Cumulative excess urinary excretion of folate in rats after repeated ethanol treatment

The folate deficiency that is produced by chronic alcohol ingestion results from poor dietary intake and from effects of ethanol on folate metabolism and absorption. Previous studies in fasted rats showed that singular treatment with ethanol produces an increase in urinary folate levels, in amounts that account for a subsequent decrease in plasma folate levels. The effects of subacute administration of ethanol on urinary folate excretion were studied in fed and fasted rats treating for 1, 2, 3 or 4 d either with ethanol orally in four doses of 1 g/kg each at hourly intervals or with glucose in isocaloric doses. Urine was collected at timed intervals up to 12 h after each daily dose. Rats were fed daily except for the evening prior to the final treatment day. Ethanol treatment produced an increase in urinary folate excretion in fed and in fasted rats, although the effect in fed rats was less marked. The increased excretion was similar on each final day, whether rats were treated for 1, 2, 3 or 4 d, indicating that there was no adaptation to the loss of folate during this subacute treatment. The excess urinary folate excretion accumulated so that the longer the rats were exposed to ethanol, the greater the urinary loss. These results suggest that when animals are chronically treated with ethanol, urinary folate loss could contribute to the development of folate deficiency.     

我国部分地区成年人血浆叶酸的地区和季节差异比较

目的：描述我国部分地区成年人群血浆叶酸在不同地区、季节的分布特征。方法：以来自南北方有代表性的城乡地区2 545人（35-64岁）为研究样本,对其血浆叶酸分布特点进行统计学分析。结果：南方人群血浆叶酸平均水平（16.9nmol/L）显著高于北方人群（8.3nmol/L）,北方人群叶酸缺乏率（37.0%）显著高于南方人群（5.8%）;南北方人群血浆叶酸水平随季节变化规律不同,南方人群夏秋季血浆叶酸水平（15.0nmol/L）低于冬春季节（18.8nmol/L）,叶酸缺乏率变化不明显;北方人群夏秋季节血浆叶酸水平（9.7nmol/L）明显高于冬春季节（7.1nmol/L）,叶酸缺乏率夏秋季节为26.2%,显著低于冬春季节的48.0%。结论：我国南北地区成年人群血浆叶酸水平差异显著;南北方人群血浆叶酸随季节变化规律不同。     

Effect of ethanol on the urinary excretion of mandelic and phenylglyoxylic acids after human exposure to styrene

Summary Administration of ethanol in several doses during human exposure to styrene can inhibit the urinary mandelic and phenylglyoxylic acid excretion in a way similar to that reported when ethanol was administered as a single dose. Sensitivity to this inhibitory effect has been found to differ with individual subjects. Differences in long-term consumption of ethanol resulting in different induction of the oxidizing enzymes are suggested to account for this finding. Intra-individual variation in the influence of acute ethanol ingestion on the excretion rate of the mentioned acids can also occur. The habit of drinking ethanol might be important, even for partial redirection of the styrene metabolism from styrene glycol oxidation to styrene glycol conjugation with -glucuronic acid and/or sulfate. The consequences of these observations for the occupational hygiene practice are briefly outlined.     

Effects of chronic ethanol and diet treatment on urinary folate excretion and development of folate deficiency in the rat

Because the folate deficiency of chronic alcoholism has been proposed to result from ethanol-induced effects on metabolism or urinary excretion of folate, the present study was designed to evaluate the role of chronic ethanol-induced urinary folate loss on folate homeostasis in the rat. Male Sprague-Dawley rats were fed nutritionally sufficient liquid diets for 12 wk with or without ethanol, folate and sulfonamide. Urinary folate excretion was increased in ethanol-fed rats consuming folate-containing diets, but not in rats fed folate deficient diets. Consumption of folate-deficient diets led to a rapid decrease in urinary folate excretion, suggesting renal adaptation to conserve folate. Tissue and plasma levels of folate were mostly unaffected by ethanol ingestion in rats fed folate-containing diets. Ethanol treatment did not consistently enhance tissue folate depletion in rats fed folate-deficient diets. The results suggest that in rats consuming diets containing high levels of folate, chronic ethanol ingestion increased urinary folate excretion, but not to a sufficient magnitude to consistently affect folate homeostasis.     

无锡地区早期妊娠妇女血液叶酸浓度季节变化趋势及影响因素

目的了解无锡地区早期妊娠妇女血液叶酸浓度,观察血液叶酸浓度随季节变动趋势,分析血液叶酸浓度的影响因素。方法研究对象为孕12周内妇女。采用面对面调查方法收集资料,每名妇女采集非空腹静脉血4ml测定血浆叶酸和红细胞叶酸浓度。采用逐步回归方法筛选血液叶酸浓度的影响因素。采用协方差分析,计算调整相关混杂因素后不同季节以及服用和不服用叶酸增补剂者的血液叶酸浓度。结果2002年12月至2003年11月共募集早期妊娠妇女596名。血浆叶酸和红细胞叶酸浓度的几何均数分别为34．1 nmol／L和902．8 nmol／L,缺乏率分别为3．0％和2．4％。但50％早期妊娠妇女的红细胞叶酸浓度低于预防神经管畸形的最佳水平(906 nmol／L)。血浆叶酸浓度4～6月最低;红细胞叶酸浓度1-3月最低。围受孕期服用叶酸增补剂可以显著提高血浆叶酸浓度和红细胞叶酸浓度;血浆叶酸浓度和红细胞叶酸浓度随妇女年龄增加而升高;农村早期妊娠妇女的血浆叶酸浓度低于城市早期妊娠妇女;每日食用1次及以上水果者的红细胞叶酸浓度高于水果食用频率不足每日1次者。对年龄和居住地调整后,围受孕期服用叶酸增补剂妇女的血浆叶酸浓度比未服用者高1倍以上(P<0．001);对年龄和食用水果频率调整后,服用叶酸增补剂妇女的红细胞叶酸浓度比未服用者高42％(P<0．001)。结论无锡地区早期妊娠妇女叶酸缺乏率不高,但有50％早期妊娠妇女的红细胞叶酸浓度低于预防胎儿神经管畸形的最佳水平。红细胞叶酸浓度1—3月处于低谷,此时受孕,胎儿神经管畸形的危险性将增加。围受孕期服用叶酸增补剂可显著提高血液叶酸浓度。在制订育龄妇女增补叶酸计划时,应结合改变膳食教育,并应重点关注农村妇女。     

Effects of ethanol ingestion and urinary acidity on the metabolism of triethylamine in man

Summary In four volunteers exposed to triethylamine (TEA) by inhalation (20 mg/m³, 8 h), the non-renal clearance of TEA into triethylamine-N-oxide (TEAO) was inhibited by 15 to 30% by intake of ethanol (blood serum level in average 25mmol/l). Ethanol intake caused a decrease of plasma levels of TEA and TEAO, and of the fractional formation of TEAO. This may partly be due to a second effect of ethanol; it caused a slight decrease of urinary pH, which led to an increase of the urinary TEA excretion rate, with a possible withdrawal of TEA from oxygenation. Indeed, this effect was efficiently counteracted by intake of sodium bicarbonate, which caused a decrease of renal clearance of TEA, and increases of plasma levels of TEA and TEAO, and of the fractional formation of TEAO. A change of urinary pH by about two units caused a change of renal clearance of TEA by a factor of three and of the oxygenation by two. The renal clearance of TEAO was not affected by urinary pH.     

Effects of ethanol ingestion and urinary acidity on the metabolism of triethylamine in man

In four volunteers exposed to triethylamine (TEA) by inhalation (20 mg/m3, 8 h), the nonrenal clearance of TEA into triethylamine-N-oxide (TEAO) was inhibited by 15 to 30% by intake of ethanol (blood serum level in average 25 mmol/l). Ethanol intake caused a decrease of plasma levels of TEA and TEAO, and of the fractional formation of TEAO. This may partly be due to a second effect of ethanol; it caused a slight decrease of urinary pH, which led to an increase of the urinary TEA excretion rate, with a possible withdrawal of TEA from oxygenation. Indeed, this effect was efficiently counteracted by intake of sodium bicarbonate, which caused a decrease of renal clearance of TEA, and increases of plasma levels of TEA and TEAO, and of the fractional formation of TEAO. A change of urinary pH by about two units caused a change of renal clearance of TEA by a factor of three and of the oxygenation by two. The renal clearance of TEAO was not affected by urinary pH.     

Opioids,benzodiazepines and intake of ethanol

Deprived rats were given the opportunity to take water or a sweetened ethanol solution for one hour/day. Across days, intake of the ethanol solution increased. Doses of morphine prior to an opportunity to drink increased avidity for the ethanol solutions, while doses of chlordiazepoxide did not. The opioid antagonist naloxone decreased intake, whereas, the benzodiazepine antagonist Ro 15-1788 failed to do so. These findings confirm that certain opioids can increase ethanol intake, and further specify that, under the same testing regimen, benzodiazepines do not reliably modify rats' propensity to drink a solution containing ethanol.     

Iodine status assessment in Campania (Italy) as determined by urinary iodine excretion

ObjectiveMild iodine deficiency was first documented in Campania in the 1990s. We assessed the urinary iodine nutritional status of schoolchildren in Campania before the introduction of legislation for salt iodization and compared the findings with previous results to evaluate to what extent “silent” iodine prophylaxis, which accompanies socioeconomic advances, affects iodine status.MethodsWe examined 10552 schoolchildren aged 9–13 y from the five Campania provinces. The study was conducted from April 1999 to October 2002. Urinary iodine excretion was measured in morning urine samples with the AutoAnalyzer 3, an automated system based on the Sandell-Kolthoff reaction. Data were interpreted according to World Health Organization criteria.ResultsThe median urinary iodine excretion level in Campania was less than 100 μμg/L, which indicates insufficient iodine intake. Mild iodine deficiency was identified in all provinces, namely Napoli, Salerno, Caserta, Avellino, and Benevento, with median urinary iodine excretions of 87, 81, 72, 64, and 61 μg/L, respectively. Overall, the analysis of frequency distribution showed values below 50 and 100 μg/L in 32% and 61% of children, respectively. These values were lower than those previously reported for Campania.ConclusionThis study confirms that Campania is a mild iodine deficiency area. The decrease in iodine deficiency versus previous studies indicates that silent prophylaxis plays a relevant role in this condition, but it is not sufficient to eradicate it. Our data will serve as a basis for future evaluations of iodine status in Campania.     

Selected opioids, ethanol and intake of ethanol

Rats were given an opportunity to drink tap water or a sweetened ethanol solution once a day. Across initial days of opportunity, rats increased their intake of the ethanol solution. Prior to some days' sessions with presented fluids, rats received either an injection of placebo (the carrier of drugs) or doses of ethylketocyclozocine, diprenorphine, or ethanol. Diprenorphine increased rats' intake of the ethanol solution compared to placebo. The other agents did not reliably modify intakes. These findings support a conclusion that selected activity in opioid systems of brain increase the propensity to drink alcoholic beverages.     

Effects of orotic acid ingestion on urinary and blood parameters in humans

Pertinent urinary and blood parameters were examined in 29 normal adults ingesting orotic acid by capsule once a week. Upon ingestion of 6 g orotic acid, urinary excretion of orotate and urate was increased in all subjects but creatinine and urea were unaffected. Mean orotate excretion was 624 mg or 10.5% of dose ingested, although individual variability was large (1–26%). In five persons studied more extensively, excretion of excess orotate was proportional to the amount ingested and was generally complete within 8 hours. Orotic acid ingestion led to uricosuria and the pattern for urate excretion was similar to that for orotate. Blood parameters before participation in the study and 24 hours after ingesting 6 g orotic acid were within normal ranges. However, serum urate and cholesterol were decreased significantly. The decrease in blood urate reflects the uricosuric effect of orotic acid. The hypocholesteremic response to orotic acid ingestion in humans warrants further investigation.     

Acute ethanol administration: effects on stress-induced gastric and duodenal ulcer in rats

Rats were given 6% ethanol (v/v) as their only source of liquid for 4 days. On the basis of ethanol consumption (g/kg/day), animals were divided into high, medium and low ethanol consuming groups. A non-ethanol exposed control group was also included. Following a 24 hr food deprivation period, animals were restrained for 3 hr. No differences in gastric ulcer frequency or severity were noted with the exception of a slight tendency toward a lower incidence among ethanol consuming rats relative to controls. An unusual observation was the high incidence of duodenal ulcer observed only among ethanol consuming rats. This ethanol-stress interaction is discussed in terms of an animal's history of ethanol exposure.     

Calculogenic potential of galactose and fructose in relation to urinary excretion of lithogenic substances in vitamin B6 deficient and control rats.

Calculogenic potential of refined sugars galactose and fructose was examined in vitamin B6 deficient and control rats in terms of their capacity to increase urinary excretion of lithogens.

Male albino rats were fed vitamin B6 deficient diet with 51.7% sucrose+ starch or galactose or fructose as the source of carbohydrate. Pair-fed controls were maintained for all the groups for a period of four weeks. Twenty-four hour urine samples obtained at weekly intervals were analyzed for creatinine, calcium, oxalate, phosphate and uric acid. Microscopic urinalysis was performed at the end of the study.

Urinary calcium excretion increased with respect to baseline in all groups except vitamin B6 control group. On day 28, galactose and fructose-fed rats demonstrated significant hypercalciuria as compared to the sucrose + starch fed group. Vitamin B6 deficient rats (irrespective of the sugar fed) excreted significantly greater urinary calcium compared to pair-fed controls. Oxalate excretion was significantly increased in rats fed galactose compared to those fed fructose or sucrose + starch. Vitamin B6 deficiency further increased oxalate excretion by 1.5, 1.9 and 1.7 fold in sucrose + starch, fructose or galactose fed animals, respectively. Urinary uric acid excretion was enhanced only in fructose-fed rats. There was no change in urinary excretion of creatinine and phosphate in different experimental and control groups. Increased urinary saturation with lithogens caused pronounced crystalluria in all the vitamin B6 deficient groups as well as galactose control group.

The results suggest galactose ingestion is associated with a greater propensity to form calcium oxalate kidney stones than fructose. Calculogenic potential of galactose and fructose is further enhanced in vitamin B6 deficiency.     

Effects of acute ethanol on urinary excretion of 5-methyltetrahydrofolic acid and folate derivatives in the rat

Acute ethanol treatment enhances the urinary excretion of endogenous folate. This effect has been implicated in the development of folate deficiency associated with chronic alcoholism. Previous studies have shown that urinary excretion of total [3H]-label after administration of [3H]folic acid is slightly higher in ethanol-treated rats because of conversion of the tracer to forms whose excretion is not affected by ethanol. Since [3H]folic acid is not the physiological substrate for the kidney, studies were performed using a high specific activity 5-methyltetrahydrofolic acid ([3H]5-CH3-H4 folic acid). Male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg, followed by infusion of [3H]5-CH3-H4 folic acid at 5 h. Urine samples were collected to 6 h, when rats were killed, and plasma, liver and kidney samples were collected. Endogenous urinary folate excretion and the fractional urinary excretion of both endogenous and [3H]5-CH3-H4 folic acid at the 5-6 h time period were significantly higher in ethanol-treated rats. The kidney had a tenfold greater specific incorporation of [3H]-label than did the liver. High performance liquid chromatography (HPLC) analysis of the plasma obtained at 6 h showed that 68% of the label was [3H]5-CH3-H4 folic acid, and HPLC analysis of the urine obtained from 5-6 h showed that only 10% of the label was [3H]5-CH3-H4 folic acid. The data indicate that [3H]5-CH3-H4 folic acid was rapidly taken up by the kidney and metabolized to other folate and nonfolate forms, which were then secreted into the renal tubule for excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphine and naloxone modulate intake of ethanol

Rats, deprived of food and water for 18 hr, were given an opportunity to drink water and sweetened ethanol solution for 1 hr prior to being fed and watered for 5 hr, daily. One group received water and sucrose solution without ethanol and other groups received water and sucrose solution with 3, 6, 12 or 24% ethanol. Prior to some days' opportunities to drink, rats were injected with morphine (2.5 mg/kg), naloxone (10 mg/kg), or saline. Morphine increased intake of solutions containing ethanol as compared to intake under placebo. Naloxone reduced intakes of both fluids. Since morphine only increased sucrose solution intake when it contained ethanol, it was concluded that increments in opioid activity increase rats' avidity for ethanol.     

叶酸与宫颈癌关系的研究进展

叶酸是1种基本的水溶性维生素,作为一碳单位的供体,在DNA、RNA、蛋白质合成、维持及DNA甲基化等生命活动过程中起着至关重要的作用,叶酸是所有上述反应的限制因素。近年研究结果显示,叶酸缺乏或代谢障碍会增加罹患宫颈癌或宫颈上皮内瘤变(CIN)的风险,但其作用机制至今尚未阐明。笔者拟就叶酸的摄取和代谢、叶酸缺乏影响正常的DNA甲基化、叶酸缺乏影响DNA的合成和修复、叶酸缺乏可以增强致癌病毒的作用等方面进行综述。     

Bioavailability of cellobiose by tolerance test and breath hydrogen excretion in humans

OBJECTIVE: Prebiotic substances have the property of intestinal fermentation. Cellobiose has a beta-1,4 linkage, so it is resistant to hydrolysis by human small intestinal disaccharidase and, hence, reaches the colon undigested. Until this study, it was unclear whether cellobiose has fermentability or bioavailability. The objectives of this study were to clarify whether cellobiose is fermented in the large intestine and to estimate the available energy from cellobiose intake by using tolerance tests and breath hydrogen tests in healthy female subjects. METHODS: Ten healthy young women (20.5 +/- 2.1 y) who did not develop diarrhea after ingesting 30 g of cellobiose in a previous experiment were recruited. Tolerance tests and breath hydrogen tests for 25 g of cellobiose or glucose were carried out at least 2 wk apart. Blood samples were collected before and at 30-min intervals up to 3 h after ingestion. Breath gas samples were collected simultaneously before and at 30-min intervals up to 6 h after ingestion of cellobiose or glucose. Blood glucose and insulin levels and the concentration of breath hydrogen were analyzed. RESULTS: When 25 g of cellobiose was ingested, there was no increase in blood glucose or insulin secretion, but these markers increased remarkably with glucose ingestion. The excretion of breath hydrogen gas after cellobiose ingestion was significantly greater than that after glucose ingestion. CONCLUSIONS: Orally ingested cellobiose was well fermented in human large intestine, and its available energy was estimated to be about 2 kcal/g.     

叶酸与甲基-CpG-结合蛋白2基因表达在宫颈癌变中的关系及交互作用

目的 探讨叶酸和甲基-CpG-结合蛋白2（MeCP2）表达在宫颈癌变中的交互作用。方法 选择经病理学确诊的宫颈鳞状细胞癌（SCC）患者41例,宫颈上皮内瘤样变（CIN）患者71例（34例CIN1和37例CIN2+）及61名宫颈正常（NC）妇女为研究对象。采用微生物法检测血清叶酸和红细胞叶酸水平,Western blot法和荧光定量PCR法检测宫颈组织中MeCP2蛋白和mRNA的表达量。利用SPSS 20.0软件进行相关资料的Kruskal-Wallis H检验、χ²检验、χ²趋势检验和Spearman秩相关分析,应用广义多因子降维模型（GMDR）评价交互作用。结果 随着宫颈病变程度的加重,血清叶酸（H=44.71,P<0.001;趋势检验 χ²=24.48,P<0.001）和红细胞叶酸（H=5.28,P<0.001;趋势检验 χ²=3.83,P<0.05）水平均呈逐渐降低趋势,且血清叶酸和红细胞叶酸水平呈正相关（r=0.270,P<0.001）;MeCP2蛋白（H=33.72,P<0.001;趋势检验χ²=14.74,P<0.001）和mRNA （H=19.50,P<0.001;趋势检验χ²=10.74,P<0.001）表达量随着宫颈病变的进展均呈逐渐升高趋势;叶酸水平与MeCP2蛋白表达量呈负相关（血清叶酸：r=-0.226,P=0.003;红细胞叶酸：r=-0.164,P=0.004）。GMDR交互作用分析表明,在SCC组和CIN2+组,血清叶酸和红细胞叶酸缺乏,MeCP2蛋白高表达与MeCP2mRNA高表达呈现交互作用。结论 叶酸缺乏和MeCP2基因异常高表达可增加宫颈癌及其癌前病变的风险,血清叶酸缺乏、红细胞叶酸缺乏、MeCP2蛋白高表达和MeCP2mRNA高表达在宫颈癌变的发展过程中具有协同作用。     

Beneficial role for folate in the prevention of colorectal and breast cancer

Summary Folate is involved in the synthesis of nucleotides and amino acid metabolism such as methylation of homocysteine to methionine. Methionine is activated by adenosine triphosphate (ATP) to produce S-adenosylmethionine (SAM), the primary intracellular methyl donor. Thus, folate is essential for the synthesis, methylation, and repair of DNA. With regard to its biochemical function it has been hypothesized that a diminished folate status may contribute to carcinogenesis by alteration of gene expression and increased DNA damage. Animal and human studies support this hypothesis, particularly with respect to colorectal cancer. Epidemiological evidence for the association between folate status and cancer was first observed among ulcerative colitis patients. Several case-control studies demonstrated reduction in colorectal cancer risk with better folate status. Two large, prospective cohort studies support the concept that high folate intake is protective against colon cancer. In contrast to colorectal cancer, the potential association of folate status and risk has been less investigated in breast cancer. Recently, convincing epidemiological data establishing a positive effect of folate status on breast cancer risk were published. This review summarizes the epidemiological evidence for the association between folate status and colorectal and breast cancer risk. In addition, a short overview is given on the discussed mechanism(s) by which folate might be involved in carcinogenesis. Received: 6 October 2000, Accepted: 13 June 2001