Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation.

Ablation of greater than 70% of renal mass in the rat results in hypertension, proteinuria, and glomerular sclerosis of the remnant kidney. Rats with a remnant kidney have increased excretion of thromboxane in the urine when compared with normal rats. Chronic oral administration of OKY 1581, an inhibitor of thromboxane synthesis, in rats with a remnant kidney increases renal blood flow and glomerular filtration rate (GFR), decreases protein and thromboxane excretion in the urine, lowers blood pressure and cardiac index, and improves renal histology. The degree of hypertrophy of the remnant kidney was unaffected by administration of OKY 1581. Calculated values for single nephron plasma flow and GFR were significantly greater in rats with remnant kidneys given OKY 1581 than in rats given saline. Acute i.v. administration of OKY 1581 increased renal plasma flow and GFR in rats with a remnant kidney but not in normal rats or rats with a remnant kidney previously treated with acetylsalicyclic acid. OKY 1581 markedly inhibited platelet aggregation. We suggest that in this model of renal disease platelet aggregation and intraglomerular thrombosis play a key role in the development of glomerulosclerosis. Inhibition of platelet aggregation prevents development of glomerulosclerosis, hypertension, and cardiac hypertrophy. We suggest that hyperperfusion and hyperfiltration per se occurring in remnant glomeruli are not directly responsible for the development of glomerulosclerosis.     

Eighteen-month clinical evaluation of two dentin adhesives applied on dry vs moist dentin

PURPOSE: To evaluate the influence of substrate moisture on the clinical behavior of two dentin adhesives after 18 months. The null hypothesis tested was that drying dentin with air upon rinsing off the acid would not influence the clinical performance of two dentin adhesives as compared to leaving the preparation visibly moist. MATERIALS AND METHODS: Thirty-five patients were enrolled in this study. One hundred twenty-eight restorations divided into 4 groups were inserted and evaluated at baseline: (1) NT/Moist - Prime & Bond NT, an acetone-based adhesive, applied on moist dentin; (2) NT/Dried - Prime & Bond NT applied on dentin dried with air for 3 to 4 s; (3) SB/Moist - Single Bond, an ethanol- and water-based adhesive, applied on moist dentin; (4) SB/Dried - Single Bond applied on dentin dried with air for 3 to 4 s. A microfilled composite resin was used for all restorations. Patients were recalled at 6 and 18 months. RESULTS: At 18 months after initial placement, 110 restorations (86% recall rate) were re-evaluated. Retention rates at 18 months were 92% for NT/Moist, 93% for NT/Dried, 100% for SB/Moist, and 89% for SB/Dried. No statistically significant differences were found among groups for retention rate. Both NT/Moist and SB/Moist resulted in a significant decrease in sensitivity to air from baseline to 18 months. When data were pooled for the variable "substrate moisture", SB resulted in an overall retention rate of 95%, while NT resulted in a retention rate of 92% (statistically similar). The marginal adaptation with SB was significantly worse at 18 months than at baseline. CONCLUSION: The moisture level of the dentin substrate in noncarious cervical lesions does not influence retention of composite restorations, but moist conditions caused less sensitivity to air. When applied as per manufacturers' instructions (moist dentin), both adhesives resulted in Class V retention rates exceeding the ADA 18-month full acceptance guidelines.     

The bone morphogenetic proteins (BMPs). Their role in renal fibrosis and renal function

Recently, a protein has emerged as a potential renotrophic factor: bone morphogenetic protein-7 (BMP-7). In a preventive protocol, BMP-7 treatment was found to significantly decrease renal injury in a rat model of ureteral obstruction (UUO), when treatment was initiated at the time of injury. Subsequent studies suggested that BMP-7 treatment also attenuated renal fibrosis when administered after renal fibrosis had begun. This treatment protocol was also found to increase significantly renal function from the levels measured in the vehicle-treated group. BMP-7 also partially reversed the diabetic nephropathy induced in rats by a single dose of streptozotocin. It restored glomerular filtration rate (GFR), decreased the excretion of protein, and restored histology towards normal. These studies also highlight the value of histological parameters as indicators of renal function and the potential of renal homeostatic factors in the treatment of kidney disease.     

Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris SW aqueous extract with anti-PLA2 activity

The Casearia sylvestris SW (Flacourtiaceae) is utilized in folk medicine (Brazil and all Latin American) to treat several pathologic processes as inflammation, cancer, microbial infection and snake bites. Studies showed that C. sylvestris aqueous extract can inhibit many toxic effects caused by snake venoms (or caused by phospholipase A₂ isolated) from different species, mainly of Bothrops genus. Inhibition of enzymatic and myotoxic activities, decrease of edema formation and increase of the survival rate of rats injected with lethal doses of bothropic venoms are some toxic effects inhibited by C. sylvestris. In this study, four ellagic acid derivatives from aqueous extracts of C. sylvestris were isolated, characterized, and tested against effects from both total venom and PLA₂ (Asp 49 BthTX-II) from the venom of Bothrops jararacussu. The isolated compounds were as follows: ellagic acid (A), 3′-O-methyl ellagic acid (B), 3,3′-di-O-methyl ellagic acid (C), 3-O-methyl-3′,4′-methylenedioxy ellagic acid (D). The inhibition constant values (Ki) for enzymatic activity, as well the IC₅₀ values found in the edematogenic and myotoxic activities, indicate that the ellagic acid is the best inhibitor of these activities, while compounds C and D are the substances with lowest capacity on inhibiting these same effects. Our results show that the presence of hydroxyls at position 3 or 3′ (compounds A and B) increases the capacity of these derivatives on inhibiting these toxic effects. However, the presence of methoxyl groups at position 3 or 3′ reduced, but did not completely inhibit the capacity of compounds C and D on inhibiting all the toxic effects studied.     

Effects of Reduced Renal Mass and Dietary Protein Intake on Amino Acid Release and Glucose Uptake by Rat Muscle In Vitro

Epitrochlearis muscles obtained from normal male Holtzman rats used as controls (C) and rats with reduced renal mass (Nx) fed isocaloric diets of varying protein content were incubated in Krebs-Ringer buffer containing 5 mM glucose for 1 or 3 h with or without insulin.Alanine (ALA) release rates from muscles of Nx rats were increased 40% above C values after 1 h of incubation regardless of protein intake. Addition of insulin decreased the ALA release from muscles of Nx rats to C values in animals fed 10 and 20% casein and chow but did not in rats fed 40% casein. After 3 h of incubation, all ALA release rates decreased by congruent with40%. The ALA release from muscles of Nx rats fed 10% casein was comparable to C values and decreased further with the addition of insulin. On the other hand, ALA release from muscles of Nx rats fed 20 and 40% casein as well as chow remained significantly elevated above C values, but responded to the addition of insulin with a reduction in release rates to C values, except from the muscles of Nx animals fed 40% casein.Tyrosine (TYR) and phenylalanine (PHE) release rates also were increased in muscles from Nx rats compared with C after 1 h of incubation. Release rates were highest in the Nx group fed 10% casein and decreased with increasing protein intake. Addition of insulin decreased the release rates of Nx rats to C values in each group. After 3 h of incubation, release rates of TYR and PHE in muscles from Nx rats remained significantly above C values for all groups, but responded to the addition of insulin with a decrease to C values. Glutamine and glutamate release were not significantly affected by reduction in renal mass.Base-line glucose uptake by all groups of muscles from Nx rats was significantly greater than corresponding C values, but maximal insulin-stimulated glucose uptake was comparable in all groups. Tissue pool sizes for glycogen, ATP, phosphocreatine, ALA, glutamate, and glutamine were unaffected by reduction in renal mass.The results indicate that Nx is associated with accelerated ALA, TYR, and PHE release from muscle. ALA release rose with increasing protein intake and decreased to values observed from C muscles after addition of insulin except in Nx animals fed 40% casein. TYR and PHE release decreased with increasing protein intake and also decreased to C values with the addition of insulin. The data also suggest that ALA release is not dependent upon glucose uptake in muscles from either C or Nx rats.