A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases

BackgroundOur aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.MethodsWe performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.ResultsOur patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0‐54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.ConclusionThe first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.     

A perspective for atherosclerosis vaccination: Is there a place for plant-based vaccines?

Alternatives to pharmacological treatments for atherosclerosis are highly desirable in terms of cost and compliance. During the last two decades several vaccination strategies have been reported as an effort to develop immunotherapeutic treatments. This approach consists on eliciting immune responses able to modulate either the atherosclerosis-associated inflammatory processes or the activity of some physiological mechanisms that are up-regulated under this pathologic condition. In particular, the apolipoprotein B100 (ApoB100) and the cholesterilester transferase protein (CETP) have been targeted in these strategies. It is considered that recent progress in the development of experimental models of oral vaccines against atherosclerosis has opened a new avenue in the field: as plant-based vaccines are considered a viable platform for vaccine production and delivery at low costs, they could serve as an oral-delivered therapeutic approach for atherosclerosis in an economical and patient-friendly manner. The rationale of the design, development and evaluation of possible plant-based vaccines against atherosclerosis is discussed in this review. We identify within this approach a significant trend that will positively impact the field of atherosclerosis vaccination.     

The 100 most influential publications pertaining to intracranial aneurysms and aneurysmal subarachnoid hemorrhage

The study of intracranial aneurysms has grown at an astounding rate since Sir Charles Symond’s association of hemorrhage within the subarachnoid space to intracranial aneurysms in 1923. These associations led to the first surgical treatment of an intracranial aneurysm with wrapping by Norman Dott in 1931, and shortly thereafter, clip ligation by Walter Dandy in 1938. Surgical outcomes were improved by the introduction of the operative microscope in the 1960s and perioperative care utilizing induced hypertension, hypovolemia, and hemodilution (“HHH therapy”). Recent monumental advancements, such as coil embolization in 1990 by Guglielmi, have continued to advance the field forward. The authors hope to highlight some of the most seminal and influential works. Herein, we utilize the technique of citation analysis to assemble a list of the 100 most influential works pertaining to aneurysmal subarachnoid hemorrhage published between the years 1900 and 2015 to honor these individuals and to provide guidance to current and future researchers in the field. We additionally calculate the effects of author, journal, topic, and study design on the overall influence of publications in this field.     

低血糖脑病患者外周血清S100β蛋白和神经元特异性烯醇化酶测定及意义

目的探讨低血糖脑病(hypoglycemic encephalopathy,HE)患者外周血清中神经生化标志物S100β蛋白和神经元特异性烯醇化酶(neuron-specific enolase,NSE)水平与神经功能损害程度的相关性。方法纳入HE患者62例(研究组),以及年龄、性别与之匹配的健康志愿者62例(对照组)。搜集受试者的一般资料和疾病信息。应用酶联免疫吸附试验(ELISA)检测两组受试者外周血清中S100β蛋白和NSE的表达水平。分析低血糖持续时间对HE患者血清S100β蛋白和NSE表达水平的影响。采用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)对治疗后3 m HE患者的神经功能进行综合评分。分析HE患者血清S100β蛋白和NSE表达水平与血糖水平、低血糖持续时间、NIHSS评分的相关性,分析NIHSS评分与血糖水平、低血糖持续时间的相关性。结果研究组血清S100β蛋白和NSE表达水平显著高于正常对照组(P<0.01)。随着低血糖持续时间延长,HE患者外周血清S100β蛋白和NSE表达水平持续升高,至24 h后基本达峰值(P<0.05)。HE患者血清S100β蛋白和NSE表达水平与血糖水平呈负相关(P<0.05),与低血糖持续时间呈正相关(P<0.05),与NIHSS评分呈正相关(P<0.05)。NIHSS评分与血糖水平呈负相关(P<0.05),与低血糖持续时间呈正相关(P<0.05)。结论HE患者外周血清中S100β蛋白和NSE的表达水能在一定程度上反映患者神经功能损害的程度,对HE的诊断及预后的判断有一定参考价值。     

Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells

Atrazine (ATZ) is probably the most widely used herbicide in the world. However there are still many controversies regarding its impacts on human health. Our investigations on the role of pesticides in liver dysfunctions have led us to detect an inhibition of FSP1 expression of 70% at 50 μm and around 95% at 500 μM of ATZ (p < 0.01). This gene encodes the protein S100a4 and is a clinical biomarker of epithelial–mesenchymal transition (EMT), a key step in the metastatic process. Here we investigated the possible effect of ATZ on cell migration and noticed that it prevents the EMT and motility of the HepG2 cells induced by the phorbol ester TPA. ATZ decreases Fak pathway activation but has no effect on the Erk1/2 pathway known to be involved in metastasis in this cell line. These results suggest that ATZ could be involved in cell homeostasis perturbation, potentially through a S100a4-dependant mechanism.