Role of CD36 in membrane transport and utilization of long-chain fatty acids by different tissues

The transmembrane glycoprotein CD36 has been identified in isolated cell studies as a putative transporter of long-chain fatty acids. To examine the physiological role of CD36, we studied FA uptake and metabolism by tissues of CD36 null mice after injection with two fatty acid analogs. Compared to controls, uptake was substantially reduced (50–80%) in heart, skeletal muscle, and adipose tissues of null mice. The reduction in uptake was associated with a large decrease in fatty acid incorporation into triglycerides, which could be accounted for by an accumulation of diacylglycerides. Thus CD36 facilitates a major fraction of fatty acid uptake by myocardial, skeletal muscle, and adipose tissues, where it is highly expressed. Its role in other tissues where its expression is low and cell-specific could not be determined in these studies.     

Monoliths with chiral surface functionalization for enantioselective capillary electrochromatography

The state-of-the-art in CEC enantiomer separations with monolithic capillary columns is comprehensively reviewed. The various types of monolithic columns comprising in situ organic polymer monoliths, molecularly imprinted polymer (MIP) monoliths, silica monoliths and monoliths made from particles are discussed with a focus on materials’ synthesis, chemistry and properties as well as column aspects. Monolithic MIP-type porous layer open-tubular (PLOT) columns are treated herein as well. From this survey of the literature, the authors come to the conclusion that monolithic silica capillaries appear to become the preferred column type for CEC enantiomer separations of low-molecular drugs and other chiral pharmaceuticals or chemicals.     

通心络胶囊对急性脑梗死患者神经功能缺损及日常生活活动能力的作用

目的观察通心络胶囊对急性脑梗死患者神经功能缺损及日常生活活动能力的改善作用,并初步探讨其机制。方法86例急性脑梗死患者随机分为通心络治疗试验组(43例)和对照组(43例),采用改良爱丁堡-斯堪的纳维亚量表(mESSS),美国国立卫生院脑卒中(NIH)量表、日常生活活动量表(BI)对急性脑梗死患者试验组和对照组分别进行从入院至病后90d系列神经功能缺损评分及日常生活活动能力评分,并检测外周血白细胞介素-1(IL-1)水平。结果试验组病后14,30,60,90d的神经功能缺损改善较对照组明显(减少值:mESSS,4.24,8.32,10.68,13.02vs2.65,4.07,5.34,6.25;NIH,3.12,5.42,6.13,6.81vs1.54,2.34,2.87,3.42),试验组病后60,90d的显效率较对照组高(χ2=9.364,11.349,P<0.005);试验组病后60,90d日常生活活动能力评分比对照组高(BI:86.55,90.83vs71.58,75.12),独立程度高(χ2=5.6279,0.010相似文献   

Carbohydrate‐derived Fulvic acid (CHD‐FA) inhibits Carrageenan‐induced inflammation and enhances wound healing: efficacy and Toxicity study in rats

The objectives of this study were to evaluate the safety and anti‐inflammatory and wound‐healing characteristics of carbohydrate‐derived fulvic acid (CHD‐FA) in rats. CHD‐FA (≥100 mg/kg p.o.) effectively reduced carrageenan‐induced paw edema in rats, which was comparable to 10 mg/kg p.o. indomethacin. Topical application of CHD‐FA, formulated to contain 1.75% active product in a cetomicrogol cream at pH 1.98, compared favorably with fusidic acid cream (10 mg/g) in accelerating the healing of excised wounds infected with Staphylococcus aureus. No signs of toxicity were observed in rats during the 6‐day acute and 6‐month chronic treatment with CHD‐FA (100 mg/kg p.o.). Topical application of CHD‐FA, formulated in UEA cream and applied to the right ears of mice at 400 mg/g body weight on days 1 and 7–38, produced no adverse events. No signs of toxicity were observed in the teratogenicity study, in which CHD‐FA was administered at 100 mg/kg p.o. to pregnant female mice 3 days before fertilization to 14 days of pregnancy. In conclusion, CHD‐FA is a safe compound with anti‐inflammatory and wound‐healing properties and merits further evaluation in the treatment of patients suffering from similar conditions. Drug Dev Res 73: 18–23, 2012. © 2011 Wiley Periodicals, Inc.     

Modeling premature brain injury and recovery

Premature birth is a growing and significant public health problem because of the large number of infants that survive with neurodevelopmental sequelae from brain injury. Recent advances in neuroimaging have shown that although some neuroanatomical structures are altered, others improve over time. This review outlines recent insights into brain structure and function in these preterm infants at school age and relevant animal models. These animal models have provided scientists with an opportunity to explore in depth the molecular and cellular mechanisms of injury as well as the potential of the brain for recovery. The endogenous potential that the brain has for neurogenesis and gliogenesis, and how environment contributes to recovery, are also outlined. These preclinical models will provide important insights into the genetic and epigenetic mechanisms responsible for variable degrees of injury and recovery, permitting the exploration of targeted therapies to facilitate recovery in the developing preterm brain.     

Identification and characterization of mutations in FANCL gene: A second case of Fanconi anemia belonging to FA‐L complementation group

Fanconi anemia (FA) is a rare autosomal recessive or X‐linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM) and three non‐FA proteins (FAAP100, FAAP24 and HES1) form an FA nuclear core complex, which is required for monoubiquitination of the FANCD2‐FANCI dimer upon DNA damage. FANCL possesses a PHD/RING‐finger domain and is a putative E3 ubiquitin ligase subunit of the core complex. In this study, we report an FA patient with an unusual presentation belonging to the FA‐L complementation group. The patient lacks an obvious FA phenotype except for the presence of a café‐au‐lait spot, mild hypocellularity and a family history of leukemia. The molecular diagnosis and identification of the FA subgroup was achieved by FA complementation assay. We identified bi‐allelic novel mutations in the FANCL gene and functionally characterized them. To the best of our knowledge, this is the second reported case belonging to the FA‐L complementation group. © 2009 Wiley‐Liss, Inc.     

扩散张量成像评估基底核区出血和缺血性病变对皮质脊髓束的影响

背景：基底核区出血性和缺血性病变,最容易造成相邻皮质脊髓束损伤,从而导致肢体运动功能程度障碍。功能磁共振扩散张量成像技术能真实有效地显示脑内白质结构,尤其是发生病变时,相邻和相关的白质纤维结构受到不同程度的影响和破坏,以扩散张量成像的各向异性指数最为敏感。 目的：应用扩散张量成像技术评估左侧基底核缺血性和出血性病变对皮质脊髓束通路的影响,并比较两种情况下皮质脊髓束通路各向异性指数的差异。 设计、时间及地点：对比观察,于2005-10/2008-12在昆明医学院第一附属医院磁共振室完成。 对象：左侧基底核出血患者20例,左侧基底核缺血性病变患者27例。 方法：利用GE 1.5T扫描仪及SUN工作站行全脑数据收集和后处理,在各向异性指数图像上分别测量延髓、脑桥、大脑脚、基底核、放射冠及半卵圆中心等层面的皮质脊髓束通路走行区各向异性指数的测量。兴趣区大小的确定由个体纤维束轴位图上其结构所决定,以不超出该结构的范围、同时有2人对兴趣区大小进行肯定为准。 主要观察指标：常规磁共振明确基底核区出血和缺血性病变患者,采集扩散张量成像数据并在工作站的扩散张量成像软件进行皮质脊髓束走行区域各向异性指数测量和分析。 结果：左侧基底核区的出血、缺血性病变对左侧皮质脊髓束通路各个水平层面结构的影响程度不同,其各向异性指数的统计学分析,α=0.05。缺血及出血性病变患者延髓水平皮质脊髓束的各向异性指数差异无显著性意义(P=0.05);脑桥水平直至半卵圆中心各层皮质脊髓束的各向异性指数差异有显著性意义(P < 0.001);尤其是基底核层面和放射冠层面的P值最小,又以放射冠层面最明显。 结论：扩散张量成像结果显示,基底核区缺血性病变对大脑脚层面及其以上的皮质脊髓束的影响较出血性病变大。     

Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian traditional medicine

Aim of the study

The aim of this randomized and double blinded pilot clinical trial was to investigate the anti-diabetic efficacy of the Rauvolfia-Citrus (RC) tea in humans. We have earlier shown that a combination of calorie-restriction and chronic administration of the RC tea to the genetic diabetic (BKS-db) mice resulted in the normalization of blood sugar, reduction in lipid accumulated in the mice eyes and prevention of the degeneration of the otherwise brittle BKS-db pancreas. The tea is made by boiling foliage of Rauvolfia vomitoria and fruits of Citrus aurantium and is used to treat diabetes in Nigerian folk medicine.

Materials and methods

The RC tea was produced using the Nigerian traditional recipe and tested in the traditional dosage on 23 Danish type 2 diabetes (T2D) patients. The participants were divided into two equivalent groups after stratification by sex, age and BMI, in a 4-month double-blinded, placebo-controlled and randomized clinical trial. Most of the study subjects (19/23) were using oral anti-diabetic agents (OADs). Mean disease duration was 6 ± 4.6 years, mean age was 64 ± 7 years and mean BMI was 28.7 ± 3.8 kg/m². Prior to starting the treatment, the participants received individual dietician consultations.

Results

At the end of the 4-month treatment period, the treated group showed an 11% decrease in 2-h postprandial plasma glucose relative to the 3% increase in the placebo group (p = 0.004). The improvement in blood glucose clearance with RC tea treatment was reflected in a 6% reduction in HbA_1c (p = 0.02) and in a 10% reduction in fasting plasma glucose (p = 0.02), when comparing the post 4-month treatment to pre-treatment baseline values. Though the basal levels of phosphorylated acetyl CoA carboxylase enzyme in skeletal muscle were significantly reduced in the treated group (p = 0.04), as compared to the placebo, only the pattern of reductions in the tissue fatty acids (FAs) differed in the two groups. While all types of FAs were reduced in placebo, only saturated (SFA) and monounsaturated (MUFA) FAs were reduced with treatment. Interestingly, a modest increase in the polyunsaturated FAs fraction was observed in the RC treated group. In addition, the reduction in SFA and MUFA with RC tea treatment came solely from the triglyceride fractions, as there was an increase in the skeletal muscle phospholipids.

Conclusions

Chronic administration of the RC tea to overweight T2D on OADs caused significant improvements in markers of glycaemic control and modifications to the fatty acid profile of skeletal muscle, without adverse effects or hypoglycaemia. Further exploration of the anti-diabetic effects of the RC tea is warranted.     

Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive-compulsive disorder: a diffusion tensor imaging study

BACKGROUND: Abnormalities of fractional anisotropy (FA) have been reported in previous diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD). However, there are some inconsistencies in the results and the apparent diffusion coefficient (ADC) has not been investigated. The goal of this study was to investigate white matter abnormalities and water diffusivity, as reflected by FA and ADC, using DTI in patients with OCD. METHODS: Fifteen patients with OCD and 15 healthy volunteers underwent DTI. Voxelwise analysis was used to compare FA in white matter and ADC in gray matter/white matter of the two groups. RESULTS: Compared with healthy volunteers, the patients had higher FA in the bilateral semioval center extending to the subinsular white matter; and a higher ADC in the left medial frontal cortex. There were no areas with a significantly lower FA or ADC in patients compared with healthy volunteers. CONCLUSIONS: A significantly higher FA was found in regions associated with the emotion of disgust and a trend for a higher ADC was found in a region associated with the regulation of emotions. These findings suggest that neurocircuits involved in disgust processing may play an important role in the pathophysiology of OCD.     

Interactions of human serum albumin with retinoic acid, retinal and retinyl acetate

Human serum albumin (HSA), a major plasma protein and plasma-derived therapeutic, interacts with a wide variety of drugs and native plasma metabolites. In this study the interactions between HSA and small lipophilic molecules all-trans retinoic acid (RA), all-trans retinaldehyde (retinal, RAL) and all-trans retinyl acetate (RAC) were investigated by UV-vis absorption spectroscopy, fluorescence spectroscopy and circular dichroism (CD). This paper focuses on investigation of the interactions between HSA and RA by the visible CD. RAL and RAC were used in this study due to their structural identity to RA to elucidate the importance of the end functional group for the complex formation. Our data demonstrate that RA specifically binds to HSA in a stable non-covalent complex at least at two internal binding sites with close but distinct affinities. Upon titration of HSA with RA, visible CD spectra clearly demonstrate the appearance of a well-defined induced positive Cotton Effect (CE) around 350 nm. Beyond ligand-to-protein ratio of 0.8 and up to saturation (2.0), CD exhibits two major bands of opposite signs, suggesting exciton coupling between the chromophore molecules in the protein interior. The fluorescence quenching data suggest proximity of the primary RA binding site to tryptophan (W214). RAC shows a weak association with HSA with stoichiometry close to that of RA, while interactions of RAL with HSA proceed non-specifically at multiple sites. Contrary to RA, the adducts of HSA with RAC and RAL do not show any induced chirality, thus indicating that despite their high structural similarity to RA, both compounds do not appear to occupy the internal binding sites, but associate with the protein exterior.