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J Sivak

Publications and source records attributed to J Sivak.

9 recordsLinked to original sources

Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B.

We have studied mechanisms controlling activation of the gelatinase B gene (matrix metalloproteinase-9) by fibroblast growth factor-2 (FGF-2) during angiogenesis, and the effects of the natural product curcuminoids on this process. Using a transgenic mouse (line 3445) harboring a gelatinase B promoter/lacZ fusion gene, we demonstrate FGF-2 stimulation of reporter gene expression in endothelial cells of invading neocapillaries in the corneal micropocket assay. Using cultured corneal cells, we show that FGF-2 stimulates DNA binding activity of transcription factor AP-1 but not NF-kappaB and that AP-1 stimulation is inhibited by curcuminoids. We further show that induction of gelatinase B transcriptional promoter activity in response to FGF-2 is dependent on AP-1 but not NF-kappaB response elements and that promoter activity is also inhibited by curcuminoids. In rabbit corneas, the angiogenic response induced by implantation of an FGF-2 pellet is inhibited by the co-implantation of a curcuminoid pellet, and this correlates with inhibition of endogenous gelatinase B expression induced by FGF-2. Angiostatic efficacy in the cornea is also observed when curcuminoids are provided to mice in the diet. Our findings provide evidence that curcuminoids target the FGF-2 angiogenic signaling pathway and inhibit expression of gelatinase B in the angiogenic process.

Angiogenesis Inhibitors↗

High-fructose feeding of streptozotocin-diabetic rats is associated with increased cataract formation and increased oxidative stress in the kidney.

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P < 0.001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P < 0.0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P < 0.0004 and P < 0.0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P < 0.01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P < 0.01). Micro-albuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.

Analysis of Variance↗

Vision of the Humboldt penguin (Spheniscus humboldti) in air and water.

Refractive states measured by retinoscopy and photorefraction indicate that the eyes of the Humboldt penguin, Spheniscus humboldti, are approximately emmetropic in air and water. Extensive myopia in air, as predicted by earlier authors and by a recent anatomical study, is non-existent. Photorefractive measurements of the refractive state, in water, of the Humboldt penguin indicate that it can accommodate sufficiently to make up the loss of the refractive power of the cornea. The cornea of the Humboldt penguin is flattened relative to the overall size of the eye. In all these respects (corneal flattening, and accommodation in air and water) the eyes of Humboldt penguins are like those of gentoo, (Pygoscelis papua), rockhopper (Eudyptes crestatus), Magellanic (Spheniscus magellanicus), and king penguins (Aptenodytes patagonica).

Animals↗

Crystalline lens dispersion.

The spectral dispersions of rabbit, rat, pigeon, and human crystalline lens material have been measured with a Pulfrich refractometer. The refractive indices all increase rapidly at the violet end of the spectrum so tat the chromatic aberrations of the eyes of these species cannot be derived adequately from Cornu's formula, as had previously been assumed.

Aged↗