(1) Background: 12-lipoxygenase (12-LO) is involved in the development of diabetic nephropathy (DN). In the present study, we investigated whether 12-LO inhibition may ameliorate type-2 DN (T2DN) by interfering with insulin resistance (IR); (2) Methods: Rat glomerular mesangial cells, glomeruli and skeletal muscles were isolated and used in this study. Kidney histological changes were confirmed by periodic-acid Schiff staining; mRNA expression was detected by competitive reverse transcription polymerase chain reaction; and the protein level was determined by Western blot and the enzyme-linked immunosorbent assay, respectively; (3) Results: The inhibition of 12-LO attenuated microalbuminuria (MAU) increases in type-2 diabetic rats, but not in type-1 diabetic rats. Infusion of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly increased the expression of angiotensin II (Ang II) and Ang II type 1 receptor (AT1R), but decreased the expression of AT1R-associated protein (ATRAP) in rat glomeruli, compared to the control. An in vitro study revealed that both 12(S)-HETE and insulin upregulated AT1R expression in rat mesangial cells. In the presence of p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190, the 12(S)-HETE-induced ATRAP reduction was significantly abolished. Interestingly, 12-LO inhibition did not influence AT1R expression in type-1 diabetic rats, but significantly abolished the increased AT1R and Ang II expression in glomeruli of type-2 diabetic rats. Furthermore, the inhibition of 12-LO significantly corrected impaired insulin sensitivity and fast serum insulin level, as well as the p-AMP-activated protein kinase (AMPK) reduction in skeletal muscle of type-2 diabetic rats; (4) Conclusion: The inhibition of 12-LO potentially ameliorated MAU by preventing IR through the downregulation of glomerular AT1R expression in T2DN.
1 December 2013 in Journal of Cardiothoracic Surgery
Esophageal duplication cyst (EDC) is a congenital malformation of the posterior primitive foregut, which mainly occurs in the thoracic esophagus. Here, we describe a 3-year-old Han Chinese boy afflicted with intermittent fever of acute onset and dry cough. Thoracic computed tomography revealed an 10 cm × 5.4 cm × 5.8 cm oval-shaped, cyst-like tumor located in the extrapleural space, extending along the right paravertebral gutter and compressing the trachea forward. An additional small-sized, oval-shaped cyst was identified in the posterior mediastinum, between the esophagus and the spinal column, at the T1 level. During open thoracotomy, under general anesthesia, an opaque, thick-walled, esophageal cyst was revealed not to be in communication with the esophageal lumen or the trachea. This cyst was subsequently resected in an en bloc manner. The small (1-cm) esophageal cyst was left untreated based on a “wait-and-see” policy. Histological analysis showed that the resected cyst was walled by hyperplastic, fibrous tissues and locally lined with gastric mucosa inherent glands. This finding was consistent with a diagnosis of EDC, with ectopic gastric mucosa. The respiratory tract symptoms resolved immediately after the operation. Computed tomography obtained at the 6-month follow-up showed that no disease, residual or recurrence, was present after the resection of the large-sized cyst, and the small-sized cyst remained unchanged in size.