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Sample records for mechanical thrombectomy combined

  1. Septic thrombophlebitis: percutaneous mechanical thrombectomy and thrombolytic therapies.

    PubMed

    Kar, Subrata; Webel, Richard

    2014-01-01

    Suppurative thrombophlebitis (Lemierre's syndrome) of the internal jugular vein is a rare and sometimes fatal complication. It commonly occurs from oropharyngeal infections, peripheral lines, complications from dental procedures, gingivitis, or central venous catheterizations. Empiric antibiotics are the initial treatment of choice followed by thrombolytics or surgical thrombectomy in refractory cases. We present a case of septic thrombophlebitis of the right internal jugular vein from a peripherally inserted central venous catheter. We also review the current percutaneous mechanical thrombectomy and thrombolytics therapies for such a rare disorder. Mechanical thrombectomy includes rotational thrombectomy or rheolytic therapies. Devices include the Amplatz thrombectomy device (Microvena), the Arrow-Trerotola Percutaneous thrombolytic device (Arrow), and the Cragg-Casteneda thrombolytic brush (Microtherapeutics). Rheolytic therapies include Angiojet, the Hydrolyzer, and the Oasis Thrombectomy System. Percutaneous mechanical thrombectomy techniques include rotational fragmentation, aspiration or suction thrombectomy, and hydrodynamic thrombectomy. AngioJet catheters may be used for percutaneous embolectomy in conjunction with pulse spray techniques, which instill thrombolytics locally. Thrombolytics include streptokinase, urokinase, and recombinant-tissue plasminogen activator. Mechanical thrombectomy combined with thrombolytics provide optimal treatment results secondary to their complementary effects. Therefore, patients who are refractory to standard medical therapy and considered poor surgical candidates may benefit from combined percutaneous mechanical thrombectomy with thrombolytics to achieve superior results if no contraindications exist for thrombolytics.

  2. Combined use of stent angioplasty and mechanical thrombectomy for acute tandem internal carotid and middle cerebral artery occlusion

    PubMed Central

    Gao, Feng; Joyce Lo, WaiTing; Sun, Xuan; Xu, XiaoTong

    2015-01-01

    Purpose Tandem internal carotid and middle cerebral artery occlusion carries a grave prognosis, with intravenous and intra-arterial thrombolytics having low efficacy. Currently, endovascular therapy is a promising means for treatment in which the proximal carotid lesion can be treated with angioplasty and stenting, whilst mechanical thrombectomy can be used for the treatment of the distal occlusion. Two approaches can be used – the antegrade (proximal-to-distal) approach or the retrograde (distal-to-proximal) approach, although there has not yet been any consensus on which is the better approach. Case report We present two patients with tandem occlusions, one treated using the antegrade and one using the retrograde approach, with different revascularization outcomes, despite having similar functional outcome on follow-up. Conclusion The combined use of stent angioplasty and mechanical thrombectomy can be used to treat tandem occlusions, and with procedural modifications, the antegrade approach may more easily achieve technical success. PMID:26246102

  3. Mechanical Thrombectomy of Hemodialysis Fistulae and Grafts

    SciTech Connect

    Patel, Aalpen A. Tuite, Catherine M.; Trerotola, Scott O.

    2005-12-15

    In this article, the authors present approaches they use in performing dialysis access intervention-in particular clotted access. It is not meant to be a comprehensive review of dialysis access management. At our institution, mechanical thrombectomy is the primary mode of treatment for clotted hemodialysis access. We will present physical examination findings in clotted dialysis access and contraindications for mechanical thrombectomy in dialysis access. We will also discuss the devices for mechanical thrombectomy and the techniques we use. Finally, we will discuss the difficulties encountered in these procedures and their solutions.

  4. [Percutaneous mechanical thrombectomy by means of rotational thrombectomy. Current study situation].

    PubMed

    Lichtenberg, Michael

    2010-10-01

    Acute and subacute ischemia of the limbs is still one of the most frequent reasons for amputation. There are different therapy options for reperfusion therapy including balloon thrombectomy, local lysis and rotational thrombectomy. Balloon thrombectomy, the standard surgical treatment, has proven an effective tool for the treatment of acute vascular obstructions. Nevertheless technical problems and complications can occur. Localized lysis on the other hand could be time - consuming and cost intensive, requiring intensive care monitoring and reangiograms. To achieve a successful result, at least one lower limb artery or major collateral has to be reopened to establish a sufficient situation. During the last years considerable advances have been made in endovascular interventions for the treatment of acute and subacute limb ischemia. The Straub Rotarex is one of the modern peripheral mechanical thrombectomy device, which combines mechanical thrombus fragmentation and removal of the material using negative pressure. There are different clinical and experimental studies, which have shown promising results in restoring blood flow to the occluded vessels. Studies mainly exist for the lower extremities. Some case reports showed effective treatment of the subclavian and axillary arteries. The advantages of the Rotarex system is simple handling, a short intervention time and the avoidance of lytic substances with consequent reduced risk of hemorrhage complications. In this article an overview about the main Rotarex studies is given which analyzed the results of percutaneous rotational thrombectomy in patients with subacute an acute thrombotic occlusions in peripheral arteries.

  5. Mechanical Thrombectomy of Iliocaval Thrombosis Using a Protective Expandable Sheath

    SciTech Connect

    Truong, Tri H.; Spuentrup, Elmar; Staatz, Gundula; Wildberger, Joachim E.; Schmitz-Rode, Thomas; Nolte-Ernsting, Claus C.A.; Guenther, Rolf W.; Haage, Patrick

    2004-09-15

    We report a case of successful percutaneous treatment of a subacute ilio-caval venous thrombosis in a 64-year-old female patient by using a novel combination of a rotatory fragmentation device (percutaneous thrombectomy device: PTD) and large wire basket (temporary Guenther basket filter) under temporary caval filter protection using an expandable sheath. Because the patient had multiple myeloma with increased risk for contrast media-induced renal failure, the therapeutic angiographic procedure was performed without iodinated contrast medium. Non-contrast-enhanced MR venography (high-resolution True FISP) confirmed the effective thrombus removal by the percutaneous mechanical thrombectomy procedure.

  6. Mechanical Thrombectomy for Early Treatment of Massive Pulmonary Embolism

    SciTech Connect

    Reekers, Jim A. Baarslag, Henk Jan; Koolen, Maria G.J.; Delden, Otto van; Beek, Edwin J.R. van

    2003-06-15

    We report our technique and results of percutaneous mechanical thrombectomy in a consecutive series of eight patients with massive PE. We also discuss the possible role of mechanical PE thrombectomy. Eight consecutive patients with acute massive PE, with or without hemodynamic impairment, were treated with mechanical thrombectomy. We used a modified 7-fr hydrolyzer catheter. The treatment was combined with systemic fibrinolysis. From the logistic and technical point we encountered no problems. All patients showed significant improvement while still in the angiography suite. There were no bleeding complications and no other events related to the procedure. Despite the clinical improvement, one patient died shortly after the procedure from cardiac failure. In all patients there was an acute increase in PO2 to normal values. Only a mean of about 50% of all local thrombus could be removed (range 30-80%). The mean PAP pre-intervention decreased only minimally from 42.5 mmHg to 36.3 mm Hg post-intervention (not significant). In three patients, the PAP continues to remain high at follow-up. The most important feature of mechanical thrombectomy for massive PE is the immediate improvement of the cardiac output, PO2, and clinical situation, overcoming the first critical hours after massive PE. The amount of thrombus reduction seems not to be an important parameter.

  7. Successful Recanalization of Acute Superior Mesenteric Artery Thromboembolic Occlusion by a Combination of Intraarterial Thrombolysis and Mechanical Thrombectomy with a Carotid Filter

    SciTech Connect

    Zelenak, Kamil; Sinak, Igor; Janik, Jan; Mikolajcik, Anton; Mistuna, Dusan

    2013-06-15

    Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease, and acute intestinal ischemia develops from the sudden decrease in perfusion to the intestines. The key to saving the patient's life is early diagnosis, and prompt revascularization of the SMA can prevent intestinal infarction and decrease the risk of bowel segment necrosis. Computed tomographic angiography may be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an 80-year-old man with a combination of intraarterial thrombolysis and mechanical thrombectomy with a carotid filter.

  8. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

    PubMed

    Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D

    2016-07-01

    Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.

  9. Stent-based mechanical thrombectomy in acute basilar artery occlusion.

    PubMed

    Cohen, José E; Leker, Ronen R; Moscovici, Samuel; Attia, Moshe; Itshayek, Eyal

    2011-12-01

    Stent-based mechanical thrombectomy was recently proposed as an effective alternative to other mechanical techniques to achieve recanalization of large-vessel embolic occlusions in the anterior circulation. To our knowledge, there are no reports of the use of this technique in acute basilar artery occlusion (ABAO). We present a patient with complete endovascular recanalization of ABAO using a stent-based thrombectomy technique. Advantages and limitations of this technique in the management of ABAO are discussed. The stent-thrombectomy technique is promising, and will need further evaluation in posterior circulation stroke.

  10. Superior Mesenteric Artery Embolism Treated with Percutaneous Mechanical Thrombectomy

    SciTech Connect

    Popovic, Peter Kuhelj, Dimitrij; Bunc, Matjaz

    2011-02-15

    A case of acute superior mesenteric artery embolism treated with percutaneous thrombus aspiration is described. A 63-year-old man with chronic atrial fibrillation was admitted to the hospital with progressive abdominal pain. Computed tomography angiography revealed an occlusion of the distal part of the superior mesenteric artery. The patient was effectively treated using transaxillary percutaneous mechanical thrombectomy using a 6F Aspirex thrombectomy catheter.

  11. Influence of Thrombus Age on the Mechanical Thrombectomy Efficacy of the Amplatz Thrombectomy Device In Vitro

    SciTech Connect

    Grimm, Jan Jahnke, Thomas; Muhle, Claus; Heller, Martin; Mueller-Huelsbeck, Stefan

    2003-06-15

    Purpose: To determine the efficacy of thrombectomy for the Amplatz Thrombectomy Device (ATD) according to the age of the thrombus. Methods: Thrombectomy was performed with the 7 Fr or 8 Fr ATD. Five-day-old or 8-day-old thrombi were made from porcine blood by clotting within silicone tubes to be used in a flow model. Emboli sizes, weight, remaining thrombus and activation time were evaluated. Results: The age of the thrombus had no influence on the activation time necessary for complete thrombolysis. A significant difference was found in the overall amount of embolization only with the 7 Fr device although a similar trend was shown with the 8 Fr device. The amount of embolized thrombotic material was higher for both devices if older thrombi (i.e., 8 days old) we reprocessed. The overall impression was that the 8 Fr device showed slightly better results (less remaining thrombus and embolization). Conclusion: A tendency toward higher amounts of embolization was observed if older thrombi were used in the model. Therefore the interventional radiologist should be aware of the potentially higher risk of peripheral embolization when performing mechanical thrombectomy(with the ATD) in older thrombotic occlusions, especially since the higher rate of embolization was mainly due to an increased proportion of larger embolic particles (1 mm), which are clinically more significant.

  12. Mechanical Thrombectomy of Occluded Hemodialysis Native Fistulas and Grafts Using a Hydrodynamic Thrombectomy Catheter: Preliminary Experience

    SciTech Connect

    Sahni, Vikram Kaniyur, Sunil; Malhotra, Anmol; Fan, Stanley; Blakeney, Charles; Fotheringham, Tim; Sobeh, Mohammed; Matson, Matthew

    2005-12-15

    The purpose of this study was to evaluate the efficacy and safety of a new hydrodynamic percutaneous thrombectomy catheter in the treatment of thrombosed hemodialysis fistulas and grafts. Twenty-two patients (median age: 47 years; range: 31-79 years) underwent mechanical thrombectomy for thrombosed hemodialysis fistulas or polytetrafluoroethylene (PTFE) grafts. In all cases, an Oasis hydrodynamic catheter was used. Five patients had native fistulas and 17 had PTFE grafts. Six patients required repeat procedures. All patients with native fistulas and 15 of the 17 with PTFE grafts also underwent angioplasty of the venous limb following the thrombectomy. Major outcome measures included technical success, clinical success, primary and secondary patency, and complication rates. Twenty-eight procedures were performed in total. The technical success rate was 100% and 90% and clinical success was 86% and 76% for native fistulas and grafts, respectively. The primary patency at 6 months was 50% and 59% for fistulas and grafts, respectively, and the secondary patency at 6 months was 75% and 70% for fistulas and grafts, respectively. Two patients died of unrelated causes during the follow-up period. The Oasis catheter is an effective mechanical device for the percutaneous treatment of thrombosed hemodialysis access. Our initial success rate showed that the technique is safe in the treatment of both native fistulas and grafts.

  13. A Novel Mechanical Thrombectomy Device for Retrieval of Intravascular Thrombus

    SciTech Connect

    Monsky, Wayne L.; Finitsis, Stephanos; Cicco, Dino De; Brock, John M.; Kucharczyk, John; Latchaw, Richard E.

    2011-04-15

    Purpose: Thrombotic and embolic vascular occlusion represents a leading cause of morbidity and mortality. Currently available thrombectomy devices have limitations, including difficulty removing organized thrombus and clot fragmentation with distal embolization. A novel mechanical thrombectomy device (MTD), designed to remove both hard and soft thrombus without trauma to the blood vessel, was tested in preclinical porcine models evaluating efficacy, safety, and ease of use. Materials and Methods: A total of 26 vessels in 14 pigs underwent mechanical thrombectomy with MTD. Thrombectomy was performed in nine superficial femoral arteries, eight subclavian arteries, five primary branches of the subclavian artery, lateral thoracic artery or the thyrocervical trunk, and four external carotids. Subacute organized fibrin-laden thrombus was injected into the arteries producing vascular occlusion. The MTD was then used for thrombectomy to restore patency and blood flow. Results: Intact thrombus was retrieved from 24 of 26 of the vessels with a single pass of the MTD, resulting in complete restoration of patency in 21 vessels and partial patency in 4 vessels. In 8 cases that used an early design, the embolic material fragmented during withdrawal from the access sheath. In 4 procedures that used an early design, the MTD failed to deploy fully and the embolus was not completely captured. No intraprocedural complications or vascular damage occurred. Conclusions: The present pilot studies demonstrate basic safety and efficacy of a novel MTD with design attributes suitable for retrieval of intact acute and organized chronic thrombus. The device has potential intracranial and peripheral utility.

  14. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications. PMID:27621948

  15. Percutaneous mechanical thrombectomy for treatment of acute femoropopliteal bypass occlusion.

    PubMed

    Lichtenberg, Michael; Käunicke, Matthias; Hailer, Birgit

    2012-01-01

    Acute and subacute ischemia of the legs in acute and subacute femoropopliteal bypass occlusion is a dramatic situation that endangers the survival of the limbs, depending on the severity of the ischemia. Different therapy options like percutaneous mechanical thrombectomy procedures, which include rotational thrombectomy, have become available in recent years, in addition to local lysis and surgical thrombectomy. Surgical thrombectomy using the Fogarty catheter technique, in particular, shows an increased incidence of perioperative complications but only small technical success rates in randomized trials. On the other hand, local lysis is associated with increased costs due to resource-consuming measures, such as intensive monitoring and repeat angiographies, in addition to bleeding complications. In the past, further development of the Straub Rotarex(®) system as an endovascular therapy option has demonstrated good success leading to amputation-free survival in multiple studies. At the same time, a low rate of complications with use has been documented. Most examinations have been conducted in the thigh. To date, there are little investigational data on its use in acutely and subacutely occluded femoropopliteal bypasses. In this paper, the current study-based significance of the Rotarex system for this indication is analyzed based on the existing literature and the authors' own experiences with 22 patients.

  16. Percutaneous mechanical thrombectomy for treatment of acute femoropopliteal bypass occlusion

    PubMed Central

    Lichtenberg, Michael; Käunicke, Matthias; Hailer, Birgit

    2012-01-01

    Acute and subacute ischemia of the legs in acute and subacute femoropopliteal bypass occlusion is a dramatic situation that endangers the survival of the limbs, depending on the severity of the ischemia. Different therapy options like percutaneous mechanical thrombectomy procedures, which include rotational thrombectomy, have become available in recent years, in addition to local lysis and surgical thrombectomy. Surgical thrombectomy using the Fogarty catheter technique, in particular, shows an increased incidence of perioperative complications but only small technical success rates in randomized trials. On the other hand, local lysis is associated with increased costs due to resource-consuming measures, such as intensive monitoring and repeat angiographies, in addition to bleeding complications. In the past, further development of the Straub Rotarex® system as an endovascular therapy option has demonstrated good success leading to amputation-free survival in multiple studies. At the same time, a low rate of complications with use has been documented. Most examinations have been conducted in the thigh. To date, there are little investigational data on its use in acutely and subacutely occluded femoropopliteal bypasses. In this paper, the current study-based significance of the Rotarex system for this indication is analyzed based on the existing literature and the authors’ own experiences with 22 patients. PMID:22661895

  17. Aspiration thrombectomy in concert with stent thrombectomy.

    PubMed

    Dumont, Travis M; Mokin, Maxim; Sorkin, Grant C; Levy, Elad I; Siddiqui, Adnan H

    2013-07-12

    In the SWIFT and TREVO 2 trials, aspiration thrombectomy was not able to be performed. Outside these studies, in post-market application, the interventionist can use aspiration thrombectomy in addition to stent device thrombectomy. This technique is described in detail in the present report. Combined aspiration/stentriever thrombectomy may improve recanalization efforts, simplify a second thrombectomy attempt if necessary and may limit distal embolization.

  18. Mechanical Thrombectomy in Patients with Deep Venous Thrombosis

    SciTech Connect

    Delomez, Maxence; Beregi, Jean-Paul; Willoteaux, Serge; Bauchart, Jean-Jacques; D'Othee, Bertrand Janne; Asseman, Philippe; Perez, Nessim; Thery, Claude

    2001-01-15

    Purpose: To report our experience with mechanical thrombectomy in proximal deep vein thrombosis (DVT).Methods: Eighteen patients with a mean ({+-} SD) age of 37.6 {+-} 16.1 years who presented with DVT in the iliac and femoral vein (n = 3), inferior vena cava (n = 5), or inferior vena cava and iliac vein (n = 10), were treated with the Amplatz Thrombectomy Device after insertion of a temporary caval filter.Results: Successful recanalization was achieved in 15 of 18 patients (83%). Overall, the percentage of thrombus removed was 66 {+-} 29%: 73 {+-} 30% at caval level and 55 {+-} 36% at iliofemoral level. Complementary interventions (seven patients) were balloon angioplasty (n = 2), angioplasty and stenting (n = 2), thrombo-aspiration alone (n = 1), thrombo-aspiration, balloon angioplasty, and permanent filter (n = 1), and permanent filter alone (n = 1). There was one in-hospital death. Follow-up was obtained at a mean of 29.6 months; three patients had died (two cancers, one myocardial infarction); 10 had no or minimal sequelae; one had post-phlebitic limb.Conclusion: Mechanical thrombectomy is a potential therapeutic option in patients presenting with proximal DVT.

  19. Evolution of endovascular mechanical thrombectomy for acute ischemic stroke

    PubMed Central

    Przybylowski, Colin J; Ding, Dale; Starke, Robert M; Durst, Christopher R; Crowley, R Webster; Liu, Kenneth C

    2014-01-01

    Acute ischemic stroke (AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, but key limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy. PMID:25405185

  20. Evolution of endovascular mechanical thrombectomy for acute ischemic stroke.

    PubMed

    Przybylowski, Colin J; Ding, Dale; Starke, Robert M; Durst, Christopher R; Crowley, R Webster; Liu, Kenneth C

    2014-11-16

    Acute ischemic stroke (AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, but key limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy.

  1. New Cerebral Microbleeds After Mechanical Thrombectomy for Large-Vessel Occlusion Strokes.

    PubMed

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Gonzalez, Nestor R; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Ali, Latisha K; Starkman, Sidney; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2015-11-01

    The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2*-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13-13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome.

  2. Mechanical Thrombectomy with Rotarex System in Buerger's Disease.

    PubMed

    Kilickesmez, Ozgur; Oguzkurt, Levent

    2015-01-01

    We report the case of a patient with 2-month history of chronic thromboembolism of the distal superficial femoral and popliteal arteries with diagnostic features of thromboangiitis obliterans disease. The occlusion could not be crossed by antegrade approach and was achieved retrogradely via dorsalis pedis artery puncture followed by mechanical removal of the thrombus with Rotarex system (Straub Medical AG, Wangs, Switzerland). Subsequent ballooon angioplasties achieved exclusion of the thrombus, and straight-line flow established to the foot through the anterior tibial Artery. The present case report demonstrates the success of mechanical thrombectomy in a patient with Buerger's vasculitis.

  3. Mechanical Thrombectomy with Rotarex System in Buerger's Disease

    PubMed Central

    Kilickesmez, Ozgur; Oguzkurt, Levent

    2015-01-01

    We report the case of a patient with 2-month history of chronic thromboembolism of the distal superficial femoral and popliteal arteries with diagnostic features of thromboangiitis obliterans disease. The occlusion could not be crossed by antegrade approach and was achieved retrogradely via dorsalis pedis artery puncture followed by mechanical removal of the thrombus with Rotarex system (Straub Medical AG, Wangs, Switzerland). Subsequent ballooon angioplasties achieved exclusion of the thrombus, and straight-line flow established to the foot through the anterior tibial Artery. The present case report demonstrates the success of mechanical thrombectomy in a patient with Buerger's vasculitis. PMID:25861548

  4. Comparison of a Balloon Guide Catheter and a Non-Balloon Guide Catheter for Mechanical Thrombectomy.

    PubMed

    Velasco, Aglaé; Buerke, Boris; Stracke, Christian P; Berkemeyer, Shoma; Mosimann, Pascal J; Schwindt, Wolfram; Alcázar, Pedro; Cnyrim, Christian; Niederstadt, Thomas; Chapot, René; Heindel, Walter

    2016-07-01

    Purpose To evaluate the effectiveness of mechanical thrombectomy with the use of a stent retriever in acute ischemic stroke, performed by using a balloon guide catheter or non-balloon guide catheter. Materials and Methods In accordance with the institutional review board approval obtained at the two participating institutions, retrospective analysis was performed in 183 consecutive patients treated between 2013 and 2014 for occlusions in the middle cerebral artery or carotid terminus by using a stent retriever with a balloon guide catheter (n = 102) at one center and a non-balloon guide catheter (n = 81) at the other center. Data on procedure duration, number of passes, angiographic findings, type of stent retriever used, and expertise of the operators were collected. Successful recanalization was defined as grade 3 or 2b modified Treatment in Cerebral Ischemia recanalization accomplished in up to three passes. Univariate and multivariate subgroup analyses were conducted to control for the confounding variables of prior thrombolysis, location of occlusion, and operator expertise. Results Successful recanalization with the balloon guide catheter was achieved in 89.2% of thrombectomies (91 of 102) versus 67.9% (55 of 81) achieved with the non-balloon guide catheter (P = .0004). The one-pass thrombectomy rate with the balloon guide catheter was significantly higher than for that with the non-balloon guide catheter (63.7% [65 of 102] vs 35.8% [29 of 81], respectively; P = .001). The procedure duration was significantly shorter by using the balloon guide catheter than the non-balloon guide catheter (median, 20.5 minutes vs 41.0 minutes, respectively; P < .0001). Conclusion The effectiveness of mechanical thrombectomy with stent retrievers in acute ischemic stroke in the anterior circulation in terms of angiographic results and procedure duration was improved when performed in combination with the balloon guide catheter. (©) RSNA, 2016.

  5. Massive intravascular hemolysis with mechanical rheolytic thrombectomy of a hemodialysis arteriovenous fistula.

    PubMed

    Carrera, Louis A; Reddy, Rachita; Pamoukian, Vicken N; Michelis, Michael F; DeVita, Maria V; Rosenstock, Jordan

    2013-01-01

    A 57-year-old man with chronic kidney disease stage 5 presented for ambulatory evaluation of his arteriovenous fistula. He underwent rheolytic thrombectomy with tissue plasminogen activator infusion, angioplasty, and brachial artery stenting under local sedation. His immediate postoperative course was complicated by hypotension, cardiac dysrhythmias and hyperkalemia requiring emergent hemodialysis, due to severe intravascular hemolysis. This case illustrates that mechanical thrombectomy can cause clinically significant intravascular hemolysis, thus careful postoperative monitoring is recommended.

  6. The blower: a useful tool to complete thrombectomy of the mechanical prosthetic valve.

    PubMed

    Aroussi, Aziz Alami; Sami, Ibrahim Mohamed; Leguerrier, Alain; Verhoye, Jean Phillippe

    2006-05-01

    Thrombectomy could be an excellent approach on one condition (ie, that all parts of the thrombus are removed). We propose to use a tool (ie, the blower) to complete thrombectomy of the prosthetic mechanical valve. The blower is a vaporizer that mixes air and heparinized saline with regulator of flow and proportion used in beating heart surgery. For thrombectomy, we have modified the air-water mixing part and intensity until we obtained a jet that enabled us to remove the micro thrombus that covered the prosthetic valve and surrounding tissues. The blower completely cleaned the prosthetic valve. With this tool, thrombectomy seems easier, more complete, and more reliable with the advantages of short cross-clamping time.

  7. Percutaneous mechanical thrombectomy of superior mesenteric artery embolism

    PubMed Central

    Kuhelj, Dimitrij; Kavcic, Pavel; Popovic, Peter

    2013-01-01

    Background The present series present three consecutive cases of successful percutaneous mechanical embolectomy in acute superior mesenteric artery ischemia. Superior mesenteric artery embolism is a rare abdominal emergency that commonly leads to bowel infarction and has a very high mortality rate. Prompt recognition and treatment are crucial for successful outcome. Endovascular therapeutic approach in patients with acute SMA embolism in median portion of its stem is proposed. Case reports. Three male patients had experienced a sudden abdominal pain and acute superior mesenteric artery embolism in median portion of its stem was revealed on computed tomography angiography. No signs of intestinal infarction were present. The decision for endovascular treatment was made in concordance with the surgeons. In one patient 6 French gauge Rotarex® device was used while in others 6 French gauge Aspirex® device were used. All patients experienced sudden relief of pain after the procedure with no signs of intestinal infarction. Minor procedural complication – rupture of a smaller branch of SMA during Aspirex® treatment was successfully managed by coiling while transient paralytic ileus presented in one patient resolved spontaneously. All three patients remained symptom-free with patent superior mesenteric artery during the follow-up period. Conclusions Percutaneous mechanical thrombectomy seems to be a rapid and effective treatment of acute superior mesenteric artery embolism in median portion of its stem in absence of bowel necrosis. Follow-up of our patients showed excellent short- and long-term results. PMID:24133388

  8. Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison

    PubMed Central

    Mokin, Maxim; Ionita, Ciprian N; Nagesh, Swetadri Vasan Setlur; Rudin, Stephen; Levy, Elad I; Siddiqui, Adnan H

    2014-01-01

    Background Artificial stroke models can be used for testing various thrombectomy devices. Objective To determine the value of combined stentriever–aspiration thrombectomy compared with the stentriever-alone approach. Methods We designed an in vitro model of the intracranial circulation with a focus on the middle cerebral artery (MCA) that closely resembles the human intracranial circulation. After introducing fresh clot in the MCA, we used conventional biplane angiography and microangiographic fluoroscopy to compare recanalization rates and occurrence of emboli in new, unaffected territory for thrombectomy approaches in which a stentriever (Solitaire flow restoration stentriever, Covidien) was used alone or in combination with continuous manual aspiration through a Navien catheter (Covidien). Results In a total of 22 experiments (11 for each approach), successful clot delivery to the MCA was achieved in all cases. Successful angiographic recanalization (thrombolysis in cerebral infarction score of 2b–3) was achieved more frequently with the combined stentriever–aspiration approach than with the stentriever-alone approach (in 10 vs 4 experiments, p=0.023). Emboli in new territory occurred in three experiments with the stentriever-alone approach, and none were seen with the combined approach (p=0.21). Conclusions The combined stentriever–aspiration approach to thrombectomy leads to better angiographic recanalization rates than use of the stentriever alone. Further experiments are needed to test the value of balloon-guide catheters and aspiration performed using other types of catheters and modes of aspiration. PMID:24789594

  9. Mechanical thrombectomy for acute stroke in childhood: how much does restricted diffusion matter?

    PubMed

    Ladner, Travis R; He, Lucy; Jordan, Lori C; Cooper, Calvin; Froehler, Michael T; Mocco, J

    2015-12-01

    Mechanical thrombectomy holds promise for children with large cerebral arterial occlusions, although there are few reports in this population. We report a case of retrievable stent-assisted mechanical thrombectomy in a 5-year-old with basilar artery occlusion, despite late presentation and extensive initial diffusion-weighted imaging (DWI) restriction. This resulted in successful Thrombolysis in Cerebral Infarction 2B reperfusion and excellent clinical outcome. At 6-week follow-up he was completely back to baseline with no residual deficits (pediatric stroke outcome measure=0, modified Rankin scale=0). At 3-month follow-up the patient has not had any recurrent stroke or concern for stroke-like symptoms. We review the literature on mechanical thrombectomy and DWI changes in acute stroke in early to middle childhood (<12 years old).

  10. Simple mechanical thrombectomy with intrapulmonary arterial thrombolysis in pulmonary thromboembolism: a small case series

    PubMed Central

    Ahmed, Khurshid; Munawar, Muhammad; Andina Munawar, Dian; Hartono, Beny

    2014-01-01

    Pulmonary thromboembolism (PTE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. We report a series of three patients who presented with acute and subacute submassive PTE. They were successfully treated by simple catheter-based mechanical thrombectomy and intrapulmonary arterial thrombolysis. Mechanical fragmentation and aspiration of thrombus was performed by commonly used J-wire, multi-purpose and Judkin Right guiding catheters and this obviated the need of specific thrombectomy devices. PMID:25593584

  11. The Rotarex® and Aspirex® mechanical thrombectomy devices.

    PubMed

    Horsch, Alexander D; van Oostayen, Jacques; Zeebregts, Clark J; Reijnen, Michel M P J

    2009-04-01

    The Rotarex® and Aspirex® are newly developed over-the-wire rotational thrombectomy catheters. These devices combine mechanical clot fragmentation and active negative-pressure removal of thrombus particles to prevent distal embolization. Several successful in vitro studies have been followed by the pursuit of different applications, and the device has been used successfully in the treatment of acute to chronic thrombo-embolic arterial occlusions in the limbs, hemodialysis access grafts, bypasses, stents, pulmonary artery occlusion, and inferior vena cava and aortohepatic bypass occlusions. Widespread clinical use so far has not been achieved, and more specific indications must be identified to extend the experience with the Rotarex® and Aspirex® devices.

  12. Developments in mechanical thrombectomy devices for the treatment of acute ischemic stroke.

    PubMed

    Mordasini, Pasquale; Gralla, Jan

    2016-01-01

    Several recent prospective randomized controlled trials of endovascular stroke therapy using latest generation thrombectomy devices, so called stent-retrievers, have shown significantly improved clinical outcome compared to the standard treatment with intra-venous thrombolysis using r-tPA alone. Despite some differences in inclusion criteria between these studies, all required non-invasive vessel imaging to proof occlusion of a major brain supplying vessel. Furthermore, in most studies additional imaging techniques were used to exclude patients with already established large cerebral infarction or unfavorable collateral or penumbral status. Patients with small infarct volume, severe neurological deficits and in whom thrombectomy can be initiated within the first 6 hours after symptom onset seem to benefit the most. Therefore, mechanical thrombectomy using stent-retrievers in addition to intra-venous thrombolysis is recommended for the treatment of acute ischemic stroke with proven major vessel occlusion in the anterior circulation.

  13. Mechanical Thrombectomy in Inferior Vena Cava Thrombosis After Caval Filter Placement: A Report of Three Cases

    SciTech Connect

    Poon, W.L.; Luk, S.H.; Yam, K.Y.; Lee, Anselm C.W.

    2002-10-15

    Inferior vena caval (IVC) filter thrombosis inpatients with contraindications to anticoagulant therapy is a difficult and challenging clinical problem. We report our experience in treating three such patients using a mechanical thrombectomy device, which resulted in rapid symptomatic relief until anticoagulant therapy could be safely introduced.

  14. Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. Methods We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. Results There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88–3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60–1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66–1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for

  15. Recanalization with stent-based mechanical thrombectomy in anterior circulation major ischemic stroke.

    PubMed

    Cohen, José E; Gomori, John M; Leker, Ronen R; Moscovici, Samuel; Ramirez-Denoriega, Fernando; Itshayek, Eyal

    2012-01-01

    We report the use of a self-expanding stent as a thrombectomy device in 17 patients (mean age 64.3 years) with major ischemic stroke secondary to large vessel occlusion. The patients had a mean National Institutes of Health Stroke Scale (NIHSS) score of >12, no cerebral hemorrhage or early infarction signs that affected more than 1/3 of the endangered territory, and an insufficient collateral supply. Within 8 hours of symptom onset, a stent (Solitaire; ev3, Irvine, CA, USA) was deployed across the occluded segment (endovascular bypass step). A repeat angiogram was performed to evaluate reconstituted flow. The guide-catheter balloon was inflated for proximal carotid occlusion. The partially deployed stent was slowly pulled back (mechanical thrombectomy step) under continuous aspiration. Complete recanalization (TIMI grade 3 flow) was achieved in fewer than 66 minutes after femoral access in all patients, with complete clot removal in a mean of two thrombectomy attempts. No stent was permanently implanted. Two patients developed asymptomatic hemorrhagic transformation (11.8%). Two patients presented post-recanalization parenchymal hemorrhage (11.8%); one suffered an intracerebral and intraventricular hemorrhage 12 hours after a successful and uneventful procedure and died 10 days later. The modified Rankin Scale scores were 0 to 2 in 15 patients (88.2%) and 3 in one patient (5.9%) at 1 month. In our preliminary experience, rapid stent-based mechanical thrombectomy has had unprecedented success.

  16. Twelve months outcome after percutaneous mechanical thrombectomy for treatment of acute femoropopliteal bypass occlusion.

    PubMed

    Lichtenberg, Michael; Stahlhoff, Wilhelm; Boese, Dirk; Hailer, Birgit

    2013-04-01

    Acute and subacute ischemia of the legs in acute and subacute femoropopliteal bypass occlusion is a dramatic situation that endangers the survival of the limbs, depending on the severity of the ischemia. Different therapy options like percutaneous mechanical thrombectomy procedures, which include rotational thrombectomy, have become available in recent years in addition to local lysis and surgical thrombectomy. Rotational thrombectomy with the Straub Rotarex(®) System as an endovascular therapy option has demonstrated promising results leading to amputation-free survival in multiple studies. We recently provided data of 22 patients with acute femoropopliteal bypass occlusion where we examined the feasibility of the Rotarex(®) System in this indication. A technical success rate of 82% was demonstrated. During a follow-up period of 6 months, no reinterventions in these patients had to be performed. We now provide patency rates in 21 patients of our study group after a follow-up period of 12 months. The average ABI after 12 months was 0.80 ± 0.1. One patient showed a hemodynamic restenosis in a Nitinolstent distal to the femoropopliteal bypass which was implanted in the index procedure. No reocclusion of the femoropopliteal bypasses occurred in all patients.

  17. Mechanical Thrombectomy of Iliac Vein Thrombosis in a Pig Model Using the Rotarex and Aspirex Catheters

    SciTech Connect

    Minko, P. Bücker, A.

    2013-06-08

    PurposeTo investigate the efficacy and safety of mechanical thrombectomy for iliac vein thrombosis using Rotarex and Aspirex catheters in a pig model.Materials and MethodsIliac vein thrombosis was induced in six pigs by means of an occlusion-balloon catheter and thrombin injection. The presence of thrombi was verified by digital subtraction angiography (DSA) and computed tomography (CT). Thrombectomy was performed using 6F and 8F Rotarex and 6F, 8F, and 10F Aspirex catheters (Straub Medical AG, Wangs, Switzerland). After intervention, DSA and CT were repeated to evaluate the efficacy of mechanical thrombectomy and to exclude local complications. In addition, pulmonary CT was performed to rule out pulmonary embolism. Finally, all pigs were killed, and iliac veins were dissected to perform macroscopic and histological examination.ResultsThrombus induction was successfully achieved in all animals as verified by DSA and CT. Subsequent thrombectomy lead to incomplete recanalization of the iliac veins with residual thrombi in all cases. However, the use of the 6F and 8F Rotarex catheters caused vessel perforation and retroperitoneal hemorrhage in all cases. Application of the Aspirex device caused one small transmural perforation in a vessel treated with a 10F Aspirex catheter, and this was only seen microscopically. Pulmonary embolism was detected in one animal treated with the Rotarex catheters, whereas no pulmonary emboli were seen in animals treated with the Aspirex catheters.ConclusionThe Aspirex catheter allowed subtotal and safe recanalization of iliac vein thrombosis. In contrast, the use of the Rotarex catheter caused macroscopically obvious vessel perforations in all cases.

  18. Efficacy and Safety of Thrombectomy Combined with Intracoronary Administration of Tirofiban in ST-segment Elevation Myocardial Infarction (STEMI).

    PubMed

    Gao, Lu; Cao, Zhenhua; Zhang, Hong

    2016-07-31

    BACKGROUND No/slow reflow gives rise to serious complications in STEMI patients undergoing PCI, and can lead to worse outcomes. Several measures are used to prevent no/slow reflow, including thrombus removal processes and intensive use of anticoagulant agents. Our study was designed to evaluate the efficacy and safety of thrombectomy and intracoronary administration of GPIIb/IIIa inhibitors in STEMI patients undergoing PPCI. MATERIAL AND METHODS We randomly assigned 240 STEMI patients into 3 groups. Before PPCI, patients in group A received thrombectomy and intracoronary administration of tirofiban. Patients in group B received thrombectomy, and patients in group C neither of these 2 treatments. Their demographic data and coronary angiography results were recorded. TIMI grade flow was used to evaluate the effect. After the follow-up, major adverse cardiac events were regarded as study endpoints in evaluating the safety of the combined therapy. RESULTS We found no significant differences among the 3 groups in demographic and clinical characteristics (p>0.05). Patients in group A had better TIMI grade classifications and ST-segment elevation (p=0.005), and lower incidence of no/slow reflow (p=0.031) and MACE. During 6-month follow-up, the MACE rate was lower in group A than in groups B and C (p=0.038). CONCLUSIONS The use of thrombectomy combined with intracoronary administration of tirofiban is relatively effective and safe in STEMI patients undergoing PPCI.

  19. Prospective, Multi-Centre, Single-Arm Study of Mechanical Thrombectomy using Solitaire FR in Acute Ischemic Stroke-STAR

    PubMed Central

    Pereira, Vitor M; Gralla, Jan; Davalos, Antoni; Bonafé, Alain; Castaño, Carlos; Chapot, Rene; Liebeskind, David S; Nogueira, Raul G; Arnold, Marcel; Sztajzel, Roman; Liebig, Thomas; Goyal, Mayank; Besselmann, Michael; Moreno, Alfredo; Schroth, Gerhard

    2013-01-01

    Background and Purpose Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire FR in patients with acute ischemic stroke. Methods STAR was an international, multicenter, prospective, single-arm study of Solitaire FR thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary endpoint was the revascularization rate (3TICI 2b) of the occluded vessel as determined by an independent core lab. The secondary endpoint was the rate of good functional outcome (defined as 90-day modified Rankin scale (mRS) 0–2). Results A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale (NIHSS) was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and/or procedure related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic. Conclusions In this single arm study, treatment with the Solitaire™ FR device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days. Clinical Trial Registration This study is registered with ClinicalTrials.gov, number NCT01327989. PMID:23908066

  20. Transjugular Intrahepatic Portosystemic Shunt, Mechanical Aspiration Thrombectomy, and Direct Thrombolysis in the Treatment of Acute Portal and Superior Mesenteric Vein Thrombosis

    SciTech Connect

    Ferro, Carlo; Rossi, Umberto G. Bovio, Giulio; Dahamane, M'Hamed; Centanaro, Monica

    2007-09-15

    A patient was admitted because of severe abdominal pain, anorexia, and intestinal bleeding. Contrast-enhanced multidetector computed tomography demonstrated acute portal and superior mesenteric vein thrombosis (PSMVT). The patient was treated percutaneously with transjugular intrahepatic portosystemic shunt (TIPS), mechanical aspiration thrombectomy, and direct thrombolysis, and 1 week after the procedure, complete patency of the portal and superior mesenteric veins was demonstrated. TIPS, mechanical aspiration thrombectomy, and direct thrombolysis together are promising endovascular techniques for the treatment of symptomatic acute PSMVT.

  1. Improvement of Stent Retriever Design and Efficacy of Mechanical Thrombectomy in a Flow Model

    SciTech Connect

    Wenger, Katharina; Nagl, Frank; Wagner, Marlies Berkefeld, Joachim

    2013-02-15

    In vitro experiments were performed to evaluate the efficacy of mechanical intracranial thrombectomy comparing the newly developed Aperio stent retriever and standard devices for stroke treatment. The Aperio (A), with an increased working length of 4 cm and a special cell design for capturing and withholding clots, was compared to three benchmark devices: the Solitaire retrievable stent (B), the Merci X6 (C), and the Merci L5 retriever (D). In a vascular glass model with pulsatile flow, reminiscent of the M1 segment of the middle cerebral artery, we repeatedly induced occlusion by generating thrombi via a modified Chandler loop system. The numbers of recanalization attempts, peripheral embolizations, and recanalizations at the site of occlusion were recorded during 10 retrieval experiments with each device. Eleven devices were able to remove the blood clots from the occluded branch. In 34 of 40 experiments, restoration of flow was obtained in 1-3 attempts. The main differences between the study devices were observed in terms of clot withholding and fragmentation during retrieval. Although there was only one fragmentation recorded for device A, disengagement of the whole clot or peripheral embolization of fragments occurred more frequently (5-7 times) with devices B, C, and D. In a vascular model, the design of device A was best at capturing and withholding thrombi during retrieval. Further study will be necessary to see whether this holds true in clinical applications.

  2. Acute Pancreatitis after Percutaneous Mechanical Thrombectomy: Case Report and Review of the Literature

    SciTech Connect

    Hershberger, Richard C. Bornak, Arash; Aulivola, Bernadette; Mannava, Krishna

    2011-02-15

    Purpose: We describe a case of severe acute pancreatitis after percutaneous mechanical thrombectomy (PMT) and review the literature for the occurrence of this complication. Materials and Methods: A 53-year-old man with a history of bilateral external iliac artery stent placement sought care for acute onset of lifestyle-limiting left claudication. Angiography confirmed left external iliac stent occlusion, and PMT with the AngioJet Xpeedior catheter (Possis Medical, Minneapolis MN) was performed. Results: After PMT of the occluded external iliac artery, a residual in-stent stenosis required the placement of a second iliac stent. The procedure was complicated by severe acute pancreatitis. Other causes of pancreatitis were eliminated during the patient's hospital stay. A literature review revealed nine cases of acute pancreatitis after PMT. Conclusion: Although rare, pancreatitis can be a devastating complication of PMT. The development of pancreatitis seems to be related to the products of extensive hemolysis triggering an inflammatory process. To prevent this complication, we recommend that close attention be paid to the duration and extent of PMT, thereby avoiding extensive hemolysis and subsequent complications.

  3. The use of mechanical thrombectomy in the treatment of basilar artery occlusion--case report.

    PubMed

    Knap, Daniel; Honkowicz, Maciej; Kirmes, Tomasz; Koroński, Marcin; Kysiak, Marzena; Bukański, Mateusz; Sieroń, Dominik; Dymon, Izabela; Baron, Jan

    2015-01-01

    Occlusion of the basilar artery (BAO) is a rare cause of stroke, making up approximately 1% of all cases. Ischemic stroke within the basilar artery is associated with serious complications and high mortality (75-91%). BAO may occur initially in the form of mild prodromal symptoms with neurological disorders, the consequences of which can lead to death. For these reasons, BAO requires rapid diagnosis and treatment. We report the case of a 26-year-old man who suffered basilar artery occlusion and was treated with endovascular therapy. The patient was disqualified from intra-venous thrombolysis and endovascular treatment due to exceeding the therapeutic time window. Despite this, due to the location of ischemia and age of the patient, it was decided to proceed with a mechanical thrombectomy (TM). Vessel patency was restored using the Solitaire FR stent. Treatment continued with antiplatelet therapy. Despite a significant overshoot of the time window the procedure was successful and complete recanalization was achieved. During hospitalization, significant neurological symptom reductions were observed. There is no accurate data on which method of treatment of ischemic stroke is best for BAO. Expectations about the effectiveness of endovascular techniques are high.

  4. Development of a recalcitrant, large clot burden, bifurcation occlusion model for mechanical thrombectomy.

    PubMed

    Srinivasan, Visish M; Chen, Stephen R; Camstra, Kevin M; Chintalapani, Gouthami; Kan, Peter

    2017-04-01

    OBJECTIVE Stroke is a major cause of disability and death in adults. Several large randomized clinical trials have shown the significant benefit of mechanical thrombectomy with modern stent retrievers in the treatment of large-vessel occlusions. However, large clots located at bifurcations remain challenging to treat. An in vivo model of these recalcitrant clots needs to be developed to test future generations of devices. METHODS Autologous blood was drawn from anesthetized swine via a femoral sheath. Blood was then mixed with thrombin, calcium chloride, and saline, and injected into silicone tubing to form cylindrical clots in the standard fashion. Matured clots were then delivered in an unfragmented fashion directly into the distal extracranial vasculature, at branch points where vessel sizes mimic the human middle cerebral artery, by using Penumbra aspiration tubing and the Penumbra ACE68 reperfusion catheter. RESULTS A total of 5 adult swine were used to develop the model. The techniques evolved during experiments in the first 3 animals, and the last 2 were used to establish the final model. In these 2 swine, a total of 8 autologous clots, 15-20 mm, were injected directly into 8 distal extracranial vessels at branch points to mimic a bifurcation occlusion in a human. All clots were delivered directly at a distal bifurcation or trifurcation in an unfragmented fashion to cause an occlusion. Ten revascularization attempts were made, and none of the branch-point occlusions were fully revascularized on the first attempt. CONCLUSIONS Using novel large-bore distal access catheters, large unfragmented clots can be delivered into distal extracranial vessels in a swine occlusion model. The model mimics the clinical situation of a recalcitrant bifurcation occlusion and will be valuable in the study of next-generation stroke devices and in training settings.

  5. Acute thromboembolic occlusion of the superior mesenteric artery following covered stent occlusion in the superior mesenteric artery: endovascular therapy using mechanical rotational thrombectomy.

    PubMed

    Goltz, Jan P; Petritsch, Bernhard; Spor, Leo; Hahn, Dietbert; Kickuth, Ralph

    2012-09-01

    Acute thromboembolic occlusion of the superior mesenteric artery is a rare and often fatal condition in which surgery represents the golden standard in therapy. We present a case in which a patient was treated with covered stent implantation for acute bleeding from the superior mesenteric artery following pancreatic resection, radiation, and embolization of a hepatic artery pseudoaneurysm. Some weeks later clinical signs were suggestive of acute thromboembolic occlusion of the superior mesenteric artery and digital subtraction angiography showed occlusion of the previously implanted covered stents. The patient was successfully treated transfemorally with percutaneous mechanical instent thrombectomy using a 6F Rotarex® catheter. We conclude that in selected cases percutaneous mechanical thrombectomy may represent a minimally-invasive alternative to open surgical thrombectomy for treatment of acute thromboembolic occlusion of the superior mesenteric artery.

  6. Efficacy of Balloon-Guiding Catheter for Mechanical Thrombectomy in Patients with Anterior Circulation Ischemic Stroke

    PubMed Central

    Oh, Jae-Sang; Yoon, Seok-Mann; Shim, Jai-Joon; Doh, Jae-Won; Bae, Hack-Gun; Lee, Kyeong-Seok

    2017-01-01

    Objective To evaluate the efficacy of balloon guiding catheter (BGC) during thrombectomy in anterior circulation ischemic stroke. Methods Sixty-two patients with acute anterior circulation ischemic stroke were treated with thrombectomy using a Solitaire stent from 2011 to 2016. Patients were divided into the BGC group (n=24, 39%) and the non-BGC group (n=38, 61%). The number of retrievals, procedure time, thrombolysis in cerebral infarction (TICI) grade, presence of distal emboli, and clinical outcomes at 3 months were evaluated. Results Successful recanalization was more frequent in BGC than in non-BGC (83% vs. 66%, p=0.13). Distal emboli occurred less in BGC than in non-BGC (23.1% vs. 57.1%, p=0.02). Good clinical outcome was more frequent in BGC than in non-BGC (50% vs. 16%, p=0.03). The multivariate analysis showed that use of BGC was the only independent predictor of good clinical outcome (odds ratio, 5.19: 95% confidence interval, 1.07–25.11). More patients in BGC were successfully recanalized in internal carotid artery (ICA) occlusion with small retrieval numbers (<3) than those in non-BGC (70% vs. 24%, p=0.005). In successfully recanalized ICA occlusion, distal emboli did not occur in BGC, whereas nine patients had distal emboli in non-BGC (0% vs. 75%, p=0.001) and good clinical outcome was superior in BGC than in non-BGC (55.6% vs. 8.3%, p=0.01). Conclusion A BGC significantly reduces the number of retrievals and the occurrence of distal emboli, thereby resulting in better clinical outcomes in patients with anterior circulation ischemic stroke, particularly with ICA occlusion. PMID:28264235

  7. A Comparison between Mechanical Thrombectomy and Intra-arterial Fibrinolysis in Acute Basilar Artery Occlusion: Single Center Experiences

    PubMed Central

    Jung, Seunguk; Jung, Cheolkyu; Bae, Yun Jung; Choi, Byung Se; Kim, Jae Hyoung; Lee, Sang-Hwa; Chang, Jun Young; Kim, Beom Joon; Han, Moon-Ku; Bae, Hee-Joon; Kwon, Bae Ju; Cha, Sang-Hoon

    2016-01-01

    Background and Purpose Recent advances in intra-arterial techniques and thrombectomy devices lead to high rate of recanalization. However, little is known regarding the effect of the evolvement of endovascular revascularization therapy (ERT) in acute basilar artery occlusion (BAO). We compared the outcome of endovascular mechanical thrombectomy (EMT) versus intra-arterial fibrinolysis (IAF)-based ERT in patients with acute BAO. Methods After retrospectively reviewed a registry of consecutive patients with acute ischemic stroke who underwent ERT from September 2003 to February 2015, 57 patients with acute BAO within 12 hours from stroke onset were enrolled. They were categorized as an IAF group (n=24) and EMT group (n=33) according to the primary technical option. We compared the procedural and clinical outcomes between the groups. Results The time from groin puncture to recanalization was significantly shorter in the EMT group than in the IAF group (48.5 [25.3 to 87.8] vs. 92 [44 to 179] minutes; P=0.02) The rate of complete recanalization was significantly higher in the EMT group than in the IAF group (87.9% vs 41.7%; P<0.01). The good outcome of the modified Rankin Scale score≤2 at 3 months was more frequent in the EMT group than in the IAF group, but it was not statistically significant (39.4% vs 16.7%; P=0.06). Conclusions EMT-based ERT in patients with acute BAO is superior to IAF-based ERT in terms of the reduction of time from groin puncture to recanalization and the improvement of the rate of complete recanalization. PMID:27283281

  8. Initial clinical use of a novel mechanical thrombectomy device, XCOIL™, in hemodialysis graft and fistula declot procedures

    PubMed Central

    Monsky, Wayne L.; Latchaw, Richard E.

    2016-01-01

    PURPOSE We aimed to evaluate the safety and effectiveness of a novel catheter-based mechanical thrombectomy device, XCOIL™, as a first line therapy to restore patency of thrombosed dialysis grafts and fistulae. METHODS In 2010, 18 consecutive/sequential patients (11 male, 7 female; median age, 52 years; age range, 32–69 years) with occluded arteriovenous grafts (n=15) or fistulae (n=3) were treated with XCOIL™ (NexGen Medical Systems Inc.) without adjunctive thrombolytic drugs. XCOIL™ was advanced distal to the thrombus within the outflow vein as well as distal to the arterial inflow platelet thrombin plug, using a 4F angiographic catheter. The percentage of thrombus cleared, primary patency, procedure time, and XCOIL™ performance were documented. RESULTS Thrombosis occurred 1–30 days prior to the procedure. Thrombosed segments of graft/fistula measured 10–50 cm. Pre- and postprocedure angiography demonstrated that in 15 of 18 cases (83%) XCOIL™ removed 80%–100% of the venous outflow thrombus. In 11 of 14 cases (79%), the platelet thrombin plug was also removed. Thrombectomy procedure time averaged 8 min, with one to three passes with the XCOIL™ required. No evidence of distal embolization or graft/vessel injury was found on angiography following clot removal. In four cases in whom patency was not restored with XCOIL™, subsequent use of other clot removal devices also failed to restore patency. In one case with severe venous stenosis, the device failed to deploy and the thrombus was not captured. No intraprocedural complications related to XCOIL™ use occurred. CONCLUSION XCOIL™ is an effective and safe first-line therapy option for the treatment of thrombosed hemodialysis grafts/fistulae. Rapid removal of intact thrombus and platelet thrombin plug can be achieved without adjunctive thrombolytics. PMID:27015445

  9. Assessment of factors associated with prominent changes in blood pressure during an early mobilization protocol for patients with acute ischemic stroke after mechanical thrombectomy

    PubMed Central

    YAGI, Maiko; WATANABE, Sato; KONDO, Chika; KAIHOKO, Yukiko; ENDO, Koji; MIYASHITA, Fumio; TAKADA, Tatsuro; UEDA, Toshihiro

    2016-01-01

    Objective: To assess factors associated with changes in blood pressure during early mobilization protocol for patients with acute ischemic stroke who were treated with mechanical thrombectomy. Design: Retrospective observational study. Method: We analyzed patients with acute ischemic stroke who were treated with mechanical thrombectomy (MT group, n=60) and patients who received conservative medical management (control group, n=60) matched by age and National Institute Health of Stroke Score at admission from April 2009 to July 2014. The proportion of patients with prominent blood pressure change during an early mobilization protocol was compared between the MT group and control group. Factors associated with prominent blood pressure change were also analyzed using multivariable logistic regression analysis. Result: The deviation in blood pressure response was much more significant in the MT than control group (13.3 vs. 1.7%, p<0.016). Logistic regression analysis showed the interval from admission to being able to sit in a wheelchair associated with prominent changes in blood pressure (odds ratio, 1.604; 95% confidence interval, 1.196-2.150; p<0.002). Conclusion: Our results showed that prominent changes in blood pressure during an early mobilization protocol can occur easily in patients with acute ischemic stroke after mechanical thrombectomy. PMID:28289575

  10. Eligibility for mechanical thrombectomy in acute ischemic stroke: A phase IV multi-center screening log registry.

    PubMed

    Tsivgoulis, Georgios; Goyal, Nitin; Mikulik, Robert; Sharma, Vijay K; Katsanos, Aristeidis H; Zand, Ramin; Paliwal, Prakash R; Roussopoulou, Andromachi; Volny, Ondrej; Pandhi, Abhi; Zompola, Christina; Elijovich, Lucas; Safouris, Apostolos; Chang, Jason; Alexandrov, Andrei V; Alexandrov, Anne W

    2016-12-15

    No eligibility screening logs were kept in recent mechanical thrombectomy (MT) RCTs establishing safety and efficacy of endovascular reperfusion therapies for acute ischemic stroke (AIS). We sought to evaluate the potential eligibility for MT among consecutive AIS patients in a prospective international multicenter study. We prospectively evaluated consecutive AIS patients admitted in four tertiary-care stroke centers during a twelve-month period. Potential eligibility for MT was evaluated using inclusion criteria from MR CLEAN & REVASCAT. Our study population consisted of 1464 AIS patients (mean age 67±14years, 56% men, median admission NIHSS-score: 5, IQR: 3-10). A total of 123 (8%, 95% CI: 7%-10%) and 82 (6%, 95% CI: 5%-7%) patients fulfilled the inclusion criteria for MR CLEAN&REVASCAT respectively. No evidence of heterogeneity (p>0.100) was found in the eligibility for MT across the participating centers. Absence of proximal intracranial occlusion (69%) and hospital arrival outside the eligible time window (38% for MR CLEAN & 35% for REVASCAT) were the two most common reasons for ineligibility for MT. Our everyday clinical practice experience suggests that approximately one out of thirteen to seventeen consecutive AIS may be eligible for MT if inclusion criteria for MR CLEAN and REVASCAT are strictly adhered to.

  11. Forced Arterial Suction Thrombectomy Using Distal Access Catheter in Acute Ischemic Stroke

    PubMed Central

    Lee, Ho-Cheol; Kang, Dong-Hun; Hwang, Yang-Ha; Kim, Yong-Sun

    2017-01-01

    Historical innovations in mechanical thrombectomy devices and strategies for ischemic stroke have resulted in improved angiographic outcomes and better clinical outcomes. Various devices have been used, but the two most common approaches are aspiration thrombectomy and stent-retrieval thrombectomy. Aspiration thrombectomy has advanced from the traditional Penumbra system to forced arterial suction thrombectomy and a direct aspiration first-pass technique. Newer generation aspiration catheters with flexible distal tips and a larger bore have demonstrated faster and better recanalization relative to older devices. Recently, several species of distal access catheters have similar structural characteristics to the Penumbra reperfusion catheter. Therefore, we used the distal access catheter for forced arterial suction thrombectomy in three patients with acute ischemic stroke. In each case, we achieved fast and complete recanalization without significant complications. Forced arterial suction thrombectomy using a distal access catheter might provide another option for mechanical thrombectomy in patients with acute ischemic stroke. PMID:28316869

  12. Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN.

    PubMed

    Wahlgren, Nils; Moreira, Tiago; Michel, Patrik; Steiner, Thorsten; Jansen, Olav; Cognard, Christophe; Mattle, Heinrich P; van Zwam, Wim; Holmin, Staffan; Tatlisumak, Turgut; Petersson, Jesper; Caso, Valeria; Hacke, Werner; Mazighi, Mikael; Arnold, Marcel; Fischer, Urs; Szikora, Istvan; Pierot, Laurent; Fiehler, Jens; Gralla, Jan; Fazekas, Franz; Lees, Kennedy R

    2016-01-01

    The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

  13. Mechanical Thrombectomy Using Solitaire in a 6-Year-Old Child

    PubMed Central

    Huded, Vikram; Kamath, Vikram; Chauhan, Bhumir; de Souza, Romnesh; Nair, Rithesh; Sapare, Anil; Kekatpure, Minal

    2015-01-01

    A six-year-old boy was diagnosed as recurrent posterior circulation stroke secondary to basilar artery occlusion with rapid progression of symptoms. Etiology of stroke was a dissection of V3 segment of left vertebral artery, which was treated using endovascular technique 26 hours after worsening of symptoms. Since the guidelines for acute revascularization in pediatric stroke are not well established, there is limited experience in the use of mechanical devices for acute ischemic stroke revascularization in children. To our knowledge, this is one of the youngest reported cases of acute ischemic stroke from Asia managed with newer mechanical clot removal devices. PMID:26060522

  14. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    SciTech Connect

    Yang, Shuofei Liu, Baochen Ding, Weiwei He, Changsheng Wu, Xingjiang Li, Jieshou

    2015-02-15

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  15. Endovascular stroke treatment now and then—procedural and clinical effectiveness and safety of different mechanical thrombectomy techniques over time

    PubMed Central

    von Gadow, Niels; Freiherr, Jessica; Block, Frank; Reich, Arno; Fesl, Gunther; Wiesmann, Martin

    2017-01-01

    Background The most essential development in endovascular stroke treatment (EST) was the shift from intra-arterial thrombolysis to endovascular thrombectomy with dedicated thrombectomy devices, most notably the introduction of stent-retrievers. We evaluated procedural and clinical effectiveness and safety of different EST techniques over time. Methods We retrospectively analyzed EST cases that were treated by the same interventionalist before (n=36) and after (n=50) stent-retrievers were established as the treatment device of first choice. EST techniques in the first cohort comprised intra-arterial thrombolysis (n=24), manual thrombus aspiration (n=15), the use of the Penumbra thrombectomy system (n=13) and the Phenox clot retriever (n=3), intracranial stenting (n=10), and EST with stent-retrievers as a salvage procedure (n=11). In the second cohort, EST with stent-retrievers was the treatment option of first choice (n=47). Intra-arterial thrombolysis (n=15) and stenting of the occluded vessel (n=1) were performed, whenever EST with stent-retrievers failed. Results In both cohorts, revascularization rates (TICI ≥2b) were high (91.7% and 86.0%, respectively). A significantly lower number of interventional techniques per case were required in the second cohort (mean ± SD, 1.4±0.5 vs. 2.1±0.9, P<0.001). Recanalization was achieved almost twice as fast in the second cohort (85 vs. 163 minutes on average, P<0.001). The rate of patients achieving good functional outcome (mRS ≤2) was higher in the second cohort (40.0% vs. 22.2%, P=0.083). Conclusions Our findings imply that when stent-retrievers were established as first-line the treatment device a significantly lower number of interventional techniques per case were required and recanalization was achieved almost twice as fast. PMID:28275555

  16. Presumed Pulmonary Embolism Following Power-Pulse Spray Thrombectomy of Upper Extremity Venous Thrombosis

    SciTech Connect

    Tsai, Jason; Georgiades, Christos S.; Hong, Kelvin; Kim, Hyun S.

    2006-08-15

    To achieve more effective thrombolysis in a shorter treatment time, percutaneous mechanical thrombectomy has been increasingly used in the treatment of deep venous thrombosis (DVT). The power-pulse spray is a new technique to combine chemical and rheolytic effects on clots. We present a case of presumed pulmonary embolism following power-pulse spray treatment for upper extremity DVT which necessitated resuscitation and intubation. The power-pulse spray technique should be used with caution when treating DVT.

  17. Does Mechanical Thrombectomy in Acute Embolic Stroke Have Long-term Side Effects on Intracranial Vessels? An Angiographic Follow-up Study

    SciTech Connect

    Kurre, Wiebke Perez, Marta Aguilar; Horvath, Diana; Schmid, Elisabeth; Baezner, Hansjoerg; Henkes, Hans

    2013-06-15

    Purpose. Mechanical thrombectomy (mTE) proved to be effective treating acute vessel occlusions with an acceptable rate of procedural complications. Potential long-term side effects of the vessel wall trauma caused by mechanical irritation of the endothelium are unknown up to now. Methods. From a retrospectively established database of 640 acute stroke treatments, we selected 261 patients with 265 embolic vessel occlusions treated successfully by mTE without permanent implantation of a stent. Analysis comprised the type of devices used and the number of passes performed. Digital subtraction angiography immediately after treatment was evaluated for vasospasm, dissection, and extravasation. Control angiographic images were evaluated for any morphological change compared to the immediate posttreatment angiographic run. Results. Recanalization was achieved with a median of one (range 1-10) mTE maneuvers. Vasospasm occurred in 69 territories (26.0 %) and was treated with glyceroltrinitrate in three. Dissection was observed in one vessel (0.4 %). Intraprocedural hemorrhage in two patients (0.8 %) was either wire or device induced. Follow-up digital subtraction angiography was available for 117 territories after a median of 107 days, revealing target vessel occlusion in one segment (0.9 %) and a de novo stenosis of four segments (3.4 %). All findings were clinically asymptomatic. Posttreatment vasospasm was more frequent in patients with de novo stenosis and occlusion (p = 0.038). Conclusion. De novo stenoses and occlusions occur in a small proportion of patients after mTE. Because all lesions were clinically asymptomatic, this finding does not affect the overall benefit of the treatment. Vasospasm may predict late vessel wall changes.

  18. Amplatz Thrombectomy Device: Unexpected Interaction with the Cragg Endoprosthesis

    SciTech Connect

    Schwarzenberg, Helmut; Mueller-Huelsbeck, Stefan; Heller, Martin

    1998-01-15

    In a 74-year-old woman, a Dacron-covered Cragg endoprosthesis was implanted into the left superficial femoral artery after successful recanalization of a 6-cm-long occlusion. At 4.5 months after discharge the endoprosthesis was occluded. In order to perform a thrombectomy, an Amplatz thrombectomy device (ATD) was activated and advanced into the occluded graft. Suddenly, a mechanical failure of the ATD occurred. Extraction of the ATD was achieved only after repeated attempts at rotating motion and jerky pullback maneuvers. The most likely explanation is that one of the graft-struts had advanced into the tip of the ATD and resulted in a broken drive shaft. Recanalization was completed by performing percutaneous transluminal angioplasty and pharmacological thrombolysis with recombinant human-tissue plasminogen activator. In conclusion, users of the ATD have to be aware of interactions of the ATD with the struts of implanted stents or grafts during thrombectomy.

  19. Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

    SciTech Connect

    Wagner, Marlies; Kyriakou, Yiannis; Mesnil de Rochemont, Richard du; Singer, Oliver C.; Berkefeld, Joachim

    2013-08-01

    PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.

  20. The Penumbra 5MAX ACE Catheter Is Safe, Efficient, and Cost Saving as a Primary Mechanical Thrombectomy Device for Large Vessel Occlusions in Acute Ischemic Stroke

    PubMed Central

    Vidal, Gabriel A.; Milburn, James M.

    2016-01-01

    catheter can be considered a first-line approach to mechanical thrombectomy for large vessel occlusions. Our results demonstrated high rates of successful reperfusion in a timely manner with excellent clinical outcomes, although our sample size was small. In addition, this direct-aspiration technique has important cost-savings potential compared to stent retrievers. PMID:27999507

  1. Endovascular Mechanical Thrombectomy of an Occluded Superior Division Branch of the Left MCA for Acute Cardioembolic Stroke

    SciTech Connect

    Schumacher, H. C. Meyers, P. M.; Yavagal, D. R.; Harel, N. Y.; Elkind, M. S. V.; Mohr, J. P.; Pile-Spellman, J.

    2003-06-15

    Cardiac embolism accounts for a large proportion of ischemic stroke. Revascularization using systemic or intra-arterial thrombolysis is associated with increasing risks of cerebral hemorrhageas time passes from stroke onset. We report successful mechanicalthrombectomy from a distal branch of the middle cerebral artery (MCA)using a novel technique. A 72-year old man suffered an acute ischemic stroke from an echocardiographically proven ventricular thrombus due toa recent myocardial infarction. Intra-arterial administration of 4 mgrt-PA initiated at 5.7 hours post-ictus failed to recanalize an occluded superior division branch of the left MCA. At 6 hours,symptomatic embolic occlusion persisted. Mechanical extraction of the clot using an Attracter-18 device (Target Therapeutics, Freemont, CA) resulted in immediate recanalization of the MCA branch. Attracter-18 for acute occlusion of MCA branches may be considered in selected patients who fail conventional thrombolysis or are nearing closure of the therapeutic window for use of thrombolytic agents.

  2. Mechanical thrombectomy using Rotarex system and stent-in-stent placement for treatment of distal femoral artery occlusion secondary to stent fracture – a case report and literature review

    PubMed Central

    Dys, Krzysztof; Drelichowska-Durawa, Justyna; Dołega-Kozierowski, Bartosz; Lis, Michał; Sokratous, Kyriakos; Iwanowski, Wojciech; Drelichowski, Stanisław; Witkiewicz, Wojciech

    2013-01-01

    Summary Background: Treatment of peripheral arterial diseases may be distinguished into conservative and interventional management; the latter is divided into surgical and endovascular procedures. Management of peripheral artery stenosis and occlusion with vascular stents is associated with the risk of late complications such as restenosis, stent fracture or dislocation. Case Report: A 62-year-old woman with generalized atherosclerosis, particularly extensive in lower limb arteries, was admitted to the Department of Angiology 11 months after having an endovascular procedure performed due to critical ischemia of left lower limb. Because of stent occlusion, a decision to perform angiographic examination of lower limb arteries was made. Examination revealed occlusion of the superficial femoral artery along its entire length, including previously implanted stents. Distal stent was fractured with slight dislocation of the proximal segment. A decision was made to perform mechanical thrombectomy using a Rotarex system followed by a stent-in-stent placement procedure. Follow-up angiography and ultrasound scan performed 24 hours after the procedure revealed a patent vessel with satisfactory blood flow. Discussion: Nowadays, imaging diagnostics of peripheral artery stenosis involves non-invasive examinations such as ultrasound, minimally invasive examinations such as angio-MRI and MDCT, or invasive examinations such as DSA and IVUS. DSA examinations are used to confirm significant stenosis or occlusion of a vessel, particularly when qualifying a patient for endovascular treatment. Due to their anatomic location, the superficial femoral artery and the popliteal artery are subject to various forces e.g. those exerted by the working muscles. Mechanical thrombectomy and atherectomy are efficient methods of arterial recanalization used in the treatment of acute, subacute or even chronic occlusions or stenosis of peripheral vessels. Conclusions: Frequency of angioplasty and

  3. Stent retriever thrombectomy for acute ischemic stroke: Indications, results and management in 2015.

    PubMed

    Gory, B; Riva, R; Labeyrie, P E; Turjman, F

    2016-02-01

    The functional benefit of stent retriever thrombectomy in acute ischemic stroke has been clearly demonstrated in recent positive MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT and THRACE trials. Thrombectomy, in association with intravenous thrombolysis, should now be offered to patients with documented occlusion of the distal internal carotid or proximal middle cerebral arteries, with a relatively normal unenhanced computed tomography (CT), and within 6hours after the onset of symptoms. Thrombectomy results in a mean absolute decrease in handicap of 22% (14 to 31%). Of the 3 up to 8 patients treated, 1 is independent at 3 months according to the initial selection. In case of a contraindication to thrombolysis, early primary thrombectomy should be considered. In acute basilar artery occlusion, thrombectomy should be performed alone or combined with thrombolysis. In an effort to increase the number of patients treated, a very rapid transfer to interventional neuroradiology centers is mandatory. In the future, thrombectomy should be evaluated in patients with distal arterial occlusion, or beyond 6hours after the onset of symptoms, or when the time of symptoms onset is unknown.

  4. Emergent Right Coronary Artery Thrombectomy with a Jet Aspiration Thrombectomy Catheter

    SciTech Connect

    Yamauchi, Teiyu; Furui, Shigeru; Isshiki, Takaaki; Toyoizumi, Hideki; Kohtake, Hiroshi; Takeshita, Kohji; Suzuki, Shigeru; Harasawa, Arimi; Sasaki, Yasushi

    1999-07-15

    A saline-jet aspiration thrombectomy (JAT) catheter was used in a patient with acute myocardial infarction. A right coronary arteriogram showed complete thrombotic occlusion at the proximal segment. With this catheter the thrombus was removed without complications in 5 sec. The patient underwent percutaneous transluminal coronary angioplasty and placement of a Palmaz-Schatz stent after successful thrombectomy. Thrombectomy with a JAT catheter was very useful in this patient.0.

  5. The transient intraluminal filament middle cerebral artery occlusion model as a model of endovascular thrombectomy in stroke.

    PubMed

    Sutherland, Brad A; Neuhaus, Ain A; Couch, Yvonne; Balami, Joyce S; DeLuca, Gabriele C; Hadley, Gina; Harris, Scarlett L; Grey, Adam N; Buchan, Alastair M

    2016-02-01

    The clinical relevance of the transient intraluminal filament model of middle cerebral artery occlusion (tMCAO) has been questioned due to distinct cerebral blood flow profiles upon reperfusion between tMCAO (abrupt reperfusion) and alteplase treatment (gradual reperfusion), resulting in differing pathophysiologies. Positive results from recent endovascular thrombectomy trials, where the occluding clot is mechanically removed, could revolutionize stroke treatment. The rapid cerebral blood flow restoration in both tMCAO and endovascular thrombectomy provides clinical relevance for this pre-clinical model. Any future clinical trials of neuroprotective agents as adjuncts to endovascular thrombectomy should consider tMCAO as the model of choice to determine pre-clinical efficacy.

  6. Successful carbon dioxide angiography guided endovascular thrombectomy of the superficial femoral artery in a young patient with critical limb ischemia.

    PubMed

    Giusca, Sorin; Eisele, Tom; Raupp, Dorothea; Eisenbach, Christoph; Korosoglou, Grigorios

    2017-03-01

    Currently, the treatment of thromboembolic ischemia of the lower extremities includes percutaneous rotational thrombectomy and aspiration devices. However, the standard approach for endovascular treatment requires the administration of iodine contrast agents, which is problematic in patients with pre-existing renal disease and diabetes. Herein, we describe a case of a CO2 angiography guided endovascular thrombectomy of the superficial femoral artery (SFA) in a young patient with critical limb ischemia. Mechanical thrombectomy using the Rotarex system, catheter aided aspiration and subsequent stent placement in the SFA was entirely guided using CO2 angiography.

  7. Anchor technique: Use of stent retrievers as an anchor to advance thrombectomy catheters in internal carotid artery occlusions

    PubMed Central

    Wolfe, Stacey Q; Janjua, Rashid M; Hedayat, Hirad; Burnette, Christofer

    2015-01-01

    In three recent cases of acute complete internal artery occlusions, we used stent retriever deployed through the mechanical aspiration/distal access catheters to achieve recanalization. In all cases the stent retriever was used as an anchor and supplemented mechanical thrombectomy. This report describes the technical details of the procedure and presents an alternative plan of action in difficult cases when standard thrombectomy techniques do not work. PMID:26494404

  8. Massive Pulmonary Embolism: Treatment with the Rotarex Thrombectomy System

    SciTech Connect

    Liu Sheng; Shi Haibin; Gu Jianping; Yang Zhengqiang; Chen Liang; Lou Wensheng; He Xu; Zhou Weizhong; Zhou Chungao; Zhao Linbo; Xia Jinguo; Li Linsun

    2011-02-15

    This study was designed to evaluate the efficacy and safety of percutaneous mechanical thrombectomy (PMT) for acute massive pulmonary embolism (PE). Fourteen patients (8 men, 6 women) with a mean age of 55.4 (range, 38-71) years with acute massive PE were initially diagnosed by computed tomography (CT) and confirmed by pulmonary angiography. All patients presented with acute PE symptoms and hemodynamic compromise. Each patient was treated with Straub Rotarex thrombectomy device and five patients received additional thrombolysis. Technique success and clinical improvement were achieved in all patients without major complications. The mean pulmonary artery pressure (PAP) decreased from 37.6 {+-} 6.6 to 29 {+-} 6.4 mmHg (P < 0.01) after PMT. Partial arterial pressures of O{sub 2} (PaO{sub 2}) increased from 61.1 {+-} 9.2 to 88 {+-} 5.1 mmHg (P < 0.01). The Miller index was 0.67 {+-} 0.11 and 0.37 {+-} 0.13 (P < 0.01), respectively, before and after PMT (P < 0.01). Eleven patients had no recurrence of PE on a mean follow-up of 28.3 months, whereas the other three patients were lost to follow-up. The preliminary experience in our series suggests that the Straub Rotarex thrombectomy device, which has been utilized in peripheral arteries, also is useful for the treatment of acute massive PE.

  9. Infective Endocarditis Complicated by Acute Ischemic Stroke from Septic Embolus: Successful Solitaire FR Thrombectomy

    PubMed Central

    Liang, Jackson J; Bishu, Kalkidan G; Anavekar, Nandan S

    2012-01-01

    Infective endocarditis (IE) is often complicated by systemic embolization. Acute stroke due to septic emboli is a particularly dreaded complication. Optimal treatment for acute stroke in IE has not been well outlined. Fibrinolytic therapy may be associated with increased risk for hemorrhagic transformation in patients with acute stroke in the setting of IE. We present a case of IE complicated by acute stroke which was successfully treated with mechanical thrombectomy. This case illustrates a role of mechanical thrombectomy devices in this patient population.

  10. Percutaneous Venous Thrombectomy Using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with Temporary Caval Filtration: In Vitro Investigations

    SciTech Connect

    Wildberger, Joachim Ernst Haage, Patrick; Bovelander, Jan; Pfeffer, Joachim; Weiss, Claudia; Vorwerk, Dierk; Schmitz-Rode, Thomas; Guenther, Rolf W.

    2005-04-15

    Purpose. To evaluate the size and quantity of downstream emboli after thrombectomy using the Arrow-Trerotola Percutaneous Thrombolytic Device (PTD) with or without temporary filtration for extensive iliofemoral and iliocaval thrombi in an in vitro flow model. Methods. Iliocaval thrombi were simulated by clotted bovine blood in a flow model (semilucent silicone tubings, diameter 12-16 mm). Five experimental set-ups were performed 10 times each; thrombus particles and distribution were measured in the effluent. First, after retrograde insertion, mechanical thrombectomy was performed using the PTD alone. Then a modified self-expanding tulip-shaped temporary vena cava stent filter was inserted additionally at the beginning of each declotting procedure and removed immediately after the intervention without any manipulation within or at the filter itself. In a third step, the filter was filled with thrombus only. Here, two experiments were performed: Careful closure within the flow circuit without any additional fragmentation procedure and running the PTD within the filter lumen, respectively. In the final set-up, mechanical thrombectomy was performed within the thrombus-filled tubing as well as in the filter lumen. The latter was closed at the end of the procedure and both devices were removed from the flow circuit. Results. Running the PTD in the flow circuit without filter protection led to a fragmentation of 67.9% ({+-}7.14%) of the clot into particles {<=}500 {mu}m; restoration of flow was established in all cases. Additional placement of the filter safely allowed maceration of 82.9% ({+-}5.59%) of the thrombus. Controlled closure of the thrombus-filled filter within the flow circuit without additional mechanical treatment broke up 75.2% ({+-}10.49%), while additional mechanical thrombectomy by running the PTD within the occluded filter led to dissolution of 90.4% ({+-}3.99%) of the initial clot. In the final set-up, an overall fragmentation rate of 99.6% ({+-}0

  11. Evolution of thrombectomy approaches and devices for acute stroke: a technical review.

    PubMed

    Spiotta, Alejandro M; Chaudry, M Imran; Hui, Ferdinand K; Turner, Raymond D; Kellogg, Ryan T; Turk, Aquilla S

    2015-01-01

    While intravenous administration of tissue plasminogen activator (tPA) remains the only FDA-approved treatment modality for acute ischemic stroke, many patients do not meet the criteria for intravenous tPA and are offered intra-arterial therapy. Rapid advances in devices and approaches have marked the evolution of thrombectomy over the past decade from rudimentary mechanical disruption, followed by intra-arterial thrombolytic infusions to increasingly effective thrombectomy devices. We review the critical advancements in thrombectomy technique that have evolved and the key anatomic and technical challenges they address, from first-generation Merci retrieval systems to second-generation Penumbra aspiration systems and third-generation stent retrievers, as well as nuances of their uses to maximize their effectiveness. We also highlight more recent advances that offer patients hope for more expedient vessel recanalization.

  12. Massive Pulmonary Embolism: Percutaneous Emergency Treatment Using an Aspirex Thrombectomy Catheter

    SciTech Connect

    Popovic, Peter; Bunc, Matjaz

    2010-10-15

    Massive pulmonary embolism (PE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. A 51-year-old woman with a massive PE and contraindication for thrombolytic therapy was treated with percutaneous mechanical thrombectomy using an Aspirex 11F catheter (Straub Medical AG, Wangs, Switzerland). The procedure was successfully performed and showed a good immediate angiographic result. The patient made a full recovery from the acute episode and was discharged on heparin treatment. Our case report indicates that in patients with contraindications to systemic thrombolysis, catheter thrombectomy may constitute a life-saving intervention for massive PE.

  13. Surgical Thrombectomy for Phlegmasia Cerulea Dolens

    PubMed Central

    Yang, Shin-Seok; Yun, Woo-Sung

    2016-01-01

    Phlegmasia cerulea dolens (PCD) is a medical emergency that can lead to venous gangrene of the lower extremity. Early diagnosis and prompt treatment is crucial for limb salvage. There are two treatment options (endovascular or surgical). In the endovascular era, catheter-directed thrombolysis is the treatment of choice to achieve venous outflow. However, surgical thrombectomy is indicated in certain cases. The authors report successful surgical thrombectomy in a 75-year-old man with PCD and review the treatment of PCD. PMID:28042562

  14. Massive pulmonary embolism: treatment with the rotarex thrombectomy system.

    PubMed

    Liu, Sheng; Shi, Hai-Bin; Gu, Jian-Ping; Yang, Zheng-Qiang; Chen, Liang; Lou, Wen-Sheng; He, Xu; Zhou, Wei-Zhong; Zhou, Chun-Gao; Zhao, Lin-Bo; Xia, Jin-Guo; Li, Lin-Sun

    2011-02-01

    This study was designed to evaluate the efficacy and safety of percutaneous mechanical thrombectomy (PMT) for acute massive pulmonary embolism (PE). Fourteen patients (8 men, 6 women) with a mean age of 55.4 (range, 38-71) years with acute massive PE were initially diagnosed by computed tomography (CT) and confirmed by pulmonary angiography. All patients presented with acute PE symptoms and hemodynamic compromise. Each patient was treated with Straub Rotarex thrombectomy device and five patients received additional thrombolysis. Technique success and clinical improvement were achieved in all patients without major complications. The mean pulmonary artery pressure (PAP) decreased from 37.6 ± 6.6 to 29 ± 6.4 mmHg (P < 0.01) after PMT. Partial arterial pressures of O(2) (PaO(2)) increased from 61.1 ± 9.2 to 88 ± 5.1 mmHg (P < 0.01). The Miller index was 0.67 ± 0.11 and 0.37 ± 0.13 (P < 0.01), respectively, before and after PMT (P < 0.01). Eleven patients had no recurrence of PE on a mean follow-up of 28.3 months, whereas the other three patients were lost to follow-up. The preliminary experience in our series suggests that the Straub Rotarex thrombectomy device, which has been utilized in peripheral arteries, also is useful for the treatment of acute massive PE.

  15. Effect of Coronary Thrombectomy in Cardiogenic Shock Complicating ST-Segment Elevation Myocardial Infarction.

    PubMed

    Suzuki, Makoto; Sumiyoshi, Tetsuya; Miyachi, Hideki; Yamashita, Jun; Yamasaki, Masao; Miyauchi, Katsumi; Yamamoto, Takeshi; Nagao, Ken; Tomoike, Hitonobu; Takayama, Morimasa

    2015-06-15

    Optimal coronary reflow is the critical key issue to ameliorate clinical outcomes in patients with cardiogenic shock complicating ST-segment elevation myocardial infarction (Shock-STEMI). We investigated our hypothesis that pre-percutaneous coronary intervention (PCI) procedural coronary thrombectomy may provide clinical advantages to attempt optimal coronary reflow in patients with Shock-STEMI. Of 7,650 patients with acute myocardial infarction registered in the Tokyo CCU Network Scientific Council from January 2009 to December 2011, a total of 180 consecutive patients (144 men, 68 ± 13 years) with Shock-STEMI who showed pre-PCI procedural Thrombolysis in Myocardial Infarction flow grade 0 (absent initial coronary flow) were recruited. Achievements of post-PCI procedural Thrombolysis in Myocardial Infarction flow grade 3 (optimal coronary reflow) and also in-hospital mortality were evaluated in those in accordance with and without coronary thrombectomy. Coronary thrombectomy was performed in 128 patients with Shock-STEMI (71% of all). Overall in-hospital mortality was 41% and that in anterior Shock-STEMI with a necessity of mechanical circulatory support increased by 59% (i.e., profound shock). Coronary thrombectomy did not affect any improvements in the achievement of optimal coronary reflow (65% vs 58%, p = 0.368) and in-hospital mortality (42% vs 37%, p = 0.484) in these patients. Even when focused on 76 patients with profound shock, neither an achievement of optimal coronary reflow (56% vs 47%, p = 0.518) nor in-hospital mortality (58% vs 65%, p = 0.601) were different between with and without coronary thrombectomy. Multivariate logistic analysis did not demonstrate any association of coronary thrombectomy (p = 0.798), left main Shock-STEMI (p = 0.258), and use of mechanical circulatory support (p = 0.119) except a concentration of hemoglobin (for each 1 g/dl increase, odds ratio 1.247, 95% confidence interval 1.035 to 1.531, p = 0.019) with optimal

  16. Endovascular treatment of acute limb ischemia and proximal deep vein thrombosis using rotational thrombectomy: A review of published literature.

    PubMed

    Lichtenberg, Michael; Stahlhoff, Friedrich-Wilhelm; Boese, Dirk

    2013-01-01

    Acute and subacute ischemia of the lower extremity is still a common reason for amputation. The treatment of this condition includes the well known procedure of local thrombolysis, surgical thrombectomy and, in recent times, percutaneous mechanical thrombectomy procedures such as rotational thrombectomy. However, in randomized studies Fogarty's procedure of surgical thrombectomy was associated with a high rate of perioperative complications and, in part, low technical success rates. On the other hand, local thrombolysis is associated with hemorrhage as well as high costs because of measures requiring substantial resources, such as intensive care monitoring or repeat angiographies. In several studies, the endovascular therapy options of Straub Rotarex® and Aspirex® systems, both products of technical advancements in the field, were shown to be successful in terms of amputation-free survival. Their use was also associated with low complication rates. The majority of studies were focused on arterial blood flow in the femur. However, in the meantime several registers and studies have shown that the systems can also be effectively used to treat proximal deep vein thrombosis. In the present report we review the current study-based value of rotational thrombectomy in the venous and arterial system.

  17. [Thrombectomy and plication of veins as a method of preventing pulmonary artery thromboembolism at a multidisciplinary surgical hospital].

    PubMed

    Galkin, S V; Pashin, N V; Dedyukhin, I G; Aleksandrov, A G; Lebedeva, M V

    2016-01-01

    The authors assessed efficacy and safety of the operation of plication of deep veins of lower extremities, pelvic veins, and the inferior vena cava as a method of preventing fatal pulmonary artery thromboembolism. A total of 48 patients were operated on. Of these, 23 patients belonged to traumatological-and-orthopaedical cohort, 3 to general surgical cohort, 4 to gynaecological, and 18 to vascular cohort (isolated deep vein thrombosis). The length of the floating head of the thrombus varied from 2 to 10 cm. The presence of a floating thrombus in traumatological, surgical and gynaecological patients, regardless of the length of the floating part was an absolute indication for thrombectomy and venous plication. Vascular patients were operated on in accordance with the National Guidelines (with the length of the thrombus floating portion of not less than 4 cm). In all cases, surgical management envisaged direct and indirect thrombectomy. Plication was always performed above the level of venotomy. It was shown that thrombectomy combined with plication of major veins is a reliable and safe method of prophylaxis, being in some cases the only possible method of preventing fatal pulmonary artery thromboembolism. The operation of plication makes it possible not to cancel a scheduled surgical intervention in patients with a detected floating thrombus of major veins. The operation of thrombectomy and plication above the level of the floating head of the thrombus may be considered an operation of choice in the conditions where there is no possibility to use endovascular methods of treatment (implantation of a cava filter, endovascular catheter thrombectomy), as well as in pregnant women. Restoration of the venous lumen occurs at safe terms spontaneously, not requiring repeat surgical intervention. Simultaneous plication of the vein does not complicate the course of the postoperative period of the main surgical intervention. Thrombectomy and plication do not lead to the

  18. Right atrial thrombi: Percutaneous mechanical thrombectomy

    SciTech Connect

    Beregi, Jean-Paul; Aumegeat, Valerie; Loubeyre, Christophe; Coullet, Jean-Michel; Asseman, Philippe; Debacker-Steckelorom, Caroline; Bauchart, Jean-Jacques; Liu Pengcheng; Thery, Claude

    1997-03-15

    The current therapeutic options for right atrial thrombi-surgical embolectomy and thrombolysis- are associated with high mortality and such patients often have contraindications to these therapeutic options. the purpose of this study was to evaluate the feasibility of endovascular right atrial embolectomy. Two patients with contraindications to thrombolysis and surgery were treated by a femoral approach. A catheter was placed in the right atrium, under fluoroscopic control, and a basket device was used to trap the thrombus. The location and extent of the thrombus was established before the procedure by transesophageal echocardiography (TEE) and the procedure was performed with TEE and fluoroscopy. Thrombi were withdrawn in the basket into the inferior vena cava (IVC) and a filter was inserted by a jugular approach and positioned in the IVC, just above the thrombi. The basket was removed leaving the thrombus below the filter. One patient died immediately after the procedure. In conclusion, endovascular extraction of right atrial thrombi may represent a potential therapeutic alternative, particularly in patients with contraindications to thrombolysis and surgery.

  19. Safety and Efficacy of Solitaire Stent Thrombectomy

    PubMed Central

    Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

    2016-01-01

    Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent

  20. [RADICAL LAPAROSCOPIC NEPHRECTOMY WITH INFERIOR VENA CAVA THROMBECTOMY].

    PubMed

    Perlin, D V; Aleksandrov, I V; Zipunnikov, V P; Ljaljuev, A M

    2015-01-01

    Laparoscopic radical nephrectomy has proven itself as the "gold standard" treatment of renal cell carcinoma. Inferior vena cava (IVC) tumor thrombus is a complicating factor that occurs in 5% to 10% of patients with renal cell carcinoma. In world literature, there are only anecdotal reports on using laparoscopic approach for IVC thrombectomy in patients with renal cell carcinoma. Herein we report our experience of laparoscopic radical nephrectomy and thrombectomy of the level II tumor thrombus in the IVC. Two patients (79-year-old female and 48-year-old male) underwent radical nephrectomy with thrombectomy from IVC for renal cell carcinoma T3bNxM0 complicated by the formation of a tumor thrombus in the IVC. To do this, IVC was isolated, the right gonadal and lumbar veins were ligated and transected. The IVC and the left renal vein blood flow were controlled with a plastic clip and Satinski clamp. After thrombectomy and resection of the IVC, the wall the defect was sutured with continuous Prolene suture. Laparoscopic radical nephrectomy with thrombectomy without conversion to open surgery was successfully carried out in both patients. During 6-18 months follow-up no local recurrence or distant metastasis were observed. Laparoscopic radical nephrectomy with thrombectomy for renal cell carcinoma complicated with tumor thrombus level II is a safe and reproducible method, which can be applied to a specific population of patients.

  1. Catheter directed lysis and thrombectomy of submassive pulmonary embolism.

    PubMed

    Krichavsky, Marc Z; Rybicki, Frank J; Resnic, Frederic S

    2011-01-01

    Acute pulmonary embolism (PE) is a common and potentially highly morbid disease. However, there are a broad range of clinical presentations, varying from asymptomatic to life-threatening hemodynamic compromise. Accordingly, the aggressiveness of treatment for acute PE must be adjusted to the acuity of the presentation and patient-specific comorbidities. Thrombolysis is FDA approved for massive PE with hemodynamic compromise. However, this therapy has associated risk, most notably intracranial hemorrhage and other bleeding complications. This has prompted interest in catheter-directed therapies to mechanically remove thrombus and to locally deliver reduced doses of thrombolytics. Guidelines support use of this catheter-based strategy in cases of increased bleeding risk or high acuity with insufficient time for systemic pharmacologic therapy to be effective. We present the case of an 83-year-old man with acute high-risk PE and worsening hemodynamic and respiratory status who was treated with catheter-directed thrombolysis and rheolytic thrombectomy. There was significant improvement in thrombus burden, symptoms, and hemodynamic parameters including right ventricular function and pulmonary artery pressures. However, his course was complicated by intracranial hemorrhage and access site hematoma, demonstrating that even reduced doses and local delivery of thrombolytics do not ensure freedom from bleeding complications.

  2. AngioJet Thrombectomy for Occluded Dialysis Fistulae: Outcome Data

    SciTech Connect

    Littler, Peter Cullen, Nicola; Gould, Derek; Bakran, Ali; Powell, Steven

    2009-03-15

    This study evaluates AngioJet thrombectomy of occluded autogenous dialysis fistulae and polytetrafluoroethylene (PTFE) grafts in a UK hemodialysis population. Comparison is made with published data of alternative percutaneous thrombectomy methods. All patients with occluded dialysis fistulae who sought care at the Royal Liverpool University Hospital between October 2006 and June 2008 were included in the study. All patients were treated with the AngioJet Rheolytic Thrombectomy Device (Possis, Minneapolis, MN). Demographics, time of occlusion, adjunctive therapies, complications, and follow-up data have been prospectively recorded. A total of 64 thrombectomy procedures were performed in 48 patients. Forty-four autogenous fistulas were treated in 34 patients (19 brachiocephalic, 8 radiocephalic, and 7 transposed brachiobasilic). Twenty PTFE grafts were treated in 14 patients (9 brachioaxillary, 3 brachiocephalic loop grafts, 1 brachiobasilic, and 1 femoro-femoral). The average length of occlusion was 24 cm. Average time to intervention was 4 days. Immediate primary patency was 91%. Primary patency at 1, 3, and 6 months, respectively, was 71%, 60%, and 37%. Secondary patency at 3, 6, and 12 months was 87%, 77%, and 62%, respectively. Angioplasty was carried out in all procedures. Patients required stent insertion in 34 of the 64 thrombectomies to treat angioplasty-resistant stenoses. Complications included a puncture-site hematoma, and three angioplasty-related vein ruptures in one patient, all treated with covered stent grafts. Two cases of distal brachial arterial embolization were successfully treated by thrombosuction. AngioJet thrombectomy in dialysis access occlusion is safe and effective, comparing favorably with other methods.

  3. A New Rotational Thrombectomy Catheter: System Design and First Clinical Experiences

    SciTech Connect

    Schmitt, Hans-Erich; Jaeger, Kurt A.; Jacob, Augustinus L.; Mohr, Helmuth; Labs, Karl-Heinz; Steinbrich, Wolfgang

    1999-11-15

    Purpose: To describe a new catheter for the percutaneous mechanical removal of fresh and organized thrombi, and to assess its efficacy and safety in vitro and in vivo. Methods: The catheter consists of a coated stainless steel spiral that rotates at 40,000 rpm over a guidewire inside the whole length of an 8 Fr, single-lumen, polyurethane catheter, driving a dual-blade cutting crown. Abraded occlusion material is sucked into the catheter head through distal side holes and transported by the spiral into a reservoir at the proximal end. The efficacy of the device was tested in arterial models and fresh bovine carotid arteries (n = 72). In a clinical pilot study 10 patients (8 women, 2 men; mean age 70.6 {+-} 10.1 years) with occlusions of the superficial femoral artery (2-12 cm, mean 5.8 cm), not older than 4 weeks, underwent thrombectomy with the new catheter. Results: In arterial models and bovine cadaver arteries the catheter completely removed fresh thrombi. Occlusion material of higher consistency was cut into particles of 100-500 {mu}m and transported outside. Thrombectomy was successful and vessel patency restored in all 10 patients. The ankle/brachial pressure index significantly (p < 0.0005) increased from 0.41 {+-} 0.18 before intervention to 0.88 {+-} 0.15 after 48 hr and to 0.84 {+-} 0.20 after 3 months. Two reocclusions occurred within 14 days after the intervention. Conclusion: Thrombectomy with the new device appears to be feasible and safe in patients with acute and subacute occlusions of the femoropopliteal artery.

  4. Guidewire-Controlled Advancement of the Amplatz Thrombectomy Device

    SciTech Connect

    Mueller-Huelsbeck, Stefan; Schwarzenberg, Helmut; Heller, Martin

    1998-01-15

    The Amplatz Thrombectomy Device (ATD) is a percutaneous rotational catheter proven to homogenize thrombus. The catheter design allows neither application over a coaxial running guidewire nor the use of the device as a monorail system. We report a technical modification that provides guided advancement of the catheter over a wire in order to prevent failure of application and to facilitate the interventional procedure.

  5. Balloon catheter dilatation and thrombectomy for acute aortoiliac occlusion

    PubMed Central

    Archie, Joseph P.

    1981-01-01

    A case of acute distal aortic thrombosis in an elderly high-risk patient was successfully managed with intraoperative thrombectomy and balloon catheter dilatation of the common iliac arteries. Balloon catheter dilatation may be indicated prior to bypass grafting in high-risk patients with acute aortoiliac thrombosis. PMID:15216181

  6. Catheter-Directed Thrombolysis with Percutaneous Rheolytic Thrombectomy Versus Thrombolysis Alone in Upper and Lower Extremity Deep Vein Thrombosis

    SciTech Connect

    Kim, Hyun S. Patra, Ajanta; Paxton, Ben E.; Khan, Jawad; Streiff, Michael B.

    2006-12-15

    Purpose. To compare the efficacy of catheter-directed thrombolysis (CDT) alone versus CDT with rheolytic percutaneous mechanical thrombectomy (PMT) for upper and lower extremity deep vein thrombosis (DVT). Methods. A retrospective cohort of consecutive patients with acute iliofemoral or brachiosubclavian DVT treated with urokinase CDT was identified, and a chart review was conducted. Demographic characteristics, treatment duration, total lytic dose, clot lysis rates and complications were compared in patients treated with urokinase CDT alone or combined CDT and rheolytic PMT. Results. Forty limbs in 36 patients were treated with urokinase CDT alone. Twenty-seven limbs in 21 patients were treated with urokinase CDT and rheolytic PMT. The mean treatment duration for urokinase CDT alone was 48.0 {+-} 27.1 hr compared with 26.3 {+-} 16.6 hr for urokinase CDT and rheolytic PMT (p = 0.0004). The mean urokinase dose required for CDT alone was 5.6 {+-} 5.3 million units compared with 2.7 {+-} 1.8 million units for urokinase CDT with rheolytic PMT (p = 0.008). Complete clot lysis was achieved in 73% (29/40) of DVT treated with urokinase CDT alone compared with 82% (22/27) treated with urokinase CDT with rheolytic PMT. Conclusion. Percutaneous CDT with rheolytic PMT is as effective as CDT alone for acute proximal extremity DVT but requires significantly shorter treatment duration and lower lytic doses. Randomized studies to confirm the benefits of pharmacomechanical thrombolysis in the treatment of acute proximal extremity DVT are warranted.

  7. Prototype fabrication and preliminary in vitro testing of a shape memory endovascular thrombectomy device.

    PubMed

    Small, Ward; Wilson, Thomas S; Buckley, Patrick R; Benett, William J; Loge, Jeffrey M; Hartman, Jonathan; Maitland, Duncan J

    2007-09-01

    An electromechanical microactuator comprised of shape memory polymer (SMP) and shape memory nickel-titanium alloy (nitinol) was developed and used in an endovascular thrombectomy device prototype. The microactuator maintains a straight rod shape until an applied current induces electro-resistive (Joule) heating, causing the microactuator to transform into a corkscrew shape. The straight-to-corkscrew transformation geometry was chosen to permit endovascular delivery through (straight form) and retrieval of (corkscrew form) a stroke-causing thrombus (blood clot) in the brain. Thermal imaging of the microactuator during actuation in air indicated that the steady-state temperature rise caused by Joule heating varied quadratically with applied current and that actuation occurred near the glass transition temperature of the SMP (86 degrees C). To demonstrate clinical application, the device was used to retrieve a blood clot in a water-filled silicone neurovascular model. Numerical modeling of the heat transfer to the surrounding blood and associated thermal effects on the adjacent artery potentially encountered during clinical use suggested that any thermal damage would likely be confined to localized areas where the microactuator was touching the artery wall. This shape memory mechanical thrombectomy device is a promising tool for treating ischemic stroke without the need for infusion of clot-dissolving drugs.

  8. Combined mechanical loading of composite tubes

    NASA Technical Reports Server (NTRS)

    Derstine, Mark S.; Pindera, Marek-Jerzy; Bowles, David E.

    1988-01-01

    An analytical/experimental investigation was performed to study the effect of material nonlinearities on the response of composite tubes subjected to combined axial and torsional loading. The effect of residual stresses on subsequent mechanical response was included in the investigation. Experiments were performed on P75/934 graphite-epoxy tubes with a stacking sequence of (15/0/ + or - 10/0/ -15), using pure torsion and combined axial/torsional loading. In the presence of residual stresses, the analytical model predicted a reduction in the initial shear modulus. Experimentally, coupling between axial loading and shear strain was observed in laminated tubes under combined loading. The phenomenon was predicted by the nonlinear analytical model. The experimentally observed linear limit of the global shear response was found to correspond to the analytically predicted first ply failure. Further, the failure of the tubes was found to be path dependent above a critical load level.

  9. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial

    PubMed Central

    Muir, Keith W; Ford, Gary A; Messow, Claudia-Martina; Ford, Ian; Murray, Alicia; Clifton, Andrew; Brown, Martin M; Madigan, Jeremy; Lenthall, Rob; Robertson, Fergus; Dixit, Anand; Cloud, Geoffrey C; Wardlaw, Joanna; Freeman, Janet; White, Philip

    2017-01-01

    Objective The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0–2 at day 90. Results Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13–21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0–1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0–2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). Conclusions The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability

  10. Multi-mechanism vibration harvester combining inductive and piezoelectric mechanisms

    NASA Astrophysics Data System (ADS)

    Marin, Anthony; Priya, Shashank

    2012-04-01

    With increasing demand for wireless sensor nodes in automobile, aircraft and rail applications, the need for energy harvesters has been growing. In these applications, energy harvesters provide a more robust and inexpensive power solution than batteries. In order to enhance the power density of existing energy harvesters, a variety of multimodal energy harvesting techniques have been proposed. Multi-modal energy harvesters can be categorized as: (i) Multi-Source Energy Harvester (MSEH), (ii) Multi-Mechanism Energy Harvester (MMEH), and (iii) Single Source Multi-Mode Energy Harvester (S2M2EH). In this study, we focus on developing MMEH which combines the inductive and piezoelectric mechanisms. The multi-mechanism harvester was modeled using FEM techniques and theoretically analyzed to optimize the performance and reduce the overall shape and size similar to that of AA battery. The theoretical model combining analytical and FEM modeling techniques provides the system dynamics and output power for specific generator and cymbal geometry at various source conditions. In the proposed design, a cylindrical tube contains a magnetic levitation cavity where a center magnet oscillates through a copper coil. Piezoelectric cymbal transducers were mounted on the top and bottom sections of the cylindrical shell. In response to the external vibrations, electrical energy was harvested from the relative motion between magnet and coil through Faraday's effect and from the piezoelectric material through the direct piezoelectric effect. Experimental results validate the predictions from theoretical model and show the promise of multimodal harvester for powering wireless sensor nodes in automobile, aircraft, and rail applications.

  11. Retrievable stent thrombectomy in the treatment of acute ischemic stroke: analysis of a revolutionizing treatment technique.

    PubMed

    Walcott, Brian P; Boehm, Kevin M; Stapleton, Christopher J; Mehta, Brijesh P; Nahed, Brian V; Ogilvy, Christopher S

    2013-10-01

    Acute ischemic stroke resulting from intracranial vessel occlusion is associated with high morbidity and mortality. The mainstays of therapy are fibrinolytics and mechanical thrombectomy in properly selected patients. A new Food and Drug Administration-approved technology to perform thrombectomy, retrievable stenting, may provide superior revascularization rates and improved patient outcomes. We analyzed the cumulative human experience reported for the Trevo Pro Retrieval System (Stryker, Kalamazoo, MI, USA) and the Solitaire FR Revascularization Device (ev3, Irvine, CA, USA) as the definitive treatment for acute ischemic stroke. A literature search was undertaken to identify studies using the retrievable stents published up to September 2012. Nineteen studies identified a total of 576 patients treated with either the Trevo (n=221) or Solitaire (n=355) devices. Pooled data analysis identified median baseline National Institutes of Health Stroke Scale scores of 18.5 ± 0.289 (standard error of the mean) and 17.9 ± 0.610, and time to recanalization of 53.9 ± 23.6 minutes and 59.0 ± 8.0 minutes for the Trevo and Solitaire groups, respectively. Recanalization was variably defined by individual studies, most commonly achieving at least a thrombolysis in cerebral infarction score of 2a-3 or a thrombolysis in myocardial infarction score of 2-3. Revascularization (83%, 82%), mortality (31%, 14%), hemorrhage (8%, 6%), device complications (5%, 6%), and good patient outcomes (51%, 47%) were found with the Trevo and Solitaire devices, respectively. Preliminary analysis reveals excellent clinical outcomes for retrievable stent technology. This may be attributable to both high rates of revascularization with a relatively short time to perfusion restoration.

  12. Thrombectomy for Acute Stroke in Childhood: A Case Report, Literature Review, and Recommendations.

    PubMed

    Buompadre, Maria Celeste; Andres, Kathleen; Slater, Lee-Anne; Mohseni-Bod, Hadi; Guerguerian, Anne-Marie; Branson, Helen; Laughlin, Suzanne; Armstrong, Derek; Moharir, Mahendranath; deVeber, Gabrielle; Humpl, Tilman; Honjo, Osami; Keshavjee, Shaf; Ichord, Rebecca; Pereira, Vitor; Dlamini, Nomazulu

    2017-01-01

    The updated American Heart Association/American Stroke Association guidelines include recommendation for thrombectomy in certain adult stroke cases. The safety and efficacy of thrombectomy in children are unknown. An 8-year-old girl experienced acute stroke symptoms on two occasions while therapeutically anticoagulated on Novalung. Computed tomography scans showed proximal vessel thrombi, which were retrieved using a Trevo device without hemorrhagic complications. Postprocedural assessment found respective decreases in the National Institutes of Health Stroke Scale score from 10 to 4 and 12 to 7. The indications for treatment and early benefits observed in our case are consistent with other pediatric thrombectomy cases reported. However, publication bias and the heterogeneity of reported cases prevent drawing conclusions about the safety and efficacy of thrombectomy in children. Anticipating that updates to adult stroke guidelines would likely incite stroke providers to consider thrombectomy in children, our institution developed guidelines for thrombectomy before the index patient. Establishing institutional guidelines before considering thrombectomy in children may optimize patient safety.

  13. Thrombectomy using a stent retriever with artificially induced vertebral artery vasospasm in a patient with acute basilar artery occlusion: a case report

    PubMed Central

    Kim, Sanghyeon; Choi, Jae-Hyung

    2015-01-01

    An acute basilar artery occlusion is not an uncommon cause of stroke. It represents 6–10% of large vessel strokes and has been associated with poor clinical outcomes. Multimodal treatments have been introduced to recanalise a basilar artery occlusion successfully. However, all mechanical thrombectomy devices are not always usable in an emergent situation. We present a case of basilar artery occlusion treated with a stent retriever assisted by a vertebral artery vasospasm. We attempted thrombectomy with a stent retriever several times. However, the captured thrombus was not pulled out and migrated to the distal basilar artery and posterior cerebral artery due to anterograde flow of the vertebral artery. We carefully advanced the catheter into the distal vertebral artery and generated a vasospasm. The vertebral artery vasospasm reduced the forward flow significantly like a balloon-guided catheter. The thrombus was pulled out with the stent. PMID:26678752

  14. Combined Hydrophobicity and Mechanical Durability through Surface Nanoengineering

    PubMed Central

    Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; Furrer, David U.; Burlatsky, Sergei F.; Filburn, Thomas P.

    2015-01-01

    This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability. PMID:25851026

  15. Combined hydrophobicity and mechanical durability through surface nanoengineering

    DOE PAGES

    Elliott, Paul R.; Stagon, Stephen P.; Huang, Hanchen; ...

    2015-04-08

    This paper reports combined hydrophobicity and mechanical durability through the nanoscale engineering of surfaces in the form of nanorod-polymer composites. Specifically, the hydrophobicity derives from nanoscale features of mechanically hard ZnO nanorods and the mechanical durability derives from the composite structure of a hard ZnO nanorod core and soft polymer shell. Experimental characterization correlates the morphology of the nanoengineered surfaces with the combined hydrophobicity and mechanical durability, and reveals the responsible mechanisms. Such surfaces may find use in applications, such as boat hulls, that benefit from hydrophobicity and require mechanical durability.

  16. Iliocaval Stenosis and Iliac Venous Thrombosis in Retroperitoneal Fibrosis: Percutaneous Treatment by Use of Hydrodynamic Thrombectomy and Stenting

    SciTech Connect

    Vorwerk, Dierk; Guenther, Rolf W.; Wendt, Georg; Neuerburg, Joerg; Schuermann, Karl

    1996-11-15

    A case of bilateral iliac stenosis and caval stenosis due to retroperitoneal fibrosis was treated by caval stenting and iliac balloon angioplasty, but was complicated by subsequent iliac thrombosis. Venous thrombectomy was successfully achieved by hydrodynamic thrombectomy, and iliac patency was stabilized by bilateral stent insertion.

  17. The Role of Manual Aspiration Thrombectomy in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI.

    PubMed

    Alak, Aiman; Jolly, Sanjit S

    2016-03-01

    In STEMI, primary PCI restores macrovascular coronary blood flow effectively but microvascular perfusion remains a challenge. Thrombus has the potential to embolize to the microvasculature limiting effective coronary blood flow. Thrombus burden is associated with a higher mortality and manual aspiration thrombectomy has the potential to reduce thrombus burden. The first large trial of routine aspiration thrombectomy (TAPAS, N = 1071) showed an improvement in myocardial blush and an unexpected reduction in mortality. Reinforcing the enthusiasm for this finding meta-analysis of small trials also showed a reduction in mortality, which led to routine manual thrombectomy becoming a class IIa recommendation in the American and European Guidelines for STEMI. Subsequently; however, large trials such as TOTAL (N = 10,732) and TASTE (N = 7244) and meta-analysis showed an increase in the risk of stroke with routine manual thrombectomy but no improvement in mortality, myocardial infarction, stent thrombosis, or severe heart failure. As such, manual thrombectomy should not be routinely used instead saving it as a bailout procedure as indicated.

  18. Percutaneous hydrodynamic thrombectomy of acute thrombosis in transjugular intrahepatic portosystemic shunt (TIPS): A feasibility study in five patients

    SciTech Connect

    Raat, Henricus; Stockx, Luc; Ranschaert, Eric; Nevens, Frederik; Wilms, Guy; Baert, Albert L.

    1997-05-15

    Purpose. To evaluate the feasibility of percutaneous hydrodynamic thrombectomy in restoring patency of acutely thrombosed stent-shunts after transjugular intrahepatic portosystemic shunt (TIPS).MethodsPercutaneous hydrodynamic thrombectomy was performed in five consecutive patients with angiographically documented complete thrombosis of the stent-shunt which developed within 2 weeks after the TIPS procedure. Thrombectomy was performed with a hydrolytic suction thrombectomy catheter, introduced via a transjugular approach.ResultsIn all patients, immediate restoration of patency of the stent-shunt was achieved after deploying additional stent(s) to cover residual adherent mural thrombus. In two patients early reocclusion occurred.ConclusionPercutaneous hydrolytic suction thrombectomy in acutely thrombosed intrahepatic portosystemic shunts is technically feasible.

  19. Pulmonary Hypertension Among End-Stage Renal Failure Patients Following Hemodialysis Access Thrombectomy

    SciTech Connect

    Harp, Richard J.; Stavropoulos, S. William; Wasserstein, Alan G.; Clark, Timothy W.I.

    2005-01-15

    Purpose: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy.Methods: A retrospective case-control study was performed. Cases (n = 88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n = 100, group 1), and controls with ESRD but no prior thrombectomy procedures (n = 117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression.Results: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n = 23), 10% (n = 9) and 16% (n = 14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p = 0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n = 49), 10% (n = 12) and 4% (n = 5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR = 1.5), although this failed to reach statistical significance (p = 0.14).Conclusion: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial hypertension

  20. Stentriever thrombectomy with distal protection device for carotid free floating thrombus: a technical case report.

    PubMed

    Giragani, Suresh; Balani, Ankit; Agrawal, Vikas

    2017-01-18

    We report the clinical details, imaging findings and management of a 45-year-old man who presented with recurrent transient ischemic attacks due to carotid free floating thrombus. Free floating thrombus of the carotid artery is a very rare condition with a high risk of distal embolic shower. The optimal treatment options are debatable and include medical management, surgical thrombectomy and endovascular thrombectomy. We describe the use of a stentriever with filter protection in the management of carotid free floating thrombus as a novel treatment option.

  1. Stentriever thrombectomy with distal protection device for carotid free floating thrombus: a technical case report.

    PubMed

    Giragani, Suresh; Balani, Ankit; Agrawal, Vikas

    2017-01-25

    We report the clinical details, imaging findings and management of a 45-year-old man who presented with recurrent transient ischemic attacks due to carotid free floating thrombus. Free floating thrombus of the carotid artery is a very rare condition with a high risk of distal embolic shower. The optimal treatment options are debatable and include medical management, surgical thrombectomy and endovascular thrombectomy. We describe the use of a stentriever with filter protection in the management of carotid free floating thrombus as a novel treatment option.

  2. Combination of metformin with chemotherapeutic drugs via different molecular mechanisms.

    PubMed

    Peng, Mei; Darko, Kwame Oteng; Tao, Ting; Huang, Yanjun; Su, Qiongli; He, Caimei; Yin, Tao; Liu, Zhaoqian; Yang, Xiaoping

    2017-03-01

    Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits. Interestingly, metformin experiences a diversity of molecular mechanisms when it combines different chemotherapeutic drugs. For example, AMPK/mTOR signaling pathway activation plays a major role when it combines with hormone modulating drugs. In contrast, suppression of HIF-1, p-gp and MRP1 protein expression is its main mechanism when metformin combines with anti-metabolites. Furthermore, when combining of metformin with antibiotics, inhibition of oxidative stress and inflammatory signaling pathway becomes a novel pharmaceutical mechanism for its cardio-protective effect. Induction of apoptotic mitochondria and nucleus could be the major player for the synergistic effect of its combination with cisplatin. In contrast, down-regulation of lipoprotein or cholesterol synthesis might be the undefined molecular base when metformin combines with taxane. Thus, deep exploration of molecular mechanisms of metformin with these different drugs is critical to understand its synergistic effect and help for personalized administration. In this mini-review, detailed molecular mechanisms of these combinations are discussed and summarized. This work will promote better understanding of molecular mechanisms of metformin and provide precise targets to identify specific patient groups to achieve satisfactory treatment efficacy.

  3. Endovascular treatment of iliofemoral deep vein thrombosis in pregnancy using US-guided percutaneous aspiration thrombectomy

    PubMed Central

    Gedikoglu, Murat; Oguzkurt, Levent

    2017-01-01

    PURPOSE We aimed to describe ultrasonography (US)-guided percutaneous aspiration thrombectomy in pregnant women with iliofemoral deep vein thrombosis. METHODS This study included nine pregnant women with acute and subacute iliofemoral deep vein thrombosis, who were severe symptomatic cases with massive swelling and pain of the leg. Patients were excluded from the study if they had only femoropopliteal deep vein thrombosis or mild symptoms of deep vein thrombosis. US-guided percutaneous aspiration thrombectomy was applied to achieve thrombus removal and uninterrupted venous flow. The treatment was considered successful if there was adequate venous patency and symptomatic relief. RESULTS Complete or significant thrombus removal and uninterrupted venous flow from the puncture site up to the iliac veins were achieved in all patients at first intervention. Complete relief of leg pain was achieved immediately in seven patients (77.8%). Two patients (22.2%) had a recurrence of thrombosis in the first week postintervention. One of them underwent a second intervention, where percutaneous aspiration thrombectomy was performed again with successful removal of thrombus and establishment of in line flow. Two patients were lost to follow-up after birth. None of the remaining seven patients had rethrombosis throughout the postpartum period. Symptomatic relief was detected clinically in these patients. CONCLUSION Endovascular treatment with US-guided percutaneous aspiration thrombectomy can be considered as a safe and effective way to remove thrombus from the deep veins in pregnant women with acute and subacute iliofemoral deep vein thrombosis. PMID:27801353

  4. Coronary artery embolism from infectious endocarditis treated with catheter thrombectomy using a GuideLiner catheter.

    PubMed

    Oestreich, Brett A; Sommer, Per; Armstrong, Ehrin J

    2016-04-01

    A 27-year-old male with history of IV drug use and recurrent endocarditis necessitating bioprosthetic mitral and tricuspid valve replacements presented with 2 weeks of fevers and chest pain. ECG revealed inferior ST-elevation myocardial infarction and he was taken urgently to the cardiac catheterization laboratory. Coronary angiography revealed thrombotic occlusion of the distal right coronary artery (RCA) with no angiographic evidence of atherosclerotic disease. Aspiration thrombectomy was performed followed by rheolytic thrombectomy. Despite multiple attempts at thrombectomy, significant residual organized thrombus persisted in the distal RCA. Therefore, further thrombectomy was performed by placing a GuideLiner catheter (Vascular Solutions, Minneapolis, MN) deep within the right coronary artery near the bifurcation into the posterior descending and posterior left ventricular arteries. After repeat aspiration, there was significant improvement with thrombolysis in myocardial infarction 3 flow. Intravascular ultrasound of the RCA revealed a normal-appearing vessel without evidence of atherosclerotic disease and mild residual thrombus. The decision was made to not pursue stent placement, given the concern for a likely embolic source. Following the procedure, the patient's chest pain resolved and his ST-segments normalized.

  5. [Thrombosis of the right atrium after umbilical venous catheterization. Favourable outcome after early thrombectomy].

    PubMed

    Paupe, A; Lenclen, R; Blanc, P; Chassevent, J; Hoenn, E; Molho, M; Zannier, D; Olivier-Martin, M

    1992-02-01

    A case of right atrial thrombosis after venous umbilical catheterization in a 21 day-old premature newborn is reported. The initiating factors of such an accident and its clinical signs are evocated. The authors emphasize the value of a systematic ultrasonographic supervision of newborns with central catheters for a long period of time and the value of surgical thrombectomy.

  6. Thrombectomy reduces the systemic complications in device-related right atrial septic thrombosis

    PubMed Central

    Sontineni, Siva Prasad; White, Michael; Singh, Sindhu; Arouni, Amy; Cloutier, David; Nair, Chandra K; Mohiuddin, Syed M

    2009-01-01

    BACKGROUND: Septic thrombosis of the right atrium is an unusual complication associated with the use of indwelling devices. The optimal management of this condition is unclear. Our experience with a patient with hemodialysis catheter-related septic thrombosis of the right atrium illustrates the difficulties associated with this condition. OBJECTIVES: To determine the effects of surgical thrombectomy compared with nonsurgical treatment with antibiotics (with or without anticoagulation) on mortality rates and complications in patients with device-related septic thrombosis of the right atrium. METHODS: A retrospective analysis of all reported cases of device-related right heart septic thrombosis in which therapy and outcome were reported was conducted using a PubMed search in the English-language literature (1985 to 2006). RESULTS: Forty cases of device-related right atrial septic thromboses were reported in the literature during the chosen time period. The treatments administered were none (12.5%), antibiotics (12.5%), antibiotics and anticoagulation (20%), and thrombectomy (55%). The mean clot size was significantly larger in patients who underwent thrombectomy. All untreated patients died. Excluding the untreated patients from the analysis, systemic complications were significantly lower in the thrombectomy group than in the groups receiving nonsurgical therapies. Using multivariate modelling with survival as the primary outcome, age, sex, clot size, clot location, microbial organism or type of treatment were not predictive of the outcome. CONCLUSION: Device-related right atrial septic thrombosis is associated with significant mortality and is uniformly fatal if untreated. Surgical thrombectomy is associated with less frequent systemic complications. A well-designed prospective, randomized trial is needed to determine the optimal treatment of this condition. PMID:19214299

  7. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Allowable mechanisms and combinations of mechanisms. 280.94 Section 280.94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... OPERATORS OF UNDERGROUND STORAGE TANKS (UST) Financial Responsibility § 280.94 Allowable mechanisms...

  8. View Combination: A Generalization Mechanism for Visual Recognition

    ERIC Educational Resources Information Center

    Friedman, Alinda; Waller, David; Thrash, Tyler; Greenauer, Nathan; Hodgson, Eric

    2011-01-01

    We examined whether view combination mechanisms shown to underlie object and scene recognition can integrate visual information across views that have little or no three-dimensional information at either the object or scene level. In three experiments, people learned four "views" of a two dimensional visual array derived from a three-dimensional…

  9. Combined quantum mechanical/molecular mechanics modeling for large organometallic and metallobiochemical systems

    NASA Astrophysics Data System (ADS)

    Leong, Max Kangchien

    A method of combined quantum mechanics/molecular mechanics has been developed to model larger organometallic and metallobiochemical systems where neither quantum mechanics nor molecular mechanics, applied separately, can solve the problem. An electronically transparent interface, which allows charge transfers between the quantum and classical fragments, is devised and realized by employing a special iterative procedure of double (intrafragment and interfragment) self-consistent calculations. The combined QM/MM scheme was successfully applied to model iron picket-fence porphyrin, vitamin B12, aquocobalamin, and vitamin B12 coenzyme molecules.

  10. Surgical thrombectomy and transluminal balloon angioplasty for failed above-knee femoropopliteal polytetrafluoroethylene bypass grafts.

    PubMed

    Costanza, Michael J; Neschis, David G; Queral, Luis A; Flinn, William R

    2004-03-01

    Endovascular therapy offers an alternative to redo bypass or surgical graft revision for failed above-knee femoropopliteal PTFE bypass grafts. We evaluated the outcome of surgical thrombectomy and balloon angioplasty for the treatment of thrombosed bypass grafts. Thirty selected patients with thrombosed above-knee femoropopliteal PTFE bypass grafts were treated. Under local anesthesia, a surgical thrombectomy followed by bypass graft angiography and balloon angioplasty of perianastomotic stenoses was performed. Stents were used selectively for suboptimal angioplasty results. Patients underwent duplex scanning of the bypass graft postoperatively and at 6-month intervals. Life-table analysis and log-rank (Mantel-Cox) comparisons were performed. Patients were categorized into two groups on the basis of time elapsed from initial bypass graft construction to graft failure. Group 1 included 21 patients with a mean time to graft failure of 10 months (range, 0-20). Surgical thrombectomy was successful in 20 grafts (95%) and 17 patients had a stent placed after angioplasty. Rethrombosis occurred within 30 days in seven grafts (33%) in group 1 and major amputations were performed in six patients (28%). Group 2 included nine patients with a mean time to initial bypass graft failure of 48 months (range, 29-96). All patients in group 2 had a successful surgical thrombectomy and all received a stent. None of the grafts treated in group 2 reoccluded within 30 days of intervention and one patient (11%) went on to require a major amputation. By life-table analysis, the 6- and 12-month patency for group 1 was 15.3% and 5.1%, compared to 58.3% and 38.9% for group 2 (p = 0.027). Surgical thrombectomy along with balloon angioplasty has an unacceptably high rate of failure and limb loss in patients treated for early (<2 years) femoropopliteal PTFE bypass graft thrombosis. Surgical graft revision or redo bypass is recommended to achieve successful revascularization in these patients

  11. Behavior of cracked cylinders under combined thermal and mechanical loading

    SciTech Connect

    Ignaccolo, S.

    1996-12-01

    Nuclear pressure vessels and pipings can be submitted in their life to severe mechanical and thermal loadings. Engineering methods easy to apply, but sufficiently accurate, are needed to assess the flaws. In the field of non-linear fracture mechanics a lot of work has been achieved for structures submitted to mechanical loadings. But for thermal loadings, and particularly for thermal gradients, only few contributions are available. The authors propose, here, to present the main results of a complete set of finite element computations, conducted in France by CEA, EDF and FRAMATOME, on cracked cylinders submitted to combined mechanical and thermal loads. The interaction between these two types of loads is analyzed in the cases of austenitic and ferritic structures. Moreover, these results are compared to the predictions obtained by simplified engineering methods (R6 procedure, J{sub SA16}, and J{sub EDF} approaches). Their domain of validity is also discussed.

  12. 40 CFR 280.94 - Allowable mechanisms and combinations of mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Allowable mechanisms and combinations of mechanisms. 280.94 Section 280.94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) TECHNICAL STANDARDS AND CORRECTIVE ACTION REQUIREMENTS FOR OWNERS...

  13. Antiphospholipid syndrome and acute myocardial infarction: treatment with thrombectomy and abciximab.

    PubMed

    Martí, Vicens; Seixo, Filipe; Santaló, Miguel; Serra, Antonio

    2014-01-01

    Antiphospholipid syndrome (APS) is an autoimmune coagulation disorder that manifests clinically as venous and arterial thrombosis, and may affect any tissue or organ. Coronary artery involvement, however, is very rare. Case reports in the literature describing patients with coronary acute syndrome and APS treated with coronary angioplasty show conflicting results. We report an adult male patient with APS who presented with an acute myocardial infarction. Given the high risk of thrombosis in these patients, he was treated percutaneously with thrombectomy and abciximab. We review the few cases of coronary angioplasty in patients with APS reported to date. To our knowledge, this is the first case in which acute myocardial infarction due to thrombotic coronary occlusion was treated with thrombectomy and abciximab without stenting the artery.

  14. Supradiaphragmatic Inferior Vena Caval Thrombectomy Without Cardiopulmonary Bypass: A Case Series at a Single Center

    PubMed Central

    Soleimani, Mohammad; Mohammadi, Reza; Masoumi, Navid; Safarinejad, Mohammad Reza

    2016-01-01

    Introduction Inferior vena cava tumor thrombectomy in renal cell carcinoma patients is a challenging procedure, frequently requiring the vascular bypass technique for high-level thrombi with additional complications. Adopting a technique such as intrapericardial control in selected cases will circumvent these problems. Here, we present the results of our intrapericardial control technique during supradiaphragmatic inferior vena caval tumor thrombectomy. Case Presentation The records of six patients with supradiaphragmatic tumor thrombi, who underwent radical nephrectomy and thrombectomy at our center with intrapericardial control between the years 2008 and 2015, were retrospectively reviewed. The patients’ characteristics, intra- and postoperative data, histology, and follow-up records were gathered and compared. There were no immediate or 30-day postoperative deaths. The mean age of the patients was 61.3 years (range 46 - 75). The total mean duration of surgery was 315 minutes and the mean amount of transfused red blood cells was 4.33 units during surgery and 0.8 units in the postoperative period. The average hospitalization duration was 8 days (range 5 - 17). Tumor stage was T3 in four patients and T4 in two, due to ipsilateral adrenal involvement. The mean duration of follow-up was 33.5 months. Only one of the patients developed recurrences, first in the tumor bed and then at the site of the skin incision; these were excised with no apparent complications. Conclusions Radical nephrectomy and tumor thrombectomy by intrapericardial control without cardiopulmonary bypass and hypothermic circulatory arrest is a safe and effective procedure that can avoid serious intra- and postoperative complications while providing acceptable cancer-control and mortality results. PMID:27878115

  15. Rheolytic Thrombectomy of an Acutely Thrombosed Transjugular Intrahepatic Portosystemic Stent Shunt

    SciTech Connect

    Mueller-Huelsbeck, Stefan; Link, Johann; Hoepfner, Michael; Loeser, Christian; Heller, Martin

    1996-04-15

    As an alternative to chemical thrombolysis, an acutely occluded transjugular intrahepatic portosystemic stent shunt in a 72-year-old woman was successfully recanalized using a 5 Fr rheolytic catheter system. No adjunctive thrombectomy treatment was necessary. The underlying stenotic leason was treated with percutaneous transluminal angioplasty and a Palmaz stent. Immediately after the intervention optimal shunt flow was achieved. Ascites vanished within a few days and no further bleeding complications appeared.

  16. Thrombolysis and thrombectomy in patients treated with dabigatran with acute ischemic stroke: Expert opinion.

    PubMed

    Diener, H C; Bernstein, R; Butcher, K; Campbell, B; Cloud, G; Davalos, A; Davis, S; Ferro, J M; Grond, M; Krieger, D; Ntaios, G; Slowik, A; Touzé, E

    2017-01-01

    Systemic thrombolysis with rt-PA is contraindicated in patients with acute ischemic stroke anticoagulated with dabigatran. This expert opinion provides guidance on the use of the specific reversal agent idarucizumab followed by rt-PA and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran. The use of idarucizumab followed by rt-PA is covered by the label of both drugs.

  17. Feasibility of Crosslinked Acrylic Shape Memory Polymer for a Thrombectomy Device

    PubMed Central

    Muschenborn, Andrea D.; Hearon, Keith; Volk, Brent L.; Conway, Jordan W.; Maitland, Duncan J.

    2014-01-01

    Purpose To evaluate the feasibility of utilizing a system of SMP acrylates for a thrombectomy device by determining an optimal crosslink density that provides both adequate recovery stress for blood clot removal and sufficient strain capacity to enable catheter delivery. Methods Four thermoset acrylic copolymers containing benzylmethacrylate (BzMA) and bisphenol A ethoxylate diacrylate (Mn~512, BPA) were designed with differing thermomechanical properties. Finite element analysis (FEA) was performed to ensure that the materials were able to undergo the strains imposed by crimping, and fabricated devices were subjected to force-monitored crimping, constrained recovery, and bench-top thrombectomy. Results Devices with 25 and 35 mole% BPA exhibited the highest recovery stress and the highest brittle response as they broke upon constrained recovery. On the contrary, the 15 mole % BPA devices endured all testing and their recovery stress (5 kPa) enabled successful bench-top thrombectomy in 2/3 times, compared to 0/3 for the devices with the lowest BPA content. Conclusion While the 15 mole% BPA devices provided the best trade-off between device integrity and performance, other SMP systems that offer recovery stresses above 5 kPa without increasing brittleness to the point of causing device failure would be more suitable for this application. PMID:25414549

  18. Treatment of acute embolic occlusions of the subclavian and axillary arteries using a rotational thrombectomy device.

    PubMed

    Zeller, T; Frank, U; Bürgelin, K; Sinn, L; Horn, B; Schwarzwälder, U; Roskamm, H; Neumann, F J

    2003-05-01

    Acute embolic or local thrombotic ischaemia of the upper limbs can be treated by embolectomy or by endovascular techniques. We report here on the endovascular thrombectomy of acute embolic occlusions of subclavian and axillary arteries in two patients using a rotational thrombectomy device and give an overview about the actual literature. Two female patients, each with a history of multivessel coronary disease and intermittent atrial fibrillation, complained of sudden onset of pain at rest and paleness of the left and right arm, respectively. Duplex ultrasound showed a localized embolic occlusion of the left subclavian artery and the bifurcation of the brachial artery in the first patient and a localized embolic occlusion of the distal right subclavian and axillary artery in the second patient. In the first patient, the left subclavian artery was reopened using a 8F-Rotarex device via the femoral access, while the bifurcation of the brachial artery was reopened by local thrombolysis using 25 mg rt-PA because of the insufficient length of the thrombectomy device of 80 cm. In the second patient, the right subclavian and axillary arteries were reopened using a 6F-Rotarex device. Follow-up examinations before discharge and after 6 months showed normalized perfusion of the arms of both patients.

  19. Performance of a thrombectomy device for aspiration of thrombus with various sizes based on a computational fluid dynamic modeling.

    PubMed

    Soleimani, Sajjad; Dubini, Gabriele; Pennati, Giancarlo

    2016-06-01

    It is important to thoroughly remove the thrombus within the course of aspiration thrombectomy; otherwise, it may lead to further embolization. The performance of the aspiration thrombectomy device with a generic geometry is studied through the computational approach. In order to model the thrombus aspiration, a real left coronary artery is chosen while thrombi with various sizes are located at the bifurcation area of the coronary artery and, depending on the size of the thrombus, it is stretched toward the side branches. The thrombus occupies the artery resembling the blood current obstruction in the coronary vessel similar to the situation that leads to heart attack. It is concluded that the aspiration ability of the thrombectomy device is not linked to the thrombus size; it is rather linked to the aspiration pressure and thrombus age (organized versus fresh thrombus). However, the aspiration time period correlates to the thrombus size. The minimum applicable aspiration pressure is also investigated in this study.

  20. Gelled Complex Fluids: Combining Unique Structures with Mechanical Stability.

    PubMed

    Stubenrauch, Cosima; Gießelmann, Frank

    2016-03-01

    Gelled complex fluids are soft materials in which the microstructure of the complex fluid is combined with the mechanical stability of a gel. To obtain a gelled complex fluid one either adds a gelator to a complex fluid or replaces the solvent in a gel by a complex fluid. The most prominent example of a "natural" gelled complex fluid is the cell. There are various strategies by which one can form a gelled complex fluid; one such strategy is orthogonal self-assembly, that is, the independent but simultaneous formation of two coexisting self-assembled structures within one system. The aim of this Review is to describe the structure and potential applications of various man-made gelled complex fluids and to clarify whether or not the respective system is formed by orthogonal self-assembly.

  1. Manual Aspiration Thrombectomy with Stent Placement: Rapid and Effective Treatment for Phlegmasia Cerulea Dolens with Impending Venous Gangrene

    SciTech Connect

    Oguzkurt, Levent Tercan, Fahri; Ozkan, Ugur

    2008-01-15

    Phlegmasia cerulea dolens is an uncommon but potentially life-threatening complication of acute deep vein thrombosis. It is an emergency and delay in treatment may cause death or loss of the patient's limb. Surgical thrombectomy is the recommended treatment in venous gangrene. Catheter-directed intrathrombus thrombolysis has been reported as successful, but it may require a lengthy infusion. Manual aspiration thrombectomy may clear the entire thrombus with no need for thrombolytic administration and provide rapid and effective treatment for patients with phlegmasia cerulea dolens with impending venous gangrene.

  2. Apparent-Strain Correction for Combined Thermal and Mechanical Testing

    NASA Technical Reports Server (NTRS)

    Johnson, Theodore F.; O'Neil, Teresa L.

    2007-01-01

    Combined thermal and mechanical testing requires that the total strain be corrected for the coefficient of thermal expansion mismatch between the strain gage and the specimen or apparent strain when the temperature varies while a mechanical load is being applied. Collecting data for an apparent strain test becomes problematic as the specimen size increases. If the test specimen cannot be placed in a variable temperature test chamber to generate apparent strain data with no mechanical loads, coupons can be used to generate the required data. The coupons, however, must have the same strain gage type, coefficient of thermal expansion, and constraints as the specimen to be useful. Obtaining apparent-strain data at temperatures lower than -320 F is challenging due to the difficulty to maintain steady-state and uniform temperatures on a given specimen. Equations to correct for apparent strain in a real-time fashion and data from apparent-strain tests for composite and metallic specimens over a temperature range from -450 F to +250 F are presented in this paper. Three approaches to extrapolate apparent-strain data from -320 F to -430 F are presented and compared to the measured apparent-strain data. The first two approaches use a subset of the apparent-strain curves between -320 F and 100 F to extrapolate to -430 F, while the third approach extrapolates the apparent-strain curve over the temperature range of -320 F to +250 F to -430 F. The first two approaches are superior to the third approach but the use of either of the first two approaches is contingent upon the degree of non-linearity of the apparent-strain curve.

  3. Thrombectomy assisted by carotid stenting in acute ischemic stroke management: benefits and harms.

    PubMed

    Steglich-Arnholm, Henrik; Holtmannspötter, Markus; Kondziella, Daniel; Wagner, Aase; Stavngaard, Trine; Cronqvist, Mats E; Hansen, Klaus; Højgaard, Joan; Taudorf, Sarah; Krieger, Derk Wolfgang

    2015-12-01

    Extracranial carotid artery occlusion or high-grade stenosis with concomitant intracranial embolism causes severe ischemic stroke and shows poor response rates to intravenous thrombolysis (IVT). Endovascular therapy (EVT) utilizing thrombectomy assisted by carotid stenting was long considered risky because of procedural complexities and necessity of potent platelet inhibition-in particular following IVT. This study assesses the benefits and harms of thrombectomy assisted by carotid stenting and identifies factors associated with clinical outcome and procedural complications. Retrospective single-center analysis of 47 consecutive stroke patients with carotid occlusion or high-grade stenosis and concomitant intracranial embolus treated between September 2011 and December 2014. Benefits included early improvement of stroke severity (NIHSS ≥ 10) or complete remission within 72 h and favorable long-term outcome (mRS ≤ 2). Harms included complications during and following EVT. Mean age was 64.3 years (standard deviation ±12.5), 40 (85%) patients received IVT initially. Median NIHSS was 16 (inter-quartile range 14-19). Mean time from stroke onset to recanalization was 311 min (standard deviation ±78.0). Early clinical improvement was detected in 22 (46%) patients. Favorable outcome at 3 months occurred in 32 (68%) patients. Expedited patient management was associated with favorable clinical outcome. Two (4%) patients experienced symptomatic hemorrhage. Eight (17%) patients experienced stent thrombosis. Four (9%) patients died. Thrombectomy assisted by carotid stenting seems beneficial and reasonably safe with a promising rate of favorable outcome. Nevertheless, adverse events and complications call for additional clinical investigations prior to recommendation as clinical standard. Expeditious patient management is central to achieve good clinical outcome.

  4. Suction Thrombectomy of Thrombotic Occlusion of the Subclavian Artery in a Case of Takayasu's Arteritis

    SciTech Connect

    Purkayastha, Sukalyan; Jayadevan, E.R.; Kapilamoorthy, T.R.; Gupta, A.K. E-mail: gupta@sctimst.ac.in

    2006-04-15

    Takayasu's arteritis, also known as pulseless disease, is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. Percutaneous removal of arterial thrombus with the use of several devices has been reported, with mixed results. We present a case of Takayasu's arteritis with thrombotic occlusion of the subclavian artery in which pulsed urokinase injection and suction thrombectomy were used to revascularize a threatened limb and to establish the sole arterial supply to the brain.

  5. Atomistic insight into the catalytic mechanism of glycosyltransferases by combined quantum mechanics/molecular mechanics (QM/MM) methods.

    PubMed

    Tvaroška, Igor

    2015-02-11

    Glycosyltransferases catalyze the formation of glycosidic bonds by assisting the transfer of a sugar residue from donors to specific acceptor molecules. Although structural and kinetic data have provided insight into mechanistic strategies employed by these enzymes, molecular modeling studies are essential for the understanding of glycosyltransferase catalyzed reactions at the atomistic level. For such modeling, combined quantum mechanics/molecular mechanics (QM/MM) methods have emerged as crucial. These methods allow the modeling of enzymatic reactions by using quantum mechanical methods for the calculation of the electronic structure of the active site models and treating the remaining enzyme environment by faster molecular mechanics methods. Herein, the application of QM/MM methods to glycosyltransferase catalyzed reactions is reviewed, and the insight from modeling of glycosyl transfer into the mechanisms and transition states structures of both inverting and retaining glycosyltransferases are discussed.

  6. Inactivation mechanism of glycerol dehydration by diol dehydratase from combined quantum mechanical/molecular mechanical calculations.

    PubMed

    Doitomi, Kazuki; Kamachi, Takashi; Toraya, Tetsuo; Yoshizawa, Kazunari

    2012-11-13

    Inactivation of diol dehydratase during the glycerol dehydration reaction is studied on the basis of quantum mechanical/molecular mechanical calculations. Glycerol is not a chiral compound but contains a prochiral carbon atom. Once it is bound to the active site, the enzyme adopts two binding conformations. One is predominantly responsible for the product-forming reaction (G(R) conformation), and the other primarily contributes to inactivation (G(S) conformation). Reactant radical is converted into a product and byproduct in the product-forming reaction and inactivation, respectively. The OH group migrates from C2 to C1 in the product-forming reaction, whereas the transfer of a hydrogen from the 3-OH group of glycerol to C1 takes place during the inactivation. The activation barrier of the hydrogen transfer does not depend on the substrate-binding conformation. On the other hand, the activation barrier of OH group migration is sensitive to conformation and is 4.5 kcal/mol lower in the G(R) conformation than in the G(S) conformation. In the OH group migration, Glu170 plays a critical role in stabilizing the reactant radical in the G(S) conformation. Moreover, the hydrogen bonding interaction between Ser301 and the 3-OH group of glycerol lowers the activation barrier in G(R)-TS2. As a result, the difference in energy between the hydrogen transfer and the OH group migration is reduced in the G(S) conformation, which shows that the inactivation is favored in the G(S) conformation.

  7. Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology.

    PubMed

    van der Kamp, Marc W; Mulholland, Adrian J

    2013-04-23

    Computational enzymology is a rapidly maturing field that is increasingly integral to understanding mechanisms of enzyme-catalyzed reactions and their practical applications. Combined quantum mechanics/molecular mechanics (QM/MM) methods are important in this field. By treating the reacting species with a quantum mechanical method (i.e., a method that calculates the electronic structure of the active site) and including the enzyme environment with simpler molecular mechanical methods, enzyme reactions can be modeled. Here, we review QM/MM methods and their application to enzyme-catalyzed reactions to investigate fundamental and practical problems in enzymology. A range of QM/MM methods is available, from cheaper and more approximate methods, which can be used for molecular dynamics simulations, to highly accurate electronic structure methods. We discuss how modeling of reactions using such methods can provide detailed insight into enzyme mechanisms and illustrate this by reviewing some recent applications. We outline some practical considerations for such simulations. Further, we highlight applications that show how QM/MM methods can contribute to the practical development and application of enzymology, e.g., in the interpretation and prediction of the effects of mutagenesis and in drug and catalyst design.

  8. Primary combined androgen blockade in localized disease and its mechanism.

    PubMed

    Namiki, Mikio; Kitagawa, Yasuhide; Mizokami, Atsushi; Koh, Eitetsu

    2008-04-01

    In spite of clinical practice guidelines such as NCI-PDQ - in which primary androgen deprivation therapy (PADT) is not recommended as the primary treatment for localized prostate cancer - many patients have been treated with PADT. One of the reasons is that urologists themselves permit patients' desire because they know the effectiveness of PADT for some patients in their experiences. In this review we demonstrate basic mechanisms and the clinical efficacy of primary combined androgen blockade (PCAB) for localized or locally advanced prostate cancer. Then we discuss which patients are candidates for PCAB, and show that more than 30% of low- or intermediate-risk localized prostate cancers could be controlled in the long term with only PCAB. Short-term or intermittent PADT could not be recommended because of the possibilities of changing the character of the cancer cells by incomplete androgen ablation. We propose algorithms for the treatment of localized prostate cancer not only in low- and intermediate-risk groups but also in the high-risk group.

  9. [Sorption and mechanism of surfactants on bentonite in combined pollution].

    PubMed

    Sun, Xiao-Hui; Lu, Ying-Ying; Chen, Shu-Guang; Li, Ling-Jian; Shen, Xue-You

    2007-04-01

    Sorption of cationic surfactant cetyl pyridinium chloride (CPC), anionic surfactant sodium dodecylbenzene sulfonate (SDBS) and nonionic surfactant Triton X-100 (TX-100) on bentonite was studied. The influences of cation-exchange capacity (CEC), temperature and salinity on the sorption of CPC were also discussed. The results indicate that the sorption of CPC on Na-bentonite is greater than that of TX-100 and SDBS, and SDBS hardly shows any sorption. CPC is adsorbed to Na-bentonite through a combination of hydrophobic bonding and cation-exchange. While TX-100 is adsorbed to Na-bentonite via the formation of an adsorption layer of twain surfactant molecule and hydrogenolysis of silicon-oxygen surface of bentonite and TX-100. The amount of SDBS adsorbed on Ca-bentonite increases with increasing surfactant concentration, reaching a maximum at 1.5 critical micelle concentration (CMC), and then decreases with increasing surfactant loading. The mechanism of the retention appears to be formation of a sparingly soluble Ca-SDBS species, and dissolution in the micelle. The amount of CPC adsorbed on bentonite decreases with increasing temperature, and increases with increasing CEC. NaCl can enhance the sorption of CPC on bentonite.

  10. Development of a surgical safety checklist for the performance of radical nephrectomy and tumor thrombectomy

    PubMed Central

    2012-01-01

    Background The surgical management of renal cell carcinoma with invasion of the renal vein or inferior vena cava is associated with significant rates of perioperative morbidity and mortality. In this report we propose a surgical checklist aimed at reducing adverse events associated with the resection of these tumors. Methods This review describes the development of an evidence- and experience-based surgical checklist aimed at improving the perioperative safety of patients undergoing radical nephrectomy and tumor thrombectomy. Results Reducing the risk of complications during the surgical management of renal tumors with venous invasion begins with appropriate pre-operative imaging aimed at defining the cranial extent of the tumor thrombus, thus facilitating accurate preoperative planning. Other key elements of the checklist are aimed at ensuring clear and precise pre-, intra- and postoperative communication between members of the multidisciplinary-care team. Conclusion A standardized surgical checklist may help to increase the perioperative safety of patients undergoing radical nephrectomy and tumor thrombectomy. Future validation studies are required to determine the clinical feasibility and post-implementation safety profile of this new checklist. PMID:23241448

  11. Percutaneous Introducibility of the Expandable Vascular Sheath System and Injury Potential of Balloon-Assisted Thrombectomy: Preliminary In Vivo Results

    SciTech Connect

    Brossmann, Joachim; Haghighi, Parviz; Bookstein, Joseph J.

    1999-01-15

    Purpose: To test the percutaneous introducibility of the expandable vascular sheath (EVS) system and the safety of percutaneous balloon-assisted thrombectomy. Methods: The EVS was inserted directly (n= 9) or through a 9.5 Fr regular vascular introducer sheath (n= 9) into the femoral arteries and veins and carotid arteries in four dogs (18-21 kg). Balloon-assisted thrombectomies were simulated in iliac arteries. Histologic examinations were done at sites of funnel deployment immediately (n= 4) and 25 days (n= 8) after the intervention. Results: The EVS was successfully introduced into six of nine vessels by a direct percutaneous approach. Balloon-assisted thrombectomy using the EVS device caused localized intimal denudation, disruption of the internal elastic lamina, and mild hemorrhages into the media; one arterial dissection at the site of funnel deployment was seen. All indirect insertions and funnel deployments were successful. Twenty-five days after the experiments, intimal hyperplasia was noted in all cases. Conclusion: Percutaneous balloon-assisted thrombectomy may cause mild vascular injuries. Direct percutaneous introduction of the EVS device cannot be recommended yet.

  12. Laser-activated shape memory polymer intravascular thrombectomy device

    NASA Astrophysics Data System (ADS)

    Small, Ward, IV; Wilson, Thomas S.; Benett, William J.; Loge, Jeffrey M.; Maitland, Duncan J.

    2005-10-01

    A blood clot (thrombus) that becomes lodged in the arterial network supplying the brain can cause an ischemic stroke, depriving the brain of oxygen and often resulting in permanent disability. As an alternative to conventional clot-dissolving drug treatment, we are developing an intravascular laser-activated therapeutic device using shape memory polymer (SMP) to mechanically retrieve the thrombus and restore blood flow to the brain. Thermal imaging and computer simulation were used to characterize the optical and photothermal behavior of the SMP microactuator. Deployment of the SMP device in an in vitro thrombotic vascular occlusion model demonstrated the clinical treatment concept.

  13. Oscillating probe aspiration thrombectomy: comparative in vitro evaluation of two concepts.

    PubMed

    Schmitz-Rode, T; Günther, R W

    1992-01-01

    Aspiration thrombectomy supported by an oscillating metal probe within the catheter allows continuous aspiration of large thrombi without catheter obstruction. Thrombus aspiration assisted by an ultrasound-driven probe (frequency 26 kHz) and by an electric motor-driven probe (frequency 40 Hz) was compared in two different in vitro models: aspiration of large clots from a Petri dish and recanalization of thrombotic occlusions in a flow model. Comparable results were found for a 1 mm ultrasound-driven probe and a 0.5 mm motor-driven probe. The motor-driven device, however, seems to be more appealing for in vivo application because of its simplicity, probe flexibility, absence of thermal effects, and low cost.

  14. Successful interventional thrombectomy of a basilar artery thrombus in a long-term LVAD patient.

    PubMed

    Zerdzitzki, Matthaeus; Schmid, Christof; Hirt, Stephan; Wendl, Christina; Schlachetzki, Felix; Camboni, Daniele

    2015-01-01

    Cerebral thromboembolism builds the Achilles heel for patients on left ventricular support (LVAD). Thrombolytic therapy is usually contraindicated considering the increased risk of intracranial hemorrhage in patients with LVAD under therapeutic oral anticoagulation with concomitant platelet inhibition. We report on an alternative approach to this dilemma. On day 1,091 of LVAD support (INCOR Berlin Heart), a 69 year-old male patient was admitted to a rural hospital unconscious with a left-sided hemiplegia. Cerebral computed tomography (CT) with CT angiography revealed a thromboembolic distal basilar artery occlusion. The patient was immediately transported to our medical center, where an interventional thrombectomy restored full patency of the vessel. The patient recovered without neurologic sequelae within days. This case highlights the fact that patients on LVAD support with a neurologic event should be immediately transferred to a neurovascular center for appropriate treatment including a neurointervention.

  15. YinYang atom: a simple combined ab initio quantum mechanical molecular mechanical model.

    PubMed

    Shao, Yihan; Kong, Jing

    2007-05-10

    A simple interface is proposed for combined quantum mechanical (QM) molecular mechanical (MM) calculations for the systems where the QM and MM regions are connected through covalent bonds. Within this model, the atom that connects the two regions, called YinYang atom here, serves as an ordinary MM atom to other MM atoms and as a hydrogen-like atom to other QM atoms. Only one new empirical parameter is introduced to adjust the length of the connecting bond and is calibrated with the molecule propanol. This model is tested with the computation of equilibrium geometries and protonation energies for dozens of molecules. Special attention is paid on the influence of MM point charges on optimized geometry and protonation energy, and it is found that it is important to maintain local charge-neutrality in the MM region in order for the accurate calculation of the protonation and deprotonation energies. Overall the simple YinYang atom model yields comparable results to some other QM/MM models.

  16. Soluble collagen approach to a combination tannage mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although complex salts of Cr(III) sulfate are currently the most effective tanning agents, salts of other metals, including aluminum, have been used either alone or in combination with vegetable tannins or other organic chemicals. In the present study, the interactions of metallic sulfates, and cond...

  17. Soluble collagen approach to a combination tannage mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although complex salts of Cr(III) sulfate are currently the most effective tanning agents, salts of other metals, including aluminum, have been used either alone or in combination with vegetable tannins or other organic chemicals. In the present study, the interactions of aluminum sulfate, and quebr...

  18. Combined Mechanical and Electrical Study of Polymers of Biological Origin

    NASA Astrophysics Data System (ADS)

    Zsoldos, G.; Szoda, K.; Marossy, K.

    2017-02-01

    Thermally Simulated Depolarization Current measurement is an excellent but not widely used method for identifying relaxation processes in polymers. The DMA method is used here to analyze the mechanical changes depend on temperature in biopolymers. The two techniques take advantage of the energy changes involved in the various phase transitions of certain polymer molecules. This allows for several properties of the material to be ascertained; melting points, enthalpies of melting, crystallization temperatures, glass transition temperatures and degradation temperatures. The examined biopolymer films are made from biological materials such as proteins and polysaccharides. These materials have gained wide usage in pharmaceutical, medical and food areas. The uses of biopolymer films depend on their structure and mechanical properties. This work is based on pectin and gelatin films. The films were prepared by casting. The casting technique used aqueous solutions in each case of sample preparation. The manufacturing process of the pectin and gelatin films was a single stage solving process.

  19. In Vitro Evaluation of a Rheolytic Thrombectomy System for Clot Removal from Five Different Temporary Vena Cava Filters

    SciTech Connect

    Buecker, Arno; Neuerburg, Joerg; Schmitz-Rode, Thomas; Vorwerk, Dierk; Guenther, Rolf W.

    1997-11-15

    Purpose: To evaluate the feasibility of thrombus removal from temporary vena cava filters using a rheolytic thrombectomy device and to assess the embolization rate of this procedure. Methods: Five temporary vena cava filters together with porcine thrombi were placed in a vena cava flow model (semitranslucent silicone tube of 23 mm diameter, pulsatile flow at a mean flow rate of 4 L/min). A rheolytic thrombectomy system (Hydrolyser) was used with a 9 Fr guiding catheter to remove the clots. The effluent was passed through filters of different size and the amount of embolized particles as well as the remaining thrombus were measured. Results: Thrombus removal rates ranged from 85% to 100%. Embolization rates between 47% and 60% were calculated for the different filters. Conclusion: The Hydrolyser is able to remove sufficiently high amounts of thrombus from temporary vena cava filters. However, the amount of embolized particles makes it impossible to utilize this method without special precautions against embolization.

  20. Acute Middle Cerebral Artery Occlusion Treated by Thrombectomy in a Patient with Myelodysplastic Syndrome and Severe Thrombocytopenia

    PubMed Central

    Onder, Halil; Murat Arsava, E.; Arat, Anıl; Akif Topcuoglu, M.

    2015-01-01

    Objective Experience on thrombolysis and/or thrombectomy for acute major ischemic strokes in the setting of deep (less than 40,000/mm3) thrombocytopenia is limited. Methods Case report and review of the literature. Results A 63-year-old female with myelodysplastic syndrome presented with left middle cerebral artery stroke within 2 hours of symptom onset. Severe thrombocytopenia (10.000/mm3) precluded systemic thrombolysis. However, endovascular thrombectomy provided successful recanalization and dramatic clinical recovery with NIHSS score decreasing from 20 to 2 soon after the procedure. Her modified Rankin scale was 1 at the end of the third month. Conclusion This exceptional case highlights that neurothrombectomy could be feasible and of justifiable merit even in the setting of critically low thrombocytopenia if a meticulous procedure is followed in subjects with severe acute stroke. PMID:26576212

  1. Connecting caddisworm silk structure and mechanical properties: combined infrared spectroscopy and mechanical analysis

    PubMed Central

    Ashton, Nicholas N.; Pan, Huaizhong; Stewart, Russell J.

    2016-01-01

    The underwater silk of an aquatic casemaking caddisfly larvae (Hesperophylax occidentalis) is viscoelastic, and displays distinct yield behaviour, large strain cycle hysteresis and near complete recovery of its initial strength and stiffness when unloaded. Yield followed by a stress plateau has been attributed to sequential rupture of serial Ca2+-cross-linked phosphoserine (pS) β-domains. Spontaneous recovery has been attributed to refolding of the Ca2+/pS domains powered by an elastic network. In this study, native Ca2+ ions were exchanged with other metal ions, followed by combined mechanical and FTIR analysis to probe the contribution of pS/metal ion complexes to silk mechanical properties. After exchange of Ca2+ with Na+, the fibres are soft elastomers and the infrared spectra are consistent with Cv3 symmetry of the – groups. Multivalent metal ions decreased the – symmetry and the symmetric stretching modes (vs) split in a manner characteristic of ordered phosphate compounds, such as phosphate minerals and lamellar bilayers of phosphatidic acid lipids. Integrated intensities of the vs bands, indicative of the metal ion's effect on transition dipole moment of the P–O bonds, and thereby the strength of the phosphate metal complex, increased in the order: Na+ < Mg2+ < Sr2+ < Ba2+ < Ca2+ < Eu3+ < La3+ < Zn2+ < Fe2+. With a subset of the metal ion series, the initial stiffness and yield stress of metal ion-exchanged fibres increased in the same order: establishing the link between phosphate transition dipole moments and silk fibre strength. PMID:27278649

  2. Predictive Factors for Good Outcome and Mortality After Stent-Retriever Thrombectomy in Patients With Acute Anterior Circulation Stroke

    PubMed Central

    Yoon, Woong; Kim, Seul Kee; Park, Man Seok; Baek, Byung Hyun; Lee, Yun Young

    2017-01-01

    Background and Purpose Predictive factors associated with stent-retriever thrombectomy for patients with acute anterior circulation stroke remain to be elucidated. This study aimed to investigate clinical and procedural factors predictive of good outcome and mortality after stent-retriever thrombectomy in a large cohort of patients with acute anterior circulation stroke. Methods We analyzed clinical and procedural data in 335 patients with acute anterior circulation stroke treated with stent-retriever thrombectomy. A good outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between clinical, imaging, and procedural factors and good outcome and mortality, respectively, were evaluated using logistic regression analysis. Results Using multivariate analysis, age (odds ratio [OR], 0.965; 95% confidence interval [CI], 0.944-0.986; P=0.001), successful revascularization (OR, 4.658; 95% CI, 2.240-9.689; P<0.001), parenchymal hemorrhage (OR, 0.150; 95% CI, 0.049-0.460; P=0.001), and baseline NIHSS score (OR, 0.908; 95% CI, 0.855-0.965; P=0.002) were independent predictors of good outcome. Independent predictors of mortality were age (OR, 1.043; 95% CI, 1.002-1.086; P=0.041), successful revascularization (OR, 0.171; 95% CI, 0.079-0.370; P<0.001), parenchymal hemorrhage (OR, 2.961; 95% CI, 1.059-8.276; P=0.038), and a history of previous stroke/TIA (OR, 3.124; 95% CI, 1.340-7.281; P=0.008). Conclusions Age, revascularization status, and parenchymal hemorrhage are independent predictors of both good outcome and mortality after stent retriever thrombectomy for acute anterior circulation stroke. In addition, NIHSS score on admission is independently associated with good outcome, whereas a history of previous stroke is independently associated with mortality. PMID:28178407

  3. Combined holographic-mechanical optical tweezers: Construction, optimization, and calibration

    SciTech Connect

    Hanes, Richard D. L.; Jenkins, Matthew C.; Egelhaaf, Stefan U.

    2009-08-15

    A spatial light modulator (SLM) and a pair of galvanometer-mounted mirrors (GMM) were combined into an optical tweezers setup. This provides great flexibility as the SLM creates an array of traps, which can be moved smoothly and quickly with the GMM. To optimize performance, the effect of the incidence angle on the SLM with respect to phase and intensity response was investigated. Although it is common to use the SLM at an incidence angle of 45 deg., smaller angles give a full 2{pi} phase shift and an output intensity which is less dependent on the magnitude of the phase shift. The traps were calibrated using an active oscillatory technique and a passive probability distribution method.

  4. Combining two proven mechanical tenderness measurements in one steak.

    PubMed

    Callahan, Z D; Belk, K E; Miller, R K; Morgan, J B; Lorenzen, C L

    2013-09-01

    This research was performed to determine the true efficacy of measuring both Warner-Bratzler shear force (WBSF) and slice shear force (SSF) in the same steak. The objectives were to compare cooking methods commonly used in preparing steaks for WBSF and SSF procedures and compare them at different cooling times. United States Department of Agriculture select strip loins (n = 240) were aged for either 7 or 14 d to increase the variation in tenderness. Each strip loin was then frozen and cut into 2.54-cm steaks. Steaks were then cooked to an internal temperature of 71°C using a convection conveyor oven (conveyor), a convection oven, clamshell grill, or an open hearth grill. Steaks were allotted to 4 different cooling times to create the combinations of: WBSF 4 h/SSF 0 h, WBSF 4 h/SSF 4 h, WBSF 24 h/SSF 0 h, WBSF 24 h/SSF 24 h. Five 1.25-cm cores were used for WBSF and one 1- by 5-cm slice for SSF. The WBSF from steaks cooked with conveyor were tougher than convection oven cooked steaks [51.9 Newtons (N) vs. 46.1 N; P < 0.05]. However, SSF were tougher when cooked in oven compared with those cooked in conveyor (267.5 N vs. 237.2 N; P < 0.05). Correlations for WBSF and SSF performed in the same steak ranged from 0.51 to 0.88 (P < 0.0001). The WBSF 24 h/SSF 0 h and WBSF 4 h/SSF 4 h had the strongest relationships (0.88 and 0.82, respectively; P < 0.05) between WBSF and SSF when using clamshell method. Performing WBSF and SSF in the same steak was successful based on moderate to high correlation values but the magnitude of the relationship is dependent on the combination of cooking method and cooling time.

  5. Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

    NASA Astrophysics Data System (ADS)

    Ojeda-May, Pedro; Pu, Jingzhi

    2015-11-01

    The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r-1 term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN2 reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN2 reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical reactions.

  6. Treating electrostatics with Wolf summation in combined quantum mechanical and molecular mechanical simulations

    SciTech Connect

    Ojeda-May, Pedro; Pu, Jingzhi

    2015-11-07

    The Wolf summation approach [D. Wolf et al., J. Chem. Phys. 110, 8254 (1999)], in the damped shifted force (DSF) formalism [C. J. Fennell and J. D. Gezelter, J. Chem. Phys. 124, 234104 (2006)], is extended for treating electrostatics in combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations. In this development, we split the QM/MM electrostatic potential energy function into the conventional Coulomb r{sup −1} term and a term that contains the DSF contribution. The former is handled by the standard machinery of cutoff-based QM/MM simulations whereas the latter is incorporated into the QM/MM interaction Hamiltonian as a Fock matrix correction. We tested the resulting QM/MM-DSF method for two solution-phase reactions, i.e., the association of ammonium and chloride ions and a symmetric SN{sub 2} reaction in which a methyl group is exchanged between two chloride ions. The performance of the QM/MM-DSF method was assessed by comparing the potential of mean force (PMF) profiles with those from the QM/MM-Ewald and QM/MM-isotropic periodic sum (IPS) methods, both of which include long-range electrostatics explicitly. For ion association, the QM/MM-DSF method successfully eliminates the artificial free energy drift observed in the QM/MM-Cutoff simulations, in a remarkable agreement with the two long-range-containing methods. For the SN{sub 2} reaction, the free energy of activation obtained by the QM/MM-DSF method agrees well with both the QM/MM-Ewald and QM/MM-IPS results. The latter, however, requires a greater cutoff distance than QM/MM-DSF for a proper convergence of the PMF. Avoiding time-consuming lattice summation, the QM/MM-DSF method yields a 55% reduction in computational cost compared with the QM/MM-Ewald method. These results suggest that, in addition to QM/MM-IPS, the QM/MM-DSF method may serve as another efficient and accurate alternative to QM/MM-Ewald for treating electrostatics in condensed-phase simulations of chemical

  7. Discovery, mechanisms of action and combination therapy of artemisinin.

    PubMed

    Cui, Liwang; Su, Xin-zhuan

    2009-10-01

    Despite great international efforts, malaria still inflicts an enormous toll on human lives, especially in Africa. Throughout history, antimalarial medicines have been one of the most powerful tools in malaria control. However, the acquisition and spread of parasite strains that are resistant to multiple antimalarial drugs have become one of the greatest challenges to malaria treatment, and are associated with the increase in morbidity and mortality in many malaria-endemic countries. To deal with this grave situation, artemisinin-based combinatory therapies (ACTs) have been introduced and widely deployed in malarious regions. Artemisinin is a new class of antimalarial compounds discovered by Chinese scientists from the sweet wormwood Artemisia annua. The potential development of resistance to artemisinins by Plasmodium falciparum threatens the usable lifespan of ACTs, and therefore is a subject of close surveillance and extensive research. Studies at the Thai-Cambodian border, a historical epicenter of multidrug resistance, have detected reduced susceptibility to artemisinins as manifested by prolonged parasite-clearance times, raising considerable concerns on resistance development. Despite this significance, there is still controversy on the mode of action of artemisinins. Although a number of potential cellular targets of artemisinins have been proposed, they remain to be verified experimentally. Here, we review the history of artemisinin discovery, discuss the mode of action and potential drug targets, and present strategies to elucidate resistance mechanisms.

  8. Discovery, mechanisms of action and combination therapy of artemisinin

    PubMed Central

    Cui, Liwang; Su, Xin-zhuan

    2009-01-01

    Despite great international efforts, malaria still inflicts an enormous toll on human lives, especially in Africa. Throughout history, antimalarial medicines have been one of the most powerful tools in malaria control. However, the acquisition and spread of parasite strains that are resistant to multiple antimalarial drugs have become one of the greatest challenges to malaria treatment, and are associated with the increase in morbidity and mortality in many malaria-endemic countries. To deal with this grave situation, artemisinin-based combinatory therapies (ACTs) have been introduced and widely deployed in malarious regions. Artemisinin is a new class of antimalarial compounds discovered by Chinese scientists from the sweet wormwood Artemisia annua. The potential development of resistance to artemisinins by Plasmodium falciparum threatens the usable lifespan of ACTs, and therefore is a subject of close surveillance and extensive research. Studies at the Thai–Cambodian border, a historical epicenter of multidrug resistance, have detected reduced susceptibility to artemisinins as manifested by prolonged parasite-clearance times, raising considerable concerns on resistance development. Despite this significance, there is still controversy on the mode of action of artemisinins. Although a number of potential cellular targets of artemisinins have been proposed, they remain to be verified experimentally. Here, we review the history of artemisinin discovery, discuss the mode of action and potential drug targets, and present strategies to elucidate resistance mechanisms. PMID:19803708

  9. Retrograde rotational thrombectomy with the Rotarex® catheter system: treatment option for an acute thrombotic occlusion of a subclavian artery

    PubMed Central

    Lichtenberg, Michael; Kaeunicke, Matthias; Lukat, Michael; Hailer, Birgit

    2011-01-01

    Purpose: The Rotarex® catheter system is an effective tool for endovascular therapy of acute occluded arteries of the lower extremities, especially for the femoral artery. The authors report the use of the Rotarex catheter system for retrograde percutaneous thrombectomy of an occluded subclavian artery. Case presentation: A 79-year-old male patient was referred because of acute pain and paleness of his left arm. Ultrasound examination and computed tomography angiography proved an occlusion of the left subclavian artery from the origin of the vessel. A retrograde recanalization was attempted using the 6F Rotarex catheter and combined with initiation of a local low-dose lytic therapy. A normal blood flow to the left arm was restored. Follow-up examination 3 months later showed a normal perfusion situation of the left upper extremity. Conclusion: The Rotarex catheter system is an effective tool for endovascular therapy of acute occluded arteries and efficacy is not restricted to the lower extremities. PMID:22102785

  10. Resizing procedure for optimum design of structures under combined mechanical and thermal loading

    NASA Technical Reports Server (NTRS)

    Adelman, H. M.; Narayanaswami, R.

    1976-01-01

    An algorithm is reported for resizing structures subjected to combined thermal and mechanical loading. The algorithm is applicable to uniaxial stress elements (rods) and membrane biaxial stress members. Thermal Fully Stressed Design (TFSD) is based on the basic difference between mechanical and thermal stresses in their response to resizing. The TFSD technique is found to converge in fewer iterations than ordinary fully stressed design for problems where thermal stresses are comparable to the mechanical stresses. The improved convergence is demonstrated by example with a study of a simplified wing structure, built-up with rods and membranes and subjected to a combination of mechanical loads and a three dimensional temperature distribution.

  11. A path-independent integral for fracture of solids under combined electrochemical and mechanical loadings

    NASA Astrophysics Data System (ADS)

    Haftbaradaran, Hamed; Qu, Jianmin

    2014-11-01

    In this study, we first demonstrate that the J-integral in classical linear elasticity becomes path-dependent when the solid is subjected to combined electrical, chemical and mechanical loadings. We then construct an electro-chemo-mechanical J-integral that is path-independent under such combined multiple driving forces. Further, we show that this electro-chemo-mechanical J-integral represents the rate at which the grand potential releases per unit crack growth. As an example, the path-independent nature of the electro-chemo-mechanical J-integral is demonstrated by solving the problem of a thin elastic film delaminated from a thick elastic substrate.

  12. Hydraulic analysis of the functional properties of saline-jet aspiration thrombectomy catheters

    NASA Astrophysics Data System (ADS)

    Yamauchi, Teiyu; Furui, Shigeru; Kohtake, Hiroshi; Harasawa, Arimi; Kaminaga, Tatsuro; Tanaka, Hiroko; Takeshita, Tohru

    1999-12-01

    The purpose of this paper is to clarify the functional properties of a saline-jet aspiration thrombectomy catheter based on hydraulics. This catheter, developed by the authors, aspirates intravascular thrombi by means of the effect of a high-speed jet. We have derived the relationships between Qs, Qa and pn, where Qs is the water supply rate, Qa is the water aspiration rate and pn is the negative pressure created in the distal lumen of the catheter. The relationships are represented by simple equations using c1 and c2, where c1 and c2 are coefficients proper to the catheter. We have obtained c1 and c2 experimentally for three types of catheter with different distal shapes. Two practical conclusions are derived from this study. First, making a short taper at the distal end increases the negative pressure created and is advantageous for thrombus aspiration. Second, making the diameter of the inner tube and nozzle smaller is essential for improving the aspiration ability of the catheter.

  13. Percutaneous Aspiration Thrombectomy for the Treatment of Arterial Thromboembolic Occlusions Following Percutaneous Transluminal Angioplasty

    SciTech Connect

    Schleder, Stephan; Diekmann, Matthias; Manke, Christoph; Heiss, Peter

    2015-02-15

    PurposeThis study was designed to evaluate the technical success and the early clinical outcome of patients undergoing percutaneous aspiration thrombectomy (PAT) for the treatment of arterial thromboembolism following percutaneous infrainguinal transluminal angioplasty (PTA).MethodsIn this single-center study, during a period of 7 years retrospectively, 47 patients (22 male, 47 %) with a mean age of 73 (range 53–96) years were identified in whom PAT was performed for the treatment of thromboembolic complications of infrainguinal PTA. Primary technical success was defined as residual stenosis of <50 % in diameter after sole PAT, whereas secondary technical success was defined as residual stenosis of <50 % in diameter after PAT and additional PTA and/or stenting. Clinical outcome parameters (e.g., need for further intervention, minor/major amputation) were evaluated for the 30-day postinterventional period.ResultsPrimary technical success was achieved in 64 % of patients (30/47); secondary technical success was obtained in 96 % of patients (45/47). Clinical outcome data were available in 38 patients. In 87 % of patients (33/38), there was no need for further intervention within the 30-day postinterventional period. In three patients, minor amputations were conducted due to preexisting ulcerations (Rutherford Category 5 respectively).ConclusionsPAT enables endovascular treatment of iatrogenic thromboembolic complications after PTA with good technical and early clinical results and minimal morbidity.

  14. In Vitro Evaluation of a New Rotational Thrombectomy Device: The Straub Rotarex Catheter

    SciTech Connect

    Zana, Katalin; Otal, Philippe; Fornet, Bela; Forrai, Gabor; Chabbert, Valerie; Smayra, Tarek; Joffre, Francis; Rousseau, Herve

    2001-09-15

    Purpose: To evaluate the efficacy of a new rotational thrombectomy device, and the procedure-related risk of particle embolization.Methods: The experiments were performed in transparent silicone tubes. The conditions of flow were as close as possible to physiological parameters. Distal embolization was detected by a mesh of nylon filters.Results: The Straub Rotarex catheter was able to remove all clots. The mean number of migrating particles larger than 1000 {mu}m was 0.17 ({+-}0.38), the mean number of 400-1000 {mu}m migrating particles was 1.08 ({+-}1.04). The mean intervention time was 67 ({+-}37) sec. The mean volume of collected liquid was 96.6 ({+-}24.7) ml.Conclusion: The in vitro results suggest that the Straub Rotarex catheter is able to remove large volumes of thrombus with a limited risk of embolization. The main limitation of our model is the absence of adhesion of the clot to the tube.

  15. Experimental evaluation of stent retrievers’ mechanical properties and effectiveness

    PubMed Central

    Machi, Paolo; Jourdan, Franck; Ambard, Dominique; Reynaud, Cedric; Lobotesis, Kyriakos; Sanchez, Mathieu; Bonafé, Alain; Costalat, Vincent

    2017-01-01

    Background Five randomized controlled trials recently appeared in the literature demonstrating that early mechanical thrombectomy in patients with acute ischemic stroke is significantly related to an improved outcome. Stent retrievers are accepted as the most effective devices for intracranial thrombectomy. Objective To analyze the mechanical properties of stent retrievers, their behavior during retrieval, and interaction with different clots and to identify device features that might correlate with the effectiveness of thrombus removal. Materials and methods All stent retrievers available in France up to June 2015 were evaluated by mechanical and functional tests aimed at investigating the variation of their radial force and their behavior during retrieval. Devices were also tested during in vitro thrombectomies using white and red experimental thrombi produced with human blood. Functional tests and in vitro thrombectomies were conducted using a rigid 3D printed vascular model. Results Mechanical tests showed a variation in radial force during retrieval for each stent. A constant radial force during retrieval was related to continuous cohesion over the vessel wall and a higher rate of clot removal efficacy. All stent retrievers failed when interacting with white large thrombi (diameter ≥6 mm). Conclusions None of the tested devices were effective in removing white clots of large diameter (≥6 mm). Constant radial force during retrieval allows constant cohesion to the vessel wall and pressure over the clot; such features allow for a higher rate of clot removal. PMID:27016318

  16. Use of the GuideLiner catheter for aspiration thrombectomy in a patient with ST-elevation myocardial infarction with a large intracoronary thrombus.

    PubMed

    Numasawa, Yohei; Motoda, Hiroyuki; Yamazaki, Hiroyuki; Kuno, Toshiki; Kodaira, Masaki; Fujisawa, Taishi

    2016-04-01

    We report a 67-year-old man with ST-elevation myocardial infarction with a large intracoronary thrombus who was successfully treated with percutaneous thrombectomy using the GuideLiner catheter. This catheter is designed for the "Mother and Child" technique with a rapid exchange system and it has a larger internal diameter than conventional aspiration devices. When aspiration thrombectomy using a conventional aspiration catheter is not feasible or fails, use of the GuideLiner catheter for aspiration of thrombus is a reasonable alternative for primary percutaneous coronary intervention in patients with acute myocardial infarction.

  17. Clinical experience with Angiojet: a comprehensive review.

    PubMed

    Ierardi, A M; Xhepa, G; Piffaretti, G; Bacuzzi, A; Tozzi, M; Carbone, M; Barile, A; Squillaci, E; Fonio, P; Brunese, L; Carrafiello, G

    2015-12-01

    The development of various sophisticated mechanical thrombectomy devices and the amassed experience of physicians in minimal invasive therapy produced a paradigm shift in vascular access management toward percutaneous declotting procedures, using pharmaceutical thrombolysis, mechanical thrombectomy, balloon thrombectomy, and a combination of the above techniques. In this setting, in the last years, AngioJet™ (Possis, Minneapolis, MN, USA) rheolytic thrombectomy (RT) showed an increasing use in emergency and election patients. The purpose of this review is to present the current status of percutaneous rheolytic thrombectomy in different fields of applications.

  18. Left Hand-assisted Laparoscopic Nephrectomy With Renal Vein Thrombectomy for Stage T3b Renal Cell Carcinoma.

    PubMed

    Ghareeb, George M; Kenleigh, Dorian A; Brown, James A

    2016-04-01

    A 60-year-old male was found to have an 8.0 cm left renal mass and associated renal vein thrombus on computed tomography. The thrombus extended 3 mm beyond the right aortic border to within 1.6 cm of the left border of the inferior vena cava. The patient underwent left nephrectomy with renal vein thrombectomy using a hand-assisted laparoscopic approach. The tumor thrombus was "milked" proximally back into left renal vein, which was then divided with an endovascular stapler. Left renal vein thrombi extending to right margin of the aorta can be managed with hand-assisted laparoscopic approach.

  19. Disaggregation of human solid tumours by combined mechanical and enzymatic methods.

    PubMed Central

    Engelholm, S. A.; Spang-Thomsen, M.; Brünner, N.; Nøhr, I.; Vindeløv, L. L.

    1985-01-01

    Two combined mechanical and enzymatic disaggregation techniques and a simple mechanical disaggregation procedure were compared. The combined procedures involved a mechanical comminution of the tumour tissue followed by incubation in trypsin. In one method, the tissue was subjected to long-term trypsinization at 4 degrees C, and in the other procedure, repeated short-term trypsinization at 37 degrees C was applied. The results were compared in terms of the yield of viable cells, plating efficiency, the ability to produce tumours in nude mice, and DNA distribution as measured by flow cytometry. The combined techniques provided reproducible cell yields of 2-10 X 10(7) viable cells g-1 of tissue, whereas only a small number of tumour cells was produced by the mechanical method. DNA analysis demonstrated that only the long-term trypsinization procedure resulted in a representative cell yield from all the tumours tested. PMID:3966975

  20. Conical intersections in solution: formulation, algorithm, and implementation with combined quantum mechanics/molecular mechanics method.

    PubMed

    Cui, Ganglong; Yang, Weitao

    2011-05-28

    The significance of conical intersections in photophysics, photochemistry, and photodissociation of polyatomic molecules in gas phase has been demonstrated by numerous experimental and theoretical studies. Optimization of conical intersections of small- and medium-size molecules in gas phase has currently become a routine optimization process, as it has been implemented in many electronic structure packages. However, optimization of conical intersections of small- and medium-size molecules in solution or macromolecules remains inefficient, even poorly defined, due to large number of degrees of freedom and costly evaluations of gradient difference and nonadiabatic coupling vectors. In this work, based on the sequential quantum mechanics and molecular mechanics (QM/MM) and QM/MM-minimum free energy path methods, we have designed two conical intersection optimization methods for small- and medium-size molecules in solution or macromolecules. The first one is sequential QM conical intersection optimization and MM minimization for potential energy surfaces; the second one is sequential QM conical intersection optimization and MM sampling for potential of mean force surfaces, i.e., free energy surfaces. In such methods, the region where electronic structures change remarkably is placed into the QM subsystem, while the rest of the system is placed into the MM subsystem; thus, dimensionalities of gradient difference and nonadiabatic coupling vectors are decreased due to the relatively small QM subsystem. Furthermore, in comparison with the concurrent optimization scheme, sequential QM conical intersection optimization and MM minimization or sampling reduce the number of evaluations of gradient difference and nonadiabatic coupling vectors because these vectors need to be calculated only when the QM subsystem moves, independent of the MM minimization or sampling. Taken together, costly evaluations of gradient difference and nonadiabatic coupling vectors in solution or

  1. Endovascular Treatment of a Ruptured Profunda Femoral Artery Branch After Fogarty Thrombectomy of a Femoro-Femoral Crossover Arterial Graft: A Case Report and Review of the Literature

    SciTech Connect

    Manousaki, Eirini; Tsetis, Dimitrios; Kostas, Theodoros; Katsamouris, Asterios

    2010-02-15

    We present a very rare case of a life-threatening rupture of a profunda femoral artery distal branch after a Fogarty thrombectomy of a thrombosed crossover synthetic graft between the ipsilateral common femoral artery and a contralateral iliac-popliteal graft; the bleeding profunda femoral artery branch was successfully embolized with metallic coils through the axillary artery approach.

  2. Clinic Predictive Factors for Insufficient Myocardial Reperfusion in ST-Segment Elevation Myocardial Infarction Patients Treated with Selective Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention.

    PubMed

    Tian, Jinfan; Liu, Yue; Song, Xiantao; Zhang, Min; Xu, Feng; Yuan, Fei; Lyu, Shuzheng

    2016-01-01

    Background. Insufficient data are available on the potential benefit of selective aspiration and clinical predictors for no-reflow in STEMI patients undergoing primary percutaneous coronary intervention (PPCI) adjunct with aspiration thrombectomy. Objective. The aim of our study was to investigate clinical predictors for insufficient reperfusion in patients with high thrombus burden treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011 till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy and PPCI were selected and 202 patients with a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study. According to a cTFC value, patients were divided into Group I (cTFC > 40), namely, insufficient reperfusion group; Group II (cTFC ≤ 40), namely, sufficient reperfusion group. Results. Univariate analysis showed that hypertension, multivessel disease, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were negative predictors for insufficient reperfusion. After multivariate adjustment, age ≧ 60 years, hypertension, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were independently associated with insufficient reperfusion in STEMI patients treated with manual aspiration thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was positively associated with improved myocardial reperfusion. Conclusion. Fully identifying risk factors will help to improve the effectiveness of selective thrombus aspiration.

  3. Clinic Predictive Factors for Insufficient Myocardial Reperfusion in ST-Segment Elevation Myocardial Infarction Patients Treated with Selective Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention

    PubMed Central

    Song, Xiantao; Zhang, Min; Xu, Feng; Yuan, Fei

    2016-01-01

    Background. Insufficient data are available on the potential benefit of selective aspiration and clinical predictors for no-reflow in STEMI patients undergoing primary percutaneous coronary intervention (PPCI) adjunct with aspiration thrombectomy. Objective. The aim of our study was to investigate clinical predictors for insufficient reperfusion in patients with high thrombus burden treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011 till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy and PPCI were selected and 202 patients with a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study. According to a cTFC value, patients were divided into Group I (cTFC > 40), namely, insufficient reperfusion group; Group II (cTFC ≤ 40), namely, sufficient reperfusion group. Results. Univariate analysis showed that hypertension, multivessel disease, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were negative predictors for insufficient reperfusion. After multivariate adjustment, age ≧ 60 years, hypertension, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were independently associated with insufficient reperfusion in STEMI patients treated with manual aspiration thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was positively associated with improved myocardial reperfusion. Conclusion. Fully identifying risk factors will help to improve the effectiveness of selective thrombus aspiration. PMID:27891513

  4. Leaf structure affects a plant's appearance: combined multiple-mechanisms intensify remarkable foliar variegation.

    PubMed

    Chen, Yun-Shiuan; Chesson, Peter; Wu, Ho-Wei; Pao, Shang-Hung; Liu, Jian-Wei; Chien, Lee-Feng; Yong, Jean W H; Sheue, Chiou-Rong

    2017-03-01

    The presence of foliar variegation challenges perceptions of leaf form and functioning. But variegation is often incorrectly identified and misinterpreted. The striking variegation found in juvenile Blastus cochinchinensis (Melastomataceae) provides an instructive case study of mechanisms and their ecophysiological implications. Variegated (white and green areas, vw and vg) and non-variegated leaves (normal green leaves, ng) of seedlings of Blastus were compared structurally with microtechniques, and characterized for chlorophyll content and fluorescence. More limited study of Sonerila heterostemon (Melastomataceae) and Kaempferia pulchra (Zingiberaceae) tested the generality of the findings. Variegation in Blastus combines five mechanisms: epidermal, air space, upper mesophyll, chloroplast and crystal, the latter two being new mechanisms. All mesophyll cells (vw, vg, ng) have functional chloroplasts with dense thylakoids. The vw areas are distinguished by flatter adaxial epidermal cells and central trichomes containing crystals, the presence of air spaces between the adaxial epidermis and a colorless spongy-like upper mesophyll containing smaller and fewer chloroplasts. The vw area is further distinguished by having the largest spongy-tissue chloroplasts and fewer stomata. Both leaf types have similar total chlorophyll content and similar  F v/F m (maximum quantum yield of PSII), but vg has significantly higher F v/F m than ng. Variegation in Sonerila and Kaempferia is also caused by combined mechanisms, including the crystal type in Kaempferia. This finding of combined mechanisms in three different species suggests that combined mechanisms may occur more commonly in nature than current understanding. The combined mechanisms in Blastus variegated leaves represent intricate structural modifications that may compensate for and minimize photosynthetic loss, and reflect changing plant needs.

  5. Endovascular Treatment of Phlegmasia Cerulea Dolens with Impending Venous Gangrene: Manual Aspiration Thrombectomy as the First-Line Thrombus Removal Method

    SciTech Connect

    Oguzkurt, Levent Ozkan, Ugur; Demirturk, Orhan S.; Gur, Serkan

    2011-12-15

    Purpose: Our purpose was to report the outcome of endovascular treatment with manual aspiration thrombectomy as the first-line thromboablative method for phlegmasia cerulea dolens. Methods: Between October 2006 and May 2010, seven consecutive patients (5 women, 2 men; age range, 31-80 years) with the diagnosis of phlegmasia cerulea dolens secondary to acute iliofemoral deep venous thrombosis had endovascular treatment with manual aspiration thrombectomy. Catheter-directed thrombolysis and stent placement were used as adjunctive procedures. Phlegmasia was left-sided in five and right-sided in two patients. Results: All patients had associated great saphenous vein thrombosis in addition to iliofemoral deep vein thrombosis (DVT). Aspiration thrombectomy completely removed the thrombus from the popliteal vein to the inferior vena cava (IVC) in all cases. Three patients with May-Thurner syndrome had stent placement in the left common iliac vein. Two patients had early recurrences. Repeated aspiration thrombectomy was unsuccessful in one patient. There were no complications related to the procedure. One patient who had been successfully treated died of sepsis and another patient who had unsuccessful repeated interventions had below-the-knee amputation. Overall, the clinical success and survival rates of patients in this study were 86%. On follow-up, three patients with successful treatment were asymptomatic with no deep venous insufficiency. One of these patients died during the 4-month follow-up period. Two patients had mild ankle swelling with deep venous insufficiency. Conclusions: Manual aspiration thrombectomy with adjunctive use of catheter-directed thrombolysis and stent placement is an effective endovascular treatment method with high clinical success and survival rates for phlegmasia cerulean dolens.

  6. Clinical study on VATS combined mechanical ventilation treatment of ARDS secondary to severe chest trauma

    PubMed Central

    Qi, Yongjun

    2016-01-01

    The aim of the study was to investigate the clinical effects of microinvasive video-assisted thoracoscopic surgery (VATS) combined with mechanical ventilation in the treatment of acute respiratory distress syndrome (ARDS) secondary to severe chest trauma. A total of 62 patients with ARDS secondary to severe chest trauma were divided into the observation and control groups. The patients in the observation groups were treated with VATS combined with early mechanical ventilation while patients in the control group were treated using routine open thoracotomy combined with early mechanical ventilation. Compared to the controls, the survival rate of the observation group was significantly higher. The average operation time of the observation group was significantly shorter than that of the control group, and the incidence of complications in the perioperative period of the observation group was significantly lower than that of the control group (p<0.05). The average application time of the observation group was significantly shorter than that of the control group, and the incidence of ventilator-associated complications was significantly lower than that of the control group (p<0.05). In conclusion, a reasonable understanding of the indications and contraindications of VATS, combined with early mechanical treatment significantly improved the success rate of the treatment of ARDS patients secondary to severe chest trauma and reduced the complications. PMID:27446317

  7. [Combined hopping-superexchange mechanism of charge transfer in DNA; a model with nearest interactions].

    PubMed

    Lakhno, V D; Sultanov, V B

    2007-01-01

    In the framework of the earlier developed combined hopping-superexchange mechanism of charge transfer in DNA, a model with all nearest interactions between nucleobases is proposed. It is shown that the transfer rates for various types of nucleotide sequences calculated within this model are in a good agreement with experimental data.

  8. Robust mechanisms of ventral furrow invagination require the combination of cellular shape changes

    NASA Astrophysics Data System (ADS)

    Conte, Vito; Muñoz, José J.; Baum, Buzz; Miodownik, Mark

    2009-03-01

    Ventral furrow formation in Drosophila is the first large-scale morphogenetic movement during the life of the embryo, and is driven by co-ordinated changes in the shape of individual epithelial cells within the cellular blastoderm. Although many of the genes involved have been identified, the details of the mechanical processes that convert local changes in gene expression into whole-scale changes in embryonic form remain to be fully understood. Biologists have identified two main cell deformation modes responsible for ventral furrow invagination: constriction of the apical ends of the cells (apical wedging) and deformation along their apical-basal axes (radial lengthening/shortening). In this work, we used a computer 2D finite element model of ventral furrow formation to investigate the ability of different combinations of three plausible elementary active cell shape changes to bring about epithelial invagination: ectodermal apical-basal shortening, mesodermal apical-basal lengthening/shortening and mesodermal apical constriction. We undertook a systems analysis of the biomechanical system, which revealed many different combinations of active forces (invagination mechanisms) were able to generate a ventral furrow. Two important general features were revealed. First that combinations of shape changes are the most robust to environmental and mutational perturbation, in particular those combining ectodermal pushing and mesodermal wedging. Second, that ectodermal pushing plays a big part in all of the robust mechanisms (mesodermal forces alone do not close the furrow), and this provides evidence that it may be an important element in the mechanics of invagination in Drosophila.

  9. A procedure for combining acoustically induced and mechanically induced loads (first passage failure design criterion)

    NASA Technical Reports Server (NTRS)

    Crowe, D. R.; Henricks, W.

    1983-01-01

    The combined load statistics are developed by taking the acoustically induced load to be a random population, assumed to be stationary. Each element of this ensemble of acoustically induced loads is assumed to have the same power spectral density (PSD), obtained previously from a random response analysis employing the given acoustic field in the STS cargo bay as a stationary random excitation. The mechanically induced load is treated as either (1) a known deterministic transient, or (2) a nonstationary random variable of known first and second statistical moments which vary with time. A method is then shown for determining the probability that the combined load would, at any time, have a value equal to or less than a certain level. Having obtained a statistical representation of how the acoustic and mechanical loads are expected to combine, an analytical approximation for defining design levels for these loads is presented using the First Passage failure criterion.

  10. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research

    PubMed Central

    Zhong, Jian; He, Dannong

    2015-01-01

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future. PMID:26265357

  11. Combination of Universal Mechanical Testing Machine with Atomic Force Microscope for Materials Research

    NASA Astrophysics Data System (ADS)

    Zhong, Jian; He, Dannong

    2015-08-01

    Surface deformation and fracture processes of materials under external force are important for understanding and developing materials. Here, a combined horizontal universal mechanical testing machine (HUMTM)-atomic force microscope (AFM) system is developed by modifying UMTM to combine with AFM and designing a height-adjustable stabilizing apparatus. Then the combined HUMTM-AFM system is evaluated. Finally, as initial demonstrations, it is applied to analyze the relationship among macroscopic mechanical properties, surface nanomorphological changes under external force, and fracture processes of two kinds of representative large scale thin film materials: polymer material with high strain rate (Parafilm) and metal material with low strain rate (aluminum foil). All the results demonstrate the combined HUMTM-AFM system overcomes several disadvantages of current AFM-combined tensile/compression devices including small load force, incapability for large scale specimens, disability for materials with high strain rate, and etc. Therefore, the combined HUMTM-AFM system is a promising tool for materials research in the future.

  12. Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect.

    PubMed

    Matsumura, Nobuko; Nakaki, Toshio

    2014-10-15

    The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na(+) and Ca(2+) channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs.

  13. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

    PubMed

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-04-01

    Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug

  14. Combination effect of ultrasound and shake as a mechanical action for textile cleaning.

    PubMed

    Gotoh, Keiko; Harayama, Kokoro; Handa, Keiko

    2015-01-01

    The ultrasonic cleaning of artificially soiled fabrics with and without shake was carried out in an aqueous anionic surfactant solution. The polyester, cotton and polyester/cotton (65/35) fabrics were soiled with oleic acid or carbon black as a model soil, and cleaned together with their original fabrics with applying ultrasound for 5min. The detergency and the soil redeposition were determined from the change in the Kubelka-Munk function of the soiled and original fabric surfaces due to the cleaning. For any fabric, the removal of oleic acid and carbon black from the soiled fabric and their redeposition onto the original fabric increased with increasing electric power consumption of ultrasound. When ultrasound and shake were applied at the same time, the detergency further increased for any electric power consumption. The maximum detergency obtained with combination of ultrasound 340W and shake 160spm was compared with detergency obtained with Wascator, a horizontal axis drum type washer. It was found that the ultrasound/shake combination cleaning enabled efficient removal of both soils from any fabric and the detergency of the polyester fabrics was comparable to that with Wascator. The mechanical action during the washing was evaluated by two mechanical action test pieces commercially available, which indicated that the ultrasound/shake combination cleaning provided gentle mechanical action to the fabric in comparison with the drum type washer. The SEM observations showed the damage of the fabric and fiber surfaces was negligibly small after the ultrasound/shake combination washing.

  15. Combined optical and mechanical scanning in optical-resolution photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Li, Lei; Yeh, Chenghung; Hu, Song; Wang, Lidai; Soetikno, Brian T.; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk; Maslov, Konstantin I.; Wang, Lihong V.

    2014-03-01

    Combined optical and mechanical scanning (COMS) in optical-resolution photoacoustic microscopy (OR-PAM) has provided five scanning modes with fast imaging speed and wide field of view (FOV). With two-dimensional (2D) galvanometer-based optical scanning, we have achieved a 2 KHz B-scan rate and 50 Hz volumetric-scan rate, which enables real-time tracking of cell activities in vivo. With optical-mechanical hybrid 2D scanning, we are able to image a wide FOV (10×8 mm2) within 150 seconds, which is 20 times faster than the conventional mechanical scan in our second-generation OR-PAM. With three-dimensional mechanical-based contour scanning, we can maintain the optimal signal-to-noise ratio and spatial resolution of OR-PAM while imaging objects with uneven surfaces, which is ideal for fast and quantitative studies of tumors and the brain.

  16. An opportunistic routing mechanism combined with long-term and short-term metrics for WMN.

    PubMed

    Sun, Weifeng; Wang, Haotian; Piao, Xianglan; Qiu, Tie

    2014-01-01

    WMN (wireless mesh network) is a useful wireless multihop network with tremendous research value. The routing strategy decides the performance of network and the quality of transmission. A good routing algorithm will use the whole bandwidth of network and assure the quality of service of traffic. Since the routing metric ETX (expected transmission count) does not assure good quality of wireless links, to improve the routing performance, an opportunistic routing mechanism combined with long-term and short-term metrics for WMN based on OLSR (optimized link state routing) and ETX is proposed in this paper. This mechanism always chooses the highest throughput links to improve the performance of routing over WMN and then reduces the energy consumption of mesh routers. The simulations and analyses show that the opportunistic routing mechanism is better than the mechanism with the metric of ETX.

  17. An Opportunistic Routing Mechanism Combined with Long-Term and Short-Term Metrics for WMN

    PubMed Central

    Piao, Xianglan; Qiu, Tie

    2014-01-01

    WMN (wireless mesh network) is a useful wireless multihop network with tremendous research value. The routing strategy decides the performance of network and the quality of transmission. A good routing algorithm will use the whole bandwidth of network and assure the quality of service of traffic. Since the routing metric ETX (expected transmission count) does not assure good quality of wireless links, to improve the routing performance, an opportunistic routing mechanism combined with long-term and short-term metrics for WMN based on OLSR (optimized link state routing) and ETX is proposed in this paper. This mechanism always chooses the highest throughput links to improve the performance of routing over WMN and then reduces the energy consumption of mesh routers. The simulations and analyses show that the opportunistic routing mechanism is better than the mechanism with the metric of ETX. PMID:25250379

  18. Successful treatment of phlegmasia cerulea dolens in a nonagenarian patient with chronic iliac vein occlusion using a Cleaner thrombectomy device.

    PubMed

    Sevuk, Utkan; Kose, Kaan; Ayaz, Firat; Ozyalcin, Sertan

    2015-08-07

    A 91-year-old man was admitted to the emergency room with a 3-day history of severe pain, swelling and cyanosis in his left leg. Duplex ultrasound findings were suggestive of acute left popliteal and iliofemoral venous thrombosis. Heparin was initiated and pharmacomechanical thrombolysis (PMT) was performed with the use of a Cleaner thrombectomy device. At the completion of PMT, repeat venography revealed chronic proximal iliac vein occlusion. After the procedure, alteplase was infused via the intra-arterial catheter at a rate of 0.5 mg/h over 24 h to clear the thrombus distal to the popliteal vein and residual thrombus. The patient's signs and symptoms improved markedly after the intervention. There were no minor or systemic bleeding problems. He was discharged home 10 days after the procedure without any complications.

  19. Combining clinical studies and analogue experiments to investigate cognitive mechanisms in posttraumatic stress disorder

    PubMed Central

    Ehring, Thomas; Kleim, Birgit; Ehlers, Anke

    2013-01-01

    Research into cognitive mechanisms in posttraumatic stress disorder (PTSD) typically comprises two types of studies. The first group of studies is conducted with survivors of traumatic events and assesses the association between PTSD and cognitive variables with questionnaires and/or information processing paradigms. In the second group of studies, healthy non-traumatized individuals are exposed to an analogue stressor (e.g., a stressful film) and cognitive variables of interest are usually experimentally manipulated to investigate their effects on analogue PTSD symptoms. This review illustrates how studies of trauma survivors and analogue studies with non-traumatized populations can be usefully combined. Two examples for this approach are presented: (1) research into the role of perceptual priming for trauma-related stimuli and (2) research into trauma-related rumination. The advantages and limitations of both types of studies are discussed and it is argued that a combination of both approaches is needed to investigate cognitive mechanisms in PTSD. PMID:23814633

  20. Polarization energy gradients in combined quantum mechanics, effective fragment potential, and polarizable continuum model calculations

    NASA Astrophysics Data System (ADS)

    Li, Hui; Gordon, Mark S.

    2007-03-01

    A method that combines quantum mechanics (QM), typically a solute, the effective fragment potential (EFP) discrete solvent model, and the polarizable continuum model is described. The EFP induced dipoles and polarizable continuum model (PCM) induced surface charges are determined in a self-consistent fashion. The gradients of these two energies with respect to molecular coordinate changes are derived and implemented. In general, the gradients can be formulated as simple electrostatic forces and torques among the QM nuclei, electrons, EFP static multipoles, induced dipoles, and PCM induced charges. Molecular geometry optimizations can be performed efficiently with these gradients. The formulas derived for EFP/PCM can be generally applied to other combined molecular mechanics and continuum methods that employ induced dipoles and charges.

  1. The Use of the 'Preclosure' Technique for Antegrade Aspiration Thrombectomy with Large Catheters in Acute Limb Ischemia

    SciTech Connect

    Funke, C. Pfiffner, R.; Husmann, M.; Pfammatter, T.

    2013-04-15

    This study was designed to assess retrospectively short- and mid-term outcomes of the use of a suture-mediated closure device to close the antegrade access in patients undergoing percutaneous aspiration thrombectomy with large catheters for acute leg ischemia. Between November 2005 and February 2010, a suture-mediated active closure system (ProGlide{sup Registered-Sign} 6F, Abbott) was placed before arterial sheath (mean 9 F, range 6-12 F) introduction in 101 patients (74 men, 73 %, mean age 70.1 {+-} 12.6 years standard deviation). Data regarding mortality, complications, and factors contributing to vascular complications at the access site was collected for 6 month after the intervention to detect device-related problems. As a coincidence, 77 patients had follow-up visits for a duplex ultrasound. There were a total of 19 vascular complications (19 %) at the puncture site, all of which were of hemorrhagic nature and none of which consisted of vessel occlusion. Two major outcome complications (2 %) occurred. A retroperitoneal hematoma and a serious inguinal bleeding required additive treatment and did not result in permanent sequelae. Nine cases involved death of which eight were not attributable to the closure and one remained unclear. Successful closure was achieved in 95 patients (94 %); additional manual compression was sufficient in the majority of the remaining patients. Numerous factors contributing to vascular complications were encountered. With acceptable short- and mid-term outcomes, the 'preclose' technique can be a reliable option for the closure of a large antegrade femoral access even for patients at a high risk of vascular complications, such as those undergoing aspiration thrombectomy.

  2. Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

    PubMed

    Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

    2013-01-01

    This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

  3. Measuring the mechanical properties of plant cells by combining micro-indentation with osmotic treatments.

    PubMed

    Weber, Alain; Braybrook, Siobhan; Huflejt, Michal; Mosca, Gabriella; Routier-Kierzkowska, Anne-Lise; Smith, Richard S

    2015-06-01

    Growth in plants results from the interaction between genetic and signalling networks and the mechanical properties of cells and tissues. There has been a recent resurgence in research directed at understanding the mechanical aspects of growth, and their feedback on genetic regulation. This has been driven in part by the development of new micro-indentation techniques to measure the mechanical properties of plant cells in vivo. However, the interpretation of indentation experiments remains a challenge, since the force measures results from a combination of turgor pressure, cell wall stiffness, and cell and indenter geometry. In order to interpret the measurements, an accurate mechanical model of the experiment is required. Here, we used a plant cell system with a simple geometry, Nicotiana tabacum Bright Yellow-2 (BY-2) cells, to examine the sensitivity of micro-indentation to a variety of mechanical and experimental parameters. Using a finite-element mechanical model, we found that, for indentations of a few microns on turgid cells, the measurements were mostly sensitive to turgor pressure and the radius of the cell, and not to the exact indenter shape or elastic properties of the cell wall. By complementing indentation experiments with osmotic experiments to measure the elastic strain in turgid cells, we could fit the model to both turgor pressure and cell wall elasticity. This allowed us to interpret apparent stiffness values in terms of meaningful physical parameters that are relevant for morphogenesis.

  4. Combined Quantum Mechanical and Molecular Mechanics Studies of the Electron-Transfer Reactions Involving Carbon Tetrachloride in Solution

    SciTech Connect

    Valiev, Marat; Bylaska, Eric J.; Dupuis, Michel; Tratnyek, Paul G.

    2008-03-27

    The reductive dechlorination of carbon tetrachloride, CC₄, was investigated using combined high level quantum mechanical and molecular mechanics (QM/MM) approach. The first electron transfer process was assumed to proceed by a concerted electron transfer-bond breaking mechanism, and reaction barriers for the first electron reduction were estimated by using the crossing point of the free energy profiles of CCl₃-Cl and CCl₃-Cl•- as a function of the CCl₃-Cl distance. The results of these calculations showed that the activation barriers for this reaction are reachable under a wide range of reduction potentials. In the gas-phase, the barrier to reduction varied from 0.8 kcal/mol for reducing agent with a -5 kcal/mol work function to 24.7 kcal/mol for a reducing agent with a 40 kcal/mol work function at the CCSD(T)/aug-cc-pVDZ level. In the aqueous phase, QM/MM calculations at the CCSD(T)/aug-cc-pVDZ level predicted that the barrier to reduction varied from 0.7 kcal/mol to 35.2 kcal/mol for -2.32 V and 0.93 V reduction potentials respectively. COSMO continuum solvation calculations were also performed for comparison. For strong reducing agents (EH < -1.5V) very little difference was seen between the QM/MM and COSMO activation barriers. For weak reducing agents (EH > 0V) the activation barriers differed by as much as 6 kcal/mol between the QM/MM and COSMO calculations. These results demonstrate that ab initio electronic structure methods coupled with explicit molecular mechanics representation of the aqueous environment offer an efficient and accurate way to calculate the free energy reaction barriers for dissociative electron transfer reactions of organochlorine compounds to identify the potentially important environmental degradation processes.

  5. Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide.

    PubMed

    Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; McDonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

    2015-12-04

    There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity.

  6. Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide

    PubMed Central

    Leggett, Mark J.; Schwarz, J. Spencer; Burke, Peter A.; McDonnell, Gerald; Denyer, Stephen P.

    2015-01-01

    There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. PMID:26637595

  7. COMBINE*: An integrated opto-mechanical tool for laser performance modeling

    NASA Astrophysics Data System (ADS)

    Rehak, M.; Di Nicola, J. M.

    2015-02-01

    Accurate modeling of thermal, mechanical and optical processes is important for achieving reliable, high-performance high energy lasers such as those at the National Ignition Facility [1] (NIF). The need for this capability is even more critical for high average power, high repetition rate applications. Modeling the effects of stresses and temperature fields on optical properties allows for optimal design of optical components and more generally of the architecture of the laser system itself. Stresses change the indices of refractions and induce inhomogeneities and anisotropy. We present a modern, integrated analysis tool that efficiently produces reliable results that are used in our laser propagation tools such as VBL [5]. COMBINE is built on and supplants the existing legacy tools developed for the previous generations of lasers at LLNL but also uses commercially available mechanical finite element codes ANSYS or COMSOL (including computational fluid dynamics). The COMBINE code computes birefringence and wave front distortions due to mechanical stresses on lenses and slabs of arbitrary geometry. The stresses calculated typically originate from mounting support, vacuum load, gravity, heat absorption and/or attending cooling. Of particular importance are the depolarization and detuning effects of nonlinear crystals due to thermal loading. Results are given in the form of Jones matrices, depolarization maps and wave front distributions. An incremental evaluation of Jones matrices and ray propagation in a 3D mesh with a stress and temperature field is performed. Wavefront and depolarization maps are available at the optical aperture and at slices within the optical element. The suite is validated, user friendly, supported, documented and amenable to collaborative development. * COMBINE stands for Code for Opto-Mechanical Birefringence Integrated Numerical Evaluations.

  8. Biodiesel production from palm oil using combined mechanical stirred and ultrasonic reactor.

    PubMed

    Choedkiatsakul, I; Ngaosuwan, K; Cravotto, G; Assabumrungrat, S

    2014-07-01

    This paper investigates the production of biodiesel from palm oil using a combined mechanical stirred and ultrasonic reactor (MS-US). The incorporation of mechanical stirring into the ultrasonic reactor explored the further improvement the transesterification of palm oil. Initial reaction rate values were 54.1, 142.9 and 164.2 mmol/L min for the mechanical-stirred (MS), ultrasonic (US) and MS-US reactors, respectively. Suitable methanol to oil molar ratio and the catalyst loading values were found to be 6 and 1 of oil, respectively. The effect of ultrasonic operating parameters; i.e. frequency, location, and number of transducer, has been investigated. Based on the conversion yield at the reactor outlet after 1 h, the number of transducers showed a relevant role in the reaction rate. Frequency and transducer location would appear to have no significant effect. The properties of the obtained biodiesel (density, viscosity, pour point, and flash point) satisfy the ASTM standard. The combined MS-US reactors improved the reaction rate affording the methyl esters in higher yield.

  9. Mechanism-based drug combinations with the DNA-strand-breaking nucleoside analog, CNDAC

    PubMed Central

    Liu, Xiaojun; Jiang, Yingjun; Nowak, Billie; Hargis, Sarah; Plunkett, William

    2016-01-01

    CNDAC (2’-C-cyano-2’-deoxy-1-β-D-arabino-pentofuranosyl-cytosine, DFP10917) and its orally bioavailable prodrug, sapacitabine, are undergoing clinical trials for hematological malignancies and solid tumors. The unique action mechanism of inducing DNA strand breaks distinguishes CNDAC from other deoxycytidine analogs. To optimize the clinical potentials of CNDAC, we explored multiple strategies combining CNDAC with chemotherapeutic agents targeting distinct DNA damage repair pathways that are currently in clinical use. The ability of each agent to decrease proliferative potential, determined by clonogenic assays, was determined in paired cell lines proficient and deficient in certain DNA repair proteins. Subsequently each agent was used in combination with CNDAC at fixed concentration ratios. The clonogenicity was quantitated by median effect analysis, and a combination index was calculated. The c-Abl kinase inhibitor, imatinib, had synergy with CNDAC in HCT116 cells, regardless of p53 status. Inhibitors of PARP1 that interfere with homologous recombination (HR) repair or base excision repair (BER) and agents such as temozolomide that cause DNA damage repaired by the BER pathway were also synergistic with CNDAC. The toxicity of the nitrogen mustards, bendamustine and cytoxan, or of platinum compounds, which generate DNA adducts repaired by nucleotide excision repair and HR, was additive with CNDAC. An additive cell killing was also achieved by the combination of CNDAC with taxane mitotic inhibitors (paclitaxel and docetaxel). At concentrations which allow survival of the majority of wild type cells, the synergistic or additive combination effects were selective in HR-deficient cells. This study provides mechanistic rationales for combining CNDAC with other active drugs. PMID:27474148

  10. Mechanisms for optimising photodynamic therapy: second-generation photosensitisers in combination with mitomycin C.

    PubMed Central

    van Geel, I. P.; Oppelaar, H.; Oussoren, Y. G.; Schuitmaker, J. J.; Stewart, F. A.

    1995-01-01

    Mechanisms for improving photodynamic therapy (PDT) were investigated in the murine RIF1 tumour using meso-tetrahydroxyphenylchlorin (m-THPC) or bacteriochlorin a (BCA) as photosensitisers and comparing these results with Photofrin-mediated PDT. The 86Rb extraction technique was used to measure changes in perfusion at various times after interstitial PDT. Non-curative combinations of light doses with m-THPC and BCA PDT markedly decreased vascular perfusion. This decrease was more pronounced for both new photosensitisers than for Photofrin. Comparison of tumour perfusion after PDT with tumour response revealed an inverse correlation for all three photosensitisers, but the relationship was less clear for m-THPC and BCA. In vivo/in vitro experiments were performed after Photofrin or m-THPC PDT in order to assess direct tumour kill (immediate plating) vs indirect vascular effects (delayed plating). For both photosensitisers, there was little direct cell killing but clonogenic survival decreased as the interval between treatment and excision increased. When m-THPC PDT was combined with mitomycin C (MMC), light doses could be decreased by a factor of 2 for equal tumour effects. Lower light and m-THPC doses could be used compared with Photofrin PDT in combination with MMC. BCA PDT with MMC did not result in a greater tumour response compared with BCA PDT alone. Reduction in both light and photosensitiser does for effective PDT regimes in combination with MMC offers substantial clinical advantages, since both treatment time and skin photosensitisation will be reduced. PMID:7640216

  11. Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans

    PubMed Central

    Li, Xiuyun; Yu, Cuixiang; Huang, Xin; Sun, Shujuan

    2016-01-01

    Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets. PMID:28006028

  12. Effect of Physical Aging on Mechanical Behavior of an Elastomeric Glass under Combined Pressure and Temperature.

    DTIC Science & Technology

    1986-12-01

    NO. 3. RECIPIENT’S CATALOG NUMBER Technical Report No. 7 C.- 4. TITLE (and Subtitle) S . TYPE OF REPORT & PERIOD COVERED Effect of Physical Aging on...Mechanical Behavior of an Elastomeric Glass Under Combined Pressure and Temperature G. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(e) S . CONTRACT OR GRANT...NUMBER( s ) K. Vijayan and K. D. Pae NOOO14-82-K-0608 9. PERFORMING r" GANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK High PrE 3,ure

  13. Surfaces with combined microscale and nanoscale structures: a route to mechanically stable superhydrophobic surfaces?

    PubMed

    Groten, Jonas; Rühe, Jürgen

    2013-03-19

    Materials with superhydrophobic properties are usually generated by covering the surfaces with hydrophobic nanoscale rough features. A major problem, however, for any practical application of such strongly water-repellent surfaces is the mechanical fragility of the nanostructures. Even moderate forces caused by touching or rubbing the surfaces are frequently strong enough to destroy the nanostructures and lead to the loss of the superhydrophobic properties. In this article, we study the mechanical stability of superhydrophobic surfaces with three different topographies: nano- and microscale features and surfaces carrying a combination of both. The surfaces are generated by silicon etching and subsequent coating with a monolayer of a fluoropolymer (PFA). We perform controlled wear tests on the different surfaces and discuss the impact of wear on the wetting properties of the different surfaces.

  14. Design and fabrication of miniaturized PEM fuel cell combined microreactor with self-regulated hydrogen mechanism

    NASA Astrophysics Data System (ADS)

    Balakrishnan, A.; Frei, M.; Kerzenmacher, S.; Reinecke, H.; Mueller, C.

    2015-12-01

    In this work we present the design and fabrication of the miniaturized PEM fuel cell combined microreactor system with hydrogen regulation mechanism and testing of prototype microreactor. The system consists of two components (i) fuel cell component and (ii) microreactor component. The fuel cell component represents the miniaturized PEM fuel cell system (combination of screen printed fuel cell assembly and an on-board hydrogen storage medium). Hydrogen production based on catalytic hydrolysis of chemical hydride takes place in the microreactor component. The self-regulated hydrogen mechanism based on the gaseous hydrogen produced from the catalytic hydrolysis of sodium borohydride (NaBH4) gets accumulated as bubbles at the vicinity of the hydrophobic coated hydrogen exhaust holes. When the built up hydrogen bubbles pressure exceeds the burst pressure at the hydrogen exhaust holes the bubble collapses. This collapse causes a surge of fresh NaBH4 solution onto the catalyst surface leading to the removal of the reaction by-products formed at the active sites of the catalyst. The catalyst used in the system is platinum deposited on a base substrate. Nickel foam, carbon porous medium (CPM) and ceramic plate were selected as candidates for base substrate for developing a robust catalyst surface. For the first time the platinum layer fabricated by pulsed electrodeposition and dealloying (EPDD) technique is used for hydrolysis of NaBH4. The major advantages of such platinum catalyst layers are its high surface area and their mechanical stability. Prototype microreactor system with self-regulated hydrogen mechanism is demonstrated.

  15. Quinolinic Acid, an endogenous molecule combining excitotoxicity, oxidative stress and other toxic mechanisms.

    PubMed

    Pérez-De La Cruz, Verónica; Carrillo-Mora, Paul; Santamaría, Abel

    2012-01-01

    Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca(2+) concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

  16. Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

    PubMed Central

    Pérez-De La Cruz, Verónica; Carrillo-Mora, Paul; Santamaría, Abel

    2012-01-01

    Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington’s disease, Alzheimer’s disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity. PMID:22408367

  17. Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    2011-01-01

    A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

  18. Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.

    2010-01-01

    A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

  19. Possible Peroxo State of the Dicopper Site of Particulate Methane Monooxygenase from Combined Quantum Mechanics and Molecular Mechanics Calculations.

    PubMed

    Itoyama, Shuhei; Doitomi, Kazuki; Kamachi, Takashi; Shiota, Yoshihito; Yoshizawa, Kazunari

    2016-03-21

    Enzymatic methane hydroxylation is proposed to efficiently occur at the dinuclear copper site of particulate methane monooxygenase (pMMO), which is an integral membrane metalloenzyme in methanotrophic bacteria. The resting state and a possible peroxo state of the dicopper active site of pMMO are discussed by using combined quantum mechanics and molecular mechanics calculations on the basis of reported X-ray crystal structures of the resting state of pMMO by Rosenzweig and co-workers. The dicopper site has a unique structure, in which one copper is coordinated by two histidine imidazoles and another is chelated by a histidine imidazole and primary amine of an N-terminal histidine. The resting state of the dicopper site is assignable to the mixed-valent Cu(I)Cu(II) state from a computed Cu-Cu distance of 2.62 Å from calculations at the B3LYP-D/TZVP level of theory. A μ-η(2):η(2)-peroxo-Cu(II)2 structure similar to those of hemocyanin and tyrosinase is reasonably obtained by using the resting state structure and dioxygen. Computed Cu-Cu and O-O distances are 3.63 and 1.46 Å, respectively, in the open-shell singlet state. Structural features of the dicopper peroxo species of pMMO are compared with those of hemocyanin and tyrosinase and synthetic dicopper model compounds. Optical features of the μ-η(2):η(2)-peroxo-Cu(II)2 state are calculated and analyzed with TD-DFT calculations.

  20. Solvent effect on the absorption spectra of coumarin 120 in water: A combined quantum mechanical and molecular mechanical study.

    PubMed

    Sakata, Tetsuya; Kawashima, Yukio; Nakano, Haruyuki

    2011-01-07

    The solvent effect on the absorption spectra of coumarin 120 (C120) in water was studied utilizing the combined quantum mechanical∕molecular mechanical (QM∕MM) method. In molecular dynamics (MD) simulation, a new sampling scheme was introduced to provide enough samples for both solute and solvent molecules to obtain the average physical properties of the molecules in solution. We sampled the structure of the solute and solvent molecules separately. First, we executed a QM∕MM MD simulation, where we sampled the solute molecule in solution. Next, we chose random solute structures from this simulation and performed classical MD simulation for each chosen solute structure with its geometry fixed. This new scheme allowed us to sample the solute molecule quantum mechanically and sample many solvent structures classically. Excitation energy calculations using the selected samples were carried out by the generalized multiconfigurational perturbation theory. We succeeded in constructing the absorption spectra and realizing the red shift of the absorption spectra found in polar solvents. To understand the motion of C120 in water, we carried out principal component analysis and found that the motion of the methyl group made the largest contribution and the motion of the amino group the second largest. The solvent effect on the absorption spectrum was studied by decomposing it in two components: the effect from the distortion of the solute molecule and the field effect from the solvent molecules. The solvent effect from the solvent molecules shows large contribution to the solvent shift of the peak of the absorption spectrum, while the solvent effect from the solute molecule shows no contribution. The solvent effect from the solute molecule mainly contributes to the broadening of the absorption spectrum. In the solvent effect, the variation in C-C bond length has the largest contribution on the absorption spectrum from the solute molecule. For the solvent effect on the

  1. Evolution of water sorption in catalyst coated membranes subjected to combined chemical and mechanical degradation.

    PubMed

    Venkatesan, Senthil velan; Lim, Chan; Rogers, Erin; Holdcroft, Steven; Kjeang, Erik

    2015-06-07

    Catalyst coated perfluorosulfonic acid ionomer membranes (CCMs) were subjected to a combined chemical/mechanical accelerated stress test (AST) designed for rapid benchmarking of in situ membrane stability in polymer electrolyte fuel cells. In order to understand the evolution of the ionomer water sorption characteristics during combined chemical/mechanical degradation, CCM samples were periodically extracted from the AST and analyzed for ionomer mass fraction and water sorption properties. In spite of severe fluoride release and membrane thinning, the water uptake per unit mass of the partially degraded CCMs was found to be essentially constant. The mass fraction of ionomer in the CCM samples determined from thermogravimetric analysis (TGA) showed significant material loss throughout the AST process due to ionomer degradation and fluoride release, up to roughly 50% at end-of-life. The effects proceeding at different stages of degradation were therefore more accurately revealed by ionomer mass-normalized data. The water uptake per unit gram of ionomer was shown to increase significantly with degradation, in contrast to the previous results normalized by CCM dry mass. Although increased water sorption may indicate enlarged solvated hydrophilic domains in the membrane, which would be beneficial for enhanced proton mobility, the proton conductivity was found to decrease. This finding suggests that the additional water sorbed in the membrane was not contributing to proton conduction and was therefore likely situated in non-ionic cavities formed through degradation rather than in the ionic clusters.

  2. Left ventricular mechanics of counterpulsation and left heart bypass, individually and in combination.

    PubMed

    Rose, E A; Marrin, C A; Bregman, D; Spotnitz, H M

    1979-01-01

    Counterpulsation and left heart bypass devices have been successfully used to salvage patients with severe left ventricular power failure following cardiopulmonary bypass. Each of these techniques is believed to reduce or minimize myocardial work, yet the effects of these devices on the force of myocardial contraction have not been defined. In the present investigation the effects of counterpulsation produced by intravascular (intra-aortic balloon pumping) and extravascular (pulsatile assist device) balloon devices, partial left atrial-aortic bypass, and total bypass on left ventricular mechanics were examined. The devices were studied individually and in combination in 10 anesthetized open-chest dogs. Left ventricular wall stress, external work, and contractility indices were calculated by computer using a changing volume spherical model of the left ventricle. Results indicate that although all currently available circulatory assist devices reduced peak left ventricular wall stress, a spectrum of relative effectiveness progressed from intra-aortic balloon pumping or pulsatile assist device alone through the combination intra-aortic balloon pumping plus the pulsatile assist device. Partial left heart bypass was more effective than intra-aortic balloon pumping plus the pulsatile assist device in reducing peak wall stress, but the difference was small. Total left heart bypass was vastly superior to any of the other modalities tested in its effects on peak wall stress as well as external work. The addition of counterpulsation to partial or total left heart bypass produced minimal changes in left ventricular systolic mechanics.

  3. Introduction of Enhanced Compressive Residual Stress Profiles in Aerospace Components Using Combined Mechanical Surface Treatments

    NASA Astrophysics Data System (ADS)

    Gopinath, Abhay; Lim, Andre; Nagarajan, Balasubramanian; Cher Wong, Chow; Maiti, Rajarshi; Castagne, Sylvie

    2016-11-01

    Mechanical surface treatments such as Shot Peening (SP) and Deep Cold Rolling (DCR) are being used to introduce Compressive Residual Stress (CRS) at the surface and subsurface layers of aerospace components, respectively. This paper investigates the feasibility of a combined introduction of both the surface and sub-surface compressive residual stress on Ti6Al4V material through a successive application of the two aforementioned processes, one after the other. CRS profiles between individual processes were compared to that of combination of processes to validate the feasibility. It was found out that shot peening introduces surface compressive residual stress into the already deep cold rolled sample, resulting in both surface and sub-surface compressive residual stresses in the material. However the drawback of such a combination would be the increased surface roughness after shot peening a deep cold rolled sample which can be critical especially in compressor components. Hence, a new technology, Vibro-Peening (VP) may be used as an alternative to SP to introduce surface stress at reduced roughness.

  4. A possible mechanism for combined arsenic and fluoride induced cellular and DNA damage in mice.

    PubMed

    Flora, Swaran J S; Mittal, Megha; Pachauri, Vidhu; Dwivedi, Nidhi

    2012-01-01

    Arsenic and fluoride are major contaminants of drinking water. Mechanisms of toxicity following individual exposure to arsenic or fluoride are well known. However, it is not explicit how combined exposure to arsenic and fluoride leads to cellular and/or DNA damage. The present study was planned to assess (i) oxidative stress during combined chronic exposure to arsenic and fluoride in drinking water, (ii) correlation of oxidative stress with cellular and DNA damage and (iii) mechanism of cellular damage using IR spectroscopy. Mice were exposed to arsenic and fluoride (50 ppm) either individually or in combination for 28 weeks. Arsenic or fluoride exposure individually led to a significant increase in reactive oxygen species (ROS) generation and associated oxidative stress in blood, liver and brain. Individual exposure to the two toxicants showed significant depletion of blood glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6PD) activity, and single-stranded DNA damage using a comet assay in lymphocytes. We also observed an increase in the activity of ATPase, thiobarbituric acid reactive substance (TBARS) and a decreased, reduced and oxidized glutathione (GSH : GSSG) ratio in the liver and brain. Antioxidant enzymes like superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were decreased and increased in liver and brain respectively. The changes were more pronounced in liver compared to brain suggesting liver to be more susceptible to the toxic effects of arsenic and fluoride. Interestingly, combined exposure to arsenic and fluoride resulted in less pronounced toxic effects compared to their individual effects based on biochemical variables, IR spectra, DNA damage (TUNEL and comet assays) and histopathological observations. IR spectra suggested that arsenic or fluoride perturbs the strength of protein and amide groups; however, the shifts in peaks were not pronounced during combined exposure. These results thus highlight the role of

  5. Mechanisms mediating enhanced neutralization efficacy of Staphylococcal enterotoxin B by combinations of monoclonal antibodies

    DOE PAGES

    Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; ...

    2015-01-08

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used tomore » validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Lastly structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.« less

  6. Mechanisms mediating enhanced neutralization efficacy of Staphylococcal enterotoxin B by combinations of monoclonal antibodies

    SciTech Connect

    Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C.; Goger, Michael; Wang, Xiaobo; Fries, Bettina C.

    2015-01-08

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Lastly structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.

  7. Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies.

    PubMed

    Dutta, Kaushik; Varshney, Avanish K; Franklin, Matthew C; Goger, Michael; Wang, Xiaobo; Fries, Bettina C

    2015-03-13

    Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class II and specific V-β chains of the T-cell receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy, even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine-mapping conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs binding to SEB. The mapping of epitopes established that a combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB·T-cell receptor·major histocompatibility complex class II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.

  8. Keratinocyte galvanotaxis in combined DC and AC electric fields supports an electromechanical transduction sensing mechanism.

    PubMed

    Hart, Francis X; Laird, Mhairi; Riding, Aimie; Pullar, Christine E

    2013-02-01

    Sedentary keratinocytes at the edge of a skin wound migrate into the wound, guided by the generation of an endogenous electric field (EF) generated by the collapse of the transepithelial potential. The center of the wound quickly becomes more negative than the surrounding tissue and remains the cathode of the endogenous EF until the wound is completely re-epithelialized. This endogenous guidance cue can be studied in vitro. When placed in a direct current (DC) EF of physiological strength, 100 V/m, keratinocytes migrate directionally toward the cathode in a process known as galvanotaxis. Although a number of membrane-bound (e.g., epidermal growth factor receptor (EGFR), integrins) and cytosolic proteins (cAMP, ERK, PI3K) are known to play a role in the downstream signaling mechanisms underpinning galvanotaxis, the initial sensing mechanism for this response is not understood. To investigate the EF sensor, we studied the migration of keratinocytes in a DC EF of 100 V/m, alternating current (AC) EFs of 40 V/m at either 1.6 or 160 Hz, and combinations of DC and AC EFs. In the AC EFs alone, keratinocytes migrated randomly. The 1.6 Hz AC EF combined with the DC EF suppressed the direction of migration but had no effect on speed. In contrast, the 160 Hz AC EF combined with the DC EF did not affect the direction of migration but increased the migration speed compared to the DC EF alone. These results can be understood in terms of an electromechanical transduction model, but not an electrodiffusion/osmosis or a voltage-gated channel model.

  9. Insight into the Phosphodiesterase Mechanism from Combined QM/MM Free Energy Simulations

    PubMed Central

    Wong, Kin-Yiu; Gao, Jiali

    2011-01-01

    Summary Molecular dynamics simulations employing a combined quantum mechanical and molecular mechanical potential have been carried out to elucidate the reaction mechanism of the hydrolysis of a cyclic nucleotide cAMP substrate by phosphodiesterase 4B (PDE4B). PDE4B is a member of the PDE superfamily of enzymes that play crucial roles in cellular signal transduction. We have determined a two-dimensional potential of mean force for the coupled phosphoryl bond cleavage and proton transfer through a general acid catalysis mechanism in PDE4B. The results indicate that the ring-opening process takes place through an SN2 reaction mechanism, followed by a proton transfer to stabilize the leaving group. The computed free energy of activation for the PDE4B-catalyzed cAMP hydrolysis is about 13 kcal/mol and an overall reaction free energy is about −17 kcal/mol, both in accord with experimental results. In comparison with the uncatalyzed reaction in water, the enzyme PDE4B provides a strong stabilization of the transition state, lowering the free energy barrier by 14 kcal/mol. We found that the proton transfer from the general acid residue His234 to the O3' oxyanion of the ribosyl leaving group lags behind the nucleophilic attack, resulting in a shallow minimum on the free energy surface. A key contributing factor to transition state stabilization is the elongation of the distance between the divalent metal ions Zn2+ and Mg2+ in the active site as the reaction proceeds from the Michaelis complex to the transition state. PMID:21595828

  10. Mechanism of Bacterial Inactivation by (+)-Limonene and Its Potential Use in Food Preservation Combined Processes

    PubMed Central

    Espina, Laura; Gelaw, Tilahun K.; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

    2013-01-01

    This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments. PMID:23424676

  11. Mechanism of bacterial inactivation by (+)-limonene and its potential use in food preservation combined processes.

    PubMed

    Espina, Laura; Gelaw, Tilahun K; de Lamo-Castellví, Sílvia; Pagán, Rafael; García-Gonzalo, Diego

    2013-01-01

    This work explores the bactericidal effect of (+)-limonene, the major constituent of citrus fruits' essential oils, against E. coli. The degree of E. coli BJ4 inactivation achieved by (+)-limonene was influenced by the pH of the treatment medium, being more bactericidal at pH 4.0 than at pH 7.0. Deletion of rpoS and exposure to a sub-lethal heat or an acid shock did not modify E. coli BJ4 resistance to (+)-limonene. However, exposure to a sub-lethal cold shock decreased its resistance to (+)-limonene. Although no sub-lethal injury was detected in the cell envelopes after exposure to (+)-limonene by the selective-plating technique, the uptake of propidium iodide by inactivated E. coli BJ4 cells pointed out these structures as important targets in the mechanism of action. Attenuated Total Reflectance Infrared Microspectroscopy (ATR-IRMS) allowed identification of altered E. coli BJ4 structures after (+)-limonene treatments as a function of the treatment pH: β-sheet proteins at pH 4.0 and phosphodiester bonds at pH 7.0. The increased sensitivity to (+)-limonene observed at pH 4.0 in an E. coli MC4100 lptD4213 mutant with an increased outer membrane permeability along with the identification of altered β-sheet proteins by ATR-IRMS indicated the importance of this structure in the mechanism of action of (+)-limonene. The study of mechanism of inactivation by (+)-limonene led to the design of a synergistic combined process with heat for the inactivation of the pathogen E. coli O157:H7 in fruit juices. These results show the potential of (+)-limonene in food preservation, either acting alone or in combination with lethal heat treatments.

  12. Reaction mechanisms of aqueous monoethanolamine with carbon dioxide: a combined quantum chemical and molecular dynamics study.

    PubMed

    Hwang, Gyeong S; Stowe, Haley M; Paek, Eunsu; Manogaran, Dhivya

    2015-01-14

    Aqueous monoethanolamine (MEA) has been extensively studied as a solvent for CO2 capture, yet the underlying reaction mechanisms are still not fully understood. Combined ab initio and classical molecular dynamics simulations were performed to revisit and identify key elementary reactions and intermediates in 25-30 wt% aqueous MEA with CO2, by explicitly taking into account the structural and dynamic effects. Using static quantum chemical calculations, we also analyzed in more detail the fundamental interactions involved in the MEA-CO2 reaction. We find that both the CO2 capture by MEA and solvent regeneration follow a zwitterion-mediated two-step mechanism; from the zwitterionic intermediate, the relative probability between deprotonation (carbamate formation) and CO2 removal (MEA regeneration) tends to be determined largely by the interaction between the zwitterion and neighboring H2O molecules. In addition, our calculations clearly demonstrate that proton transfer in the MEA-CO2-H2O solution primarily occurs through H-bonded water bridges, and thus the availability and arrangement of H2O molecules also directly impacts the protonation and/or deprotonation of MEA and its derivatives. This improved understanding should contribute to developing more comprehensive kinetic models for use in modeling and optimizing the CO2 capture process. Moreover, this work highlights the importance of a detailed atomic-level description of the solution structure and dynamics in order to better understand molecular mechanisms underlying the reaction of CO2 with aqueous amines.

  13. Selecting optimal combinations of transcription factors to promote axon regeneration: Why mechanisms matter.

    PubMed

    Venkatesh, Ishwariya; Blackmore, Murray G

    2016-12-23

    Recovery from injuries to the central nervous system, including spinal cord injury, is constrained in part by the intrinsically low ability of many CNS neurons to mount an effective regenerative growth response. To improve outcomes, it is essential to understand and ultimately reverse these neuron-intrinsic constraints. Genetic manipulation of key transcription factors (TFs), which act to orchestrate production of multiple regeneration-associated genes, has emerged as a promising strategy. It is likely that no single TF will be sufficient to fully restore neuron-intrinsic growth potential, and that multiple, functionally interacting factors will be needed. An extensive literature, mostly from non-neural cell types, has identified potential mechanisms by which TFs can functionally synergize. Here we examine four potential mechanisms of TF/TF interaction; physical interaction, transcriptional cross-regulation, signaling-based cross regulation, and co-occupancy of regulatory DNA. For each mechanism, we consider how existing knowledge can be used to guide the discovery and effective use of TF combinations in the context of regenerative neuroscience. This mechanistic insight into TF interactions is needed to accelerate the design of effective TF-based interventions to relieve neuron-intrinsic constraints to regeneration and to foster recovery from CNS injury.

  14. Mechanism of red mud combined with Fenton's reagent in sewage sludge conditioning.

    PubMed

    Zhang, Hao; Yang, Jiakuan; Yu, Wenbo; Luo, Sen; Peng, Li; Shen, Xingxing; Shi, Yafei; Zhang, Shinan; Song, Jian; Ye, Nan; Li, Ye; Yang, Changzhu; Liang, Sha

    2014-08-01

    Red mud was evaluated as an alternative skeleton builder combined with Fenton's reagent in sewage sludge conditioning. The results show that red mud combined with Fenton's reagent showed good conditioning capability with the pH of the filtrate close to neutrality, indicating that red mud acted as a neutralizer as well as a skeleton builder when jointly used with Fenton's reagent. Through response surface methodology (RSM), the optimal dosages of Fe(2+), H2O2 and red mud were proposed as 31.9, 33.7 and 275.1 mg/g DS (dry solids), respectively. The mechanism of the composite conditioner could be illuminated as follows: (1) extracellular polymeric substances (EPS), including loosely bound EPS and tightly bound EPS, were degraded into dissolved organics, e.g., proteins and polysaccharides; (2) bound water was released and converted into free water due to the degradation of EPS; and (3) morphology of the conditioned sludge exhibited a porous structure in contrast with the compact structure of raw sludge, and the addition of red mud formed new mineral phases and a rigid lattice structure in sludge, allowing the outflow of free water. Thus, sludge dewatering performance was effectively improved. The economic assessment for a wastewater treatment plant of 370,000 equivalent inhabitants confirms that using red mud conditioning, combined with Fenton's reagent, leads to a saving of approximately 411,000 USD/y or 50.8 USD/t DS comparing with using lime and ordinary Portland cement combined with Fenton's reagent, and approximately 612,000 USD/y or 75.5 USD/t DS comparing with the traditional treatment.

  15. [NB4 cell apoptosis induced by bortezomib combined with As(2)O(3) and its mechanism].

    PubMed

    Chen, Xiao-Wen; Xia, Hai-Long; Xia, Rui-Xiang

    2011-04-01

    This study was aimed to investigate the apoptosis induced by bortezomib combined with As(2)O(3) in APL cell line NB4 and its mechanism. The apoptotic cells were detected by flow cytometry with Annexin V/propidium iodide double staining; the morphology of apoptotic cells was observed by Hoechst staining, Western blot was used to measure activation of caspase-3 and -9 as well as expression of NOXA; the siRNA technique was used to specifically silence NOXA gene; the lipofectamine 2000 was used to transfect pEGFP-Noxa plasmid and pEGFP vacant vector. The results showed that the bortezomib combined with As(2)O(3) could induce significant apoptosis of NB4 cells and activation of caspase 3 and caspase 9, but As(2)O(3) (0.5 µmol/L) alone could not cause marked activation of caspase cascade and apoptosis of NB4 cells. The expression level of NOXA in NB4 cells induced by bortezomib combined with As(2)O(3) was up-regulated; the activation level of caspase-3 and apoptotic rate of NB4 cells treated by bortezomib combined with As(2)O(3) decreased after specifically silencing the NOXA gene. The high expression of NOXA induced by transfection of plasmid could enhance the caspase 3 activity induced by As(2)O(3) alone. It is concluded that bortezomib can enhance sensitivity of NB4 cells to apoptosis induced by As(2)O(3) which may be related with up-regulation of proapoptotic protein NOXA.

  16. Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations.

    PubMed

    Parchment, Ralph E; Voth, Andrea Regier; Doroshow, James H; Berzofsky, Jay A

    2016-08-01

    Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell-tumor cell proximity). Evaluating such "trans-cellular pharmacology," in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell's biological role. We have termed this form of nearest neighbor image analysis of drug action "proximity PD microscopy," to indicate the

  17. Mechanically fastened composite laminates subjected to combined bearing-bypass and shear loading

    NASA Technical Reports Server (NTRS)

    Madenci, Erdogan

    1993-01-01

    Bolts and rivets provide a means of load transfer in the construction of aircraft. However, they give rise to stress concentrations and are often the source and location of static and fatigue failures. Furthermore, fastener holes are prone to cracks during take-off and landing. These cracks present the most common origin of structural failures in aircraft. Therefore, accurate determination of the contact stresses associated with such loaded holes in mechanically fastened joints is essential to reliable strength evaluation and failure prediction. As the laminate is subjected to loading, the contact region, whose extent is not known, develops between the fastener and the hole boundary through this contact region, which consists of slip and no-slip zones due to friction. The presence of the unknown contact stress distribution over the contact region between the pin and the composite laminate, material anisotropy, friction between the pin and the laminate, pin-hole clearance, combined bearing-bypass and shear loading, and finite geometry of the laminate result in a complex non-linear problem. In the case of bearing-bypass loading in compression, this non-linear problem is further complicated by the presence of dual contact regions. Previous research concerning the analysis of mechanical joints subjected to combined bearing-bypass and shear loading is non-existent. In the case of bearing-bypass loading only, except for the study conducted by Naik and Crews (1991), others employed the concept of superposition which is not valid for this non-linear problem. Naik and Crews applied a linear finite element analysis with conditions along the pin-hole contact region specified as displacement constraint equations. The major shortcoming of this method is that the variation of the contract region as a function of the applied load should be known a priori. Also, their analysis is limited to symmetric geometry and material systems, and frictionless boundary conditions. Since the

  18. Network Bursting Dynamics in Excitatory Cortical Neuron Cultures Results from the Combination of Different Adaptive Mechanism

    PubMed Central

    Masquelier, Timothée; Deco, Gustavo

    2013-01-01

    In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN) to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABAAergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these “network spikes” (NS). The inter-NS-intervals (INSIs) proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts (“bursts of NSs”, BNS), with short (∼1 s) INSIs and separated by long silent intervals (tens of s), which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV∼0), and weak excitability led to rare BNSs, approaching a Poisson process (CV∼1). Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV∼0.5), with an adaptation timescale in the 2–8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally. PMID:24146781

  19. Network bursting dynamics in excitatory cortical neuron cultures results from the combination of different adaptive mechanisms.

    PubMed

    Masquelier, Timothée; Deco, Gustavo

    2013-01-01

    In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN) to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABAAergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these "network spikes" (NS). The inter-NS-intervals (INSIs) proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts ("bursts of NSs", BNS), with short (~1 s) INSIs and separated by long silent intervals (tens of s), which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV~0), and weak excitability led to rare BNSs, approaching a Poisson process (CV~1). Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV~0.5), with an adaptation timescale in the 2-8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally.

  20. Combined Quenching Mechanism of Anthracene Fluorescence by Cetylpyridinium Chloride in Sodium Dodecyl Sulfate Micelles.

    PubMed

    Soemo, Angela R; Pemberton, Jeanne E

    2014-03-01

    The Stern-Volmer quenching constant (KSV) for quenching of anthracene fluorescence in sodium dodecyl sulfate (SDS) micelles by pyridinium chloride has been reported previously to be 520 M(-1) based on steady state fluorescence measurements. However, such measurements cannot distinguish static versus dynamic contributions to the overall quenching. In the work reported here, the quenching dynamics of anthracene in SDS micelles by cetylpyridinium chloride (CPC), an analogue of pyridinium chloride, were investigated using both steady state and time resolved fluorescence quenching. Concurrent measurement of the decrease in fluorescence intensity and lifetime of anthracene provide a quantitative evaluation of collision induced (i.e. dynamic) versus complex formation (i.e. static) quenching of the anthracene fluorophore. The results reveal that a combined quenching mechanism is operative with approximately equal constants of 249 ± 6 M(-1) and 225 ± 12 M(-1) for dynamic and static quenching, respectively.

  1. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury.

    PubMed

    Kadoya, Ken; Tsukada, Shingo; Lu, Paul; Coppola, Giovanni; Geschwind, Dan; Filbin, Marie T; Blesch, Armin; Tuszynski, Mark H

    2009-10-29

    Despite advances in promoting axonal regeneration after acute spinal cord injury (SCI), elicitation of bridging axon regeneration after chronic SCI remains a formidable challenge. We report that combinatorial therapies administered 6 weeks, and as long as 15 months, after SCI promote axonal regeneration into and beyond a midcervical lesion site. Provision of peripheral nerve conditioning lesions, grafts of marrow stromal cells, and establishment of NT-3 gradients supports bridging regeneration. Controls receiving partial components of the full combination fail to exhibit bridging. Notably, intraneuronal molecular mechanisms recruited by delayed therapies mirror those of acute injury, including activation of transcriptional activators and regeneration-associated genes. Collectively, these findings provide evidence that regeneration is achievable at unprecedented postinjury time points.

  2. The Molecular Mechanism of Action of the CR6261-Azichromycin Combination Found through Computational Analysis

    PubMed Central

    Cui, Wei; Wang, Kui; Ruan, Jishou; Qi, Zhi; Feng, Yi; Shao, Yiming; Tuszynski, Jack A.

    2012-01-01

    Background CR6261 was found in 2008 and F10 was found in 2009. In 2010 Friesen et al experimentally showed that Oseltamivir/Zanamivir may improve the therapeutic efficacy of CR6261. As a result, the use of CR6261 combined with a drug to provide an antibody-based therapy against all influenza A viruses was proposed. Although CR8020 may neutralize group 2 influenza viruses and FI6 may neutralize both group 1 and group 2 influenza viruses as determined in 2011, the insight of Friesen et al is still interesting. Here, we address the following questions: how to uncover the molecular mechanism of a drug, which improves the therapeutic efficacy of mAbs and how to find drugs that enable CR6261 (CR8020, F10) to become a universal mAb. Methods and Findings Using the 3D structures of 3 gbn, 3 gbm, 3 ztn, 3 ztj, 3 fku and 3 sdy, we separate the 3D structures of CR6261, F10, CR8020 and FI6, and the 3D structures of trimer HAs of H3N2 and H5N1. Based on the experimental result of Friesen et al, we have found many clues, which reveal the molecular mechanism of action for a drug and an HA-mAb complex. Conclusions Oseltamivir/Zanamivir may congruously improve the therapeutic efficacies of CR6261, F10, CR8020 and FI6 by providing an additional affinity to compensate for the loss of affinity between HA and mAb resulting from mutations. However, Oseltamivir or Zanamivir are not expected to generally widen the spectrum of these mAbs. In order to enhance CR6261, CR8020, or for F10 to become universal, we may select Azichromycin, Oseltamivir, or the combination of Azichromycin and Oseltamivir, respectively. PMID:22693576

  3. Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues

    PubMed Central

    Lourenço, Tânia; Paes de Faria, Joana; Bippes, Christian A.; Maia, João; Lopes-da-Silva, José A.; Relvas, João B.; Grãos, Mário

    2016-01-01

    Extracellular matrix (ECM) proteins play a key role during oligodendrogenesis. While fibronectin (FN) is involved in the maintenance and proliferation of oligodendrocyte progenitor cells (OPCs), merosin (MN) promotes differentiation into oligodendrocytes (OLs). Mechanical properties of the ECM also seem to affect OL differentiation, hence this study aimed to clarify the impact of combined biophysical and biochemical elements during oligodendrocyte differentiation and maturation using synthetic elastic polymeric ECM-like substrates. CG-4 cells presented OPC- or OL-like morphology in response to brain-compliant substrates functionalised with FN or MN, respectively. The expression of the differentiation and maturation markers myelin basic protein — MBP — and proteolipid protein — PLP — (respectively) by primary rat oligodendrocytes was enhanced in presence of MN, but only on brain-compliant conditions, considering the distribution (MBP) or amount (PLP) of the protein. It was also observed that maturation of OLs was attained earlier (by assessing PLP expression) by cells differentiated on MN-functionalised brain-compliant substrates than on standard culture conditions. Moreover, the combination of MN and substrate compliance enhanced the maturation and morphological complexity of OLs. Considering the distinct degrees of stiffness tested ranging within those of the central nervous system, our results indicate that 6.5 kPa is the most suitable rigidity for oligodendrocyte differentiation. PMID:26879561

  4. Bacterial radiosensitization by using radiation processing in combination with essential oil: Mechanism of action

    NASA Astrophysics Data System (ADS)

    Lacroix, Monique; Caillet, Stéphane; Shareck, Francois

    2009-07-01

    Spice extracts under the form of essential oils were tested for their efficiency to increase the relative radiosensitivity of Listeria monocytogenes and Escherichia coli O157H7 in culture media. The two pathogens were treated by gamma-irradiation alone or in combination with oregano essential oil to evaluate their mechanism of action. The membrane murein composition, and the intracellular and extracellular concentration of ATP was determined. The bacterial strains were treated with two irradiation doses: 1.2 kGy to induce cell damage and 3.5 kGy to cause cell death for L. monocytogenes. A dose of 0.4 kGy to induce cell damages, 1.1 kGy to obtain viable but nonculturable (VBNC) state and 1.3 kGy to obtain a lethal dose was also applied on E. coli O157H7. Oregano essential oil was used at 0.020% and 0.025% (w/v), which is the minimum inhibitory concentration (MIC) for L. monocytogenes. For E. coli O157H7, a concentration of 0.006% and 0.025% (w/v) which is the minimum inhibitory concentration was applied. The use of essential oils in combination with irradiation has permitted an increase of the bacterial radiosensitization by more than 3.1 times. All treatments had also a significant effect ( p⩽0.05) on the murein composition, although some muropeptides did not seem to be affected by the treatment. Each treatment influenced differently the relative percentage and number of muropeptides. There was a significant ( p⩽0.05) correlation between the reduction of intracellular ATP and increase in extracellular ATP following treatment of the cells with oregano oil. The reduction of intracellular ATP was even more important when essential oil was combined with irradiation, but irradiation of L. monocytogenes alone induced a significant decrease ( p⩽0.05) of the internal ATP without affecting the external ATP.

  5. Growth inhibitive effect of betulinic acid combined with tripterine on MSB-1 cells and its mechanism.

    PubMed

    An, N; Li, H Y; Zhang, X M

    2015-12-01

    Marek's disease (MD), a highly infectious lymphoproliferative disease in chickens, is caused by a cell-associated oncogenic herpesvirus, Marek's disease virus (MDV). MSB-1 is a MD-derived lymphoblastoid cell line and can induce tumors when inoculated into susceptible chickens. Betulinic acid, which is present as one of the major effective components in many traditional Chinese medicines, has recently been reported to inhibit growth of cancer cells and employed as a potential anticancer agent. Tripterine, a major active compound extracted from the Chinese herb Tripterygium wilfordii Hook F, has now also shown anti-tumor activities in various cancers. The aim of this study was to investigate the synergistic growth-inhibitive effect of betulinic acid combined with tripterine on MSB-1 cells and its mechanism. Viability of MSB-1 cells was assessed by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) method. Cell apoptotic analysis was performed by fluorescence detection. NF-κB transcription activity was detected by measuring luciferase activity. Western blotting was used to analyze the expression of p65, IκB and Meq. Our results showed that the proliferation in the combination group was significantly decreased as compared with that of monotherapy using betulinic acid or tripterine, accompanied by an induction of apoptosis, inhibition of NF-κB transcriptional activity and its targeting oncogenic gene Meq. The results suggest that the combination of betulinic acid and tripterine at lower concentration may produce a synergistic inhibitive effect on MSB-1 cells that warrants further investigation for its potential clinical applications.

  6. [Mechanism of action of combined extremely weak magnetic field on aqueous solution of amino acid].

    PubMed

    Zhadin, M N; Bakharev, B V; Bobkova, N V

    2014-01-01

    The fundamental physical mechanisms of resonance action of an extremely weak (40 nT) alternating magnetic field at the cyclotron frequency combined with a weak (40 μT) static magnetic field, on living systems are analyzed in the present work. The experimental effects of such sort of magnetic fields were described in different papers: the very narrow resonant peaks in electrical conductivity of the aqueous solutions in the in vitro experiments and the biomedical in vivo effects on living animals of magnetic fields with frequencies tuned to some amino acids. The existing experimental in vitro data had a good repeatability in different laboratories and countries. Unfortunately, for free ions such sort of effects are absolutely impossible because the dimensions of an ion rotation radius should be measured by meters at room temperature and at very low static magnetic fields used in all the above experiments. Even for bound ions these effects should be also absolutely impossible from the positions of classic physics because of rather high viscosity of biological liquid media (blood plasma, cerebrospinal liquid, cytoplasm). Only modern quantum electrodynamics of condensed media opens the new ways for solving these problems. The proposed article is devoted to analysis of quantum mechanisms of these effects.

  7. Subchromoplast sequestration of carotenoids affects regulatory mechanisms in tomato lines expressing different carotenoid gene combinations.

    PubMed

    Nogueira, Marilise; Mora, Leticia; Enfissi, Eugenia M A; Bramley, Peter M; Fraser, Paul D

    2013-11-01

    Metabolic engineering of the carotenoid pathway in recent years has successfully enhanced the carotenoid contents of crop plants. It is now clear that only increasing biosynthesis is restrictive, as mechanisms to sequestrate these increased levels in the cell or organelle should be exploited. In this study, biosynthetic pathway genes were overexpressed in tomato (Solanum lycopersicum) lines and the effects on carotenoid formation and sequestration revealed. The bacterial Crt carotenogenic genes, independently or in combination, and their zygosity affect the production of carotenoids. Transcription of the pathway genes was perturbed, whereby the tissue specificity of transcripts was altered. Changes in the steady state levels of metabolites in unrelated sectors of metabolism were found. Of particular interest was a concurrent increase of the plastid-localized lipid monogalactodiacylglycerol with carotenoids along with membranous subcellular structures. The carotenoids, proteins, and lipids in the subchromoplast fractions of the transgenic tomato fruit with increased carotenoid content suggest that cellular structures can adapt to facilitate the sequestration of the newly formed products. Moreover, phytoene, the precursor of the pathway, was identified in the plastoglobule, whereas the biosynthetic enzymes were in the membranes. The implications of these findings with respect to novel pathway regulation mechanisms are discussed.

  8. Combined Effects of UV Exposure Duration and Mechanical Abrasion on Microplastic Fragmentation by Polymer Type.

    PubMed

    Song, Young Kyoung; Hong, Sang Hee; Jang, Mi; Han, Gi Myung; Jung, Seung Won; Shim, Won Joon

    2017-03-28

    It is important to understand the fragmentation processes and mechanisms of plastic litter to predict microplastic production in the marine environment. In this study, accelerated weathering experiments were performed in the laboratory, with ultraviolet (UV) exposure for up to 12 months followed by mechanical abrasion (MA) with sand for 2 months. Fragmentation of low-density polyethylene (PE), polypropylene (PP), and expanded polystyrene (EPS) was evaluated under conditions that simulated a beach environment. PE and PP were minimally fragmented by MA without photooxidation by UV (8.7 ± 2.5 and 10.7 ± 0.7 particles/pellet, respectively). The rate of fragmentation by UV exposure duration increased more for PP than PE. A 12-month UV exposure and 2-month MA of PP and PE produced 6084 ± 1061 and 20 ± 8.3 particles/pellet, respectively. EPS pellets were susceptible to MA alone (4220 ± 33 particles/pellet), while the combination of 6 months of UV exposure followed by 2 months of MA produced 12,152 ± 3276 particles/pellet. The number of fragmented polymer particles produced by UV exposure and mechanical abrasion increased with decreasing size in all polymer types. The size-normalized abundance of the fragmented PE, PP, and EPS particles according to particle size after UV exposure and MA was predictable. Up to 76.5% of the initial EPS volume was unaccounted for in the final volume of pellet produced particle fragments, indicating that a large proportion of the particles had fragmented into undetectable submicron particles.

  9. Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis.

    PubMed

    Meyer, Luisa A; Johnson, Michael G; Cullen, Diane M; Vivanco, Juan F; Blank, Robert D; Ploeg, Heidi-Lynn; Smith, Everett L

    2016-04-01

    , 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses.

  10. Cardiopulmonary bypass (CPB) has no significant impact on survival in patients undergoing nephrectomy and level III-IV inferior vena cava thrombectomy; a multi-institutional analysis

    PubMed Central

    Dall'Era, Marc A.; Durbin-Johnson, Blythe; Carballido, Joaquín A.; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C.; Espinós, Estefania Linares; Mandel, Philipp; Martinez-Salamanca, Juan I.; Master, Viraj A.; McKiernan, James M.; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S.; Rodriguez-Faba, Oscar; Russo, Paul; Scherr, Douglas S.; Shariat, Shahrokh F.; Spahn, Martin; Terrone, Carlo; Vergho, Daniel; Wallen, Eric M.; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A.; Evans, Christopher P.

    2016-01-01

    Purpose The impact of cardiopulmonary bypass (CPB) usage in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We sought to determine the impact of cardiopulmonary bypass (CPB) on overall and cancer specific survival, as well as surgical complication rates, and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without CPB. Patients and Methods We retrospectively analyzed 362 patients with RCC and with level III or IV tumor thrombus from 1992 to 2012 in 22 US and European centers. Cox proportional hazards models were used to compare overall and cancer-specific survival between patients with and without CPB. Perioperative mortality and complications rates were assessed using logistic regression analyses. Results The median overall survival was 24.6 months in non-CPB patients and 26.6 months in CPB patients. Overall survival and cancer-specific survival (CSS) did not differ significantly in both groups, neither in univariate analysis nor when adjusting for known risk factors. In multivariate analysis, no significant differences were seen in hospital LOS, Clavien 1-4 complication rate, intraoperative or 30 day mortality, and CSS between both groups. Limitations include the retrospective nature of the study. Conclusions In our multi-institutional analysis, the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality in the multivariate analysis. Higher surgical complications were not independently associated with the use of CPB. PMID:25797392

  11. Opioid Mechanism Involvement in the Synergism Produced by the Combination of Diclofenac and Caffeine in the Formalin Model

    PubMed Central

    Flores-Ramos, José María; Díaz-Reval, M. Irene

    2013-01-01

    Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral administration of diclofenac, caffeine, or their combination. Opioid involvement was analyzed through intracerebroventricular (i.c.v.) administration of naloxone followed by the oral administration of the study drugs. Diclofenac presented a dose-dependent effect, with a mean effective dose (ED50) of 6.7 mg/kg. Caffeine presented an analgesic effect with a 17–36% range. The combination of subeffective doses of each of the two drugs presented the greatest synergism with an effect of 57.7 ± 5.6%. The maximal antinociceptive effect was obtained with the combination of 10.0 mg/kg diclofenac and 1.0 mg/kg of caffeine, with an effect of 76.7 ± 5.6%. The i.c.v. administration of naloxone inhibited the effect of diclofenac, both separately and combined. In conclusion, caffeine produces antinociceptive synergism when administered in combination with diclofenac, and this synergism is partially mediated by opioid mechanisms at the central level. PMID:27335871

  12. Incidence and mechanisms of resistance to the combination of amoxicillin and clavulanic acid in Escherichia coli.

    PubMed Central

    Stapleton, P; Wu, P J; King, A; Shannon, K; French, G; Phillips, I

    1995-01-01

    Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 micrograms/ml for 51 (71%) of these and > or = 32-16 micrograms/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (beta-lactamase activities, > 200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 beta-lactamase, which has previously been associated with resistance to amoxicillin-clavulanic acid. Ten isolates produced increased amounts of chromosomal beta-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-67-->Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-67-->Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-241-->Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread. PMID:8585729

  13. Mechanical behavior of twinned SiC nanowires under combined tension-torsion and compression-torsion strain

    SciTech Connect

    Li, Zhijie; Wang, Shengjie; Wang, Zhiguo; Zu, Xiaotao T.; Gao, Fei; Weber, William J.

    2010-07-01

    The mechanical behavior of twinned silicon carbide (SiC) nanowires under combined tension-torsion and compression-torsion is investigated using molecular dynamics simulations with an empirical potential. The simulation results show that both the tensile failure stress and buckling stress decrease under combined tension-torsional and combined compression-torsional strain, and they decrease with increasing torsional rate under combined loading. The torsion rate has no effect on the elastic properties of the twinned SiC nanowires. The collapse of the twinned nanowires takes place in a twin stacking fault of the nanowires.

  14. Combined photosynthesis and mechanical aeration for nitrification in dairy waste stabilisation ponds.

    PubMed

    Sukias, J P S; Craggs, R J; Tanner, C C; Davies-Colley, R J; Nagels, J W

    2003-01-01

    New Zealand has 16,500 dairy farms (avg. 220 cows), with cows kept on pasture throughout the year. During the 9-month dairy season, the cows are milked twice a day (averaging 2.5-3 h per day in the dairy parlour). Urine and faecal wastes deposited in the dairy parlour are washed away with high pressure hoses, using large volumes of water. A common method of treatment is in simple two-pond (anaerobic/facultative) lagoon systems, which remove about 95% of suspended solids and BOD5, but only 75% of total-N prior to discharge. High concentrations of ammoniacal-N in the effluent can cause toxicity to aquatic organisms in receiving waters. Mechanical aeration of the second (facultative) lagoon to promote nitrification improves effluent quality by reducing oxygen demand and potential ammonia toxicity to streamlife. Mechanical aeration however is associated with considerable mixing, which may prevent algae from optimising photosynthesis in the facultative lagoon. A series of experiments was undertaken which tested the efficiency of mechanical aeration and then attempted to combine it with daytime algal oxygen production in order to maximise ammonia conversion to nitrate, while minimising costs to the farmer. An experimental facility was developed by dividing a large facultative lagoon into two, producing a matched pair of lagoons, operated in parallel with influent flow split equally. Over successive dairy seasons, various aeration regimes were compared. Continuous aeration promoted nearly complete nitrification of the ammoniacal-N (99% removal), and effluent BOD was approximately halved. However the continuous mixing reduced algal biomass, and thus daytime algal photosynthesis. Night-only aeration permitted greater algal photosynthesis to occur, as well as halving electrical power consumption. Ammoniacal-N removal reduced to 90% (10 g m(-3) remaining in the effluent), while BOD removal was also lower than in the continuously aerated lagoon (59 and 69% respectively

  15. Electrostatic vibration energy harvester with combined effect of electrical nonlinearities and mechanical impact

    NASA Astrophysics Data System (ADS)

    Basset, P.; Galayko, D.; Cottone, F.; Guillemet, R.; Blokhina, E.; Marty, F.; Bourouina, T.

    2014-03-01

    This paper presents an advanced study including the design, characterization and theoretical analysis of a capacitive vibration energy harvester. Although based on a resonant electromechanical device, it is intended for operation in a wide frequency band due to the combination of stop-end effects and a strong biasing electrical field. The electrostatic transducer has an interdigited comb geometry with in-plane motion, and is obtained through a simple batch process using two masks. A continuous conditioning circuit is used for the characterization of the transducer. A nonlinear model of the coupled system ‘transduce-conditioning circuit’ is presented and analyzed employing two different semi-analytical techniques together with precise numerical modelling. Experimental results are in good agreement with results obtained from numerical modelling. With the 1 g amplitude of harmonic external acceleration at atmospheric pressure, the system transducer-conditioning circuit has a half-power bandwidth of more than 30% and converts more than 2 µW of the power of input mechanical vibrations over the range of 140 and 160 Hz. The harvester has also been characterized under stochastic noise-like input vibrations.

  16. Potential of combining mechanical and physicochemical municipal wastewater pre-treatment with direct membrane filtration.

    PubMed

    Hey, Tobias; Väänänen, Janne; Heinen, Nicolas; la Cour Jansen, Jes; Jönsson, Karin

    2017-01-01

    At a full-scale wastewater treatment plant, raw municipal wastewater from the sand trap outlet was mechanically and physicochemically pre-treated before microfiltration (MF) in a large pilot-scale study. MF was performed using a low transmembrane pressure (0.03 bar) without backflushing for up to 159 h (∼6.6 d). Pre-filtration ensured stable MF operation compared with the direct application of raw wastewater on the membrane. The combination of physicochemical pre-treatment, such as coagulation, flocculation, and microsieving, with MF meets the European and Swedish discharge limits for small- and medium-sized wastewater treatment plants (WWTPs). The specific electricity footprint was 0.3-0.4 kWh·m(-3), which is an improvement compared to the median footprint of 0.75 kWh·m(-3) found in 105 traditional Swedish WWTPs with sizes of 1500-10,000 person equivalents. Furthermore, the biological treatment step can be omitted, and the risk of releasing greenhouse gases was eliminated. The investigated wastewater treatment process required less space than conventional wastewater treatment processes, and more carbon was made available for biogas production.

  17. Heat flux reduction mechanism induced by a combinational opposing jet and cavity concept in supersonic flows

    NASA Astrophysics Data System (ADS)

    Huang, Wei; Jiang, Yan-ping; Yan, Li; Liu, Jun

    2016-04-01

    The thermal protection on the surface of hypersonic vehicles attracts an increasing attention worldwide, especially when the vehicle enters the atmosphere at high speed. In the current study, the Reynolds-averaged Navier-Stokes (RANS) equations coupled with the Menter's shear stress transport (SST) model have been employed to investigate the heat flux reduction mechanism induced by the variations of the cavity configuration, the jet pressure ratio and the injectant molecular weight in the combinational opposing jet and cavity concept. The length of the cavity is set to be 6 mm, 8 mm and 10 mm in order to make sure that the cavity configuration is the "open" cavity, and the jet pressure ratio is set to be 0.4, 0.6 and 0.8 in order to make sure that the flow field is steady. The injectant is set to be nitrogen and helium. The obtained results show that the aft angle of the cavity only has a slight impact on the heat flux reduction, and the heat flux peak decreases with the decrease of the length of the cavity. The design of the thermal protection system for the hypersonic blunt body is a multi-objective design exploration problem, and the heat flux distribution depends on the jet pressure ratio, the aft wall of the cavity and the injectant molecular weight. The heat flux peak decreases with the increase of the jet pressure ratio when the aft angle of the cavity is large enough, and this value is 45°.

  18. Angular approach combined to mechanical model for tool breakage detection by eddy current sensors

    NASA Astrophysics Data System (ADS)

    Ritou, M.; Garnier, S.; Furet, B.; Hascoet, J. Y.

    2014-02-01

    The paper presents a new complete approach for Tool Condition Monitoring (TCM) in milling. The aim is the early detection of small damages so that catastrophic tool failures are prevented. A versatile in-process monitoring system is introduced for reliability concerns. The tool condition is determined by estimates of the radial eccentricity of the teeth. An adequate criterion is proposed combining mechanical model of milling and angular approach.Then, a new solution is proposed for the estimate of cutting force using eddy current sensors implemented close to spindle nose. Signals are analysed in the angular domain, notably by synchronous averaging technique. Phase shifts induced by changes of machining direction are compensated. Results are compared with cutting forces measured with a dynamometer table.The proposed method is implemented in an industrial case of pocket machining operation. One of the cutting edges has been slightly damaged during the machining, as shown by a direct measurement of the tool. A control chart is established with the estimates of cutter eccentricity obtained during the machining from the eddy current sensors signals. Efficiency and reliability of the method is demonstrated by a successful detection of the damage.

  19. Enhancing combined biological nitrogen and phosphorus removal from wastewater by applying mechanically disintegrated excess sludge.

    PubMed

    Zubrowska-Sudol, Monika; Walczak, Justyna

    2015-06-01

    The goal of the study was to evaluate the possibility of applying disintegrated excess sludge as a source of organic carbon to enhance biological nitrogen and phosphorus removal. The experiment, performed in a sequencing batch reactor, consisted of two two-month series, without and with applying mechanically disintegrated excess sludge, respectively. The effects on carbon, nitrogen and phosphorus removal were observed. It was shown that the method allows enhancement of combined nitrogen and phosphorus removal. After using disintegrated sludge, denitrification effectiveness increased from 49.2 ± 6.8% to 76.2 ± 2.3%, which resulted in a decline in the NOx-N concentration in the effluent from the SBR by an average of 21.4 mg NOx-N/L. Effectiveness of biological phosphorus removal increased from 28.1 ± 11.3% to 96.2 ± 2.5%, thus resulting in a drop in the [Formula: see text] concentration in the effluent by, on average, 6.05 mg PO4(3-)-P/L. The application of disintegrated sludge did not deteriorate effluent quality in terms of COD and NH4(+)-N. The concentration of NH4(+)-N in both series averaged 0.16 ± 0.11 mg NH4(+)-N/L, and the concentration of COD was 15.36 ± 3.54 mg O2/L.

  20. The neural dynamic mechanisms of asymmetric switch costs in a combined Stroop-task-switching paradigm

    PubMed Central

    Wu, Shanshan; Hitchman, Glenn; Tan, Jinfeng; Zhao, Yuanfang; Tang, Dandan; Wang, Lijun; Chen, Antao

    2015-01-01

    Switch costs have been constantly found asymmetrical when switching between two tasks of unequal dominance. We used a combined Stroop-task-switching paradigm and recorded electroencephalographic (EEG) signals to explore the neural mechanism underlying the phenomenon of asymmetrical switch costs. The results revealed that a fronto-central N2 component demonstrated greater negativity in word switch (cW) trials relative to word repeat (wW) trials, and both First P3 and P3b components over the parieto-central region exhibited greater positivity in color switch (wC) trials relative to color repeat (cC) trials, whereas a contrasting switch-related fronto-central SP effect was found to have an opposite pattern for each task. Moreover, the time-frequency analysis showed a right-frontal lower alpha band (9-11 Hz) modulation in the word task, whereas a fronto-central upper alpha band (11-13 Hz) modulation was exclusively found in the color task. These results provide evidence for dissociable neural processes, which are related to inhibitory control and endogenous control, contributing to the generation of asymmetrical switch costs. PMID:25989933

  1. Mechanism-based corrector combination restores ΔF508-CFTR folding and function

    PubMed Central

    Okiyoneda, Tsukasa; Veit, Guido; Dekkers, Johanna F.; Bagdany, Miklos; Soya, Naoto; Xu, Haijin; Roldan, Ariel; Verkman, Alan S.; Kurth, Mark; Simon, Agnes; Hegedus, Tamas; Beekman, Jeffrey M.; Lukacs, Gergely L.

    2013-01-01

    The most common cystic fibrosis (CF) mutation, ΔF508 in the nucleotide binding domain-1 (NBD1), impairs CFTR coupled-domain folding, plasma membrane (PM) expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and incompletely understood mechanism, hampering drug development. Based on the effect of second site suppressor mutations, robust ΔF508-CFTR correction likely requires stabilization of NBD1 and the membrane spanning domains (MSDs)-NBD1 interface, both established primary conformational defects. Here, we elucidated the molecular targets of available correctors; class-I stabilizes the NBD1-MSD1/2 interface, class-II targets NBD2, and only chemical chaperones, surrogates of class-III correctors, stabilize the human ΔF508-NBD1. While VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional PM expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in CF bronchial epithelial cells and intestinal organoids. Thus, structure-guided corrector combination represents an effective approach for CF therapy. PMID:23666117

  2. Interspecies diversity of erythrocyte mechanical stability at various combinations in magnitude and duration of shear stress, and osmolality.

    PubMed

    Nemeth, Norbert; Sogor, Viktoria; Kiss, Ferenc; Ulker, Pinar

    2016-10-05

    We hypothesized that the results of red blood cell mechanical stability test show interspecies differences. The comparative investigations were performed on blood samples obtained from rats, beagle dogs, pigs and healthy volunteers. Mechanical stress was applied in nine combinations: 30, 60 or 100 Pa shear stress for 100, 200 or 300 seconds. Generally, rat erythrocytes showed the highest capability of resistance. With the applied combinations of mechanical stress pig erythrocytes were the most sensitive. On human erythrocytes 60 Pa for 200 s was the minimum combination to result significant deformability deterioration. By increasing the magnitude and duration of the applied mechanical stress we experienced escalating deformability impairment in all species. 100 Pa shear stress for 300 seconds on human erythrocytes showed the largest deformability impairment. The mechanical stability test results were also dependent on osmolality. At hypoosmolar range (200 mOsmol/kg) the mechanical stress improved EI data mostly in rat and porcine blood. At higher osmolality (500 mOsmol/kg), the test did not show detectable difference, while in 250-300 mOsmol/kg range the differences were well observable. In summary, erythrocytes' capability of resistance against mechanical stress shows interspecies differences depending on the magnitude and duration of the applied stress, and on the osmolality.

  3. Transverse crack initiation under combined thermal and mechanical loading of Fibre Metal Laminates and Glass Fibre Reinforced Polymers

    NASA Astrophysics Data System (ADS)

    van de Camp, W.; Dhallé, M. M. J.; Warnet, L.; Wessel, W. A. J.; Vos, G. S.; Akkerman, R.; ter Brake, H. J. M.

    2017-02-01

    The paper describes a temperature-dependent extension of the classical laminate theory (CLT) that may be used to predict the mechanical behaviour of Fibre Metal Laminates (FML) at cryogenic conditions, including crack initiation. FML are considered as a possible alternative class of structural materials for the transport and storage of liquified gasses such as LNG. Combining different constituents in a laminate opens up the possibility to enhance its functionality, e.g. offering lower specific weight and increased damage tolerance. To explore this possibility, a test programme is underway at the University of Twente to study transverse crack initiation in different material combinations under combined thermal and mechanical loading. Specifically, the samples are tested in a three-point bending experiment at temperatures ranging from 77 to 293 K. These tests will serve as a validation of the model presented in this paper which, by incorporating temperature-dependent mechanical properties and differential thermal expansion, will allow to select optimal material combinations and laminate layouts. By combining the temperature-dependent mechanical properties and the differential thermal contraction explicitly, the model allows for a more accurate estimate of the resulting thermal stresses which can then be compared to the strength of the constituent materials.

  4. Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods.

    PubMed

    Li, Jilai; Farrokhnia, Maryam; Rulíšek, Lubomír; Ryde, Ulf

    2015-07-02

    We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular, the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerization reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site.

  5. Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study

    PubMed Central

    Chen, Wei-Chih; Chen, Hung-Hsing; Chiang, Chi-Huei; Lee, Yu-Chin; Yang, Kuang-Yao

    2016-01-01

    Background The combined therapy of inhaled corticosteroids and long-acting beta-2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange. Materials and methods Ten mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 μg/fluticasone 125 μg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed. Results Salmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration. Conclusion The combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP. PMID:26869782

  6. Effects and mechanisms of the combined pollution of lanthanum and acid rain on the root phenotype of soybean seedlings.

    PubMed

    Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

    2013-09-01

    Rare earth pollution and acid rain pollution are both important environmental issues worldwide. In regions which simultaneously occur, the combined pollution of rare earth and acid rain becomes a new environmental issue, and the relevant research is rarely reported. Accordingly, we investigated the combined effects and mechanisms of lanthanum ion (La(3+)) and acid rain on the root phenotype of soybean seedlings. The combined pollution of low-concentration La(3+) and acid rain exerted deleterious effects on the phenotype and growth of roots, which were aggravated by the combined pollution of high-concentration La(3+) and acid rain. The deleterious effects of the combined pollution were stronger than those of single La(3+) or acid rain pollution. These stronger deleterious effects on the root phenotype and growth of roots were due to the increased disturbance of absorption and utilization of mineral nutrients in roots.

  7. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    PubMed

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

  8. Thrombosis of a Superior Mesenteric Vein Aneurysm: Transarterial Thrombolysis and Transhepatic Aspiration Thrombectomy

    SciTech Connect

    Hechelhammer, L.; Crook, D.W.; Widmer, U.; Wildermuth, S.; Pfammatter, T.

    2004-09-15

    We report the case of a 31-year-old woman presenting with abdominal pain due to acute thrombosis of a superior and inferior mesenteric vein aneurysm, which was treated by a combination of arterial thrombolysis and transhepatic thrombus aspiration. At the last follow-up CT, 21 months following this procedure, there was no evidence of rethrombosis, and the patient continues to do well under oral anticoagulation. The literature regarding these uncommon mesenteric vein aneurysms without portal vein involvement, as well as their treatment options, is reviewed.

  9. [Synergistic mechanism of steam explosion combined with laccase treatment for straw delignification].

    PubMed

    Li, Guanhua; Chen, Hongzhang

    2014-06-01

    Components separation is the key technology in biorefinery. Combination of steam explosion and laccase was used, and synergistic effect of the combined pretreatment was evaluated in terms of physical structure, chemical components and extraction of lignin. The results showed that steam explosion can destroy the rigid structure and increase the specific surface area of straw, which facilitated the laccase pretreatment. The laccase pretreatment can modify the lignin structure based on the Fourier transform infrared test, as a result the delignification of straw was enhanced. Nuclei Growth model with a time dependent rate constant can describe the delignification, and the kinetics parameters indicated that the combined pretreatment improved the reaction sites and made the delignification reaction more sensitive to temperature. The combined pretreatment enhanced delignification, and can be a promising technology as an alternative to the existing pretreatment.

  10. SGLT2 inhibitor/DPP-4 inhibitor combination therapy - complementary mechanisms of action for management of type 2 diabetes mellitus.

    PubMed

    Dey, Jayant

    2017-04-03

    Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence. Two classes of glucose-lowering agents that meet these criteria are the sodium glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. This article reviews the rationale for combination therapy with these agents, and evidence from clinical trials with empagliflozin and linagliptin or dapagliflozin and saxagliptin in the management of type 2 diabetes mellitus. Both combinations have been approved as single-pill formulations.

  11. Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

    PubMed Central

    Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

    2001-01-01

    AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

  12. Single or in combination antimicrobial resistance mechanisms of Klebsiella pneumoniae contribute to varied susceptibility to different carbapenems.

    PubMed

    Tsai, Yu-Kuo; Liou, Ci-Hong; Fung, Chang-Phone; Lin, Jung-Chung; Siu, L Kristopher

    2013-01-01

    Resistance to carbapenems has been documented by the production of carbapenemase or the loss of porins combined with extended-spectrum β-lactamases or AmpC β-lactamases. However, no complete comparisons have been made regarding the contributions of each resistance mechanism towards carbapenem resistance. In this study, we genetically engineered mutants of Klebsiella pneumoniae with individual and combined resistance mechanisms, and then compared each resistance mechanism in response to ertapenem, imipenem, meropenem, doripenem and other antibiotics. Among the four studied carbapenems, ertapenem was the least active against the loss of porins, cephalosporinases and carbapenemases. In addition to the production of KPC-2 or NDM-1 alone, resistance to all four carbapenems could also be conferred by the loss of two major porins, OmpK35 and OmpK36, combined with CTX-M-15 or DHA-1 with its regulator AmpR. Because the loss of OmpK35/36 alone or the loss of a single porin combined with bla CTX-M-15 or bla DHA-1-ampR expression was only sufficient for ertapenem resistance, our results suggest that carbapenems other than ertapenem should still be effective against these strains and laboratory testing for non-susceptibility to other carbapenems should improve the accurate identification of these isolates.

  13. Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

    PubMed Central

    Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

    2015-01-01

    In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

  14. Transcriptome Analysis of Sunflower Genotypes with Contrasting Oxidative Stress Tolerance Reveals Individual- and Combined- Biotic and Abiotic Stress Tolerance Mechanisms

    PubMed Central

    Ramu, Vemanna S.; Paramanantham, Anjugam; Ramegowda, Venkategowda; Mohan-Raju, Basavaiah; Udayakumar, Makarla

    2016-01-01

    In nature plants are often simultaneously challenged by different biotic and abiotic stresses. Although the mechanisms underlying plant responses against single stress have been studied considerably, plant tolerance mechanisms under combined stress is not understood. Also, the mechanism used to combat independently and sequentially occurring many number of biotic and abiotic stresses has also not systematically studied. From this context, in this study, we attempted to explore the shared response of sunflower plants to many independent stresses by using meta-analysis of publically available transcriptome data and transcript profiling by quantitative PCR. Further, we have also analyzed the possible role of the genes so identified in contributing to combined stress tolerance. Meta-analysis of transcriptomic data from many abiotic and biotic stresses indicated the common representation of oxidative stress responsive genes. Further, menadione-mediated oxidative stress in sunflower seedlings showed similar pattern of changes in the oxidative stress related genes. Based on this a large scale screening of 55 sunflower genotypes was performed under menadione stress and those contrasting in oxidative stress tolerance were identified. Further to confirm the role of genes identified in individual and combined stress tolerance the contrasting genotypes were individually and simultaneously challenged with few abiotic and biotic stresses. The tolerant hybrid showed reduced levels of stress damage both under combined stress and few independent stresses. Transcript profiling of the genes identified from meta-analysis in the tolerant hybrid also indicated that the selected genes were up-regulated under individual and combined stresses. Our results indicate that menadione-based screening can identify genotypes not only tolerant to multiple number of individual biotic and abiotic stresses, but also the combined stresses. PMID:27314499

  15. Combination Regimens of Radiation Therapy and Therapeutic Cancer Vaccines: Mechanisms and Opportunities

    PubMed Central

    Garnett-Benson, Charlie; Hodge, James W.; Gameiro, Sofia R.

    2014-01-01

    Radiation therapy is widely used with curative or palliative intent in the clinical management of multiple cancers. Although mainly aimed at direct tumor cell killing, mounting evidence suggests that radiation can alter the tumor to become an immunostimulatory milieu. Data suggest that the immunogenic effects of radiation can be exploited to promote synergistic antitumor effects in combination with immunotherapeutic agents. Here we review concepts associated with the immunogenic consequences of radiation therapy, and highlight how preclinical findings are translating into clinical benefit for patients receiving combination regimens of radiation therapy and therapeutic cancer vaccines. PMID:25481266

  16. A combined methodology of multiplet and composite focal mechanism techniques for identifying seismologically active zones in Syria

    NASA Astrophysics Data System (ADS)

    Abdul-Wahed, Mohamad; Asfahani, Jamal; Al-Tahhan, Ibrahim

    2011-10-01

    This contribution is an attempt to enlarge the current knowledge about the focal mechanisms as well as the seismotectonic settings in Syria. The seismologically active zones have been identified by applying an appropriate methodology to the events recorded during the period 1995-2003 by the Syrian National Seismological Network (SNSN). The recorded events in Syria were classified as weak during the research period. It was extremely important to propose and apply an appropriate methodology to identify the focal mechanisms generating this seismic activity. The proposed methodology consists of applying a combination of two techniques: the multiplet and the composite focal mechanisms. The combination of many events in one composite focal mechanism was realized by a multiplet technique using the spectral coherence of the events as a measure of similarity. The application of the proposed methodology allows a data set of composite fault plane solutions to be obtained. Most of the composite fault plane solutions had strike-slip mechanisms which are in agreement with the configuration of seismogenic belts in Syria.

  17. Combined Enzymatic and Mechanical Cell Disruption and Lipid Extraction of Green Alga Neochloris oleoabundans

    PubMed Central

    Wang, Dongqin; Li, Yanqun; Hu, Xueqiong; Su, Weimin; Zhong, Min

    2015-01-01

    Microalgal biodiesel is one of the most promising renewable fuels. The wet technique for lipids extraction has advantages over the dry method, such as energy-saving and shorter procedure. The cell disruption is a key factor in wet oil extraction to facilitate the intracellular oil release. Ultrasonication, high-pressure homogenization, enzymatic hydrolysis and the combination of enzymatic hydrolysis with high-pressure homogenization and ultrasonication were employed in this study to disrupt the cells of the microalga Neochloris oleoabundans. The cell disruption degree was investigated. The cell morphology before and after disruption was assessed with scanning and transmission electron microscopy. The energy requirements and the operation cost for wet cell disruption were also estimated. The highest disruption degree, up to 95.41%, assessed by accounting method was achieved by the combination of enzymatic hydrolysis and high-pressure homogenization. A lipid recovery of 92.6% was also obtained by the combined process. The combined process was found to be more efficient and economical compared with the individual process. PMID:25853267

  18. Control of a simulated arm using a novel combination of Cerebellar learning mechanisms

    NASA Technical Reports Server (NTRS)

    Assad, C.; Hartmann, M.; Paulin, M. G.

    2001-01-01

    We present a model of cerebellar cortex that combines two types of learning: feedforward predicitve association based on local Hebbian-type learning between granule cell ascending branch and parallel fiber inputs, and reinforcement learning with feedback error correction based on climbing fiber activity.

  19. Drink Refusal Training as Part of a Combined Behavioral Intervention: Effectiveness and Mechanisms of Change

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Donovan, Dennis M.; Hartzler, Bryan

    2012-01-01

    Objective: Many trials have demonstrated the effectiveness of cognitive behavioral interventions for alcohol dependence, yet few studies have examined why particular treatments are effective. This study was designed to evaluate whether drink refusal training was an effective component of a combined behavioral intervention (CBI) and whether change…

  20. Optical-mechanical system for on-combine segregation of wheat by grain protein concentration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grain segregation by grain protein concentration (GPC) may help growers maximize revenues in markets that offer protein premiums. Our objective was to develop an on-combine system for automatically segregating wheat (Triticum aestivum L.) by GPC during harvest. A multispectral optical sensor scans...

  1. Compositional and Mechanical Properties of Peanuts Roasted to Equivalent Colors using Different Time/Temperature Combinations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanuts in North America and Europe are primarily consumed after dry roasting. Standard industry practice is to roast peanuts to a specific surface color (Hunter L-value) for a given application; however, equivalent surface colors can be attained using different roast temperature/time combinations,...

  2. Effect of Different Time/Temperature Roast Combinations on Nutritional and Mechanical Properties of Peanuts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanuts in North America and Europe are primarily consumed after dry roasting. Standard industry practice is to roast peanuts to a specific surface color (Hunter L-value) for a given application; however, equivalent surface colors can be attained using different roast temperature/time combinations....

  3. Molecular mechanisms of the cross-impact of pathological processes in combined diabetes and cancer. Research and clinical aspects.

    PubMed

    Aleksandrovski, Ya A

    2002-12-01

    The mechanisms of interaction and cross-impact of metabolic processes in a combined diabetes and cancer condition are discussed. A hypothesis is proposed whereby the processes responsible for destruction of the organism in the case of diabetes--long-term hyperglycemia and generation of methylglyoxal--may substantially impact tumor development. The hypothesis is based on the fact that both diabetes and carcinogenesis cause dysfunction of the vital cellular signal system regulated by the protein kinase C (PKC) family. Normalization of the PKC functional activity in the case of diabetes restrains development of diabetic complications and inhibits the processes of tumor growth and metastasizing in carcinogenesis. On this basis, an attempt is made to interpret both the detrimental and beneficial effects of diabetes on cancer. The resultant effect is determined by the type of tumor and the duration and level of hyperglycemia. The mechanisms of the impact of diabetes mellitus on cancer are analyzed to develop recommendations for combined cancer therapy options.

  4. Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees.

    PubMed

    Guseman, Alex J; Miller, Kaliah; Kunkle, Grace; Dively, Galen P; Pettis, Jeffrey S; Evans, Jay D; vanEngelsdorp, Dennis; Hawthorne, David J

    2016-01-01

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species.

  5. Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees

    PubMed Central

    Guseman, Alex J.; Miller, Kaliah; Kunkle, Grace; Dively, Galen P.; Pettis, Jeffrey S.; Evans, Jay D.; vanEngelsdorp, Dennis; Hawthorne, David J.

    2016-01-01

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

  6. Simultaneous mechanical stiffness and electrical potential measurements of living vascular endothelial cells using combined atomic force and epifluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Callies, Chiara; Schön, Peter; Liashkovich, Ivan; Stock, Christian; Kusche-Vihrog, Kristina; Fels, Johannes; Sträter, Alexandra S.; Oberleithner, Hans

    2009-04-01

    The degree of mechanical stiffness of vascular endothelial cells determines the endogenous production of the vasodilating gas nitric oxide (NO). However, the underlying mechanisms are not yet understood. Experiments on vascular endothelial cells suggest that the electrical plasma membrane potential is involved in this regulatory process. To test this hypothesis we developed a technique that simultaneously measures the electrical membrane potential and stiffness of vascular endothelial cells (GM7373 cell line derived from bovine aortic endothelium) under continuous perfusion with physiological electrolyte solution. The cellular stiffness was determined by nano-indentation using an atomic force microscope (AFM) while the electrical membrane potential was measured with bis-oxonol, a voltage-reporting fluorescent dye. These two methods were combined using an AFM attached to an epifluorescence microscope. The electrical membrane potential and mechanical stiffness of the same cell were continuously recorded for a time span of 5 min. Fast fluctuations (in the range of seconds) of both the electrical membrane potential and mechanical stiffness could be observed that were not related to each other. In contrast, slow cell depolarizations (in the range of minutes) were paralleled by significant increases in mechanical stiffness. In conclusion, using the combined AFM-fluorescence technique we monitored for the first time simultaneously the electrical plasma membrane potential and mechanical stiffness in a living cell. Vascular endothelial cells exhibit oscillatory non-synchronized waves of electrical potential and mechanical stiffness. The sustained membrane depolarization, however, is paralleled by a concomitant increase of cell stiffness. The described method is applicable for any fluorophore, which opens new perspectives in biomedical research.

  7. Thrombectomy and surgical reconstruction for extensive iliocaval thrombosis in a patient with agenesis of the retrohepatic vena cava and atresia of the left renal vein.

    PubMed

    La Spada, Michele; Stilo, Francesco; Carella, Giuseppe; Salomone, Ignazio; Benedetto, Filippo; De Caridi, Giovanni; Spinelli, Francesco

    2011-08-01

    In 80% of the patients presenting with deep-venous thrombosis (DVT), a risk factor can be identified. An absent or hypoplastic infrarenal vena cava is a rare risk factor for DVT in young adults. In these cases, the prevalence of congenital anomalies of the inferior vena cava (IVC) is estimated at 0.5% of the general population, up to 5% in young people. The association with coagulopathy increases the risk of DVT. We report a case of a young man who presented with a massive caval and iliofemoral-popliteal thrombosis in presence of the agenesis of retrohepatic inferior vena cava and atresia of the left renal vein. Open thrombectomy and caval reconstruction with a polytetrafluoroethylene graft were performed. Surgical option with vein reconstruction was preferred to prevent new episodes of thrombosis and the risk of acute renal failure.

  8. AngioJet rheolytic thrombectomy for thrombotic myocardial injury in a 15-year-old cystic fibrosis patient during lung transplantation.

    PubMed

    Hayes, Don; Schell, Randall M; Plunkett, Mark D; Gurley, John C; Hoopes, Charles W

    2012-08-01

    We report on an acute myocardial injury caused by thrombotic emboli during off-pump bilateral sequential lung transplantation in a 15-year-old female patient with end-stage cystic fibrosis. A few minutes after reperfusion of the right (second sequential) allograft, the patient developed hemodynamic collapse, including hypotension, acute akinesis of the anterior and lateral myocardial walls, and severe mitral regurgitation. Thrombus was noted within the left atrium and ventricle on intraoperative transesophageal echocardiogram. After emergent cannulation for cardiopulmonary bypass, the patient underwent left cardiac catheterization with AngioJet rheolytic thrombectomy and removal of the clot from the distal left anterior descending coronary artery. Reperfusion was established without the need for stent placement or further intervention. The patient required short-term life support with venoarterial extracorporeal membrane oxygenation.

  9. Membrane degradation during combined chemical and mechanical accelerated stress testing of polymer electrolyte fuel cells

    NASA Astrophysics Data System (ADS)

    Lim, C.; Ghassemzadeh, L.; Van Hove, F.; Lauritzen, M.; Kolodziej, J.; Wang, G. G.; Holdcroft, S.; Kjeang, E.

    2014-07-01

    A cyclic open circuit voltage (COCV) accelerated stress test (AST) is designed to screen the simultaneous effect of chemical and mechanical membrane degradation in polymer electrolyte fuel cells. The AST consists of a steady state OCV phase to accelerate chemical degradation and periodic wet/dry cycles to provide mechanical degradation. The membrane degradation process induced by COCV AST operation is analyzed using a standard MEA with PFSA ionomer membrane. The OCV shows an initially mild decay rate followed by a higher decay rate in the later stages of the experiment. Membrane failure, defined by a threshold convective hydrogen leak rate, is obtained after 160 h of operation. Uniform membrane thinning is observed with pinhole formation being the primary cause of failure. Mechanical tensile tests reveal that the membrane becomes stiffer and more brittle during AST operation, which contributes to mechanical failure upon cyclic humidity induced stress. Solid state 19F NMR spectroscopy and fluoride emission measurements demonstrate fluorine loss from both side chain and main chain upon membrane exposure to high temperature and low humidity OCV condition.

  10. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

    NASA Astrophysics Data System (ADS)

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-05-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm‑3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability.

  11. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

    PubMed Central

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-01-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm−3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability. PMID:27174450

  12. Top triangle moose: Combining Higgsless and topcolor mechanisms for mass generation

    SciTech Connect

    Chivukula, R. Sekhar; Christensen, Neil D.; Coleppa, Baradhwaj; Simmons, Elizabeth H.

    2009-08-01

    We present the details of a deconstructed model that incorporates both Higgsless and top-color mechanisms. The model alleviates the tension between obtaining the correct top quark mass and keeping {delta}{rho} small that exists in many Higgsless models. It does so by singling out the top quark mass generation as arising from a Yukawa coupling to an effective top Higgs which develops a small vacuum expectation value, while electroweak symmetry breaking results largely from a Higgsless mechanism. As a result, the heavy partners of the SM fermions can be light enough to be seen at the LHC. After presenting the model, we detail the phenomenology, showing that for a broad range of masses, these heavy fermions are discoverable at the LHC.

  13. Top triangle moose: Combining Higgsless and topcolor mechanisms for mass generation

    NASA Astrophysics Data System (ADS)

    Chivukula, R. Sekhar; Christensen, Neil D.; Coleppa, Baradhwaj; Simmons, Elizabeth H.

    2009-08-01

    We present the details of a deconstructed model that incorporates both Higgsless and top-color mechanisms. The model alleviates the tension between obtaining the correct top quark mass and keeping Δρ small that exists in many Higgsless models. It does so by singling out the top quark mass generation as arising from a Yukawa coupling to an effective top Higgs which develops a small vacuum expectation value, while electroweak symmetry breaking results largely from a Higgsless mechanism. As a result, the heavy partners of the SM fermions can be light enough to be seen at the LHC. After presenting the model, we detail the phenomenology, showing that for a broad range of masses, these heavy fermions are discoverable at the LHC.

  14. The calculation of the thermal rate coefficient by a method combining classical and quantum mechanics

    NASA Astrophysics Data System (ADS)

    Wahnström, Göran; Carmeli, Benny; Metiu, Horia

    1988-02-01

    We propose and test a method for computing flux-flux correlation functions (and thermal rate coefficients) which divides the degrees of freedom in two groups, one treated classically and the other quantum mechanically. The method is tested by applying it to a simple model for which we can also obtain exact results. The approximate method gives good results if the mass associated with the classical degrees of freedom exceeds 16 a.u.

  15. Photochromic Mechanism of a Bridged Diarylethene: Combined Electronic Structure Calculations and Nonadiabatic Dynamics Simulations.

    PubMed

    Wang, Ya-Ting; Gao, Yuan-Jun; Wang, Qian; Cui, Ganglong

    2017-02-02

    Intramolecularly bridged diarylethenes exhibit improved photocyclization quantum yields because the anti-syn isomerization that originally suppresses photocyclization in classical diarylethenes is blocked. Experimentally, three possible channels have been proposed to interpret experimental observation, but many details of photochromic mechanism remain ambiguous. In this work we have employed a series of electronic structure methods (OM2/MRCI, DFT, TDDFT, RI-CC2, DFT/MRCI, and CASPT2) to comprehensively study excited state properties, photocyclization, and photoreversion dynamics of 1,2-dicyano[2,2]metacyclophan-1-ene. On the basis of optimized stationary points and minimum-energy conical intersections, we have refined experimentally proposed photochromic mechanism. Only an S1/S0 minimum-energy conical intersection is located; thus, we can exclude the third channel experimentally proposed. In addition, we find that both photocyclization and photoreversion processes use the same S1/S0 conical intersection to decay the S1 system to the S0 state, so we can unify the remaining two channels into one. These new insights are verified by our OM2/MRCI nonadiabatic dynamics simulations. The S1 excited-state lifetimes of photocyclization and photoreversion are estimated to be 349 and 453 fs, respectively, which are close to experimentally measured values: 240 ± 60 and 250 fs in acetonitrile solution. The present study not only interprets experimental observations and refines previously proposed mechanism but also provides new physical insights that are valuable for future experiments.

  16. Combined quantum mechanics (TDDFT) and classical electrodynamics (Mie theory) methods for calculating surface enhanced Raman and hyper-Raman spectra.

    PubMed

    Mullin, Jonathan; Valley, Nicholas; Blaber, Martin G; Schatz, George C

    2012-09-27

    Multiscale models that combine quantum mechanics and classical electrodynamics are presented, which allow for the evaluation of surface-enhanced Raman (SERS) and hyper-Raman scattering spectra (SEHRS) for both chemical (CHEM) and electrodynamic (EM) enhancement mechanisms. In these models, time-dependent density functional theory (TDDFT) for a system consisting of the adsorbed molecule and a metal cluster fragment of the metal particle is coupled to Mie theory for the metal particle, with the surface of the cluster being overlaid with the surface of the metal particle. In model A, the electromagnetic enhancement from plasmon-excitation of the metal particle is combined with the chemical enhancement associated with a static treatment of the molecule-metal structure to determine overall spectra. In model B, the frequency dependence of the Raman spectrum of the isolated molecule is combined with the enhancements determined in model A to refine the enhancement estimate. An equivalent theory at the level of model A is developed for hyper-Raman spectra calculations. Application to pyridine interacting with a 20 nm diameter silver sphere is presented, including comparisons with an earlier model (denoted G), which combines plasmon enhanced fields with gas-phase Raman (or hyper-Raman) spectra. The EM enhancement factor for spherical particles at 357 nm is found to be 10(4) and 10(6) for SERS and SEHRS, respectively. Including both chemical and electromagnetic mechanisms at the level of model A leads to enhancements on the order of 10(4) and 10(9) for SERS and SEHRS.

  17. A combined experimental-numerical approach for determining mechanical properties of aluminum subjects to nanoindentation

    PubMed Central

    Liu, Mao; Lu, Cheng; Tieu, Kiet Anh; Peng, Ching-Tun; Kong, Charlie

    2015-01-01

    A crystal plasticity finite element method (CPFEM) model has been developed to investigate the mechanical properties and micro-texture evolution of single-crystal aluminum induced by a sharp Berkovich indenter. The load-displacement curves, pile-up patterns and lattice rotation angles from simulation are consistent with the experimental results. The pile-up phenomenon and lattice rotation have been discussed based on the theory of crystal plasticity. In addition, a polycrystal tensile CPFEM model has been established to explore the relationship between indentation hardness and yield stress. The elastic constraint factor C is slightly larger than conventional value 3 due to the strain hardening. PMID:26464128

  18. The combined influence of chemical, metallurgical and mechanical factors on environment assisted cracking

    NASA Technical Reports Server (NTRS)

    Williams, D. P., III; Pao, P. S.; Wei, R. P.

    1979-01-01

    The principal aim of the paper is to re-emphasize and focus on both the multidisciplinary nature of the environment assisted cracking or embrittlement phenomenon. The multiplicity of factors involved in the embrittlement process is indicated, the mutual dependence of these factors and the influences of mechanical and environmental conditions are considered, and the interactions of various factors in determining the overall embrittlement response are discussed. The need for an interdisciplinary approach for resolving the major differences and for understanding embrittlement is outlined.

  19. A combined experimental-numerical approach for determining mechanical properties of aluminum subjects to nanoindentation.

    PubMed

    Liu, Mao; Lu, Cheng; Tieu, Kiet Anh; Peng, Ching-Tun; Kong, Charlie

    2015-10-14

    A crystal plasticity finite element method (CPFEM) model has been developed to investigate the mechanical properties and micro-texture evolution of single-crystal aluminum induced by a sharp Berkovich indenter. The load-displacement curves, pile-up patterns and lattice rotation angles from simulation are consistent with the experimental results. The pile-up phenomenon and lattice rotation have been discussed based on the theory of crystal plasticity. In addition, a polycrystal tensile CPFEM model has been established to explore the relationship between indentation hardness and yield stress. The elastic constraint factor C is slightly larger than conventional value 3 due to the strain hardening.

  20. Deprotonation mechanism of new antihypertensive piperidinylmethylphenols: a combined experimental and theoretical study.

    PubMed

    Islas-Martínez, José Manuel; Rodríguez-Barrientos, Damaris; Galano, Annia; Angeles, Enrique; Torres, Luis A; Olvera, Fabiola; Ramírez-Silva, María Teresa; Rojas-Hernández, Alberto

    2009-08-27

    Four new antihypertensive piperidinylmethylphenol compounds were synthesized for their potential antihypertensive and antiarhythmic properties. The pKa values were determined experimentally, with the aid of the program SQUAD, by capillary zone electrophoresis (CZE) at T=298.15 K and 0.015 M ionic strength (I=0.05 M) and by UV spectrophotometry at pseudophysiological conditions (T=310.15 K and I=0.15 M), obtaining good agreement between the values determined with both techniques. A theoretical study was followed in order to propose a deprotonation mechanism for each compound.

  1. Rapid diffusion of magic-size islands by combined glide and vacancy mechanisms

    SciTech Connect

    Perez, D; Voter, A F; Uche, O U; Hamilton, J C

    2009-01-01

    Using molecular dynamics, nudged elastic band, and embedded atom methods, we show that certain 2D Ag islands undergo extremely rapid one-dimensional diffusion on Cu(001) surfaces. Indeed, below 300K, hopping rates for 'magic-size' islands are orders of magnitude faster than hopping rates for single Ag adatoms. This rapid diffusion requires both the c(10 x 2) hexagonally-packed superstructure typical of Ag on Cu(001) and appropriate 'magic-sizes' for the islands. The novel highly-cooperative diffusion mechanism presented here couples vacancy diffusion with simultaneous core glide.

  2. Insights into the mechanism of membrane pyrophosphatases by combining experiment and computer simulation

    PubMed Central

    Shah, Nita R.; Wilkinson, Craig; Harborne, Steven P. D.; Turku, Ainoleena; Li, Kun-Mou; Sun, Yuh-Ju; Harris, Sarah; Goldman, Adrian

    2017-01-01

    Membrane-integral pyrophosphatases (mPPases) couple the hydrolysis of pyrophosphate (PPi) to the pumping of Na+, H+, or both these ions across a membrane. Recently solved structures of the Na+-pumping Thermotoga maritima mPPase (TmPPase) and H+-pumping Vigna radiata mPPase revealed the basis of ion selectivity between these enzymes and provided evidence for the mechanisms of substrate hydrolysis and ion-pumping. Our atomistic molecular dynamics (MD) simulations of TmPPase demonstrate that loop 5–6 is mobile in the absence of the substrate or substrate-analogue bound to the active site, explaining the lack of electron density for this loop in resting state structures. Furthermore, creating an apo model of TmPPase by removing ligands from the TmPPase:IDP:Na structure in MD simulations resulted in increased dynamics in loop 5–6, which results in this loop moving to uncover the active site, suggesting that interactions between loop 5–6 and the imidodiphosphate and its associated Mg2+ are important for holding a loop-closed conformation. We also provide further evidence for the transport-before-hydrolysis mechanism by showing that the non-hydrolyzable substrate analogue, methylene diphosphonate, induces low levels of proton pumping by VrPPase. PMID:28345008

  3. Histopathology combined with transcriptome analyses reveals the mechanism of resistance to Meloidogyne incognita in Cucumis metuliferus.

    PubMed

    Ye, De-You; Qi, Yong-Hong; Cao, Su-Fang; Wei, Bing-Qiang; Zhang, Hua-Sheng

    2017-02-20

    Root-knot nematodes (Meloidogyne spp.) cause serious threat to cucumber production. Cucumis metuliferus, a relative of cucumber, is reported to be resistant to Meloidogyne incognita, yet the underlying resistance mechanism remains unclear. In this study, the response of resistant C. metuliferus accession PI482443 following nematode infection was studied in comparison with susceptible C. sativus cv. Jinlv No.3. Roots of selected Cucumis seedings were analysed using histological and biochemical techniques. Transcriptome changes of the resistance reaction were investigated by RNA-seq. The results showed that penetration and development of the nematode in resistant plants were reduced when compared to susceptible plants. Infection of a resistant genotype with M. incognita resulted in a hypersensitive reaction. The induction of phenylalanine ammonia lyase and peroxidase activities after infection was greater in resistant than susceptible roots. Several of the most relevant genes for phenylpropanoid biosynthesis, plant hormone signal transduction, and the plant-pathogen interaction pathway that are involved in resistance to the nematode were significantly altered. The resistance in C. metuliferus PI482443 to M. incognita was associated with reduced nematode penetration, retardation of nematode development, and hypersensitive necrosis. The expression of genes resulting in the deposition of lignin, toxic compounds synthesis, cell wall reinforcement, suppression of nematode feeding and resistance protein accumulation, and activation of several transcription factors might all contribute to the resistance response to the pest. These results may lead to a better understanding of the resistance mechanism and aid in the identification of potential targets resistant to pests for cucumber improvement.

  4. Fast Simulation of Membrane Filtration by Combining Particle Retention Mechanisms and Network Models

    NASA Astrophysics Data System (ADS)

    Krupp, Armin; Griffiths, Ian; Please, Colin

    2016-11-01

    Porous membranes are used for their particle retention capabilities in a wide range of industrial filtration processes. The underlying mechanisms for particle retention are complex and often change during the filtration process, making it hard to predict the change in permeability of the membrane during the process. Recently, stochastic network models have been shown to predict the change in permeability based on retention mechanisms, but remain computationally intensive. We show that the averaged behaviour of such a stochastic network model can efficiently be computed using a simple partial differential equation. Moreover, we also show that the geometric structure of the underlying membrane and particle-size distribution can be represented in our model, making it suitable for modelling particle retention in interconnected membranes as well. We conclude by demonstrating the particular application to microfluidic filtration, where the model can be used to efficiently compute a probability density for flux measurements based on the geometry of the pores and particles. A. U. K. is grateful for funding from Pall Corporation and the Mathematical Institute, University of Oxford. I.M.G. gratefully acknowledges support from the Royal Society through a University Research Fellowship.

  5. Mechanisms mediating the synergistic anticancer effects of combined γ-tocotrienol and sesamin treatment.

    PubMed

    Akl, Mohamed R; Ayoub, Nehad M; Sylvester, Paul W

    2012-11-01

    Epidemiological studies have highlighted the ability of phytochemicals to reduce the risk of breast cancer by attenuating specific intracellular signaling pathways that regulate cell proliferation and survival. γ-Tocotrienol is a natural form of vitamin E that displays potent anticancer activity at doses that have no discernible toxicity toward normal cells. Sesamin is an abundant phytochemical found in sesame seed oil that also shows antiproliferative and antiangiogenic activity against human breast cancer cells. In this study, the combined treatment of subeffective doses of γ-tocotrienol and sesamin caused a synergistic inhibition of murine +SA mammary epithelial cell growth, as determined by the MTT assay and immunofluorescent Ki-67 staining. Western blot studies revealed that combined low-dose treatment of γ-tocotrienol and sesamin caused a marked reduction in EGF-induced ErbB3 and ErbB4 receptors phosphorylation (activation) and a relatively large decrease in intracellular levels of total and/or phosphorylated c-Raf, MEK1/2, ERK1/2, PI3K, PDK1, Akt, p-NFκB, Jak1, Jak2, and Stat1, as compared to cells treated with only one compound or in the vehicle-treated control group. These findings demonstrate that the synergistic growth inhibitory effects of γ-tocotrienol and sesamin treatment are associated with suppression of EGF-dependent mitogenic signaling in mammary tumor cells and suggest that dietary supplementation with these phytochemicals may provide some benefits in the prevention and/or treatment of breast cancer.

  6. Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism

    PubMed Central

    Zhang, Weiying; Kang, Min; Zhang, Tingting; Li, Bo; Liao, Xueyin; Wang, Rensheng

    2016-01-01

    Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC. PMID:27999372

  7. Designing power system simulators for the smart grid: combining controls, communications, and electro-mechanical dynamics

    SciTech Connect

    Nutaro, James J

    2011-01-01

    Open source software has a leading role in research on simulation technology for electrical power systems. Research simulators demonstrate new features for which there is nascent but growing demand not yet provided for by commercial simulators. Of particular interest is the inclusion of models of software-intensive and communication-intensive controls in simulations of power system transients. This paper describes two features of the ORNL power system simulator that help it meet this need. First is its use of discrete event simulation for all aspects of the model: control, communication, and electro-mechanical dynamics. Second is an interoperability interface that enables the ORNL power system simulator to be integrated with existing, discrete event simulators of digital communication systems. The paper concludes with a brief discussion of how these aspects of the ORNL power system simulator might be inserted into production-grade simulation tools.

  8. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    PubMed

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  9. Combining 3D printed forms with textile structures - mechanical and geometrical properties of multi-material systems

    NASA Astrophysics Data System (ADS)

    Sabantina, L.; Kinzel, F.; Ehrmann, A.; Finsterbusch, K.

    2015-07-01

    The 3D printing belongs to the rapidly emerging technologies which have the chance to revolutionize the way products are created. In the textile industry, several designers have already presented creations of shoes, dresses or other garments which could not be produced with common techniques. 3D printing, however, is still far away from being a usual process in textile and clothing production. The main challenge results from the insufficient mechanical properties, especially the low tensile strength, of pure 3D printed products, prohibiting them from replacing common technologies such as weaving or knitting. Thus, one way to the application of 3D printed forms in garments is combining them with textile fabrics, the latter ensuring the necessary tensile strength. This article reports about different approaches to combine 3D printed polymers with different textile materials and fabrics, showing chances and limits of this technique.

  10. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality

    PubMed Central

    2012-01-01

    Introduction Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. Methods This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). Results We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). Conclusions β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric

  11. Bioremediation mechanisms of combined pollution of PAHs and heavy metals by bacteria and fungi: A mini review.

    PubMed

    Liu, Shao-Heng; Zeng, Guang-Ming; Niu, Qiu-Ya; Liu, Yang; Zhou, Lu; Jiang, Lu-Hua; Tan, Xiao-Fei; Xu, Piao; Zhang, Chen; Cheng, Min

    2017-01-01

    In recent years, knowledge in regard to bioremediation of combined pollution of polycyclic aromatic hydrocarbons (PAHs) and heavy metals by bacteria and fungi has been widely developed. This paper reviews the species of bacteria and fungi which can tackle with various types of PAHs and heavy metals entering into environment simultaneously or successively. Microbial activity, pollutants bioavailability and environmental factors (e.g. pH, temperature, low molecular weight organic acids and humic acids) can all affect the bioremediation of PAHs and heavy metals. Moreover, this paper summarizes the remediation mechanisms of PAHs and heavy metals by microbes via elucidating the interaction mechanisms of heavy metals with heavy metals, PAHs/PAHs metabolites with PAHs and PAHs with heavy metals. Based on the above reviews, this paper also discusses the potential research needs for this field.

  12. PARAMETRIC STUDY OF TISSUE OPTICAL CLEARING BY LOCALIZED MECHANICAL COMPRESSION USING COMBINED FINITE ELEMENT AND MONTE CARLO SIMULATION.

    PubMed

    Vogt, William C; Shen, Haiou; Wang, Ge; Rylander, Christopher G

    2010-07-01

    Tissue Optical Clearing Devices (TOCDs) have been shown to increase light transmission through mechanically compressed regions of naturally turbid biological tissues. We hypothesize that zones of high compressive strain induced by TOCD pins produce localized water displacement and reversible changes in tissue optical properties. In this paper, we demonstrate a novel combined mechanical finite element model and optical Monte Carlo model which simulates TOCD pin compression of an ex vivo porcine skin sample and modified spatial photon fluence distributions within the tissue. Results of this simulation qualitatively suggest that light transmission through the skin can be significantly affected by changes in compressed tissue geometry as well as concurrent changes in tissue optical properties. The development of a comprehensive multi-domain model of TOCD application to tissues such as skin could ultimately be used as a framework for optimizing future design of TOCDs.

  13. VUV treatment combined with mechanical strain of stretchable polymer foils resulting in cell alignment

    NASA Astrophysics Data System (ADS)

    Barb, R.-A.; Magnus, B.; Innerbichler, S.; Greunz, T.; Wiesbauer, M.; Marksteiner, R.; Stifter, D.; Heitz, J.

    2015-01-01

    Cell-alignment along a defined direction can have a direct effect on the cell functionality and differentiation. Oriented micro- or nanotopographic structures on cell culture substrates can induce cell-alignment. Surface chemistry, wettability, and stiffness of the substrate are also important material features as they strongly influence the cell-substrate interactions. For improved bio-compatibility, highly elastic polyurethane (PU) foils were exposed to the vacuum-UV (VUV) light of a Xe2* excimer lamp at 172 nm in a nitrogen containing atmosphere (N2 or NH3). The irradiation resulted in a change in the chemical surface composition. Additionally, the formation of regular parallel microgrooves was observed on the irradiated surfaces after strong uni-axial deformation (i.e., more than about 50% strain) of the photo-modified PU foils. Cell seeding experiments demonstrated that the VUV modified polymer foils strongly enhance cell adhesion and proliferation. Cells seeded onto microgrooves aligned their shapes and elongated in the direction of the grooves. A similar effect was observed for cells seeded on photo-modified PU foils subjected to cyclic mechanical stretching at lower strain levels (i.e., typically 10% strain) without groove-formation. The cells had also here an elongated shape, however they not always align in a defined direction relative to the stretching.

  14. Research on the Mechanical Properties of a Glass Fiber Reinforced Polymer-Steel Combined Truss Structure

    PubMed Central

    Liu, Pengfei; Zhao, Qilin; Li, Fei; Liu, Jinchun; Chen, Haosen

    2014-01-01

    An assembled plane truss structure used for vehicle loading is designed and manufactured. In the truss, the glass fiber reinforced polymer (GFRP) tube and the steel joint are connected by a new technology featuring a pretightened tooth connection. The detailed description for the rod and node design is introduced in this paper, and a typical truss panel is fabricated. Under natural conditions, the short-term load test and long-term mechanical performance test for one year are performed to analyze its performance and conduct a comparative analysis for a reasonable FEM model. The study shows that the design and fabrication for the node of an assembled truss panel are convenient, safe, and reliable; because of the creep control design of the rods, not only does the short-term structural stiffness meet the design requirement but also the long-term creep deformation tends towards stability. In addition, no significant change is found in the elastic modules, so this structure can be applied in actual engineering. Although the safety factor for the strength of the composite rods is very large, it has a lightweight advantage over the steel truss for the low density of GFRP. In the FEM model, simplifying the node as a hinge connection relatively conforms to the actual status. PMID:25247203

  15. Combining mechanical foaming and thermally induced phase separation to generate chitosan scaffolds for soft tissue engineering.

    PubMed

    Biswas, D P; Tran, P A; Tallon, C; O'Connor, A J

    2017-02-01

    In this paper, a novel foaming methodology consisting of turbulent mixing and thermally induced phase separation (TIPS) was used to generate scaffolds for tissue engineering. Air bubbles were mechanically introduced into a chitosan solution which forms the continuous polymer/liquid phase in the foam created. The air bubbles entrained in the foam act as a template for the macroporous architecture of the final scaffolds. Wet foams were crosslinked via glutaraldehyde and frozen at -20 °C to induce TIPS in order to limit film drainage, bubble coalescence and Ostwald ripening. The effects of production parameters, including mixing speed, surfactant concentration and chitosan concentration, on foaming are explored. Using this method, hydrogel scaffolds were successfully produced with up to 80% porosity, average pore sizes of 120 μm and readily tuneable compressive modulus in the range of 2.6 to 25 kPa relevant to soft tissue engineering applications. These scaffolds supported 3T3 fibroblast cell proliferation and penetration and therefore show significant potential for application in soft tissue engineering.

  16. Research on the mechanical properties of a glass fiber reinforced polymer-steel combined truss structure.

    PubMed

    Liu, Pengfei; Zhao, Qilin; Li, Fei; Liu, Jinchun; Chen, Haosen

    2014-01-01

    An assembled plane truss structure used for vehicle loading is designed and manufactured. In the truss, the glass fiber reinforced polymer (GFRP) tube and the steel joint are connected by a new technology featuring a pretightened tooth connection. The detailed description for the rod and node design is introduced in this paper, and a typical truss panel is fabricated. Under natural conditions, the short-term load test and long-term mechanical performance test for one year are performed to analyze its performance and conduct a comparative analysis for a reasonable FEM model. The study shows that the design and fabrication for the node of an assembled truss panel are convenient, safe, and reliable; because of the creep control design of the rods, not only does the short-term structural stiffness meet the design requirement but also the long-term creep deformation tends towards stability. In addition, no significant change is found in the elastic modules, so this structure can be applied in actual engineering. Although the safety factor for the strength of the composite rods is very large, it has a lightweight advantage over the steel truss for the low density of GFRP. In the FEM model, simplifying the node as a hinge connection relatively conforms to the actual status.

  17. Metabolic and target-site mechanisms combine to confer strong DDT resistance in Anopheles gambiae.

    PubMed

    Mitchell, Sara N; Rigden, Daniel J; Dowd, Andrew J; Lu, Fang; Wilding, Craig S; Weetman, David; Dadzie, Samuel; Jenkins, Adam M; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A T; Ranson, Hilary; Paine, Mark J I; Mayans, Olga; Donnelly, Martin J

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae.

  18. Evolution and use of combined mechanical and thermal codes for cryogenic turbopump bearings

    NASA Technical Reports Server (NTRS)

    Cody, Joe C.; Marty, David E.; Moore, James D.

    1988-01-01

    Shaft bearing system analysis codes were developed, improved, and used to investigate Space Shuttle Main Engine (SSME) Liquid Oxygen (LOX) turbopump bearing problems, and to support the Marshall Space Flight Center Bearing and Seal Materials Test (BSMT) program. Thermal network modeling uses the SINDA thermal code, and the modeling of bearing quasi-dynamic characteristics uses the SHABERTH bearing/shaft code. These codes are solved concurrently for a bearing/shaft system using software developed for this purpose. Simulation of the SSME LOX turbopump turbine and pump end bearings and the MSFC BSMT operating in liquid nitrogen (LN sub 2) and LOX was done. The thermal network models include the bearing components, bearing carriers, shaft, housing, frictional heat, and viscous fluid energy. A cage model was included to account for heat generation between the cage and rolling elements. Since most bearing surfaces operate at temperatures well above the coolant saturation temperature, and move at high speed relative to the coolant, forced convection boiling is the dominant mechanism for heat removal. Improved modeling of forced convection film boiling was incorporated to take into account the local vapor generation at the high temperature surfaces. Rearing preloads in the pump and tester are provided by preload springs. As bearing operating clearances and contact angles change due to thermal effects and loading, the bearing preload changes with these varying conditions. These characteristics were modeled and are included in the overall system models. Results from these models indicate an operational limit which, if exceeded, predicts a thermal excursion.

  19. Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference

    PubMed Central

    Sora, Ichiro; Hall, F. Scott; Andrews, Anne M.; Itokawa, Masanari; Li, Xiao-Fei; Wei, Hong-Bing; Wichems, Christine; Lesch, Klaus-Peter; Murphy, Dennis L.; Uhl, George R.

    2001-01-01

    Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development. PMID:11320258

  20. Fabrication of circular microfluidic channels by combining mechanical micromilling and soft lithography.

    PubMed

    Wilson, Mary E; Kota, Nithyanand; Kim, YongTae; Wang, Yadong; Stolz, Donna B; LeDuc, Philip R; Ozdoganlar, O Burak

    2011-04-21

    The fabrication of microfluidic channels with complex three-dimensional (3D) geometries presents a major challenge to the field of microfluidics, because conventional lithography methods are mainly limited to rectangular cross-sections. In this paper, we demonstrate the use of mechanical micromachining to fabricate microfluidic channels with complex cross-sectional geometries. Micro-scale milling tools are first used to fabricate semi-circular patterns on planar metallic surfaces to create a master mold. The micromilled pattern is then transferred to polydimethylsiloxane (PDMS) through a two-step reverse molding process. Using these semi-circular PDMS channels, circular cross-sectioned microchannels are created by aligning and adhering two channels face-to-face. Straight and serpentine-shaped microchannels were fabricated, and the channel geometry and precision of the metallic master and PDMS molds were assessed through scanning electron microscopy and non-contact profilometry. Channel functionality was tested by perfusion of liquid through the channels. This work demonstrates that micromachining enabled soft lithography is capable of fabricating non-rectangular cross-section channels for microfluidic applications. We believe that this approach will be important for many fields from biomimetics and vascular engineering to microfabrication and microreactor technologies.

  1. Combining Laser Microsurgery and Finite Element Modeling to Assess Cell-Level Epithelial Mechanics

    PubMed Central

    Hutson, M. Shane; Veldhuis, J.; Ma, Xiaoyan; Lynch, Holley E.; Cranston, P. Graham; Brodland, G. Wayne

    2009-01-01

    Abstract Laser microsurgery and finite element modeling are used to determine the cell-level mechanics of the amnioserosa—a morphogenetically crucial epithelium on the dorsal surface of fruit fly embryos (Drosophila melanogaster). In the experiments, a tightly focused laser ablates a subcellular hole (1 μm in diameter) that passes clean through the epithelium. The surrounding cells recoil from the wound site with a large range of initial recoil velocities. These depend on the embryo's developmental stage and the subcellular wound site. The initial recoil (up to 0.1 s) is well reproduced by a base finite element model, which assumes a uniform effective viscosity inside the cells, a constant tension along each cell-cell boundary, and a large, potentially anisotropic, far-field stress—one that far exceeds the stress equivalent of the cell-edge tensions. After 0.1 s, the experimental recoils slow dramatically. This observation can be reproduced by adding viscoelastic rods along cell edges or as a fine prestressed mesh parallel to the apical and basal membranes of the cell. The mesh also reproduces a number of double-wounding experiments in which successive holes are drilled in a single cell. PMID:20006944

  2. Compositional and mechanical properties of peanuts roasted to equivalent colors using different time/temperature combinations.

    PubMed

    McDaniel, Kristin A; White, Brittany L; Dean, Lisa L; Sanders, Timothy H; Davis, Jack P

    2012-12-01

    Peanuts in North America and Europe are primarily consumed after dry roasting. Standard industry practice is to roast peanuts to a specific surface color (Hunter L-value) for a given application; however, equivalent surface colors can be attained using different roast temperature/time combinations, which could affect product quality. To investigate this potential, runner peanuts from a single lot were systematically roasted using 5 roast temperatures (147, 157, 167, 177, and 187 °C) and to Hunter L-values of 53 ± 1, 48.5 ± 1, and 43 ± 1, corresponding to light, medium, and dark roasts, respectively. Moisture contents (MC) ranged from 0.41% to 1.70% after roasting. At equivalent roast temperatures, MC decreased as peanuts became darker; however, for a given color, MC decreased with decreasing roast temperature due to longer roast times required for specified color formation. Initial total tocopherol contents of expressed oils ranged from 164 to 559 μg/g oil. Peanuts roasted at lower temperatures and darker colors had higher tocopherol contents. Glucose content was roast color and temperature dependent, while fructose was only temperature dependent. Soluble protein was lower at darker roast colors, and when averaged across temperatures, was highest when samples were roasted at 187 °C. Lysine content decreased with increasing roast color but was not dependent on temperature. MC strongly correlated with several components including tocopherols (R(2) = 0.67), soluble protein (R(2) = 0.80), and peak force upon compression (R(2) = 0.64). The variation in characteristics related to roast conditions is sufficient to suggest influences on final product shelf life and consumer acceptability.

  3. Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

    PubMed

    Evans, Deborah J; Owlarn, Suthira; Tejada Romero, Belen; Chen, Chen; Aboobaker, A Aziz

    2011-01-01

    The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then

  4. Additively manufactured metallic porous biomaterials based on minimal surfaces: A unique combination of topological, mechanical, and mass transport properties.

    PubMed

    Bobbert, F S L; Lietaert, K; Eftekhari, A A; Pouran, B; Ahmadi, S M; Weinans, H; Zadpoor, A A

    2017-02-16

    Porous biomaterials that simultaneously mimic the topological, mechanical, and mass transport properties of bone are in great demand but are rarely found in the literature. In this study, we rationally designed and additively manufactured (AM) porous metallic biomaterials based on four different types of triply periodic minimal surfaces (TPMS) that mimic the properties of bone to an unprecedented level of multi-physics detail. Sixteen different types of porous biomaterials were rationally designed and fabricated using selective laser melting (SLM) from a titanium alloy (Ti-6Al-4V). The topology, quasi-static mechanical properties, fatigue resistance, and permeability of the developed biomaterials were then characterized. In terms of topology, the biomaterials resembled the morphological properties of trabecular bone including mean surface curvatures close to zero. The biomaterials showed a favorable but rare combination of relatively low elastic properties in the range of those observed for trabecular bone and high yield strengths exceeding those reported for cortical bone. This combination allows for simultaneously avoiding stress shielding, while providing ample mechanical support for bone tissue regeneration and osseointegration. Furthermore, as opposed to other AM porous biomaterials developed to date for which the fatigue endurance limit has been found to be ≈20% of their yield (or plateau) stress, some of the biomaterials developed in the current study show extremely high fatigue resistance with endurance limits up to 60% of their yield stress. It was also found that the permeability values measured for the developed biomaterials were in the range of values reported for trabecular bone. In summary, the developed porous metallic biomaterials based on TPMS mimic the topological, mechanical, and physical properties of trabecular bone to a great degree. These properties make them potential candidates to be applied as parts of orthopedic implants and/or as bone

  5. Enhanced correlation between quantitative ultrasound and structural and mechanical properties of bone using combined transmission-reflection measurement.

    PubMed

    Lin, Liangjun; Lin, Wei; Qin, Yi-Xian

    2015-03-01

    Quantitative ultrasound (QUS) is capable of predicting the principal structural orientation of trabecular bone; this orientation is highly correlated with the mechanical strength of trabecular bone. Irregular shape of bone, however, would increase variation in such a prediction, especially under human in vivo measurement. This study was designed to combine transmission and reflection modes of QUS measurement to improve the prediction for the structural and mechanical properties of trabecular bone. QUS, mechanical testing, and micro computed tomography (μCT) scanning were performed on 24 trabecular bone cubes harvested from a bovine distal femur to obtain the mechanical and structural parameters. Transmission and reflection modes of QUS measurement in the transverse and frontal planes were performed in a confined 60° angle range with 5° increment. The QUS parameters, attenuation (ATT) and velocity (UV), obtained from transmission mode, were normalized to the specimen thickness acquired from reflection mode. Analysis of covariance showed that the combined transmission-reflection modes improved prediction for the structural and Young's modulus of bone in comparison to the traditional QUS measurement performed only in the medial-lateral orientation. In the transverse plane, significant improvement between QUS and μCT was found in ATT vs bone surface density (BS/BV) (p < 0.05), ATT vs trabecular thickness (Tb.Th) (p < 0.01), ATT vs degree of anisotropy (DA) (p < 0.05), UV vs trabecular bone number (Tb.N) (p < 0.05), and UV vs Tb.Th (p < 0.001). In the frontal plane, significant improvement was found in ATT vs structural model index (SMI) (p < 0.01), ATT vs bone volume fraction (BV/TV) (p < 0.01), ATT vs BS/BV (p < 0.001), ATT vs Tb.Th (p < 0.001), ATT vs DA (p < 0.001), and ATT vs modulus (p < 0.001), UV vs SMI (p < 0.01), UV vs BV/TV (p < 0.05), UV vs BS/BV (p < 0.05), UV vs Tb.Th (p < 0.01), UV vs

  6. Enhanced correlation between quantitative ultrasound and structural and mechanical properties of bone using combined transmission-reflection measurement

    PubMed Central

    Lin, Liangjun; Lin, Wei; Qin, Yi-Xian

    2015-01-01

    Quantitative ultrasound (QUS) is capable of predicting the principal structural orientation of trabecular bone; this orientation is highly correlated with the mechanical strength of trabecular bone. Irregular shape of bone, however, would increase variation in such a prediction, especially under human in vivo measurement. This study was designed to combine transmission and reflection modes of QUS measurement to improve the prediction for the structural and mechanical properties of trabecular bone. QUS, mechanical testing, and micro computed tomography (μCT) scanning were performed on 24 trabecular bone cubes harvested from a bovine distal femur to obtain the mechanical and structural parameters. Transmission and reflection modes of QUS measurement in the transverse and frontal planes were performed in a confined 60° angle range with 5° increment. The QUS parameters, attenuation (ATT) and velocity (UV), obtained from transmission mode, were normalized to the specimen thickness acquired from reflection mode. Analysis of covariance showed that the combined transmission-reflection modes improved prediction for the structural and Young's modulus of bone in comparison to the traditional QUS measurement performed only in the medial-lateral orientation. In the transverse plane, significant improvement between QUS and μCT was found in ATT vs bone surface density (BS/BV) (p < 0.05), ATT vs trabecular thickness (Tb.Th) (p < 0.01), ATT vs degree of anisotropy (DA) (p < 0.05), UV vs trabecular bone number (Tb.N) (p < 0.05), and UV vs Tb.Th (p < 0.001). In the frontal plane, significant improvement was found in ATT vs structural model index (SMI) (p < 0.01), ATT vs bone volume fraction (BV/TV) (p < 0.01), ATT vs BS/BV (p < 0.001), ATT vs Tb.Th (p < 0.001), ATT vs DA (p < 0.001), and ATT vs modulus (p < 0.001), UV vs SMI (p < 0.01), UV vs BV/TV (p < 0.05), UV vs BS/BV (p < 0.05), UV vs Tb.Th (p < 0.01), UV vs

  7. The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model.

    PubMed

    Wang, Ying; You, Guoxing; Chen, Peipei; Li, Jianjun; Chen, Gan; Wang, Bo; Li, Penglong; Han, Dong; Zhou, Hong; Zhao, Lian

    2016-03-01

    The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs.

  8. The Mechanisms of Deformation and Damage of Mudstones: A Micro-scale Study Combining ESEM and DIC

    NASA Astrophysics Data System (ADS)

    Wang, L. L.; Bornert, M.; Héripré, E.; Chanchole, S.; Pouya, A.; Halphen, B.

    2015-09-01

    Combining environmental scanning electron microscopy (ESEM) and digital image correlation techniques, the mechanical behaviour of mudstones is studied at the scale of their composite microstructure (that is, grains of carbonate and quartz embedded in a clay matrix). A specially designed apparatus is developed to allow in-situ uniaxial compression tests on samples with controlled humidity states in the ESEM chamber. As the mechanical behavior of mudstones is sensitive to water content, two tests on samples with contrasting water contents (3.8 and 7.4 %) are performed to identify the unified mechanisms of deformation and damage. We illustrate heterogeneous local strain fields that well correlate with the microstructure of mudstones. Three types of deformation bands involving different mechanisms have been classified: orthogonal (compaction of macro-pores and closure of pre-existing cracks), parallel (micro-cracking) and inclined (shear deformation) to the uniaxial compression direction. These deformation modes are activated at different stress levels, and they strongly interact: for instance, a high-strained shear band may result in tensile micro-cracks at its tip. We also illustrate damage phenomena, particularly at the inclusion-matrix interface, which is found to be a hazardous position for nucleation of micro-cracks.

  9. Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties.

    PubMed

    Zhao, Lijia; Park, Nokeun; Tian, Yanzhong; Shibata, Akinobu; Tsuji, Nobuhiro

    2016-12-14

    Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application.

  10. Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties

    NASA Astrophysics Data System (ADS)

    Zhao, Lijia; Park, Nokeun; Tian, Yanzhong; Shibata, Akinobu; Tsuji, Nobuhiro

    2016-12-01

    Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application.

  11. Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties

    PubMed Central

    Zhao, Lijia; Park, Nokeun; Tian, Yanzhong; Shibata, Akinobu; Tsuji, Nobuhiro

    2016-01-01

    Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application. PMID:27966603

  12. Reaction mechanism and tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution: a combined Monte Carlo and quantum mechanics study.

    PubMed

    Lima, Maria Carolina P; Coutinho, Kaline; Canuto, Sylvio; Rocha, Willian R

    2006-06-08

    A combined Monte Carlo and quantum mechanical study was carried out to analyze the tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution. Second- and fourth-order Møller-Plesset perturbation theory calculations indicate that in the gas phase thiol (Pym-SH) is more stable than the thione (Pym-NH) by ca. 8 kcal/mol. In aqueous solution, thermodynamic perturbation theory implemented on a Monte Carlo NpT simulation indicates that both the differential enthalpy and Gibbs free energy favor the thione form. The calculated differential enthalpy is DeltaH(SH)(-->)(NH)(solv) = -1.7 kcal/mol and the differential Gibbs free energy is DeltaG(SH)(-->)(NH)(solv) = -1.9 kcal/mol. Analysis is made of the contribution of the solute-solvent hydrogen bonds and it is noted that the SH group in the thiol and NH group in the thione tautomers act exclusively as a hydrogen bond donor in aqueous solution. The proton transfer reaction between the tautomeric forms was also investigated in the gas phase and in aqueous solution. Two distinct mechanisms were considered: a direct intramolecular transfer and a water-assisted mechanism. In the gas phase, the intramolecular transfer leads to a large energy barrier of 34.4 kcal/mol, passing through a three-center transition state. The proton transfer with the assistance of one water molecule decreases the energy barrier to 17.2 kcal/mol. In solution, these calculated activation barriers are, respectively, 32.0 and 14.8 kcal/mol. The solvent effect is found to be sizable but it is considerably more important as a participant in the water-assisted mechanism than the solvent field of the solute-solvent interaction. Finally, the calculated total Gibbs free energy is used to estimate the equilibrium constant.

  13. Enzymatic hydrolysis combined with mechanical shearing and high-pressure homogenization for nanoscale cellulose fibrils and strong gels.

    PubMed

    Pääkkö, M; Ankerfors, M; Kosonen, H; Nykänen, A; Ahola, S; Osterberg, M; Ruokolainen, J; Laine, J; Larsson, P T; Ikkala, O; Lindström, T

    2007-06-01

    Toward exploiting the attractive mechanical properties of cellulose I nanoelements, a novel route is demonstrated, which combines enzymatic hydrolysis and mechanical shearing. Previously, an aggressive acid hydrolysis and sonication of cellulose I containing fibers was shown to lead to a network of weakly hydrogen-bonded rodlike cellulose elements typically with a low aspect ratio. On the other hand, high mechanical shearing resulted in longer and entangled nanoscale cellulose elements leading to stronger networks and gels. Nevertheless, a widespread use of the latter concept has been hindered because of lack of feasible methods of preparation, suggesting a combination of mild hydrolysis and shearing to disintegrate cellulose I containing fibers into high aspect ratio cellulose I nanoscale elements. In this work, mild enzymatic hydrolysis has been introduced and combined with mechanical shearing and a high-pressure homogenization, leading to a controlled fibrillation down to nanoscale and a network of long and highly entangled cellulose I elements. The resulting strong aqueous gels exhibit more than 5 orders of magnitude tunable storage modulus G' upon changing the concentration. Cryotransmission electron microscopy, atomic force microscopy, and cross-polarization/magic-angle spinning (CP/MAS) 13C NMR suggest that the cellulose I structural elements obtained are dominated by two fractions, one with lateral dimension of 5-6 nm and one with lateral dimensions of about 10-20 nm. The thicker diameter regions may act as the junction zones for the networks. The resulting material will herein be referred to as MFC (microfibrillated cellulose). Dynamical rheology showed that the aqueous suspensions behaved as gels in the whole investigated concentration range 0.125-5.9% w/w, G' ranging from 1.5 Pa to 105 Pa. The maximum G' was high, about 2 orders of magnitude larger than typically observed for the corresponding nonentangled low aspect ratio cellulose I gels, and G' scales

  14. The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer.

    PubMed

    Thakkar, Arvind; Sutaria, Dhruvitkumar; Grandhi, B Karthik; Wang, Jeffrey; Prabhu, Sunil

    2013-04-01

    Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with ~37,000 deaths each year. The present study evaluated the chemopreventive potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1 mM), CUR (10 µM) and SFN (5 µM) (ACS) combination reduced cell viability by ~70% (P<0.001), and also induced cell apoptosis by ~51% (P<0.001) accompanied by activation of caspase-3 and Poly(ADP-ribose) polymerase (PARP) proteins. The NF-κB DNA binding activity was inhi-bited by ~45% (P<0.01) and ~75% (P<0.001) in MIA PaCa-2 and Panc-1 cells, respectively. Mechanistic studies revealed that ACS promoted increase expression of phospho extracellular signal-regulated kinase 1/2 (P-ERK1/2), c-Jun, p38 MAPK and p53 proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partially abolished the effect of ACS on cell viability. Data from this study demonstrate that a low-dose ACS combination inhibits cell growth by inducing cell apoptosis, and proposes sustained activation of the ERK1/2 signaling pathway as one of the possible mechanisms.

  15. Physiological mechanisms contributing to the QTL-combination effects on improved performance of IR64 rice NILs under drought

    PubMed Central

    Henry, Amelia; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Torres, Rolando D.; Batoto, Tristram C.; Manalili, Mervin; Anantha, M. S.; Mandal, N. P.; Kumar, Arvind

    2015-01-01

    Characterizing the physiological mechanisms behind major-effect drought-yield quantitative trait loci (QTLs) can provide an understanding of the function of the QTLs—as well as plant responses to drought in general. In this study, we characterized rice (Oryza sativa L.) genotypes with QTLs derived from drought-tolerant traditional variety AdaySel that were introgressed into drought-susceptible high-yielding variety IR64, one of the most popular megavarieties in South Asian rainfed lowland systems. Of the different combinations of the four QTLs evaluated, genotypes with two QTLs (qDTY 2.2 + qDTY 4.1) showed the greatest degree of improvement under drought compared with IR64 in terms of yield, canopy temperature, and normalized difference vegetation index (NDVI). Furthermore, qDTY 2.2 and qDTY 4.1 showed a potential for complementarity in that they were each most effective under different severities of drought stress. Multiple drought-response mechanisms were observed to be conferred in the genotypes with the two-QTL combination: higher root hydraulic conductivity and in some cases greater root growth at depth. As evidenced by multiple leaf water status and plant growth indicators, these traits affected transpiration but not transpiration efficiency or harvest index. The results from this study highlight the complex interactions among major-effect drought-yield QTLs and the drought-response traits they confer, and the need to evaluate the optimal combinations of QTLs that complement each other when present in a common genetic background. PMID:25680791

  16. A bifurcation study to guide the design of a landing gear with a combined uplock/downlock mechanism

    PubMed Central

    Knowles, James A. C.; Lowenberg, Mark H.; Neild, Simon A.; Krauskopf, Bernd

    2014-01-01

    This paper discusses the insights that a bifurcation analysis can provide when designing mechanisms. A model, in the form of a set of coupled steady-state equations, can be derived to describe the mechanism. Solutions to this model can be traced through the mechanism's state versus parameter space via numerical continuation, under the simultaneous variation of one or more parameters. With this approach, crucial features in the response surface, such as bifurcation points, can be identified. By numerically continuing these points in the appropriate parameter space, the resulting bifurcation diagram can be used to guide parameter selection and optimization. In this paper, we demonstrate the potential of this technique by considering an aircraft nose landing gear, with a novel locking strategy that uses a combined uplock/downlock mechanism. The landing gear is locked when in the retracted or deployed states. Transitions between these locked states and the unlocked state (where the landing gear is a mechanism) are shown to depend upon the positions of two fold point bifurcations. By performing a two-parameter continuation, the critical points are traced to identify operational boundaries. Following the variation of the fold points through parameter space, a minimum spring stiffness is identified that enables the landing gear to be locked in the retracted state. The bifurcation analysis also shows that the unlocking of a retracted landing gear should use an unlock force measure, rather than a position indicator, to de-couple the effects of the retraction and locking actuators. Overall, the study demonstrates that bifurcation analysis can enhance the understanding of the influence of design choices over a wide operating range where nonlinearity is significant. PMID:25484601

  17. A bifurcation study to guide the design of a landing gear with a combined uplock/downlock mechanism.

    PubMed

    Knowles, James A C; Lowenberg, Mark H; Neild, Simon A; Krauskopf, Bernd

    2014-12-08

    This paper discusses the insights that a bifurcation analysis can provide when designing mechanisms. A model, in the form of a set of coupled steady-state equations, can be derived to describe the mechanism. Solutions to this model can be traced through the mechanism's state versus parameter space via numerical continuation, under the simultaneous variation of one or more parameters. With this approach, crucial features in the response surface, such as bifurcation points, can be identified. By numerically continuing these points in the appropriate parameter space, the resulting bifurcation diagram can be used to guide parameter selection and optimization. In this paper, we demonstrate the potential of this technique by considering an aircraft nose landing gear, with a novel locking strategy that uses a combined uplock/downlock mechanism. The landing gear is locked when in the retracted or deployed states. Transitions between these locked states and the unlocked state (where the landing gear is a mechanism) are shown to depend upon the positions of two fold point bifurcations. By performing a two-parameter continuation, the critical points are traced to identify operational boundaries. Following the variation of the fold points through parameter space, a minimum spring stiffness is identified that enables the landing gear to be locked in the retracted state. The bifurcation analysis also shows that the unlocking of a retracted landing gear should use an unlock force measure, rather than a position indicator, to de-couple the effects of the retraction and locking actuators. Overall, the study demonstrates that bifurcation analysis can enhance the understanding of the influence of design choices over a wide operating range where nonlinearity is significant.

  18. Rescue Thrombectomy in Large Vessel Occlusion Strokes Leads to Better Outcomes than Intravenous Thrombolysis Alone: A ‘Real World’ Applicability of the Recent Trials

    PubMed Central

    Nogueira, Raul G.; Zaidat, Osama O.; Castonguay, Alicia C.; Haussen, Diogo C.; Martin, Coleman O.; Holloway, William E.; Mueller-Kronast, Nils; English, Joey; Linfante, Italo; Dabus, Guilherme; Malisch, Tim W.; Marden, Franklin A.; Bozorgchami, Hormozd; Xavier, Andrew; Rai, Ansaar T.; Froehler, Michael T.; Badruddin, Aamir; Nguyen, Thanh N.; Taqi, M. Asif; Abraham, Michael G.; Janardhan, Vallabh; Yoo, Albert J.; Shaltoni, Hashem; Abou-Chebl, Alex; Chen, Peng R.; Britz, Gavin W.; Novakovic, Roberta; Nanda, Ashish; Kaushal, Ritesh; Issa, Mohammad A.; Frankel, Michael R.; Gupta, Rishi

    2016-01-01

    Background The Interventional Management of Stroke III (IMS-III) trial demonstrated no benefit for intravenous recombinant tissue plasminogen activator (IV rt-PA) followed by endovascular therapy versus IV rt-PA alone. However, IMS-III mostly included earlier generation devices. The recent thrombectomy trials have incorporated the stent-retriever technology, but their generalizability remains unknown. Methods The North American Solitaire Acute Stroke (NASA) registry recruited patients treated with the Solitaire FR™ device between March 2012 and February 2013. The NASA-IMS-III-Like Group (NILG baseline NIHSS score ≥10 who received IV rt-PA) was compared to the IV rt-PA and IV + intra-arterial (IA)-IMS-III groups and the MR CLEAN, ESCAPE, SWIFT Prime, and REVASCAT trial controls to assess the stent-retriever treatment in the ‘real-world’ setting. The NILG was also compared to non-IV rt-PA NASA patients to evaluate the impact of IV rt-PA on thrombectomy. Results A total of 136 of the 354 NASA patients fulfilled criteria for the NILG. Baseline characteristics were well balanced across groups. Time from onset to puncture was higher in NILG than IV+IA-IMS-III patients (274 ± 112 vs. 208 ± 47 min, p < 0.0001). Occlusions involving the intracranial ICA, MCA-M1, or basilar arteries were more common in NILG than IV+IA-IMS-III patients (91.2 vs. 47.2%, p < 0.00001). Modified thrombolysis in cerebral infarction ≥2b reperfusion was higher in NILG than IV+IA-IMS-III patients (74.3 vs. 39.6%, p < 0.00001). A 90-day modified Rankin Scale score ≤2 was more frequent in the NILG than IV+IA-IMS-III patients (51.9 vs. 40.8%, p = 0.03) and MR CLEAN (51.9 vs. 19.1%, p < 0.00001), ESCAPE (51.9 vs. 29.3%, p = 0.0002), SWIFT Prime (51.9 vs. 35.5%, p = 0.02), and REVASCAT (51.9 vs. 28.2%, p = 0.0003) controls. Symptomatic intracranial hemorrhage definitions varied across the different studies with rates ranging from 2.7% (ESCAPE) to 11.9% (NILG). The NILG 90-day mortality (24

  19. Mechanical energy profiles of the combined ankle-foot system in normal gait: insights for prosthetic designs.

    PubMed

    Takahashi, Kota Z; Stanhope, Steven J

    2013-09-01

    Over the last half-century, the field of prosthetic engineering has continuously evolved with much attention being dedicated to restoring the mechanical energy properties of ankle joint musculatures during gait. However, the contributions of 'distal foot structures' (e.g., foot muscles, plantar soft tissue) have been overlooked. Therefore, the purpose of this study was to quantify the total mechanical energy profiles (e.g., power, work, and work-ratio) of the natural ankle-foot system (NAFS) by combining the contributions of the ankle joint and all distal foot structures during stance in level-ground steady state walking across various speeds (0.4, 0.6, 0.8 and 1.0 statures/s). The results from eleven healthy subjects walking barefoot indicated ankle joint and distal foot structures generally performed opposing roles: the ankle joint performed net positive work that systematically increased its energy generation with faster walking speeds, while the distal foot performed net negative work that systematically increased its energy absorption with faster walking speeds. Accounting for these simultaneous effects, the combined ankle-foot system exhibited increased work-ratios with faster walking. Most notably, the work-ratio was not significantly greater than 1.0 during the normal walking speed of 0.8 statures/s. Therefore, a prosthetic design that strategically exploits passive-dynamic properties (e.g., elastic energy storage and return) has the potential to replicate the mechanical energy profiles of the NAFS during level-ground steady-state walking.

  20. Elution and Mechanical Strength of Vancomycin-Loaded Bone Cement: In Vitro Study of the Influence of Brand Combination

    PubMed Central

    Tai, Ching-Lung; Chen, Szu-Yuan; Chang, Chih-Hsiang; Chang, Yu-Han; Hsieh, Pang-Hsin

    2016-01-01

    Antibiotic-loaded bone cement (ALBC) is widely used in orthopaedic surgery for both prevention and treatment of infection. Little is known about the effect of different brand combinations of antibiotic and bone cement on the elution profile and mechanical strength of ALBC. Standardized specimens that consisted of one of the 4 brands of bone cement and one of the 3 brands of vancomycin were fashioned, producing 12 combinations of ALBC. Two dosages of vancomycin in 40g bone cement were used to represent the high (4g vancomycin) and low (1g vancomycin) dose groups. Concentrations of vancomycin elution from ALBC was measured for up to 336 hours. The ultimate compression strength was tested at axial compression using a material testing machine before and after elution. In both high-dose and low-dose groups, Lyo-Vancin in PALACOS bone cement resulted in the highest cumulative elution and Vanco in Simplex P bone cement resulted in the lowest elution (458% and 65% higher in high- and low-dose groups, respectively). The mechanical strength was not significantly compromised in all groups with low dose vancomycin (range: 70.31 ± 2.74 MPa to 87.28 ± 8.26MPa after elution). However, with the addition of high dose vancomycin, there was a mixed amount of reduction in the ultimate compression strength after cement aging, ranging from 5% (Vanco in Simplex P, 81.10 ± 0.48 MPa after elution) to 38% (Sterile vancomycin in CMW, 60.94 ± 5.74 MPa after elution). We concluded that the selection of brands of vancomycin and bone cement has a great impact on the release efficacy and mechanical strength of ALBC. PMID:27855203

  1. Traits, properties, and performance: how woody plants combine hydraulic and mechanical functions in a cell, tissue, or whole plant.

    PubMed

    Lachenbruch, Barbara; McCulloh, Katherine A

    2014-12-01

    This review presents a framework for evaluating how cells, tissues, organs, and whole plants perform both hydraulic and mechanical functions. The morphological alterations that affect dual functionality are varied: individual cells can have altered morphology; tissues can have altered partitioning to functions or altered cell alignment; and organs and whole plants can differ in their allocation to different tissues, or in the geometric distribution of the tissues they have. A hierarchical model emphasizes that morphological traits influence the hydraulic or mechanical properties; the properties, combined with the plant unit's environment, then influence the performance of that plant unit. As a special case, we discuss the mechanisms by which the proxy property wood density has strong correlations to performance but without direct causality. Traits and properties influence multiple aspects of performance, and there can be mutual compensations such that similar performance occurs. This compensation emphasizes that natural selection acts on, and a plant's viability is determined by, its performance, rather than its contributing traits and properties. Continued research on the relationships among traits, and on their effects on multiple aspects of performance, will help us better predict, manage, and select plant material for success under multiple stresses in the future.

  2. Responses to combined abiotic and biotic stress in tomato are governed by stress intensity and resistance mechanism

    PubMed Central

    Kissoudis, Christos; Sunarti, Sri; van de Wiel, Clemens; Visser, Richard G.F.; van der Linden, C. Gerard; Bai, Yuling

    2016-01-01

    Stress conditions in agricultural ecosystems can occur at variable intensities. Different resistance mechanisms against abiotic stress and pathogens are deployed by plants. Thus, it is important to examine plant responses to stress combinations under different scenarios. Here, we evaluated the effect of different levels of salt stress ranging from mild to severe (50, 100, and 150mM NaCl) on powdery mildew resistance and overall performance of tomato introgression lines with contrasting levels of partial resistance, as well as near-isogenic lines (NILs) carrying the resistance gene Ol-1 (associated with a slow hypersensitivity response; HR), ol-2 (an mlo mutant associated with papilla formation), and Ol-4 (an R gene associated with a fast HR). Powdery mildew resistance was affected by salt stress in a genotype- and stress intensity-dependent manner. In susceptible and partial resistant lines, increased susceptibility was observed under mild salt stress (50mM) which was accompanied by accelerated cell death-like senescence. In contrast, severe salt stress (150mM) reduced disease symptoms. Na+ and Cl− accumulation in the leaves was linearly related to the decreased pathogen symptoms under severe stress. In contrast, complete resistance mediated by ol-2 and Ol-4 was unaffected under all treatment combinations, and was associated with a decreased growth penalty. Increased susceptibility and senescence under combined stress in NIL-Ol-1 was associated with the induction of ethylene and jasmonic acid pathway genes and the cell wall invertase gene LIN6. These results highlight the significance of stress severity and resistance type on the plant’s performance under the combination of abiotic and biotic stress. PMID:27436279

  3. Combined quantum mechanics/molecular mechanics (QM/MM) simulations for protein-ligand complexes: free energies of binding of water molecules in influenza neuraminidase.

    PubMed

    Woods, Christopher J; Shaw, Katherine E; Mulholland, Adrian J

    2015-01-22

    The applicability of combined quantum mechanics/molecular mechanics (QM/MM) methods for the calculation of absolute binding free energies of conserved water molecules in protein/ligand complexes is demonstrated. Here, we apply QM/MM Monte Carlo simulations to investigate binding of water molecules to influenza neuraminidase. We investigate five different complexes, including those with the drugs oseltamivir and peramivir. We investigate water molecules in two different environments, one more hydrophobic and one hydrophilic. We calculate the free-energy change for perturbation of a QM to MM representation of the bound water molecule. The calculations are performed at the BLYP/aVDZ (QM) and TIP4P (MM) levels of theory, which we have previously demonstrated to be consistent with one another for QM/MM modeling. The results show that the QM to MM perturbation is significant in both environments (greater than 1 kcal mol(-1)) and larger in the more hydrophilic site. Comparison with the same perturbation in bulk water shows that this makes a contribution to binding. The results quantify how electronic polarization differences in different environments affect binding affinity and also demonstrate that extensive, converged QM/MM free-energy simulations, with good levels of QM theory, are now practical for protein/ligand complexes.

  4. Theoretical Characterization of the Spectral Density of the Water-Soluble Chlorophyll-Binding Protein from Combined Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulations.

    PubMed

    Rosnik, Andreana M; Curutchet, Carles

    2015-12-08

    Over the past decade, both experimentalists and theorists have worked to develop methods to describe pigment-protein coupling in photosynthetic light-harvesting complexes in order to understand the molecular basis of quantum coherence effects observed in photosynthesis. Here we present an improved strategy based on the combination of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations and excited-state calculations to predict the spectral density of electronic-vibrational coupling. We study the water-soluble chlorophyll-binding protein (WSCP) reconstituted with Chl a or Chl b pigments as the system of interest and compare our work with data obtained by Pieper and co-workers from differential fluorescence line-narrowing spectra (Pieper et al. J. Phys. Chem. B 2011, 115 (14), 4042-4052). Our results demonstrate that the use of QM/MM MD simulations where the nuclear positions are still propagated at the classical level leads to a striking improvement of the predicted spectral densities in the middle- and high-frequency regions, where they nearly reach quantitative accuracy. This demonstrates that the so-called "geometry mismatch" problem related to the use of low-quality structures in QM calculations, not the quantum features of pigments high-frequency motions, causes the failure of previous studies relying on similar protocols. Thus, this work paves the way toward quantitative predictions of pigment-protein coupling and the comprehension of quantum coherence effects in photosynthesis.

  5. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

    SciTech Connect

    Saldanha, Sabita N.; Kala, Rishabh; Tollefsbol, Trygve O.

    2014-05-15

    Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are

  6. Tuned and Balanced Redistributed Charge Scheme for Combined Quantum Mechanical and Molecular Mechanical (QM/MM) Methods and Fragment Methods: Tuning Based on the CM5 Charge Model.

    PubMed

    Wang, Bo; Truhlar, Donald G

    2013-02-12

    Tuned and balanced redistributed charge schemes have been developed for modeling the electrostatic fields of bonds that are cut by a quantum mechanical-molecular mechanical boundary in combined quantum mechanical and molecular mechanical (QM/MM) methods. First, the charge is balanced by adjusting the charge on the MM boundary atom to conserve the total charge of the entire QM/MM system. In the balanced smeared redistributed charge (BSRC) scheme, the adjusted MM boundary charge is smeared with a smearing width of 1.0 Å and is distributed in equal portions to the midpoints of the bonds between the MM boundary atom and the MM atoms bonded to it; in the balanced redistributed charge-2 (BRC2) scheme, the adjusted MM boundary charge is distributed as point charges in equal portions to the MM atoms that are bonded to the MM boundary atom. The QM subsystem is capped by a fluorine atom that is tuned to reproduce the sum of partial atomic charges of the uncapped portion of the QM subsystem. The new aspect of the present study is a new way to carry out the tuning process; in particular, the CM5 charge model, rather than the Mulliken population analysis applied in previous studies, is used for tuning the capping atom that terminates the dangling bond of the QM region. The mean unsigned error (MUE) of the QM/MM deprotonation energy for a 15-system test suite of deprotonation reactions is 2.3 kcal/mol for the tuned BSRC scheme (TBSRC) and 2.4 kcal/mol for the tuned BRC2 scheme (TBRC2). As was the case for the original tuning method based on Mulliken charges, the new tuning method performs much better than using conventional hydrogen link atoms, which have an MUE on this test set of about 7 kcal/mol. However, the new scheme eliminates the need to use small basis sets, which can be problematic, and it allows one to be more consistent by tuning the parameters with whatever basis set is appropriate for applications. (Alternatively, since the tuning parameters and partial charges

  7. Mechanical Revascularization for Acute Ischemic Stroke: A Single-Center, Retrospective Analysis

    SciTech Connect

    Jeromel, Miran Milosevic, Z. V. Kocijancic, I. J. Lovric, D.; Svigelj, V. Zvan, B.

    2013-04-15

    BackgroundEndovascular mechanical revascularization (thrombectomy) is an increasingly used method for intracranial large vessel recanalization in acute stroke. The purpose of the study was to analyze the recanalization rate, clinical outcome, and complication rate in our stroke patients treated with mechanical revascularization. A total of 57 patients with large vessel stroke (within 3 h for anterior and 12 h for posterior circulation) were treated with mechanical revascularization at a single center during 24 months. The primary goal of endovascular treatment using different mechanical devices was recanalization of the occluded vessel. Recanalization rate (reported as thrombolysis in cerebral infarction [TICI] score), clinical outcome (reported as National Institutes of Health Stroke Scale [NIHSS] score and modified Rankin scale [mRS] score), as well as periprocedural complications were analyzed. The mean age of the patients was 63.1 {+-} 12.9 years, with baseline median NIHSS score of 14 (interquartile range, 9.5-19). Successful recanalization (TICI 2b or 3) was achieved in 41 (72 %) patients. Twenty patients (35 %) presented with favorable outcome (mRS {<=}2) 30 days after stroke. Overall, significant neurological improvement ({>=}4 NIHSS point reduction) occurred in 36 (63 %) patients. A clinically significant procedure-related adverse events (vessel disruption, peri/postprocedural intracranial bleeding) defined with decline in NIHSS of {>=}4 or death occurred in three (5 %) patients. The study showed a high recanalization rate with improved clinical outcome and a low rate of periprocedural complications in our stroke patients treated with mechanical revascularization. Therefore, we could conclude that endovascular revascularization (primary or in combination with a bridging thrombolysis) was an effective and safe procedure for intracranial large vessel recanalization in acute stroke.

  8. Compression creep rupture of an E-glass/vinyl ester composite subjected to combined mechanical and fire loading conditions

    NASA Astrophysics Data System (ADS)

    Boyd, Steven Earl

    Polymer matrix composites are seeing increasing use in structural systems (e.g. ships, bridges) and require a quantitative basis for describing their performance under combined mechanical load and fire. Although much work has been performed to characterize the flammability, fire resistance and toxicity of these composite systems, an understanding of the structural response of sandwich type structures and laminate panels under combined mechanical and thermal loads (simulating fire conditions) is still largely unavailable. Therefore a research effort to develop a model to describe the structural response of these glass/vinyl esters systems under fire loading conditions is relevant to the continuing and future application of polymer matrix composites aboard naval ships. The main goal of the effort presented here is to develop analytical models and finite element analysis methods and tools to predict limit states such as local compression failures due to micro-buckling, residual strength and times to failure for composite laminates at temperatures in the vicinity of the glass transition where failure is controlled by viscoelastic effects. Given the importance of compression loading to a structure subject to fire exposure, the goals of this work are succinctly stated as the: (a) Characterization of the non-linear viscoelastic and viscoplastic response of the E-glass/vinyl ester composite above Tg. (b) Description of the laminate compression mechanics as a function of stress and temperature including viscoelasticity. (c) Viscoelastic stress analysis of a laminated panel ([0/+45/90/-45/0] S) using classical lamination theory (CLT). Three manuscripts constitute this dissertation which is representative of the three steps listed above. First, a detailed characterization of the nonlinear thermoviscoelastic response of Vetrotex 324/Derakane 510A--40 through Tg was conducted using the Time--Temperature--Stress--Superposition Principle (TTSSP) and Zapas--Crissman model. Second

  9. The vibrational spectrum of CaCO3 aragonite: A combined experimental and quantum-mechanical investigation

    NASA Astrophysics Data System (ADS)

    Carteret, Cédric; De La Pierre, Marco; Dossot, Manuel; Pascale, Fabien; Erba, Alessandro; Dovesi, Roberto

    2013-01-01

    The vibrational properties of CaCO3 aragonite have been investigated both theoretically, by using a quantum mechanical approach (all electron Gaussian type basis set and B3LYP HF-DFT hybrid functional, as implemented in the CRYSTAL code) and experimentally, by collecting polarized infrared (IR) reflectance and Raman spectra. The combined use of theory and experiment permits on the one hand to analyze the many subtle features of the measured spectra, on the other hand to evidentiate limits and deficiencies of both approaches. The full set of TO and LO IR active modes, their intensities, the dielectric tensor (in its static and high frequency components), and the optical indices have been determined, as well as the Raman frequencies. Tools such as isotopic substitution and graphical animation of the modes are available, that complement the analysis of the spectrum.

  10. A crystallization technique for obtaining large protein crystals with increased mechanical stability using agarose gel combined with a stirring technique

    NASA Astrophysics Data System (ADS)

    Maruyama, Mihoko; Hayashi, Yuki; Yoshikawa, Hiroshi Y.; Okada, Shino; Koizumi, Haruhiko; Tachibana, Masaru; Sugiyama, Shigeru; Adachi, Hiroaki; Matsumura, Hiroyoshi; Inoue, Tsuyoshi; Takano, Kazufumi; Murakami, Satoshi; Yoshimura, Masashi; Mori, Yusuke

    2016-10-01

    We developed a protein crystallization technique using a 0.0-2.0 w/v% agarose gel solution combined with a stirring technique for the purpose of controlling the crystal number in the gelled solutions. To confirm the stirring effect in the gelled solution, we investigated the nucleation probability and growth rate of the crystals produced using this method. The stirring operation by a rotary shaker affected the behavior of protein molecules in the gelled solution, and both a significant decrease in the nucleation rate and an enhancement of the crystal growth rate were achieved by the method. As a result, we concluded that the proposed technique, the stirring technique in a gel solution, was effective for generating protein crystals of sufficient and increased mechanical stability.

  11. Increasing reliability of gas-air systems of piston and combined internal combustion engines by improving thermal and mechanic flow characteristics

    NASA Astrophysics Data System (ADS)

    Brodov, Yu. M.; Grigor'ev, N. I.; Zhilkin, B. P.; Plotnikov, L. V.; Shestakov, D. S.

    2015-12-01

    Results of experimental study of thermal and mechanical characteristics of gas exchange flow in piston and combined engines are presented. Ways for improving intake and exhaust processes to increase reliability of gas-air engine systems are proposed.

  12. Survival mechanism of Escherichia coli O157:H7 against combined treatment with acetic acid and sodium chloride.

    PubMed

    Lee, Sun-Young; Kang, Dong-Hyun

    2016-05-01

    The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids.

  13. Combined effects of proinflammatory cytokines and intermittent cyclic mechanical strain in inhibiting osteogenicity in human periodontal ligament cells.

    PubMed

    Sun, Chaofan; Chen, Lijiao; Shi, Xinlian; Cao, Zhensheng; Hu, Bibo; Yu, Wenbin; Ren, Manman; Hu, Rongdang; Deng, Hui

    2016-09-01

    Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1β 5 ng/mL and tumor necrosis factor-α 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines.

  14. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

    PubMed Central

    Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

    2016-01-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation. PMID:27380950

  15. Material combinations and parametric study of thermal and mechanical performance of pyramidal core sandwich panels used for hypersonic aircrafts

    NASA Astrophysics Data System (ADS)

    Zhang, Ruiping; Zhang, Xiaoqing; Lorenzini, Giulio; Xie, Gongnan

    2016-11-01

    A novel kind of lightweight integrated thermal protection system, named pyramidal core sandwich panel, is proposed to be a good safeguard for hypersonic aircrafts in the current study. Such system is considered as not only an insulation structure but also a load-bearing structure. In the context of design for hypersonic aircrafts, an efficient optimization should be paid enough attention. This paper concerns with the homogenization of the proposed pyramidal sandwich core panel using two-dimensional model in subsequent research for material selection. According to the required insulation performance and thermal-mechanical properties, several suitable material combinations are chosen as candidates for the pyramidal core sandwich panel by adopting finite element analysis and approximate response surface. To obtain lightweight structure with an excellent capability of heat insulation and load-bearing, an investigation on some specific design variables, which are significant for thermal-mechanical properties of the structure, is performed. Finally, a good balance between the insulation performance, the capability of load-bearing and the lightweight has attained.

  16. A common genetic mechanism determines plasma apolipoprotein B levels and dense LDL subfraction distribution in familial combined hyperlipidemia.

    PubMed Central

    Juo, S H; Bredie, S J; Kiemeney, L A; Demacker, P N; Stalenhoef, A F

    1998-01-01

    Familial combined hyperlipidemia (FCH) is a common lipid disorder characterized by elevations of plasma cholesterol and/or triglyceride in first-degree relatives. A predominance of small, dense LDL particles and elevated apolipoprotein B (apoB) levels is commonly found in members of FCH families. Many studies have investigated the genetic mechanisms determining individuals' lipid levels, in FCH families. Previously, we demonstrated a major gene effect on LDL particle size and codominant Mendelian inheritance involved in determination of apoB levels in a sample of 40 well-defined FCH families. An elevation of apoB levels is associated metabolically with a predominance of small, dense LDL particles in FCH. To establish whether a common gene regulates both traits, we conducted a bivariate genetic analysis to test the hypothesis of a common genetic mechanism. In this study, we found that 66% of the total phenotypic correlation is due to shared genetic components. Further bivariate segregation analysis suggested that both traits share a common major gene plus individual polygenic components. This common major gene explains 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels. Our study suggests that a major gene that has pleiotropic effects on LDL particle size and apoB levels may be the gene underlying FCH in the families we studied. PMID:9683593

  17. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

    NASA Astrophysics Data System (ADS)

    Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

    2016-07-01

    Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

  18. Subchromoplast Sequestration of Carotenoids Affects Regulatory Mechanisms in Tomato Lines Expressing Different Carotenoid Gene Combinations[C][W

    PubMed Central

    Nogueira, Marilise; Mora, Leticia; Enfissi, Eugenia M.A.; Bramley, Peter M.; Fraser, Paul D.

    2013-01-01

    Metabolic engineering of the carotenoid pathway in recent years has successfully enhanced the carotenoid contents of crop plants. It is now clear that only increasing biosynthesis is restrictive, as mechanisms to sequestrate these increased levels in the cell or organelle should be exploited. In this study, biosynthetic pathway genes were overexpressed in tomato (Solanum lycopersicum) lines and the effects on carotenoid formation and sequestration revealed. The bacterial Crt carotenogenic genes, independently or in combination, and their zygosity affect the production of carotenoids. Transcription of the pathway genes was perturbed, whereby the tissue specificity of transcripts was altered. Changes in the steady state levels of metabolites in unrelated sectors of metabolism were found. Of particular interest was a concurrent increase of the plastid-localized lipid monogalactodiacylglycerol with carotenoids along with membranous subcellular structures. The carotenoids, proteins, and lipids in the subchromoplast fractions of the transgenic tomato fruit with increased carotenoid content suggest that cellular structures can adapt to facilitate the sequestration of the newly formed products. Moreover, phytoene, the precursor of the pathway, was identified in the plastoglobule, whereas the biosynthetic enzymes were in the membranes. The implications of these findings with respect to novel pathway regulation mechanisms are discussed. PMID:24249831

  19. Solvatochromic shift of phenol blue in water from a combined Car-Parrinello molecular dynamics hybrid quantum mechanics-molecular mechanics and ZINDO approach

    NASA Astrophysics Data System (ADS)

    Murugan, N. Arul; Jha, Prakash Chandra; Rinkevicius, Z.; Ruud, Kenneth; Ågren, Hans

    2010-06-01

    The present work addresses the solvatochromic shift of phenol blue (PB) dye. For this purpose the results of Car-Parrinello molecular dynamics (CPMD) simulations for PB in gas phase are compared with results obtained for PB in water from CPMD hybrid quantum mechanics-molecular mechanics (CPMD-QM/MM) calculations. The absorption spectra were obtained using the intermediate neglect of differential overlap/spectroscopic-configuration interaction (INDO/CIS) method and were calculated for a multitude of configurations of the trajectory. The calculated λmax for PB in gas phase was found to be about 535 nm, which is considerably lower than the λmax reported for PB in nonpolar solvents. Different solvation shells for PB in water have been defined based on the solute-all-atoms and solvent center of mass radial distribution function (g(rX-O)). The electronic excitation energies for PB computed in the presence of solvent molecules in an increasing number of solvation shells were calculated in a systematic way to evaluate their contributions to the solvatochrmic shift. The inclusion of solvent molecules in the hydration shell yields a λmax of 640 nm, which contributes to almost 78% of the solvatochromic shift. The inclusion of solvent molecules up to 10 Å in the g(rX-O) rdf yields a λmax of 670 nm which is in good agreement with the experimentally reported value of 654-684 nm. Overall, the present study suggests that the combined CPMD-QM/MM and INDO-CIS approach can be used successfully to model solvatochromic shifts of organic dye molecules.

  20. Solvatochromic shift of phenol blue in water from a combined Car-Parrinello molecular dynamics hybrid quantum mechanics-molecular mechanics and ZINDO approach.

    PubMed

    Murugan, N Arul; Jha, Prakash Chandra; Rinkevicius, Z; Ruud, Kenneth; Agren, Hans

    2010-06-21

    The present work addresses the solvatochromic shift of phenol blue (PB) dye. For this purpose the results of Car-Parrinello molecular dynamics (CPMD) simulations for PB in gas phase are compared with results obtained for PB in water from CPMD hybrid quantum mechanics-molecular mechanics (CPMD-QM/MM) calculations. The absorption spectra were obtained using the intermediate neglect of differential overlap/spectroscopic-configuration interaction (INDO/CIS) method and were calculated for a multitude of configurations of the trajectory. The calculated lambda(max) for PB in gas phase was found to be about 535 nm, which is considerably lower than the lambda(max) reported for PB in nonpolar solvents. Different solvation shells for PB in water have been defined based on the solute-all-atoms and solvent center of mass radial distribution function (g(r(X-O))). The electronic excitation energies for PB computed in the presence of solvent molecules in an increasing number of solvation shells were calculated in a systematic way to evaluate their contributions to the solvatochrmic shift. The inclusion of solvent molecules in the hydration shell yields a lambda(max) of 640 nm, which contributes to almost 78% of the solvatochromic shift. The inclusion of solvent molecules up to 10 A in the g(r(X-O)) rdf yields a lambda(max) of 670 nm which is in good agreement with the experimentally reported value of 654-684 nm. Overall, the present study suggests that the combined CPMD-QM/MM and INDO-CIS approach can be used successfully to model solvatochromic shifts of organic dye molecules.

  1. In vitro and in vivo inhibition of tumor cell viability by combined dihydroartemisinin and doxorubicin treatment, and the underlying mechanism

    PubMed Central

    Tai, Xiang; Cai, Xiao-Bei; Zhang, Zhang; Wei, Rui

    2016-01-01

    The natural extract artemisinin and its derivatives have good anticancer activity. The present study aimed to investigate the in vitro inhibitory effects of combined dihydroartemisinin (DHA) and doxorubicin (DOX) treatment on a variety of tumor cell lines (HeLa, OVCAR-3, MCF-7, PC-3 and A549), as well as the underlying mechanisms. In addition, the in vivo effects of DHA and DOX were evaluated using a mouse HeLa tumor model. The HeLa, OVCAR-3, MCF-7, PC-3 and A549 cells were treated with a combination of DHA and DOX, and the effect on cell viability was detected by Cell Counting kit-8. The cells were observed under a fluorescence microscope after staining with Hoechst 33258 dye to observe morphological changes in the nuclei in order to determine whether the cells in the treatment group exhibited apoptosis. Apoptosis of the cells was further detected by flow cytometry, and statistical analysis was performed. The specific inhibitors of caspase-3, −8 and −9 were used to determine the intrinsic and extrinsic pathways of cell apoptosis. The cervical cancer HeLa cells treated with the combination of DHA and DOX showed up to a 91.5% decrease in viability, which was higher than that of the same cells treated with DHA or DOX alone at the same concentration, respectively (P<0.01). The optimal concentrations of the drugs used in combination were DHA at 10 µg/ml and DOX at 10 µg/ml. DHA + DOX also had a significant inhibitory effect on the ovarian cancer (OVCAR-3), breast cancer (MCF-7), lung cancer (A549) and prostate cancer (PC-3) cells. The images observed under fluorescence microscope after Hoechst 33258 staining showed marked pyknosis in the cells treated with DHA + DOX, similar to that when treated with DHA or DOX alone, which is typical in apoptosis. As determined by flow cytometry, the apoptotic rate of the cells treated with DHA + DOX at optimal concentrations was up to 90%, which was significantly higher than that of the cells treated with DHA or DOX alone at

  2. Utility of a combined test of anorectal manometry, electromyography, and sensation in determining the mechanism of 'idiopathic' faecal incontinence.

    PubMed Central

    Sun, W M; Donnelly, T C; Read, N W

    1992-01-01

    Combined tests of anorectal manometry, sphincter electromyography and rectal sensation were carried out in 302 patients with faecal incontinence (235 women, 67 men). The results obtained were compared with 65 normal subjects (35 women, 30 men). A mechanism for incontinence was identified in all and the majority of patients had more than one abnormality. Two hundred and seventy eight patients (92%) had a weak external anal sphincter, 185 of these (67%, mostly women) also showed abnormal perineal descent, and 14 women showed clinical evidence of sphincter damage as a result of obstetric trauma. Ten per cent of patients with impaired external anal sphincter contraction showed associated evidence of spinal disease (impaired rectal sensation plus attenuated or enhanced reflex external anal sphincter activity). Unlike the other groups, the 'spinal' group contained equal numbers of men and women. Ninety seven patients (32%) had evidence of a weak internal anal sphincter. The external sphincter was also very weak and 92% of these patients also had perineal descent. Eighty two patients (27%) showed an unstable internal sphincter, characterised by prolonged 'spontaneous' anal relaxation under resting conditions and an abnormal reduction in anal pressure after conscious contraction of the sphincter or an increase in intraabdominal pressure. One hundred and forty two patients (47%) had a hypersensitive rectum associated with enhanced anorectal responses to rectal distension. All these patients had an abnormally weak external sphincter, suggesting that the hypersensitive or 'irritable' rectum should not be regarded as a cause of faecal incontinence unless accompanied by external sphincter weakness. Twenty four patients (8%) showed a normal basal and squeeze pressures and impaired rectal sensation; six showed giant rectal contractions during rectal distension. The results show that idiopathic faecal incontinence is not caused by a single abnormality, and it is suggested that

  3. Vestibular perception and action employ qualitatively different mechanisms. II. VOR and perceptual responses during combined Tilt&Translation.

    PubMed

    Merfeld, Daniel M; Park, Sukyung; Gianna-Poulin, Claire; Black, F Owen; Wood, Scott

    2005-07-01

    To compare and contrast the neural mechanisms that contribute to vestibular perception and action, we measured vestibuloocular reflexes (VOR) and perceptions of tilt and translation. We took advantage of the well-known ambiguity that the otolith organs respond to both linear acceleration and tilt with respect to gravity and investigated the mechanisms by which this ambiguity is resolved. A new motion paradigm that combined roll tilt with inter-aural translation ("Tilt&Translation") was used; subjects were sinusoidally (0.8 Hz) roll tilted but with their ears above or below the rotation axis. This paradigm provided sinusoidal roll canal cues that were the same across trials while providing otolith cues that varied linearly with ear position relative to the earth-horizontal rotation axis. We found that perceived tilt and translation depended on canal cues, with substantial roll tilt and inter-aural translation perceptions reported even when the otolith organs measured no inter-aural force. These findings match internal model predictions that rotational cues from the canals influence the neural processing of otolith cues. We also found horizontal translational VORs that varied linearly with radius; a minimal response was measured when the otolith organs transduced little or no inter-aural force. Hence, the horizontal translational VOR was dependent on otolith cues but independent of canal cues. These findings match predictions that translational VORs are elicited by simple filtering of otolith signals. We conclude that internal models govern human perception of tilt and translation at 0.8 Hz and that high-pass filtering governs the human translational VOR at this same frequency.

  4. Thiamine, pyridoxine, cyanocobalamin and their combination inhibit thermal, but not mechanical hyperalgesia in rats with primary sensory neuron injury.

    PubMed

    Wang, Zheng-Bei; Gan, Qiang; Rupert, Ronald L; Zeng, Yin-Ming; Song, Xue-Jun

    2005-03-01

    Neuropathic pain after nerve injury is severe and intractable, and current drugs and nondrug therapies offer substantial pain relief to no more than half of affected patients. The present study investigated the analgesic roles of the B vitamins thiamine (B1), pyridoxine (B6) and cyanocobalamin (B12) in rats with neuropathic pain caused by spinal ganglia compression (CCD) or loose ligation of the sciatic nerve (CCI). Thermal hyperalgesia was determined by a significantly shortened latency of foot withdrawal to radiant heat, and mechanical hyperalgesia was determined by a significantly decreased threshold of foot withdrawal to von Frey filaments stimulation of the plantar surface of hindpaw. Results showed that (1) intraperitoneal injection of B1 (5, 10, 33 and 100 mg/kg), B6 (33 and 100 mg/kg) or B12 (0.5 and 2 mg/kg) significantly reduced thermal hyperalgesia; (2) the combination of B1, B6 and B12 synergistically inhibited thermal hyperalgesia; (3) repetitive administration of vitamin B complex (containing B1/B6/B12 33/33/0.5 mg/kg, for 1 and 2 wk) produced long-term inhibition of thermal hyperalgesia; and (4) B vitamins did not affect mechanical hyperalgesia or normal pain sensation, and exhibited similar effects on CCD and CCI induced-hyperalgesia. The present studies demonstrate effects of B vitamins on pain and hyperalgesia following primary sensory neurons injury, and suggest the possible clinical utility of B vitamins in the treatment of neuropathic painful conditions following injury, inflammation, degeneration or other disorders in the nervous systems in human beings.

  5. Escherichia coli Free Radical-Based Killing Mechanism Driven by a Unique Combination of Iron Restriction and Certain Antibiotics

    PubMed Central

    Ma, Li; Gao, Yongjun

    2015-01-01

    ABSTRACT Bacterial resistance to antibiotics is precipitating a medical crisis, and new antibacterial strategies are being sought. Hypothesizing that a growth-restricting strategy could be used to enhance the efficacy of antibiotics, we determined the effect of FDA-approved iron chelators and various antibiotic combinations on invasive and multidrug-resistant extraintestinal pathogenic Escherichia coli (ExPEC), the Gram-negative bacterium most frequently isolated from the bloodstreams of hospitalized patients. We report that certain antibiotics used at sublethal concentrations display enhanced growth inhibition and/or killing when combined with the iron chelator deferiprone (DFP). Inductively coupled plasma optical emission spectrometry reveals abnormally high levels of cell-associated iron under these conditions, a response that correlates with an iron starvation response and supraphysiologic levels of reactive oxygen species (ROS). The high ROS level is reversed upon the addition of antioxidants, which restores bacterial growth, suggesting that the cells are inhibited or killed by excessive free radicals. A model is proposed in which peptidoglycan-targeting antibiotics facilitate the entry of lethal levels of iron-complexed DFP into the bacterial cytoplasm, a process that drives the generation of ROS. This new finding suggests that, in addition to restriction of access to iron as a general growth-restricting strategy, targeting of cellular pathways or networks that selectively disrupt normal iron homeostasis can have potent bactericidal outcomes. IMPORTANCE The prospect that common bacteria will become resistant to all antibiotics is challenging the medical community. In addition to the development of next-generation antibiotics, new bacterial targets that display cytotoxic properties when altered need to be identified. Data presented here demonstrate that combining subinhibitory levels of both iron chelators and certain antibiotics kills pathogenic Escherichia

  6. Combining classical molecular dynamics and quantum mechanical methods for the description of electronic excitations: The case of carotenoids.

    PubMed

    Prandi, Ingrid G; Viani, Lucas; Andreussi, Oliviero; Mennucci, Benedetta

    2016-04-30

    Carotenoids are important actors both in light-harvesting (LH) and in photoprotection functions of photosynthetic pigment-protein complexes. A deep theoretical investigation of this multiple role is still missing owing to the difficulty of describing the delicate interplay between electronic and nuclear degrees of freedom. A possible strategy is to combine accurate quantum mechanical (QM) methods with classical molecular dynamics. To do this, however, accurate force-fields (FF) are necessary. This article presents a new FF for the different carotenoids present in LH complexes of plants. The results show that all the important structural properties described by the new FF are in very good agreement with QM reference values. This increased accuracy in the simulation of the structural fluctuations is also reflected in the description of excited states. Both the energy order and the different nature of the lowest singlet states are preserved during the dynamics when the new FF is used, whereas an unphysical mixing is found when a standard FF is used.

  7. Structure and mechanical properties of Ti-Si-N films deposited by combined DC/RF reactive unbalanced magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Ding, X. Z.; Zeng, X. T.; Liu, Y. C.; Yang, Q.; Zhao, L. R.

    2004-11-01

    Ti-Si-N nanocomposite films with Si content between 0 and 13.5 at. % were deposited by combined DC/RF reactive unbalanced magnetron sputtering. The composition, structure, and mechanical properties of the as-deposited Ti-Si-N films were measured by energy dispersive analysis of x rays, x-ray diffraction (XRD), and nanoindentation experiments, respectively. All of the Ti-Si-N films exhibited a higher hardness than pure TiN films deposited under similar conditions. The highest hardness (~41 GPa) was obtained in the film with Si content of about 8 at. %. Ti-Si-N films also exhibited a higher resistance to plastic deformation (i.e., higher ratio H3/E*2) than pure TiN. XRD patterns revealed that the as-deposited films were composed of cubic TiN crystallites with a preferential orientation of (111). With increase of RF power applied to the Si targets, the TiN (111) peak intensity or TiN crystallite size increased in the lower RF power range but decreased in the higher RF power range, showing a maximum at an RF power of 500 W (power density ~1.14 W/cm2), corresponding to a Si content of about 5 at. % in the film.

  8. The combined effect of dismantling for steam sterilization and aging on the accuracy of spring-style mechanical torque devices

    PubMed Central

    Mahshid, Minoo; Sadr, Seyed Jalil; Fayyaz, Ali; Kadkhodazadeh, Mahdi

    2013-01-01

    Purpose This study aimed to assess the combined effect of dismantling before sterilization and aging on the accuracy (±10% of the target torque) of spring-style mechanical torque devices (S-S MTDs). Methods Twenty new S-SMTDs from two different manufacturers (Nobel Biocare and Straumann: 10 of each type) were selected and divided into two groups, namely, case (group A) and control (group B). For sterilization, 100 cycles of autoclaving were performed in 100 sequences. In each sequence, 10 repetitions of peak torque values were registered for aging. To measure and assess the output of each device, a Tohnichi torque gauge was used (P<0.05). Results Before steam sterilization, all of the tested devices stayed within 10% of their target values. After 100 cycles of steam sterilization and aging with or without dismantling of the devices, the Nobel Biocare devices stayed within 10% of their target torque. In the Straumann devices, despite the significant difference between the peak torque and target torque values, the absolute error values stayed within 10% of their target torque. Conclusion Within the limitations of this study, there was no significant difference between the mean and absolute value of error between Nobel Biocare and Straumann S-S MTDs. PMID:24236244

  9. A Combination of Chemometrics and Quantum Mechanics Methods Applied to Analysis of Femtosecond Transient Absorption Spectrum of Ortho-Nitroaniline

    PubMed Central

    Yi, Jing; Xiong, Ying; Cheng, Kemei; Li, Menglong; Chu, Genbai; Pu, Xuemei; Xu, Tao

    2016-01-01

    A combination of the advanced chemometrics method with quantum mechanics calculation was for the first time applied to explore a facile yet efficient analysis strategy to thoroughly resolve femtosecond transient absorption spectroscopy of ortho-nitroaniline (ONA), served as a model compound of important nitroaromatics and explosives. The result revealed that the ONA molecule is primarily excited to S3 excited state from the ground state and then ultrafast relaxes to S2 state. The internal conversion from S2 to S1 occurs within 0.9 ps. One intermediate state S* was identified in the intersystem crossing (ISC) process, which is different from the specific upper triplet receiver state proposed in some other nitroaromatics systems. The S1 state decays to the S* one within 6.4 ps and then intersystem crossing to the lowest triplet state within 19.6 ps. T1 was estimated to have a lifetime up to 2 ns. The relatively long S* state and very long-lived T1 one should play a vital role as precursors to various nitroaromatic and explosive photoproducts. PMID:26781083

  10. Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies

    PubMed Central

    Gebremeskel, Simon; Johnston, Brent

    2015-01-01

    Chemotherapy has historically been thought to induce cancer cell death in an immunogenically silent manner. However, recent studies have demonstrated that therapeutic outcomes with specific chemotherapeutic agents (e.g. anthracyclines) correlate strongly with their ability to induce a process of immunogenic cell death (ICD) in cancer cells. This process generates a series of signals that stimulate the immune system to recognize and clear tumor cells. Extensive studies have revealed that chemotherapy-induced ICD occurs via the exposure/release of calreticulin (CALR), ATP, chemokine (C–X–C motif) ligand 10 (CXCL10) and high mobility group box 1 (HMGB1). This review provides an in-depth look into the concepts and mechanisms underlying CALR exposure, activation of the Toll-like receptor 3/IFN/CXCL10 axis, and the release of ATP and HMGB1 from dying cancer cells. Factors that influence the impact of ICD in clinical studies and the design of therapies combining chemotherapy with immunotherapy are also discussed. PMID:26486085

  11. A combined stretching-tilting mechanism produces negative, zero and positive linear thermal expansion in a semi-flexible Cd(II)-MOF.

    PubMed

    Lama, Prem; Das, Raj Kumar; Smith, Vincent J; Barbour, Leonard J

    2014-06-21

    A novel semi-flexible Cd(II)-MOF has been synthesized and characterized by variable temperature powder and single-crystal X-ray diffraction. The material displays an unusual combination of thermal expansion (TE) i.e. negative, zero and positive, which is an extremely rare finding, especially for metal-organic frameworks as a result of a combined stretching-tilting mechanism.

  12. Experimental study of ultra-thin films mechanical integrity by combined nanoindentation and nano-acoustic emission

    NASA Astrophysics Data System (ADS)

    Zhang, Zihou

    Advancement of interconnect technology has imposed significant challenge on interface characterization and reliability for blurred interfaces between layers. There is a need for material properties and these miniaturized length scales and assessment of reliability; including the intrinsic film fracture toughness and the interfacial fracture toughness. The nano-meter range of film thicknesses currently employed, impose significant challenges on evaluating these physical quantities and thereby impose significant challenge on the design cycle. In this study we attempted to use a combined nano-indentation and nano-acoustic emission to qualitatively and quantitatively characterize the failure modes in ultra-thin blanket films on Si substrates or stakes of different characteristics. We have performed and analyzed an exhaustive group of testes that cove many diverge combination of film-substrate combination, provided by both Intel and IBM. When the force-indentation depth curve shows excursion, a direct measure of the total energy release rate is estimated. The collected acoustic emission signal is then used to partition the total energy into two segments, one associated with the cohesive fracture toughness of the film and the other is for the adhesive fracture toughness of the interface. The acoustic emission signal is analyzed in both the time and frequency domain to achieve such energy division. In particular, the signal time domain analysis for signal skewness, time of arrival and total energy content are employed with the proper signal to noise ratio. In the frequency domain, an expansive group of acoustic emission signals are utilized to construct the details of the power spectral density. A bank of band-pass filters are designed to sort the individual signals to those associated with adhesive interlayer cracking, cohesive channel cracking, or other system induced noise. The attenuation time and the energy content within each spectral frequency were the key elements

  13. Successful surgical treatment of Nicolau's syndrome combined with intravenous iloprost.

    PubMed

    Gormus, N; Tanyeli, O; Senaran, H; Duman, A; Solak Görmüs, Z I; Durgut, K

    2009-11-01

    A 4 year-old boy was admitted to our clinic with symptoms of pain and ecchymosis in his right leg and foot after injection of benzathine penicilline. There was a localized gangrenous area at the femoral injection site. Doppler ultrasonography showed no arterial flow in the femoral artery and clear evidence of acute thrombosis of the superficial femoral and popliteal veins. Femoral arterial and venous thrombectomy and fasciotomy were performed immediately. After surgery the boy was treated by Iloprost infusion and enoxaparine. One week later necrotic changes had regressed, fasciotomies were closed and only the distal phalanx of the third toe needed amputation. Early surgical intervention and standard management combined with Iloprost infusion may help in healing the lesions by increasing extremity perfusion and may prevent extremity loss.

  14. Multi-drug resistance transporters and a mechanism-based strategy for assessing risks of pesticide combinations to honey bees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds tha...

  15. Mechanical Removal of Migrated Onyx Due to Microcatheter Rupture During AVM Embolization: A Technical Case Report.

    PubMed

    Senturk, Cagin

    2015-12-01

    We report a case where migrated Onyx could be removed safely with a mechanical thrombectomy device after withdrawal of the damaged microcatheter. A microcatheter was retained in the superior cerebellar artery with attached Onyx fragments on its tip during embolization of a bled cerebellar AVM. During retrieval maneuvers microcatheter shaft was ruptured and Onyx fragments were released into the vertebrobasilar system causing occlusion. Finally, Onyx fragment on tip of the microcatheter could be detached with dimethyl sulfoxide injection and the microcatheter could be withdrawn. A Merci retriever device (Concentric Medical, Mountain View, CA, USA) was successfully used to retrieve most of the dislodged Onyx material and recanalize the vertebrobasilar circulation.

  16. Differential molecular mechanism of docetaxel-octreotide combined treatment according to the docetaxel-resistance status in PC3 prostate cancer cells.

    PubMed

    Lattanzio, Laura; Tonissi, Federica; Monteverde, Martino; Milano, Gerard; Merlano, Marco C; Lo Nigro, Cristiana

    2013-02-01

    To examine the effect and the molecular mechanisms of the combined treatment of the somatostatin (SST) analogue octreotide with docetaxel: analysis of proliferation, apoptosis and migration in the human prostate cancer cell line PC3, either sensitive (PC3wt) or made resistant to docetaxel (PC3R). We examined the effect of the two drugs individually or in combination on cell proliferation and migration by analysis of apoptosis and cell cycle proteins. The role of octreotide in modulating P-glycoprotein function was examined together with the modulation of SST receptors type 2 and 5 (SSTR2 and SSTR5). We observed an enhanced effect of docetaxel and octreotide given in combination or in sequence compared with either agent alone; this result was particularly evident when docetaxel was given before octreotide in PC3wt and when the two drugs were given together in PC3R cells. In contrast to lanreotide, our data indicate that octreotide does not act as a P-glycoprotein inhibitor in PC3R cells. A role of docetaxel and combined treatment in regulating SSTR2, SSTR5, proliferation and apoptosis gene expression is suggested as the possible mechanism for the enhanced effect observed. In addition, an evaluation of the effect of the combined treatment on cellular migration was examined, showing a moderate loss of invasive properties in PC3R cells. The present results confirm that SST analogues may be combined with docetaxel to increase the antitumour effect in patients with advanced prostate carcinoma.

  17. Determination of adhesion between thermoplastic and liquid silicone rubbers in hard-soft-combinations via mechanical peeling test

    NASA Astrophysics Data System (ADS)

    Kühr, C.; Spörrer, A.; Altstädt, V.

    2014-05-01

    The production of hard-soft-combinations via multi injection molding gained more and more importance in the last years. This is attributed to different factors. One principle reason is that the use of two-component injection molding technique has many advantages such as cancelling subsequent and complex steps and shortening the process chain. Furthermore this technique allows the combination of the properties of the single components like the high stiffness of the hard component and the elastic properties of the soft component. Because of the incompatibility of some polymers the adhesion on the interface has to be determined. Thereby adhesion is not only influenced by the applied polymers, but also by the injection molding parameters and the characteristics of the mold. Besides already known combinations of thermoplastics with thermoplastic elastomers (TPE), there consists the possibility to apply liquid silicone rubber (LSR) as soft component. A thermoplastic/LSR combination gains in importance due to the specific advantages of LSR to TPE. The faintly adhesion between LSR and thermoplastics is currently one of the key challenges when dealing with those combinations. So it is coercively necessary to improve adhesion between the two components by adding an adhesion promoter. To determine the promoters influence, it is necessary to develop a suitable testing method to investigate e.g. the peel resistance. The current German standard "VDI Richtlinie 2019', which is actually only employed for thermoplastic/TPE combinations, can serve as a model to determine the adhesion of thermoplastic/LSR combinations.

  18. Mechanical Thrombectomy Using the Solitaire FR system for Occlusion of the Top of the Basilar Artery: Intentional Detachment of the Device after Partial Retrieval

    PubMed Central

    Siu, Kwong Lok; Lee, Dong-Geun; Shim, Jae Ho; Suh, Dae Chul

    2014-01-01

    Acute, distal, basilar artery occlusion is a challenging neurovascular emergency. There have been several reports regarding the successful application of the Solitaire FR device for treating this lesion. However, due to the lack of a suitable, balloon-tipped, guiding catheter for the vertebral artery, during this procedure we frequently experience the occurrence of clot fragmentation and distal migration. There may be some technical solutions to solve this problem. The purpose of this report is to present a technical variation of using the Solitaire FR, and which is referred to as the 'intentional device detachment technique.' As a clot tends to re-embolize during its passage through the tortuous cranio-cervical junction level of the vertebral artery or its passage through the tip of the guiding catheter, due to the lack of proximal flow arrest, we thought that not removing the stent segment of the device which is capturing the clot could avoid this problem. We were able to successfully apply this technique in two cases. We believe that this technique can be a possible technical option for using the Solitaire FR device when a patient has little concern regarding the subsequent use of antiplatelets. PMID:24642915

  19. Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

    SciTech Connect

    Cakir, Volkan; Gulcu, Aytac; Akay, Emrah; Capar, Ahmet E.; Gencpinar, Tugra; Kucuk, Banu; Karabay, Ozalp; Goktay, A. Yigit

    2014-08-15

    PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

  20. Analysis of the combined effects of lanthanum and acid rain, and their mechanisms, on nitrate reductase transcription in plants.

    PubMed

    Xia, Binxin; Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

    2017-04-01

    Rare earth element (REE) pollution and acid rain are major global environmental concerns, and their spatial distributions overlap. Thus, both forms of pollution combine to act on plants. Nitrogen is important for plant growth, and nitrate reductase (NR) is a key plant enzyme that catalyzes nitrogen assimilation. Studying the combined effects of REEs and acid rain on plant nitrogen-based nutrients has important environmental significance. Here, soybean (Glycine max) plants, commonly used for toxicological studies, were exposed to lanthanum (La), a REE, and acid rain to study the NR activities and NR transcriptional levels in the roots. To explain how the pollution affected the NR transcriptional level, we simultaneously observed the contents of intracellular La and nutrient elements, protoplast morphology, membrane lipid peroxidation and intracellular pH. A combined treatment of 0.08mmol/L La and pH 4.5 acid rain increased the NR activity, decreased the NR transcriptional level, increased the intracellular nutrient elements' contents and caused deformations in membrane structures. Other combined treatments significantly decreased the aforementioned parameters and caused serious damage to the membrane structures. The variation in the amplitudes of combined treatments was greater than those of individual treatments. Compared with the control and individual treatments, combined treatments increased membrane permeability, the malondialdehyde content, and intracellular H(+) and La contents, and with an increasing La concentration or acid strength, the change in amplitude increased. Thus, the combined effects on NR gene transcription in soybean seedling roots were related to the intracellular nutrient elements' contents, protoplast morphology, membranous lipid peroxidation, intracellular pH and La content.

  1. In vivo anticancer synergy mechanism of doxorubicin and verapamil combination treatment is impaired in BALB/c mice with metastatic breast cancer.

    PubMed

    McCarthy, Michelle; Auda, Gregory; Agrawal, Suchi; Taylor, Amy; Backstrom, Zack; Mondal, Debasis; Moroz, Krzysztof; Dash, Srikanta

    2014-08-01

    The development of resistance to anticancer drugs is a major unsolved problem in the chemotherapy treatment of metastatic breast cancer. We have shown that increased expression of P-glycoprotein (P-gp) prevented nuclear entry of the doxorubicin molecules into murine breast cancer cells (4T1-R) leading to doxorubicin chemoresistance. This study was performed to test whether inhibition of P-gp using verapamil could overcome doxorubicin chemoresistance and eliminate multiorgan metastasis 4T1-R cells in BALB/c mouse. The 4T1-R cells were treated with doxorubicin alone, verapamil alone, and a combination of both. Multiorgan metastasis of 4T1-R cells in the presence and in the absence of combination treatment was determined in the BALB/c mouse model. Verapamil induced nuclear translocation of doxorubicin, G2-phase growth arrest and synergistically induced 100% cytotoxicity in 4T1-R cells in culture. However, the combination treatment using verapamil and doxorubicin did not improve the overall survival of BALB/c mice with metastatic breast cancer. Our results indicate that the combination treatment of verapamil and doxorubicin did not inhibit tumor growth in the lungs and liver indicating that the anticancer synergy mechanism of verapamil and doxorubicin is impaired in vivo in BALB/c mouse model with metastatic breast cancer. We propose that understanding the mechanisms as to why the combination of doxorubicin and verapamil treatment was impaired in the mouse model should allow novel approaches to improve chemotherapy response of metastatic breast cancer.

  2. Mechanism for combined action of microwaves and static magnetic field: slow non uniform rotation of charged nucleoid.

    PubMed

    Matronchik, A Y; Belyaev, I Y

    2008-01-01

    Recent data show that microwaves (MW) and extremely low-frequency (ELF) magnetic fields at low intensities affect conformation of nucleoids in bacterial E. coli cells and human lymphocytes. Experimental data suggest that magnitude of the effects of both MW and ELF depend on frequency and static magnetic field. We have previously proposed the physical model for the effects of combined ELF/static magnetic fields on the charged DNA-domain/nucleoid. In this article, we present the model of slow non uniform rotation of the charged DNA-domain/nucleoid for the combined effects of MW and static magnetic field. The solution of this model suggests that the combined action of MW and static magnetic field results in slow non uniform rotation of nucleoid with angular speed that depends on Larmor frequency. The model predicts that non thermal effects of MW are dependent on carrier frequency and also static magnetic field in the area of exposure.

  3. Structure of Low-Lying Excited States of Guanine in DNA and Solution: Combined Molecular Mechanics and High-Level Coupled Cluster Studies

    DOE PAGES

    Kowalski, Karol; Valiev, Marat

    2007-01-01

    High-level ab-initio equation-of-motion coupled-cluster methods with singles, doubles, and noniterative triples are used, in conjunction with the combined quantum mechanical molecular mechanics approach, to investigate the structure of low-lying excited states of the guanine base in DNA and solvated environments. Our results indicate that while the excitation energy of the first excited state is barely changed compared to its gas-phase counterpart, the excitation energy of the second excited state is blue-shifted by 0.24 eV.

  4. Combined toxic effects and mechanisms of microsystin-LR and copper on Vallisneria Natans (Lour.) Hara seedlings.

    PubMed

    Wang, Zhi; Zhang, Junqian; Li, Enhua; Zhang, Liang; Wang, Xuelei; Song, Lirong

    2017-04-15

    Microcystin-LR (MCLR) and copper are commonly found in eutrophic water bodies because of eutrophic run-offs, cyanobacterial blooms, and copper algicide applications. However, the ecotoxicological risk of their combination remains unknown. This study investigated the effect of MCLR, Cu, and their mixture on the growth and physiological responses of Vallisneria natans. Results showed that the combined toxicity of them was concentration dependent. Synergistic effects were elicited at low concentrations of MCLR and Cu exposure (≤0.25+0.64mg/L). Additive or antagonistic effects were induced at higher concentrations. Single and combined exposures could induce oxidative stress, such as increased superoxide anion radical levels. To cope with oxidative stress, V. natans could activate their antioxidant defense systems, such as enhanced superoxide dismutase production and changes in peroxidase activities. Exposure to combined MCLR and Cu (even only with 0.005+0.041mg/L) adversely affected their antioxidant defense systems. As a consequence, malondialdehyde levels significantly increased. The interaction of MCLR and Cu could also significantly increase the bioaccumulations of MCLR and Cu. This increase could be accounted for their synergistic toxic effects on V. natans. Our results suggested that the exacerbated ecological hazard of MCLR and Cu with environmental concentrations may harm aquatic ecosystems.

  5. Excited singlet (S1) state interactions of calixarenes with chloroalkanes: A combination of concerted and stepwise dissociative electron transfer mechanism

    NASA Astrophysics Data System (ADS)

    Mohanty, J.; Pal, H.; Nayak, S. K.; Chattopadhyay, S.; Sapre, A. V.

    2002-12-01

    Both steady-state and time-resolved studies in acetonitrile (ACN) solutions show that the excited singlet (S1) states of calixarenes (CX) undergo quenching by chloroalkanes (CA). It has been revealed by characterizing the Cl ions in the photolyzed CX-CA systems in ACN solutions that the quenching occurs due to dissociative electron transfer (DET) mechanism, whereby a C-Cl bond of the CAs undergoes dissociation on acceptance of an electron from excited CX. The bimolecular quenching constants (kq) in the present systems were correlated with the free energy changes for the concerted DET reactions based on a suitable DET theory. Such a correlation results in the recovery of an intramolecular reorganization energy, which is substantially lower to account for the C-Cl bond dissociation energy of the CAs. Comparing present results with those of an another donor-acceptor system (e.g., biphenyldiol-CA systems) where a concerted DET mechanism is applicable, it is inferred that in CX-CA systems both concerted and stepwise DET mechanisms operate simultaneously. It is proposed that the interaction of excited CXs with encaged CAs follows the stepwise mechanism whereas that with the out of cage CAs follows the concerted mechanism.

  6. Damage Detection Based on Power Dissipation Measured with PZT Sensors through the Combination of Electro-Mechanical Impedances and Guided Waves

    PubMed Central

    Sevillano, Enrique; Sun, Rui; Perera, Ricardo

    2016-01-01

    The use of piezoelectric ceramic transducers (such as Lead-Zirconate-Titanate—PZT) has become more and more widespread for Structural Health Monitoring (SHM) applications. Among all the techniques that are based on this smart sensing solution, guided waves and electro-mechanical impedance techniques have found wider acceptance, and so more studies and experimental works can be found containing these applications. However, even though these two techniques can be considered as complementary to each other, little work can be found focused on the combination of them in order to define a new and integrated damage detection procedure. In this work, this combination of techniques has been studied by proposing a new integrated damage indicator based on Electro-Mechanical Power Dissipation (EMPD). The applicability of this proposed technique has been tested through different experimental tests, with both lab-scale and real-scale structures. PMID:27164104

  7. [Inhibitory effect and the mechanism of Astragalus polysaccharide combined with cisplatin on growth of inplanted Lewis lung carcinoma in mice].

    PubMed

    Zhuang, Mengjie; Liu, Dan; Chen, Yanwen; Ming, Haixia; Li, Yang

    2017-04-01

    Objective To observe the effect of Astragalus polysaccharides (APS) combined with cisplatin (DDP) on the expressions of cytochrome C (CytC) and high temperature required serine protease A2 (Omi/HtrA2) in the mice with Lewis lung carcinoma (LLC) transplantated tumors. Methods Ninty C57BL/6J mice were randomly divided into normal control group, model group, and (50, 100, 200) μg/mL APS groups, 6 mg/kg DDP group, 3 mg/kg DDP combined with (50, 100, 200) μg/mL APS groups. Each group included 10 mice. Except the mice in the normal group, the rest mice were inoculated subcutaneously with LLC cells (1×10(7) mL) at the right fore axillary fossa to establish tumor-bearing mouse models. In the second day of building models, the mice in the treatment group were given intraperitoneal injection of 0.3 mL of the drug. DDP was given once a week, and the other drugs once a day. The mice in the normal group and the model group were administrated the same amount of saline injection for continuous 20 days. All mice were killed at the 21st day. The pathological changes of tumor tissues were observed by HE staining. The expressions and location of CytC and Omi/HtrA2 proteins in the transplanted tumor tissues were detected by immunohistochemical staining and image analysis. Results The mass of tumor decreased in the mice of (100, 200) μg/mL APS group and 3 mg/kg DDP combined with (100, 200) μg/mL APS group. Compared with the model group, the necrosis of tumor tissues in 200 μg/mL APS combined with 3 mg/kg DDP group was the most obvious. The expressions of CytC and Omi/HtrA2 increased in the treatment groups, and the increase was the most remarkable in 200 μg/mL APS combined with 3 mg/kg DDP group. Conclusion APS and APS combined with DDP can restrain the growth of Lewis Lung cancer in C57BL/6J mice, which may be related to the increased expressions of CytC and Omi/HtrA2.

  8. Biomechanical aspects of segmented arch mechanics combined with power arm for controlled anterior tooth movement: A three-dimensional finite element study.

    PubMed

    Ozaki, Hiroya; Tominaga, Jun-Ya; Hamanaka, Ryo; Sumi, Mayumi; Chiang, Pao-Chang; Tanaka, Motohiro; Koga, Yoshiyuki; Yoshida, Noriaki

    2015-01-01

    The porpose of this study was to determine the optimal length of power arms for achieving controlled anterior tooth movement in segmented arch mechanics combined with power arm. A three-dimensional finite element method was applied for the simulation of en masse anterior tooth retraction in segmented power arm mechanics. The type of tooth movement, namely, the location of center of rotation of the maxillary central incisor in association with power arm length, was calculated after the retraction force was applied. When a 0.017 × 0.022-in archwire was inserted into the 0.018-in slot bracket, bodily movement was obtained at 9.1 mm length of power arm, namely, at the level of 1.8 mm above the center of resistance. In case a 0.018 × 0.025-in full-size archwire was used, bodily movement of the tooth was produced at the power arm length of 7.0 mm, namely, at the level of 0.3 mm below the center of resistance. Segmented arch mechanics required shorter length of power arms for achieving any type of controlled anterior tooth movement as compared to sliding mechanics. Therefore, this space closing mechanics could be widely applied even for the patients whose gingivobuccal fold is shallow. The segmented arch mechanics combined with power arm could provide higher amount of moment-to-force ratio sufficient for controlled anterior tooth movement without generating friction, and vertical forces when applying retraction force parallel to the occlusal plane. It is, therefore, considered that the segmented power arm mechanics has a simple appliance design and allows more efficient and controllable tooth movement.

  9. Mechanisms of Zn(II) binded to collagen and its effect on the capacity of eco-friendly Zn-Cr combination tanning system.

    PubMed

    Cao, Shan; Liu, Bing; Cheng, Baozhen; Lu, Fuping; Wang, Yanping; Li, Yu

    2017-01-05

    The eco-friendly combination tanning process has been developed to reduce chromium in existing researches, which is based on zinc tanning agents. This can be considered as a less-chrome substitute for current tanning process. To gain deeper understanding of the binding mechanisms of zinc-collagen interaction, which are affected by tanning pH, experiments have been carried out. Analysis in this paper reveals how chemical bonds from the collagen's main function groups combine with zinc. XPS and NIR data was analyzed for further understanding of where the zinc binding sites lie on collagen fibers at different pH. The results indicate that high pH is helpful to amino-binding sites while low pH promotes carboxyl-binding sites on collagen fibers. Furthermore, from the effect of Zinc-chrome combination tanning, we can see that the new method reduces the chromium dosage in tanning process compared to the conventional chrome tanning method.

  10. Sorption mechanisms of arsenate on Mg-Fe layered double hydroxides: A combination of adsorption modeling and solid state analysis.

    PubMed

    Hudcová, Barbora; Veselská, Veronika; Filip, Jan; Číhalová, Sylva; Komárek, Michael

    2017-02-01

    Layered double hydroxides have been proposed as effective sorbents for As(V), but studies investigating adsorption mechanisms usually lack a comprehensive mechanistic/modeling approach. In this work, we propose coupling surface complexation modeling with various spectroscopic techniques. To this end, a series of batch experiments at different pH values were performed. Kinetic data were well fitted by a pseudo-second order kinetic model, and the equilibrium data were fitted by the Freundlich model. Moreover, the pH-dependent As(V) sorption data were satisfactorily fitted by a diffuse layer model, which described the formation of >SOAsO3H(-) monodentate and >(SO)2AsO2(-) bidentate inner-sphere complexes (">S" represents a crystallographically-bound group on the surface). Additionally, XPS analyses confirmed the adsorption mechanisms. The sorption mechanisms were affected by anion exchange, which was responsible for the formation of outer sphere complexes, as identified by XRD and FTIR analyses. Furthermore, a homogenous distribution of As(V) was determined by HR-TEM with elemental mapping. Using low-temperature Mössbauer spectroscopy on isotope (57)Fe, a slight shift of the hyperfine parameters towards higher values following As(V) sorption was measured, indicating a higher degree of structural disorder. In general, mechanistic adsorption modeling coupled with solid state analyses presents a powerful approach for investigating the adsorption mechanism of As(V) on Mg-Fe LDH or other sorbents.

  11. Absorption and fluorescence of PRODAN in phospholipid bilayers: a combined quantum mechanics and classical molecular dynamics study.

    PubMed

    Cwiklik, Lukasz; Aquino, Adelia J A; Vazdar, Mario; Jurkiewicz, Piotr; Pittner, Jiří; Hof, Martin; Lischka, Hans

    2011-10-20

    Absorption and fluorescence spectra of PRODAN (6-propionyl-2-dimethylaminonaphthalene) were studied by means of the time-dependent density functional theory and the algebraic diagrammatic construction method. The influence of environment, a phosphatidylcholine lipid bilayer and water, was taken into account employing a combination of quantum chemical calculations with empirical force-field molecular dynamics simulations. Additionally, experimental absorption and emission spectra of PRODAN were measured in cyclohexane, water, and lipid vesicles. Both planar and twisted configurations of the first excited state of PRODAN were taken into account. The twisted structure is stabilized in both water and a lipid bilayer, and should be considered as an emitting state in polar environments. Orientation of the excited dye in the lipid bilayer significantly depends on configuration. In the bilayer, the fluorescence spectrum can be regarded as a combination of emission from both planar and twisted structures.

  12. Elimination of HCV via a non-ISG-mediated mechanism by vaniprevir and BMS-788329 combination therapy in human hepatocyte chimeric mice.

    PubMed

    Uchida, Takuro; Hiraga, Nobuhiko; Imamura, Michio; Yoshimi, Satoshi; Kan, Hiromi; Miyaki, Eisuke; Tsuge, Masataka; Abe, Hiromi; Hayes, C Nelson; Aikata, Hiroshi; Ishida, Yuji; Tateno, Chise; Ellis, Joan D; Chayama, Kazuaki

    2016-02-02

    We previously reported that interferon (IFN)-free direct-acting antiviral combination treatment succeeded in eradicating genotype 1b hepatitis C virus (HCV) in human hepatocyte chimeric mice. In this study, we examined the effect of vaniprevir (MK7009, NS3/4A protease inhibitor) and BMS-788329 (NS5A inhibitor) combination treatment on HCV genotype 1b and the expression of IFN-stimulated genes (ISGs) using a subgenomic replicon system and the same animal model. Combination treatment with vaniprevir and BMS-788329 significantly reduced HCV replication compared to vaniprevir monotherapy in HCV replicon cells (Huh7/Rep-Feo cells). HCV genotype 1b-infected human hepatocyte chimeric mice were treated with vaniprevir alone or in combination with BMS-788329 for four weeks. Vaniprevir monotherapy reduced serum HCV RNA titers in mice, but viral breakthrough was observed in mice with high HCV titers. Ultra-deep sequence analysis revealed a predominant replacement by drug-resistant substitutions at 168 in HCV NS3 region in these mice. Conversely, in mice with low HCV titers, HCV was eradicated by vaniprevir monotherapy without viral breakthrough. In contrast to monotherapy, combination treatment with vaniprevir and BMS-788329 succeeded in completely eradicating HCV regardless of serum viral titer. IFN-alpha treatment significantly increased ISG expression; however, vaniprevir and BMS-788329 combination treatment caused no increase in ISG expression both in cultured cells and in mouse livers. Therefore, combination treatment with vaniprevir and BMS-788329 eliminated HCV via a non-ISG-mediated mechanism. This oral treatment might offer an alternative DAA combination therapy for patients with chronic hepatitis C.

  13. Combined effects of ventilation mode and positive end-expiratory pressure on mechanics, gas exchange and the epithelium in mice with acute lung injury.

    PubMed

    Thammanomai, Apiradee; Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Suki, Béla

    2013-01-01

    The accepted protocol to ventilate patients with acute lung injury is to use low tidal volume (V(T)) in combination with recruitment maneuvers or positive end-expiratory pressure (PEEP). However, an important aspect of mechanical ventilation has not been considered: the combined effects of PEEP and ventilation modes on the integrity of the epithelium. Additionally, it is implicitly assumed that the best PEEP-V(T) combination also protects the epithelium. We aimed to investigate the effects of ventilation mode and PEEP on respiratory mechanics, peak airway pressures and gas exchange as well as on lung surfactant and epithelial cell integrity in mice with acute lung injury. HCl-injured mice were ventilated at PEEPs of 3 and 6 cmH(2)O with conventional ventilation (CV), CV with intermittent large breaths (CV(LB)) to promote recruitment, and a new mode, variable ventilation, optimized for mice (VV(N)). Mechanics and gas exchange were measured during ventilation and surfactant protein (SP)-B, proSP-B and E-cadherin levels were determined from lavage and lung homogenate. PEEP had a significant effect on mechanics, gas exchange and the epithelium. The higher PEEP reduced lung collapse and improved mechanics and gas exchange but it also down regulated surfactant release and production and increased epithelial cell injury. While CV(LB) was better than CV, VV(N) outperformed CV(LB) in recruitment, reduced epithelial injury and, via a dynamic mechanotransduction, it also triggered increased release and production of surfactant. For long-term outcome, selection of optimal PEEP and ventilation mode may be based on balancing lung physiology with epithelial injury.

  14. Rational combination of targeted therapies as a strategy to overcome the mechanisms of resistance to inhibitors of EGFR signaling.

    PubMed

    Bianco, Roberto; Damiano, Vincenzo; Gelardi, Teresa; Daniele, Gennaro; Ciardiello, Fortunato; Tortora, Giampaolo

    2007-01-01

    The epidermal growth factor receptor (EGFR) has been widely used as a target for novel anticancer agents, such as blocking antibodies and small molecular weight tyrosine kinase compounds. In spite of recent advances in cancer cell biology, leading to the introduction of clinically active new drugs, such as cetuximab, panitumumab and erlotinib, unfortunately disease control remains unsuccessful due to the presence of constitutive resistance to EGFR inhibitors in most patients and the development of acquired resistance in the responders. A large number of molecular abnormalities in tumor cells seem to partly contribute to their resistance to anti-EGFR therapy: increased angiogenesis, constitutive activation of downstream mediators, overexpression of other tyrosine kinase receptors. Moreover, some mutations in the EGFR receptor kinase domain seem to play a crucial role in determining the sensitivity of cancer cells to specific inhibitors by altering the conformation of the receptor and its activity. The development of rational combinations of anticancer agents and EGFR inhibitors, able to exert synergistic cytotoxic interactions, has been widely accepted and used in both preclinical and clinical studies. Although the failure of large clinical trial based on empirical combination of anti-EGFR and classic chemotherapeutic agents, several preclinical data seems to support the hypothesis that combining EGFR inhibitors and other novel agents could efficiently inhibit tumor growth and overcome intrinsic resistance to a single-agent based therapy. This review focuses on the role of complementary signalling pathways in the development of resistance to EGFR targeting agents and the rationale to combine novel inhibitors as anticancer therapy.

  15. Lipid-based nanoformulation of irinotecan: dual mechanism of action allows for combination chemo/angiogenic therapy.

    PubMed

    Waterhouse, Dawn N; Yapp, Donald; Verreault, Maite; Anantha, Malathi; Sutherland, Brent; Bally, Marcel B

    2011-11-01

    A number of studies have outlined the antiangiogenic effects of cytotoxic agents when administered frequently at low doses. These studies suggest that the effect of the cytotoxic agent is on the vasculature within the tumor and it is assumed that there is little or negligible cytotoxicity. Liposomal drug delivery systems have the ability to provide a dual mechanism of activity where tumor accumulation can deliver high local concentrations of the drug at the site of action with concomitant slow release of the drug from carriers in the blood compartment that results in antivascular effects, similar to that achieved when dosing frequently at low levels. Although this dual mechanism of activity may be linked to other lipid nanoparticle formulations of anticancer drugs, this article summarizes the evidence supporting direct (cytotoxic) and indirect (antivascular) actions of a liposomal formulation of irinotecan.

  16. A new water absorbable mechanical Epidermal skin equivalent: the combination of hydrophobic PDMS and hydrophilic PVA hydrogel.

    PubMed

    Morales-Hurtado, M; Zeng, X; Gonzalez-Rodriguez, P; Ten Elshof, J E; van der Heide, E

    2015-06-01

    Research on human skin interactions with healthcare and lifestyle products is a topic continuously attracting scientific studies over the past years. It is possible to evaluate skin mechanical properties based on human or animal experimentation, yet in addition to possible ethical issues, these samples are hard to obtain, expensive and give rise to highly variable results. Therefore, the design of a skin equivalent is essential. This paper describes the design and characterization of a new Epidermal Skin Equivalent (ESE). The material resembles the properties of epidermis and is a first approach to mimic the mechanical properties of the human skin structure, variable with the length scale. The ESE is based on a mixture of Polydimethyl Siloxane (PDMS) and Polyvinyl Alcohol (PVA) hydrogel cross-linked with Glutaraldehyde (GA). It was chemically characterized by XPS and FTIR measurements and its cross section was observed by macroscopy and cryoSEM. Confocal Microscope analysis on the surface of the ESE showed an arithmetic roughness (Ra) between 14-16 μm and contact angle (CA) values between 50-60°, both of which are close to the values of in vivo human skins reported in the literature. The Equilibrium Water Content (ECW) was around 33.8% and Thermo Gravimetric Analysis (TGA) confirmed the composition of the ESE samples. Moreover, the mechanical performance was determined by indentation tests and Dynamo Thermo Mechanical Analysis (DTMA) shear measurements. The indentation results were in good agreement with that of the target epidermis reported in the literature with an elastic modulus between 0.1-1.5 MPa and it showed dependency on the water content. According to the DTMA measurements, the ESE exhibits a viscoelastic behavior, with a shear modulus between 1-2.5MPa variable with temperature, frequency and the hydration of the samples.

  17. The effect of combined conventional and modified ultrafiltration on mechanical ventilation and hemodynamic changes in congenital heart surgery

    PubMed Central

    Ziyaeifard, Mohsen; Alizadehasl, Azin; Aghdaii, Nahid; Rahimzadeh, Poupak; Masoumi, Gholamreza; Golzari, Samad EJ; Fatahi, Mostafa; Gorjipur, Farhad

    2016-01-01

    Background: Cardiopulmonary bypass is associated with increased fluid accumulation around the heart which influences pulmonary and cardiac diastolic function. The aim of this study was to compare the effects of modified ultrafiltration (MUF) versus conventional ultrafiltration (CUF) on duration of mechanical ventilation and hemodynamic status in children undergoing congenital heart surgery. Materials and Methods: A randomized clinical trial was conducted on 46 pediatric patients undergoing cardiopulmonary bypass throughout their congenital heart surgery. Arteriovenous MUF plus CUF was performed in 23 patients (intervention group) and sole CUF was performed for other 23 patients (control group). In MUF group, arterial cannula was linked to the filter inlet through the arterial line, and for 10 min, 10 ml/kg/min of blood was filtered and returned via cardioplegia line to the right atrium. Different parameters including hemodynamic variables, length of mechanical ventilation, Intensive Care Unit (ICU) stay, and inotrope requirement were compared between the two groups. Results: At immediate post-MUF phase, there was a statistically significant increase in the mean arterial pressure, systolic blood pressure, and diastolic blood pressure (P < 0.05) only in the study group. Furthermore, there was a significant difference in time of mechanical ventilation (P = 0.004) and ICU stay (P = 0.007) between the two groups. Inotropes including milrinone (P = 0.04), epinephrine (P = 0.001), and dobutamine (P = 0.002) were used significantly less frequently for patients in the intervention than the control group. Conclusion: Administration of MUF following surgery improves hemodynamic status of patients and also significantly decreases the duration of mechanical ventilation and inotrope requirement within 48 h after surgery. PMID:28255321

  18. A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation

    PubMed Central

    Stenzig, Justus; Biermann, Daniel; Jelinek, Marisa; Reichenspurner, Hermann; Eschenhagen, Thomas; Ehmke, Heimo; Schwoerer, Alexander P.

    2016-01-01

    Objectives Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats. Methods To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations. Results 50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading. Discussion Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure. PMID:26841021

  19. [Mechanisms for the increased fertilizer nitrogen use efficiency of rice in wheat-rice rotation system under combined application of inorganic and organic fertilizers].

    PubMed

    Liu, Yi-Ren; Li, Xiang; Yu, Jie; Shen, Qi-Rong; Xu, Yang-Chun

    2012-01-01

    A pot experiment was conducted to study the effects of combined application of organic and inorganic fertilizers on the nitrogen uptake by rice and the nitrogen supply by soil in a wheat-rice rotation system, and approach the mechanisms for the increased fertilizer nitrogen use efficiency of rice under the combined fertilization from the viewpoint of microbiology. Comparing with applying inorganic fertilizers, combined application of organic and inorganic fertilizers decreased the soil microbial biomass carbon and nitrogen and soil mineral nitrogen contents before tillering stage, but increased them significantly from heading to filling stage. Under the combined fertilization, the dynamics of soil nitrogen supply matched best the dynamics of rice nitrogen uptake and utilization, which promoted the nitrogen accumulation in rice plant and the increase of rice yield and biomass, and increased the fertilizer nitrogen use efficiency of rice significantly. Combined application of inorganic and organic fertilizers also promoted the propagation of soil microbes, and consequently, more mineral nitrogen in soil was immobilized by the microbes at rice early growth stage, and the immobilized nitrogen was gradually released at the mid and late growth stages of rice, being able to better satisfy the nitrogen demand of rice in its various growth and development stages.

  20. Molecular mechanism of inhibitory effects of C-phycocyanin combined with all-trans-retinoic acid on the growth of HeLa cells in vitro.

    PubMed

    Yang, Fan; Li, Bing; Chu, Xian-Ming; Lv, Cong-Yi; Xu, Ying-Jie; Yang, Peng

    2014-06-01

    We studied the effects of all-trans-retinoic acid (ATRA), C-phycocyanin (C-PC), or ATRA+C-PC on the growth of cervical cells (HeLa cells), cell cycle distribution, and apoptosis. The anticancer mechanism of the drug combination was revealed. MTT assay was adopted to determine the effects of C-PC and ATRA on the growth of HeLa cells. The expression quantities of cyclin-dependent kinase (CDK) 4, cyclin D1, Bcl-2, caspase-3, and CD59 were determined by in situ hybridization, immunofluorescence, immunohistochemistry staining, Western blot, and RT-PCR. TUNEL assay was adopted to determine the cellular apoptosis levels. Both C-PC and ATRA could inhibit the growth of HeLa cells, and the combination of ATRA+C-PC functioned cooperatively to induce apoptosis in HeLa cells. The dosage of ATRA was reduced when it cooperated with C-PC to reduce the toxicity. ATRA treated with C-PC could induce more cell cycle arrests than the single drug used by decrease in cyclin D1 and CDK4 expression. The combination of the two drugs could upregulate caspase-3 and downregulate the Bcl-2 gene and induce cell apoptosis. Moreover, the combination therapy has an important immunological significance in decreased expression of the CD59 protein. Singly, C-PC or ATRA could inhibit the growth of HeLa cells, and the effects of treatment were further enhanced in the combination group. In combination with C-PC, the dosage of ATRA was effectively reduced. The C-PC + ATRA combination might take effect by inhibiting the progress of the cell cycle, inducing cell apoptosis and promoting complement-mediated cytolysis.

  1. Mechanisms for independent and combined effects of calorie restriction and acute exercise on insulin-stimulated glucose uptake by skeletal muscle of old rats.

    PubMed

    Sharma, Naveen; Wang, Haiyan; Arias, Edward B; Castorena, Carlos M; Cartee, Gregory D

    2015-04-01

    Either calorie restriction [CR; consuming 60-65% of ad libitum (AL) intake] or acute exercise can independently improve insulin sensitivity in old age, but their combined effects on muscle insulin signaling and glucose uptake have previously been unknown. Accordingly, we assessed the independent and combined effects of CR (beginning at 14 wk old) and acute exercise (3-4 h postexercise) on insulin signaling and glucose uptake in insulin-stimulated epitrochlearis muscles from 30-mo-old rats. Either CR alone or exercise alone vs. AL sedentary controls induced greater insulin-stimulated glucose uptake. Combined CR and exercise vs. either treatment alone caused an additional increase in insulin-stimulated glucose uptake. Either CR or exercise alone vs. AL sedentary controls increased Akt Ser(473) and Akt Thr(308) phosphorylation. Combined CR and exercise further elevated Akt phosphorylation on both sites. CR alone, but not exercise alone, vs. AL sedentary controls significantly increased Akt substrate of 160 kDa (AS160) Ser(588) and Thr(642) phosphorylation. Combined CR and exercise did not further enhance AS160 phosphorylation. Exercise alone, but not CR alone, modestly increased GLUT4 abundance. Combined CR and exercise did not further elevate GLUT4 content. These results suggest that CR or acute exercise independently increases insulin-stimulated glucose uptake via overlapping (greater Akt phosphorylation) and distinct (greater AS160 phosphorylation for CR, greater GLUT4 for exercise) mechanisms. Our working hypothesis is that greater insulin-stimulated glucose uptake in the combined CR and exercise group vs. CR or exercise alone relies on greater Akt activation, leading to greater phosphorylation of one or more Akt substrates other than AS160.

  2. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability.

    PubMed

    Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant'Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2015-11-23

    Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p < 0.05) than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05) in the groups fed with high content carotenoid crops (sweet potato or pumpkin). The PB group presented lower (p < 0.05) TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity.

  3. Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

    PubMed Central

    Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant’Ana, Helena Maria; Martino, Hércia Stampini Duarte

    2015-01-01

    Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p < 0.05) than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05) in the groups fed with high content carotenoid crops (sweet potato or pumpkin). The PB group presented lower (p < 0.05) TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity. PMID:26610564

  4. Drag and heat reduction mechanism induced by a combinational novel cavity and counterflowing jet concept in hypersonic flows

    NASA Astrophysics Data System (ADS)

    Sun, Xi-wan; Guo, Zhen-yun; Huang, Wei; Li, Shi-bin; Yan, Li

    2016-09-01

    The drag and heat reduction problem of hypersonic reentry vehicles has always attracted the attention worldwide, and many novel schemes have been proposed recently. In the current study, the research progress of the combinational configuration of the forward-facing cavity and the counterflowing jet has been reviewed, and the conventional cavity configuration has been substituted by an approximate maximum thrust nozzle contour for better heat and surface pressure reduction efficiency. The Reynolds-average of Navier-Stokes (RANS) equations coupled with the SST k-ω turbulence model have been employed to calculate its surrounding flow fields. A validation metric and the grid convergence index (GCI) have been employed to conduct the turbulence model assessment and the grid independence analysis respectively. The axisymmetric assumption has been verified by three-dimensional computational results as well. The obtained results show that the SST k-ω model is more suitable for the novel drag and heat flux reduction scheme proposed in this article, and the axisymmetric assumption is approximately reasonable. After investigating the influence of jet pressure ratio, the novel combinational configuration has been verified to be more effective in heat and surface pressure reduction, and this is because the approximate maximum thrust nozzle contour contributes to better expansion and avoids total pressure loss of the jet.

  5. Mechanical regulation of the proangiogenic factor CCN1/CYR61 gene requires the combined activities of MRTF-A and CREB-binding protein histone acetyltransferase.

    PubMed

    Hanna, Mary; Liu, Haibo; Amir, Jawaria; Sun, Yi; Morris, Stephan W; Siddiqui, M A Q; Lau, Lester F; Chaqour, Brahim

    2009-08-21

    Smooth muscle-rich tissues respond to mechanical overload by an adaptive hypertrophic growth combined with activation of angiogenesis, which potentiates their mechanical overload-bearing capabilities. Neovascularization is associated with mechanical strain-dependent induction of angiogenic factors such as CCN1, an immediate-early gene-encoded matricellular molecule critical for vascular development and repair. Here we have demonstrated that mechanical strain-dependent induction of the CCN1 gene involves signaling cascades through RhoA-mediated actin remodeling and the p38 stress-activated protein kinase (SAPK). Actin signaling controls serum response factor (SRF) activity via SRF interaction with the myocardin-related transcriptional activator (MRTF)-A and tethering to a single CArG box sequence within the CCN1 promoter. Such activity was abolished in mechanically stimulated mouse MRTF-A(-/-) cells or upon inhibition of CREB-binding protein (CBP) histone acetyltransferase (HAT) either pharmacologically or by siRNAs. Mechanical strain induced CBP-mediated acetylation of histones 3 and 4 at the SRF-binding site and within the CCN1 gene coding region. Inhibition of p38 SAPK reduced CBP HAT activity and its recruitment to the SRF.MRTF-A complex, whereas enforced induction of p38 by upstream activators (e.g. MKK3 and MKK6) enhanced both CBP HAT and CCN1 promoter activities. Similarly, mechanical overload-induced CCN1 gene expression in vivo was associated with nuclear localization of MRTF-A and enrichment of the CCN1 promoter with both MRTF-A and acetylated histone H3. Taken together, these data suggest that signal-controlled activation of SRF, MRTF-A, and CBP provides a novel connection between mechanical stimuli and angiogenic gene expression.

  6. Probing protein environment in an enzymatic process: All-electron quantum chemical analysis combined with ab initio quantum mechanical/molecular mechanical modeling of chorismate mutase

    NASA Astrophysics Data System (ADS)

    Ishida, Toyokazu

    2008-09-01

    In this study, we investigated the electronic character of protein environment in enzymatic processes by performing all-electron QM calculations based on the fragment molecular orbital (FMO) method. By introducing a new computational strategy combining all-electron QM analysis with ab initio QM/MM modeling, we investigated the details of molecular interaction energy between a reactive substrate and amino acid residues at a catalytic site. For a practical application, we selected the chorismate mutase catalyzed reaction as an example. Because the computational time required to perform all-electron QM reaction path searches was very large, we employed the ab initio QM/MM modeling technique to construct reliable reaction profiles and performed all-electron FMO calculations for the selected geometries. The main focus of the paper is to analyze the details of electrostatic stabilization, which is considered to be the major feature of enzymatic catalyses, and to clarify how the electronic structure of proteins is polarized in response to the change in electron distribution of the substrate. By performing interaction energy decomposition analysis from a quantum chemical viewpoint, we clarified the relationship between the location of amino acid residues on the protein domain and the degree of electronic polarization of each residue. In particular, in the enzymatic transition state, Arg7, Glu78, and Arg90 are highly polarized in response to the delocalized electronic character of the substrate, and as a result, a large amount of electrostatic stabilization energy is stored in the molecular interaction between the enzyme and the substrate and supplied for transition state stabilization.

  7. Probing protein environment in an enzymatic process: All-electron quantum chemical analysis combined with ab initio quantum mechanical/molecular mechanical modeling of chorismate mutase.

    PubMed

    Ishida, Toyokazu

    2008-09-28

    In this study, we investigated the electronic character of protein environment in enzymatic processes by performing all-electron QM calculations based on the fragment molecular orbital (FMO) method. By introducing a new computational strategy combining all-electron QM analysis with ab initio QM/MM modeling, we investigated the details of molecular interaction energy between a reactive substrate and amino acid residues at a catalytic site. For a practical application, we selected the chorismate mutase catalyzed reaction as an example. Because the computational time required to perform all-electron QM reaction path searches was very large, we employed the ab initio QM/MM modeling technique to construct reliable reaction profiles and performed all-electron FMO calculations for the selected geometries. The main focus of the paper is to analyze the details of electrostatic stabilization, which is considered to be the major feature of enzymatic catalyses, and to clarify how the electronic structure of proteins is polarized in response to the change in electron distribution of the substrate. By performing interaction energy decomposition analysis from a quantum chemical viewpoint, we clarified the relationship between the location of amino acid residues on the protein domain and the degree of electronic polarization of each residue. In particular, in the enzymatic transition state, Arg7, Glu78, and Arg90 are highly polarized in response to the delocalized electronic character of the substrate, and as a result, a large amount of electrostatic stabilization energy is stored in the molecular interaction between the enzyme and the substrate and supplied for transition state stabilization.

  8. Generation of mesenchymal stem cell from human umbilical cord tissue using a combination enzymatic and mechanical disassociation method.

    PubMed

    Tong, Chih Kong; Vellasamy, Shalini; Tan, Boon Chong; Abdullah, Maha; Vidyadaran, Sharmili; Seow, Heng Fong; Ramasamy, Rajesh

    2011-03-01

    MSCs (mesenchymal stem cells) promise a great potential for regenerative medicine due to their unique properties of self-renewal, high plasticity, modulation of immune response and the flexibility for genetic modification. Therefore, the increasing demand for cellular therapy necessitates a larger-scale production of MSC; however, the technical and ethical issues had put a halt on it. To date, studies have shown that MSC could be derived from human UC (umbilical cord), which is once considered as clinical waste. We have compared the two conventional methods which are classic enzymatic digestion and explant method with our newly tailored enzymatic-mechanical disassociation method to generate UC-MSC. The generated UC-MSCs from the methods above were characterized based on their immunophenotyping, early embryonic transcription factors expression and mesodermal differentiation ability. Our results show that enzymatic-mechanical disassociation method increase the initial nucleated cell yield greatly (approximately 160-fold) and maximized the successful rate of UC-MSC generation. Enzymatic-mechanical disassociation-derived UC-MSC exhibited fibroblastic morphology and surface markers expression of CD105, CD73, CD29, CD90 and MHC class I. Furthermore, these cells constitutively express early embryonic transcription factors (Nanog, Oct-4, Sox-2 and Rex-1), as confirmed by RT-PCR, indicating their multipotency and high self-renewal capacity. They are also capable of differentiating into osteoblasts and adipocytes when given an appropriate induction. The present study demonstrates a new and efficient approach in generating MSC from UC, hence serving as ideal alternative source of mesenchymal stem cell for clinical and research use.

  9. Modification mechanism of praseodymium doping for the photocatalytic performance of TiO2: a combined experimental and theoretical study.

    PubMed

    Duan, Zhi-Gang; Zhao, Zong-Yan; Shi, Qing-Nan

    2015-07-15

    Impurity doping is a simple and efficient modification method to improve the photocatalytic performance of wide band gap photocatalysts. However, some basic and important issues about the mechanism of impurity doping modification still need to be further confirmed and explained. In the present work, Pr-doped TiO2 with a mono-phase crystal structure was prepared by a sol-gel method. Then, the crystal structure, binding information, optical absorption, and photocatalytic activity were systematically investigated. The experimental results show that Pr doping could significantly enhance the photocatalytic activity of TiO2, and the effects of modification on rutile TiO2 are more obvious than for anatase TiO2. In order to understand the underlying mechanism, density functional theory was utilized to calculate the crystal structure and electronic structure of pure and Pr-doped TiO2. The differences in electronic structure between anatase and rutile phases lead to the above photocatalytic performance. The experimental measurements and theoretical calculations mutually support each other in the present work. Two points are confirmed: the position of the band edge determines the redox activity of the photocatalyst, and the shallow energy bands induced by impurity doping could improve the photocatalytic performance.

  10. Combined Isolated Laugier's Fracture and Distal Radial Fracture: Management and Literature Review on the Mechanism of Injury

    PubMed Central

    Osman, Walid; Alaya, Zeineb; Naouar, Nader; Ben Ayeche, Mohamed

    2016-01-01

    Introduction. Isolated fracture of the trochlea is an uncommon condition requiring a particular mechanism of injury. Its association with a distal radial fracture is rare. We aimed through this case report to identify the injury mechanism and to assess surgical outcomes. Case Presentation. We report a 26-year-old female who was admitted to our department for elbow trauma following an accidental fall on her outstretched right hand with her elbow extended and supinated. On examination, the right elbow was swollen with tenderness over the anteromedial aspect of the distal humerus. The elbow range was restricted. Standard radiographs showed an intra-articular half-moon-shaped fragment lying proximal and anterior to the distal humerus. There was a comminuted articular fracture of the distal radius with an anterior displacement. A computed tomography revealed an isolated shear fracture of the trochlea without any associated lesion of the elbow. The patient was surgically managed. Anatomical reduction was achieved and the fracture was fixed with 2 Kirschner wires. The distal radial fracture was treated by open reduction and plate fixation. The postoperative course was uneventful with a good recovery. Conclusion. Knowledge of such entity would be useful to indicate the suitable surgical management and eventually to obtain good functional outcomes. PMID:28070435

  11. Combined experimental and quantum chemical study on the adsorption mechanism of phosphorous anions on the hydrotalcite surfaces

    NASA Astrophysics Data System (ADS)

    Mishima, Kenji; Zhang, Shuang; Minagawa, Sho; Kano, Naoki

    2016-08-01

    In the present work, the hydrotalcite-like compound [Mg6Al2(OH)16]CO3ṡ nH2O (shorted as MgAl-CO3) is synthesized and the adsorption of phosphorous anions, their adsorption performance on the surface of hydrotalcites, and its mechanism are analyzed. To theoretically clarify the adsorption mechanism and adsorption structures, we perform quantum chemistry calculations of reactants, locally stable states, transition states, and products among phosphorous anion, water, and hydrotalcite in a variety of pH ranges. The experimental result shows that the efficiency of phosphate removal does not depend on pH of the solution, with which the numerical results are consistent. In particular, we identify the factors of influencing the adsorption ratio in different pH ranges from the quantum chemistry calculations: the stability of locally stable states, and the energies and locations of potential barriers along the reaction pathway relative to those of the locally stable states. The results suggest that hydrotalcites synthesized in this work are suitable as sorbent materials for the adsorption and removal of phosphorous anions from aqueous solutions.

  12. Correlating mechanical properties and anti-wear performance of tribofilms formed by ionic liquids, ZDDP and their combinations

    SciTech Connect

    Landauer, Alexander K.; Barnhill, William C.; Qu, Jun

    2016-03-10

    Here we examine the elasticity, hardness, and resistance-to-plastic-deformation (P/S2) measured via nanoindentation of several tribofilms and correlates these properties to friction and wear behavior. The tribofilms were generated by ball-on-plate reciprocating sliding lubricated by a base oil containing an ionic liquid, phosphonium-organophosphate or ammonium-organophosphate, zinc dialkyldithiophosphate (ZDDP), or combination of IL and ZDDP. Nanoindentation was conducted at room and elevated temperatures. While there seems little correlation between the tribofilm hardness and tribological behavior, a higher modulus generally leads to better friction and wear performance. Interestingly, a lower P/S2 ratio tends to reduce friction and improve wear protection, which is in an opposite trend as reported for bulk materials. Ultimately, this is likely attributable to the dynamic, self-healing characteristics of tribofilms.

  13. Microstructure and Low-Temperature Mechanical Properties of 304 Stainless Steel Joints by PAW + GTAW Combined Welding

    NASA Astrophysics Data System (ADS)

    Liu, Kun; Li, Yajiang; Wang, Juan

    2016-10-01

    The combined double-pass process of plasma arc welding (PAW) + gas tungsten arc welding (GTAW) was performed on 304 austenitic stainless steel with the thickness of 12 mm. Results indicated that two different morphologies of ferrite (e.g., lathy δ-ferrite and skeletal δ-ferrite) were formed within the austenite matrix in PAW weld metal (PAW-WM). GTAW weld metal (GTAW-WM) was mainly composed of fine austenite and skeletal δ-ferrite. In transition zone between PAW-WM and GTAW-WM, epitaxial growth contributed to cellular dendritic crystals transforming into columnar crystals. The tensile strength of joint is about 700 MPa. The impact toughness of WM varied from 281 J (20 °C) to 122 (-196 °C), while the impact toughness of heat-affected zone (HAZ) varied from 205 J (20 °C) to 112 J (-196 °C).

  14. Correlating mechanical properties and anti-wear performance of tribofilms formed by ionic liquids, ZDDP and their combinations

    DOE PAGES

    Landauer, Alexander K.; Barnhill, William C.; Qu, Jun

    2016-03-10

    Here we examine the elasticity, hardness, and resistance-to-plastic-deformation (P/S2) measured via nanoindentation of several tribofilms and correlates these properties to friction and wear behavior. The tribofilms were generated by ball-on-plate reciprocating sliding lubricated by a base oil containing an ionic liquid, phosphonium-organophosphate or ammonium-organophosphate, zinc dialkyldithiophosphate (ZDDP), or combination of IL and ZDDP. Nanoindentation was conducted at room and elevated temperatures. While there seems little correlation between the tribofilm hardness and tribological behavior, a higher modulus generally leads to better friction and wear performance. Interestingly, a lower P/S2 ratio tends to reduce friction and improve wear protection, which is inmore » an opposite trend as reported for bulk materials. Ultimately, this is likely attributable to the dynamic, self-healing characteristics of tribofilms.« less

  15. ELECTROSPUN MESOFIBERS, A NOVEL BIODEGRADABLE PHEROMONE DISPENSER TECHNOLOGY, ARE COMBINED WITH MECHANICAL DEPLOYMENT FOR EFFICIENT IPM OF LOBESIA BOTRANA IN VINEYARDS.

    PubMed

    Hummel, Hans E; Langner, S S; Breuer, M

    2015-01-01

    Behaviour modifying pheromones are well known agents for disrupting mating communication of pest insects. For optimal activity, they must be dispensed in time and space at a quantitatively measurable, predetermined release rate covering the flight period of the target species. Pheromones appeal to environmentally conscientious entomologists for their biodegradability, non-toxicity and ecological compatibility. In attempts of combining the virtues of pheromones, suitable slow release dispensers, and their mechanical deployment, an ecologically sensible, reasonably priced and patented procedure was developed and tested with the vineyard pest Lobesia botrana (Lep.: Tortricidae). It is characterized by (1) Electrospun mesofibers with diameters ranging from 0.6 to 3.5 micrometres, containing disruptants and dispensing it by slow release diffusion into the crop, (2) simultaneous application of the fully biodegradable combination of pheromone with Ecoflex polyester mesofiber, (3) combination of mechanical deployment by multi-purpose cultivators of the prefabricated pheromone dispensers with other simultaneous cultivation measures, and thus further reducing labour time and treatment costs. The dispensers are biodegradable within half a year without leaving any objectionable residues. In the standard eco-toxicology tests pheromone dispensers are harmless to non-target organisms. The disruptive effect of one treatment lasts for seven weeks which covers well one of several flight periods of L. botrana.

  16. Design and validation of a novel bioreactor principle to combine online micro-computed tomography monitoring and mechanical loading in bone tissue engineering.

    PubMed

    Hagenmüller, Henri; Hitz, Marco; Merkle, Hans P; Meinel, Lorenz; Müller, Ralph

    2010-01-01

    Mechanical loading plays an important role in bone remodeling in vivo and, therefore, has been suggested as a key parameter in stem cell-based engineering of bone-like tissue in vitro. However, the optimization of loading protocols during stem cell differentiation and subsequent bone-like tissue formation is challenged by multiple input factors, which are difficult to control and validate. These include the variable cellular performance of cells harvested from different patients, nonstandardized culture media components, the choice of the biomaterial forming the scaffold, and its morphology, impacting a broader validity of mechanical stimulation regimens. To standardize the cell culture of bone-like tissue constructs, we suggest the involvement of time-lapsed feedback loops. For this purpose we present a prototype bioreactor that combines online, nondestructive monitoring using micro-computed tomography and direct mechanical loading of three-dimensional tissue engineering constructs. Validation of this system showed displacement steps down to 1 microm and cyclic sinusoidal loadings of up to 10 Hz. Load detection resolution was 0.01 N, and micro-computed tomography data were of high quality. For the first time, the developed bioreactor links time-lapsed, nondestructive, and dynamic imaging with mechanical stimulation, designed for cell culture under sterile conditions. This system is believed to substantially improve today's experimental options to study and optimize osteogenic stem cell culture and differentiation at the interface with mechanical stimulation.

  17. A MRI-Compatible Combined Mechanical Loading and MR Elastography Setup to Study Deformation-Induced Skeletal Muscle Damage in Rats

    PubMed Central

    de Graaf, Larry; Traa, Willeke A.; Schreurs, Tom J. L.; Moerman, Kevin M.; Nederveen, Aart J.; Sinkus, Ralph; Oomens, Cees W. J.; Nicolay, Klaas; Strijkers, Gustav J.

    2017-01-01

    Deformation of skeletal muscle in the proximity of bony structures may lead to deep tissue injury category of pressure ulcers. Changes in mechanical properties have been proposed as a risk factor in the development of deep tissue injury and may be useful as a diagnostic tool for early detection. MRE allows for the estimation of mechanical properties of soft tissue through analysis of shear wave data. The shear waves originate from vibrations induced by an external actuator placed on the tissue surface. In this study a combined Magnetic Resonance (MR) compatible indentation and MR Elastography (MRE) setup is presented to study mechanical properties associated with deep tissue injury in rats. The proposed setup allows for MRE investigations combined with damage-inducing large strain indentation of the Tibialis Anterior muscle in the rat hind leg inside a small animal MR scanner. An alginate cast allowed proper fixation of the animal leg with anatomical perfect fit, provided boundary condition information for FEA and provided good susceptibility matching. MR Elastography data could be recorded for the Tibialis Anterior muscle prior to, during, and after indentation. A decaying shear wave with an average amplitude of approximately 2 μm propagated in the whole muscle. MRE elastograms representing local tissue shear storage modulus Gd showed significant increased mean values due to damage-inducing indentation (from 4.2 ± 0.1 kPa before to 5.1 ± 0.6 kPa after, p<0.05). The proposed setup enables controlled deformation under MRI-guidance, monitoring of the wound development by MRI, and quantification of tissue mechanical properties by MRE. We expect that improved knowledge of changes in soft tissue mechanical properties due to deep tissue injury, will provide new insights in the etiology of deep tissue injuries, skeletal muscle damage and other related muscle pathologies. PMID:28076414

  18. A Combination Fluorescence Assay Demonstrates Increased Efflux Pump Activity as a Resistance Mechanism in Azole-Resistant Vaginal Candida albicans Isolates

    PubMed Central

    Bhattacharya, Somanon; Sobel, Jack D.

    2016-01-01

    Candida albicans is a pathogenic fungus causing vulvovaginal candidiasis (VVC). Azole drugs, such as fluconazole, are the most common treatment for these infections. Recently, azole-resistant vaginal C. albicans isolates have been detected in patients with recurring and refractory vaginal infections. However, the mechanisms of resistance in vaginal C. albicans isolates have not been studied in detail. In oral and systemic resistant isolates, overexpression of the ABC transporters Cdr1p and Cdr2p and the major facilitator transporter Mdr1p is associated with resistance. Sixteen fluconazole-susceptible and 22 fluconazole-resistant vaginal C. albicans isolates were obtained, including six matched sets containing a susceptible and a resistant isolate, from individual patients. Using quantitative real-time reverse transcriptase PCR (qRT-PCR), 16 of 22 resistant isolates showed overexpression of at least one efflux pump gene, while only 1 of 16 susceptible isolates showed such overexpression. To evaluate the pump activity associated with overexpression, an assay that combined data from two separate fluorescent assays using rhodamine 6G and alanine β-naphthylamide was developed. The qRT-PCR results and activity assay results were in good agreement. This combination of two fluorescent assays can be used to study efflux pumps as resistance mechanisms in clinical isolates. These results demonstrate that efflux pumps are a significant resistance mechanism in vaginal C. albicans isolates. PMID:27431223

  19. Combined Spectroscopic and Calorimetric Studies to Reveal Absorption Mechanisms and Conformational Changes of Protein on Nanoporous Biomaterials

    PubMed Central

    Ahmadi, Saharnaz; Farokhi, Maryam; Padidar, Parisa; Falahati, Mojtaba

    2015-01-01

    In this study the effect of surface modification of mesoporous silica nanoparticles (MSNs) on its adsorption capacities and protein stability after immobilization of beta-lactoglobulin B (BLG-B) was investigated. For this purpose, non-functionalized (KIT-6) and aminopropyl-functionalized cubic Ia3d mesoporous silica ([n-PrNH2-KIT-6]) nanoparticles were used as nanoporous supports. Aminopropyl-functionalized mesoporous nanoparticles exhibited more potential candidates for BLG-B adsorption and minimum BLG leaching than non-functionalized nanoparticles. It was observed that the amount of adsorbed BLG is dependent on the initial BLG concentration for both KIT-6 and [n-PrNH2-KIT-6] mesoporous nanoparticles. Also larger amounts of BLG-B on KIT-6 was immobilized upon raising the temperature of the medium from 4 to 55 °C while such increase was undetectable in the case of immobilization of BLG-B on the [n-PrNH2-KIT-6]. At temperatures above 55 °C the amounts of adsorbed BLG on both studied nanomaterials decreased significantly. By Differential scanning calorimetry or DSC analysis the heterogeneity of the protein solution and increase in Tm may indicate that immobilization of BLG-B onto the modified KIT-6 results in higher thermal stability compared to unmodified one. The obtained results provide several crucial factors in determining the mechanism(s) of protein adsorption and stability on the nanostructured solid supports and the development of engineered nano-biomaterials for controlled drug-delivery systems and biomimetic interfaces for the immobilization of living cells. PMID:26230687

  20. Time-frequency methods and voluntary ramped-frequency breathing: a powerful combination for exploration of human neurophysiological mechanisms

    PubMed Central

    Stankovski, Tomislav; Cooke, William H.; Rudas, László; Stefanovska, Aneta

    2013-01-01

    We experimentally altered the timing of respiratory motoneuron activity as a means to modulate and better understand otherwise hidden human central neural and hemodynamic oscillatory mechanisms. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations, and muscle sympathetic nerve activity in 13 healthy supine young men who gradually increased or decreased their breathing frequencies between 0.05 and 0.25 Hz over 9-min periods. We analyzed results with traditional time- and frequency-domain methods, and also with time-frequency methods (wavelet transform, wavelet phase coherence, and directional coupling). We determined statistical significance and identified frequency boundaries by comparing measurements with randomly generated surrogates. Our results support several major conclusions. First, respiration causally modulates both sympathetic (weakly) and vagal motoneuron (strongly) oscillations over a wide frequency range—one that extends well below the frequency of actual breaths. Second, breathing frequency broadly modulates vagal baroreflex gain, with peak gains registered in the low frequency range. Third, breathing frequency does not influence median levels of sympathetic or vagal activity over time. Fourth, phase relations between arterial pressure and sympathetic and vagal motoneurons are unaffected by breathing, and are therefore likely secondary to intrinsic responsiveness of these motoneurons to other synaptic inputs. Finally, breathing frequency does not affect phase coherence between diastolic pressure and muscle sympathetic oscillations, but it augments phase coherence between systolic pressure and R-R interval oscillations over a limited portion of the usual breathing frequency range. These results refine understanding of autonomic oscillatory processes and those physiological mechanisms known as the human respiratory gate. PMID:24114700

  1. A combined binding mechanism of nonionic ethoxylated surfactants to bovine serum albumin revealed by fluorescence and circular dichroism.

    PubMed

    Iovescu, Alina; Băran, Adriana; Stîngă, Gabriela; Cantemir-Leontieş, Anca Ruxandra; Maxim, Monica Elisabeta; Anghel, Dan Florin

    2015-12-01

    The study systematically investigates aqueous mixtures of fixed bovine serum albumin (BSA) and various ethoxylated nonionic surfactants belonging to a homologous series or not. Mono-disperse tetra-(C12E4), hexa-(C12E6) and octa-ethyleneglycol mono-n-dodecyl ether (C12E8), and poly-disperse eicosa-ethyleneglycol mono-n-tetradecyl ether (C14EO20) are respectively employed. Fluorescence and circular dichroism measurements are performed at surfactant/protein molar ratios (rm)s lower and higher than one. We aim to get new insights into the binding mechanism of these species and to differentiate among the interaction abilities of these surfactants. The relative magnitude of the binding thermodynamic parameters by fluorescence, and the increase of α-helix prove that hydrogen bonding drives the interaction next to the hydrophobic attraction. C12En (n=4,6,8) develop more H bonds with the albumin than C14EO20 owing to a zigzag conformation of their short ethyleneoxide chains. Among the homologous surfactants, C12E6 has a slightly stronger interaction with BSA due to a maximal number of H bonds at a minimal hindering. Static fluorescence and dynamic fluorescence indicate an inter-conversion between the tryptophan (Trp) rotamers which happens around the surfactants critical micellar concentration. For C14EO20, the meander conformation of the polar group determines a less evident conversion of the Trp rotamers and smaller α-helix rise. Binding isotherms of the homologous surfactants and the fluorescence quenching mechanism by C12E6 are also provided.

  2. Combined Spectroscopic and Calorimetric Studies to Reveal Absorption Mechanisms and Conformational Changes of Protein on Nanoporous Biomaterials.

    PubMed

    Ahmadi, Saharnaz; Farokhi, Maryam; Padidar, Parisa; Falahati, Mojtaba

    2015-07-29

    In this study the effect of surface modification of mesoporous silica nanoparticles (MSNs) on its adsorption capacities and protein stability after immobilization of beta-lactoglobulin B (BLG-B) was investigated. For this purpose, non-functionalized (KIT-6) and aminopropyl-functionalized cubic Ia3d mesoporous silica ([n-PrNH2-KIT-6]) nanoparticles were used as nanoporous supports. Aminopropyl-functionalized mesoporous nanoparticles exhibited more potential candidates for BLG-B adsorption and minimum BLG leaching than non-functionalized nanoparticles. It was observed that the amount of adsorbed BLG is dependent on the initial BLG concentration for both KIT-6 and [n-PrNH2-KIT-6] mesoporous nanoparticles. Also larger amounts of BLG-B on KIT-6 was immobilized upon raising the temperature of the medium from 4 to 55 °C while such increase was undetectable in the case of immobilization of BLG-B on the [n-PrNH2-KIT-6]. At temperatures above 55 °C the amounts of adsorbed BLG on both studied nanomaterials decreased significantly. By Differential scanning calorimetry or DSC analysis the heterogeneity of the protein solution and increase in Tm may indicate that immobilization of BLG-B onto the modified KIT-6 results in higher thermal stability compared to unmodified one. The obtained results provide several crucial factors in determining the mechanism(s) of protein adsorption and stability on the nanostructured solid supports and the development of engineered nano-biomaterials for controlled drug-delivery systems and biomimetic interfaces for the immobilization of living cells.

  3. Fracture mechanics evaluation of progressive fatigue damage in a circular-hole-notched GRP composite under combined tension/torsion loading

    NASA Astrophysics Data System (ADS)

    Takemura, Kenichi; Fujii, Toru

    Progressive failure from a circular hole in glass-fiber-reinforced plastics (GRP) under combined tension/torsion cyclic loading has been investigated. Thin-walled tubular specimens were used. The composition of the specimens was the same as in previous work. As pseudo-crack growth was observed under fatigue loading leading to the final failure, fracture mechanics methods were applied to characterize the fatigue failure process. The energy release rate was used as a parameter for progressive failure. Fatigue life under combined cyclic loading was estimated on the basis of the relationship between pseudo-crack-growth rate and energy release rate. The prediced S/N lines agree with the experimental results in all except a few cases.

  4. Mechanisms behind injecting the combination of nano-clay particles and polymer solution for enhanced oil recovery

    NASA Astrophysics Data System (ADS)

    Khalili Nezhad, Seyyed Shahram; Cheraghian, Goshtasp

    2016-08-01

    Laboratory investigations and field applications have proved injection of polymer solution to be an effective means to improve oil recovery for reservoirs of medium oil viscosity. The incremental oil produced in this case is the result of an increase in areal and vertical sweep efficiencies. Biopolymers and synthetic polymers are the major categories used in the petroleum industry for specific reasons. Biopolymers like xanthan are limited in their application as they are more susceptible to biodegradation. Synthetic polymers like Hydrolyzed PolyAcrylaMide (HPAM) have a much wider application as they are less susceptible to biodegradation. Furthermore, development of nanotechnology has successfully provided technical and economical viable alternatives for present materials. The objective of this study is to investigate the effect of combining clay nanoparticles with polymer solution on oil recovery. This paper includes a history match of both one-dimensional and two-dimensional polymer floods using a three-dimensional numerical model for fluid flow and mass transport. Results indicated that the amount of polymer adsorption decreased when clay nanoparticles were added to the PolyAcrylaMide solution; however, mobility ratio improvement is believed to be the main contributor for the proposed method in order to enhance much oil recovery compared to xanthan flood and HPAM flood.

  5. The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

    PubMed

    Fu, Qiang; Deng, Chen-Liang; Zhao, Ren-Yan; Wang, Ying; Cao, Yilin

    2014-01-01

    Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen.

  6. Improving thermal dewatering characteristics of mechanically dewatered sludge: response surface analysis of combined lime-heat treatment.

    PubMed

    Tunçal, Tolga

    2011-05-01

    In this study, disintegration of dewatered sludge (dry solids content [DS%] = 23 +/- 2) was studied to assess the possibility of enhancing the overall performance of a thermal dewatering processes. Powdered lime was used as an alkaline disintegrator. The combined effects of drying temperature, powdered lime dosage, and organic content on the thermal drying rate of dewatered sludge were investigated in a full-scale wastewater treatment plant. Effects of selected design parameters on the sludge drying rate were modeled using a response surface method. In addition, the possible interaction between lost on ignition and total organic carbon parameters also was investigated statistically. Specific resistance to filtration and free water contents of raw and disintegrated mixed sludge (DS% = 1.0 to 1.8) samples were compared statistically. The obtained results indicated that all of the selected design parameters have a significant effect on thermal dewatering characteristics, and the alkaline disintegration technique could remarkably improve thermal evaporation rate of dewatered sludge. These results are important because they could help to establish a sustainable sludge management model, which is critical in reducing environmental health risks.

  7. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    PubMed

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production.

  8. Development of a 3D parallel mechanism robot arm with three vertical-axial pneumatic actuators combined with a stereo vision system.

    PubMed

    Chiang, Mao-Hsiung; Lin, Hao-Ting

    2011-01-01

    This study aimed to develop a novel 3D parallel mechanism robot driven by three vertical-axial pneumatic actuators with a stereo vision system for path tracking control. The mechanical system and the control system are the primary novel parts for developing a 3D parallel mechanism robot. In the mechanical system, a 3D parallel mechanism robot contains three serial chains, a fixed base, a movable platform and a pneumatic servo system. The parallel mechanism are designed and analyzed first for realizing a 3D motion in the X-Y-Z coordinate system of the robot's end-effector. The inverse kinematics and the forward kinematics of the parallel mechanism robot are investigated by using the Denavit-Hartenberg notation (D-H notation) coordinate system. The pneumatic actuators in the three vertical motion axes are modeled. In the control system, the Fourier series-based adaptive sliding-mode controller with H(∞) tracking performance is used to design the path tracking controllers of the three vertical servo pneumatic actuators for realizing 3D path tracking control of the end-effector. Three optical linear scales are used to measure the position of the three pneumatic actuators. The 3D position of the end-effector is then calculated from the measuring position of the three pneumatic actuators by means of the kinematics. However, the calculated 3D position of the end-effector cannot consider the manufacturing and assembly tolerance of the joints and the parallel mechanism so that errors between the actual position and the calculated 3D position of the end-effector exist. In order to improve this situation, sensor collaboration is developed in this paper. A stereo vision system is used to collaborate with the three position sensors of the pneumatic actuators. The stereo vision system combining two CCD serves to measure the actual 3D position of the end-effector and calibrate the error between the actual and the calculated 3D position of the end-effector. Furthermore, to

  9. Reaction Mechanism of N-Acetylneuraminic Acid Lyase Revealed by a Combination of Crystallography, QM/MM Simulation, and Mutagenesis

    PubMed Central

    2014-01-01

    N-Acetylneuraminic acid lyase (NAL) is a Class I aldolase that catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac). Aldolases are finding increasing use as biocatalysts for the stereospecific synthesis of complex molecules. Incomplete understanding of the mechanism of catalysis in aldolases, however, can hamper development of new enzyme activities and specificities, including control over newly generated stereocenters. In the case of NAL, it is clear that the enzyme catalyzes a Bi-Uni ordered condensation reaction in which pyruvate binds first to the enzyme to form a catalytically important Schiff base. The identity of the residues required for catalysis of the condensation step and the nature of the transition state for this reaction, however, have been a matter of conjecture. In order to address, this we crystallized a Y137A variant of the E. coli NAL in the presence of Neu5Ac. The three-dimensional structure shows a full length sialic acid bound in the active site of subunits A, B, and D, while in subunit C, discontinuous electron density reveals the positions of enzyme-bound pyruvate and ManNAc. These ‘snapshot’ structures, representative of intermediates in the enzyme catalytic cycle, provided an ideal starting point for QM/MM modeling of the enzymic reaction of carbon–carbon bond formation. This revealed that Tyr137 acts as the proton donor to the aldehyde oxygen of ManNAc during the reaction, the activation barrier is dominated by carbon–carbon bond formation, and proton transfer from Tyr137 is required to obtain a stable Neu5Ac-Lys165 Schiff base complex. The results also suggested that a triad of residues, Tyr137, Ser47, and Tyr110 from a neighboring subunit, are required to correctly position Tyr137 for its function, and this was confirmed by site-directed mutagenesis. This understanding of the mechanism and geometry of the transition states along the C

  10. Kinetic analysis of acid orange 7 degradation by pulsed discharge plasma combined with activated carbon and the synergistic mechanism exploration.

    PubMed

    Guo, He; Wang, Huijuan; Wu, Qiangshun; Zhou, Guangshun; Yi, Chengwu

    2016-09-01

    The synergistic technique of pulsed discharge plasma (PDP) and activated carbon (AC) was built to investigate the kinetics of acid orange 7 (AO7) degradation under different conditions of AC addition, electrode gap, initial pH value of solution, gas variety and gas flow rate. Emission spectra of OH and O, UV-vis absorption spectra of the AO7 solution and TOC removal were measured to illustrate the synergistic mechanism of the PDP and the AC. The obtained results indicated that the kinetic constant of AO7 degradation increased from 0.00947 min(-1) to 0.01419 min(-1) when 4 g AC was added into the PDP system; AO7 degradation was higher in the case of alkaline solution when oxygen was used as the flow gas in the PDP/AC system, 2 L/min oxygen flow was more favorable for the degradation. Results of the relative emission intensities of OH and O indicated the catalytic effect of the AC on the active species formation as well as the important role of the two radicals for the AO7 degradation. There was no new peaks appeared by the UV-vis analysis of the AO7 solution after 60 min treatment. The highest TOC removal in the PDP/AC system was 30.3%, which was achieved under the condition of 4 L/min air flow rate and 3 initial pH value.

  11. Unfolding the mechanism of the AAA+ unfoldase VAT by a combined cryo-EM, solution NMR study

    PubMed Central

    Huang, Rui; Ripstein, Zev A.; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E.; Rubinstein, John L.

    2016-01-01

    The AAA+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous AAA+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded. PMID:27402735

  12. Chemoprotective epigenetic mechanisms in a colorectal cancer model: Modulation by n-3 PUFA in combination with fermentable fiber

    PubMed Central

    Triff, Karen; Kim, Eunjoo; Chapkin, Robert S.

    2015-01-01

    Colorectal cancer is the third major cause of cancer-related mortality in both men and women worldwide. The beneficial role of n-3 polyunsaturated fatty acids (PUFA) in preventing colon cancer is substantiated by experimental, epidemiological, and clinical data. From a mechanistic perspective, n-3 PUFA are pleiotropic and multifaceted with respect to their molecular mechanisms of action. For example, this class of dietary lipid uniquely modulates membrane and nuclear receptors, sensors/ion channels, and membrane structure/cytoskeletal function, thereby regulating signaling processes that influence patterns of gene expression and cell phenotype. In addition, n-3 PUFA can synergize with other potential chemoprotective agents known to reprogram the chromatin landscape, such as the fermentable fiber product, butyrate. Nutri-epigenomics is an emerging field of research that is focused on the interaction between nutrition and epigenetics. Epigenetics refers to a group of heterogeneous processes that regulate transcription without changing the DNA coding sequence, ranging from DNA methylation, to histone tail modifications and transcription factor activity. One implication of the nutri-epigenome is that it may be possible to reprogram epigenetic marks that are associated with increased disease risk by nutritional or lifestyle interventions. This review will focus on the nutri-epigenomic role of n-3 PUFA, particularly DHA, as well as the combinatorial effects of n-3 PUFA and fermentable fiber in relation to colon cancer. PMID:25938013

  13. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Haka, Abigail S.; Kramer, John R.; Dasari, Ramachandra R.; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ~40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque.

  14. Combined effect of pulse electron beam treatment and thin hydroxyapatite film on mechanical features of biodegradable AZ31 magnesium alloy

    NASA Astrophysics Data System (ADS)

    Surmeneva, M. A.; Tyurin, A. I.; Teresov, A. D.; Koval, N. N.; Pirozhkova, T. S.; Shuvarin, I. A.; Surmenev, R. A.

    2015-11-01

    The morphology, elemental, phase composition, nanohardness, and Young's modulus of the hydroxyapatite (HA) coating deposited via radio frequency (RF) magnetron sputtering onto the AZ31 surface were investigated by atomic force microscopy (AFM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and nanoindentationtechniques. The calcium phosphate (Ca/P) molar ratio of the HA coating deposited via RF-magnetron sputtering onto AZ31 substrates according to EDX was 1.57+0.03. The SEM experiments revealed significant differences in the morphology of the HA film deposited on untreated and treated with the pulsed electron beam (PEB) AZ31 substrate. Nanoindentation studies demonstrated significant differences in the mechanical responses of the HA film deposited on the initial and PEB-modified AZ31 substrates. The nanoindentation hardness and the Young's modulus of the HA film on the magnesium alloy modified using the PEB treatment were higher than that of the HA layer on the untreated substrate. Moreover, the HA film fabricated onto the PEB-treated surface was more resistant to plastic deformation than the same film on the untreated AZ31 surface.

  15. Combined approach to damaged wire ropes life-time assessment based on NDT results and rope mechanics

    NASA Astrophysics Data System (ADS)

    Vorontsov, A.; Volokhovsky, V.; Slesarev, D.

    2011-07-01

    Principles of strength assessment and life-time prediction of deteriorated wire ropes based on magnetic NDT technique are presented. The measured loss of metallic cross-section area due to abrasion, corrosion etc. and local wire breaks are treated as input data for mechanical model of rope structure. The rope is interpreted as a system with two degrees of freedom that enables to calculate the strains and stresses in each wire when the rope is subjected to tension, torsion and bending. Stress safety factor is considered as a generalized parameter that specifies the rope degradation and may be used for predicting the instant lifetimes during the rope operating history. The rope discard criterion refers to residual life-time calculated with respect to minimal allowable strength factor. Examples of integrity analysis of mine hoisting rope and jib crane rope under tension-bending fatigue loading are demonstrated. The residual strength estimates give the rope inspector further information that helps to make a valid decision on testing policy.

  16. Combined electromagnetic and permanent magnet undulator to achieve higher field and easier field variation without mechanical movement

    SciTech Connect

    Bogachenkov, V.A.; Papadichev, V.A.

    1995-12-31

    Hybrid or pure permanent magnet undulators (PMU) are widely used because they have high field quality, allow easy field correction and do not consume power. Their main drawback is the necessity of moving one half of the magnet relative to the other to change field value, which requires a high precision, remotely controlled (and thus costly) driving system On the other hand, electromagnetic undulatory (EMU) have no problem with field variation, but consume too much power (100 - 400 kW) for high fields. Adding permanent magnets to EMU results in a considerable decrease of power consumption, while retaining the advantage of easily changing field level. A model of a CW combined EM+PM plane undulator having a 4.8 cm period and 8 periods long is described. It is simple in design and cheap in manufacturing: magnet yokes are made of soft steel rings in which 1.6 cm air gaps were cut to form pole faces. Odd yokes are placed to one side of the undulator axis and even yokes to the other with the air gaps on the axis. Each set of yokes is excited by its own separate winding of simple racetrack shape. Undulator deflection parameter K = 1.1 (B = 2.4 kG) can be reached at a 0.78kW power level, i.e., less than 100 W per period, while without PM only a maximum K = 0.8 can be obtained and requires 4 kW power. No water cooling is needed, which greatly simplifies undulator design. The undulator was not optimized relative to the axial-air-gap to ring-width ratio: one might expect some increase in field level for thinner rings. Field amplitude depends also on relative transverse position of odd and even pole faces.

  17. Combining displacement field and grip force information to determine mechanical properties of planar tissue with complicated geometry.

    PubMed

    Nagel, Tina M; Hadi, Mohammad F; Claeson, Amy A; Nuckley, David J; Barocas, Victor H

    2014-11-01

    Performing planar biaxial testing and using nominal stress-strain curves for soft-tissue characterization is most suitable when (1) the test produces homogeneous strain fields, (2) fibers are aligned with the coordinate axes, and (3) strains are measured far from boundaries. Some tissue types [such as lamellae of the annulus fibrosus (AF)] may not allow for these conditions to be met due to their natural geometry and constitution. The objective of this work was to develop and test a method utilizing a surface displacement field, grip force-stretch data, and finite-element (FE) modeling to facilitate analysis of such complex samples. We evaluated the method by regressing a simple structural model to simulated and experimental data. Three different tissues with different characteristics were used: Superficial pectoralis major (SPM) (anisotropic, aligned with axes), facet capsular ligament (FCL) (anisotropic, aligned with axes, bone attached), and a lamella from the AF (anisotropic, aligned off-axis, bone attached). We found that the surface displacement field or the grip force-stretch data information alone is insufficient to determine a unique parameter set. Utilizing both data types provided tight confidence regions (CRs) of the regressed parameters and low parameter sensitivity to initial guess. This combined fitting approach provided robust characterization of tissues with varying fiber orientations and boundaries and is applicable to tissues that are poorly suited to standard biaxial testing. The structural model, a set of C++ finite-element routines, and a Matlab routine to do the fitting based on a set of force/displacement data is provided in the on-line supplementary material.

  18. Combining biochemical with (1)H NMR-based metabolomics approach unravels the antidiabetic activity of genipin and its possible mechanism.

    PubMed

    Shen, Xiao-Li; Liu, Huan; Xiang, Huan; Qin, Xue-Mei; Du, Guan-Hua; Tian, Jun-Sheng

    2016-09-10

    Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins. Genipin possesses a wide spectrum of biological activities including ameliorating effects on diabetes, but the definite mechanism of this effect remains unknown. To investigate the antidiabetic activities of genipin and explore the biochemical changes of serum endogenous metabolites on diabetic rats induced by alloxan, (1)H NMR spectroscopy coupled with multivariate data analysis was used to. All rats were randomly divided into six groups including negative control (NC) group, diabetic mellitus (DM) group, metformin hydrochloride group, high dose group of genipin, middle dose group of genipin and low dose group of genipin. Diabetes was induced by a single intraperitoneal injection of 120mg/kg body weight of alloxan. Serum samples were collected for the (1)H NMR-based metabolomics and clinical biochemical analysis. Daily oral administration of genipin (25, 50 and 100mg/kg body weight) and metformin hydrochloride (125mg/kg) for two weeks showed beneficial effects on blood glucose level (P<0.01). Significant differences in the metabolic profile as well as the result of biochemical parameters between the diabetic group and the control group were observed. The PLS-DA scores and corresponding loading plots demonstrated that genipin significantly restored the abnormal metabolic state. Detailed analysis of the altered metabolite levels indicated that genipin significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism and amino acid metabolism. Genipin showed the best anti-diabetic effects at a dose of 100mg/kg in rats. This finding indicates that chemical and metabolomic approaches could be powerful tools for the investigation of the biochemical changes in pathological conditions or drug treatment.

  19. Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.

    PubMed

    Wiciński, Michał; Węclewicz, Mateusz M; Miętkiewicz, Mateusz; Malinowski, Bartosz; Grześk, Elżbieta; Klonowska, Joanna

    2017-03-01

    Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.

  20. COMBINED THEORETICAL AND EXPERIMENTAL INVESTIGATION OF MECHANISMS AND KINETICS OF VAPOR-PHASE MERCURY UPTAKE BY CARBONACOUES SURFACES

    SciTech Connect

    Radisav D. Vidic

    2002-05-01

    The first part of this study evaluated the application of a versatile optical technique to study the adsorption and desorption of model adsorbates representative of volatile polar (acetone) and non-polar (propane) organic compounds on a model carbonaceous surface under ultra high vacuum (UHV) conditions. The results showed the strong correlation between optical differential reflectance (ODR) and adsorbate coverage determined by temperature programmed desorption (TPD). ODR technique was proved to be a powerful tool to investigate surface adsorption and desorption from UHV to high pressure conditions. The effects of chemical functionality and surface morphology on the adsorption/desorption behavior of acetone, propane and mercury were investigated for two model carbonaceous surfaces, namely air-cleaved highly oriented pyrolytic graphite (HOPG) and plasma-oxidized HOPG. They can be removed by thermal treatment (> 500 K). The presence of these groups almost completely suppresses propane adsorption at 90K and removal of these groups leads to dramatic increase in adsorption capacity. The amount of acetone adsorbed is independent of surface heat treatment and depends only on total exposure. The effects of morphological heterogeneity is evident for plasma-oxidized HOPG as this substrate provides greater surface area, as well as higher energy binding sites. Mercury adsorption at 100 K on HOPG surfaces with and without chemical functionalities and topological heterogeneity created by plasma oxidation occurs through physisorption. The removal of chemical functionalities from HOPG surface enhances mercury physisorption. Plasma oxidation of HOPG provides additional surface area for mercury adsorption. Mercury adsorption by activated carbon at atmospheric pressure occurs through two distinct mechanisms, physisorption below 348 K and chemisorption above 348 K. No significant impact of oxygen functionalities was observed in the chemisorption region. The key findings of this study

  1. Resolving the mechanism of bacterial inhibition by plant secondary metabolites employing a combination of whole-cell biosensors.

    PubMed

    Chan, Andrea C; Ager, Duane; Thompson, Ian P

    2013-06-01

    Tightening regulations regarding the use of biocides have stimulated interest in investigating alternatives to current antimicrobial strategies. Plant essential oils and their constituent compounds are promising candidates as novel antimicrobial agents because of their excellent ability in killing microbes while being non-toxic to humans at antimicrobially-active concentrations. Allyl isothiocyanate (AIT), carvacrol, cinnamaldehyde (CNAD), citral, and thymol were investigated for their antibacterial activity against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The five compounds were screened via disc diffusion assay and broth microdilution method, by which inhibition zone diameters, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs) were determined. AIT and CNAD displayed the greatest inhibitory effects against all species tested, with AIT yielding MICs of 156.25mg/L and MBCs of 156.25 to 312.5mg/L, and CNAD yielding MICs of 78.125 to 156.25mg/L and MBCs of 78.125 to 312.5mg/L. Based on these results, AIT and CNAD were selected for closer examination of their toxic effects. Two complementary bioluminescence-based bacterial biosensors, E. coli HB101_pUCD607_lux and Acinetobacter baylyi ADP1_recA_lux, were employed to examine the dose-response relationships and mechanism of action of AIT and CNAD. This is the first reported study to employ a lux-based biosensor assay coupled with parallel plate count experiments to demonstrate that AIT and CNAD not only damaged cell membranes, but also disrupted cellular metabolism and energy production in bacteria. It is also the first to use genotoxicity-sensing whole-cell bioreporters to demonstrate that neither AIT nor CNAD induced expression of the universal DNA repair gene, recA. This suggests that AIT and CNAD were not genotoxic. As an antimicrobial agent, it is advantageous that the compound be genetically non-damaging so that toxicity towards

  2. Mechanical and chemical processes affecting the chalk during burial, insights from combined reflection seismics, well data and field work

    NASA Astrophysics Data System (ADS)

    Moreau, Julien; Boussaha, Myriam; Nielsen, Lars; Thibault, Nicolas; Stemmerik, Lars

    2014-05-01

    The chalk must undergo several phases of grain reorganisation and chemical reactions during its diagenetic evolution from a carbonaceous ooze to a sedimentary rock. Some of these transformations could be observed on structures from the kilometre- to the micrometre-scale with seismic reflection and cores analyses, respectively. However, few sites allow to combine all the different scale of observation for chalk diagenesis. Onshore and offshore high resolution seismics, two fully cored >350 m wells with wireline logging tools and very high quality exposures from a coastal cliff and a quarry form such an exceptional dataset in the Stevns peninsula area, eastern Danish Basin (Denmark). The studied chalk interval in the area is of Maastrichtian to Danian age. The chalk has been divided in 4 lithofacies, chalk-marl alternations, white chalk, white chalk with flint layers and bryozoan chalk. Advanced stratigraphic works have been performed with astronomical calibration based on stable isotope stratigraphy, wireline logs as well as several palaeontological proxies and detailed sedimentological analysis. Since a couple of decades, a specific kind of fractures has been described in the Chalk of Denmark, the so-called hairline fractures. They have recently been interpreted as compaction bands associated with the pore collapse of the chalk. We have observed these fractures on the field and on the cores in specific intervals. At depth, these fractures are in genetic relation with the formation of some stylolithes. The pressure-solution allows the formation of carbonate seams in the hairline fractures. At larger scale, on the field are observed faults which are sealed with flint precipitations. They slightly offset (<1 m) strata underlined by flint bands. On the onshore and offshore seismic reflection profiles, numerous strata-bound faults form noisy intervals as well as amplitude anomalies. Their normal offsets are less than 25 m. Their branching patterns, and their restriction

  3. Probability of pipe fracture in the primary coolant loop of a PWR plant. Volume 5. Probabilistic fracture mechanics analysis. Load Combination Program Project I final report

    SciTech Connect

    Harris, D.O.; Lim, E.Y.; Dedhia, D.D.

    1981-06-01

    The primary purpose of the Load Combination Program covered in this report is to estimate the probability of a seismic induced LOCA in the primary piping of a commercial pressurized water reactor (PWR). Best estimates, rather than upper bound results are desired. This was accomplished by use of a fracture mechanics model that employs a random distribution of initial cracks in the piping welds. Estimates of the probability of cracks of various sizes initially existing in the welds are combined with fracture mechanics calculations of how these cracks would grow during service. This then leads to direct estimates of the probability of failure as a function of time and location within the piping system. The influence of varying the stress history to which the piping is subjected is easily determined. Seismic events enter into the analysis through the stresses they impose on the pipes. Hence, the influence of various seismic events on the piping failure probability can be determined, thereby providing the desired information.

  4. Determining the Mechanical Constitutive Properties of Metals as Function of Strain Rate and temperature: A Combined Experimental and Modeling Approach

    SciTech Connect

    Ian Robertson

    2007-04-28

    Development and validation of constitutive models for polycrystalline materials subjected to high strain-rate loading over a range of temperatures are needed to predict the response of engineering materials to in-service type conditions. To account accurately for the complex effects that can occur during extreme and variable loading conditions, requires significant and detailed computational and modeling efforts. These efforts must be integrated fully with precise and targeted experimental measurements that not only verify the predictions of the models, but also provide input about the fundamental processes responsible for the macroscopic response. Achieving this coupling between modeling and experiment is the guiding principle of this program. Specifically, this program seeks to bridge the length scale between discrete dislocation interactions with grain boundaries and continuum models for polycrystalline plasticity. Achieving this goal requires incorporating these complex dislocation-interface interactions into the well-defined behavior of single crystals. Despite the widespread study of metal plasticity, this aspect is not well understood for simple loading conditions, let alone extreme ones. Our experimental approach includes determining the high-strain rate response as a function of strain and temperature with post-mortem characterization of the microstructure, quasi-static testing of pre-deformed material, and direct observation of the dislocation behavior during reloading by using the in situ transmission electron microscope deformation technique. These experiments will provide the basis for development and validation of physically-based constitutive models. One aspect of the program involves the direct observation of specific mechanisms of micro-plasticity, as these indicate the boundary value problem that should be addressed. This focus on the pre-yield region in the quasi-static effort (the elasto-plastic transition) is also a tractable one from an

  5. Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: transcriptomic analysis using RNA-seq.

    PubMed

    Guo, Yue; Su, Zheng-Yuan; Zhang, Chengyue; Gaspar, John M; Wang, Rui; Hart, Ronald P; Verzi, Michael P; Kong, Ah-Ng Tony

    2017-03-03

    Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA+1% CUR were given to mice from 1 week prior to the AOM injection until the experiment was terminated 22 weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects

  6. Study of the mechanism of acetonitrile stacking and its application for directly combining liquid-phase microextraction with micellar electrokinetic chromatography.

    PubMed

    Sun, Jingru; Feng, Jing; Shi, Ludi; Liu, Laping; He, Hui; Fan, Yingying; Hu, Shibin; Liu, Shuhui

    2016-08-26

    Acetonitrile stacking is an online concentration method that is distinctive due to its inclusion of a high proportion of organic solvent in sample matrices. We previously designed a universal methodology for the combination of liquid-phase microextraction (LPME) and capillary electrophoresis (CE) using acetonitrile stacking and micellar electrokinetic chromatography (MEKC) mode, thereby achieving large-volume injection of the diluted LPME extractant and the online concentration. In this report, the methodology was extended to the analysis of highly substituted hydrophobic chlorophenols in wines using diethyl carbonate as the extractant. Additionally, the mechanism of acetonitrile stacking was studied. The results indicated that the combination of LPME and MEKC exhibited good analytical performance: with ∼40-fold concentration by LPME, a 20-cm (33% of the total length) sample plug injection of an eight-fold dilution of diethyl carbonate with the organic solvent-saline solution produced enrichments higher by a factor of 260-791. Limits of qualification ranged from 5.5 to 16.0ng/mL. Acceptable reproducibilities of lower than 1.8% for migration time and 8.6% for peak areas were obtained. A dual stacking mechanism of acetonitrile stacking was revealed, involving transient isotachophoresis plus pH-junction stacking. The latter was associated with a pH shift induced by the presence of acetonitrile. The pseudo-stationary phase (Brij-35) played an important role in reducing the CE running time by weakening the isotachophoretic migration of the analyte ions following Cl(-) ions. The combination of acetonitrile stacking and nonionic micelle-based MEKC appears to be a perfect match for introducing water-immiscible LPME extractants into an aqueous CE system and can thus significantly expand the application of LPME-CE in green analytical chemistry.

  7. The combined effect of aging and accumulative roll bonding on the evolution of the microstructure and mechanical characteristics of an Al-0.2 wt % Zr alloy

    NASA Astrophysics Data System (ADS)

    Azad, B.; Semnani, H. M.; Borhani, E.

    2017-01-01

    This work is devoted to the effect of processes initiated by the combined action of aging (A) and accumulative roll bonding (ARB) on the evolution of the microstructure and the mechanical characteristics of an Al-0.2 wt % Zr alloy. Upon solution treatment (ST), followed by aging at temperatures of 350 and 450°C, the specimens were subjected to deformation to a degree of deformation of 80% using ARB. The evolution of the microstructure was examined using atomic force microscopy and the mechanical characteristics of the specimens were determined using tensile tests and Vickers microhardness measurements. The results have shown that, upon ten ARB cycles, the grain size decreased to 0.3, 0.4, and 0.32 μm in the specimens subjected to ST followed by ARB (ST-ARB), ST followed by A at a temperature of 350°C and ARB (350°C-A-ARB), and ST followed by A at a temperature of 450°C and ARB (450°C-A-ARB), respectively. This study has also shown that the combined use of preliminary A and subsequent ARB holds promise in enhancing the mechanical characteristics of the alloy due to precipitates that appear in the course of annealing. Fracture surfaces of the rolled specimens subjected to the tensile tests were examined using scanning electron microscopy. The results of these examinations have shown that in the specimens subjected to ST followed by ARB brittle fracture has been observed at the stage of the final ARB cycles, while in the A-ARB specimens cleavage facets (sites of fracture over the cleavage plane) and river lines have appeared on the fracture surfaces.

  8. A versatile method for combining different biopolymers in a core/shell fashion by 3D plotting to achieve mechanically robust constructs.

    PubMed

    Akkineni, Ashwini Rahul; Ahlfeld, Tilman; Lode, Anja; Gelinsky, Michael

    2016-10-07

    Three-dimensional extrusion of two different biomaterials in a core/shell (c/s) fashion has gained much interest in the last couple of years as it allows for fabricating constructs with novel and interesting properties. We now demonstrate that combining high concentrated (16.7 wt%) alginate hydrogels as shell material with low concentrated, soft biopolymer hydrogels as core leads to mechanically stable and robust 3D scaffolds. Alginate, chitosan, gellan gum, gelatin and collagen hydrogels were utilized successfully as core materials-hydrogels which are too soft for 3D plotting of open-porous structures without an additional mechanical support. The respective c/s scaffolds were characterized concerning their morphology, mechanical properties and swelling behavior. It could be shown that core as well as shell part can be loaded with growth factors and that the release depends on core composition and shell thickness. Neither the plotting process nor the crosslinking with 1M CaCl2 denatured the proteins. When core and shell were loaded with different growth factors (VEGF and BMP-2, respectively) a dual release was achieved. Finally, live human endothelial cells were integrated in the core material, demonstrating that this new strategy can be used for bioprinting purposes as well.

  9. Combined Pharmacomechanical Thrombolysis of Complete Portomesenteric Thrombosis in a Liver Transplant Recipient

    SciTech Connect

    Lorenz, Jonathan M. Bennett, Shelby; Patel, Jay; Ha, Thuong G. Van; Funaki, Brian

    2013-01-30

    Treatment options for portomesenteric venous thrombosis range from anticoagulation to surgery, depending on chronicity, severity of symptoms, extent of thrombosis, and the availability of local expertise. For acute and subacute cases, a variety of endovascular options have been described in limited published series and case reports, including thrombolysis and mechanical thrombectomy. We report what is to our knowledge the first case in which the Trellis pharmacomechanical thrombolysis device was used successfully to treat complete acute thrombosis of the entire superior mesenteric vein and the entire portal vein with extension into all segmental intrahepatic portal branches in a young adult after liver transplantation. This device, coupled with adjunctive techniques using balloon catheters, facilitated complete restoration of flow, resulting in graft salvage and long-term patency.

  10. Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches

    PubMed Central

    Goicolea, Isabel; Vives-Cases, Carmen; Hurtig, Anna-Karin; Marchal, Bruno; Briones-Vozmediano, Erica; Otero-García, Laura; García-Quinto, Marta; San Sebastian, Miguel

    2015-01-01

    Background Health care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence. Methods A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software. Results The emerging programme theory highlighted the importance of the combination of each team’s self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence. Conclusions Interventions to improve primary health care teams’ response to intimate partner violence should focus on strengthening team’s self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the

  11. PD-L1 (B7-H1) and PD-1 Pathway Blockade for Cancer Therapy: Mechanisms, Response Biomarkers and Combinations

    PubMed Central

    Zou, Weiping; Wolchok, Jedd D.; Chen, Lieping

    2016-01-01

    PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable anti-tumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic and biological studies focused on the human cancer microenvironment have yielded significant insight into this issue. In this Review, we focus on tumor microenvironment; evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, microbiota, and their mechanisms of action and roles in shaping, being shaped and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment. PMID:26936508

  12. [Effect of propofol-based combined anesthesia on the development of adaptive mechanisms to the prolonged one-lung artificial ventilation].

    PubMed

    Kurilova, O A; Vyzhigina, M A; Sandrikov, V A; Mizikov, V M; Kulagina, T Iu; Zhukova, S G; Parshin, V D

    2010-01-01

    The paper deals with the assessment of the adequacy and safety of multicomponent anesthesia based on propofol at lung surgery requiring one-lung ventilation (OLV) in patients with chronic respiratory diseases and with the evaluation of the effect of propofol on the development of adaptive mechanisms in various ventilation modalities in thoracic surgery. The pressor, resistive, and volume characteristics of pulmonary blood flow, systemic and intracardiac hemodynamics under artificial ventilation (AV) and OLV of a duration of up to 1.5 hours by a combination of pulmonal and transpulmonal thermodilution on a PiCCO plus device with a VOLEF attachment were compared. Multicomponent balanced anesthesia based on continuous graduated propofol infusion provides adequate protection of patients during thoracic operations, including those with concomitant respiratory abnormality.

  13. [Investigating mechanism of toxicity reduction by combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata on terms of proteins self-assembly].

    PubMed

    Li, Bing-jie; Shen, Yong; Liao, Ri-tao; Gao, Guan-zhen; Ke, Li-jing; Zhou, Jian-wu; Rao, Ping-fan

    2015-02-01

    The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 ± 2.02) nm and (238.20 ± 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.

  14. Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy.

    PubMed

    Zhang, Zijiao; Sheng, Hongwei; Wang, Zhangjie; Gludovatz, Bernd; Zhang, Ze; George, Easo P; Yu, Qian; Mao, Scott X; Ritchie, Robert O

    2017-02-20

    Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dual function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness.

  15. Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy

    NASA Astrophysics Data System (ADS)

    Zhang, Zijiao; Sheng, Hongwei; Wang, Zhangjie; Gludovatz, Bernd; Zhang, Ze; George, Easo P.; Yu, Qian; Mao, Scott X.; Ritchie, Robert O.

    2017-02-01

    Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dual function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness.

  16. Atomic-scale and pit-free flattening of GaN by combination of plasma pretreatment and time-controlled chemical mechanical polishing

    SciTech Connect

    Deng, Hui; Endo, Katsuyoshi; Yamamura, Kazuya

    2015-08-03

    Chemical mechanical polishing (CMP) combined with atmospheric-pressure plasma pretreatment was applied to a GaN (0001) substrate. The irradiation of a CF{sub 4}-containing plasma was proven to be very useful for modifying the surface of GaN. When CMP was conducted on a plasma-irradiated surface, a modified layer of GaF{sub 3} acted as a protective layer on GaN by preventing the formation of etch pits. Within a short duration (8 min) of CMP using a commercially available CeO{sub 2} slurry, an atomically flat surface with a root mean square (rms) roughness of 0.11 nm was obtained. Moreover, etch pits, which are inevitably introduced in conventional CMP, could not be observed at the dislocation sites on the polished GaN surface. It was revealed that CMP combined with the plasma pretreatment was very effective for obtaining a pit-free and atomically flat GaN surface.

  17. Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy

    PubMed Central

    Zhang, Zijiao; Sheng, Hongwei; Wang, Zhangjie; Gludovatz, Bernd; Zhang, Ze; George, Easo P.; Yu, Qian; Mao, Scott X.; Ritchie, Robert O.

    2017-01-01

    Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dual function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness. PMID:28218267

  18. Influence of the Sol pH on Electrochemical and Mechanical Behaviors of Siloxane-PMMA Hybrid Films Combined with UV Ink

    NASA Astrophysics Data System (ADS)

    Kunst, Sandra Raquel; Longhi, Marielen; Baldin, Estela Knopp Kerstner; Boniatti, Rosiana; Beltrami, Lilian Vanessa Rossa; de Fraga Malfatti, Célia

    2017-01-01

    Pre-treatments with a siloxane-PMMA base have shown promising results when combined with the new ink technology with curing by ultraviolet (UV) radiation. Tinplate sheets were coated with a hybrid film obtained from a sol with alkoxides precursors consisting of 3-(trimethoxysilylpropyl) methacrylate and tetraethoxysilane and adding an organic phase composed of poly(methyl methacrylate). The hydrolysis reactions were catalyzed with a nitric acid solution (pH = 1 and pH = 3). The hybrid films were obtained by a dip-coating process, coated with red-colored paint UV curing and characterized for their electrochemical and mechanical behavior. The results showed that a more acidic pH (pH = 1) promotes the formation of a hybrid film with better protective properties, presented a better electrochemical performance and higher values of layer thickness. However, the hybrid film obtained with pH = 3 combined with the UV coating presented the best performance. This result is probably due to a better anchorage and adhesion verified in this sample.

  19. Mechanism of synergistic action of a combination of ampicillin and dicloxacillin against a beta-lactamase-producing strain of Citrobacter freundii.

    PubMed Central

    Mizoguchi, J; Suginaka, H; Kotani, S

    1979-01-01

    The mechanism of synergistic activity of a combination of ampicillin and dicloxacillin was studied on beta-lactamase-producing Citrobacter freundii GN346 and its derived beta-lactamaseless mutant GN346/16. The synergistic activity was exhibited against the parent strain but not against the mutant strain. Precultivation of the parent strain with the combination reduced the amount of the subsequent binding of [14C]penicillin G to the membrane fraction from the treated cells, but no reduction was observed in the case of cells treated with ampicillin or dicloxacillin alone. On the other hand, the amount of binding of [14C]penicillin G to the membrane fraction from the mutant strain was reduced by ampicillin treatment alone. These results clearly indicated that dicloxacillin inhibited the beta-lactamase activity produced by the parent strain, and, consequently, ampicillin can penetrate through the outer membrane and periplasmic beta-lactamase barrier into its target sites on the cytoplasmic membrane. PMID:316307

  20. The combined effects of BDE47 and BaP on oxidatively generated DNA damage in L02 cells and the possible molecular mechanism.

    PubMed

    An, Jing; Yin, Lingling; Shang, Yu; Zhong, Yufang; Zhang, Xinyu; Wu, Minghong; Yu, Zhiqiang; Sheng, Guoying; Fu, Jiamo; Huang, Yuecheng

    2011-04-03

    Polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) coexist widely in the environment and have generated adverse effects on the environment and human health. The purpose of this study was to investigate the combined toxic effects of these chemicals and the related mechanism. L02 cells were exposed to BDE47 (5, 10μmol/L) or/and BaP (50μmol/L) in different administration order. The cell growth and survival, DNA strand breaks, oxidative stress index (ROS, SOD, GSH, and MDA), LDH release and the expression level of CYP1 family members were measured. The result showed that BDE47 or/and BaP had no effect on the cell growth and survival under the present conditions. However, compared with the groups treated with BDE47 or BaP alone, the combined-treated groups induced significantly elevated DNA strand breaks, ROS production, and MDA level. Especially, pretreatment with BDE47 followed by BaP led to the strongest effects. Addition of the antioxidant N-acetyl-l-cysteine (NAC) markedly reduced the ROS level and partly suppressed the DNA strand breaks induced by BDE47 or/and BaP. Meanwhile, the combined treatment groups also markedly increased the SOD activity, GSH content, and LDH release level compared with the control group. The real-time PCR results showed that BaP could significantly induce the expression of CYP1A1 and CYP1B1, however, the pre-treatment with BDE47 appeared to attenuate the BaP-induced CYP1 expression. All of above findings indicated that BDE47 and BaP had a synergistic effect on oxidatively generated DNA damage in L02 cells via regulation on the oxidative stress response and the expression of CYP1 metabolism enzymes.

  1. Dislocation structure and mechanical behavior of Rh3X L12 intermetallic alloys: combined ab-initio-Peierls-Nabarro model approach

    NASA Astrophysics Data System (ADS)

    Kontsevoi, O. Yu.

    2005-03-01

    Alloys based on Pt-group metals are promising materials for ultra-high temperature applications. Among them, Rh-based alloys are attractive due to a combination of high melting point, strength and superior oxidation resistance. Unfortunately, there is no information about dislocation properties and mechanisms driving their mechanical behavior. We analyzed the structure and mobility of dislocations in Rh3X, where X = Ti, Zr, Hf, V, Nb, Ta, within the modified Peierls-Nabarro model with generalized stacking fault energetics calculated using the FLAPW methodootnotetextWimmer, Krakauer, Weinert, and Freeman, PRB 24, 864 (1981). Superdislocations with type I core structure (APB-bounded) are preferred in Rh3Ti and Rh3Ta, whereas superdislocations with type II core (SISF-bounded) are predicted in Rh3V and Rh3Nb. An unusual superdislocation core structure (SISF-bounded type II^' with different sequence of Shockley partials), resulting from the unstable APB energy, was found in Rh3Hf and Rh3Zr. Based on our analysis of dislocation structure and mobility, we provide predictions of temperature yield stress behavior of Rh-based intermetallics, and show that their dislocation properties are closely connected with features of the electronic structure and the instability of the L12 phase with respect to D019 and D024.

  2. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer.

    PubMed

    Bracci, L; Schiavoni, G; Sistigu, A; Belardelli, F

    2014-01-01

    Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

  3. Virtual screening of LPXTG competitive SrtA inhibitors targeting signal transduction mechanism in Bacillus anthracis: a combined experimental and theoretical study.

    PubMed

    Selvaraj, Chandrabose; Sivakamavalli, Jeyachandran; Baskaralingam, Vaseeharan; Singh, Sanjeev Kumar

    2014-06-01

    Members of the sortase enzyme super family decorate the surfaces of Bacillus anthracis cell wall with proteins that play key roles in microbial pathogenesis and its biofilm formation. Bacillus anthracis Sortase-A (Ba-SrtA) is a potential target for new therapeutics as it is required for B. anthracis survival and replication within macrophages. An understanding of the binding site pocket and substrate recognition mechanism by SrtA enzymes may serve to be beneficial in the rational development of sortase inhibitors. Here, the LPXTG signal peptide-based competitive inhibitors are screened against the Ba-SrtA and compounds with reasonable inhibition, specificity, and mechanisms of inactivation of SrtA have been covered. The screened compounds are experimentally validated against the phylogenetically similar Gram-positive pathogen B. cereus. In situ microscopic visualizations suggest that these screened compounds showed the microbial and biofilm inhibitory activity against B. cereus. It facilitates the further development of these molecules into useful anti-infective agents to treat infections caused by B. anthracis and other Gram-positive pathogens. These results provide insight into basic design principles for generating new clinically relevant lead molecules. It also provides an alternative strategy where a screened ligand molecule can be used in combination to battle increasingly against the Gram-positive pathogens.

  4. Stepwise Catalytic Mechanism via Short-Lived Intermediate Inferred from Combined QM/MM MERP and PES Calculations on Retaining Glycosyltransferase ppGalNAcT2

    PubMed Central

    Trnka, Tomáš; Kozmon, Stanislav; Tvaroška, Igor; Koča, Jaroslav

    2015-01-01

    The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi). The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals. PMID:25849117

  5. Elucidating the degradation mechanism of the cathode catalyst of PEFCs by a combination of electrochemical methods and X-ray fluorescence spectroscopy.

    PubMed

    Monzó, J; van der Vliet, D F; Yanson, A; Rodriguez, P

    2016-08-10

    In this study, we report a methodology which enables the determination of the degradation mechanisms responsible for catalyst deterioration under different accelerated stress protocols (ASPs) by combining measurements of the electrochemical surface area (ECSA) and Pt content (by X-ray fluorescence). The validation of this method was assessed on high surface area unsupported Pt nanoparticles (Pt-NPs), Pt nanoparticles supported on TaC (Pt/TaC) and Pt nanoparticles supported on Vulcan carbon (Pt/Vulcan). In the load cycle protocol, the degradation of Pt-NPs and Pt/Vulcan follows associative processes (e.g. agglomeration) in the first 2000 cycles, however, in successive cycles the degradation goes through dissociative processes such as Pt dissolution, as is evident from a similar decay of ECSA and Pt content. In contrast, the degradation mechanism for Pt nanoparticles dispersed on TaC occurs continuously through the dissociative processes (e.g. Pt dissolution or particle detachment), with similar decay rates of both Pt content and ECSA. In the start-up/shut-down protocol, high surface area Pt-NPs follow associative processes (e.g. Ostwald ripening) in the first 4000 cycles, after which the degradation continues through dissociative processes. On the other hand, dissociative mechanisms always govern the degradation of Pt/TaC under start-up/shut-down protocol conditions. Finally, we report that Pt nanoparticles supported on TaC exhibit the highest catalytic activity and long term durability of the three nanoparticle systems tested. This makes Pt/TaC a potentially valuable catalyst system for application in polymer electrolyte fuel cell cathodes.

  6. Mechanical Properties of Normal and Diseased Cerebrovascular System

    PubMed Central

    Ebrahimi, Ali P.

    2009-01-01

    Background: Blood vessel mechanics has traditionally been of interest to researchers and clinicians. Changes in mechanical properties of arteries have been associated with various diseases. Objective: To provide a comprehensive review directed towards understanding the basic biomechanical properties of cerebral arteries under normal and diseased conditions. Methods: Literature review supplemented by personal knowledge. Results: The mechanical properties of vascular tissue may depend on several factors including macromolecular volume fraction, molecular orientation, and volume or number of cells such as smooth muscle cells. Mechanical properties of a blood vessel have been characterized using different methods such as in vitro tensile testing, non-invasive ultrasound examination, and mathematical models. Experiments are complicated by the variation in properties and content of materials that make up the vessel wall and more challenging as the size of the vessel of interest decreases. Therapeutic interventions aiming to alter the mechanical response are either pharmaceutical: including calcium channel blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and β-blockers; or, mechanical interventions such as angioplasty, stent placement, mechanical thrombectomy, or embolization procedures. Conclusion: It is apparent from the literature that macromolecular and cellular mechanics of blood vessels are not fully understood. Therefore, further studies are necessary to better understand contribution of these mechanisms to the overall mechanics of the vascular tissue. PMID:22518247

  7. Decomposition of acetaminophen in water by a gas phase dielectric barrier discharge plasma combined with TiO2-rGO nanocomposite: Mechanism and degradation pathway.

    PubMed

    Zhang, Guyu; Sun, Yabing; Zhang, Chunxiao; Yu, Zhongqing

    2017-02-05

    Acetaminophen (APAP) served as the model pollutant to evaluate the feasibility of pollutant removal by gas phase dielectric barrier discharge plasma combined with the titanium dioxide-reduced Graphene Oxide (TiO2-rGO) nanocomposite. TiO2-rGO nanocomposite was prepared using the modified hydrothermal method and characterized by TEM and XPS before and after plasma process. The results indicated that the APAP degradation efficiency was significantly improved to 92% after 18min of discharge plasma treatment coupling 0.25gL(-1) TiO2-rGO 5%wt at 18kV, compared with the plasma alone and plasma combined with P25 TiO2. The degradation mechanism for APAP in this system was studied by investigating the effects of the operational variables (e.g. discharge voltage and pH value) and the amount of the generated active species; and the results showed that O3 and H2O2 yields were influenced notably by adding TiO2-rGO. Also, it was observed that, compared with unused TiO2-rGO, the photocatalytic performance of used TiO2-rGO declined after several recirculation times due to the further reduction of Graphene Oxide in plasma system. Finally, intermediate products were analyzed by UV-vis spectrometry and HPLC/MS, and possible transformation pathways were identified with the support of theoretically calculating the frontier electron density of APAP.

  8. Development of Combined Dry Heat and Chlorine Dioxide Gas Treatment with Mechanical Mixing for Inactivation of Salmonella enterica Serovar Montevideo on Mung Bean Seeds.

    PubMed

    Annous, Bassam A; Burke, Angela

    2015-05-01

    Foodborne outbreaks have been associated with the consumption of fresh sprouted beans. The sprouting conditions of mung bean seeds provide optimal conditions of temperature and relative humidity for any potential pathogenic contaminant on the seeds to grow. The lack of a kill step postsprouting is a major safety concern. Thus, the use of a kill step on the seeds prior to a sprouting step would enhance the safety of fresh sprouts. The objective of this work was to evaluate the effectiveness of the combined thermal and chlorine dioxide gas (3.5 mg/liter of air) treatment with mechanical mixing (tumbling) to eliminate Salmonella on artificially inoculated mung bean seeds. Although no viable Salmonella was recovered from seeds treated in hot water at 60°C for 2 h, these treated seeds failed to germinate. Dry heat treatments (55, 60, or 70°C) for up to 8 h reduced Salmonella populations in excess of 3 log CFU/g. The use of tumbling, while treating the seeds, resulted in up to 1.6 log CFU/g reduction in Salmonella populations compared with no tumbling. Dry heat treatment at 65°C for 18 h with tumbling resulted in a complete inactivation of Salmonella populations on inoculated seeds with low inoculum levels (2.83 log CFU/g) as compared with high inoculum levels (4.75 log CFU/g). The increased reductions in pathogenic populations on the seeds with the use of tumbling could be attributed to increased uniformity of heat transfer and exposure to chlorine dioxide gas. All treated seeds were capable of germinating, as well as the nontreated controls. These results suggest that this combined treatment would be a viable process for enhancing the safety of fresh sprouts.

  9. Energetics and structure in solvent: A dielectric continuum model of solvation combined with molecular mechanics, Ab Initio, and Semi-empirical molecular orbital treatments of the solute

    SciTech Connect

    Tawa, G.J.; Pratt, L.R.; Martin, R.L.

    1996-12-31

    We present a method for computing the electrostatic component of the solvation free energy, {Delta}G{sup el}, of a solute molecule in the presence of solvent modeled as a dielectric continuum. The method is based on an integral form of Poisson`s equation which is solved to obtain a distribution of induced polarization charge at the solute-solvent dielectric interface. The solution of Poisson`s equation is obtained by application of a boundary element procedure. The method is tested by comparing its predictions of {Delta}G{sup el} to exact values for several model problems. The method is then used in a variety of contexts to assess its qualitative prediction ability. It is first combined with a molecular mechanics treatment of the solute to evaluate the effects of aqueous solvent on the conformational equilibria of several small molecules of interest-these are N-methyl acetamide and alanine dipeptide. For both molecules dielectric continuum solvation predicts torsional free energies of solvation that are in accord with other more complete treatments of solvation. The method is then combined with ab initio and semi-empirical molecular orbital theory for the solute. Self consistent reaction field calculations (SCRF) are performed to evaluate the correlation is in general very good. Relative agreement with experiment is best for ions where electrostatics predominate and worst for non-polar neutral molecules were electrostatics are minor. Semi-empirical configuration interaction SCRF calculations are also performed in the presence of solvent in order to determine ground-to-excited state absorption energy shifts for formaldehyde and indole mine ground-to-excited state absorption energy shifts for formaldehyde and indole when placed in water. We find a rough correlation between transition energy shifts and the dipole moments of the initial and final states involved in the transition.

  10. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

    SciTech Connect

    Rossi-George, A.; Virgolini, M.B.; Weston, D.; Cory-Slechta, D.A.

    2009-01-01

    Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 {mu}g/kg (females) or 100 or 150 {mu}g/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments.

  11. Insights into the mechanisms underlying mercury-induced oxidative stress in gills of wild fish (Liza aurata) combining (1)H NMR metabolomics and conventional biochemical assays.

    PubMed

    Cappello, Tiziana; Brandão, Fátima; Guilherme, Sofia; Santos, Maria Ana; Maisano, Maria; Mauceri, Angela; Canário, João; Pacheco, Mário; Pereira, Patrícia

    2016-04-01

    Oxidative stress has been described as a key pathway to initiate mercury (Hg) toxicity in fish. However, the mechanisms underlying Hg-induced oxidative stress in fish still need to be clarified. To this aim, environmental metabolomics in combination with a battery of conventional oxidative stress biomarkers were applied to the gills of golden grey mullet (Liza aurata) collected from Largo do Laranjo (LAR), a confined Hg contaminated area, and São Jacinto (SJ), selected as reference site (Aveiro Lagoon, Portugal). Higher accumulation of inorganic Hg and methylmercury was found in gills of fish from LAR relative to SJ. Nuclear magnetic resonance (NMR)-based metabolomics revealed changes in metabolites related to antioxidant protection, namely depletion of reduced glutathione (GSH) and its constituent amino acids, glutamate and glycine. The interference of Hg with the antioxidant protection of gills was corroborated through oxidative stress endpoints, namely the depletion of glutathione peroxidase and superoxide dismutase activities at LAR. The increase of total glutathione content (reduced glutathione+oxidized glutathione) at LAR, in parallel with GSH depletion aforementioned, indicates the occurrence of massive GSH oxidation under Hg stress, and an inability to carry out its regeneration (glutathione reductase activity was unaltered) or de novo synthesis. Nevertheless, the results suggest the occurrence of alternative mechanisms for preventing lipid peroxidative damage, which may be associated with the enhancement of membrane stabilization/repair processes resulting from depletion in the precursors of phosphatidylcholine (phosphocholine and glycerophosphocholine), as highlighted by NMR spectroscopy. However, the observed decrease in taurine may be attributable to alterations in the structure of cell membranes or interference in osmoregulatory processes. Overall, the novel concurrent use of metabolomics and conventional oxidative stress endpoints demonstrated to be

  12. Extending the boundaries of mechanical properties of Ti-Nb low-carbon steel via combination of ultrafast cooling and deformation during austenite-to-ferrite transformation

    NASA Astrophysics Data System (ADS)

    Deng, Xiangtao; Fu, Tianliang; Wang, Zhaodong; Liu, Guohuai; Wang, Guodong; Misra, R. D. K.

    2017-01-01

    We underscore here a novel approach to extend the boundaries of mechanical properties of Ti-Nb low-carbon steel via combination of ultrafast cooling and deformation during austenite-to-ferrite transformation. The proposed approach yields a refined microstructure and high density nano-sized precipitates, with consequent increase in strength. Steels subjected to ultra-fast cooling during austenite-to-ferrite transformation led to 145 MPa increase in yield strength, while the small deformation after ultra-fast cooling process led to increase in strength of 275 MPa. The ultra-fast cooling refined the ferrite and pearlite constituents and enabled uniform dispersion, while the deformation after ultra-fast cooling promoted precipitation and broke the lamellar pearlite to spherical cementite and long thin strips of FexC. The contribution of nano-sized precipitates to yield strength was estimated to be 247.9 MPa and 358.3 MPa for ultrafast cooling and deformation plus ultrafast cooling processes. The nano precipitates carbides were identified to be (Ti, Nb)C and had a NaCl-type crystal structure, and obeyed the Baker-Nutting orientation relationship with the ferrite matrix.

  13. Understanding the adsorption of CuPc and ZnPc on noble metal surfaces by combining quantum-mechanical modelling and photoelectron spectroscopy.

    PubMed

    Huang, Yu Li; Wruss, Elisabeth; Egger, David A; Kera, Satoshi; Ueno, Nobuo; Saidi, Wissam A; Bucko, Tomas; Wee, Andrew T S; Zojer, Egbert

    2014-03-07

    Phthalocyanines are an important class of organic semiconductors and, thus, their interfaces with metals are both of fundamental and practical relevance. In the present contribution we provide a combined theoretical and experimental study, in which we show that state-of-the-art quantum-mechanical simulations are nowadays capable of treating most properties of such interfaces in a quantitatively reliable manner. This is shown for Cu-phthalocyanine (CuPc) and Zn-phthalocyanine (ZnPc) on Au(111) and Ag(111) surfaces. Using a recently developed approach for efficiently treating van der Waals (vdW) interactions at metal/organic interfaces, we calculate adsorption geometries in excellent agreement with experiments. With these geometries available, we are then able to accurately describe the interfacial electronic structure arising from molecular adsorption. We find that bonding is dominated by vdW forces for all studied interfaces. Concomitantly, charge rearrangements on Au(111) are exclusively due to Pauli pushback. On Ag(111), we additionally observe charge transfer from the metal to one of the spin-channels associated with the lowest unoccupied π-states of the molecules. Comparing the interfacial density of states with our ultraviolet photoelectron spectroscopy (UPS) experiments, we find that the use of a hybrid functionals is necessary to obtain the correct order of the electronic states.

  14. Toward the complete utilization of rice straw: Methane fermentation and lignin recovery by a combinational process involving mechanical milling, supporting material and nanofiltration.

    PubMed

    Sasaki, Kengo; Okamoto, Mami; Shirai, Tomokazu; Tsuge, Yota; Fujino, Ayami; Sasaki, Daisuke; Morita, Masahiko; Matsuda, Fumio; Kikuchi, Jun; Kondo, Akihiko

    2016-09-01

    Rice straw was mechanically milled using a process consuming 1.9MJ/kg-biomass, and 10g/L of unmilled or milled rice straw was used as the carbon source for methane fermentation in a digester containing carbon fiber textile as the supporting material. Milling increased methane production from 226 to 419mL/L/day at an organic loading rate of 2180mg-dichromate chemical oxygen demand/L/day, corresponding to 260mLCH4/gVS. Storage of the fermentation effluent at room temperature decreased the weight of the milled rice straw residue from 3.81 to 1.00g/L. The supernatant of the effluent was subjected to nanofiltration. The black concentrates deposited on the nanofiltration membranes contained 53.0-57.9% lignin. Solution nuclear magnetic resonance showed that lignin aromatic components such as p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) were retained primarily, and major lignin interunit structures such as the β-O-4-H/G unit were absent. This combinational process will aid the complete utilization of rice straw.

  15. Novel quantum mechanical/molecular mechanical method combined with the theory of energy representation: Free energy calculation for the Beckmann rearrangement promoted by proton transfers in the supercritical water

    NASA Astrophysics Data System (ADS)

    Takahashi, Hideaki; Tanabe, Kohsuke; Aketa, Masataka; Kishi, Ryohei; Furukawa, Shin-ichi; Nakano, Masayoshi

    2007-02-01

    The Beckmann rearrangement of acetone oxime promoted by proton transfers in the supercritical water has been investigated by means of the hybrid quantum mechanical/molecular mechanical approach combined with the theory of energy representation (QM/MM-ER) recently developed. The transition state (TS) structures have been explored by ab initio calculations for the reaction of hydrated acetone oxime on the assumption that the reaction is catalyzed by proton transfers along the hydrogen bonds connecting the solute and the solvent water molecules. Up to two water molecules have been considered as reactants that take part in the proton transfers. As a result of the density functional theory calculations with B3LYP functional and aug-cc-pVDZ basis set, it has been found that participation of two water molecules in the reaction reduces the activation free energy by -12.3kcal/mol. Furthermore, the QM/MM-ER simulations have revealed that the TS is more stabilized than the reactant state in the supercritical water by 2.7kcal/mol when two water molecules are involved in the reaction. Solvation free energies of the reactant and the TS have been decomposed into terms due to the electronic polarization of the solute, electron density fluctuation, and others to elucidate the origin of the stabilization of the TS as compared with the reactant. It has been revealed that the promotion of the chemical reaction due to the hydration mainly originates from the interaction between the nonpolarized solute and the solvent water molecules at the supercritical state.

  16. Analgesic combinations

    PubMed Central

    Raffa, Robert B.; Pergolizzi, Joseph V.; Tallarida, Ronald J.

    2010-01-01

    When the pathophysiology of a medical condition is multi-modal, i.e., related to multiple physiological causes or mediated by multiple pathways, the optimal strategy can be to use a drug or a combination of drugs that contribute multiple mechanisms to the therapeutic endpoint. In such situations, a rational multi-modal approach can also result in the fewest adverse effects. We discuss the quantitative analysis of multi-modal action using the treatment of pain as a practical example and give examples of its application to some widely used analgesic drugs. PMID:20338825

  17. Cellular and Molecular Mechanisms Underlie the Anti-Tumor Activities Exerted by Walterinnesia aegyptia Venom Combined with Silica Nanoparticles against Multiple Myeloma Cancer Cell Types

    PubMed Central

    Badr, Gamal; Al-Sadoon, Mohamed K.; Abdel-Maksoud, Mostafa A.; Rabah, Danny M.; El-Toni, Ahmed M.

    2012-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC50 values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, BclXL and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and the

  18. Cellular and molecular mechanisms underlie the anti-tumor activities exerted by Walterinnesia aegyptia venom combined with silica nanoparticles against multiple myeloma cancer cell types.

    PubMed

    Badr, Gamal; Al-Sadoon, Mohamed K; Abdel-Maksoud, Mostafa A; Rabah, Danny M; El-Toni, Ahmed M

    2012-01-01

    Multiple myeloma (MM) is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV) alone or in combination with silica nanoparticles (WEV+NP) on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC(50) values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs) were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml) and WEV+NP (10 ng/ml) decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor) on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12) to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2) family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, Bcl(XL) and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV+NP and

  19. Is non-insulin dependent glucose uptake a therapeutic alternative? Part 2: Do such mechanisms fulfil the required combination of power and tolerability?

    PubMed

    Wiernsperger, N F

    2005-12-01

    The worldwide burden of diabetes, the unavoidable worsening which is observed in long-term clinical trials despite treatment and the close link between glycaemia and microangiopathy appeal for much stronger treatment strategies. This, in turn, either requires polypharmacy (with new risks) or new, more powerful drugs to be invented. The first part of this review dealt with a thorough analysis of pros and cons for some selected pathways which could potentially increase glucose uptake without necessitating insulin. The choice of such targets for developing completely new drugs, however, requires a favourable background from existing tentatives with either drugs or cell biology approaches. Moreover, because vascular complications are what must ultimately be avoided when treating diabetic patients, we must be sure that increasing glucose uptake in a fashion which is no more controlled by normal physiology is compatible with the physiology of vascular cells (long-term tolerance). The aspect of drug side-effects must therefore be considered systematically. For reasons which are individually developed, it appears that each of the potential pathways analyzed either lacks sufficient power and/or is likely to induce side effects which are not acceptable for long-term application. The fact that GLUT-1 transporters are ubiquitously distributed even extends this cardinal question to the general principle of increasing glucose uptake. In conclusion a precise evaluation suggests that, although non-insulin dependent glucose uptake represents (3/4) of whole body glucose transport, it is difficult to consider such mechanisms able to generate a new treatment fulfilling the unavoidable request of combined efficacy and tolerability.

  20. Antibiotic trapping by plasmid-encoded CMY-2 β-lactamase combined with reduced outer membrane permeability as a mechanism of carbapenem resistance in Escherichia coli.

    PubMed

    Goessens, Wil H F; van der Bij, Akke K; van Boxtel, Ria; Pitout, Johann D D; van Ulsen, Peter; Melles, Damian C; Tommassen, Jan

    2013-08-01

    A liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS) Escherichia coli strain, but during admission, a carbapenem-resistant (CR) E. coli strain was isolated. Analysis of the outer membrane protein profiles showed that both CS and CR E. coli lacked the porins OmpF and OmpC. Furthermore, PCR and sequence analysis revealed that both CS and CR E. coli possessed bla(CTX-M-15) and bla(OXA-1). The CR E. coli strain additionally harbored bla(CMY-2) and demonstrated a >15-fold increase in β-lactamase activity against nitrocefin, but no hydrolysis of meropenem was detected. However, nitrocefin hydrolysis appeared strongly inhibited by meropenem. Furthermore, the CMY-2 enzyme demonstrated lower electrophoretic mobility after its incubation either in vitro or in vivo with meropenem, indicative of its covalent modification with meropenem. The presence of the acyl-enzyme complex was confirmed by mass spectrometry. By transformation of the CMY-2-encoding plasmid into various E. coli strains, it was established that both porin deficiency and high-level expression of the enzyme were needed to confer meropenem resistance. In conclusion, carbapenem resistance emerged by a combination of elevated β-lactamase production and lack of porin expression. Due to the reduced outer membrane permeability, only small amounts of meropenem can enter the periplasm, where they are trapped but not degraded by the large amount of the β-lactamase. This study, therefore, provides evidence that the mechanism of "trapping" by CMY-2 β-lactamase plays a role in carbapenem resistance.

  1. Mechanism of enhanced responses after combination photodynamic therapy (cPDT) in carcinoma cells involves C/EBP-mediated transcriptional upregulation of the coproporphyrinogen oxidase (CPO) gene

    NASA Astrophysics Data System (ADS)

    Anand, Sanjay; Hasan, Tayyaba; Maytin, Edward V.

    2013-03-01

    Photodynamic therapy (PDT) with aminolevulinate (ALA) is widely accepted as an effective treatment for superficial carcinomas and pre-cancers. However, PDT is still suboptimal for deeper tumors, mainly due to inadequate ALA penetration and subsequent conversion to PpIX. We are interested in improving the effectiveness of photodynamic therapy (PDT) for deep tumors, using a combination approach (cPDT) in which target protoporphyrin (PpIX) levels are significantly enhanced by differentiation caused by giving Vitamin D or methotrexate (MTX) for 3 days prior to ALAPDT. In LNCaP and MEL cells, a strong correlation between inducible differentiation and expression of C/EBP transcription factors, as well as between differentiation and mRNA levels of CPO (a key heme-synthetic enzyme), indicates the possibility of CPO transcriptional regulation by the C/EBPs. Sequence analysis of the first 1300 base pairs of the murine CPO upstream region revealed 15 consensus C/EBP binding sites. Electrophoretic Mobility Shift Assays (EMSA) proved that these sites form specific complexes that have strong, moderate or weak affinities for C/EBPs. However, in the context of the full-length CPO promoter, inactivation of any type of site (strong or weak) reduced CPO promoter activity (luciferase assay) to nearly the same extent, suggesting cooperative interactions. A comparative analysis of murine and human CPO promoters revealed possible protein-protein interactions between C/EBPs and several neighboring transcription factors such as NFkB, Sp1, AP-1, CBP/p300 and CREB (an enhanceosome complex). Overall, these results confirm that C/EBP's are important for CPO expression via complex mechanisms which upregulate PpIX and enhance the outcome of cPDT.

  2. The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the Senescent Mouse Model Induced by a Combination of D-gal and AlCl3.

    PubMed

    Peng, Xiao-Ming; Gao, Li; Huo, Shi-Xia; Liu, Xin-Min; Yan, Ming

    2015-08-01

    Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d-galactose and AlCl3 , and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step-down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase-3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss.

  3. Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways.

    PubMed

    Wee, Lee Heng; Morad, Noor Azian; Aan, Goon Jo; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

    2015-01-01

    The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.

  4. The effect of a combined biological and thermo-mechanical pretreatment of wheat straw on energy yields in coupled ethanol and methane generation.