AMP-activated protein kinase inhibits TGF-ß-, angiotensin II-, aldosterone-, high glucose-, and albumin-induced epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is a novel mechanism that promotes renal fibrosis. Transforming growth factor-ß (TGF-ß), angiotensin II, aldosterone, high glucose, and urinary albumin are well-known causes of EMT and renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed EMT induced by the above agents in tubular epithelial cells. All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. Exposure of tubular cells to TGF-ß (10 ng/ml), angiotensin II (1 µM), aldosterone (100 nM), high glucose (30 mM), and albumin (5 mg/ml) for 5 days induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ROS and NADPH oxidase 4 (Nox4) expression were increased, and antioxidants such as tiron and N-acetylcysteine inhibited EMT induction. Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin. An AMPK inhibitor (compound C) and AMPK small interfering RNA blocked the effect of metformin, and another AMPK activator [5-aminoimidazole-4-carboxamide-1ß riboside (AICAR)] exerted the same effects as metformin. In conclusion, AMPK activation might be beneficial in attenuating the tubulointerstitial fibrosis induced by TGF-ß, angiotensin II, aldosterone, high glucose, and urinary albumin.

Does stage III chronic kidney disease always progress to end-stage renal disease? A ten-year follow-up study.

OBJECTIVE: Clinically, it may be appropriate to subdivide patients with stage 3 chronic kidney disease (CKD) into two subgroups, as they show different risks for kidney outcomes. This study evaluated the proportion of patients with stage 3 CKD who progressed to stage 4 or 5 CKD over 10 years and independent predictors of progression of renal dysfunction. It sought to validate whether stage 3 CKD patients should be subdivided. MATERIAL AND METHODS: This retrospective cohort study enrolled 347 stage 3 CKD patients between January 1997 and December 1999, who were followed up through June 2010. The baseline clinical characteristics and outcomes were compared in patients with stage 3A [45

Combination treatment with intrahepatic arterial infusion and intratumoral injection chemotherapy in patients with far-advanced hepatocellular carcinoma and arterioportal or arteriovenous shunts: preliminary results.

BACKGROUND/AIMS: Combination treatment consisting of hepatic arterial infusion chemotherapy with epirubicin and cisplatin (HAIC-EC) and systemic infusion of low-dose 5-fluorouracil (5-FU) are sometimes effective against advanced hepatocellular carcinoma (HCC). However, there is no effective treatment for advanced HCCs with arterioportal shunts (APS) or arteriovenous shunts (AVS). METHODS: We investigated a response and adverse events of a new combination protocol of repeated HAIC-EC and percutaneous intratumoral injection chemotherapy with a mixture of recombinant interferon-gamma (IFN-γ) and 5-FU (PIC-IF) in patients with far-advanced HCCs with large APSs or AVSs. RESULTS: There was a complete response (CR) for the large vascular shunts in all three patients and for all tumor burdens in two patients. Significant side effects were flu-like symptoms (grade 2) and bone marrow suppression (grade 2 or 3) after each cycle, but these were well-tolerated. CONCLUSIONS: These results suggest that the combination of HAIC-EC and PIC-IF is a new and promising approach for advanced HCC accompanied by a large APS or AVS.

[A case of acute phlegmonous gastritis causing gastroparesis and cured with medical treatment alone].

Acute phlegmonous gastritis is an uncommon disease, often fatal condition characterized by suppurative bacterial infection of the gastric wall. It has a high mortality rate mainly because the diagnosis is usually made late. Until recently, gastrectomy in combination with antibiotics was recommended. We had experienced a case of 66-year-old man presented with epigastric pain, nausea, vomiting, and hematemesis, followed by aspiration pneumonia. At upper gastrointestinal endoscopy, the gastric lumen was narrow, and the mucosa was severely inflamed, which was erythematous, swelled, and showed necrotic areas covered with purulent exudate. Klebsiella oxytoca and Acinetobacter lwoffii were isolated in the gastric tissue culture. Contrast-enhanced computerized tomography scan of abdomen demonstrated diffuse gastric wall thickening and an intramural abscess in the gastric antral wall. Although delayed gastric emptying by gastroparesis prolonged the in-hospital period, the only medical treatment with antibiotics alone successfully cured the patient without gastrectomy.