Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E mice

The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E^−/− mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E^−/− mice.     

上颌组牙三维有限元模型的建立及Carrière Distalizer矫治器的力学分析

目的建立一侧有效的自然排列的上颌尖牙和第一磨牙及周围牙槽骨的三维有限元模型,分析在Carrière Distalizer矫治器作用下,组牙的应力分布及其位移特点。方法通过螺旋CT扫描获得精确的组牙及颌骨DICOM格式的图像信息,采用Mimics三维建模软件和Ansys有限元分析软件建立及拟合上颌骨中正常位置的上颌组牙及其周围牙槽骨的三维有限元模型,模拟Carrière Distalizer矫治器的力学实验并进行相关分析。结果成功建立了上颌组牙及其周围牙槽骨的三维有限元模型。力学实验显示,尖牙和磨牙颈部剖面腭侧应力分布及位移明显小于颊侧、远中和近中,表现为类似旋转移动的柱状图形;而尖牙和磨牙整个远中剖面的应力分布及位移规律基本相同,均表现为自牙颈部向牙根部逐渐衰减的倾斜移动的曲线。结论本实验创建的上颌组牙及其周围牙槽骨的三维有限元模型,达到了几何外形和生物力学的相似性,可用于精确的生物力学分析;尖牙和磨牙在CD的作用下,应力分布及位移规律均呈现有旋转和倾斜移动的趋势。     

Comparison of antithrombotic and hemorrhagic effects of edoxaban,a novel factor Xa inhibitor,with unfractionated heparin,dalteparin, lepirudin and warfarin in rats

Background

Edoxaban is a novel, potent and orally active direct Factor Xa (FXa) inhibitor under development for prophylaxis and treatment of thromboembolic diseases. Properties of dose response and margin of safety of anticoagulants are the key factors for a positive risk/benefit of novel oral anticoagulants.

Objectives

To compare the dose response of antithrombotic effect and margin of safety between antithrombotic and hemorrhagic effects of edoxaban with conventional anticoagulants, unfractionated heparin (UFH), dalteparin (low molecular weight heparin), lepirudin, and warfarin in rat models of thrombosis and hemorrhage.

Methods

Rats were treated with edoxaban, UFH, dalteparin, and lepirudin by continuous intravenous (iv) infusion, or with oral warfarin for 4 days before inducing thrombosis or bleeding. Thrombosis was induced by inserting a platinum wire into the inferior vena cava for 60 minutes. Tail template bleeding time was measured after making an incision on the tail.

Results

In rats, iv infusion of edoxaban inhibited venous thrombosis in a dose-dependent manner. The other anticoagulants also exerted dose-dependent antithrombotic effects. The slopes of the dose–response curves of edoxaban were significantly shallower than the slopes of UFH, dalteparin, and warfarin. At supratherapeutic doses, edoxaban prolonged bleeding time in a rat tail bleeding model. To determine bleeding risk, the margins between antithrombotic and bleeding-time prolongation were compared. The margins of safety of edoxaban were wider than those of UFH, dalteparin, lepirudin, and warfarin.

Conclusions

These results suggest that edoxaban may be more easily controlled and has the potential for a more positive risk/benefit ratio compared to conventional anticoagulants.     

口服胸腺素对小鼠免疫功能的影响

分别用sc环磷酰胺及~(40)Coγ线一次性全身照射方法造成小鼠免疫功能低下的动物模型,观察口服胸腺素对小鼠外周血白细胞数及免疫功能的影响。结果表明,小鼠连续口服胸腺素7d后,外周血白细胞数有明显的上升,对受大剂量照射的小鼠可提高30％～50％存活率,并对小鼠血清溶血素、抗体形成细胞、小鼠腹腔巨噬细胞吞噬鸡红细胞及~3H-TdR掺入等几个免疫学指标均有明显的提高。     

Fundamentals of Digestive Cancers Immunology,Especially Gastric and Hepatocellular Carcinomas<br/>Fondamentaux de l’immunologie des Cancers Digestifs (Gastriques et Hépatocellulaires)

Immunotherapy for digestive cancers is booming and for the first time an immune checkpoint inhibitor has been granted marketing authorization for the treatment of digestive cancer. In order to better understand the mecanism of action of these treatments, their adverse events and the escape mecansim, it is necessary to know the fundamentals of cancer immunology. The innate and adaptive immune system allows the elimination of cancer cells by direct non-specific cytotoxicity (Natural Killer cells), by the development of an adaptive cell-mediated response (dendritic cells becoming antigen presenting cells, allowing the differentiation of lymphocytes naive in CD4 and CD8 T lymphocytes) and by humoral immunity (via B lymphocytes). A state of equilibrium can be established. One of the oncogenesis processes is then the escape of tumor cells from immune control, by the loss of their antigen presentation capacity, by the recruitment of immunosuppressive cells or by the expression on their surface of inhibitory costimulatory molecules (PD-L1, Galectin 9) interacting with their ligand on the lymphocyte (PD-1, Tim-3) and resulting in inactivation of the immune response. These proteins correspond to immune checkpoints and are the target of major immunotherapy molecules currently in use. A panorama of knowledge on the prognostic value of the tumor microenvironment of gastric cancers and hepatocarcinomas is then made.

Résumé:
L’immunothérapie des cancers digestifs est en plein essor et pour la première fois un inhibiteur de point de contrôle immunitaire a obtenu une autorisation de mise sur le marché pour le traitement d’un cancer digestif. Afin d’appréhender au mieux le mécanisme d’action de ces traitements, leurs effets secondaires et l’échappement à ces traitement, il est nécessaire de connaître les fondamentaux de l’immunologie des cancers. Le système immunitaire inné et adaptatif permet l’élimination des cellules cancéreuses par cytotoxicité directe non spécifique (cellules Natural Killer), par le développement d’une réponse adaptative à médiation cellulaire (cellules dendritiques devenant cellules présentatrices d’antigène, permettant la différenciation des lymphocytes naïfs en lymphocytes T CD4 et CD8) et par immunité humorale (par l’intermédiaire des lymphocytes B). Un état d’équilibre peut s’établir. Un des processus d’oncogenèse est ensuite l’échappement des cellules tumorales au contrôle immunitaire, par la perte de leur capacité de présentation antigénique, par le recrutement de cellules immunosuppressives ou par l’expression à leur surface de molécules de costimulation inhibitrice (PD-L1, Galectine 9) interagissant avec leur ligand sur le lymphocyte (PD-1, Tim-3) et aboutissant à une inactivation de la réponse immunitaire. Ces protéines correspondent aux points de contrôle immunitaire et sont la cible des principales molécules d’immunothérapie actuellement utilisées. Il est ensuite fait un panorama des connaissances sur la valeur pronostique du micro environnement tumoral des cancers gastriques et des hépatocarcinomes.     

Pseudouchyłek powikłaniem długotrwałego zalegania ciała obcego w przełyku u 5,5-rocznego chłopca

We present a case of a 5.5-year-old boy with complications after long-term retention of a foreign body in the esophagus. The patient presented certain symptoms such as dysphagia, odynophagia, cough and vomiting. The case mentioned above proves that in children with chronic respiratory symptoms (such as cough, stridor) or gastrointestinal ones (dysphagia, odynophagia) the possibility of foreign body ingestion should always be considered as the cause of these complaints.     

“颞颥”部位义试诠

文章运用语言学知识和中医学原理,分析了唐代以前古医籍中"颞颥"的用法,认为"颞颥"的部位义指颞肌所在部位,即头侧、眼眶外后方的体表处。范围从额侧眼眶骨外后方、耳上方直到耳后。     

A physiologically based pharmacokinetic model for atrazine and its main metabolites in the adult male C57BL/6 mouse

Atrazine (ATR) is a chlorotriazine herbicide that is widely used and relatively persistent in the environment. In laboratory rodents, excessive exposure to ATR is detrimental to the reproductive, immune, and nervous systems. To better understand the toxicokinetics of ATR and to fill the need for a mouse model, a physiologically based pharmacokinetic (PBPK) model for ATR and its main chlorotriazine metabolites (Cl-TRIs) desethyl atrazine (DE), desisopropyl atrazine (DIP), and didealkyl atrazine (DACT) was developed for the adult male C57BL/6 mouse. Taking advantage of all relevant and recently made available mouse-specific data, a flow-limited PBPK model was constructed. The ATR and DACT sub-models included blood, brain, liver, kidney, richly and slowly perfused tissue compartments, as well as plasma protein binding and red blood cell binding, whereas the DE and DIP sub-models were constructed as simple five-compartment models. The model adequately simulated plasma levels of ATR and Cl-TRIs and urinary dosimetry of Cl-TRIs at four single oral dose levels (250, 125, 25, and 5 mg/kg). Additionally, the model adequately described the dose dependency of brain and liver ATR and DACT concentrations. Cumulative urinary DACT amounts were accurately predicted across a wide dose range, suggesting the model's potential use for extrapolation to human exposures by performing reverse dosimetry. The model was validated using previously reported data for plasma ATR and DACT in mice and rats. Overall, besides being the first mouse PBPK model for ATR and its Cl-TRIs, this model, by analogy, provides insights into tissue dosimetry for rats. The model could be used in tissue dosimetry prediction and as an aid in the exposure assessment to this widely used herbicide.     

Hesperetin protects testicular toxicity of doxorubicin in rat: Role of NFκB, p38 and caspase-3

Doxorubicin is a widely used chemotherapeutic agent causing serious dose-dependent toxicity to non-target tissues such as testis. Its testicular toxicity is mainly due to the induction of oxidative stress. Hesperetin exerts its beneficial effects against oxidative stress-induced cellular damage. In the present investigation, doxorubicin was administered intraperitoneally at the dose of 4 mg/kg bw/week for a period of 5 consecutive weeks. Hesperetin was administered at the doses of 25, 50 and 100 mg/kg bw per oral by gavage for 5 consecutive days in a week for 5 weeks. Animals were sacrificed 1 week after the last injection of doxorubicin. The results of the present study clearly indicate the prevention of oxidative stress, DNA damage and the cellular toxicity by hesperetin treatment as evident from the analysis of biochemical parameters, comet assay, halo assay, Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assay, immunohistochemistry and histology. Hesperetin protection against doxorubicin-induced germ cell toxicity was further evident from the sperm count and sperm head morphological evaluation. Moreover, the role of nuclear factor-kappa B, p38 and caspase-3 on hesperetin-mediated protection against doxorubicin-induced testicular toxicity was also investigated. The present study clearly revealed the amelioration of doxorubicin-induced testicular toxicity by the intervention with hesperetin.