Oxidized alkyl phospholipids stimulate sodium transport in proximal tubules via a nongenomic PPARγ-dependent pathway.

Oxidized phospholipids have been shown to exhibit pleiotropic effects in numerous biological contexts. For example, 1-O-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine (azPC), an oxidized phospholipid formed from alkyl phosphatidylcholines, is a peroxisome proliferator-activated receptor gamma (PPARγ) nuclear receptor agonist. Although it has been reported that PPARγ agonists including thiazolidinediones can induce plasma volume expansion by enhancing renal sodium and water retention, the role of azPC in renal transport functions is unknown. In the present study, we investigated the effect of azPC on renal proximal tubule (PT) transport using isolated PTs and kidney cortex tissues and also investigated the effect of azPC on renal sodium handling in vivo. We showed using a microperfusion technique that azPC rapidly stimulated Na+/HCO3- cotransporter 1 (NBCe1) and luminal Na+/H+ exchanger (NHE) activities in a dose-dependent manner at submicromolar concentrations in isolated PTs from rats and humans. The rapid effects (within a few minutes) suggest that azPC activates NBCe1 and NHE via nongenomic signaling. The stimulatory effects were completely blocked by specific PPARγ antagonist GW9662, ERK kinase inhibitor PD98059, and CD36 inhibitor sulfosuccinimidyl oleate. Treatment with an siRNA against PPAR gamma completely blocked the stimulation of both NBCe1 and NHE by azPC. Moreover, azPC induced ERK phosphorylation in rat and human kidney cortex tissues, which were completely suppressed by GW9662 and PD98059 treatments. These results suggest that azPC stimulates renal PT sodium-coupled bicarbonate transport via a CD36/PPARγ/mitogen-activated protein/ERK kinase/ERK pathway. We conclude that the stimulatory effects of azPC on PT transport may be partially involved in volume expansion.

[Asynchronous Bilateral Neuroendocrine Breast Carcinoma - A Case Report].

We report a case of asynchronous bilateral neuroendocrine breast carcinoma. The patient was a 49-year-old woman presenting with a bloody nipple discharge from the right breast. We suspected intraductal papilloma and performed a microdochectomy. A pathological analysis of the resected specimen confirmed the diagnosis as neuroendocrine carcinoma. The tumor was positive for estrogen receptor, progesterone receptor, chromogranin A, and synaptophysin, but negative for the HER2/neu marker. The Ki-67 labeling-index was 40%. As the tumor margin was positive, breast-conserving surgery plus level II axillary lymph node dissection was performed. After surgery, radiotherapy(total dose of 50 Gy)was administered for treating residual breast involvement. Adjuvant hormonal therapy was performed for 5 years. Ten years after surgery, ultrasonography revealed a 12mm irregular hypoechoic mass in the left breast. The mass was diagnosed as a solid tubular carcinoma based on core needle biopsy findings. Subsequently, we performed breast-conserving surgery. The pathological diagnosis was a neuroendocrine carcinoma, and the tumor was positive for estrogen receptor, progesterone receptor, chromogranin A, synaptophysin, and CD56, but negative for the HER2/neu marker. The Ki-67 labeling-index was 50%. We report our experiences with a rare case of asynchronous bilateral neuroendocrine breast carcinoma. In this case, ultrasonography was a useful modality for detecting both the lesions.

Serum adiponectin and leptin in a patient with Cushing's syndrome before and after adrenalectomy.

We measured the serum adiponectin and leptin concentrations before and after successful removal of a left adrenal adenoma in a 46-year-old woman with Cushing's syndrome. The serum adiponectin level was 6.0 microg/ml before the operation and rose to 8.1 microg/ml after adrenalectomy. However, the serum leptin level was markedly high (24.8 ng/ml) before the operation and decreased to within the normal range (6.0 ng/ml) 6 months after adrenalectomy, concomitant with weight reduction and normalization of the serum cortisol level.