Theranostic Strategy of Focused Ultrasound Induced Blood-Brain Barrier Opening for CNS Disease Treatment

Focused Ultrasound (FUS) in combination with gaseous microbubbles has emerged as a potential new means of effective drug delivery to the brain. Recent research has shown that, under burst-type energy exposure with the presence of microbubbles, this modality can transiently permeate the blood-brain barrier (BBB). The bioavailability of therapeutic agents is site-specifically augmented only in the zone where the FUS energy is targeted. The non-invasiveness of this approach makes FUS-induced BBB opening a novel and attractive means to perform localized CNS therapeutic agent delivery. Over the past decade, FUS-BBB opening has been preclinically confirmed to successfully enhance CNS penetration of therapeutic agents including chemotherapeutic agents, therapeutic peptides, monoclonal antibodies, and nanoparticles. Recently, a number of clinical human trials have begun to explore clinical utility. This review article, explores this technology through its physical mechanisms, summarizes the existing preclinical findings (including current medical device designs and technical approaches), and summarizes current ongoing clinical trials

Predictors of intra-abdominal coagulopathic hemorrhage after living donor liver transplantation

AbstractBackgroundResults of preoperative conventional coagulation assays are a poor predictor of hemorrhage after liver transplantation. In this study, we evaluated the factors that are predictive of intra-abdominal coagulopathic hemorrhage after living donor liver transplantation surgery.MethodsDuring the period from January 2009 to December 2012, 118 adults underwent living donor liver transplantation (LDLT) in our institution. Of those patients, 18 (15.3%) developed intra-abdominal coagulopathic hemorrhage (n = 7) or hemorrhage due to non-coagulopathic causes (n = 11) that required emergency medical, radiological, or surgical intervention within the first month after LDLT. Possible predictors of postoperative coagulopathic hemorrhage included donor-related factors, age, body mass index, MELD score, INR value, intra-operative blood transfusion, graft/recipient weight ratio, anhepatic phase, cold ischemia time, operative time, APACHE II score, onset of re-bleeding, and hemoglobin levels during rebleeding episodes.ResultsThere were no differences in any of the variables between the two groups (coagulopathic and noncoagulopathic hemorrhage) except for cold ischemia time. We found that cold ischemia time was significantly longer in patients with postoperative coagulopathic hemorrhage (160.50 ± 45.02 min) than in patients with hemorrhage due to non-coagulopathic causes (113.55 ± 29.31 min; P = 0.027).ConclusionProlonged cold ischemia time is associated with postoperative intra-abdominal coagulopathic hemorrhage in patients after LDLT. It is, therefore, necessary to shorten the cold ischemia time in order to reduce the risk of postoperative intra-abdominal hemorrhage due to coagulopathic causes

Preparation of TiO2 Nanocrystallite Powders Coated with 9 mol% ZnO for Cosmetic Applications in Sunscreens

The preparation of TiO2 nanocrystallite powders coated with and without 9 mol% ZnO has been studied for cosmetic applications in sunscreens by a co-precipitation process using TiCl4 and Zn(NO3)2·6H2O as starting materials. XRD results show that the phases of anatase TiO2 and rutile TiO2 coexist for precursor powders without added ZnO (T-0Z) and calcined at 523 to 973 K for 2 h. When the T-0Z precursor powders are calcined at 1273 K for 2 h, only the rutile TiO2 appears. In addition, when the TiO2 precursor powders contain 9 mol% ZnO (T-9Z) are calcined at 873 to 973 K for 2 h, the crystallized samples are composed of the major phase of rutile TiO2 and the minor phases of anatase TiO2 and Zn2Ti3O8. The analyses of UV/VIS/NIR spectra reveal that the absorption of the T-9Z precursor powders after being calcined has a red-shift effect in the UV range with increasing calcination temperature. Therefore, the TiO2 nanocrystallite powders coated with 9 mol% ZnO can be used as the attenuate agent in the UV-A region for cosmetic applications in sunscreens

Antitumor Effect of Periplocin in TRAIL-Resistant Human Hepatocellular Carcinoma Cells through Downregulation of IAPs

Cortex periplocae is the dried root bark of Periploca sepium Bge., a traditional Chinese herb medicine. It contains high amounts of cardiac glycosides. Several cardiac glycosides have been reported to inhibit tumor growth or induce tumor cell apoptosis. We extracted and purified cortex periplocae and identified periplocin as the active ingredient that inhibited the growth of TNF-related apoptosis-inducing ligand-(TRAIL-) resistant hepatocellular carcinoma cells. The antitumor activity of periplocin was further increased by TRAIL cotreatment. Periplocin sensitized TRAIL-resistant HCC through the following two mechanisms. First, periplocin induced the expression of DR4 and FADD. Second, the cotreatment of TRAIL and periplocin suppressed several inhibitors of apoptosis (IAPs). Both mechanisms resulted in the activation of caspase 3, 8, and 9 and led to cell apoptosis. In addition, intraperitoneal injection (IP) of periplocin repressed the growth of hepatocellular carcinoma (HCC) in xenograft tumor model in mice. In summary, periplocin sensitized TRAIL-resistant HCC cells to TRAIL treatment and resulted in tumor cell apoptosis and the repression of tumor growth in vivo

Transport of Riverine Material From Multiple Rivers in the Chesapeake Bay: Important Control of Estuarine Circulation on the Material Distribution

Driven by estuarine circulation, material released from lower Chesapeake Bay tributaries has the potential to be transported to the upper Bay. How far and what fraction of the material from tributaries can be carried to the upper estuary have not been quantitatively investigated. For an estuary system with multiple tributaries, the relative contribution from each tributary can provide valuable information for source assessment and fate prediction for riverine materials and passive moving organisms. We conducted long-term numerical simulations using multiple passive tracers that are independently released in the headwater of five main rivers (i.e., Susquehanna, Potomac, Rappahannock, York, and James Rivers) and calculated the relative contribution of each river to the total material in the mainstem. The results show that discharge from Susquehanna River exerts the dominant control on the riverine material throughout the entire mainstem. Despite the smaller contribution from the lower-middle Bay tributaries to the total materials in the mainstem, materials released from these rivers have a high potential to be transported to the middle-upper Bay through the bottom inflow by the persistent estuarine circulation. The fraction of the tributary material transported to the upper Bay depends on the location of the tributary. Materials released near the mouth are subject to a rapid flushing process, small retention time, and strong shelf current. Our results reveal three distinct spatial patterns for materials released from the main river, tributary, and coastal oceans. This study highlights the important control of estuarine circulation over horizontal and vertical distributions of materials in the mainstem

Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery

Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome. Methods A multicenter prospective observational study based on the NSARF ( National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 +/- 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006. Results The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality. Conclusions The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification