Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Folic acid improves endothelial function in children and adolescents with type 1 diabetes

OBJECTIVE: To evaluate the effect of folate supplementation on endothelial function in children and adolescents with type 1 diabetes. STUDY DESIGN: Thirty-six subjects with type 1 diabetes age 13.6+/-2.6 years completed a randomized, double-blind, placebo-controlled crossover trial. Each subject received 8 weeks of oral folic acid (5 mg/d) and 8 weeks of placebo, with an 8-week washout period. Before and after each intervention, we assessed endothelial function by using brachial artery responses to flow (flow-mediated dilatation [FMD]) and glyceryl trinitrate, von Willebrand factor, glucose, hemoglobin A1c, total plasma homocyst(e)ine (tHcy), vitamin B(12), serum folate, and red cell folate (RCF). RESULTS: Folic acid increased FMD by 2.58 (3.1-5.7) % (95% confidence interval, 1.28-3.88), whereas placebo did not change FMD (-0.42%; 95% confidence interval, -1.67 to 0.83; P<.001). Folic acid increased serum folate by 14 nmol/L (6.2 ng/mL, P<.001) and RCF by 467.2 nmol/L (206 ng/mL, P<.001). Change in FMD was related to change in serum folate (r=0.46, P=.005) and RCF (r=0.39, P=.02). Glyceryl trinitrate responses, von Willebrand factor, tHcy, and hemoglobin A1c were not affected by the intervention. CONCLUSIONS: Short-term high-dose folic acid improves endothelial function in children and adolescents with type 1 diabetes and normal folate status independently of tHcy.     

Red blood cell folate and serum vitamin B12 status in children with sickle cell disease

PURPOSE: To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters. PATIENTS AND METHODS: Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years. RESULTS: Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P < 0.01) decreased with increasing age. CONCLUSIONS: More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.     

Plasma homocysteine levels in children and adolescents with type 1 diabetes

OBJECTIVE: Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease. The objective was to investigate total plasma homocysteine concentrations in children and adolescents with type 1 diabetes and a control group. METHOD: Twenty-seven children with type 1 diabetes and 27 subjects of an age- and sex-matched control group were recruited. Fasting samples were collected for plasma total homocysteine, serum vitamin B12, folate, and creatinine. RESULTS: Fasting total homocysteine concentrations showed no difference between patients and controls (5.6 +/- 2.9 micromol/L vs 5.7 +/- 2.2 micromol/L; p greater than 0.05). The diabetic patients had significantly higher serum folate than the healthy controls (11.4 +/- 3.3 ng/mL vs 9.4 +/- 4.1 ng/mL; P = 0.02 and higher serum B12 than the control group (282.8 +/- 119 pg/mL vs 228.5 +/- 50.9 pg/mL; P = 0.03). Total plasma homocysteine concentration correlated with age (r = 0.44, P = 0.02), weight (r = 0.56, P = 0.002), body mass index (r = 0.57, P = 0.002), folate (r = -0.48, P = 0.01), and creatinine (r = 0.41, P = 0.03) in diabetic patients. In stepwise multivariate regression model for diabetics, the independent correlates for total plasma homocysteine concentration was folate (P = 0.002). CONCLUSION: We concluded that fasting plasma total homocysteine concentrations were within normal limits in children and adolescents with type 1 diabetes who were without any clinical evidence of microvascular and macrovascular complications.     

备孕人群膳食叶酸营养状况横断面调查

目的调查上海市备孕人群膳食叶酸摄入量、膳食叶酸来源和血液叶酸水平,并评估上海市备孕人群的叶酸营养状况。方法采取横断面整群抽样的方法对在上海市闵行区妇幼保健院孕前门诊接受孕前检查的备孕夫妇进行调查。采用连续3 d 24 h膳食回顾法和食物频率表法对研究人群的膳食状况进行调查。应用《孕前膳食营养素补充剂调查表》调查研究对象近3个月的叶酸等营养素补充剂使用情况。采集空腹静脉EDTA抗凝全血和非抗凝血各5 mL,通过化学发光微粒子免疫法检测血清叶酸浓度及红细胞叶酸浓度。结果共纳入研究对象535例,女性276例（51.6%）、男性259例,平均年龄（29.4±4.1)岁。研究人群平均膳食叶酸摄入量为296.3 μg·d-1,503例（94.0%）低于推荐摄入量,女性和男性的平均膳食叶酸摄入量分别为 267.2和327.3 μg·d-1。血清叶酸水平中位数为5.8 ng·mL-1,血清叶酸缺乏率16.3%;红细胞叶酸水平中位数为214.6 ng·mL-1,红细胞叶酸缺乏率为87.3%。女性血清叶酸浓度（7.0 ng·mL-1 vs 4.8 ng·mL-1）及红细胞叶酸浓度（231.2 ng·mL-1 vs 193.7 ng·mL-1）显著高于男性（P＜0.001）。结论上海地区备孕人群中,绝大多数人群处于红细胞叶酸缺乏的状况,膳食叶酸摄入量低于推荐值。     

Homocysteine, MTHFR C677 T, vitamin B12, and folate levels in Thai children with ischemic stroke: a case-control study

Hyperhomocysteinemia has been identified as a risk factor for venous and arterial thrombosis especially in adult populations. Twenty-eight patients with an initial diagnosis of ischemic stroke and 100 controls, aged 相似文献   

Reduced total plasma homocyst(e)ine in children and adolescents with type 1 diabetes

OBJECTIVES: The objective was to investigate total plasma homocyst(e)ine (tHcy), methylenetetrahydrofolate reductase (MTHFR) genotype, and the contribution of diet to homocysteine values in children and adolescents with type 1 diabetes and a control group. STUDY DESIGN: A total of 78 children with type 1 diabetes and 59 members of an age- and sex-matched control group were recruited. Fasting samples were collected for tHcy, MTHFR genotype, serum vitamin B(12), serum folate, red cell folate, and plasma creatinine. Food frequency questionnaires targeted intake of folate, vitamin B(6), and vitamin B(12). RESULTS: Fasting tHcy was reduced in patients compared with the control group (4.7 vs 5.9 micromol/L, P <.001). Serum folate (P =.002), red cell folate(P <.001), and serum vitamin B(12) (P =.005) were higher, and plasma creatinine was lower. A significant difference in tHcy values between patients and the control group persisted after correction was done for these factors (r = 0.1, P =.02). No difference was seen in the frequency of MTHFR polymorphisms. tHcy was not elevated in those patients with the 677TT or 677T/1298C genotypes, although red cell folate was significantly higher in members of the case (P =.01) and control groups (P =.05) with a 677 TT genotype. Dietary intake of folate correlated with serum folate (r = 0.4,P =.005). CONCLUSION: tHcy values are lower in children and adolescents with type 1 diabetes. Higher serum levels of folic acid and vitamin B(12), reflecting differences in dietary intake between children with diabetes and members of a control group, partially account for this difference.     

Circulating L-selectin concentrations in children with recent-onset IDDM

To clarify conflicting claims of altered serum concentrations of soluble L-selectin (sCD62L) in recent-onset IDDM, sCD62L was measured in 89 children and adolescents with IDDM (35 recent-onset, 12 during the first year of insulin treatment, and 42 with long-standing (> 1 yr) treatment) alongside 124 controls. Children < 14 yr of age both with and without IDDM (n = 160) had grossly elevated sCD62L concentrations (20.2 +/- 4.9 nmol/l), as compared with adolescents (14-18 yr, n = 23; 15.9 +/- 3.9 nmol/l) and adults (> 18 yr, n = 30; 11.2 +/- 2.3 nmol/l) (p < 0.0001). Multivariate analysis confirmed the strong inverse association between age and sCD62L (p < 0.001) while revealing that sCD62L concentrations were slightly elevated in recent-onset IDDM, as compared with insulin-treated IDDM patients or nondiabetic controls (p = 0.028). Actual sCD62L concentrations in the 35 recent-onset IDDM patients were 22.2 +/- 4.9 nmol/L vs 19.6 +/- 3.6 nmol/l in 35 non-diabetic controls matched for age (p = 0.022). While this significant but small rise of systemic sCD62L reflects leukocyte activation, it is obscured by the inverse association between sCD62L and chronological age in children and adolescents. Therefore, determining sCD62L serum concentrations appears to be of limited value for clinical investigators caring for children and adolescents with IDDM.     

Alanine amino transferase concentrations are linked to folate intakes and methylenetetrahydrofolate reductase polymorphism in obese adolescent girls

OBJECTIVE: The objective of this study was to investigate the consequences of low dietary folate intake and the impact of the 677 C-->T methylenetetrahydrofolate reductase (MTHFR) common mutation on liver function in obese adolescents. METHODS: Fifty-seven obese girls (BMI = 36.1 +/- 6.0 kg/m) aged 14.1 +/- 1.5 years were included before starting a weight reduction program. Dietary intakes for folate were assessed by means of an adapted food frequency questionnaire (n = 50). Liver enzymes, plasma lipids, glucose metabolism parameters, ferritin, homocysteine and erythrocyte folate content were measured in plasma or blood obtained under fasting conditions. The MTHFR 677 C-->T polymorphism, which is associated with decreased enzyme activity, was determined using PCR. Body composition was assessed using dual x-ray absorptiometry. RESULTS: Twenty-three subjects were heterozygote (CT) for the mutation and 5 were homozygote (TT). An increase in alanine amino transferase (ALT) and ALT/aspartate aminotransferase ratio was associated with the mutation (F = 4.46, P = 0.016 and F = 5.92, P = 0.0049, respectively). Alanine amino transferase was correlated negatively to folate intake (r = -0.32, P = 0.024) (n = 50) and positively to homocysteine concentrations (r = 0.30, P = 0.025). Body composition was similar among the 3 genotypic groups. Ferritin was also correlated to ALT concentrations of the entire group (P = 0.009). CONCLUSION: Our data suggest that folate intake and the MTHFR polymorphism represent a part of the link between antioxidant status and liver disease in obese adolescent girls.     

Nicotine patch therapy in 101 adolescent smokers: efficacy, withdrawal symptom relief, and carbon monoxide and plasma cotinine levels

OBJECTIVES: To determine the efficacy of nicotine patch therapy in adolescents who want to stop smoking and to assess biochemical markers of smoking and nicotine intake. DESIGN: Nonrandomized, open-label trial using a 15 mg/16 h patch. SETTING: Two midwestern cities. SUBJECTS: One hundred one adolescents aged 13 through 17 years smoking at least 10 cigarettes per day (cpd). INTERVENTION: Six weeks of nicotine patch therapy and follow-up visits at 12 weeks and 6 months. MAIN OUTCOME MEASURES: Self-reported smoking abstinence verified by expired-air carbon monoxide (CO) level of no more than 8 ppm, nicotine withdrawal symptoms, and plasma cotinine level. RESULTS: Forty-one participants were female (mean [+/- SD] age, 16.5 [+/- 1.1] years). Median baseline smoking rate was 20.0 cpd (range, 10-40 cpd). Biochemically confirmed point prevalence smoking abstinence was 10.9% (11/101) at 6 weeks and 5.0% (5/101) at 6 months. The mean (+/- SD) plasma cotinine level at baseline was 1510.9 +/- 732.7 nmol/L; for nonsmoking subjects at weeks 3 and 6, 607.8 +/- 386.2 and 710.0 +/- 772.5 nmol/L, respectively. Plasma cotinine levels were correlated with CO levels at baseline (r = 0.27; P = .006), week 3 (r = 0.34; P = .004), and week 6 (r = 0.26; P = .03) and with mean cigarettes smoked per day during weeks 3 (r = 0.24; P = .04) and 6 (r = 0.30; P = .02). Mean smoking rates decreased significantly during the study, an effect that lessened at 12 weeks and 6 months. CONCLUSIONS: Nicotine patch therapy plus minimal behavioral intervention does not appear to be effective for treatment of adolescent smokers. Plasma cotinine and CO levels appear to be valid measures of smoking rates during the cessation process, but not at baseline. Smoking rates were reduced throughout the study. Additional pharmacological and behavioral treatments should be considered in adolescent smokers.     

窒息新生儿血清同型半胱氨酸与叶酸的变化

目的：探讨血清中高同型半胱氨酸（Hcy）血症及低叶酸水平与新生儿窒息的发生是否具有相关性,并对性别、胎龄等因素对血清中同型半胱氨酸及叶酸水平是否有一定影响进行分析。方法：应用酶联免疫吸附实验方法检测血清中Hcy水平,应用放射免疫法测定血中叶酸浓度。结果：①与无窒息对照组相比, 新生儿窒息患儿血清Hcy水平显著升高,而叶酸水平显著降低;②窒息组男婴血清Hcy、叶酸水平分别为15.82 ±2.51 μmol/L; 2.49 ±0.19 ng/mL,女婴为10.50±2.19 μmol/L; 2.38±0.40 ng/mL,男、女婴之间比较差异无显著性;③窒息组足月儿血清Hcy、叶酸水平为12.34 ±2. 01 μmol/L,2.58 ±0.19 ng/mL;早产儿为21.25±5.01 μmol/L; 2.14±0.34 ng/mL。早产儿Hcy水平显著高于足月儿（P<0.05）。结论：①新生儿窒息与血清Hcy及叶酸水平具有显著相关性。②血清Hcy及叶酸水平在性别上无显著差异。③缺氧窒息合并早产者血清Hcy水平升高最为显著。     

Low vitamin D status in children with sickle cell disease

OBJECTIVES: To examine vitamin D status in children with sickle cell disease (SCD)-SS and its relation to season and dietary intake. STUDY DESIGN: Growth, dietary intake, 25-hydroxyvitamin D (25-OHD), and parathyroid hormone levels were measured. Children with low and normal vitamin D status were compared. Low vitamin D status was defined as a serum concentration of 25-OHD <27.5 nmol/L. Serum 25-OHD and parathyroid hormone levels were compared among children with SCD-SS and healthy children. RESULTS: Children with SCD-SS (n=65), 5 to 18 years of age, were evaluated. Mean (+/-SD) serum 25-OHD concentration was 25.5 +/- 12.8 nmol/L; 65% of subjects had low vitamin D status. Low vitamin D prevalence was highest during spring (100%). Children with SCD-SS were at higher risk for low vitamin D status than healthy children. Vitamin D intake was lower in subjects with SCD-SS and low vitamin D than those with normal serum vitamin D status (P <.05). CONCLUSIONS: Low serum vitamin D status was highly prevalent in black children with SCD-SS. Vitamin D status was associated with season and dietary intake.     

Corticotropin releasing hormone stimulation test and nocturnal cortisol levels in normal children.

This study examined hypothalamic-pituitary-adrenal axis functioning in a group (n = 25) of very carefully screened normal children with considerable attention to issues of adaptation and procedural stress. The subjects (mean age 10.3 +/- 1.6 y) were selected as "supernormal" controls as a part of a large psychobiologic study of childhood depression. After careful acclimatization over 24 h, the subjects underwent all-night sampling of plasma cortisol every 20 min, then the following evening had a corticotropin releasing hormone (CRH) stimulation test (using human CRH). Human CRH resulted in a rapid stimulation of adrenocorticotropin and cortisol. Adrenocorticotropin levels increased from 6.8 +/- 3.5 (+/- SD) pmol/L (30.7 +/- 16.1 pg/dL) to a peak of 11.6 +/- 5.5 pmol/L (52.9 +/- 24.8 pg/mL) at 15 min with return to baseline levels by 60 min. Cortisol levels increased from 131.4 +/- 59.7 nmol/L (4.8 +/- 2.2 micrograms/dL) to a peak of 427.0 +/- 113.5 nmol/L (15.5 +/- 4.1 micrograms/dL) at 30 min with return to baseline by 120 min. The cortisol peak was significantly greater (p less than 0.05) in boys [474.6 +/- 129.7 nmol/L (17.2 +/- 4.7 micrograms/dL)] than in girls [366.9 +/- 52.4 nmol/L (13.3 +/- 1.9 micrograms/dL, p less than 0.05)]. Age, body mass index, and pubertal status were not significantly related to hypothalmic-pituitary-adrenal axis measures. Nocturnal cortisol reached a nadir at 160 +/- 60 min after sleep onset (0102 h) and a peak 480 +/- 60 min after sleep onset (0612 h). Nocturnal cortisol levels were significantly (positively) correlated with human CRH-stimulated cortisol (r = 0.56, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary prevention of neural tube defects with folate in Western Australia: the value of the Western Australian Birth Defects Registry

This paper reviews the role of the Western Australian Birth Defects Registry in the primary prevention of neural tube defects. The Registry provides complete and up-to-date information on all neural tube defects (NTD), including terminations of pregnancy. These data have been used to determine a baseline rate of NTD and to monitor trends in NTD over time, when health promotion of folic acid supplement use and voluntary fortification of food with folate were introduced. The register has also been used to investigate NTD in special populations (Indigenous infants in Australia) and as a sampling frame for case control studies. The data derived from these studies have been used to assist in assessing whether mandatory food fortification in Australia is indicated to prevent NTD.     

Bone mineral density of the lumbar spine in children and adolescents with celiac disease on a gluten-free diet in São Paulo, Brazil

BACKGROUND: To compare bone mineral density (BMD) in children and adolescents with celiac disease (CD) and control subjects and to evaluate diet adequacy and calcium metabolism in patients with CD. METHODS: Thirty patients with asymptomatic CD (17 children, 13 adolescents), on a gluten-free diet, and 23 healthy subjects were studied. BMD of the lumbar spine (dual energy x-ray absorptiometry) was performed on all patients and control subjects. In patients, food diaries for nine nonconsecutive days were obtained and analyzed. In patients, laboratory tests pertaining to calcium balance were obtained. RESULTS: The mean weight and height of the adolescents with CD were lower than those of control subjects (weight: 45.8 +/- 10.5 kg v 55.3 +/- 10.5 kg, P = 0.037; height: 153.0 +/- 11.0 cm v 167 +/- 12.0 cm, P = 0.007). The mean BMD in adolescents with CD was significantly lower than that of the control subjects (0.917 +/- 0.116 g/cm2 v 1.060 +/- 0.158 g/cm2, P = 0.015), whereas no significant difference was found between children with CD and control subjects (P = 0.595). A multiple-regression model shows that increases in BMD relative to height were lower in adolescents with CD than in control subjects. The proportion of adolescents who had started a gluten-free diet after 2 years of age was higher than that of children with CD (P < 0.001). High percentages of magnesium, calcium, and phosphorous deficiencies were present in CD patients' diets. The serum levels of ionized and total calcium and parathormone were normal. CONCLUSIONS: The BMD of adolescents with CD was lower than that of the control subjects, whereas no difference was found between the BMD of children with CD and that of control subjects.     

Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide

OBJECTIVE: To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma. METHODS: Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment. RESULTS: Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003). CONCLUSION: FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.     

盐酸二甲双胍改善代谢综合征青少年脂联素水平和胰岛素敏感性的研究

目的观察盐酸二甲双胍治疗青少年代谢综合征(MS)前后血清脂联素水平和胰岛素敏感性的变化。方法对348例(男208例,女140例)7~16岁[(11.47±2.12)岁]中、重度肥胖青少年进行体检和生化检测、口服葡萄糖耐量试验,检出其中符合MS诊断标准的36例,设为MS组,无生化检测异常的单纯性肥胖61例,设为单纯肥胖组。另设24例非肥胖青少年为对照组。对三组进行总体胰岛素敏感指数、稳态模型胰岛素抵抗指数(HOMA-IR)和血清脂联素等的比较。对MS组患儿中20例给予连续口服盐酸二甲双胍治疗3个月,观察治疗前后的HOMA-IR和血清脂联素、生化指标的变化。结果(1)HOMA-IR水平由低到高依次为对照组、单纯性肥胖组、MS组;胰岛素敏感指数和血清脂联素水平排序正好相反;HOMA-IR、胰岛素敏感指数和血清脂联素在3组间比较,差异均有统计学意义(均P<0.01)。(2)连续应用盐酸二甲双胍治疗满3个月的20例MS患儿:HOMA-IR下降[治疗前5.7(1.9~12.4),治疗后2.9(0.9~7.4),t=5.05,P<0.01],血清脂联素上升[治疗前(3.0±0.9)mg/L,治疗后(6.1±1.9)mg/L,t=6.19,P<0.01],血压、2 h血糖、甘油三酯、胆固醇、肝酶均有不同程度下降,治疗前后比较,差异有统计学意义(均P<0.01)。结论MS青少年脂联素水平和胰岛素敏感性比单纯性肥胖更低;应用盐酸二甲双胍治疗后MS青少年的脂联素水平上升,胰岛素敏感性改善,临床多项指标好转。     

Effect of vitamin K1 on glucose-6-phosphate dehydrogenase deficient neonatal erythrocytes in vitro

AIM: To determine whether vitamin K1, which is routinely administered to neonates, could act as an exogenous oxidising agent and be partly responsible for haemolysis in glucose-6-phosphat-dehydrogenase (G-6-PD). METHODS: G-6-PD deficient (n = 7) and control (n = 10) umbilical cord blood red blood cells were incubated in vitro with a vitamin K1 preparation (Konakion). Two concentrations of Vitamin K1 were used, both higher than that of expected serum concentrations, following routine injection of 1 mg vitamin K1. Concentrations of reduced glutathione (GSH) and methaemoglobin, indicators of oxidative red blood cell damage, were determined before and after incubation, and the mean percentage change from baseline calculated. RESULTS: Values (mean (SD)) for GSH, at baseline, and after incubation with vitamin K1 at concentrations of 44 and 444 microM, respectively, and percentage change from baseline (mean (SD)) were 1.97 + 0.31 mumol/g haemoglobin, 1.89 +/- 0.44 mumol/g (-4.3 +/- 13.1%), and 1.69 +/- 0.41 mumol/g (-14.5 +/- 9.3%) for the G-6-PD deficient red blood cells, and 2.27 +/- 0.31 mumol/g haemoglobin, 2.09 +/- 0.56 mumol/g (-7.2 +/- 23.2%), and 2.12 +/- 0.38 mumol/g (-6.0 + 14.1%) for the control cells. For methaemoglobin (percentage of total haemoglobin), the corresponding values were 2.01 +/- 0.53%, 1.93 +/- 0.37% (-0.6 +/- 17.4%) and 2.06 +/- 0.43% (5.7 +/- 14.2%) for the G-6-PD deficient red blood cells, and 1.56 +/- 0.74%, 1.70 +/- 0.78% (12.7 +/- 21.9%), and 1.78 +/- 0.71% (20.6 +/- 26.8%) for the control red blood cells. None of the corresponding percentage changes from baseline was significantly different when G-6-PD deficient and control red blood cells were compared. CONCLUSIONS: These findings suggest that G-6-PD deficient red blood cells are not at increased risk of oxidative damage from vitamin K1.     

Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India

The relative importance of calcium vs. vitamin D deficiency in the etiology of nutritional rickets in the tropics may be different in children compared with adolescents. We studied calcium intake, sun exposure, serum alkaline phosphatase, and 25 hydroxyvitamin D in 24 children and 16 adolescents with rickets/osteomalacia. The values were compared with those obtained in control subjects (34 children and 19 adolescents). We found that young children with rickets had lower calcium intake compared with controls (285 +/- 113 vs. 404 +/- 149 mg/day, p < 0.01), but similar sun exposure (55 +/- 28 vs. 56 +/- 23 min x m2/day) and 25 hydroxyvitamin D (49 +/- 38 vs. 61 +/- 36 nmol/l). Sixteen of 24 children with rickets had 25 hydroxyvitamin D above the rachitic range (> 25 nmol/l), in contrast to one of 16 adolescents. Adolescent patients had low calcium intake vs. controls (305 +/- 196 vs. 762 +/- 183 mg, p < 0.001), and lower sunshine exposure (16 +/- 15 vs. 27 +/- 17 min x m2/day, p < 0.01) and serum 25 hydroxyvitamin D (12.6 +/- 7.1 vs. 46 +/- 45.4 nmol/l, p < 0.001). The odds ratio for developing rickets with a daily calcium intake below 300 mg was 4.8 (95 per cent CI, 1.9 - 12.4, p = 0.001). Subjects with rickets were randomized to receive 1 g calcium daily, with or without vitamin D. Children showed complete healing in 3 months, whether they received calcium alone or with vitamin D. Adolescents showed no response to calcium alone, but had complete healing with calcium and vitamin D in 3-9 months (mean 5.3 months). Thus deficient calcium intake is universal among children and adolescents with rickets/osteomalacia. Inadequate sun exposure and vitamin D deficiency are important in the etiology of adolescent osteomalacia.