Synergistic actions of the vitamin D analogue MC 1288 and 15-deoxyspergualin in xenotransplantation

Abstract: The vitamin D analogue MC 1288 (20-epi-1α,25-dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25-dihydroxycholecalciferol, the active form of vitamin D. 1α,25-Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin-2, interferon-γ, granulocyte macrophage colony-stimulating factor, and interleukin-12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse-to-rat cardiac xenografts, alone and in combination with 15-deoxyspergualin (DSG). Combined treatment with MC 1288 (given days -1 to 9) and DSG (given day -1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production.     

锌离子对大鼠海马突触体Ca^2＋—Mg^2＋ATP酶活性及蛋白合成的影响

行为实验己经证明，锌过多或缺锌均可影响脑功能。锌作为体内重要的微量元素，影响多种酶的活性及蛋白质和核酸的台成。本实验通过体外分离大鼠脑海马突触体，观察不同浓度锌离子对Ca2 －Mg2 ATP酶的活性和3H－Leu掺入突触蛋白合成的影响．结果表明：1．锌离子浓度在25μmol／L时增加该酶的活性（＜0．01），并促进3H－Leur掺入蛋白质的合成（＜0．05）。2．锌离子在50,100，200μmol／L的较高浓度时对Co2 －M2 ATP酶的活性有显著的抑制作用（分别为：P＜0.05．P＜0．01，P＜0.01），仅200μmol／L对3H—Leu掺入突触蛋白合成有抑制作用。本研究提示：适量的锌对突触体功能的维持是必要的，但剂量过高则起相反作用。     

Localization of Putative Receptors for Tetanus Toxin and Botulinum Neurotoxin Type A in Rat Central Nervous System

Clostridial neurotoxins (tetanus and botulinum toxins) are potent blockers of neurotransmitter release. These toxins act specifically on the nervous system by interacting with still non-identified protein receptors together with gangliosides. Whereas many biochemical data are available on their binding properties to neuronal membranes in vitro , there is poor morphological evidence of their binding to mammalian central nervous system. In the present study, the binding of tetanus and botulinum neurotoxin type A to rat brain sections is reported. Both toxins bound to nerve terminals with a broad distribution in brain. Tetanus toxin additionally bound to nerve fibres. The staining patterns were clearly shown to be due to the interaction of the heavy chains, which contain the binding moiety, with the tissue. In an attempt to investigate the nature of the acceptors present in the tissue, some sections were pre-incubated with periodic acid. This treatment resulted in the additional binding of botulinum neurotoxin type A to nerve fibres. Since the extended staining of nerve terminals was not modified by this pretreatment, it is suggested that protein receptors of clostridial neurotoxins are located at the nerve terminals, which may be common constituents of the synapses.     

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5-HT Relationship in the Rat Suprachiasmatic Area

The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the Suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA_B agonist (RS-baclofen), the 5-HT metabolism was studied in the Suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats. Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the Suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the Suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the Suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectomized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the Suprachiasmatic area.     

大白鼠肾上腺的血管构筑

本实验采用血管铸型扫描电镜,注射明胶卡红组织切片显微镜下观察和注射铅丹乳胶追踪血管来源三种方法对14只健康大白鼠肾上腺血管构筑进行了研究。大白鼠肾上腺动脉发自腹主动脉和肾动脉。它们在行程中发出分支至腺体表面,再次分支穿入囊内,逐级分支至毛细血管。皮质动脉发自囊内血管,它们在皮质中分支分布。球状带的毛细血管与囊的毛细血管相连,毛细血管在球状带围绕细胞团形成网眼状;在束状带呈放射状排列;在网状带吻合增多形成网状。髓质动脉亦发自囊的血管,它们在皮质中不发分支直抵髓质,在髓质分成毛细血管。网状带的毛细血管越向髓质口径越粗,它们在皮髓交界处互相吻合形成更粗的静脉,这些静脉逐级吻合,最后形成一主干——中央静脉,它穿出皮质出现于肾上腺门处。左侧的中央静脉注入在肾静脉,右侧的注入下腔静脉。     

大鼠食管颈段神经形态的组化研究

本文采用多种组化方法结合神经银染技术,对大鼠的食管颈段神经形态观察发现:延髓内双侧疑核的咀侧端及迷走神经背核闩平而附近,分别见散在的多极和梭形标记细胞;颈前、中节、颈胸节和胸交感节(T_2-T_4),结状节,脊神经节(C_2-C_8)内均见标记细胞。 食管壁内的神经束及分支,由粗、细两类神经纤维组成。其中AchE阳性的胆碱能纤维占优势,分别见于外膜丛、肌内丛、粘膜下丛,腺体血管周围和粘膜肌内,粗纤维末梢伸向上皮基部和上皮之间,肌内的神经末梢呈结状膨大。外膜和肌肉见有神经节和散在的神经细胞。而食管壁内肾上腺素能纤维稀少,仅见于神经束和分支内及血管壁周围。     

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols.zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence,zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.     

Neurotrophin-like immunoreactivity in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the neurotrophin (NT) proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. The NT-like immunoreactive structures were unevenly distributed and showed regional differences among cerebellar lobules and folia. NGF-, NT-4-, and NT-3-positive neuronal perikarya were observed in all specimens examined. At variance with the other neurotrophins, the BDNF antiserum labelled neuronal cell bodies only in newborn life and infancy, as well as extensive nerve fibre systems, whose density increased with age. The NT-antibodies, tested by Western blot on human cerebellum homogenates, revealed immunoreactive bands corresponding to proteins of heterogenous molecular weight. The results obtained provide a first demonstration of the tissue localization of the NTs in the human cerebellum from perinatal to adult age, thus suggesting their involvement in the development, differentiation and maintenance of the cerebellar connectivity. Codistribution of the four NTs or sets of them was observed in cortical and deep nuclei neurons. Multiple trophic roles for NTs, encompassing the classic target-derived and local mechanisms of support, are envisaged as significant in development, differentiation, and maintenance of the human cerebellar connectivity.     

The use of the rat facial nerve model to assess the effect of differing nerve anastomotic agents on the facial nerve

There are relatively few papers which prove that one nerve anastomotic agent for the facial nerve is superior to any other. Previous experiments on the division and anastomosis of the facial nerve have failed to consider the indeterminate variables involved, i.e. operator variability, controls and the reaction of the materials on normal nerve tissue. In this experiment, a variety of anastomotic agents were tested to see if the anastomotic agents themselves affected the extra-temporal facial nerve function. The absorbable suture, non-absorbable suture, glue and tube wrap used had no effect on normal nerve tissue or on the anastomosis of the sectioned facial nerve of the rat compared with simple laying together of the divided ends of the divided nerve.     

硫酸镁联合亚低温治疗对大鼠局灶性脑缺血的保护作用

目的　探讨硫酸镁对SD大鼠局灶性脑缺血损伤的保护作用。方法　将 4 0只大鼠随机分成模型对照组、硫酸镁治疗组、亚低温治疗组、硫酸镁联合亚低温治疗组。采用线栓法建立大鼠局灶性脑缺血模型。通过计算大鼠神经功能缺陷评分 ,测量脑梗死体积 ,观察神经元超微结构改变 ,评定硫酸镁联合亚低温治疗作用。结果各治疗组大鼠神经功能评分及脑梗死体积均显著低于对照组 (P <0 0 5 ) ,联合治疗组大鼠明显低于对照组 (P<0 0 1) ;联合治疗组神经元超微结构改变轻微。结论　硫酸镁联合亚低温治疗对大鼠局灶脑缺血有明显保护作用