Necrotizing myopathy with paracrystalline inclusion bodies in hypervitaminosis E

Summary A necrotizing, nonprogressive myopathy with unusual paracrystalline inclusion bodies is described in a patient who underwent long-term treatment with megadoses of vitamin E. The clinical course and morphological findings suggest a close relationship to the administration of the vitamin. The theoretical pathogenesis of muscle damage and the possible origin of paracrystalline inclusion bodies are discussed.Presented at the Jahrestagung der österreichischen Gesellschaft für Neuropathologie in Bad Ischl, on April 17, 1986This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Ba 916)     

Calcium absorption following small bowel resection in man. Evidence for an adaptive response

Seventeen patients who had undergone extensive small bowel resection were studied for calcium absorption (FACa) and plasma vitamin D metabolites. FACa was measured by a double radio-tracer technique and expressed as percentage of total oral dose. FACa was decreased compared with controls (34%, range: 3-46 v 65%, range: 57-73, P less than 0.01). A positive correlation (r = 0.49, P = 0.05) was found between FACa and the remaining length of small bowel (SBL). As wide variations in both SBL and duration after surgery were observed among the seventeen investigated patients, we were led to individualize less heterogeneous subgroups of patients. Better correlations were found when the patients were divided into two subgroups according to whether the time interval between the resection and the investigation was shorter (r = 0.75, n = 11, P less than 0.02) or longer (r = 0.89, n = 6, P = 0.05) than 2 years. In thirteen patients who had a SBL shorter than 100 cm, a positive correlation was observed between FACa and the time interval after surgery (months): r = 0.65, P less than 0.05. Plasma 1,25 (OH)2D was markedly reduced in the whole group (31 pmol l-1, range: 8-108) compared with controls (103 pmol-1, range: 59-134, P less than 0.01). The present study shows that in extensively small bowel resected patients, calcium absorption is reduced, the alteration being dependent both on the length of the remnant small bowel and on the time after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

OBJECTIVE: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1-25[OH]2 D3). METHODS: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 microg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 microg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. RESULTS: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. CONCLUSIONS: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol.     

硒和/或维生素E预防大鼠内皮细胞损伤的实验研究

用含硒（Ｓｅ０．５ｍｇ／ｋｇ）和／或维生素Ｅ（ＶＥ０．６ｇ／ｋｇ）的高脂饲料喂养成年雄性Ｗｉｓｔａｒ大鼠１２周。结果：高脂对照组大鼠血浆前列腺素Ｆｌα（６－酮－ＰＧＦ１α）水平下降，而血清脂质过氧化物（ＬＰＯ）、血浆血栓素（ＴＸＢ２）及内皮素（ＥＴ）水平上升；补Ｓｅ、ＶＥ及Ｓｅ＋ＶＥ可明显降低大鼠血清ＬＰＯ、血浆ＴＸＢ２、ＥＴ及ＴＸＢ２／６－酮－ＰＧＦ１α比值。同时，除了明显提高血浆谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活力外，血浆６－酮－ＰＧＦ１α浓度明显升高。实验提示，Ｓｅ和／或ＶＥ有调节花生四烯酸代谢及保护内皮细胞的作用。     

Cyclosporin A upregulates prostaglandin E2 production in human gingival fibroblasts challenged with tumor necrosis factor alpha in vitro

The effect of Cyclosporin A (CsA) on prostaglandin E₂ (PGE₂) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-α) was studied. TNF-α (1-100 ng/ml) dose-dependently stimulated PGE₂; formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE₂; formation itself but potentiated TNF-α induced PGE; formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-α. TNF-α (10 ng/ml) stimulated the release of [³H]-arachidonic acid (A.A) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 μM/ml) to the cells resulted in enhanced PGE₂: formation that was not potentiated by CsA (100 ng/mi). Furthermore. CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-α (10 ng/ml). although PGE₂ formation was enhanced. The results indicate that CsA and TNF-α act in concert on PGE₂ formation in gingival fibroblasts. which may be of importance in the pathogenesis of gingival overgrowth induced by the drug.     

Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine

Abstract: A prospective, randomized study was conducted to evaluate the role of vitamin B₁₂ and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4 + cell counts < 500/mm³ were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B₁₂ (1000 μg monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B₁₂ and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm³ and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B₁₂ or folate levels and development of myelosuppression. Vitamin B₁₂ and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.     

Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta

Summary We examined the effect in rats of 2 months of streptozotocin-induced diabetes mellitus on relaxation and contraction of aortas in vitro. A further diabetic group was treated from time of diabetes induction with a 1% dietary supplement of vitamin E. Diabetes caused a 26.5% deficit (p<0.001) in maximum endothelium-dependent relaxation to acetylcholine in phenylephrine-precontracted aortas. This was 64.3% attenuated (p<0.01) by vitamin E treatment; maximum relaxation was not significantly altered compared to non-diabetic rats. Vitamin E treatment of non-diabetic rats did not significantly affect acetylcholine-induced relaxation. Diabetes or treatment did not significantly alter acetylcholine sensitivity. Endothelium-independent relaxation response to glyceryl trinitrate was not affected by diabetes or vitamin E treatment, indicating that vascular smooth muscle responses to nitric oxide remained unaltered. There was a 35.4% reduction in the maximum contractile response to phenylephrine with diabetes (p<0.05) which was unaffected by vitamin E treatment. The data suggest that the chronic deficit in nitric oxide-mediated endothelium-dependent relaxation in diabetes depends largely upon excess activity of reactive oxygen species. Treatment with vitamin E to increase free radical scavenging specifically protected vascular endothelium although it had no effect on deficits in vascular smooth muscle contractile responses.Abbreviations NO Nitric oxide - ARI aldose reductase inhibitor - ACH acetylcholine - GTN glyceryl trinitrate - GSH reduced form of glutathione - EC₅₀ effective concentration for 50% of the maximal response     

Influence of age on faecal carriage of P-fimbriated Escherichia coli and other gram-negative bacteria in hospitalized neonates

The aerobic faecal flora of 953 infants aged over 5 days was studied on discharge from 22 neonatal wards in Swedish hospitals. Klebsiella/enterobacter was isolated from 74% of infants and dominated the aerobic gram-negative flora in 19 wards. Escherichia coli was carried by 42% and showed a slight dominance in two wards. Initially klebsiella/enterobacter dominated the flora but became increasingly mixed with and taken over by E. coli, carriage increasing from 21% in infants discharged after 5-7 days to 57% after 3 weeks or later. Among infants with E. coli, P-fimbriated strains were demonstrated in 23% (range 0-67) and were independent of age. Occasional clustering of such strains was observed in 3/22 wards during the study period. It is postulated that the general and local colonization patterns observed reflect differences between individual strains of E. coli and klebsiella in both their capacity for transmission and their persistence in the newborn gut. The role of P-fimbriae in intestinal colonization of neonates by E. coli was, however, not supported.