The role of nitrate,nitrite and N-nitrosamines in carcinogenesis of colon tumours following ureterosigmoidostomy

Summary Urinary diversion in both a rat model for ureterosigmoidostomy and in ureterosigmoidostomy patients result in an increased incidence of colon tumours. Bacterial and chemical investigations on feces-urine mixtures from both the rat model and ureterosigmoidostomy patients showed the presence of a complex nitrate-reducing bacterial flora in both rats and humans. This bacterial flora actively reduced urinary nitrate to nitrite in humans and increased the endogenous formation of N-nitroso compounds. No evidence of urinary nitrate reduction and increased nitrosamine formation in the rectosigmoid of rats was found. The results support the N-nitrosamine theory of carcinogenesis of the colon following ureterosigmoidostomy in humans, but not in rats. As the rat model induces colon carcinomas, factors other than the increased endogenous formation of N-nitroso compounds in the rectosigmoid may contribute to the initiation of colon carcinomas following ureterosigmoidostomy.     

Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients

BACKGROUND: The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in calcium stone-forming patients. METHODS: Forty-seven adult calcium stone-forming patients received either 1 g (N=23) or 2 g (N=24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. RESULTS: Fasting urinary pH did not change after 1 g (5.8 +/- 0.6 vs. 5.8 +/- 0.7) or 2 g vitamin C (5.8 +/- 0.8 vs. 5.8 +/- 0.7). A significant increase in mean urinary oxalate was observed in calcium stone-forming patients receiving either 1 g (50 +/- 16 vs. 31 +/- 12 mg/24 hours) or 2 g (48 +/- 21 vs. 34 +/- 12 mg/24 hours) of vitamin C and in healthy subjects (25 +/- 12 vs. 39 +/- 13 mg/24 hours). A significant increase in mean Tiselius index was observed in calcium stone-forming patients after 1 g (1.43 +/- 0.70 vs. 0.92 +/- 0.65) or 2 g vitamin C (1.61 +/- 1.05 vs. 0.99 +/- 0.55) and in healthy subjects (1.50 +/- 0.69 vs. 0.91 +/- 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 +/- 23 vs. 26 +/- 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. CONCLUSION: These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of calcium oxalate crystallization in calcium stone-forming patients.     

Malignancy following ureterosigmoidostomy in patients with exstrophy

Forty-two patients with exstrophy underwent a urothelial colonic anastomosis. Eight developed a tumour at the ureterocolic anastomosis and in another two patients a malignant lesion occurred in the bladder remnant.     

Effect of vitamin C on glycosylation of proteins.

Twelve nondiabetic subjects consumed 1 g/day vitamin C for 3 mo. A fasting blood sample was taken at the start of the study and at the end of each month for the measurement of plasma and intraerythrocyte glucose, vitamin C, glycosylated hemoglobin (affinity chromatography and electrophoresis), and glycosylated albumin (affinity chromatography). Although there were no significant changes in fasting glycemia, glycosylated hemoglobin (affinity chromatography) decreased 18%, from 6.18 +/- 0.48% (mean +/- SD) at the start to 5.05 +/- 0.50% (P less than 0.0001) after 3 mo, whereas, HbA1 measured by electrophoresis increased 16%, from 6.17 +/- 0.61 to 7.16 +/- 0.59% (P less than 0.0001) in this period. Glycosylated albumin decreased 33%, from 1.56 +/- 0.24 to 1.04 +/- 1.01% (P less than 0.0001) after 3 mo. This discrepancy between glycosylated hemoglobin measured by electrophoresis and affinity chromatography was due to methodological differences between the two techniques, with affinity chromatography measuring "true" glycosylated hemoglobin. The greater decrease found with glycosylated albumin was probably due to the different distribution of vitamin C between plasma and within the erythrocyte, levels after 1 mo of supplementation being 109 +/- 19 and 59 +/- 9 microM, respectively (P less than 0.001). This indicates that administration of oral vitamin C may inhibit the glycosylation of proteins in vivo by a competitive mechanism.     

Effect of vitamin C supplementation on black mineworkers.

Subclinical vitamin C deficiency frequently occurs in Black mineworkers, in spite of an apparently adequate daily intake. A study was undertaken to establish the minimum rate of supplementation that would effectively reduce the incidence of subclinical vitamin C deficiency. Two levels of supplementation were tested in relation to a control group. It was found that a supplementation rate of at least 235 mg/head/day is required to maintain reasonably adequate serum levels. It was also found that effective control measures are required to ensure that the supplement is added to the magou, the staple beverage of the miners. It is strongly recommended that the intake of every Black mineworker be supplemented at a rate of 200 - 250 mg/day.     

维生素C对大鼠肾结石模型体内活性氧及成石的影响

目的　观察不同剂量维生素C(VitC)对大鼠肾结石模型体内活性氧 (ROS)的影响及VitC、ROS与肾结石形成的关系。　方法　用乙二醇诱导Wistar大鼠产生肾草酸钙结石。 30只大鼠分为正常组 ,成石组 ,治疗组 (分三个不同剂量 ,VitC 2 5、10 0、4 0 0mg·kg-1·d-1) ,喂养 15d。测定血和右肾组织中丙二醛 (MDA)、过氧化氢酶 (CAT)、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶(GSH Px)含量 ;左肾冰冻切片 ,偏光显微镜观察结晶情况。　结果　成石组血和组织中的MDA分别为 (43.89± 5 .10 )nmol/ml和 (6 .2 0± 2 .0 0 )nmol/gpr,较正常组增高 ,差别有显著性意义 (P <0 .0 1和P <0 .0 0 1) ,而抗氧化酶显著降低 (P <0 .0 1和P <0 .0 0 1)。VitC 4 0 0mg·kg-1·d-1治疗组血MDA(30 .80± 4 .6 9)nmol/ml,较成石组降低 (P <0 .0 5 ) ,与正常组比较差别无显著性意义 (P >0 .0 5 ) ,血SOD较成石组降低 (P <0 .0 5 ) ,血CAT、GSH Px较成石组升高 (P <0 .0 1) ;VitC 4 0 0mg·kg-1·d-1治疗组肾组织中MDA(11.96± 2 .4 4 )nmol/gpr ,较成石组升高 (P <0 .0 5 ) ,SOD较成石组升高 (P <0 .0 5 ) ,CAT、GSH Px较成石组有所降低。肾组织晶体形成与VitC剂量呈正相关 (r =0 .6 6 85 ,P <0 .0 1)。　结论　高草酸尿可使机体活性     

Results of a survey on the daily activities of patients following ureterosigmoidostomy

Results of a questionnaire study on the daily life of patients undergoing ureterosigmoidostomy are reported. Nine patients who survived for more than 1 year after the operation were subjected to this study. At the time of their regular checkup, they were asked questions including the frequency of febrile attack, degree of daily work, bathing, complaints, frequency of urination and incontinence and feeling towards ureterosigmoidostomy. These patients had neither serious complications nor complaints. All except for 1 patient were satisfied and were enjoying daily life after ureterosigmoidostomy.     

Hemorrhage associated with vitamin C deficiency in surgical patients

BACKGROUND: Diffuse hemorrhage in surgical patients with normal coagulation parameters may be caused by vitamin C deficiency and is rapidly reversed by vitamin C replacement. METHODS: Patients treated on a surgical service were entered into a clinical registry over a 12-month period if they experienced diffuse hemorrhage in the face of normal coagulation parameters and a plasma ascorbic acid level < 0.6 mg/dL (normal 0.6-2.0 mg/dL). Oral vitamin C replacement was administered after determination of plasma ascorbic acid level. Response to therapy, including subsequent bleeding events, need for blood transfusions, and demographic data including social and dietary history were retrospectively reviewed from hospital and outpatient clinic records. RESULTS: Twelve patients with bleeding diatheses and low plasma ascorbic acid levels were identified. Plasma ascorbic acid levels were 0.1 to 0.5 mg/dL (mean, 0.3 mg/dL). There were 6 men and 6 women; age ranged from 46 to 90 years (mean, 78 years). Coagulation parameters were normal in all patients. Diffuse postoperative bleeding from nonsurgical causes was evident in 10 of 12 patients. Four patients, 2 of whom had operations, presented with chronic recurrent blood loss from the gastrointestinal tract. Each patient received 250 to 1000 mg of vitamin C replacement daily. Within 24 hours of vitamin C administration, there was no further evidence of clinical bleeding nor need for subsequent blood transfusions in any patient. CONCLUSIONS: Vitamin C deficiency should be included in the differential diagnosis of nonspecific bleeding in surgical patients. Prolonged hospitalization, severe illness, and poor diet create vitamin C deficiency with significant clinical consequences. Oral vitamin C replacement rapidly reverses the effects of this disorder.     

Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation.

Twenty rats were randomized into a vesicosigmoidostomy and an unoperated control group. In both groups the 24 hour excretion of secondary amines, nitrate, nitrite and nitrosamines was measured before and after gavage of proline and nitrate, piperazine and nitrate, N-nitrosoproline, mono-N-nitrosopiperazine. The urinary nitrosamine concentrations were not significantly different between both groups neither before nor after application of the several substances. Thirty rats were randomized into two vesicosigmoidostomy groups with and without antibiotic coverage and an unoperated control group. After ligation of distal rectum and mesosigmoid the rectosigmoids were removed. No significant concentrations of volatile nitrosamines could be measured in the rectosigmoid contents of the three groups. One hundred and twenty rats randomized into three groups following vesicosigmoidostomy received the potential nitrosamine antidotes sodium-2-mercaptoethane sulfonate or sodiumpentosan-polysulfate or acted as controls. 12/118 (10.2%) developed adenomas and 25/118 (21.2%) adenocarcinomas at the vesico-colonic anastomosis with no significant differences between the three groups concerning tumor incidence or mortality. The results show that colon carcinomas occur in a rat model for ureterosigmoidostomy without evidence for thus induced nitrosamine formation. This and the missing effect of nitrosamine antidotes suggest that other factors than nitrosation must be responsible for colon carcinogenesis following urinary diversion via intestine.     

抗氧化治疗对糖尿病肾脏病患者肾功能的保护作用

目的探讨维生素E联合维生素C抗氧化治疗对2型糖尿病肾脏病患者肾功能的保护作用。方法选择我院2型糖尿病肾脏病患者80例,随机分为2组,对照组（A组）接受常规治疗;抗氧化治疗组（B组）除常规治疗外,口服维生素E（0．1g／次,每日1次）、维生素C（0．2g／次,每日3次）。每3个月随访1次,观察记录患者的肾功能,以血肌酐（SCr）升高1倍为随访终点,SCr升高1倍所经历的时间为肾功能生存时间,最长随访时间为2年。结果A组肾功能平均生存时间为（14．78±0．64）个月;B组平均生存时间为（18．16±0．68）个月,2组比较有统计学差异（P〈0．05）。结论维生素E联合维生素c抗氧化治疗对糖尿病肾脏病患者肾功能具有保护作用。     

The effect of vitamin C intake on plasma oxalate in patients on regular haemodialysis

Plasma oxalate was measured on two occasions in 18 patients with end-stage renal failure on regular haemodialysis treatment: once while on a routine dose of vitamin C (100 mg/day) and subsequently after 2 weeks administration of a larger dose of vitamin C (500 mg/day). Pre- and post-dialysis concentrations were all markedly increased, reflecting the reduced glomerular filtration rate of end-stage renal failure. Both pre- and post-dialysis oxalate increased significantly following the increase in ascorbate dose but there was no significant correlation between plasma oxalate and ascorbate results. Considerations governing dosage of vitamin C in patients with chronic renal failure are discussed.     

Effect of vitamin C supplementation on renal oxalate deposits in five-sixths nephrectomized rats

We have previously reported that hyperoxalemia can be aggravated by vitamin C supplementation in regular hemodialysis patients. The present study was undertaken to examine the validity of this observation in an experimental setting. Fifty five-sixths nephrectomized rats were divided into two groups: 30 rats were allowed free access to water containing 8 mg/ml of vitamin C (100-160 mg/100 g/24 h) and the remainder given tap water without vitamin C. The serum creatinine increased and the Hct decreased gradually; however, there was no difference between the two groups. Plasma vitamin C, oxalate and urinary oxalate levels were higher in the vitamin -treated group than the nontreated rats. Histological examination revealed glomerular and interstitial fibrosis and round cell infiltration as well as tubular cyst formation. Oxalate deposits in renal tubules were found only in vitamin C-treated rats with advanced renal failure. Nontreated animals with equally advanced renal impairment showed no oxalate deposits. These results confirm our previous clinical findings that vitamin C supplementation aggravates the secondary oxalosis of chronic renal failure.     

Effect of vitamin E-bonded dialyzer on eosinophilia in haemodialysis patients.

BACKGROUND: Eosinophilia in haemodialysis patients probably results from allergy to haemodialysis-related materials, including dialyzer membranes. We examined the effects of vitamin E-bonded dialyzers on eosinophil counts in haemodialysis patients. METHODS: We enrolled seven patients who were on regular haemodialysis and had sustained eosinophilia. White blood cell, eosinophil, CD4- and CD8-positive lymphocyte counts, and serum interleukin-5 (IL-5) and IgE levels were determined before, 2 and 4 weeks after switching to vitamin E-bonded dialyzers. RESULTS: Eosinophil and CD4-positive lymphocyte counts and serum IL-5 were significantly (P = 0.003, 0.003 and 0.031, respectively) decreased after switching to vitamin E-bonded dialyzers. CD8-positive lymphocyte counts and serum IgE levels were unaltered. Crossover tests in two cases reproduced the higher eosinophilia within 4 weeks after returning to the original non-vitamin E-bonded dialyzer. Conclusion: Vitamin E-bonded dialyzers may ameliorate eosinophilia through a mechanism mediated by a decrease in IL-5 secretion by CD4-positive lymphocytes.     

Effect of vitamin C on fracture healing in elderly Osteogenic Disorder Shionogi rats

We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly.     

Effect of vitamin D on serum magnesium concentration in intermittently haemodialyzed patients

Serum magnesium before and after haemodialysis was examined in six uraemic patients without, and six uraemic patients with vitamin D treatment [10 mg of vitamin D₂ (Spofa) per week]. In the group without vitamin D treatment the mean values of serum magnesium were significantly higher than in the normals, both in the predialysis and postdialysis samples. In the group of vitamin D treated patients the mean values of serum magnesium both in predialysis and postdialysis samples were significantly higher than in the patients without vitamin D treatment. The data suggest that in patients with chronic renal insufficiency intestinal magnesium resorption may be significantly increased by vitamin D treatment.