Amorphous Solid Dispersion of Meloxicam Enhanced Oral Absorption in Rats With Impaired Gastric Motility

Meloxicam (MEL) shows a slow onset of action in severe pain patients on account of delayed gastric motility. This study aimed to develop an amorphous solid dispersion (ASD) of MEL to achieve rapid oral absorption in severe pain patients. ASD formulations of MEL with hydroxypropylmethylcellulose (ASD-MEL/HPMC) and polyacrylates and polymethacrylates (ASD-MEL/EUD) were prepared and physicochemically characterized. Oral absorption behavior of MEL samples was also clarified in both normal and propantheline (PPT)-pretreated rats with impaired gastric motility. MEL in the formulations was amorphous, and ASD formulations of MEL exhibited high dissolution behavior in acidic solution. After oral administration of crystalline MEL (1 mg-MEL/kg), a 69% reduction in AUC_0-4 was observed between normal and PPT-pretreated rats. For orally dosed ASD-MEL/HPMC (1 mg-MEL/kg), there were approximately 9- and 12-fold increases of AUC_0-4 in normal and PPT-pretreated rats, respectively, in comparison with crystalline MEL (1 mg-MEL/kg). However, the oral absorption behavior of ASD-MEL/EUD (1 mg-MEL/kg) was low and similar to that of crystalline MEL. The infrared spectroscopic study revealed potent interactions between MEL and EUD, possibly leading to marked attenuation of MEL absorption. This ASD approach might provide rapid oral absorption of MEL in severe pain patients, possibly leading to better clinical outcomes.     

转铁蛋白受体mRNA在MEL细胞中表达的调节

转铁蛋白受体(TfR)的主要功能是调节细胞的铁摄取量。它的表达除受细胞内铁含量影响外,在红系细胞还与血红素的合成和细胞的增殖状态有关,但在非红系细胞,则仅与细胞的增殖状态相关。本实验通过对小鼠红白血病(MEL)细胞在二甲基亚砜(DMSO)诱导分化前后、不同的铁状态和不同的血红素合成条件下,采用Northern印迹方法,观察TfR mRNA含量的变化。结果为:①在未诱导的MEL细胞,随着细胞的增殖,TfR mRNA含量增加;诱导的MEL细胞,虽然随着细胞分化成熟而丧失增殖能力,但当存在血红素合成时,TfR mRNA含量也增高,且增高幅度较非诱导组高。②在未诱导的MEL细胞,降低细胞内铁含量(培养液中加入去铁胺式抗TfR单克隆抗体),可刺激TfR mRNA表达;增加细胞内铁含量(培养液中加入转铁蛋白),则抑制TfR mRNA的表达;在诱导的MEL细胞,采用相同条件的铁状态时,细胞内TfR mRNA水平发生类似的改变,但变化的程度较小。③在未诱导的MEL细胞,加入血红素合成抑制剂(培养液中加入异烟肼),不改变TfR mRNA的表达;在诱导的MEL细胞,血红素合成抑制剂既抑制红系细胞的分化,也抑制TfR mRNA的表达。④当培养液中加入EPO,则促进诱导的MEL细胞内TfR mRNA的表达。上述结果提示,在红系细胞,TfR mRNA的表达除受细胞内铁调节外,也受细胞内血红素合成的     

鸡视网膜MEL受体的表达及部分电生理,药理特性的研究

褪黑激素（ＭＥＬ）是松果体和视网膜分泌的一种重要内分泌激素,它参与生物季节周期昼夜节律,视网膜信号调制及其他多种重要生理功能的调节。关于鸟类视网膜中ＭＥＬ受体的定位和亲和性类型的研究已有报道,然而由于所用方法的限制,对它的电生理特性知之甚少。我们首次成功地在爪蟾卵母细胞上表达了鸡视网膜ＭＥＬ受体,并利用双电极电压箝技术及常用的药物灌流的方法研究了它的部分电生理、药理学特性。我们发现,这种表达的ＭＥ     

甘露糖赤藓糖醇脂的分批发酵动力学

在台式发酵罐上研究了Candidaantarctic以豆油为碳源生产生物表面活性剂甘露糖赤藓糖醇脂 (MEL)的分批发酵动力学 ,考察了不同的植物油作为碳源对生产MEL的影响 ,发现精制豆油为最佳碳源 ;在分批发酵实验中发现 ,pH值对C .antarctica的MEL生产影响不大 ,豆油质量浓度过高对菌体生长有一定的抑制作用 .     

Nrf2通过调控EZH2的表达促进DMSO诱导的MEL细胞红系分化

目的 探讨Nrf2/EZH2通路参与DMSO诱导MEL细胞红系分化的作用及相关分子机制.方法 以MEL细胞为靶细胞,DMSO为刺激源,联苯胺染色法检测细胞红系分化情况;免疫印迹检测EZH2和Nrf2蛋白表达水平.结果 DMSO可显著诱导MEL细胞红系分化,同时EZH2和Nrf2表达水平也明显升高.通过使用Nrf2诱导剂TBHQ及Nrf2 shRNA,证明Nrf2调控MEL细胞中EZH2的表达.敲低Nrf2和EZH2的表达能够抑制DMSO诱导的MEL细胞红系分化.结论 Nrf2可通过调控EZH2的蛋白水平从而发挥促进MEL细胞红系分化的作用.     

四例t(1;3)(p36;q21)骨髓增生异常综合征的临床和实验室研究

目的 研究t（1；3）（p36；q21）骨髓增生异常综合征（MDS）患者的临床特征和受累基因的表达。方法 报告4例t（1；3）（p36；q21）MDS患者。用半定量RT-PCR方法检测正常胎儿组织、2名健康正常人和3例t（1；3）（p36；q21）MDS患者骨髓细胞MEL1（MDS1／EVI1-like gene）基因两种转录形式（全长的MEL1和短型MEL1s）的表达水平。结果 t（1；3）（p36；q21）MDS患者临床表现主要以乏力等贫血症状为主，为大细胞性贫血，白细胞计数正常，血小板计数正常或增高，骨髓细胞形态有粒系、红系和巨核细胞系三系发育异常改变，以巨核细胞发育异常表现为主，患者预后差。正常人骨髓细胞和正常胎儿组织主要表达全长的MEL1，而t（1；3）（p36；q21）MDS患者骨髓以MEL1s表达为主，或仅表达MEL1S。结论 t（1；3）（p36；q21）MDS可能为一个独立临床病理遗传学病种，MEL1s的过表达在其发病机制中起重要作用。     

Quantitative risk assessment for skin sensitisation: Consideration of a simplified approach for hair dye ingredients

With the availability of the local lymph node assay, and the ability to evaluate effectively the relative skin sensitizing potency of contact allergens, a model for quantitative-risk-assessment (QRA) has been developed. This QRA process comprises: (a) determination of a no-expected-sensitisation-induction-level (NESIL), (b) incorporation of sensitization-assessment-factors (SAFs) reflecting variations between subjects, product use patterns and matrices, and (c) estimation of consumer-exposure-level (CEL). Based on these elements an acceptable-exposure-level (AEL) can be calculated by dividing the NESIL of the product by individual SAFs. Finally, the AEL is compared with the CEL to judge about risks to human health.     

A No Observable Adverse Effects Level (NOAEL) for pigs fed melamine and cyanuric acid

Ingesting melamine adulterated milk products led to kidney stones in many infants in 2008. This differs from the renal failure caused by intratubular crystal formation after co-ingestion of melamine (MEL) and cyanuric acid (CYA) in adulterated pet foods in 2007. To better understand the potential risk of developing crystal nephropathy following co-ingestion of MEL and CYA, we fed 16 weanling pigs 0, 1, 3.3, 10, 33, or 100 mg/kg bw/day of each MEL and CYA, or 200 mg/kg bw/day of either compound individually for 7 days. Crystals were found in the renal medulla and cortex and urine sediments of all pigs fed both MEL and CYA each at 10 mg/kg bw/day (or greater). Crystals were also found in one of the two pigs fed 200 mg/kg bw/day MEL-only. In a 28 day study, 36 weanling pigs were fed 0, 1, or 3.3 mg/kg bw/day of MEL and CYA or 200 mg/kg bw/day MEL-only. Only one of the 3.3 mg/kg MEL and CYA pig kidneys contained crystals. The no-observed-adverse-effect level (NOAEL) for pigs fed MEL and CYA for 28 days was concluded to be 1.0 mg/kg bw/day corresponding to 25 mg/kg (ppm) MEL and 25 mg/kg (ppm) CYA in dry feed.     

NEW DESIGNED HMBA AGENTS AS INDUCERS OFERYTHROLEUKEMIA CELL DIFFERENTIATION

INTRODUCTIONHMBA（hexamethylenebisacetamide）istheproto－typeofhybridpolarcytodifferentiationagents（１）andhasbeenprovedtoinduceawidevarietyoftransformedcellstodifferentiate，suchasHL－６０（２）humanpromyelocyticleukemia，ratprostateadenocarcinoma（３）