Increased urinary excretion of N-acetylglucosaminidase in subjects with impaired glucose tolerance

N-acetylglucosaminidase (NAG) is a lysosomal enzyme produced by renal proximal tubular cells and has been widely used as a marker, which indicates a degree of renal tubular damage. An increase in urinary NAG excretion is though to result from the renal tubular damage. The aim of this study was to evaluate whether even mild hyperglycemia causes an increase in urinary excretion of NAG, which is a renal tubular protein. We examined urinary NAG excretion in overnight urine in 22 Japanese men with impaired glucose tolerance (IGT) for more than two years (IGT group) and 41 healthy control subjects matched in age, gender, BMI and blood pressure (control group). Urinary NAG excretion levels of IGT group and control group were 2.89 (1.23-7.97) and 2.22 (0.60-4.93) U/g creatinine, median (range), respectively. The IGT group showed significantly higher urinary excretion of NAG compared to the control group (p < 0.01). Several studies have indicated that plasma proteins filtered through the glomerular capillary may have intrinsic renal toxicity. Recently, we have reported that urinary excretion of plasma proteins (ceruloplasmin, IgG4 and IgG) with molecular radii of approximately 45-55 A is increased in subjects with IGT compared to healthy control subjects with normal glucose tolerance. Considering the present result together with our recent finding, we suggest that increased urinary excretion of NAG in the mildly hyperglycemic subjects may be due to the adverse effects of the plasma proteins highly filtered through the glomerular capillary on tubular cells.     

Aggressive antihypertensive treatment and serum lipid lowering therapy are necessary to prevent deterioration of the renal function even in elderly type 2 diabetic patients with persistent albuminuria

BACKGROUND: In elderly patients with diabetic nephropathy, clinical information aiming at preventing a decline of the renal function is limited. OBJECTIVE: To clarify factors that could be related to changes in renal function in elderly diabetic patients with persistent albuminuria. METHODS: We studied the relationships between the declining rate of creatinine clearance (Ccr) and other clinical features - glycemic control, blood pressure (BP), the degree of albuminuria, and other confounding factors - retrospectively in elderly diabetic patients with persistent albuminuria. RESULTS: We analyzed 17 elderly diabetic patients with persistent albuminuria (4 men and 13 women, mean age 68.0 +/- 5.7 years at the beginning of the observation period) for 3.7 +/- 1.5 (SD) years. We found that the last value of the urinary albumin excretion (UAE) of the observation period and the individual mean values of systolic BP, mean BP, and serum cholesterol closely correlated with the rate of decline in Ccr estimated by Cockcroft's formula. The last UAE closely correlated with the individual mean values of systolic BP and mean BP. For patients such as the present subjects, adequate retardation of decline in renal function requires that the estimated goal of antihypertensive treatment should be a BP below 130/70 mm Hg. The level of glycemic control and the use of angiotensin-converting enzyme inhibitors did not correlate with the rate of decline in Ccr. CONCLUSION: Aggressive antihypertensive treatment and serum lipid lowering therapy may be necessary to prevent deterioration of the renal function in elderly type 2 diabetic patients with persistent albuminuria.     

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

The Cerebellum - Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event...     

A case of renal juxtaglomerular cell tumor: usefulness of segmental sampling to prove autonomic secretion of the tumor.

A 27-year-old female patient had been treated for hypertension with conventional therapy for years, because renal vein renin levels failed to show lateralization in renal venous samplings and a renal juxtaglomerular cell tumor (RJGCT) had gone undiagnosed. Abdominal computed tomography revealed a mass at the middle of the right kidney. The right renal venogram demonstrated distinct segmental veins from the upper pole and from the middle and lower poles in the right kidney. On segmental renin sampling from each renal vein, the plasma renin concentration (PRC) of the segmental veins from the middle and lower poles was higher than that from other sites. We diagnosed RJGCT of the right kidney and performed right-sided nephrectomy. After the resection, the PRC rapidly decreased. Immunohistochemical studies using antihuman renin antibodies revealed positive staining of the tumor cells. It is an important strategy to make a segmental sampling at the site as close as possible to the RJGCT.     

Time course and spacial distribution of UV effects on human skin in organ culture

Apoptosis plays an important role in eliminating cells from populations when cells have been exposed to UV irradiation and damaged. Studies of cells in culture have provided some details of the mechanisms involved when stress response genes act after exposure to UV irradiation and other environmental stresses. However, little is known about the responses of intact sections of human skin growing in organ culture to UV irradiation. In the work reported here, it was found that the response of organ-cultured human skin after exposure to UV irradiation is different than the response of cultured cells. At wavelengths below 300 nm, the action spectrum obtained from organ-cultured skin samples showed a lower sensitivity than that observed at 300 nm, indicating that the overlying stratum corneum and upper epidermal cell layers had probably caused a selective absorption of incident UV radiation at some wavelengths. At 3 hours after UV irradiation, p53 was phosphorylated at Ser 15 and Ser 46, and accumulated in the cell nuclei, notably after exposure to 280-320 nm wavelengths. Accumulations of Bax, active Caspase-3 and cleaved PARP were detected in apoptotic cells at 24 hours post-exposure, along with a reduction of Bcl-2 levels, notably after exposure to 300-365 nm light. This difference in apoptotic responses may result from the characteristics of the different irradiation wavelengths used, and from details in the skin's structure. The data obtained in this study using an organ-culture system utilized direct measurements of the biological effects of different wavelengths of UV lights.