Effect of dietary soy protein on tumor necrosis factor productivity in macrophages from nephritic and hepatoma-bearing rats.

The present study investigated the effect of dietary soy protein isolate (SPI) on tumor necrosis factor-alpha (TNF) productivity in peritoneal macrophages from nephritic and hepatoma-bearing rats. Dietary SPI significantly inhibited the elevated production of TNF by lipopolysaccharide-stimulated macrophages in nephritic and hepatoma-bearing rats compared with dietary casein, while it exerted no influence on the TNF productivity in normal rats. Removal of the minor components contained in SPI by ethanol extraction could significantly or partially restore the reduced TNF production caused by SPI in nephritic and hepatoma-bearing rats, respectively. These results suggest that dietary SPI could suppress the enhanced productivity of TNF associated with the progression of nephritis and hepatoma, and some factors existing in the ethanol extract of SPI are suggested to be involved in suppressing TNF productivity by macrophages.

Activity of a novel PDGF beta-receptor enhancer during the cell cycle and upon differentiation of neuroblastoma.

PDGF acts as an autocrine and paracrine factor in certain tumors through upregulation of the PDGF beta-receptor expression. In order to elucidate the control mechanism for the receptor expression, we have isolated an enhancer from two P1 clones that together contain a 102 kb NotI region covering the entire human PDGFRB gene. They were partially digested with TspI and cloned into the PDGFRB enhancer trap vector to make a library for identification of enhancers. The digested DNA containing enhancer was identified by expression of GFP when transfected in PDGF beta-receptor expressing cells. One of the enhancer clones was further examined by making several deletion mutants in a luciferase vector. This enhancer was most active in neuroblastoma cells, IMR32 and BE2, but less active in hemangioma and in smooth muscle cell lines. Chip assay revealed that SP1, AP2, and GATA2 bound the enhancer in BE2 cells. Their interaction occurred dependently of the cell cycle and synchronously with their binding to the promoter. Transfection of GATA2 alone or with Ets, which binds adjacent to GATA, resulted in differentiation of BE2 cells in parallel with increased PDGF beta-receptor expression. Furthermore, over-expression of the PDGF beta-receptor in BE2 cells induced neurite extension.

Comparison of the effects of angiotensin receptor antagonist, angiotensin converting enzyme inhibitor, and their combination on regression of left ventricular hypertrophy of diabetes type 2 patients on recent onset hemodialysis therapy.

Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy of diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. In patients with hypertension and LVH, both an angiotensin converting enzyme (ACE) inhibitor and an angiotensin type 1 receptor (AT1) antagonist regress LVH. However, it remains controversial whether dual blockade of the renin-angiotensin system will regress LVH in these patients using a combination of ACE inhibitor and AT1 antagonist. Thirty-three type II diabetic patients with end-stage renal disease who had just entered into hemodialysis therapy and were diagnosed as having LVH evaluated by echocardiography were selected from three dialysis units staffed by the faculty of Saitama Medical School, Saitama, Japan between 1999 and 2001. The study was carried out for 1 year. All patients were assigned randomly to three groups with equal number: group I, an ACE inhibitor, enalapril 10 mg daily; group II, an AT1 antagonist, losartan 100 mg daily; group III, combination of enalapril 10 mg and losartan 100 mg daily. All antihypertensive drugs were given 30 min after the cessation of dialysis therapy. LVH was evaluated by echocardiography before the start of administration of drugs, at 6 months and 12 months after the start of drug therapy. Systolic blood pressure levels less than 140 mmHg were the target for the three groups. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive decreases over time in left ventricular mass index, posterior wall thickness and interventricular septum thickness. There were no significant differences in regression of LVH as well as blood pressure control between enalapril and losartan groups; however, dual blockade induced an additional 28% reduction in left ventricular mass index compared with any type of monotherapy. Both ACE inhibitors and AT1 antagonists benefit the regression of LVH in diabetic patients who start dialysis therapy. Moreover, combination therapy with ACE inhibitors and AT1 antagonists would provide more beneficial effects on LVH in these patients than monotherapy.

Angiotensin receptor antagonist regresses left ventricular hypertrophy associated with diabetic nephropathy in dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy for diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. Angiotensin type 1 receptor (AT1) antagonists may be able to regress LVH by mechanisms independent of their antihypertensive effects in diabetic patients. It is not known whether AT1 antagonists are able to reverse LVH in diabetic patients on dialysis therapy. METHOD: Twenty-four type II diabetic patients with end-stage renal disease who had just entered into hemodialysis therapy, and were diagnosed as having LVH evaluated by echocardiography, were selected from 3 dialysis units staffed by the faculty of Saitama Medical School between 1998 and 2001. The study was carried out for 1 year. All patients were randomly assigned to 2 groups. One group received an AT 1 antagonist, losartan 100 mg daily 30 minutes after the cessation of dialysis therapy on dialysis days, or in the evening when dialysis therapy did not occur. The control group received placebo. LVH was evaluated by echocardiography before the start of administration of drugs, at 4 and 8 months, and again at 12 months after the start of drug therapy. A systolic blood pressure of less than 140 mm Hg was the target blood pressure in both groups. RESULTS: Using repeated measures analysis of variance, applied to those with 4 echocardiograms, there were progressive decreases over time in the left ventricular mass index (LVMi), posterior wall thickness, and intraventricular wall thickness in patients receiving losartan. The biggest changes in mass and the other parameters occurred between baseline and at month 6. Compared with these changes in the patients receiving losartan, left ventricular internal diameters and their derived parameters (e.g., ejection fraction) remained unchanged throughout the study. In spite of a similar reduction of bp in the patients receiving placebo, no significant changes in echocardiographic parameters were found in these patients. CONCLUSION: An AT 1 antagonist, losartan, is beneficial for the regression of LVH in diabetic patients who started dialysis therapy under adequate blood pressure control.