FA值在急性缺血性脑梗塞诊断中的临床应用

目的:探讨不同时期( ＜72 h、8～ 14 d)脑梗塞患者梗死侧病变FA值及对应正常脑组织FA值,旨在分析FA值性急性脑梗死的临床价值.方法:收集2011年1月～2012年1月于新疆医科大学第二附属医院神经内科明确诊断为急性缺血性脑梗死的患者34例,男性19例,女性15例,年龄35～73岁,平均年龄58±2.4岁.对所有患者在急性期(发病时间＜72 h)行1.5T常规头颅MRI检查DTI及DTT检查,测量梗死灶和对侧相应正常脑组织的部分各向异性值(FA值)、表面扩散系数(ADC值),皮质脊髓束( corticospinal tract,CST)与梗死灶的关系分为相邻、部分穿过及完全穿过三组,来分析FA的变化及其与病程时间的关系.结果:分析不同病程中脑梗死侧与相对应健侧的FA值及ADC值,结果显示急性期梗死灶白质的FA值及ADC值均比对侧正常白质的FA值和ADC值降低;同时,梗死灶FA值下降率与发病时间存在相关关系,即急性期梗死灶FA值的下降率与发病时间呈正相关关系,具有统计学意义(P＜0.05);结论:急性期梗死灶白质FA值及ADC值均比对侧正常白质的FA值和ADC值降低;同时,梗死灶FA值下降率与病程时间存正相关关系.     

Postpartum changes in maternal and infant erythrocyte fatty acids are likely to be driven by restoring insulin sensitivity and DHA status

Introduction

Perinatal changes in maternal glucose and lipid fluxes and de novo lipogenesis (DNL) are driven by hormones and nutrients. Docosahexaenoic acid (DHA) reduces, whereas insulin augments, nuclear abundance of sterol-regulatory-element-binding-protein-1 (SREBP-1), which promotes DNL, stearoyl-CoA-desaturase (SCD, also Δ9-desaturase), fatty acid-(FA)-elongation (Elovl) and FA-desaturation (FADS). Decreasing maternal insulin sensitivity with advancing gestation and compensatory hyperinsulinemia cause augmented postprandial glucose levels, adipose tissue lipolysis and hepatic glucose- and VLDL-production. Hepatic VLDL is composed of dietary, body store and DNL derived FA. Decreasing insulin sensitivity increases the contribution of FA from hepatic-DNL in VLDL-triacylglycerols, and consequently saturated-FA and monounsaturated-FA (MUFA) in maternal serum lipids increase during pregnancy. Although other authors described changes in maternal serum and RBC essential-FA (EFA) after delivery, none went into detail about the changes in non-EFA and the mechanisms behind -and/or functions of- the observed changes.

Hypothesis

Postpartum FA-changes result from changing enzymatic activities that are influenced by the changing hormonal milieu after delivery and DHA-status.

Empirical data

We studied FA-profiles and FA-ratios (as indices for enzymatic activities) of maternal and infant RBC at delivery and after 3 months exclusive breastfeeding in three populations with increasing freshwater-fish intakes. DNL-, SCD- and FADS2-activities decreased after delivery. Elongation-6 (Elovl-6)- and FADS1-activities increased. The most pronounced postpartum changes for mothers were increases in 18:0, linoleic (LA), arachidonic acid (AA) and decreases in 16:0, 18:1ω9 and DHA; and for infants increases in 18:1ω9, 22:5ω3, LA and decreases in 16:0 and AA. Changes were in line with the literature.

Discussion

Postpartum increases in 18:0, and decreases in 16:0 and 18:1ω9, might derive from reduced insulin-promoted DNL-activity, with more reduced SCD- than Elovl-activity that leaves more 16:0 to be converted to 18:0 (Elovl-activity) than to MUFA (SCD-activity). Postpartum changes in ΣDNL, saturated-FA and MUFA related negatively to RBC-DHA. This concurs with suppression of both SCD- and Elovl-6 activities by DHA, through its influence on SREBP. Infant MUFA and LA increased at expense of their mothers. Sustained transport might be important for myelination (MUFA) and skin barrier development (LA). Maternal postpartum decreases in FADS2-, and apparent increases in FADS1-activity, together with increases in LA, AA, and 22:5ω3, but decrease in DHA, confirm that FADS2 is rate limiting in EFA-desaturation. Maternal LA and AA increases might be the result of rerouting from transplacental transfer to the incorporation into milk lipids and discontinued placental AA-utilization.

Implications

Perinatal changes in maternal and infant FA status may be strongly driven by changing insulin sensitivity and DHA status.     

指长波动性不对称与冠心病的相关性

目的 探讨指长波动性不对称（FA）与宁夏汉族男性冠心病的相关性。方法 采用体质测量法,探讨宁夏汉族男性304例（正常对照组152例,冠心病患者152例）指长FA（2FA、3FA、4FA、5FA）及复合FA(CFA)的均值,并比较其均值的差异性。结果 宁夏汉族男性正常对照组与冠心病患者组各指长FA均值均呈现2FA＞4FA＞3FA＞5FA的趋势;冠心病患者组各指长FA均值均高于正常对照组,2FA（P≤0.001）、3FA（P<0.05）、4FA（P<0.05）、CFA（P≤0.01）有显著性差异,且2FA差异最显著;冠心病患者组2FA在|L-R|≥0.04组显著增高（P<0.05）;冠心病患者组2FA均值与发病年龄呈负相关（P<0.001）。结论 FA尤其是2FA水平可能是冠心病早期筛查的重要参考指标之一。     

Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data

There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.     

Diffusion tensor imaging patterns differ in bulbar and limb onset amyotrophic lateral sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is characterized by pronounced clinical heterogeneity in terms of onset and disease progression. Widespread changes in white matter fibres could be observed by diffusion tensor imaging (DTI), which detects alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement. The aim of the current study was to determine whether different ALS onset types were reflected in different DTI brain patterns.

Methods

Seventeen patients with a diagnosis of ALS (6 bulbar, 11 limb onset) and seventeen age-matched controls received 1.5T DTI, where FA and ADC were analyzed using statistical parametric mapping.

Results

In ALS patients, an increased diffusivity in the white matter was found below the precentral gyrus and along the corticospinal tract (CST) right into the internal capsule. The FA was decreased in the posterior limb of internal capsule and in the subcortical white matter in the precentral gyrus. In bulbar onset increased diffusivity was found in the CST, whilst in limb onset, frontal subcortical areas displayed an increased diffusivity.

Conclusion

DTI changes can be regarded as prominent features in ALS. Herein we were able to demonstrate discriminating brain DTI patterns due to bulbar or limb onset.     

White matter lateralization and interhemispheric coherence to auditory modulations in normal reading and dyslexic adults

Neural activation of slow acoustic variations that are important for syllable identification is more lateralized to the right hemisphere than activation of fast acoustic changes that are important for phoneme identification. It has been suggested that this complementary function at different hemispheres is rooted in a different degree of white matter myelination in the left versus right hemisphere.     

叶酸对阿霉素所致心肌损伤的保护作用研究

目的探讨叶酸对阿霉素所致心肌损伤的保护作用。方法将24只小鼠随机分成4组：对照组，叶酸组，阿霉素组，阿霉素+叶酸组，每组6只。阿霉素组：采用腹腔内注射阿霉素（每次2.5mg/kg，每周3次，共6次，总量15mg/kg），建立小鼠阿霉素心脏毒性模型，常规喂养4周；叶酸组：以等量0.9%氯化钠溶液代替阿霉素作腹腔内注射，并给予叶酸灌胃[10mg/（kg·d），共4周]；阿霉素+叶酸组：按上两组方法和剂量给予阿霉素和叶酸。对照组：以等量0.9%氯化钠溶液代替阿霉素做腹腔内注射，常规喂养4周。4周后B超测定小鼠心脏功能，TUNEL法测定小鼠心肌细胞凋亡率，并利用Westernblot法分析凋亡相关蛋白Bax、Bcl-2的表达。结果阿霉素组各项心功能指标、心肌细胞凋亡率、Bax/Bcl-2比值与对照组比较均有统计学差异（均P＜0.05）；而阿霉素+叶酸组各项心功能指标、心肌细胞凋亡率、Bax/Bcl-2比值与阿霉素组比较均有明显改善（均P＜0.05）。结论叶酸对小鼠阿霉素心肌损伤有明显的保护作用。     

Reactivation of PPARα alleviates myocardial lipid accumulation and cardiac dysfunction by improving fatty acid β-oxidation in Dsg2-deficient arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2^?/?). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2^?/? mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2^?/? mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR–4EBP1–PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.