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The effect of pitavastatin and pravastatin treatment on renal function was compared in type 2 diabetic patients with nephropathy in a randomized, controlled, open-label, parallel and multi-centre study. Type 2 diabetic patients with modest renal impairment (serum creatinine level <1.4 mg/dl) accompanied by albuminuria (30-600 mg/g creatinine) were randomly assigned to receive 2 mg of pitavastatin (n = 44) or 10 mg of pravastatin (n = 43) for 12 months. At 12 months, pitavastatin significantly reduced urinary albumin-to-creatinine ratio than pravastatin in subjects with macroalbuminuria (−67.2% vs. +14.5%, p = 0.0040), but not in subjects with microalbuminuria. There was no significant difference in the change in estimated glomerular filtration rate between the two groups. Pitavastatin is more effective than pravastatin for the reduction of albuminuria in type 2 diabetic patients with early stage of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Recent studies have uncovered various pleiotrophic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase-inhibiting drugs (statins). Several studies have identified a beneficial effect of statins on diabetic nephropathy; however, the molecular mechanisms are unclear. In this study, we show that statin ameliorates nephropathy in db/db mice, a rodent model of type 2 diabetes, via downregulation of NAD(P)H oxidase NOX4, which is a major source of oxidative stress in the kidney. Pitavastatin treatment for 2 weeks starting at 12 weeks of age significantly reduced albuminuria in the db/db mice concomitant with a reduction of urinary 8-hydroxy-2′-deoxyguanosine and 8-epi-prostaglandin F2α. Immunohistochemical analysis found increased amounts of 8-hydroxy-2′-deoxyguanosine and NOX4 protein in the kidney of db/db mice. Quantitative reverse transcription-polymerase chain reaction also showed increased levels of NOX4 mRNA. Pitavastatin normalized all of these changes in the kidneys of diabetic animals. Additionally, 12-week treatment with the statin completely normalized the levels of transforming growth factor-β1 and fibronectin mRNA as well as the mesangial expansion characteristic of diabetic nephropathy. Our study demonstrates that pitavastatin ameliorates diabetic nephropathy in db/db mice by minimizing oxidative stress by downregulating NOX4 expression. These findings may provide insight into the mechanisms of statin therapy in early stages of diabetic nephropathy.Kidney International (2007) 72, 473–480; doi:10.1038/sj.ki.5002366; published online 13 June 2007 [ABSTRACT FROM AUTHOR]

The presence of metabolic syndrome (MetS) and its individual components is related to an increased IMT. MetS and increasing numbers of individual MetS components predicted future progression of IMT. Improvement of MetS was related to smaller increases in IMT, especially in females. These findings may suggest a benefit of intervention for MetS, which needs to be confirmed by prospective studies. [ABSTRACT FROM AUTHOR]

Background: Inner ear malformations may cause sensorineural hearing loss (SNHL). However, the correlation between the small lateral semi-circular canal (LSCC) and SNHL is controversial. Purpose: To determine whether there is a correlation between the two using CT-based measurement. Material and Methods: We retrospectively reviewed the high-resolution CT images of the temporal bone obtained from consecutive patients. A total 136 ears of 68 patients (25 men and 43 women; age range 20-85 years, mean 49.8 years) were included in this study. Patients who were clinically suspected to have otosclerosis were also excluded. Two radiologists independently measured the width and cross-sectional area of the bony island of LSCC. We evaluated the correlation between LSCC bone island width or cross-sectional area and hearing level in all cases using Pearson correlation co-efficients. In addition, we compared hearing levels among the patient group with normal-sized LSCC (≧mean-SD), small LSCC (Results: A total 136 ears of 68 patients (25 men and 43 women; age range 20-85 years, mean 49.8 years) were included in this study. No significant correlation was shown between LSCC bony island width or cross-sectional area and hearing level (P > 0.05). No significant difference in hearing levels were found among groups of the normal-sized, small and very small LSCC (P > 0.05). Conclusion: We conclude that there is no correlation between isolated small LSCC and SNHL. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 micromol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome. [ABSTRACT FROM AUTHOR]

Gap junction is thought to have a crucial role in maintaining tissue homeostasis. We examined the effect of a high glucose level on gap junctional intercellular communication (GJIC) activity in cultured vascular smooth muscle cells (VSMCs) using the fluorescent dye transfer method. After a 48-h incubation with 22 mmol/l glucose (high glucose level), GJIC activity of VSMCs was significantly reduced compared with incubation with 5.5 mmol/l glucose (normal glucose level) (P < 0.05). Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA; 5 x 10(-8) mol/l), a protein kinase C (PKC) activator, for 1 h also reduced GJIC activity (P < 0.01). In addition, treatment of the cells with calphostin C, a specific PKC inhibitor, for 3 h completely restored the GJIC activity inhibited by the high glucose level. Western blot analysis showed that connexin 43 (Cx43), which is the major functional protein of gap junction, is present in multiphosphorylated forms: a nonphosphorylated form (P0) and phosphorylated forms (P1, P2, and P3). Incubation of VSMCs with a high glucose level significantly increased the density ratio of P3/P0 compared with a normal glucose level (P < 0.05). Similarly, treatment of the cells with TPA significantly increased the P3/P0 ratio compared with controls (P < 0.01). In addition, the increase in the P3/P0 density ratio induced by a high glucose level was restored to the control level by both staurosporine and calphostin C. These results suggest that the high glucose level induced the inhibition of GJIC activity in cultured VSMCs through excessive phosphorylation of Cx43, mediated by PKC activation. This may contribute to the development of the macroangiopathy associated with diabetes. [ABSTRACT FROM AUTHOR]