Intraluminal thrombus thickness is not related to lower concentrations of trace elements in the wall of infrarenal abdominal aortic aneurysms

BackgroundIntraluminal thrombus (ILT) formation plays a significant role in the progression of infrarenal abdominal aortic aneurysms (AAA). Potentially, as ILT thickness increases the availability of trace elements in the aneurysm wall could decrease thereby leading to oxidative stress and intensifying pro-inflammatory cytokine generation.AimTo determine if thrombus thickness is related to the concentration of trace elements in the wall of infrarenal AAA.Patients and methodsThe concentrations of trace elements in the wall of the aneurysm sack and ILT obtained from 19 consecutive patients during surgery for infrarenal AAA were determined using emission spectrometry.ResultsThe concentrations of magnesium, zinc, manganese, and lead in the wall of AAA were significantly greater than in the ILT. Only the concentration of copper was lower in the AAA wall compared with the thrombus. The concentration of calcium, phosphorus, zinc, lead, copper, and magnesium increased with ILT thickness. The concentrations of no other trace elements in the wall of AAA were found to be related to the ILT thickness.ConclusionsIntraluminal thrombus thickness is not associated with a lower concentration of trace elements in the wall of the infrarenal AAA. Thus, the intraluminal thrombus participates in the progression of AAA by mechanisms independent of trace element supply to the wall of the aneurysm sack.     

Compressive mechanical properties of the intraluminal thrombus in abdominal aortic aneurysms and fibrin-based thrombus mimics

An intraluminal thrombus (ILT) forms in the majority of abdominal aortic aneurysms (AAAs). While the ILT has traditionally been perceived as a byproduct of aneurysmal disease, the mechanical environment within the ILT may contribute to the degeneration of the aortic wall by affecting biological events of cells embedded within the ILT. In this study, the drained secant modulus (E₅～modulus at 5% strain) of ILT specimens (luminal, medial, and abluminal) procured from elective open repair was measured and compared using unconfined compression. Five groups of fibrin-based thrombus mimics were also synthesized by mixing various combinations of fibrinogen, thrombin, and calcium. Drained secant moduli were compared to determine the effect of the components’ concentrations on mimic stiffness. The stiffness of mimics was also compared to the native ILT. Preliminary data on the water content of the ILT layers and mimics was measured. It was found that the abluminal layer (E₅=19.3 kPa) is stiffer than the medial (2.49 kPa) and luminal (1.54 kPa) layers, both of which are statistically similar. E₅ of the mimics (0.63, 0.22, 0.23, 0.87, and 2.54 kPa) is dependent on the concentration of all three components: E₅ decreases with a decrease in fibrinogen (60–20 and 20–15 mg/ml) and a decrease in thrombin (3–0.3 units/ml), and E₅ increases with a decrease in calcium (0.1–0.01 M). E₅ from two of the mimics were not statistically different than the medial and luminal layers of ILT. A thrombus mimic with similar biochemical components, structure, and mechanical properties as native ILT would provide an appropriate test medium for AAA mechanobiology studies.     

Effect of macroscale formation of intraluminal thrombus on blood flow in abdominal aortic aneurysms

A mathematical approach of blood flow within an abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) is presented. The macroscale formation of ILT is modeled as a growing porous medium with variable porosity and permeability according to values proposed in the literature. The model outlines the effect of a porous ILT on blood flow in AAAs. The numerical solution is obtained by employing a structured computational mesh of an idealized fusiform AAA geometry and applying the Galerkin weighted residual method in generalized curvilinear coordinates. Results on velocity and pressure fields of independent cases with and without ILT are presented and discussed. The vortices that develop within the aneurysmal cavity are studied and visualized as ILT becomes more condensed. From a mechanistic point of view, the reduction of bulge pressure, as ILT is thickening, supports the observation that ILT could protect the AAA from a possible rupture. The model also predicts a relocation of the maximum pressure region toward the zone proximal to the neck of the aneurysm. However, other mechanisms, such as the gradual wall weakening that usually accompany AAA and ILT formation, which are not included in this study, may offset this effect.     

The biaxial mechanical behaviour of abdominal aortic aneurysm intraluminal thrombus: Classification of morphology and the determination of layer and region specific properties

Intraluminal thrombus (ILT) is present in 75% of clinically-relevant abdominal aortic aneurysms (AAAs) yet, despite much research effort, its role in AAA biomechanics remains unclear. The aim of this work is to further evaluate the biomechanics of ILT and determine if different ILT morphologies have varying mechanical properties.     

Prediction of wall stress and oxygen flow in patient-specific abdominal aortic aneurysms: the role of intraluminal thrombus

Biomechanics and Modeling in Mechanobiology - In this study, the biomechanical role of intraluminal thrombus (ILT) in an abdominal aortic aneurysm (AAA) is investigated. The implications of ILT in...     

Interactions of F1 fractions from different strains of shape Paracoccidioides brasiliensis with human complement and with human neutrophils

The aim of our study was to investigate differences that might exist in the activation of the human complement system by F1 fractions from four different isolates of P. brasiliensis. Isolates HC and 18 (virulent), 265 (low virulence), and 9 (intermediate virulence, attenuated) were used; before the experiments, the virulence of isolates HC and 18 was recovered by in vivo passage in guinea pigs. The four isolates of the fungus were processed for purification of F1 fractions and the activation of the human complement system was studied by a kinetic method of hemolytic activity measurement. The incubation of F1 fractions in normal human serum resulted in different degrees of inhibition of the classical and alternative pathways. The F1 fraction from the low virulence isolate was more efficient than the F1 fraction from the virulent isolates (HC and 18). Previous absorption of sera with F1 fractions completely abolished classical pathway activation. Using zymosan, instead of F1, in the absorption process caused the same phenomenon, suggesting that natural or nonspecific antibodies are responsible for the classical pathway activation. The alternative pathway activation did not depend on these antibodies, but was enhanced by their presence. On the other hand, F1 fractions from virulent isolates were more active in the stimulation of neutrophil chemiluminescence compared with the F1 fraction from the low virulence isolate. Whole P. brasiliensis yeast cells (WYC) from two distinct strains, 18 and 265, showed the same patterns of response of those observed with the F1 fractions in the functions tested. These differences in the behavior of the F1 fractions as well as WYC in relation to human complement activation and consequently to neutrophil stimulation may correlate with the virulence of individual isolates and may contribute to the understanding of the inflammatory response generation and maintenance processes in paracoccidioidomycosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm

The regional distribution of wall thickness and failure properties in human abdominal aortic aneurysm (AAA) was explored. Three unruptured and one ruptured AAA were harvested as a whole during necropsy. Thickness was measured at about every 1.5 cm² wall surface area for an average of 100 measurement sites per AAA. Multiple longitudinally oriented rectangular specimen strips were cut at various locations from each AAA for a total of 48 strips. The strips were subjected to uniaxial extension until failure. Wall thickness varied regionally and between AAA from as low as 0.23 mm at a rupture site to 4.26 mm at a calcified site (median=1.48 mm). Wall thickness was slightly lower in the posterior and right regions. The failure tension (ultimate) of specimen strips varied regionally and between AAA from 5.5 N/cm close to a blister site in the ruptured AAA to 42.3 N/cm at the undilated neck of a 4 cm diameter unruptured AAA (median=14.8 N/cm). Failure stress (ultimate) varied from 33.6 to 235.1 N/cm² (median=126.6 N/cm²). There was no perceptible pattern in failure properties along the circumference. Failure tension of specimen strips at or close to blisters was mostly low. The rupture site in the ruptured aneurysm had the lowest recorded wall thickness of 0.23 mm with only slightly higher readings within a 1 cm radius. The failure tension of the specimen strip close to the rupture site was low (11.1 N/cm) compared to its neighborhood in the ruptured aneurysm.     

Model studies of the flow in abdominal aortic aneurysms during resting and exercise conditions

Pulsatile flow in abdominal aortic aneurysm (AAA) models has been examined in order to understand the hemodynamics that may contribute to growth of an AAA. The model studies were conducted by experiments (flow visualization and laser Doppler velocimetry) and by numerical simulation using physiologically realistic resting and exercise flow conditions. We characterize the flow for two AAA model shapes and sizes emulating early AAA development through moderate AAA growth (mean and peak Reynolds numbers of 362<Re_mean<1053 and 3308<Re_peak<5696 with Womersley parameter 16.4<<21.2). The results of our investigation indicate that AAA flow can be divided into three flow regimes: (i) Attached flow over the entire cycle in small AAAs at resting conditions, (ii) vortex formation and translation in moderate size AAAs at resting conditions, and (iii) vortex formation, translation and turbulence in moderate size AAAs under exercise conditions. The second two regimes are classified in the medical literature as disturbed flow conditions that have been correlated with atherogenesis as well as thrombogenesis. Thus, AAA disturbed hemodynamics may be a contributing factor to AAA growth by accelerating the degeneration of the arterial wall. Our investigation also concluded that vortex development is considerably weaker in an asymmetric AAA. Furthermore, turbulence was not observed in the asymmetric model. Finally, our investigation suggests a new mode of transition to turbulence: vortex ring instability and bursting to turbulence. The transition process depends on a combination of the pulsatile flow conditions and the tube cross-sectional area change.     

Thrombus aspiration in a series of patients with stable or unstable angina pectoris and lesion-site thrombus formation

Background. In acute myocardial infarction, thrombus aspiration prior to percutaneous coronary interventions (PCI) is often beneficial, but this approach has never been studied in patients without acute myocardial infarction. The aim of this retrospective study is to shed light on that topic based on our initial experience with manual thrombus aspiration in patients with stable or unstable angina pectoris and angiographic evidence of lesion-site thrombus. Methods. We assessed the feasibility (thrombus aspiration without predilatation) of this approach; in addition, we determined angiographic coronary flow and myocardial blush grade. Results. During 33 months in which a total of 4725 PCI were performed in our centre, manual thrombus aspiration was attempted in 14 patients with stable or unstable angina pectoris with angiographic evidence of thrombus. In nine of these 14 patients, the aspiration catheter could be advanced into the lesion without predilatation; in eight patients visible thrombus was obtained. The corrected TIMI frame count improved during the entire interventional procedure (21.1±11.2 vs. 12.8±5.9 frames; p=0.015). Myocardial blush grade, which overall improved during PCI (p<0.001), tended to show greater improvement in patients in whom thrombus aspiration could be achieved (1.6±0.9 vs. 0.7±0.5; p=0.06). Conclusions. Preliminary evidence suggests that manual thrombus aspiration may occasionally be considered in selected patients without acute myocardial infarction but with angiographic evidence of lesion-site thrombus. Nevertheless, prospective studies are required to clearly define the role of this approach in clinical practice. (Neth Heart J 2010;18:423-9.)     

Pravastatin increases the expression of the tissue inhibitor of matrix metalloproteinase-1 and the oncogene Bax in human aortic abdominal aneurysms

The effect of pravastatin on matrix metalloproteinase-9 (MMP-9) and the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 was studied in explants of human abdominal aortic aneurysm (AAA) obtained from 13 patients. The effect of pravastatin on the apoptotic status of human AAA explants was also examined. Total MMP-9 content did not differ in human AAA explants incubated in vitro in the presence or absence of pravastatin (10-6 mol/L) for 48 h. TIMP-1 levels were significantly increased in pravastatin-incubated AAA explants, but TIMP-2 production was not modified by pravastatin. Western blot experiments showed that, whereas Bax expression was increased in pravastatin-incubated AAA explants, the expression of Bcl-2 was not modified. On the other hand, the ratio of the expression of Bax to Bcl-2, an apoptotic index, was not modified by pravastatin. In the human AAA explants, the increase in Bax expression, but not the increase in TIMP-1 expression elicited by pravastatin, was reversed by L-mevalonate, a downstream HMG-CoA reductase metabolite, suggesting that the expression of Bax and TIMP-1 followed HMG-CoA reductase-dependent and -independent pathways, respectively. In conclusion, pravastatin increases both TIMP-1 and Bax expression in human AAA explants without changes in either MMP-9 activity or the apoptotic status.     

Mechanisms of portal vein tumour thrombus formation and development in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Portal vein tumour thrombus (PVTT) is considered one of most fearful complications of HCC and is strongly associated with a poor prognosis. Clarification of the mechanisms underlying the formation and development of PVTT is crucial for developing novel therapeutic strategies for HCC patients. Several studies have been made to uncover that tumour microenvironment, stem cells, abnormal gene expression and non-coding RNAs deregulation are associated with PVTT in patients with HCC in the last decade. However, the exact molecular mechanisms of PVTT in patients with HCC are still largely unknown. In the present review, we briefly summarized the molecular mechanisms underlying the formation and development of PVTT in HCC.     

Cell wall proteins in apoplastic fluids of Arabidopsis thaliana rosettes: identification by mass spectrometry and bioinformatics

Weakly bound cell wall proteins of Arabidopsis thaliana were identified using a proteomic and bioinformatic approach. An efficient protocol of extraction based on vacuum-infiltration of the tissues was developed. Several salts and a chelating agent were compared for their ability to extract cell wall proteins without releasing cytoplasmic contaminants. Of the 93 proteins that were identified, a large proportion (60%) was released by calcium chloride. From bioinformatics analysis, it may be predicted that most of them (87 out of 93) had a signal peptide, whereas only six originated from the cytoplasm. Among the putative apoplastic proteins, a high proportion (67 out of 87) had a basic pI. Numerous glycoside hydrolases and proteins with interacting domains were identified, in agreement with the expected role of the extracellular matrix in polysaccharide metabolism and recognition phenomena. Ten proteinases were also found as well as six proteins with unknown functions. Comparison of the cell wall proteome of rosettes with the previously published cell wall proteome of cell suspension cultures showed a high level of cell specificity, especially for the different members of several large multigenic families.     

A definite measure of occupancy exposures,seeking with non-radiolabeled in vivo 5-HT2A receptor occupancy and in vitro free fractions

Abstract

Unbound drug concentration in the brain would be the true exposure responsible for specific target occupancy. Drug exposures from preclinical are total concentrations of those over/underestimate the clinical dose projection. With the application of mass spectrometry, the current work proposes a definite measure of test drug exposures at serotonin-2A occupancy. The 5-HT_2A occupancy of antagonist in the rat brain has determined with non-radiolabeled tracer MDL-100,907 at an optimized dose (3?µg/kg) and treatment time (30?min). Equilibrium dialysis method determines the in vitro free fraction of the test antagonist in untreated rat brain homogenates and plasma. Drug-free fractions derived the unbound concentration (EC₅₀) in plasma and brain at test doses. The corresponding binding affinities (Ki) correlated with the unbound concentrations. Except for quetiapine, the ED₅₀ values in the dose-occupancy curves of antagonists are close and ranged from 1 to 3?mg/kg. The test drug quetiapine, eplivanserin, and clozapine showed high free fractions in plasma, but for ketanserin and olanzapine, the brain free fraction was higher. The correlation between the unbound EC₅₀ of the antagonists and corresponding Ki values was good (r²=0.828). The improved EC₅₀ accuracy with unbound concentrations was 10–250 folds in plasma and 10–170 folds in the brain. Further, the free fractions (f_{u, plasma}/f_{u, brain}) of test drugs had shown a correlation of ～83% with brain permeability (C_{total brain}/C_{total plasma}), a limiting factor. Thus, correlating the occupancy with unbound exposure and pharmacology would result in an accurate measurement of drug potency and optimizes in selecting the clinical dose.     

The effects of mass and age on standard metabolic rate in house crickets

Abstract. This study employed flow-through respirometry to measure the oxygen consumption rates (VO₂) of inactive male house crickets, Acheta domesticus L. (Orthoptera: Gryllidae), and to quantify the effects of body mass and adult age on standard metabolic rate (SMR). The Vo₂ increased with male body mass at a rate similar to that found in other studies of insect aerobic metabolism. The data reported in this study are combined with published data from other species of Orthoptera to generate a consensus allometric relationship between SMR and body mass for the Order. In general, the Orthoptera expend 2–3 times the energy per unit of body mass when inactive as compared to other arthropods, such as tenebrionid beetles, ants and spiders. Possible explanations for this substantial difference are discussed. By contrast to body mass, mass-specific Vo₂ decreased with increasing male age. This age effect has previously been reported for mammals but is not well established for insects, and its implications for the preference of cricket females for older mates is discussed. As energy expended for metabolic maintenance comprises 78% of a male cricket's daily energy budget, changes in SMR may have a substantial effect on the energy available for reproduction.     

闽江河口互花米草入侵湿地土壤无机硫赋存形态及其影响因素

选择闽江河口鳝鱼滩的互花米草湿地为研究对象,基于时空互代法,探讨了不同互花米草入侵年限（SA1： 5-6 年;SA2： 8-10 年;SA3： 12-14年）湿地土壤的无机硫赋存形态及其主要影响因素。结果表明,随着互花米草入侵年限的增加,湿地土壤的水溶性硫（H₂O-S）含量整体呈增加趋势,而吸附性硫（Adsorbed-S）、盐酸可溶性硫（HCl-Soluble-S）和盐酸挥发性硫（HCl-Volatile-S）含量整体均呈降低趋势。相对于SA1,SA2、SA3土壤的H₂O-S含量分别增加了10.02%和2.68%,而其Adsorbed-S、HCl-Soluble-S和HCl-Volatile-S含量分别降低了9.02%、10.95%、7.57%和15.61%、32.89%、15.14%。湿地土壤的总无机硫（TIS）含量、TIS储量及其占全硫（TS）储量的比例均随互花米草入侵年限的增加而降低,且这种降低主要取决于Adsorbed-S、HCl-Soluble-S和HCl-Volatile-S的贡献。此外,随着互花米草入侵年限的增加,影响湿地土壤不同形态无机硫赋存的环境因子均发生了较大变化,其中土壤颗粒组成、EC和pH的改变对无机硫赋存形态的影响最为明显。研究发现,随着互花米草入侵年限的增加以及该区对互花米草定期刈割活动的进行,湿地土壤无机硫养分可能将继续降低并逐渐趋于缺乏状态,长期而言将减弱互花米草自身的入侵能力。