Sphingomyelin changes in rat cerebral cortex during focal ischemia

Abstract

To better define the sphingolipid metabolism during focal brain ischemia, levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by occlusion of the middle cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid composition of ceramide was solely nonhydroxylated fatty acid similar to sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked cerebroside didn't occur for 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. These results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia. [Neurol Res 1996; 18: 337-341]     

Interaction between ACE and ADD1 gene polymorphisms in the progression of IgA nephropathy in Japanese patients

An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi2=6.062, P=0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P=0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P=0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.     

The Change in Body Composition After Bilateral Lung Volume Reduction Surgery for Underweight Patients with Severe Emphysema

The aim of this study was to examine the short-term effect of lung volume reduction surgery (LVRS) on body composition and other nutritional indicators in 28 patients with emphysema underwent thoracoscopic LVRS. Functional tests, body weight (BW), and body composition were measured before and 6 months after surgery. Mean daily caloric intake (CI) was estimated by 3-day dietary record as well. Fat-free mass (FFM) and fat mass (FM) were assessed by bioelectrical impedance analysis (BIA). FEV_1.0 and Vo _2max have improved after LVRS by 35.2% and 23.8%, respectively. Preoperatively, 75% of patients were underweight (% ideal body weight (%IBW) <90) with the mean %IBW at 84.5%. BW, CI, and FFM increased significantly after LVRS, whereas FM was unchanged. The change in BW correlated significantly with the change in FEV_1.0, MVV, and Vo _2max (p < 0.01) but not with CI. Bilateral LVRS results in an increase in FFM and functional improvement for underweight patients with severe emphysema, and it may contribute to the improvement in maximal exercise capacity. Accepted for publication: 12 December 2000