Arterial remodeling: the role of mitochondrial metabolism in vascular smooth muscle cells.

Arterial remodeling is a common pathological basis of cardiovascular diseases such as atherosclerosis, vascular restenosis, hypertension, pulmonary hypertension, aortic dissection, and aneurysm. Vascular smooth muscle cells (VSMCs) are not only the main cellular components in the middle layer of the arterial wall but also the main cells involved in arterial remodeling. Dedifferentiated VSMCs lose their contractile properties and are converted to a synthetic, secretory, proliferative, and migratory phenotype, playing key roles in the pathogenesis of arterial remodeling. As mitochondria are the main site of biological oxidation and energy transformation in eukaryotic cells, mitochondrial numbers and function are very important in maintaining the metabolic processes in VSMCs. Mitochondrial dysfunction and oxidative stress are novel triggers of the phenotypic transformation of VSMCs, leading to the onset and development of arterial remodeling. Therefore, pharmacological measures that alleviate mitochondrial dysfunction reverse arterial remodeling by ameliorating VSMCs metabolic dysfunction and phenotypic transformation, providing new options for the treatment of cardiovascular diseases related to arterial remodeling. This review summarizes the relationship between mitochondrial dysfunction and cardiovascular diseases associated with arterial remodeling and then discusses the potential mechanism by which mitochondrial dysfunction participates in pathological arterial remodeling. Furthermore, maintaining or improving mitochondrial function may be a new intervention strategy to prevent the progression of arterial remodeling.

Life history responses of the small brown planthopper Laodelphax striatellus to temperature change.

Temperature is a key environmental factor in ectotherms and influences many life history traits. In the present study, the nymphal development time, sex ratio and wing dimorphism of the small brown planthopper Laodelphax striatellus were examined under the conditions of constant temperatures, naturally varying temperatures (or different generations), and different temperatures combined with different photoperiod. The results showed that from 18 to 28 °C, the developmental time of nymphs was gradually shortened with the increase of temperature, whereas the high temperatures of 30 and 32 °C in the third to fifth instar nymphal stages and high summer temperature of 28.8 and 29.7 °C significantly delayed developmental time and resulted in higher mortality of nymphs. In all treatments, the developmental time was longer in females than males. The nymphs took significantly longer time to develop in the short daylength of 12 h than in longer daylengths of 13, 14, 15 and 16. Differences in developmental time were also found between wing morph, with long-winged individuals being significantly longer than the short-winged individuals at lower temperatures and significantly shorter than the short-winged individuals at higher temperatures. In all treatments, the sex ratio was stable, approaching 1:1, without being affected by temperature, generations and photoperiod. Photoperiod and temperature had significantly influence on the wing dimorphism. Long daylength combined with different temperatures resulted in significantly higher proportions of long-winged morph, whereas the low temperatures combined with the short daylengths in autumn and winter resulted in significantly high proportion of short-winged morph. This study broadens our understanding of the life-history traits of this planthopper and provides basic data for analyzing the effects of climate change on the planthopper reproduction.

Inheritance of key life-history traits in crosses between northern and southern populations of the cabbage beetle Colaphellus bowringi (Coleoptera: Chrysomelidae).

A southern population (S) from Xiushui County (29°1'N, 114°4'E) and a northern population (N) from Shenyang city (41°48'N, 123°23'E) of the cabbage beetle, Colaphellus bowringi vary greatly in their life-history traits, and may serve as an excellent model with which to study the inheritance of life-history traits. In the present study, we performed intraspecific hybridization using the two populations, comparing the key life-history traits (fecundity, development time, body weight, growth rate, and sexual size dimorphism (SDD)) between the two populations (S♀ × S♂ and N♀ × N♂) and their two hybrid populations (S♀ × N♂ and N♀ × S♂ populations) at 19, 22, 25, and 28°C. Our results showed that there were significant differences in life-history traits between the two parental populations, with the S population having a significantly higher fecundity, shorter larval development time, larger body weight, higher growth rate, and greater weight loss during metamorphosis than the N population at almost all temperatures. However, these life-history traits in the two hybrid populations were intermediate between those of their parents. The life-history traits in the S × N and N × S populations more closely resembled those of the maternal S population and N population, respectively, showing maternal effects. Weight loss for both sexes was highest in the S population, followed by the S × N, N × S, and N populations at all temperatures, suggesting that larger pupae lost more weight during metamorphosis. The changes in SSD with temperature were similar between the S and the S × N populations and between the N and the N × S populations, also suggesting a maternal effect. Overall, our results showed no drastic effect of hybridization on C. bowringi, being neither negative (hybrid inferiority) nor positive (heterosis). Rather, the phenotypes of hybrids were intermediate between the phenotypes of their parents.

Transcatheter Closure of Large Coronary-Cameral Fistulas Using the Patent Ductus Arteriosus Occluder or Amplatzer Vascular Plugs.

Transcatheter closure (TCC) has emerged as the first-line treatment for coronary artery fistulas. However, limited data exist regarding the long-term outcomes and technical aspects of this procedure. We aimed to report the long-term outcomes and technical aspects of TCC of large coronary-cameral fistulas (CCFs).All patients with large CCFs who underwent attempted TCC using the patent ductus arteriosus (PDA) occluder or Amplatzer vascular plug (AVP), from June 2002 to December 2017, were retrospectively reviewed. A total of 23 patients with large CCFs underwent attempted TCC using the PDA occluder or AVP. Most CCFs originated from the right coronary artery and drained predominantly into the right heart chamber. Procedural success was achieved in 21 (91.3%) patients. Devices were deployed using the arteriovenous loop in 15, transarterial approach in 4, and arterio-artery loop approach in 2 patients. Procedural complications included coronary spasm in one and side branch occlusion in one patient. Among these 21 patients with successful device implantation, follow-up angiograms or computed tomography angiograms were obtained in 14 (66.7%) patients at a median of 11.0 (range, 9.8-16.3) months. Late complications included thrombosis of residual fistula segment without myocardial infarction (MI) in one, coronary thrombosis resulting in MI in one, and recanalization necessitating re-intervention in one patient. No death and device embolization occurred.TCC of large CCFs using the PDA occluder or AVP is an effective therapy in anatomically suitable candidates, with favorable long-term outcomes. Given that potentially hazardous complications may occur late after the procedure, long-term periodic evaluation is mandatory.

Transcatheter Closure of Complex Post-Myocardial Infarction Left Ventricular Pseudoaneurysm and Unique Post-Traumatic Right Ventricular Pseudoaneurysm.

Ventricular pseudoaneurysm (PSA) is a rare, yet life-threatening complication of myocardial infarction, cardiac surgery, and transcatheter valve replacement. Although conventional surgery is the preferred treatment strategy, transcatheter closure has emerged as an effective alternative in selected candidates. In this report, we describe successful transcatheter closure of two unique cases of ventricular pseudoaneurysm (PSA): first, a complex post-myocardial infarction left ventricular PSA (LVPSA) with multi-communications, and second, a case of post-traumatic right ventricular PSA (RVPSA) following blunt chest injury caused by domestic violence.

Management and Outcome of Ventricular Septal Rupture Complicating Acute Myocardial Infarction: What Is New in the Era of Percutaneous Intervention?

BACKGROUND: Postinfarction ventricular septal rupture (PI-VSR) is a rare but devastating complication of acute myocardial infarction (AMI). Risk stratification in the acute phase is crucial for decision-making, and this study analyzed the risk factors for early mortality and the effects of various management options on the outcome of PI-VSR patients in the era of percutaneous intervention. METHODS: A total of 96 patients with PI-VSR were identified and divided into an acute-phase survivor group (n = 46, survived ≥2 weeks after admission) and a nonsurvivor group (n = 50, died within 2 weeks after admission). Percutaneous closure was considered in acute-phase survivors. Patients were followed up for a mean 47 (quartiles 15-71) months by clinical visit or telephone interview. RESULTS: The overall acute-phase (i.e., < 2 weeks after the diagnosis of PI-VSR) mortality rate was 52%. Female sex and Killip Class III-IV at admission were associated with an increased risk of acute-phase death. Of the 46 patients who survived ≥2 weeks, 20 underwent interventional occlusion and the procedure was successful in 19. Percutaneous closure in the acute-phase survivor group improved the immediate (21% in-hospital mortality rate) and long-term (53% mortality) outcomes. CONCLUSIONS: Patients with PI-VSR are at a high risk of acute-phase mortality. Female sex and severe cardiac dysfunction at admission are linked with a high rate of acute-phase deaths. Percutaneous closure in acute-phase survivors results in favorable short- and long-term benefits for PI-VSR patients.

Severe Mechanical Hemolysis After Transcatheter Closure of a Traumatic Ventricular Septal Defect Using the Amplatzer Atrial Septal Occluder.

Traumatic ventricular septal defect (VSD) resulting from chest trauma, either penetrating or blunt, is a relatively rare occurrence. Herein, we describe the case of a previously healthy 26-year-old man who presented with congestive heart failure, which was secondary to a large traumatic VSD following violent blunt chest trauma. The traumatic VSD was initially closed percutaneously using an Amplatzer atrial septal defect occluder. Post-device closure, however, the patient developed severe intravascular hemolysis refractory to medical treatment. The patient subsequently underwent surgical removal of the Amplatzer device, with concomitant VSD patch closure.

Asymmetric Dimethyl-L-Arginine is a Biomarker for Disease Stage and Follow-Up of Pulmonary Hypertension Associated with Congenital Heart Disease.

This study investigated the clinical value of plasma asymmetrical dimethyl-L-arginine (ADMA) level in the diagnosis, staging, and treatment response in congenital heart disease (CHD) patients with pulmonary arterial hypertension (PAH). This was a single-center prospective observational study in 80 CHD patients. Plasma ADMA levels were measured by enzyme-linked immunosorbent assay. Plasma ADMA levels were significantly increased in CHD patients with PAH compared with CHD patients without PAH (P < 0.01) and healthy controls (P < 0.001). In CHD patients with severe PAH, plasma ADMA levels were significantly higher in patients with Eisenmenger's syndrome (ES) than in patients exhibiting low pulmonary vascular resistance (P < 0.001). The plasma ADMA levels significantly correlated with pulmonary arterial pressure (P < 0.001) and pulmonary vascular resistance (P < 0.001) in patients with CHD. Severe PAH was identified by plasma ADMA with a cutoff value of 0.485 µmol/L (P < 0.001) with a specificity of 82.8 % and a sensitivity of 90 %. ES was identified by plasma ADMA with a cutoff value of 0.85 µmol/L (P < 0.05) with a specificity of 85.2 % and a sensitivity of 64.3 %. ADMA levels were significantly decreased after sildenafil therapy for 6 months compared with before therapy levels (0.91 ± 0.22 vs. 0.57 ± 0.30, P < 0.01). Our study suggests that plasma ADMA level may be used as a biomarker for identifying PAH in patients with CHD, assessing pulmonary vascular remodeling, and evaluating the treatment response of CHD patients with PAH to sildenafil.

Compounds from the Chinese black ant (Polyrhachis dives) and NMR behavior of the isomers with formamide group.

Two new dopamine derivatives divesamides A (1) and B (2), along with six known N-containing compounds were isolated from the Chinese black ant (Polyrhachis dives). Their structures were determined on the basis of spectroscopic methods. Compound 1 is a racemate, and chiral HPLC separation yielded a pair of antipodes. The absolute configuration of (+)-1 was assigned by a computational method. The double signals in the (1)H and (13)C NMR spectra of 2 that resulted from the presence of a formamide group were discussed. The T- and B-lymphocytes proliferation assay showed that 2 has moderate immunosuppressive activity toward T- and B-lymphocytes proliferation at a concentration of 20 µM.

Periplanosides A-C: new insect-derived dihydroisocoumarin glucosides from Periplaneta americana stimulating collagen production in human dermal fibroblasts.

Three new dihydroisocoumarin glucosides, termed periplanosides A-C (1-3), a known analog, pericanaside (4), and the other twenty known compounds were isolated from the insect Periplaneta americana. Their structures including absolute configurations were determined by comprehensive spectroscopic analyses and computational methods. Biological evaluation showed that compound 2 could stimulate collagen production by 31.2% in human dermal fibroblasts-adult (HDFa) at the concentration of 30 µM, indicating its significance in skin repair and ulcer.

Long-term outcomes of transcatheter closure of ruptured sinus valsalva aneurysms using patent ductus arteriosus occluders.

BACKGROUND: Transcatheter closure (TCC) of ruptured sinus of Valsalva aneurysm (RSVA) is an alternative strategy to surgery, but there is a lack of long-term outcome data. METHODS AND RESULTS: From 2004 to 2012, 17 patients (8 males, 9 females) were treated with patent ductus arteriosus (PDA) occluders by antegrade venous approach and were followed for 18-102 months. Of the 17 patients, transthoracic echocardiography revealed rupture of the right coronary sinus into the right ventricle in 9 and into the right atrium in 4, and noncoronary sinus rupture into the right ventricle in 3 and into the right atrium in 1. Most (10/17) were in New York Heart Association (NYHA) functional class III or IV. Aortography showed that the size of the defect was 7.71±2.84 mm (4-15 mm). TCC was attempted using PDA occluders 2-5 mm larger than the aortic end of the defects. The device sizes ranged from 8/6 to 18/16 mm (median, 10/8 mm). The procedure was successful in 16 (94.1%), and all of them had complete occlusion at discharge. On a median follow-up of 42 months, 14 patients were in NYHA class I and 2 were in class II, and there was no residual shunt, device embolization, infective endocarditis, or aortic regurgitation. CONCLUSIONS: TCC of RSVA is a safe and effective alternative to surgery with favorable long-term follow-up results.

Embolisation of perimembranous ventricular septal defect occluder and transcatheter retrieval.

AIMS: In this study, we aim to summarise our experience with techniques used for the transcatheter retrieval of embolised devices. METHODS: We retrospectively reviewed the transcatheter retrieval of embolised devices in seven patients who underwent an attempted transcatheter closure of perimembranous ventricular septal defects (PMVSDs) between October 2002 and October 2013. The incidence, the main causes for the device's embolisation, and the techniques for transcatheter retrieval of the embolised device are discussed. RESULTS: The incidence of device embolisation in our centre was 0.82% (seven embolisations in 852 device placements). The main causes for device embolisation included undersized devices and inadequate subaortic rims. Among the seven embolisations, six of the devices were retrieved percutaneously without mortality, while one was retrieved during surgery. Of these patients, five had a HeartR(TM) Membranous VSD occluder of their PMVSDs, and the remaining two had surgical PMVSD closures. CONCLUSIONS: Our approach to the transcatheter retrieval of the embolised devices is associated with good results.

The metabolism of trifluoperazine (TFP) exhibits atypical kinetic behavior in both human liver microsomes (HLMs) and monkey liver microsomes (MyLM).

Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie-Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 µM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 µM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.

Research progress on plant functional traits in agroecosystems.

Plant functional traits have an essential role in community formation and ecosystem function. Unlike natu-ral ecosystems, agroecosystems are affected by natural conditions and human management. Plant (i.e., crop)functional traits in the agroecosystems are thus shaped by natural and human selection. We reviewed the development of functional trait research, focusing on crop functional traits, research methods of agroecosystems based on traits, and the application of functional traits in agriculture. We then elaborated on the effect of domestication on crop trait trade-offs, the relationship between community functional structure and agroecosystem services, and the application of functional traits in weed management, cover cropping, and intercropping systems. Future research directions of crop functional traits include enriching the types of agroecosystems and crop species in studies, buil-ding up a crop functional trait database, and focusing on agroecosystem multifunctionality.

A multi-year dormancy strategy in a cabbage beetle population in southeastern China.

The life cycle of the cabbage beetle Colaphellus bowringi in southeastern China is complex due to four options for adult development: summer diapause, winter diapause, prolonged diapsuse, and nondiapause. However, detailed information on the multi-year emergence patterns of diapausing individuals in this beetle has not been documented. In this study, we monitored the adult emergence patterns of diapausing individuals and estimated the influence of the diapause-inducing temperature and photoperiod on the incidence of prolonged diapause under seminatural conditions for several years. The duration of diapause for adults collected from the vegetable fields in different years varied from several months to 5 years. Approximately 25.9%-29.2% of individuals showed prolonged diapause (emergence more than 1 year after entering diapause) over the 5 years of observation. Furthermore, regardless of insect age, the emergence of diapausing adults from the soil always occurred between mid-February and March in spring and between late August and mid-October in autumn, when the host plants were available. The influence of diapause-inducing temperatures (22, 25, and 28°C) combined with different photoperiods (L:D 12:12 h and L:D 14:10 h) on diapause duration was tested under seminatural conditions. Pairwise comparisons of diapause duration performed by the log-rank test revealed that the low temperature of 22°C combined with the long photoperiod of L:D 14:10 h induced the longest diapause duration, whereas the low temperature of 22°C combined with the short photoperiod of L:D 12:12 h induced the highest proportion of prolonged diapause. This study indicates that C. bowringi adopts a multi-year dormancy strategy to survive local environmental conditions and unpredictable risks.

Using aquatic animals as partners to increase yield and maintain soil nitrogen in the paddy ecosystems.

Whether species coculture can overcome the shortcomings of crop monoculture requires additional study. Here, we show how aquatic animals (i.e. carp, crabs, and softshell turtles) benefit paddy ecosystems when cocultured with rice. Three separate field experiments and three separate mesocosm experiments were conducted. Each experiment included a rice monoculture (RM) treatment and a rice-aquatic animal (RA) coculture treatment; RA included feed addition for aquatic animals. In the field experiments, rice yield was higher with RA than with RM, and RA also produced aquatic animal yields that averaged 0.52-2.57 t ha-1. Compared to their corresponding RMs, the three RAs had significantly higher apparent nitrogen (N)-use efficiency and lower weed infestation, while soil N contents were stable over time. Dietary reconstruction analysis based on 13C and 15N showed that 16.0-50.2% of aquatic animal foods were from naturally occurring organisms in the rice fields. Stable-isotope-labeling (13C) in the field experiments indicated that the organic matter decomposition rate was greater with RA than with RM. Isotope 15N labeling in the mesocosm experiments indicated that rice used 13.0-35.1% of the aquatic animal feed-N. All these results suggest that rice-aquatic animal coculture increases food production, increases N-use efficiency, and maintains soil N content by reducing weeds and promoting decomposition and complementary N use. Our study supports the view that adding species to monocultures may enhance agroecosystem functions.

Monoculture, where only one type of crop is grown to the exclusion of any other organism, is a pillar of modern agriculture. Yet this narrow focus disregards how complex inter-species interactions can increase crop yield and biodiversity while decreasing the need for fertilizers or pesticides. For example, many farmers across Asia introduce carps, crabs, turtles or other freshwater grazers into their rice paddies. This coculture approach yields promising results but remains poorly understood. In particular, it is unclear how these animals' behaviours and biological processes benefit the ecosystem. To examine these questions, Guo, Zhao et al. conducted three separate four-year field experiments; they compared rice plots inhabited by either carp, mitten crabs or Chinese softshell turtles with fields where these organisms were not present. With animals, the rice paddies had less weeds, better crop yields and steady levels of nitrogen (a natural fertiliser) in their soil. These ecosystems could breakdown organic matter faster, use it better and had a reduced need for added fertilizer. While animal feed was provided in the areas that were studied, carp, crabs and turtles obtained up to half their food from the field itself, eating weeds, algae and pests and therefore reducing competition for the crops. This work helps to understand the importance of species interactions, showing that diversifying monocultures may boost yields and make agriculture more sustainable.

Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization.

Arsenic trioxide (As2O3, ATO) has limited therapeutic benefit to treat solid tumors, whether used alone or in combination. Nanoscale drug delivery vehicles have great potential to overcome the limitation of the utility of ATO by rapid renal clearance and dose-limiting toxicity. Polymeric materials ranging from gelatin foam to synthetic polymers such as poly(vinyl alcohol) were developed for vascular embolic or chemoembolic applications. Recently, we have introduced sevelamer, an oral phosphate binder, as a new polymeric embolic for vascular interventional therapy. In this paper, sevelamer arsenite nanoparticle with a polygonal shape and a size of 50-300 nm, synthesized by anionic exchange from sevelamer chloride, was developed as a Pi-responsive bifunctional drug carrier and embolic agent for chemoembolization therapy. At the same arsenic dosage, sevelamer arsenite-induced severer tumor necrosis than ATO on the VX2 cancer model. In vitro tests evidenced that Pi deprivation by sevelamer could enhance ATO's anticancer effect. The results showed that ATO in Pi starvation reduced cell viability, induced more apoptosis, and diminished the mitochondrial membrane potential (Δψm) of cells since Pi starvation helps ATO to further down-regulate Bcl-2 expression, up-regulate Bax expression, enhance the activation of caspase-3 and increase the release of cytochrome c, and the production of excessive reactive oxygen species (ROS). Sevelamer arsenite not only plays a Pi-activated nano-drug delivery system but also integrated anticancer drug with embolic for interventional therapy. Therefore, our results presented a new administration route of ATO as well as an alternative chemoembolization therapy.

Intratumoral Pi deprivation benefits chemoembolization therapy via increased accumulation of intracellular doxorubicin.

It is a decade-long controversy that transarterial chemoembolization (TACE) has definite priority over transarterial embolization (TAE) in treating patients with hepatocellular carcinoma (HCC), since HCC cells are regularly resistant to chemotherapy by enhanced expression of proteins that confer drug resistance, and ABC transporters pump the intracellular drug out of the cell. We addressed this issue by modulating the chemo-environment. In an animal model, sevelamer, a polymeric phosphate binder, was introduced as an embolic agent to induce intratumoral inorganic phosphate (Pi) starvation, and trans-arterially co-delivered with doxorubicin (DOX). The new type of TACE was named as DOX-TASE. This Pi-starved environment enhanced DOX tumoral accumulation and retention, and DOX-TASE thereby induced more severe tumor necrosis than that induced by conventional TACE (C-TACE) and drug-eluting bead TACE (D-TACE) at the same dose. In vitro tests showed that Pi starvation increased the cellular accumulation of DOX in an irreversible manner and enhanced cytotoxicity and cell apoptosis by suppressing the expression of ABC transporters (P-glycoprotein (P-gp), BCRP, and MRP1) and the production of intracellular ATP. Our results are indicative of an alternative interventional therapy combining chemotherapy with embolization more effectively.

Evaluation of the safety and efficacy of transarterial sevelamer embolization in a rabbit liver cancer model: A challenge on the size rule for vascular occlusion.

As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 µm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE (n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques.

The effect of the fibrinolytic enzyme FIIa from Agkistrodon acutus venom on acute pulmonary thromboembolism.

AIM: To evaluate the effects of the fibrinolytic enzyme FII(a) from Agkistrodon acutus venom on acute pulmonary thromboembolism (APT) in animal models. METHODS: Both rabbit and dog APT models were used. For the rabbit APT model, the thrombi weight before and after administration was measured. Central venous pressure (CVP) and mean arterial pressure (MAP) were measured before and 15, 30, 60, and 120 min after the injection of the blood clot. Partial thromboplastin time (APTT), prothrombin time (PT), platelet count, and fibrinogen concentration were measured using auto analyzers. Plasminogen activity was measured based on chromogenic substrates. In the dog APT model, pulmonary blood flow was recorded using pulmonary angiography. RESULTS: Intravenous administration of FIIa (0.1-5.0 mg/kg) improved the APT-induced hemodynamic derangements and reduced thrombi weight. The angiography evidence also showed that the pulmonary emboli had almost disappeared after FII(a) infusion. FII(a) (0.1, 0.5, or 1.0 mg/kg) did not impair the coagulation pathways, although very high doses of FII(a) (5.0 mg/kg) could stimulate the production of plasminogen and result in impairment of the pathways. CONCLUSION: FII(a) could effectively protect against APT via degradation of thrombi with less activation of plasminogen, and may provide a novel fibrinolytic enzyme for targeting the main pathological processes of the disease.