We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.

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Repeated administration of low doses of puromycin aminonucleoside (PAMN) to rats induces a proteinuric renal disease that resembles focal segmental glomerulosclerosis (FSGS). Reactive oxygen molecules may be involved in the progressive course of this nephropathy. Therefore we evaluated whether taurine, an endogenous antioxidant, could limit the extent of renal injury. Sprague-Dawley rats received low-dose injections of PAMN, 2 mg/100 g body wt, over a 12-wk period. Two groups were studied: 1) controls given tap water (n = 23), and 2) an experimental group that drank 1% taurine-supplemented water (n = 22). Taurine-treated nephrotic rats had a reduction in albuminuria, as assessed by the urinary albumin-to-creatinine ratio (26 +/- 4 vs. 44 +/- 4, P less than 0.0001). After 12 wk, creatinine clearance was 0.33 +/- 0.03 (experimental) vs. 0.17 +/- 0.03 ml.min-1.100 g body wt-1 (control) (P less than 0.001), and inulin clearance (n = 6 pairs) was 0.26 +/- 0.04 (experimental) vs. 0.13 +/- 0.02 ml.min-1.100 g body wt-1 (control) (P less than 0.025). Administration of taurine reduced the percentage of segmentally sclerosed glomeruli (9.8 +/- 1.7 vs. 16.2 +/- 1.8%, P less than 0.02) and the tubulointerstitial injury score (1.36 +/- 0.19 vs. 2.61 +/- 0.25, P less than 0.0025) in experimental vs. control rats. Taurine treatment normalized the elevated renal cortical malondialdehyde level in rats with PAMN nephropathy (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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Between 1956 and 1980 closed mitral valvotomies were performed in 3724 consecutive patients (male:female ratio 1.1:1) with mitral stenoses. Their ages ranged from 6 to 69 years, with a mean (SD) of 27.3 (9.3). Mitral stenosis in the younger age group is a unique condition and a great majority of these patients rapidly develop significant pulmonary hypertension and congestive cardiac failure. In this study a large number of subjects belonged to functional class IV (41.5%). Hospital mortality was 1.5% over the last 5 years. After valvotomy, 11 patients (0.3%) developed severe mitral regurgitation that made valve replacement necessary in the immediate postoperative period. Early postoperative embolism occurred in 0.4% of those who were in atrial fibrillation and had preoperative anticoagulation whereas it occurred in 0.95% of those in sinus rhythm who had no anticoagulation. Late postoperative embolism occurred at a rate of 0.3 to 1.6 per 1000 patients per year over a 20 year period. Rheumatic reactivity occurred at a rate of 1.3 to 2.2 per 1000 patients per year during the same period. Rate of occurrence of restenosis varied from 4.2 to I 11.4 per 1000 patients per year between the fifth and fifteenth year of follow-up. Closed transventricular revalvotomy for restenosis was accomplished in 130 subjects with a 6.7% mortality. Excellent symptomatic improvement was evident in 86% of long-term survivors at the end of 15 years. Actuarial survival was 95%, 93.1%, 89.5%, and 84.2% at 6, 12, 18, and 24 years, respectively, after closed mitral valvotomy. Late deaths occurred in 4.3%. This study serves to highlight the excellent palliative effect of closed valvotomy for mitral stenosis without significant valvular calcification, substantial regurgitation, or significant associated valvular lesion. Circulation 68, No. 5, 891-896, 1983

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