尿毒症及血透对血清一氧化氮浓度的影响及其临床意义

为研究尿毒症及血液透析对血清一氧化氮 (NO)浓度的影响及其临床意义 ,应用硝酸盐还原酶法检测了 1 0例尿毒症未透析患者、1 4例维持性血液透析患者透析前后及 1 0例正常对照者血清NO浓度。结果 :尿毒症未透析及血透患者NO水平均较正常对照显著升高 (P <0 .0 5) ,且尿毒症未透析患者血NO浓度与肿瘤坏死因子 α水平呈显著性正相关 (r =0 .858,P <0 .0 0 1 )。血液透析后NO浓度较透析前显著降低 (P <0 .0 5) ,但透析间期又会导致其蓄积。结果提示 :NO的蓄积对尿毒症的临床表现可能有一定影响。     

糖尿病患者血清中IL-4、TNF-a的检测及分析

目的 探讨白介素４（ＩＬ－４）、肿瘤坏死因子（ＴＮＦ－ａ）水平与糖尿病关系。方法 采用ＥＬＩＳＡ法测定５４例糖尿病患者及４０例健康人血清ＩＬ－４、ＴＮＦ－ａ含量。结果 糖尿病患者ＩＬ－４平均含量明显低于健康人（Ｐ〈０．０５）,且与血糖一负相关（ｒ＝－０．３４７,Ｐ〈０．０５）。ＴＮＦ－ａ含量略高于对照组,但无统计学意义。结论 糖尿病患者内存在细胞免疫功功能紊乱,自身免疫功能调节失衡影响糖尿病的发生     

GNAS gene mutations affecting XLαs and bone health: A long neglected relationship

The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation.     

类风湿性关节炎患者血清IL-6、TNF水平变化及其意义探讨

采用细胞生物学方法测定类风湿性关节炎（ Ｒ Ａ）１４ 例血清 Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 水平,均显著高于正常对照组（ Ｐ＜ ０ ．００１） 。相关分析显示 Ｉ Ｌ－ ６ 与 Ｔ Ｎ Ｆ 水平变化呈正相关（ Ｐ＜ ０ ．０１） , Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 与血沉亦呈正相关（ Ｐ＜０ ．０５） 。认为, Ｉ Ｌ－ ６ 、 Ｔ Ｎ Ｆ 参与 Ｒ Ａ 的发病,两者在致病中有协同相同;其水平变化与 Ｒ Ａ 的活动性及血沉相关。     

Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis

Increased plasma tumour necrosis factor (TNF) concentration correlates with mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to inhibit TNF production, may improve survival and attenuate clinical symptoms of sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both groups were subjected to the same conventional therapy. TNF was evaluated before and after PTXF or placebo administration on the 1 st and 3rd days of therapy. There was a statistically significant decrease in plasma TNF level in the PTXF group when the values before the first and after the last PTXF infusion were compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1; med: 11.5;P<0.000004]. In the placebo group, decrease was not significant [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0]. A significantly higher plasma TNF level, evaluated after the last PTXF infusion, was found in the placebo group [246,9 pg/ml vs 41.0 pg/ml;P<0.001]. Only one of four infants with signs of shock in the placebo group survived, whereas all of five newborns with symptoms of shock in the PTXF group survived [P<0.04]. An increased incidence of metabolic acidosis [P<0.05], necrotizing enterocolitis [P<0.04] and renal insufficiency [P<0.05] was observed in infants in the placebo group.Conclusion PTXF inhibits production of TNF and may have therapeutic value in the treatment of premature infants with sepsis complicatea by shock.     

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.