外周血Tim-4 mRNA的表达变化及临床意义。方法 选取2015年2月~2019年4月我院收治的溃疡性结肠炎患者38例作为观察组,另选取同期来我院体检的健康者30名作为对照组,采用荧光定量PCR测定外周血Tim-4 mRNA表达水平,比较两组Tim-4 mRNA、C反应蛋白（CRP）、红细胞沉降率（ESR）表达水平及观察组Tim-4 mRNA与CRP和ESR的相关性。结果 观察组Tim-4 mRNA、CRP、ESR表达均高于对照组[（0.79±0.37）vs（0.33±0.20）]、[（6.08±3.21）mg/L vs（0.99±0.87）mg/L]、[（19.12±12.13）mm/h vs（5.58±4.10）mm/h],差异有统计学意义（P＜0.05）。观察组外周血单个核细胞Tim-4 mRNA表达水平与CRP呈正相关（r=0.376,P＜0.05）,而与ESR无相关性（r=0.077,P＞0.05）。结论 溃疡性结肠炎患者Tim-4 mRNA异常上调,并与CRP密切相关,可能参与溃疡性结肠炎的致病过程。     

Complicated central effects of endothelin on blood pressure in rats

The role of endothelin (ENT) in the control of systemic blood pressure (BP) was examined in conscious rats. Intracerebroventricular (i.c.v.) administration of ENT (0.002 or 0.2 micrograms, i.e., 0.78 or 78 pmol/2 microliters 0.9% saline) to conscious rats had complicated effects on BP. A significant fall in BP occurred in the initial 2-4 min after administration; and then after recovery toward the control level, BP decreased again within 17 min, following which a constant rise in BP occurred. In addition to the changes in BP, 3 of 9 rats which received 0.2 micrograms lapsed into severe barrel rotation-like behavior only to die 6-8 min after i.c.v. injection. It was therefore assumed that ENT had central effects on BP regulation and motor activity.     

The role of alveolar macrophages in the pathogenesis of aspiration pneumonitis

RATIONALE: A robust TNFalpha response is seen following aspiration of food particles, while there is only a modest response to acid. OBJECTIVES: To examine the direct effects of acid and particulate components of gastric content on local and systemic macrophages. METHODS: Pathogen-free Long-Evans rats were injured with intratracheal instillation of normal saline (SHAM), low pH saline (ACID), small non-acidic particles (SNAP) or acidified particles (CASP). The alveolar (local) and the peritoneal (systemic) macrophages were harvested following the injury. MEASUREMENTS: We examined the phagocytic activity and TNFalpha release by the alveolar and peritoneal macrophages following in vivo and in vitro exposure to acid and/or food particles. TNFalpha release by macrophages was examined in response to E. coli lipopolysaccharide (LPS) stimulation. MAIN RESULTS: In rats injured with gastric particles, the number of the mononuclear cells was higher than those obtained from acid-injured animals. Both in vivo and in vitro exposure of the alveolar macrophages to SNAP resulted in increased production of TNFalpha within 8 hours. Transient exposure of the alveolar macrophages to a low pH environment suppressed LPS-induced production of this cytokine. Additionally, the phagocytic activity of the alveolar macrophages was inhibited by in vitro exposure of the macrophages to acid. CONCLUSIONS: We conclude that the two components of gastric aspiration have diverse effects on local and systemic macrophages. Although there is a synergy between acid and gastric particulate in producing an acute lung injury, the modulatory effects of these injuries on the alveolar macrophages are averse.     

GABA(A) receptor activation in the lateral parabrachial nucleus induces water and hypertonic NaCl intake

Inhibitory serotonergic and cholecystokinergic mechanisms in the lateral parabrachial nucleus and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. In the present study we investigated if the GABA(A) receptors in the lateral parabrachial nucleus are involved in the control of water, NaCl and food intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. Bilateral injections of muscimol (0.2 nmol/0.2 microl) into the lateral parabrachial nucleus strongly increased 0.3 M NaCl (20.3+/-7.2 vs. saline: 2.6+/-0.9 ml/180 min) without changing water intake induced by the treatment with the diuretic furosemide combined with low dose of the angiotensin converting enzyme inhibitor captopril s.c. In euhydrated and satiated rats, bilateral lateral parabrachial nucleus injections of muscimol (0.2 and 0.5 nmol/0.2 microl) induced 0.3 M NaCl intake (12.1+/-6.5 and 32.5+/-7.3 ml/180 min, respectively, vs. saline: 0.4+/-0.2 ml/180 min) and water intake (5.2+/-2.0 and 7.6+/-2.8 ml/180 min, respectively, vs. saline: 0.8+/-0.4 ml/180 min), but no food intake (2+/-0.4 g/240 min vs. saline: 1+/-0.3 g/240 min). Bilateral lateral parabrachial nucleus injections of the GABA(A) antagonist bicuculline (1.6 nmol/0.2 microl) abolished the effects of muscimol (0.5 nmol/0.2 microl) on 0.3 M NaCl and water intake. Muscimol (0.5 nmol/0.2 microl) into the lateral parabrachial nucleus also induced a slight ingestion of water (4.2+/-1.6 ml/240 min vs. saline: 1.1+/-0.3 ml/240 min) when only water was available, a long lasting (for at least 2 h) increase on mean arterial pressure (14+/-4 mm Hg, vs. saline: -1+/-1 mm Hg) and only a tendency to increase urinary volume and Na+ and K+ renal excretion. Therefore the activation of GABA(A) receptors in the lateral parabrachial nucleus induces strong NaCl intake, a small ingestion of water and pressor responses, without changes on food intake.     

Inflammation Markers in Individuals with History of Mental Health Crisis

The association between temporary emotional states and systemic inflammation has never been studied. We measured the levels of systemic inflammation markers in the peripheral blood of individuals with history of mental health crisis. Erythrocyte sedimentation rate (ESR), fibrinogen plasma level, high-sensitivity C-reactive protein (hs-CRP) serum level, and white blood cell count (WBCC) were measured for each individual during routine screening examinations. History of mental health crisis was self-reported. Individuals taking psychotropic agents were excluded. A total of 4,669 males and 2,576 females were included. One hundred forty-eight (2.0%) individuals (77 males and 71 females) reported a history of mental health crisis, and 7,097 (98.0%) individuals (4,592 males and 2,505 females) did not report a history of mental health crisis. After adjustment for multiple confounders which had been associated with elevated systemic inflammation markers, the levels of systemic inflammation markers were significantly higher among males with history of mental health crisis compared with males with no history of mental health crisis, including fibrinogen plasma levels (294+/-6.1 vs. 279+/-1.9 mg/dl, p=0.010), and WBCC (7.2+/-0.2 vs. 6.8+/-0.1 x 10(3) cells/dl, p=0.039). The levels of systemic inflammation markers were not significantly higher among females with history of mental health crisis compared with females with no history of mental health crisis. History of mental health crisis might be associated with systemic inflammation in males. This finding may be relevant to the pathophysiology of cardiovascular disease in males.     

Delivery of basic fibroblast growth factor with a pH-responsive, injectable hydrogel to improve angiogenesis in infarcted myocardium

A pH- and temperature-responsive, injectable hydrogel has been designed to take advantage of the acidic microenvironment of ischemic myocardium. This system can improve therapeutic angiogenesis methods by providing spatio-temporal control of angiogenic growth factor delivery. The pH- and temperature-responsive random copolymer, poly(N-isopropylacrylamide-co-propylacrylic acid-co-butyl acrylate) (p[NIPAAm-co-PAA-co-BA]), was synthesized by reversible addition fragmentation chain transfer polymerization. This polymer was a liquid at pH 7.4 and 37?°C but formed a physical gel at pH 6.8 and 37?°C. Retention of biotinylated basic fibroblast growth factor (bFGF) between 0 and 7 days after injection into infarcted rat myocardium was 10-fold higher with hydrogel delivery versus saline. Following 28 days of treatment in vivo, capillary and arteriolar densities were increased 30-40% by polymer?+?bFGF treatment versus saline?+?bFGF or polymer-only controls. Treatment with polymer?+?bFGF for 28 days resulted in a 2-fold improvement in relative blood flow to the infarct region versus day 0, whereas saline?+?bFGF or polymer-only had no effect. Fractional shortening determined by echocardiography was significantly higher following treatment with polymer?+?bFGF (30?±?1.4%) versus saline (25?±?1.2%) and polymer alone (25?±?1.8%). By responding to local changes in pH- and temperature in an animal model of ischemia, this hydrogel system provided sustained, local delivery of bFGF, improved angiogenesis, and achieved therapeutic effects in regional blood flow and cardiac function.