Metformin Ameliorates Lipotoxic ß-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action.

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic ß-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic ß-cells. We therefore examined the effects of metformin on pancreatic ß-cells under lipotoxic stress. METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis. RESULTS: We found that metformin has protective effects on palmitate-induced ß-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK. CONCLUSION: This study suggests that the action of metformin on ß-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic ß-cell dysfunction through inhibition of oxidative stress and ER stress.

Biliary stone removal through the percutaneous transhepatic biliary drainage route, focusing on the balloon sphincteroplasty flushing technique: a single center study with 916 patients.

PURPOSE: To present our experience in biliary stone removal (BSR) through the percutaneous transhepatic biliary drainage (PTBD) route in 916 patients, and discuss its clinical usefulness. MATERIALS AND METHODS: From 2001 to 2015, 916 patients (479 male patients and 437 female patients; age range, 22-92 years; mean age, 67 years) with 52 recurring cases, so a total of 968 cases, were enrolled in this study and retrospectively reviewed. PTBD was performed in all patients. BSR was performed using a combination of a balloon sphincteroplasty flushing technique, a pushing technique after sphincteroplasty, and classical extraction technique, decided case by case. RESULTS: A complete removal was achieved in 893 cases (92.3%) and the overall clinical success rate was 99.3%. Failure occurred in 7 cases (0.7%), and the causes of failure were stone impaction (n = 5) and intrahepatic bile duct stricture (n = 2). Sphincteroplasty was performed in 902 cases (93.2%). Balloon sphincteroplasty flushing technique was used in 829 (85.6%) cases. There was no major complication. Transient minor complications were seen in 86 cases (8.9%). CONCLUSIONS: BSR through the PTBD route using a combination of techniques, including balloon sphincteroplasty flushing, is a safe and effective treatment modality to remove biliary stones.

Endovascular management of hemosuccus pancreaticus, a rare case report of gastrointestinal bleeding.

BACKGROUND: Hemorrhage from the pancreatic duct, or hemosuccus pancreaticus (HP), is an unusual cause of intermittent gastrointestinal bleeding. HP is most often diagnosed in patients with chronic pancreatitis, and is usually due to the rupture of an aneurysm in the splenic artery. The traditional treatment for HP is surgery, although most cases can be managed by angioembolization. CASE PRESENTATION: We present a case of HP in a patient with no history or evidence of chronic pancreatitis. Repeated endoscopy revealed fresh bleeding from the papilla of Vater. Angiography revealed an aneurysm of the splenic artery, which was the suspected cause of the intermittent bleeding from the pancreatic duct. Angiography demonstrated extravasation of contrast from the aneurysm. A peripheral Jostent stent-graft was hand-mounted on an angioplasty balloon and then inserted into the aneurysm. Arteriography revealed successful occlusion of the aneurysm with the stent-graft. No recurrent gastrointestinal bleeding was observed during the five years follow-up periods. CONCLUSION: HP should be included in the differential diagnosis of intermittent gastrointestinal bleeding in patients with histories of chronic alcoholism, even when they do not have a history of chronic pancreatitis. We recommend an interventional procedure with a metal stent for the initial treatment of HP.

Evaluation of engraftment of superparamagnetic iron oxide-labeled mesenchymal stem cells using three-dimensional reconstruction of magnetic resonance imaging in photothrombotic cerebral infarction models of rats.

OBJECTIVE: To evaluate engraftment by visualizing the location of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) three-dimensionally in photothrombotic cerebral infarction (PTCI) models of rats. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of an agarose block containing superparamagnetic iron oxide (SPIO)-labeled hBM-MSCs was performed using a 3.0-T MRI, T2-(T2WI), T2(*)-(T2(*)WI), and susceptibility-weighted images (SWI). PTCI was induced in 6 rats, and 2.5 × 10(5) SPIO-labeled hBM-MSCs were infused through the ipsilateral internal carotid artery (ICA group) or tail vein (IV group). MRI was performed on days 1, 3, 7, and 14 after stem cell injection. Dark signal regions were confirmed using histology. Three-dimensional MRI reconstruction was performed using the clinical workflow solution to evaluate the engraftment of hBM-MSCs. Volumetric analysis of the engraftment was also performed. RESULTS: The volumes of SPIO-labeled hBM-MSCs in the phantom MRI were 129.3, 68.4, and 25.9 µL using SWI, T2(*)WI, and T2WI, respectively. SPIO-labeled hBM-MSCs appeared on day 1 after injection, encircling the cerebral infarction from the ventral side. Dark signal regions matched iron positive cells and human origin (positive) cells. The volume of the engraftment was larger in the ICA group on days 1, 3, and 7, after stem cell injection (p < 0.05 on SWI). SWI was the most sensitive MRI pulse sequence (p < 0.05). The volume of infarction decreased until day 14. CONCLUSION: The engraftment of SPIO-labeled hBM-MSCs can be visualized and evaluated three-dimensionally in PTCI models of rats. The engraftment volume was larger in the ICA group than IV group on early stage within one week.

Sensitivity of susceptibility-weighted imaging in detecting superparamagnetic iron oxide-labeled mesenchymal stem cells: a comparative study.

BACKGROUND: Susceptibility-weighted imaging (SWI) is extremely sensitive in the detection of superparamagnetic iron oxide (SPIO) nanoparticle-labeled cells. However, no study has compared molecular imaging for stem cell detection using SWI and other MRI pulse sequences. OBJECTIVES: This study aims to assess the sensitivity of SWI in detecting SPIO nanoparticle-labeled, human bone marrow-derived mesenchymal stem cells (SPIO-hMSCs) compared with that of T2- and T2*-weighted imaging (T2WI and T2*WI, respectively) in a phantom and in vivo study in rats. MATERIALS AND METHODS: A phantom was prepared with various cell concentrations. In one normal rat, SPIO-hMSCs were implanted directly through burr holes into both caudate putamens, while in three rats without and six rats with photothrombotic infarction, 2.5 × 10(5)/ml SPIO-hMSCs were infused into the ipsilateral internal carotid artery (ICA). T2WI, T2*WI, and SWI findings were compared for dark regions representing SPIO-hMSCs. RESULTS: SWI and T2*WI detected 15 µL of 13 SPIO-hMSCs/µL and 15 µL of 27 SPIO-hMSCs/µL in the phantom, respectively and 3 µL of 333 SPIO-hMSCs/µL and 3 µL of 167 SPIO-hMSCs/µL in the normal rat brain (direct implantation). In the normal rat brain (ICA infusion), one of the three cases showed numerous foci of dark regions dispersed throughout the brain on T2*WI and SWI. Dark regions surrounded the infarcts in all six infracted rat brains. The dark region was most prominent on SWI, followed by T2*WI and T2WI in all six rats (P = 0.002). Implanted SPIO-hMSCs were confirmed using Prussian blue staining. CONCLUSIONS: SWI is the most sensitive in the detection of SPIO-hMSCs, with the dark regions representing SPIO-hMSCs being more prominent on SWI than on T2*WI and T2WI.

Microfluidic-assisted fabrication of flexible and location traceable organo-motor.

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

MRI traceability of superparamagnetic iron oxide nanoparticle-embedded chitosan microspheres as an embolic material in rabbit uterus.

PURPOSE: We aimed to compare polyvinyl alcohol (PVA) particles with calibrated superparamagnetic iron oxide (SPIO) nanoparticle-loaded chitosan microspheres in a rabbit model, specifically regarding the relative distribution of embolic agents within the uterus based on magnetic resonance imaging (MRI) and pathological evaluation. METHODS: Twelve New Zealand white rabbits underwent uterine artery embolization using either standard PVA particles (45-150 µm or 350-500 µm) or calibrated SPIO-embedded chitosan microspheres (45-150 µm or 300-500 µm). MRI and histopathological findings were compared one week after embolization. RESULTS: Calibrated SPIO-loaded chitosan microspheres 45-150 µm in size were detected on T2-weighted images. On histological analysis, calibrated SPIO-embedded chitosan microspheres were found in both myometrium and endometrium, whereas PVA particles were found only in the perimyometrium or extrauterine fat pads. A proportional relationship was noted between the calibrated SPIO-embedded chitosan microsphere size and the size of the occluded artery. CONCLUSION: Calibrated SPIO-embedded chitosan microspheres induced greater segmental arterial occlusion than PVA particles and showed great potential as a new embolic material. SPIO-embedded chitosan microspheres can be used to follow distribution of embolic particles through MRI studies.

Susceptibility-weighted imaging for stem cell visualization in a rat photothrombotic cerebral infarction model.

BACKGROUND: In cell therapy, magnetic resonance imaging (MRI) has been used to visualize superparamagnetic iron oxide (SPIO)-labeled stem cells homing to a lesion. Improving traceability is to utilize the sequence that maximizes sensitivity to the susceptibility effect of SPIO. PURPOSE: To explore the best method by comparing the MRI sequences to visualize mesenchymal stem cells (MSCs) labeled with SPIO. MATERIAL AND METHODS: Human bone marrow (hBM)-derived MSCs were labeled by internalization of SPIO nanoparticles. In vitro MRI was performed for the SPIO-labeled hBM-MSCs in tubes with T2-weighted (T2W), T2*-weighted (T2*W), and susceptibility-weighted images (SWI). Contrast-to-noise ratio (CNR) and volumes of dark signal of SPIO-labeled hBM-MSCs were obtained on images of each sequence. Photothrombotic cerebral infarction (PTCI) was induced in eight rats, and 2.5 × 10(5) SPIO-labeled hBM-MSCs were infused through the tail vein on the third day. In vivo MRI of the rat brain was performed using a 3.0 T MRI on the first, third, seventh, and 14th days. CNRspio was obtained on T2W imaging, T2*W imaging, and SWI. The dark signals were compared with the SPIO-positive cells of Prussian blue staining. RESULTS: In vitro MRI of 5 × 10(5) SPIO-labeled hBM-MSCs showed the CNR and volume of dark signal to be 63, 517 mm(3) in SWI, 41, 228 mm(3) in T2*W imaging, and 56, 41 mm(3) in T2W imaging, respectively. In vivo MRI showed a dark signal surrounding the high signal intensity of PTCI. Pathologically, the dark signals were matched with SPIO-labeled hBM-MSC in the corresponding rat. The dark signal was most prominent in SWI, then T2*W imaging, and finally in T2W imaging (P <0.05). In SWI, other causes of dark signals were matched with the veins and the choroid plexuses on histopathology. CONCLUSION: SWI can visualize SPIO-labeled hBM-MSCs more sensitively, earlier, and with larger size and greater contrast than T2W imaging and T2*W imaging.

Preparation and evaluation of poly(2-hydroxyethyl aspartamide)-hexadecylamine-iron oxide for MR imaging of lymph nodes.

The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl aspartamide)-C16-iron oxide (PHEA-C16-iron oxide) nanoparticles and to evaluate their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes. The PHEA-C16-iron oxide nanoparticles were synthesized by coprecipitation method. The core size of the PHEA-C16-iron oxide nanoparticles was about 5 to 7 nm, and the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous solution. The size of the nanoparticles was controlled by the amount of C16. The 3.0-T MRI signal intensity of a rabbit lymph node was effectively reduced after intravenous administration of PHEA-C16-iron oxide with the size of 20 nm. The in vitro and in vivo toxicity tests revealed the high biocompatibility of PHEA-C16-iron oxide nanoparticles. Therefore, PHEA-C16-iron oxide nanoparticles with 20-nm size can be potentially useful as T2-weighted MR imaging contrast agents for the detection of lymph nodes.

Mathematical modeling of radiofrequency ablation for varicose veins.

We present a three-dimensional mathematical model for the study of radiofrequency ablation (RFA) with blood flow for varicose vein. The model designed to analyze temperature distribution heated by radiofrequency energy and cooled by blood flow includes a cylindrically symmetric blood vessel with a homogeneous vein wall. The simulated blood velocity conditions are U = 0, 1, 2.5, 5, 10, 20, and 40 mm/s. The lower the blood velocity, the higher the temperature in the vein wall and the greater the tissue damage. The region that is influenced by temperature in the case of the stagnant flow occupies approximately 28.5% of the whole geometry, while the region that is influenced by temperature in the case of continuously moving electrode against the flow direction is about 50%. The generated RF energy induces a temperature rise of the blood in the lumen and leads to an occlusion of the blood vessel. The result of the study demonstrated that higher blood velocity led to smaller thermal region and lower ablation efficiency. Since the peak temperature along the venous wall depends on the blood velocity and pullback velocity, the temperature distribution in the model influences ablation efficiency. The vein wall absorbs more energy in the low pullback velocity than in the high one.

Recoverability of freeze-dried doxorubicin-releasing chitosan embolic microspheres.

The purpose of this study is to investigate the recoverability of freeze-dried chitosan microspheres (MS). The factors influencing the integrity of chitosan MS during freeze-drying and rehydration procedures were determined, with focusing on choosing a suitable rehydration method and a freeze-drying excipient. Mean MS size, size distribution and sphericity of recovered chitosan MS were evaluated. Furthermore, the impacts of freeze-drying and rehydration procedure on the elasticity of chitosan MS were explored and the release profiles were evaluated. The recoverability of lyophilized chitosan MS was largely dependent on rehydration method and freeze-drying excipients. When using the optimized recovery processes, deformable drug-loaded chitosan MS can be rapidly recovered to exhibit the initial physico-mechanical properties such as elasticity. Release profiles also were not significantly changed after rehydration procedure. It is therefore expected drug-loaded chitosan MS can be stably freeze-dried with the prevention of drug release during storage and rapidly recovered to be used as deformable embolic materials possibly applicable for anti-cancer embolotherapy.

Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

Antiglycolytic therapy combined with an image-guided minimally invasive delivery strategy for the treatment of breast cancer.

PURPOSE: The antiglycolytic agent 3-bromopyruvate (3-BrPA) promotes anticancer effects in multiple tumor models. This study evaluated the therapeutic efficacy of ultrasound (US)-guided intratumoral delivery of 3-BrPA in an orthotopic tumor model of breast cancer. MATERIALS AND METHODS: Human breast cancer cell line MDA MB 231 was used for in vitro and in vivo studies. The anticancer effect of 3-BrPA was evaluated by viability assay, quantification of adenosine triphosphate (ATP) and lactate levels, and activity of matrix metalloproteinase (MMP)-9. In animal experiments, 15 nude mice with MDA MB 231 breast tumors were divided into three groups for US-guided intratumoral treatment with 1.75 mM 3-BrPA (group 1), 5 mM 3-BrPA (group 2), and saline solution (group 3). Tumor size was measured and subjected to histopathologic examination. RESULTS: In vitro, treatment with 3-BrPA resulted in a dose-dependent decrease in cell viability. A decrease in ATP and lactate levels, invasion, and MMP9 activity and expression was observed after treatment with concentrations of 3-BrPA that did not affect cell viability. In vivo, a significant difference in tumor volume was observed between 3-BrPA-treated and control animals. At the end of the study, tumor volumes in the 3-BrPA groups were 1,876 mm(3)±346 and 426 mm(3)±180 in the 1.75-mM and 5-mM 3-BrPA groups, respectively, versus 4,447 mm(3)±571 in the control group (P< .05). CONCLUSIONS: US-guided intratumoral injection of 3-BrPA effectively blocks breast cancer progression in an orthotopic mouse tumor model.

A long-term outcome of therapeutic angiogenesis by transplantation of peripheral blood stem cells in critical limb ischemia after interventional revascularization.

A 61-year-old male patient with atherosclerotic critical limb ischemia in the left leg underwent stent insertion into the left superficial femoral artery. Stenting procedures improved Rutherford grade from III-5 to II-4. Granulocyte colony-stimulating factor stimulated the production of white blood cells over four-fold and mononuclear cells (MNCs) 1.5-fold in the whole blood. Transplantation of 7.9x10(9) autologous MNCs into the left femoral artery rapidly decreased the leg pain intensity, with further improvement of Rutherford grades from II-4 to 0-0 without any side effects. In the four-year follow-up, significant improvement was found in terms of ankle brachial index, from nondetectable to 0.67, and peak systolic velocity, from 14.8 to 36.1 cm/s. Limb salvage and decreased resting pain were the notable outcomes of the treatment.

Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.

OBJECTIVE: This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. METHODS: Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2(*) weighted image (T2(*)WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. RESULTS: Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. CONCLUSION: In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

Design of deformable chitosan microspheres loaded with superparamagnetic iron oxide nanoparticles for embolotherapy detectable by magnetic resonance imaging.

The purpose of this study was to design chitosan microspheres (MS) loaded with superparamagnetic iron oxide nanoparticles (SPIO) suitable for anti-cancer embolotherapy detectable by MRI. Deformable chitosan MS loaded with varying SPIO concentrations (SPIO-chitosan MS) were prepared by ionotropic gelation and a porogenic technique using polyethylene glycol, followed by genipin crosslinking. Adding SPIO nanoparticles to chitosan MS did not significantly affect the chitosan MS morphology. An in vitro phantom study led to selecting SPIO-chitosan MS prepared with 1.0 mM SPIO for an in vivo MR traceability study. SPIO-chitosan MS could be identified following embolization in the renal artery by MRI at 18 weeks. Histological and pathological evidence also showed that SPIO-chitosan MS blocked and remained in the target vessels. Therefore, deformable SPIO-chitosan MS is MR-detectable embolic material with a possible application for anti-cancer embolotherapy.

Design and characterisation of doxorubicin-releasing chitosan microspheres for anti-cancer chemoembolisation.

The aims of this study were to design and characterise doxorubicin-loaded chitosan microspheres for anti-cancer chemoembolisation. Doxorubicin-loaded chitosan microspheres were prepared by emulsification and cross-linking methods. Doxorubicin-chitosan solution was initially complexed with tripolyphosphate (TPP) to improve drug loading capabilities. Doxorubicin-loaded chitosan microspheres were highly spherical and had approximately diameters of 130-160 µm in size. Drug loading amount and loading efficiency were in the range 3.7-4.0% and 68.5-85.8%, respectively, and affected by TPP concentration, drug levels and cross-linking time. Doxorubicin release was affected by TPP complexation, cross-linking time and release medium. Especially, lysozyme in release media considerably increased drug release. Synergistic anti-cancer activities of doxorubicin-releasing chitosan microspheres were confirmed to VX2 cells in the rabbit auricle model compared with blank microspheres. Doxorubicin-loaded chitosan microspheres can efficiently be prepared by TPP gelation and cross-linking method and developed as multifunctional anti-cancer embolic material.

Tracing of the Bile-chemotactic migration of juvenile Clonorchis sinensis in rabbits by PET-CT.

BACKGROUND: Adult Clonorchis sinensis live in the bile duct and cause clonorchiasis. It is known that the C. sinensis metacercariae excyst in the duodenum and migrate up to the bile duct through the common bile duct. However, no direct evidence is available on the in vivo migration of newly excysted C. sinensis juveniles (CsNEJs). Advanced imaging technologies now allow the in vivo migration and localization to be visualized. In the present study, we sought to determine how sensitively CsNEJs respond to bile and how fast they migrate to the intrahepatic bile duct using PET-CT. METHODOLOGY/PRINCIPAL FINDINGS: CsNEJs were radiolabeled with (18)F-fluorodeoxyglucose ((18)F-FDG). Rabbits with a gallbladder contraction response to cholecystokinin-8 (CCK-8) injection were pre-screened using cholescintigraphy. In these rabbits, gallbladders contracted by 50% in volume at an average of 11.5 min post-injection. The four rabbits examined were kept anesthetized and a catheter inserted into the mid duodenum. Gallbladder contraction was stimulated by injecting CCK-8 (20 ng/kg every minute) over the experiment. Anatomical images were acquired by CT initially and dynamic PET was then carried out for 90 min with a 3-min acquisition per frame. Twelve minutes after CCK-8 injection, about 3,000 (18)F-FDG-labeled CsNEJs were inoculated into the mid duodenum through the catheter. Photon signals were detected in the liver 7-9 min after CsNEJs inoculation, and these then increased in the whole liver with stronger intensity in the central area, presenting that the CsNEJs were arriving at the intrahepatic bile ducts. CONCLUSION: In the duodenum, CsNEJs immediately sense bile and migrate quickly with bile-chemotaxis to reach the intrahepatic bile ducts by way of the ampulla of Vater.

A radiofrequency electrode catheter-guide wire system for arterial occlusion.

PURPOSE: To describe the design of a radiofrequency (RF) electrode catheter/guide wire system to allow endovascular coagulation of vessels. MATERIALS AND METHODS: A circuit was created by modifying an ordinary microcatheter. An electrically conductive ring was placed at a microcatheter tip, and an extension lead at the hub site. They were each connected to an inherent coil mesh. The rings (ie, cathodes) were 1, 3, 5, 10, and 20 mm in length. In egg white, a coagulation study was performed by changing the length of the guide wire (ie, anode; 1, 3, 5, 10, 20, and 40 mm) in each cathode at 20 W. The coagulation time and site were analyzed. In rabbits, the renal artery was ablated with the use of a 20-mm cathode and 10-mm anode. RESULTS: In the egg white study, the coagulation time was proportionally increased and was dependent on the lengths of the cathode and anode (P < .05). Coagula developed at the anode to the 3-mm protrusion for the 1-mm cathode, to the 5-mm protrusion for the 3-mm cathode, to the 5-mm protrusion for the 5-mm cathode, to the 10-mm protrusion for the 10-mm cathode, and to the 20-mm protrusion for the 20-mm cathode. In rabbits, the renal artery was successfully occluded. Pathologic examination showed occlusion of the renal artery with organization, and the presence of a necrotic arterial wall with fibrosis, inflammation, and intact internal elastic lamina. CONCLUSIONS: The RF electrode catheter/guide wire system successfully coagulated egg white and occluded the rabbit renal artery.

Glycol chitosan/heparin immobilized iron oxide nanoparticles with a tumor-targeting characteristic for magnetic resonance imaging.

We described the preparation of the glycol chitosan/heparin immobilized iron oxide nanoparticles (composite NPs) as a magnetic resonance imaging agent with a tumor-targeting characteristic. The iron oxide nanoseeds used clinically as a magnetic resonance imaging agent were immobilized into the glycol chitosan/heparin network to form the composite NPs. To induce the ionic interaction between the iron oxide nanoseeds and glycol chitosan, gold was deposited on the surface of iron oxide nanoseeds. After the immobilization of gold-deposited iron oxide NPs into the glycol chitosan network, the NPs were stabilized with heparin based on the ionic interaction between cationic glycol chitosan and anionic heparin. FE-SEM (field emission-scanning electron microscopy) and a particle size analyzer were used to observe the formation of the stabilized composite NPs, and a Jobin-Yvon Ultima-C inductively coupled plasma-atomic emission spectrometer (ICP-AES) was used to measure the contents (%) of formed iron oxide nanoseeds as a function of reaction temperature and formed gold deposited on the iron oxide nanoparticles. We also evaluated the time-dependent excretion profile, in vivo biodistribution, circulation time, and tumor-targeting ability of the composite NPs using a noninvasive NIR fluorescence imaging technology. To observe the MRI contrast characteristic, the composite NPs were injected into the tail veins of tumor-bearing mice to demonstrate their selective tumoral distribution. The MR images were collected with conventional T(2)-weighted spin echo acquisition parameters.