A study of the native kidneys in patients with chronic renal failure. Report 1: Morphological changes and occurrence of acquired cysts of the native kidneys in patients with chronic renal failure

As morphological changes of the native kidneys, the presence of acquired cysts, intra-renal calcification and renal tumor was investigated mainly by ultrasonography and computed tomography in 151 patients with chronic renal failure. 1) Among 140 uremic patients caused by medical diseases. 40 patients had simple cysts, and 37 had acquired cystic disease of the kidneys (ACDK). However 4, uremic patients caused by urological diseases were not seen to be with an acquired cysts. 2) The patients with ACDK were with significantly longer durations of dialysis therapy than those with simple cysts or no cysts. Furthermore, the patients with ACDK were younger than those of the other groups. 3) Intra-renal calcification was more frequently found in patients with cystic disease (simple cyst, ACDK and polycystic disease) than in those without cystic disease with statistic significance. 4) Native kidneys became larger after the occurrence of ACDK. 5) Three cases of renal tumor were found.     

Skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) by inhibiting activation of the IGF-I signaling pathways.

We showed that unloading markedly diminished the effects of IGF-I to activate its signaling pathways, and the disintegrin echistatin showed a similar block in osteoprogenitor cells. Furthermore, unloading decreased alphaVbeta3 integrin expression. These results show that skeletal unloading induces resistance to IGF-I by inhibiting activation of the IGF-I signaling pathways at least in part through downregulation of integrin signaling. INTRODUCTION: We have previously reported that skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) with respect to bone formation. However, the underlying mechanism remains unclear. The aim of this study was to clarify how skeletal unloading induces resistance to the effects of IGF-I administration in vivo and in vitro with respect to bone formation. MATERIALS AND METHODS: We first determined the response of bone to IGF-I administration in vivo during skeletal unloading. We then evaluated the response of osteoprogenitor cells isolated from unloaded bones to IGF-I treatment in vitro with respect to activation of the IGF-I signaling pathways. Finally we examined the potential role of integrins in mediating the responsiveness of osteoprogenitor cells to IGF-I. RESULTS: IGF-I administration in vivo significantly increased proliferation of osteoblasts. Unloading markedly decreased proliferation and blocked the ability of IGF-I to increase proliferation. On a cellular level, IGF-I treatment in vitro stimulated the activation of its receptor, Ras, ERK1/2 (p44/42 MAPK), and Akt in cultured osteoprogenitor cells from normally loaded bones, but these effects were markedly diminished in cells from unloaded bones. These results were not caused by altered phosphatase activity or changes in receptor binding to IGF-I. Inhibition of the Ras/MAPK pathway was more impacted by unloading than that of Akt. The disintegrin echistatin (an antagonist of the alphaVbeta3 integrin) blocked the ability of IGF-I to stimulate its receptor phosphorylation and osteoblast proliferation, similar to that seen in cells from unloaded bone. Furthermore, unloading significantly decreased the mRNA levels both of alphaV and beta3 integrin subunits in osteoprogenitor cells. CONCLUSION: These results indicate that skeletal unloading induces resistance to IGF-I by inhibiting the activation of IGF-I signaling pathways, at least in part, through downregulation of integrin signaling, resulting in decreased proliferation of osteoblasts and their precursors.     

ENDOSCOPIC PANCREATIC STENTING IN CHRONIC PANCREATITIS WITH DUCTAL DILATION PROXIMAL TO A STRICTURE: A SAFE and EFFECTIVE PROTOCOL

After removal of intraductal stones, a 10‐Fr or 7‐Fr pancreatic stent was placed in 16 patients with upstream ductal dilation proximal to a stricture of the main pancreatic duct. Stents were removed after a mean duration of 52.5 days. Nine patients underwent repeated stenting. About one year after removal of the initial stent, when the remaining upstream ductal dilation was found on follow‐up pancreatograms, the next stent was replaced. Repeated stenting improved outflow of pancreatic juice more effectively than one‐time stenting. Correlation between long‐term pain relief without recurrence of intraductal stones and reduction of duct diameter was also shown. Stent occlusion was observed in 14 of 30 stents. Stent occlusion was frequently associated with recurrence of pancreatitis and intraductal stones, and was also associated with morphologic changes in the pancreatic ductal system. Although there were no significant differences between stent patency of the initial stents and that of the next stents, stent patency of 10‐Fr stents was superior to that of 7‐Fr stents. 10‐Fr stents should be removed within 8 weeks and 7‐Fr stents should be removed within 4 weeks for the prevention of stent occlusion. Repeated stenting with short‐term stenting is therefore considered a safe and effective protocol of endoscopic pancreatic stenting.     

Bezafibrate improves hypertension and insulin sensitivity in humans.

We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140 +/- 2.6 to 131.8 +/- 2.6 mmHg, mean +/- SEM), diastolic blood pressure (DBP) (87.8 +/- 2.0 to 82.8 +/- 2.6 mmHg), fasting plasma triglyceride concentration (225.5 +/- 23.5 to 102.9 +/- 10.9 mg/dl), fasting plasma insulin concentration (9.6 +/- 0.8 to 7.1 +/- 0.8 microU/ml), and homeostasis model assessment scores (HOMA-R, 2.4 +/- 0.2 to 1.7 +/- 0.2), and significantly improved the insulin sensitivity index (56.0 +/- 3.0 to 70.7 +/- 4.8 mg x l2/mmol x mU x min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r = 0.50, p < 0.01) and SFA (r = 0.39, p < 0.05), and negatively correlated with PUFA (r = -0.45, p < 0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders.