烧伤后红细胞损伤的机制——过氧化脂质、维生素E与溶血的关系

本实验发现大鼠体表面积20％Ⅲ°烧伤后,皮肤内产生了大量丙二醛(MDA),第二天达最高,第七天有第二高峰,血浆和红细胞(RBC)MDA第三天达最高,血浆和RBC维生素E(VE)于伤后第二天后迅速下降,RBC溶血第三天最甚。对皮肤MDA、血浆MDA、RBCMDA、血浆VE、BBC VE、1％H_2O_2溶血进行相关分析后发现在不同时相,有不同的相关关系,但基本遵循烧伤皮肤MDA增加、血浆MDA增加、RBC MDA增加、血浆和RBC VE降低,溶血增加的规律。文中讨论了RBC损伤的机制。     

尿毒症患者血透中血液动力学监测

目的：观察尿毒症患者血透过程中血液动力学改变，方法：尿毒症患者20例，均在透析放血前，放血后，30min,60min,120min,180min，回血前，回因后测定血压，脉搏，中心静脉压，平均直接动脉压，结果：透析过程中血压，脉搏以及直接平均动脉压较稳定，中心静脉压放血前较正常为高，且高于血透过程中其它时间段（P＜0．05），结论：血透过程中血液动力学稳定，且中心静脉压的变化有利于心功能的改善。     

输精管结扎对家兔心功能及心肌NE含量的影响

本实验用日本大耳白兔复制输精管结扎的长期动物模型，分为结扎２５月组（ＶＧ２５），同龄假手术２５月组（ＳＯＧ２５）；结扎６月组（ＶＧ６），同龄假手术６月组（ＳＯＧ６）。记录各组家兔心功能，检测心肌及血清ＮＥ含量，称取心重（ＷＨ）。结果表明，左心室收缩期末压（ＬＶＳＰ），ＶＧ略高于ＳＯＧ；左心室舒张末压（ＬＶＥＤＰ），Ｖ６２５显著的低于ＳＯＧ２５Ｐ＜０．０５），ＶＧ６与５ＯＧ６比较虽无显著差异，也呈低值；±ｄｐ／ｄｔｍａｘ，ＶＧ均明显高于ＳＯＧ（Ｐ＜０．０１）。相关检验表明，＋ｄｐ／ｄｔｍａｘ与血清及心肌ＮＥ含量无相关性；心重与＋ｄｐ／ｄｔｍａｘ呈明显正相关，Ｐ＜０．０５；在２５月组，ＬＶＳＰ与＋ｄｐ／ｄｔｍａｘ呈正相关，Ｐ＜０．０５。提示输精管结扎可提高心肌收缩功能。     

羟磷灰石加阿霉素瘤内注射治疗小鼠肝癌的实验研究

作者通过动物实验研究了羟磷灰石(HA)的抑癌效果及其机理。将80只移植有H_(22)肝癌的BALB/c小鼠分为4组:Ⅰ组HA加阿霉素(ADM)瘤内注射;Ⅱ组HA瘤内注射;Ⅲ组ADM瘤内注射;Ⅳ组未给药。结果Ⅰ～Ⅲ组的肿瘤生长抑制率分别为65.9％、41.9％及51.1％。Ⅰ～Ⅳ组的生存时间分别为32、22、26及18天。作者认为HA抑癌作用的机理可能是:①直接界面作用;②诱导组织纤维化;③免疫激活作用;④药物载体和缓释作用。结果显示HA加ADM瘤内注射可能成为一种治疗恶性肿瘤的新方法。     

Pygmaeoherin: A Novel Coumarin from Pygmaeopremna herbacea

A new 6-oxygenated coumarin, pygmaeoherin, was isolated from roots of PYGMAEOPREMNA HERBACEA. Its structure was determined by spectroscopic methods. An NOE experiment played an important role in confirming the structure.     

GALC transduction leads to morphological improvement of the twitcher oligodendrocytes in vivo

Globoid cell leukodystrophy (GLD, Krabbe disease) is a severe demyelinating disease caused by a genetic defect of beta-galactocerebrosidase (GALC). To date treatment to GLD is limited to hematopoietic stem cell transplantation. Experimental approaches by means of gene therapy in twitcher mouse, an authentic murine model of human GLD, showed significant but only marginal improvements of the disease. To clarify whether the introduction of GALC could provide beneficial effects on the oligodendrocytes in GLD, we transduced twitcher oligodendrocytes by stereotactically injecting recombinant retrovirus encoding GALC-myc-tag fusion gene into the forebrain subventricular zone of neonatal twitcher mouse. In vivo effects of exogenous GALC on twitcher oligodendrocytes were studied histologically by combined immunostaining for the myc-epitope and the oligodendroglial specific marker, pi form of glutathione-S-transferase, at around 40 days of age. We show here that GALC transduction led to dramatic morphological improvement of the twitcher oligodendrocytes comparing with those in untreated twitcher controls. This study provided direct in vivo evidence that GALC transduction could prevent or correct aberrant morphology of oligodendrocytes in GLD which may be closely related to the dysfunction and/or degeneration of oligodendrocytes and the demyelination in this disease.     

Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin

Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.     

多脏器恶性肿瘤术后肝黏膜相关淋巴组织淋巴瘤

目的 探讨肝黏膜相关淋巴组织淋巴瘤的临床病理特征。方法 对1例罕见多脏器恶性肿瘤术后肝黏膜相关淋巴瘤病例结合文献进行临床、病理和免疫组化分析。结果 患者于8年和3年前先后发生胃恶性间质瘤、阴囊阴茎皮肤湿疹样癌，有长期化疗史。肿瘤组织学以单核样B细胞为主，并有淋巴滤泡和淋巴上皮病变形成。免疫表型示瘤细胞CD45、CD79α、CD20阳性，CD5、CD10、ALK、TdT阴性，bcl—2、Ki—67少数肿瘤细胞阳性。结论 肝黏膜相关淋巴瘤可以发生于多脏器恶性肿瘤术后，其发病可能与长期使用免疫抑制剂有关，诊断本病时需与肝继发性淋巴瘤及肝的炎性假瘤鉴别。     

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.     

Characterization of Hprt mutations in cDNA and genomic DNA of T-cell mutants from control and 1,3-butadiene-exposed male B6C3F1 mice and F344 rats

A multiplex PCR procedure for analysis of genomic DNA mutations in the mouse hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene was developed and then used with other established methods for the coincident identification of large- and small-scale genetic alterations in the Hprt gene of mutant T-cell isolates propagated from sham- and 1,3-butadiene (BD)-exposed mice and rats. The spectra data for RT-PCR/cDNA analysis and multiplex PCR of genomic DNA from Hprt mutants were combined, and statistical analyses of the mutant fractions for the classes of mutations identified in control versus exposed animals were conducted. Under the assumption that the mutant fractions are distributed as Poisson variates, BD exposure of mice significantly increased the frequencies of (1) nearly all types of base substitutions; (2) single-base deletions and insertions; and (3) all subcategories of deletions. Significantly elevated fractions of G:C-->C:G and A:T-->T:A transversions in the Hprt gene of BD-exposed mice were consistent with the occurrence of these substitutions as the predominant ras gene mutations in multiple tumor types increased in incidence in carcinogenicity studies of BD in mice. BD exposure of rats produced significant increases in (1) base substitutions only at A:T base pairs; (2) single-base insertions; (3) complex mutations; and (4) deletions (mainly 5' partial and complete gene deletions). Future coincident analyses of large- and small-scale mutations in rodents exposed to specific BD metabolites should help identify species differences in the sources of deletion mutations and other types of mutations induced by BD exposures in mice versus rats.