Regulation of von Willebrand factor by ADAMTS13 ameliorates lipopolysaccharide-induced lung injury in mice.

The relationship between von Willebrand factor (VWF) and inflammation has attracted considerable attention in recent years. VWF, which is stored in the Weibel-Palade bodies (WPBs) of endothelial cells (ECs), is released from WPBs in response to inflammatory stimuli and is thought to contribute to inflammation by promoting leukocyte extravasation. In this study, lung injury model mice were produced by intratracheal injection with lipopolysaccharides. The severity of lung inflammation was evaluated in mice with different genotypes (wild-type, Vwf-/-, Adamts13-/-) and mice treated with drugs that inhibit VWF function. Lung inflammation was significantly ameliorated in Vwf-/- mice compared with wild-type mice. Furthermore, inflammation was significantly suppressed in wild-type mice treated with anti-VWF A1 antibody or recombinant human ADAMTS13 compared with the untreated control group. The underlying mechanism appears to be an increased VWF/ADAMTS13 ratio at the site of inflammation and the interaction between blood cell components, such as leukocytes and platelets, and the VWF A1 domain, which promotes leukocyte infiltration into the lung. This study suggested that ADAMTS13 protein and other VWF-targeting agents may be a novel therapeutic option for treatment of pulmonary inflammatory diseases.

Oxidative stress upregulates zinc uptake activity via Zrt/Irt-like protein 1 (ZIP1) in cultured mouse astrocytes.

AIMS: Zinc released from glutamatergic boutons and astrocytes acts as neuro- and glio-transmitters, and thus its extracellular level has to be strictly regulated. We previously revealed that uptake of zinc by astrocytes plays a critical role in its clearance, and zinc transporter Zrt/Irt-like protein 1 (ZIP1) is the molecule responsible for the uptake. However, it is unknown whether or not the functionality of the zinc clearance system is altered under oxidative stress-loaded conditions. Here, we characterized zinc uptake by oxidative stress-loaded astrocytes. MAIN METHODS: Cultured mouse astrocytes were treated with hydrogen peroxide (H2O2) to load oxidative stress. Functional expression of ZIP1 in astrocytes was evaluated by means of (65)Zn uptake, Western blotting and immunocytochemical analysis. KEY FINDINGS: Treatment of astrocytes with 0.4mM H2O2 for 24h increased the expression levels of glial fibrillary acidic protein and 4-hydroxynonenal without significant decreases in their viability, indicating that induction of oxidative stress in astrocytes. Under oxidative stress-loaded conditions, astrocytes exhibited increased (65)Zn uptake activity, and the maximum uptake velocity for the uptake was significantly increased compared to that in the control group, while there was no change in the Michaelis constants, which were almost identical to that of mouse ZIP1. In the H2O2-treated astrocytes, the expression levels of ZIP1 were significantly increased in the cellular and plasma membrane fractions. SIGNIFICANCE: It appears that under oxidative stress-loaded conditions, astrocytes exhibit increased zinc clearance activity and this is due, at least in part, to increased ZIP1 expression.

Percutaneous transhepatic duodenostomy for a gastrectomy case with CT guidance and real-time visualization by an ultrasound and endoscopy.

After gastrectomy, the remnant stomach, a small stomach behind the lateral segment of the liver, is thought to be a relative contraindication to receiving a percutaneous endoscopy-guided gastrostomy (PEG). We successfully performed a percutaneous duodenostomy in a case with remnant stomach. We used a transhepatic pull method with computed tomography (CT) guidance and real-time visualization by using ultrasound (US) and an endoscopy. The procedure was as follows: 1. Full stretching of the remnant stomach; 2. Insertion of a fine injection needle into the duodenal lumen through the lateral segment of the liver without an intrahepatic vascular and biliary injury using real-time visualization through US; 3. Confirmation of the location of the fine needle using abdominal CT, which showed the fine needle penetrating through the lateral segment and the duodenal lumen; 4. Insertion of the thick needle of the PEG kit just laterally of the fine needle; 5. Confirmation of the location of the thick needle using a repeated CT; 6. Endoscopic confirmation of the location of the two needles; 7. Changing the direction of the thick needle using guidance with endoscopy, inserting the thick needle into the duodenal lumen, and removing the fine needle; 8. Insertion of the guide wire through the thick needle; and 9. Placement of the PEG tube using the pull method. Using a real-time US scan, we detected the puncture of the anterior wall of the duodenum or stomach and avoided intrahepatic major vascular and biliary injuries.

Successful nutritional support for a dysphagic patient with massive cirrhotic ascites and intrathoracic stomach using percutaneous endoscopic gastrostomy (PEG).

Although massive cirrhotic ascites is generally considered a contraindication for the placement of percutaneous endoscopic gastrostomy (PEG), such patients are usually poorly nourished. Preceding paracentesis of ascites is one method for controlling ascites and allowing the safe placement of PEG, but it often results in overuse of albumin. Preceding peritoneal-venous (P-V) shunting can avoid excessive use of albumin, but this introduces the risk of infectious contamination. We encountered an 88-y-old woman with massive cirrhotic ascites, a giant esophageal hernia with dislocation of the proximal stomach into the mediastinum, hypertrophy of the lateral segment of the liver, and malnutrition who had suffered from appetite loss and a swallowing disorder for 4 mo. She underwent PEG using a staged sequential introduction method using a Funada-style gastric wall fixation kit as follows: 1) full stretching and pushing out of the stomach from the mediastinum into the peritoneal cavity by deep insertion and a turning-over procedure of the endoscope, 2) full distention by air to adhere the gastric wall to the peritoneal wall without migration of the colon, 3) four-point square fixation under gastroenterological endoscopy without migration of the visceral organ, and 4) puncture of the needle introducer of the PEG tube in the center of the fixations under repeated gastroenterological endoscopy 3 d after the fixation. She underwent P-V shunting under local anesthesia on the 28th day after placement of PEG and enteral nutrition. Her case shows that we can achieve proper enteral nutritional support even for patients with massive cirrhotic ascites.