Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

慢性肾血管性高血压大鼠脑细胞膜游离脂肪酸水平变化

采用SD大鼠慢性肾血管性高血压模型,气-液色谱法测定高血压组(n=8)、对照组(n=9)脑细胞膜游离脂肪酸(Free Fatty Acid,FFA)单组分水平。结果显示高血压组脑细胞膜FFA组份中C20:4、C22:6水平显著高于对照组(PO.05)。提示继发性高血压大鼠存在脑细胞膜FFA代谢障碍。     

ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

医学生"网络成瘾症"产生的原因和对策

文章针对目前医学生“网络成瘾症”的现状进行了分析,并指出了产生的原因和解决问题的办法,以求达到标本兼治。最后提出三点预防医学生“网络成瘾症”的对策：一是高校及其附属医院要为医学生营造宽松愉快的学习、生活环境;二是呼吁家长关注医学生身心发展的特殊规律,建立良好的家庭环境;三是建立和完善与网络社会相应的法律法规,规范医学生的网上行为。     

ACTIVIT OF HUMAN PLACENTAL GAMMA GLOBULININ BLOCKING IMMUNE FUNCTIONS IN VITRO AND IN ABROGATING THE XENOGENEIC, LOCAL GRAFT-VERSUS-HOST-REEACTEON

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft – versus –host disease (GCHD) following bone marrow transplantation (BMT) ,we have examined the effect of PGG in vitro and in a model of the xenogeneic , local graft –ver- sus – host reaction (LGVHR) .PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P<0.005) and depressed interleukin -2 (IL-2) levels in such cultures at 72 hours (P<0.01) . In contrast phytohemagglutinin (PHA) –and pokeweed mitogen (PWM) –induced T and B lymphocyte blastogenesis was not affected by such PGG treatment .PGG treatment .PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability .Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation . An immunosuppressive effect of PGG on the LGCHR was tested in a model of intracutaneous transplantation of PGG –treat human lymphocytes into cyclophosphamide – immunosuppressed rats. Lymphoprep – separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing：（1）PGG,4mg/ml,(2) human plasma albumin,4mg/ml,(3)mitomycin-C,25ug/ml, or (4) no additive. Cell of each preparation (3x107cells in 0.1ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells ,each rat received [125 I]IUdR (10uCi) intraperitoneally and was killed after 5 hours. For each site of injection, the diameters of induration were measured and 125 I was counted . There was no difference between buffer – treated and a ibumin – treated groups either in the diameter of the area of induration (t=0.66;P>0.5)or in radioactive counts(t=0.22;P>0.05).In the PGG –treated group, the induration and radioactivity measurements were significantly less than in control groups (t=3.72 and P<0.1;t=2.62 and P<0.02,respectively ) Cytophilic antibodies in PGG were thought to inhibit an early phase of T cell activation, and not to be cytotoxicity .In the LGVHR, the immune response might be abrogated either by immuno- regulatory suppression of T cell function or by toxicity to the infused lymphoid cells. For some clinical purposes, immuno- modulating, human antibodies might be preferred to murine, monoclonal antibodies.     

复发性脑胶质瘤及其放射治疗

1976～1986年肿瘤科收治脑胶质瘤42例,10例复发,其中6例采用单纯放疗,用~60钴γ线。5例脑胶质瘤予肿瘤区局部照射,DT44～57Gy/6-7周,1例髓母细胞瘤予全脑、肿瘤区及全脊髓照射、脑中平面量DT38Gy/5周;肿瘤区51Gy/7周;脊髓18Gy/8周。结果:有效1例,显效2例,无效3例。本研究提示对于已不能釆用其他手段治疗的复发病人,放疗仍有一定效果。     

Distribution of rat facial motoneurons and its reorganization following nerve reinnervation]

OBJECTIVE: To examine the distribution of rat facial motoneurons contributing different branches under normal situation and when nerve reinnervation occurred following facial nerve axotomy. METHODS: The normal distribution of motoneurons innervated both buccal and marginal mandibular branches and its reorganization after facial nerve reinnervation was observed using retrograde labeling with fluorescein. RESULTS: Under normal situation, the motoneurons contributing buccall and marginal mandibular branches were primarily distributed in the intermedial and lateral subnucleus in facial nucleus and almost completely overlapped. The two types labeled neurons organized closely, but there were no double-labeled neurons. Although the motoneurons contributing buccall and marginal mandibular branches were primarily overlapped 4 month post-anastomosis, the number of the labeled neurons obviously decreased and the organization got more scattered. There were 10% of buccall branches, 5% of marginal mandibular motoneurons in the dorsal subnuleus, 1% of buccall and 4% of marginal mandibular in dorsal ventral and medial subnucleus. The distribution pattern of the motoneurons 6 month post-anastomosis was similar to that of 4 month post-anastomosis, but the number of the labeled neurons increased, and there were 1%-2% double-labeled neurons. CONCLUSION: The distribution pattern of motoneurons innervated both buccal and marginal mandibular branches indicates that it should exist wide-spread communicating branches, and its reorganization after facial nerve reinnervation suggests that misdirected regeneration occurs among motoneurons innervating different branches.