Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis.

The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were >2.0-fold up-regulated and 243 genes that were <0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis.

Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial.

OBJECTIVE: Equol is a metabolite of the isoflavone daidzein and may play a critical role in preventing bone loss by soy isoflavones in postmenopausal women. However, results from clinical trials have not been published. The aim of this study was to investigate the effects of equol on bone metabolism and serum sex and thyroid hormone levels in postmenopausal Japanese women. METHODS: We performed a 1-year double-blind, randomized, placebo-controlled trial with natural S-equol supplements for 93 non-equol-producing menopausal Japanese women. Participants were randomly assigned to four groups receiving the following: placebo, 2 mg of equol supplement per day, 6 mg of equol supplement per day, and 10 mg of equol supplement per day. RESULTS: Equol intervention increased equol concentrations in serum and urine in a dose-dependent manner. Urinary deoxypyridinoline was significantly decreased, with a -23.94% change in the group that received 10 mg of equol supplement per day as compared with a -2.87% change in the group that received placebo after 12 months of intervention (P = 0.020). Thus, 10 mg/day of equol supplement markedly inhibited bone resorption. Treatment with 10 mg/day of equol prevented a decrease in bone mineral density in the entire body in postmenopausal women after 12 months. Sex and thyroid hormone concentrations in serum did not differ among the four groups after intervention. CONCLUSIONS: These findings suggest that 10 mg/day of natural S-equol supplementation contributes to bone health in non-equol-producing postmenopausal women without adverse effects.

The mechanism of renal stone formation and renal failure induced by administration of melamine and cyanuric acid.

Renal stone formation and renal failure among Chinese infants administered melamine-containing formula were increasingly reported in 2008. We investigated the mechanism by which melamine and cyanuric acid induce renal stone formation and renal failure. Ten-week-old rats were administered either melamine [2.4, 24, or 240 mg/kg/day], both melamine and cyanuric acid [each at 1.2, 12, or 120 mg/kg/day], or water (controls). Blood and 24-h urine samples and kidney sections were evaluated on days 3, 7, and 14. In rats administered melamine alone or the low-dose melamine/cyanuric acid combination [1.2 mg/kg/day], crystals were not detected. On day 3, crystal formation was observed in the renal distal tubular lumens and collecting ducts of rats administered the intermediate-dose melamine/cyanuric acid [12 mg/kg/day], and the number of crystals increased during the course of the experiment. In rats administered the high-dose melamine/cyanuric acid [120 mg/kg/day], crystals were found in the proximal tubular lumens of the renal cortex on day 3, but acute renal failure resulted in death by day 7. Polarized light optical microphotography and scanning electron microscopy revealed tubular lumens occluded by a layer of axle-shaped crystals. X-ray diffraction findings revealed a nitrogen component but no calcium. The upper regions of occluded tubes were expanded, and the epithelium was thin. Melamine and cyanuric acid in combination, but not by melamine alone induce crystal formation and affected renal functioning. Renal failure due to melamine cyanurate crystals appears to occur via tubular occlusion.

[A case of colon cancer with multiple liver, lung and bone metastases successfully treated with combined weekly high-dose 5-FU (WHF) chemotherapy with UFT and CPT-11].

A 54-year-old woman who had ascending colon cancer with multiple liver and lung metastases underwent rt. hemicolectomy and catheter insertion into the gastroduodenal artery for arterial infusion chemotherapy. On postoperative day 7, she had nausea and vomiting due to the enlarged multiple liver metastases on lateral segment. Intraarterial infusion of 5-FU 1,000 mg/m(2) for 5 hours weekly (WHF: weekly high-dose 5-FU) was started at first. After 3 courses, her symptoms improved, oral intake could be started, and liver metastases showed significant reduction on abdominal CT. Three months after surgery, bone scinti revealed multiple bone metastases. Combined HAI (5-FU: 600 mg/m(2)/3 hr) chemotherapy with UFT (400 mg/body) + CPT-11(80/body) and UFT (400 mg/body)/LV (75 mg/body) + CPT-11(100 mg/body) were effective for highly advanced colon cancer in terms of QOL. Eight months after surgery, she was doing well and the chemotherapy was continued. WHF therapy was effective for digestive symptoms due to liver metastasis.