Renal connective tissue growth factor induction in experimental diabetes is prevented by aminoguanidine.

The aim of this study was to determine whether aminoguanidine (AG), an inhibitor of advanced glycation, prevents expression of the profibrotic cytokine, connective tissue growth factor (CTGF), as well as accumulation of the previously reported CTGF-dependent matrix protein, fibronectin, in a model of experimental diabetic nephropathy. Diabetic animals were randomly allocated into groups receiving 32 wk of AG or vehicle. Diabetic rats showed increases in CTGF mRNA and protein expression as well as in advanced glycation end-product (AGE) and fibronectin immunostaining, compared with nondiabetic rats. In the diabetic kidney, the increase in CTGF gene and protein expression as well as expression of the extracellular matrix protein fibronectin were prevented by AG. To further explore the relationship between AGEs and mesangial CTGF and fibronectin production, cultured human mesangial cells were exposed in vitro to soluble AGE-BSA and carboxymethyl lysine-BSA, and this led to induction of both CTGF and fibronectin. On the basis of our in vitro findings in mesangial cells linking AGEs to CTGF expression, the known prosclerotic effects of CTGF, and the ability of AG to attenuate mesangial expansion, it is postulated that the antifibrotic effects of AG in this animal model may be partially mediated by CTGF.

The effects of aminoguanidine on renal changes in a baboon model of Type 1 diabetes.

BACKGROUND: The efficacy of aminoguanidine (AG) on primary prevention of diabetic nephropathy was investigated in a nonhuman primate model of Type 1 diabetes over a period of 4 years. METHODS: Adolescent male baboons (Papio hamadryas) were assigned to four groups: control, diabetic, and control and diabetic treated with AG. Diabetes was induced with streptozocin (60 mg/kg) and treated with insulin to maintain a mean HbA1c level of about 9%. AG was given subcutaneously (10 mg/kg) each day. All animals had annual renal biopsies and 24-h urine collections for measurements of glomerular basement membrane (GBM) thickness, fractional mesangium volume (FMV), albumin excretion rate (AER), and creatinine clearance. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were also determined. RESULT: The diabetic animals had increased GBM after 2 years of diabetes, but there was no increase in FMV over the study period. AG prevented the thickening of GBM at the 3- and 4-year time points. AG and diabetes synergistically increased the GFR. All diabetic animals developed increased albuminuria during the study although lower than the conventionally accepted microalbuminuria range. AG was not able to prevent this and, in fact, led to the nondiabetic animals also developing albuminuria. CONCLUSION: This is the first study to investigate the early use of AG in ameliorating renal damage in a primate model of Type 1 diabetes. The structural and functional changes in the kidney of these animals resemble those seen in the early stages of the human disease. AG was able to significantly reduce the thickening of GBM due to diabetes. This may suggest a potential role for this in primary prevention of diabetic nephropathy in the future.

A comparison of the effect of refresh plus and bion tears on dry eye symptoms and ocular surface health in myopic LASIK patients.

PURPOSE: To compare the effect of artificial tears (0.5% carboxymethylcellulose [CMC] in lactate buffer vs. 0.3% hydroxypropyl methylcellulose and 0.1% dextran in bicarbonate buffer [HPMC]) on the preservation of ocular surface health in postoperative laser in situ keratomileusis (LASIK) patients. METHODS: Nonrandomized, comparative, retrospective analysis of a clinical database. Patients (n = 519; 985 eyes) had undergone LASIK in a single refractive surgery center performed by a single surgeon using the same LASIK technique (Nidek EC5000 laser and ACS keratome). Patients (n = 254) were given CMC (Refresh Plus/Cellufresh) or HPMC (Bion Tears) four times per day and were evaluated at presurgery, week 2, and months 1, 3, and 6. Included patients were those with complete clinical data through the month I follow-up visit. RESULTS: There were no significant between-group differences in any baseline variable. Following LASIK, fewer CMC patients (n = 111) reported dry eye symptoms than HPMC patients (n = 143) at the week 2 (13.5% vs. 30.8%; P = .001) and month 1 (19.8% vs. 38.5%; P = .001) follow-up visits. CMC patients also had significantly lower mean ocular surface staining scores than HPMC patients at week 2 (0.09 vs. 0.30; P = .015) and month 1 (0.05 vs. 0.28; P = .008). There were no between-group differences in either measure at months 3 or 6 (P < or = .728). CONCLUSIONS: CMC was more effective than HPMC in controlling dry eye symptoms and preserving ocular surface health in the immediate postoperative period in myopic post-LASIK patients, possibly due to the greater muco-adhesive properties of CMC. These results warrant further investigation as to the most effective postoperative LASIK lubricant.