新生儿缺氧缺血性脑病临床分度与血清同型半胱氨酸及叶酸、维生素B12水平变化的临床研究

目的 探讨血清中高同型半胱氨酸（Hcy）及低叶酸、维生素B12水平与新生儿缺氧缺血性脑病（HIE）临床分度的相关性,为HIE患儿的诊疗提供参考。方法 2010年4月—2011年4月天津市儿童医院新生儿内科收治的患有不同程度HIE的新生儿共94例,其中轻度32例、中度40例、重度22例,对照组为同期收治的诊断为新生儿咽下综合征的新生儿20例。比较各组新生儿血清Hcy、叶酸及维生素B12水平。结果4组新生儿血清Hcy、叶酸、维生素B12水平差异均有统计学意义（均P＜0.05）。与对照组相比,HIE新生儿血清Hcy水平随着HIE临床分度加重而逐渐升高（P＜0.05）;患儿血清叶酸和维生素B12浓度均低于对照组,且重度组维生素B12水平低于中度组（P＜0.05）。结论 HIE患儿血清Hcy水平在对其病情严重程度的评估中具有一定参考价值。对HIE患儿及时给予叶酸及维生素B12的补充可能在疾病的治疗过程中发挥积极作用。     

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Purpose

Alterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.

Methods

We recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.

Results

After 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.

Conclusions

These results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.     

幽门螺杆菌感染与血清铁和维生素B12及叶酸的关系

目的探讨幽门螺杆菌(Hp)感染与血清铁、维生素B12、叶酸水平的关系;明确Hp感染导致微量营养素(血清铁、维生素B12、叶酸)缺乏的复合模式。方法选择该院门诊患者120例,进行快速尿素酶试验和13C尿素呼气试验检查,根据检查结果分为Hp阳性胃炎组及Hp阴性胃炎组,比较两组患者血清铁、维生素B12、叶酸的水平。结果 Hp阳性胃炎组患者血清铁、维生素B12和叶酸明显低于Hp阴性胃炎组分别为[(10.891±2.980)μmol/L与(19.232±4.298)μmol/L、(443.865±79.183)μg/L与(602.419±83.860)μg/L、(5.329±1.710)ng/L与(9.033±1.935)ng/L],差异有统计学意义(P<0.01)。结论Hp感染能够造成血清铁、维生素B12、叶酸水平下降,从而导致微量营养素(血清铁、维生素B12、叶酸)的缺乏。     

Treatment of depression: time to consider folic acid and vitamin B12

We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.     

The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine

The objective of the present study was to examine the relationship between serum folate, vitamin B12, and homocysteine levels and the timing of clinical improvement to fluoxetine in major depressive disorder (MDD) patients. A total of 110 outpatients with MDD who responded to an 8-wk trial of fluoxetine had serum folate, B12, and homocysteine measurements at baseline (prior to fluoxetine initiation). Onset of clinical improvement was defined as a 30% decrease in Hamilton Depression Scale scores that led to a 50% decrease by week 8. Patients with low folate levels (0.05). In conclusion, low serum folate levels were found to be associated with a delayed onset of clinical improvement during treatment with fluoxetine in MDD by, on average, 1.5 wk.     

血浆同型半胱氨酸与脑分水岭梗死的关系探讨

目的 探讨同型半胱氨酸(Hcy)与脑分水岭梗死(CWI)的关系.方法 58例CWI患者(观察组)和56例健康者(对照组),采用荧光偏振免疫分析法检测两组及CWI各亚组的Hcy、叶酸和维生素B12水平.结果 CWI患者Hcy水平明显高于对照组,维生素B12及叶酸水平则明显低于对照组,差异均有统计学意义(t=2.013、2.842、3.051,均P＜0.05);CWI患者不同亚组之间血浆Hcy、叶酸和维生素B12水平差异均无统计学意义(均P＞0.05).结论 高血浆Hcy可能是CWI发生的重要原因之一.     

The effect of folic acid supplementation on the pharmacokinetics and pharmacodynamics of oral methotrexate during the remission-induction period of treatment for moderate-to-severe plaque psoriasis

Objective We assessed the effect of folic acid (FA) on the pharmacokinetics and pharmacodynamics of low-dose oral methotrexate (MTX) during the remission-induction phase of psoriasis treatment. Methods In a 32-week, open-label, two-way cross-over study, patients (n = 20, seven men, aged 35–70 years) with moderate-to-severe plaque psoriasis were randomly assigned to receive MTX plus FA (20 mg/week) for 16 weeks followed by MTX monotherapy (three doses of MTX separated by 12-h intervals once a week) for an additional 16 weeks (treatment arm A, n = 10) or to receive the opposite sequence of treatments (arm B, n = 10). Dosing of MTX was individualised with the help of pre-study evaluation of plasma MTX pharmacokinetics. The Psoriasis Area and Severity Index (PASI), biochemistry and haematology tests and erythrocyte concentration of MTX polyglutamates (MTXPG) were evaluated throughout the study. Results In arms A and B, the mean (range) concentrations of MTXPG (nmol/L) were comparable [week 16: 96.2 (32.0–157) vs. 111 (73.7–175), P = 0.32; week 32: 103 (55.8–173) vs. 83.6 (27.4–129), P = 0.24]. After 16 weeks, the mean±SEM PASI decreased from 20.1 ± 2.1 to 8.8 ± 1.3 in arm A, while a greater reduction from 27.2 ± 2.1 to 5.1 ± 1.0 occurred in arm B (P < 0.001). Positive correlations were found between the percent improvement in PASI at week 16 and the ratios of the concentration of MTXPG to plasma folate (rho = 0.59, P = 0.008) or RBC folate concentration (rho = 0.56, P = 0.013). Due to an accelerated decline in PASI in arm A and a trend to its worsening in arm B after crossing over of treatments, the mean absolute PASI scores in both arms were comparable at week 32. Conclusion The antipsoriatic effect of MTX during the remission-induction phase of treatment is influenced by folate status and may be significantly less if combined treatment with FA is used, irrespective of pre-treatment folate levels. The individual tailoring of MTX dosing needs further attention because the mean percent PASI improvement from baseline was 83% and the inter-patient variability in response was low after 16 weeks of monotherapy with MTX.     

滥用止咳药水与叶酸缺乏相关研究

目的:探讨止咳药水滥用与叶酸缺乏的关系。方法:根据入选标准收集2008年4月至2012年4月间住院的止咳药水成瘾患者200例为病例组;同期健康体检者200例为对照组,检测两组血清叶酸、维生素B12水平。结果:病例组(止咳药水滥用组)血清叶酸水平显著低于对照组,差异有统计学意义(P<0.001);病例组血小板计数显著高于对照组(P<0.05);病例组血清维生素B12水平显著低于对照组(P<0.01)。病例组中,血清叶酸和维生素B12缺乏的发生率分别为40%(对照组6%,P<0.001,RR=6.0)和25%(对照组0%)。维生素B12水平和血清叶酸水平之间存在正相关(P=0.004,R=0.28)。结论:叶酸缺乏可能与止咳药水滥用有关。     

Plasma folate and homocysteine levels may be related to interictal "schizophrenia-like" psychosis in patients with epilepsy

Genetic and clinical data suggest that folate and homocysteine may play a role in the pathogenesis of psychiatric disorders. The total plasma homocysteine level is a sensitive measure of a functional folate deficiency. We thus investigated whether a functional folate deficiency and/or elevated levels of plasma homocysteine may be related to interictal "schizophrenia-like" psychosis (interictal psychosis ) of epilepsy. We studied the plasma folate, vitamin B12, and homocysteine levels of 32 age- and sex-matched epileptic patients with or without interictal psychosis. Each group included 25 localization-related epilepsies and 7 generalized epilepsies. The epileptic patients with interictal psychosis had significantly lower folate levels and higher homocysteine levels than those without interictal psychosis. There were no significant differences in the vitamin B12 levels between the two groups. The present study suggests that low plasma folate and high plasma homocysteine levels may be related to the pathophysiology of interictal psychosis of epilepsy. In future studies, we should investigate whether folate supplementation, in addition to antipsychotics, might play a beneficial role in the treatment of interictal psychosis in epileptic patients. Furthermore, the present findings should be confirmed by prospective longitudinal studies in a larger group of patients with epilepsy.     

脑梗死患者血清同型半胱氨酸、叶酸、维生素B12水平的测定及临床意义

目的 探讨血清同型半胱氨酸(Hcy)、叶酸(FA)及VitB12与脑梗死的关系及临床意义.方法 采用酶循环法和电化学发光免疫分析法分别检测100例脑梗死患者血清Hcy、FA及VitB12水平,并与同期60例健康体检者进行比较.结果 脑梗死组患者血清Hcy水平(16.35±5.52)μmol/L,升高比例(22％),明显高于对照组[(8.62±3.45)μmol/L,6.7％,P<0.01];血清FA和VitB12降低的脑梗死组患者升高比例(19％和24％)显著高于健康对照组(5.0％,11.7％,P<0.01),而血清FA水平(13.62±5.98)nmol/L和VitB12水平(527.35±288.65)pmol/L显著低于对照组[(18.45±6.70)nmol/L,(565.24±282.72)pmol/L,P<0.01].脑梗死组患者血清FA和VitB12水平与Hcy水平均呈负相关(r1=-0.365,r2=-0.625,P<0.05).结论 Hcy血症为脑梗死的高危因素,与FA和VitB12水平下降有关,Hcy、FA、VitB12的检测在脑梗死患者的预防与治疗中有重要的临床价值.     

A partially overlapping treatment course with lamivudine and interferon in hepatitis B e antigen-negative chronic hepatitis B

BACKGROUND: Treatment of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHBe-) with interferon or lamivudine alone is inefficient and reports of combination treatment with both drugs, equivocal so far. AIM: To investigate the efficacy of a lamivudine-interferon combination therapy in 36 patients HBeAg-negative CHBe-. METHODS: Lamivudine was administered from 1 to 12 months and interferon-alpha2b from 7 to 18 months. A historical control group of 36 CHBe- patients, matched for age and sex and treated with the same dosage of interferon-alpha2b was used. All patients were followed up for > or =12-month post-treatment. RESULTS: The biochemical response rate at the end of treatment was 78% in lamivudine-interferon and 52.8% in interferon-control group (P = 0.026) and at 12-month post-treatment 38.9% and 22.2%, respectively (P = 0.125). Alanine aminotransferase normalization and serum HBV-DNA levels < or =30 000 cp/mL were observed in 50.0% of lamivudine-interferon-treated and 30.6% of interferon-treated patients at the end of treatment (P =0.093) and in 22.2% and 13.9% of patients, respectively, at 12-month post-treatment (P = 0.358). Moreover, alanine aminotransferase normalization and undetectable serum HBV-DNA (<400 cp/mL) was observed in 30.6% of lamivudine-interferon-treated and 8.3% of interferon-treated patients at the end of treatment (P = 0.017) and in 8.3% and 0% of patients, respectively, at 12-month post-treatment (P = 0.076). CONCLUSIONS: In CHBe-, 12 months after ending a lamivudine-interferon partially overlapping 18-month combination course, 22% of patients still maintain normal alanine aminotransferase and HBV-DNA levels < or =30 000 cp/mL. However, a 12-month interferon monotherapy course may achieve similar responses.     

Nutritional and life style determinants of plasma homocysteine in schizophrenia patients.

Recently, homocysteine levels have been reported to be elevated in young male schizophrenic patients. Since smoking, obesity, low folate or low vitamin B12 and various medications can increase homocysteine levels, we studied these variables and other clinical variables in 258 schizophrenic patients. A multiple linear regression for plasma homocysteine was performed on variables that were significantly related to plasma homocysteine. Variables predicting homocysteine levels in schizophrenic patients include gender, plasma folate levels, plasma vitamin B12 levels, mean red blood cell corpuscular volume and diastolic blood pressure. Only 24% of the variance in male patients was explained by the model. The reason for elevated plasma homocysteine in some schizophrenic populations remains unclear.     

Thalassaemia, iron, and pregnancy.

Haematological values of 35 pregnant women with beta-thalassaemia trait were followed during pregnancy. The discriminant function, calculated from haematological indices, was of no value in diagnosing beta-thalassaemia trait during pregnancy. Initially patients were given iron supplements only if the serum iron and total iron binding capacity levels indicated iron deficiency, but bone marrow biopsies performed in the first 22 patients at 32 weeks indicated deficient iron stores. These patients were therefore given iron irrespective of their serum iron level. All subsequent patients with beta-thalassaemia were also put on iron routinely at booking. Retrospectively the patients were divided into two groups. Patients in group 1 (18 patients) had received iron for less than 12 weeks, and their haemoglobin levels fell significantly during pregnancy (P less than 0-001). Haemoglobin levels in 16 patients who had received iron for more than 12 weeks (group 2), however, did not fall significantly during pregnancy (P less than 0-6). It is suggested (contrary to common practice) that patients with beta-thalassaemia trait should be given iron supplements during pregnancy. Serum folate and vitamin B12 levels did not change significantly in these patients and there was no increase in the incidence of maternal or fetal complications.     

The effect of vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and testosterone deficiency

BackgroundAutoimmune (Hashimoto’s thyroiditis) is characterized by a strong female preponderance, which may suggest that sex hormones have an impact on thyroid autoimmunity. The aim of this study was to investigate whether testosterone determines vitamin D action on thyroid antibody titers and thyroid function tests in men with autoimmune thyroiditis and low testosterone levels.MethodsThe study included 36 men with testosterone deficiency, 17 of whom had been treated for at least 26 weeks with oral testosterone undecanoate (120 mg daily). Because of coexistent euthyroid Hashimoto’s thyroiditis, all participants were then treated with vitamin D (100 μg daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin, free thyroid hormones, testosterone and 25-hydroxyvitamin D, as well as Jostel’s thyrotropin index, SPINA-GT and SPINA-GD were assessed before vitamin D treatment and 26 weeks later.ResultsWith the exception of testosterone levels, there were no significant differences between both study groups in serum hormone levels, antibody titers and thyroid function tests. All participants completed the study. In addition to increasing 25-hydroxyvitamin D levels, vitamin D increased SPINA-GT and reduced thyroid peroxidase and thyroglobulin antibody titers. In testosterone-treated men, vitamin D increased testosterone levels. Vitamin D did not affect serum levels of thyrotropin, free thyroid hormones, Jostel’s thyrotropin index and SPINA-GD. Treatment-induced changes in thyroid antibody titers and SPINA-GT were more pronounced in testosterone-treated than testosterone-naïve men.ConclusionsThe obtained results suggest that the beneficial effect on thyroid autoimmunity and thyroid secretory function is stronger in men receiving testosterone therapy.     

Negative association between circulating total homocysteine and proinflammatory chemokines MCP-1 and RANTES in prepubertal lean, but not in obese, children

This study investigated in prepubertal obese children (POC), compared with prepubertal lean children (PLC), a possible relation among plasma total homocysteine (tHcy)-an independent risk factor for future atherosclerosis-and MCP-1 and RANTES, two circulating chemokines inducing leukocyte transendothelial migration (TEM), implicated in the initial stages of the inflammatory part of the atherosclerotic process. Seventy-two POC were evaluated for circulating tHcy, MCP-1, and RANTES, and compared with 42 healthy PLC. The mean adjusted (for age, sex as well as log10total insulin, vitB12, folate, total cholesterol, HDL cholesterol, log10triglycerides, and log10glucose levels) differences in tHcy, MCP-1, and RANTES levels between PLC and POC were all significant [1.16 nmol/mL (P = 0.03), 26.6 pg/mL (P = 0.02), and 52.9 pg/mL (P = 0.03), respectively]. In PLC, but not in POC, tHcy levels were negatively associated with both circulating MCP-1 (B = -1.68, P = 0.007) and RANTES (B = -1.16, P = 0.01) after adjusting for age, sex, BMI, as well as log10total insulin, vitB12, folate, total cholesterol, HDL cholesterol, log10triglycerides, and log10glucose levels. In conclusion, in POC there is a lack, in contrast to PLC, of a possibly autoregulatory, negative association of elevated tHcy levels to increased MCP-1 and RANTES levels. This could contribute to future, homocysteine-induced atherosclerosis.     

Serum concentrations of p, p'-DDE, HCB, PCBs and reproductive hormones among men of reproductive age

Exposure to polychlorinated biphenyls (PCBs) has been associated with changes in reproductive hormone levels, however most groups studied have been highly exposed. We investigated the association of PCBs, hexachlorobenzene (HCB) and p, p'-DDE with serum sex hormones in 341 adult men from a US infertility clinic with exposure levels consistent with those observed in the general population. In crude regression models we observed several negative associations of PCBs and HCB with steroid hormone-binding globulin (SHBG) and total and free testosterone. After adjustment for lipids, age and BMI, nearly all significant associations were attenuated. A negative relationship remained between PCB 118 and SHBG (p<0.01), and relationships of dioxin-like PCBs with SHBG and total testosterone, and between PCB 118 and total testosterone, were suggestive. These results suggest a minimal relationship between PCB exposures at low background levels similar to those observed in the general population of the US and circulating reproductive hormones.     

The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland

Low plasma folate and its derivatives have been linked with depressive disorders in studies dating back over 30 years. A thermolabile variant (677C>T) of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T genotype frequencies in a cohort of patients (mean age 48 years) with depressive disorder (n = 100) were compared with those in age- and sex-matched controls. Serum levels of folate, homocysteine and vitamin B(12) were also compared between groups. The thermolabile variant of MTHFR was significantly more common in the group with a history of depressive disorder (P= 0.03). Serum levels of folate, homocysteine and vitamin B(12) did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.     

The role of pterins and related factors in the biology of early postpartum depression.

Plasma tryptophan and other putative amino acids, cortisol, folate and vitamin B12 and urinary biopterin (B) and neopterins (N) were measured in three groups of women: 62 women in the early postpartum period, 23 pregnant and 38 non-gravid controls. Sixty-two postpartum women were screened for depression by the Edinburgh postnatal depression scale (EPDS) on day 7 after delivery. Postpartum women had significantly lower tryptophan, vitamin B12 and significantly greater levels of cortisol, folate, neopterins and biopterins than controls. Comparisons between women who were classified on the EPDS as cases and non-cases revealed only a statistically significant difference for lower N:B (P<0.01) and lower folate (P<0.01) ratio in cases than non-cases. Multiple regression analysis showed a significant contribution for low tryptophan to increased EPDS which also showed significant correlations with low methionine, low tyrosine, low N:B ratio and high vitamin B12.     

甲状腺功能紊乱对男女生殖系统的影响

甲状腺功能亢进、甲状腺功能减退是常见的甲状腺功能紊乱疾病,甲状腺功能紊乱会导致男女不孕不育,目前研究机制包括：（1）甲状腺功能紊乱会影响男女性激素水平,甲状腺功能亢进会引起卵泡刺激素（FSH）、黄体生成素（LH）、性激素结合蛋白（SHBG）、雌二醇（E2）、睾酮（TT）升高,甲状腺功能减退会引起泌乳素（PRL）升高,E2、TT水平的降低;（2）甲状腺激素对性腺有一定作用,高剂量的甲状腺激素会对卵巢、睾丸产生损坏作用,进而影响其功能;（3）甲状腺功能紊乱造成女性月经紊乱、排卵异常、男女性功能异常、心理异常,造成性生活不满意.因此,正常的甲状腺功能有助于维持生殖系统的稳定,甲状腺功能紊乱的患者需提前治疗,这将会提高受孕率,降低流产率、死胎率.     

中老年脑白质疏松症同型半胱氨酸叶酸及维生素B12测定的临床意义

目的 探讨中老年脑白质疏松症(leukoaraiosis,LA)与同型半胱氨酸(Homocysteine,Hcy)、叶酸及维生素B12的相关性.方法 选择CT、MRI证实的中老年LA患者30例,测定其血浆总Hcy、血清叶酸及维生素B12水平,与对照组比较.结果 中老年LA患者血浆总Hcy升高,血清叶酸、维生素B12降低,与对照组相比差异有统计学意义(P＜0.001),即Hcy水平与中老年LA呈正相关,叶酸、维生素B12水平与中老年LA呈负相关.结论 Hcy、叶酸及维生素B12与中老年LA具有相关性,是中老年LA的重要危险因素.