Biomedical subjects

Zenji Makita

Publications and source records attributed to Zenji Makita.

21 records · Page 2Linked to original sources

PubMed2002

CS-886, a new angiotensin II type 1 receptor antagonist, ameliorates glomerular anionic site loss and prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats.

BACKGROUND: Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Previous studies have documented that angiotensin converting enzyme (ACE) inhibitors consistently reduce albuminuria and retard the progression of diabetic nephropathy. However, the involvement of angiotensin II in diabetic nephropathy is not fully understood. MATERIALS AND METHODS: In this study we compared the effects of CS-866, a new angiotensin II type 1 receptor antagonist, to that of an ACE inhibitor, temocapril hydrochloride, on the development and progression of diabetic nephropathy using Otsuka Long-Evans Tokushima fatty rats, a type II diabetes mellitus model animal. RESULTS: High doses of CS-866 or temocapril treatment were found to significantly improve urinary protein and beta(2)-microglobulin excretions in diabetic rats. In electron microscopic analysis, loss of glomerular anionic sites, one of the causes of glomerular hyperpermeability in diabetic nephropathy, was found to be significantly prevented by CS-866 treatment. Light microscopic examinations revealed that both treatments ameliorated glomerular sclerosis and tubulointerstitial injury in diabetic rats. Furthermore, high doses of CS-866 or temocapril treatment significantly reduced the positive stainings for transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, and type IV collagen in glomeruli of diabetic rats. CONCLUSIONS: These results indicate that intrarenal angiotensin II type 1 receptor activation plays a dominant role in the development and progression of diabetic nephropathy. Our study suggests that CS-866 represents a valuable new drug for the treatment of diabetic patients with nephropathy.

Angiotensin II Type 1 Receptor Blockers↗

PubMedDate not supplied

Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes.

We investigated whether serum levels of N-(carboxymethyl)lysine (CML), non-CML advanced glycation endproducts (AGEs), or pentosidine are associated with severity of diabetic microvascular complications in patients with Type 1 diabetes. Serum levels of CML, non-CML AGE, and pentosidine were measured by an enzyme-linked immunosorbent assay in 38 males and 47 females aged 31+/-8 years (mean+/-S.D.) with Type 1 diabetes for 18.7+/-7.0 years. There was a significant correlation between serum levels of CML or non-CML AGE and current HbA(1c) level (P<.01 and P<.05, respectively). The serum levels of non-CML AGE, but not CML or pentosidine, were significantly increased as normal renal status advanced to microalbuminuria, clinical nephropathy, and hemodialysis (P<.0001) and were positively correlated with urinary albumin excretion (UAE) in patients with Type 1 diabetes (P<.0001). A significant elevation of serum non-CML AGE was found in association with the severity of diabetic retinopathy (P<.0001). We found in the present study that CML levels were also increased in the stage of simple retinopathy, the early stage of clinically evident retinopathy (P<.05). Serum levels of non-CML AGE were significantly associated with the severity of diabetic nephropathy and retinopathy, suggesting a role of non-CML AGE in the progression of microvascular complications in patients with Type 1 diabetes. Since serum levels of CML were significantly increased in patients with simple retinopathy, CML may participate in the initiation of diabetic retinopathy.

Adult↗

PubMedDate not supplied

AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes.

Advanced glycation end product (AGE) engagement of a cell surface receptor for AGE (RAGE) has been implicated in the development of diabetic complications. In this study, we determined the RAGE mRNA levels in monocytes from type 1 diabetic patients and analyzed their relationship with diabetic vascular complications. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the monocyte expression of RAGE mRNA was significantly lower in patients with retinopathy than in those without retinopathy and was also significantly down-regulated in patients with nephropathy in comparison with those without nephropathy. Experiments with monocyte-enriched cultures revealed that RAGE mRNA and protein levels were down-regulated by the exposure to glyceraldehyde-derived AGE-the recently identified high-affinity RAGE ligand. Accordingly, we then assayed for the serum levels of glyceraldehyde-derived AGE as well as those of carboxymethyllysine (CML)-the known RAGE ligand and related them to the monocyte levels of RAGE mRNA. This screen revealed a negative correlation between the two parameters. The results thus suggest that the decrease in monocyte RAGE expression can be at least partly accounted for by the ligand engagement and may be a factor contributing to the development of diabetic vascular complications.

Adolescent↗