Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth

Improving the repeatability of heterochromatic flicker photometry for measurement of macular pigment optical density

Background: Heterochromatic flicker photometry (HFP) is a psychophysical technique used to measure macular pigment optical density (MPOD). We used the MPS 9000 (MPS) HFP device. Our aim was to determine if the repeatability of the MPS could be improved to make it more suitable for monitoring MPOD over time. Methods: Intra-session repeatability was assessed in 25 participants (aged 20-50 years). The resulting data was explored in detail, e.g., by examining the effect of removal and adjustment of data with less than optimal quality parameters. A protocol was developed for improved overall reliability, which was then tested in terms of inter-session repeatability in a separate group of 27 participants (aged 19-52 years). Results: Removal and adjustment of data reduced the intra-session coefficient of repeatability (CR) by 0.04, on average, and the mean individual standard deviation by 0.004. Raw data observation offered further insight into ways of improving repeatability. The proposed protocol resulted in an inter-session CR of 0.08. Conclusions: Removal and adjustment of less than optimal data improved repeatability, and is therefore recommended. To further improve repeatability, in brief we propose that each patient perform each part of the test twice, and a third time where necessary (described in detail by the protocol). Doing so will make the MPS more useful in research and clinical settings. © 2012 Springer-Verlag

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? A prospective cohort study.

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants \u3c 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman\u27s Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels

MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults.</p> <p>Methods</p> <p>A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks.</p> <p>Results</p> <p>After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (<it>P </it>< 0.05 for either of these genotypes) and TT genotype in the high FA group (<it>P </it>< 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, <it>P </it>= 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, <it>P </it>= 0.989).</p> <p>Conclusions</p> <p>This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.</p

Homocysteine, vitamin B12 and folate levels in premature coronary artery disease

BACKGROUND: Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD. METHODS: We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran. RESULTS: After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia. CONCLUSION: We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia

Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

<p>Abstract</p> <p>Background</p> <p>Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR) and albuminuria independently of each other. We also investigated the association of <it>MTHFR </it>polymorphisms related to homocysteine with albuminuria to get further insight into causality.</p> <p>Methods</p> <p>This was a cross-sectional population-based study in Caucasians (<it>n </it>= 5913). Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g.</p> <p>Results</p> <p>Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, <it>P </it>< 0.001). The prevalence of albuminuria increased across increasing homocysteine categories (from 6.4% to 17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced GFR, <it>P </it>for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence interval: 1.60-3.08, <it>P </it>< 0.001) and elevated serum uric acid (OR = 1.27, 1.08-1.50, per 100 μmol/L, <it>P </it>= 0.004) were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. <it>MTHFR </it>alleles related to higher homocysteine were associated with increased risk of albuminuria.</p> <p>Conclusions</p> <p>In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.</p

Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke.</p> <p>Methods</p> <p>The study employed both a case-control and prospective follow-up design to study hospitalized adults with first – ever acute ischaemic stroke presenting within 48 hours of onset. Clinical histories, neurological evaluation (including National Institutes of Health Stroke Scale (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on fasting samples drawn from controls and stroke cases (within 24 hours of hospitalization). Outcome at 4 weeks was assessed in stroke patients using the Glasgow Outcome Scale (GOS).</p> <p>Results</p> <p>We evaluated 155 persons (69 acute ischaemic stroke and 86 healthy controls). The mean age ± SD of the cases was 58.8 ± 9.8 years, comparable to that of controls which was 58.3 ± 9.9 years (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization was 43.5 ± 38.8 hours, and mean admission NIHSS score was 10.1 ± 7.7. Total fasting Hcy in stroke patients was 10.2 ± 4.6 umol/L and did not differ significantly from controls (10.1 ± 3.6 umol/L; P = 0.88). Hyperhomocysteinemia, defined by plasma Hcy levels > 90^thpercentile of controls (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 – 2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score (P < 0.0001).</p> <p>Conclusion</p> <p>This exploratory study found that homocysteine levels are not significantly elevated in Nigerians with acute ischaemic stroke, and admission Hcy level is not a determinant of short-term (4 week) stroke outcome.</p

Disinhibition Mediates a Form of Hippocampal Long-Term Potentiation in Area CA1

The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs) followed rapidly by feedforward (disynaptic) inhibitory postsynaptic potentials (IPSPs). Long-term potentiation (LTP) of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs), required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain

Metabolite profiling reveals new insights into the regulation of serum urate in humans

Albrecht E, Waldenberger M, Krumsiek J, et al. Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics. 2013;10(1):141-151.Serum urate, the final breakdown product of purine metabolism, is causally involved in the pathogenesis of gout, and implicated in cardiovascular disease and type 2 diabetes. Serum urate levels highly differ between men and women; however the underlying biological processes in its regulation are still not completely understood and are assumed to result from a complex interplay between genetic, environmental and lifestyle factors. In order to describe the metabolic vicinity of serum urate, we analyzed 355 metabolites in 1,764 individuals of the population-based KORA F4 study and constructed a metabolite network around serum urate using Gaussian Graphical Modeling in a hypothesis-free approach. We subsequently investigated the effect of sex and urate lowering medication on all 38 metabolites assigned to the network. Within the resulting network three main clusters could be detected around urate, including the well-known pathway of purine metabolism, as well as several dipeptides, a group of essential amino acids, and a group of steroids. Of the 38 assigned metabolites, 25 showed strong differences between sexes. Association with uricostatic medication intake was not only confined to purine metabolism but seen for seven metabolites within the network. Our findings highlight pathways that are important in the regulation of serum urate and suggest that dipeptides, amino acids, and steroid hormones are playing a role in its regulation. The findings might have an impact on the development of specific targets in the treatment and prevention of hyperuricemia