Evaluation of the grafted ascending aorta with computed tomography. Complications caused by suture dehiscence

Patients who have undergone surgery on the thoracic aorta and placement of a synthetic tubular graft need close, long-term radiological follow-up, as they are at risk of not only complications and progression of the underlying disease (atherosclerosis, dissection, or cystic medial necrosis) but also complications of the procedure, notably suture dehiscence leading to formation of an aneurysm around the graft. In a series of 14 asymptomatic postoperative patients studied by computed tomography (CT), the authors detected leakage of contrast material around the graft in 6 patients, 2 of whom required re-operation to correct suture dehiscence. CT is a noninvasive and sensitive method of postoperative evaluation of patients who have undergone an aortic graft.     

The mouse alpha-globin locus regulatory element

We have identified and cloned the major alpha globin locus regulatory element in the mouse (m alpha RE). This element shows a high level of sequence homology to its human counterpart (HS -40) and lies between the same two exons of an upstream, widely expressed gene in both species. Footprinting and band shift studies of the core element show conservation of many (but not all) of the protein binding sites identified as functionally important in HS -40. The functional equivalence of the mouse element was shown by attaching it to a human alpha globin gene and examining expression in transgenic mice. Readily detectable levels of human alpha mRNA were produced in these mice but they were lower than the endogenous gene expression and did not show copy number dependence. These results suggest that sequences additional to this major regulatory element may be necessary to obtain complete regulation of the alpha globin genes in both species.     

Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus

We have investigated the role of plasminogen activator inhibitor 1 (PAI- 1) in the regulation of fibrinolysis using a model thrombus composed of thrombin-stimulated platelets, fibrin(ogen), plasminogen, and recombinant tissue-type plasminogen activator. Laser light scattering kinetic measurements showed that clot lysis was significantly delayed both by thrombin-stimulated platelets and their cell-free releasate. This delay in lysis was almost fully reversed by the addition of a PAI- 1-specific monoclonal antibody that blocks the ability of PAI-1 to inhibit plasminogen activators. Lysis half-times exhibited a linear dependence on the concentration of PAI-1 antigen present, as determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecylsulfate- polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting confirmed the presence of PAI-1 antigen in the platelet releasates. Scanning electron micrographs of the model thrombus components sampled late in lysis showed considerable unproteolyzed fibrin still attached to platelets. Immunogold cytochemistry detected large amounts of PAI-1 antigen in the partially lysed platelet-fibrin thrombi. This PAI-1 appeared to be bound to the fibrin network rather than to the platelet surface itself. We conclude that the residual clots observed late in lysis represent platelet-associated fibrin to which platelet-released PAI-1 has bound, rendering it less susceptible to degradation.     

Expression and effect of fibroblast growth factor 9 in bovine theca cells

Fibroblast growth factor 9 (FGF9) protein affects granulosa cell (GC) function but is mostly localized to theca cell (TC) and stromal cell of rat ovaries. The objectives of this study were to determine the 1) effects of FGF9 on TC steroidogenesis, gene expression, and cell proliferation; 2) mechanism of action of FGF9 on TCs; and 3) hormonal control of FGF9 mRNA expression in TCs. Bovine ovaries were collected from a local slaughterhouse and TCs were collected from large (8-22?mm) follicles and treated with various hormones in serum-free medium for 24 or 48?h. FGF9 caused a dose-dependent inhibition (P<0.05) of LH- and LH+IGF1-induced androstenedione and progesterone production. Also, FGF9 inhibited (P<0.05) LH+IGF1-induced expression of LHCGR, CYP11A1, and CYP17A1 mRNA (via real-time RT-PCR) in TCs. FGF9 had no effect (P>0.10) on STAR mRNA abundance. Furthermore, FGF9 inhibited dibutyryl cAMP-induced progesterone and androstenedione production in LH+IGF1-treated TCs. By contrast, FGF9 increased (P<0.05) the number of bovine TCs. Abundance of FGF9 mRNA in GCs and TCs was several-fold greater (P<0.05) in small (1-5?mm) vs large follicles. Tumor necrosis factor α and WNT5A increased (P<0.05) abundance of FGF9 mRNA in TCs. In summary, expression of FGF9 mRNA in TCs is developmentally and hormonally regulated. FGF9 may act as an autocrine regulator of ovarian function in cattle by slowing TC differentiation via inhibiting LH+IGF1 action via decreasing gonadotropin receptors and the cAMP signaling cascade while stimulating proliferation of TCs.     

Body fluid derived exosomes as a novel template for clinical diagnostics

Background

GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats.

Methods

Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight^-1 * day^-1) for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states). ATP synthesis in isolated mitochondria was determined by an enzymatic method.

Results

Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations.

Conclusions

We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.     

Follow-up of newborns treated with extracorporeal membrane oxygenation: a nationwide evaluation at 5 years of age

Introduction  

Extracorporeal membrane oxygenation (ECMO) is a supportive cardiopulmonary bypass technique for babies with acute reversible cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of five years, when they start primary school and major decisions for their school careers must be made.     

可吸收性珊瑚羟基磷灰石与人骨髓间充质干细胞诱导成骨细胞复合培养及碱性成纤维细胞生长因子的作用

目的:观察人骨髓间充质干细胞诱导的成骨细胞与珊瑚羟基磷灰石的相容性及碱性成纤维细胞生长因子的作用。方法:实验于2003-02/2005-10在大连医科大学附属第一医院中心实验室及上海第二医科大学完成。实验材料:①可吸收性珊瑚羟基磷灰石。②人骨髓间充质干细胞:取自单纯性骨囊肿行自体骨髓注射治疗的患者(年龄10～16岁,平均14.5岁),患者均知情同意。实验分组:使用含地塞米松、β甘油磷酸钠和抗坏血酸的条件培养基诱导骨髓间充质干细胞分化为成骨细胞,与珊瑚羟基磷灰石复合培养,分为实验组(RPMI1640完全培养液 成骨细胞 可吸收性珊瑚羟基磷灰石),促增殖组(完全培养液 成骨细胞 可吸收性珊瑚羟基磷灰石 10μg/L碱性成纤维细胞生长因子),正常培养组(完全培养液 同等数量的成骨细胞)。实验评估:①采用扫描电镜观察成骨细胞与可吸收性珊瑚羟基磷灰石复合培养6h,1,3,7d时细胞形态。②成骨细胞附着于材料表面后生长增殖特性:于接种后24h,各组均取6孔细胞用胰蛋白酶消化贴壁细胞,包括材料上贴附的细胞,计数孔内细胞数及平均细胞数,绘制细胞生长曲线。③成骨细胞分泌碱性磷酸酶活性的测定:于接种后1,3,5,7d采用酶联免疫监测仪测410nm波长的吸光度值,计算每1000个细胞的吸光度值。结果:①成骨细胞与可吸收性珊瑚羟基磷灰石复合培养后细胞形态:复合培养6h,细胞多为单层结构,形态多样,有数个突起;复合培养1d,成骨细胞附着于可吸收性珊瑚羟基磷灰石表面并深入到材料的孔隙内,与材料牢固结合,并在材料表面伸展,细胞表面可见大量微绒毛;复合培养7d,细胞数量增多,可见少量胞体表面及细胞间有颗粒状钙盐结晶沉积,细胞形态无明显差异。②成骨细胞附着于材料表面后生长增殖特性:实验组细胞接种后,随时间延长数量逐渐增加,仍可保持正常的分裂增殖速度,与正常培养组相比差异无显著性意义(P>0.05)。复合培养4,5,6,7d后促增殖组细胞附着载体后数量增长明显高于实验组、正常培养组,差异均有显著性意义(P<0.05)。③成骨细胞分泌碱性磷酸酶活性的测定:随着培养时间的增加,3组细胞碱性磷酸酶含量(每1000个细胞的平均吸光度值)均逐渐增高(以实验组为例,复合培养1,3,5,7d分别为0.0121±0.0014,0.0154±0.0013,0.0172±0.0012,0.0183±0.0015),差异无显著性意义(P>0.05)。结论:①人骨髓间充质干细胞诱导的成骨细胞可以在一定的生物载体上正常生长、增殖,并保持生理功能。②10μg/L碱性成纤维细胞生长因子可促进此过程中细胞增殖。     

Deep white matter infarction: correlation of MR imaging and histopathologic findings

Focal and confluent areas of periventricular hyperintensity have been reported on magnetic resonance (MR) images in 30% of patients over 60 years of age. In order to better understand the pathologic basis of these lesions, the authors studied 14 formalin-fixed brains with MR imaging. Multiple focal areas of hyperintensity were identified in the periventricular white matter in three of the 14 brains studied (21%). Subsequent gross and microscopic pathologic examination of both hyperintense and normal-intensity areas was performed on 87 tissue sections. The larger lesions were characterized centrally by necrosis, axonal loss, and demyelination and therefore represent true infarcts. Reactive astrocytes oriented along the degenerated axons were identified at distances of up to several centimeters from the central infarct. This is called isomorphic gliosis and is associated with increased intensity on T2-weighted images that increases the apparent size of the central lesion.     

Extracorporeal shockwave therapy compared with standard care for diabetic foot ulcer healing: An updated systematic review

Emerging evidence suggests that extracorporeal shockwave therapy (ESWT) may improve time to DFU healing. The aim of this review was to appraise the evidence on role of ESWT in DFU healing and impact of different ESWT doses. Databases were searched for trials comparing ESWT plus standard care to standard care alone in participants with DFUs. Search results were reviewed by two independent reviewers. The Cochrane Risk of Bias 2 tool and GRADE approach was used to assess bias and certainty. The primary outcome was time to healing. The search identified 345 papers after duplicates removed. Six trials consisting of 471 participants were included. There was unclear or high risk of bias across all domains. Time to ulcer healing was probably shorter in patients treated with ESWT compared with standard ulcer care alone (GRADE: low certainty). Patients treated with ESWT were more likely to heal at 20 weeks post-ESWT compared with those treated with standard ulcer care alone (GRADE: low certainty). There was significant heterogeneity. ESWT remains a promising new treatment but the translation into routine clinical practice is still limited by the low certainty of evidence surrounding its effectiveness, case selection and optimum dose.