A high-yield and simplified procedure for the synthesis of α-[C]Methyl-l-tryptophan

Alpha-[¹¹C]methyl-l-tryptophan (AMT) has been synthesized by stereoselective methylation with [¹¹C]methyl iodide of the lithium-enolate generated by treating dimethyl 2(S),3a(R),8a(S)-(+)-hexahydro-8(phenylsulfonyl) pyrrolo[2,3-b]indole-1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at −55 °C, followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of the protecting groups. The crude product was purified by a simple reverse-phase C-18 Sep-Pak procedure. The purified product was isolated with an average radiochemical yield of 53 ± 12% (decay corrected) in 30–35 min from [¹¹C]methyl iodide. At end of synthesis (EOS), 138 ± 35 mCi (n = 24) of product was collected with a specific activity of ca. 1–1.3 Ci/μmol (EOS) (4–5 Ci/μmol @ EOB) starting from 1.5 Ci (EOB) of [¹¹C]CO₂.     

The possible role of TNF-α and IL-2 in inducing tumor-associated metabolic alterations

This study was conducted to investigate the role of tumor necrosis factor- (TNF-) and interleukin-2 (IL-2) in inducing cancer cachexia, and the results were compared with those obtained from our previous study on Fisher 344 rats with methylcholanthrene-induced sarcoma. Three groups of male Fisher 344 rats received one of the following regimens: 4×10⁴ IU of human recombinant TNF- per rat per day subcutaneously (sc) for 5 consecutive days (n=5), 3.5×10⁵ U human recombinant IL-2 per rat per day sc for 14 consecutive days (n=5), or normal saline (n=5). The activities of both phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME) were increased slightly in the IL-2 group. Furthermore, LPL activity was significantly increased in the adipose tissue of the TNF group and in the cardiac muscle of the IL-2 group, but not in that of the TNF group. These results show that there is a significant difference between the metabolic alterations seen in the tumor-bearing state and those induced by either TNF- or IL-2 alone. Thus, it is unlikely that IL-2 or TNF- is the sole mediator of cancer cachexia in this tumor and rat model.     

Further studies of the turnover of dog antithrombin III. Study of 131I-labelled antithrombin protease complexes

Fresh plasma containing 131I-antithrombin III (*I-AT) was coagulated and incubated at 37 degrees C for 2 hr. A "complex peak," separated on heparin-agarose contained AT and *I-AT antigen but no heparin cofactor activity. Crossed immunoelectrophoresis showed only AT complexes. SDS PAGE showed 80% of the *I-AT in a major band (approximately 80,000 daltons), 15% in a minor band (approximately 100,000 daltons) and the rest in trace bands (approximately 60,000 and/or 115,000 daltons). Ammonia treatment of the complex peak released alpha-thrombin. After i.v. injection 80% of the complexed *I-AT, chiefly as the major band, left the plasma with t 1/2 approximately 15 min and was almost immediately catabolized to low molecular weight breakdown products. A major catabolic site was the liver. A simple kinetic model describes the findings approximately.     

Apoptose bei multipler Sklerose Ätiopathogenetische Relevanz und Perspektiven für neue therapeutische Strategien

Apoptosis, or programmed cell death, is a physiological cell suicide program mainly leading to selective elimination of useless cells. This mechanism is important for the homeostasis of the immune system and presumably plays a two-sided role in the pathogenesis of multiple sclerosis (MS). On the one hand, evidence has been provided that impaired apoptosis might result in increased numbers or persistence of activated myelin-specific T cells, thus inducing the pathophysiologic processes in MS. On the other hand, local tissue damage might involve apoptosis of glial and neuronal cells and lead to the clinical symptoms. Here, an overview is presented on the current knowledge of the role of apoptosis in the pathogenesis of MS, and implications for related therapeutic strategies are discussed.     

5α-还原酶抑制剂对过度训练大鼠雄激素作用的影响

 目的探讨非甾体类5α-还原酶抑制剂DQI对大运动量游泳训练大鼠血清雄激素水平、EPO水平及肾脏组织EPO合成能力的影响。方法以渐增游泳训练为大鼠运动应激模型，运用酶免和放免分析法观察了血睾、血清EPO及血清5α-双氢睾酮的含量，以及运用RT PCR法观察了肾脏组织EPOmRNA的表达水平。结果本运动模型可提高靶组织睾酮向5α-双氢睾酮的转化，而DQI可以显著抑制这一过程，并可以提高肾脏组织EPO的合成能力及血清EPO含量。结论非甾体类5α-还原酶抑制剂DQI对维持及恢复运动能力有一定作用。其机制与整合内源性睾酮及增加内源性EPO有关。     

丹参关节内注射对兔膝骨关节炎细胞因子IL-1及TNF的影响

为了解丹参注射液膝关节内注射对兔膝骨性关节炎中白细胞介素(IL-1)和肿瘤坏死因子(TNF)水平的影响，探讨其治疗骨性关节炎的机理，将64只兔随机分为4组，采用兔膝关节腔内注入木瓜蛋白酶造成骨关节炎的病理模型，以丹参与激素分别行关节腔内注射治疗进行对比观察，于造模后2、4、6、8周分别取材，采用双抗体夹心酶联免疫吸附实验(ELISA)法，分别测定各组、各期兔膝关节液中IL-1及TNF水平。结果显示，造模组IL-1及TNF的水平明显高于丹参组及激素组，有显著差异；空白组未能测出IL-1及TNF；激素组低于丹参组，有统计学差异。表明IL-1及TNF在骨性关节炎发病过程中可能起重要作用，丹参能有效降低骨性关节炎中IL-1及TNF的水平，其效果低于激素组，表明丹参关节内注射能有效治疗骨性关节炎，但效果略次于激素。     

马来酸二乙酯对半乳糖胺/脂多糖致小鼠急性肝损伤发生中核转录因子表达的影响

目的　耗竭肝脏还原型谷胱甘肽 (GSH)导致氧化还原失平衡后 ,是否可通过改变库普弗细胞核转录因子表达而影响肝损伤发生。方法　给小鼠注射马来酸二乙酯 (DEM) ,耗竭 GSH。结果　马来酸二乙酯在一定程度上 ,抑制了半乳糖胺 /脂多糖 (Galn/ L PS)诱导胞质 IκBα的降解和核 NF- κBp6 5的表达。结论　 DEM可能是通过抑制 IκBα降解 ,影响 NF-κBp6 5易位入核 ,从而抑制肿瘤坏死因子 (TNF) -α释放 ,减轻肝损伤     

雌二醇促进巨噬细胞释放TNF-α及信使分子的参与

肿瘤坏死因子 (TNF α)在子宫内膜异位症 (内异症 )中参与异位内膜的种植、生长、血管形成以及炎症、不孕症状的形成等多个环节。本文探讨了 1 7β 雌二醇 (E2 )对巨噬细胞产生TNF α的影响 ,以探讨内异症TNF α的诱导因素及其产生的途径。1　方法　　按文献[1 ] 方法取大鼠腹腔巨噬细胞。TNF α的活性采用L92 9细胞毒法[6 ] 。2　结果2 .1　E2 对巨噬细胞释放TNF α的影响　细胞培养 1 2h后加入E2 ,继续培养不同时间取上清液 ,测TNF α活性。结果可见E2 0 0 1～ 1 0 0 0nmol·L- 1 诱导巨噬细胞产生TNF α,其中以 1 0 0nmol·…     

环磷酰胺对鼠根尖周炎中IL-1α、TNF-α基因表达的影响

目的　观察环磷酰胺对IL 1α和TNF αmRNA在鼠根尖周炎组织中表达的影响 ,了解免疫抑制在根尖周炎中的作用。方法　 16只SD大鼠开髓术前每周 1次腹腔注射环磷酰胺 ,共 3wk ,另 16只大鼠作对照 ;用原位杂交技术 ,测定免疫抑制鼠根尖周炎组织中IL 1α和TNF αmRNA表达 ,并对其进行半定量分析 ,与免疫正常组进行比较。结果　免疫抑制鼠根尖周组织阳性染色细胞计数 ,1～ 3wk逐渐2 0 0 2 0 6 13收稿 ,2 0 0 3 0 6 2 8修回 安徽省教育厅资助课题 ,No 2 0 0 1kj1181 上海第二医科大学附属第九人民医院 ,上海　 2 0 0 0 11作者简介 :梅陵宣 ,男 ,39岁 ,医学博士 ,副教授 ,硕士生导师。Tel:0 5 5 1 5 118677 82 0 1;刘　正 ,女 ,71岁 ,教授 ,博士生导师增加 ,4wk后降低 ,并与根尖阴影面积呈正相关关系 (IL 1α :r=0 881,P <0 0 1;TNF α:r =0 85 5 ,P <0 0 1) ;各时间段IL 1α和TNF αmRNA表达量与免疫正常组无差别 ,阳性表达细胞类型亦无差别。结论　外周血白细胞减少对鼠根尖周炎的发生及局部IL 1α和TNF α表达无影响