A-23187 evoked transmitter release from rabbit pulmonary artery and its inhibition by reactivation of sodium-pump

1. The spontaneous [3H]-release has been measured from the isolated main pulmonary artery of the rabbit preloaded with [3H]noradrenaline in the presence of uptake blockers (cocaine, 3 x 10(-5) M; corticosterone, 5 x 10(-5) M). 2. The Ca-ionophore A-23187 (3 x 10(-7)-3 x 10(-5) M) increased the outflow of [3H] by a concentration dependent manner. 3. Inhibition of Na+-pump by removal of K+ from the external medium also increased the release of labelled noradrenaline. 4. In the absence of external K+, the applied A-23187 (3 x 10(-6) M; EC50) further increased the release of [3H]. 5. Reactivation of Na+-pump by readmission of K+ (5.9 mM) to the external medium abolished the [3H]-release which had previously been increased in "K+-free" solution. 6. The reactivated Na+-pump significantly inhibited the transmitter releasing action of A-23187. 7. This latter was antagonized by an increase of external Ca2+ (7.5 mM). 8. It is concluded that the reactivated Na+-pump caused re-establishment of Na+-gradient is capable to counteract the Ca-ionophore facilitated Ca2+-influx and release from internal stores, which can be antagonized by excess Ca2+.     

Preclinical screening and analysis of the immunotoxic and immunomodulatory activity using a multiple immunoassay (MIA) in mice

Screening and analysis of immunotoxic and immunomodulatory activity has become an integral component in preclinical studies of pharmaceuticals and xenobiotics. In an attempt to replace laborious and expensive batteries of assays used at present we developed a multiple immunoassay (MIA) enabling the determination, in a single mouse, of: the weight of the thymus, spleen and a group of lymph nodes; delayed type hypersensitivity and antibody response to SRBC; phagocytic activity of peritoneal macrophages and the responsiveness of spleen lymphocytes to "T" (PHA, ConA) and "B" (LPS) mitogens in vitro. The MIA responsiveness to two prototype immunostimulators (Thymostimulin and Listeria factor Ei) was tested at two time periods after antigenic stimulation, not only in normal mice, but also in animals with selectively depressed T-systems (anti-Thy1.2 monoclonal antibody) and B-systems (cyclophosphamide); in both dexamethasone-treated and irradiated animals. The findings indicate, that this MIA is capable of reflecting both immunosuppressive and immunostimulatory activities of the tested agents and permits partial insight into the mechanisms underlying these activities.     

PSMA6/PSMC6/PSMA3基因多态性与系统性红斑狼疮发病的相关性

目的:明确蛋白酶体(PSM)相关基因单核苷酸多态性与中国人群系统性红斑狼疮(SLE)的相关性。方法:PCR扩增101例SLE患者和143名正常对照者外周血目的基因片段,通过二代测序对目的基因片段进行测序检测蛋白酶体20 s亚单位和相关ATP酶基因的4个目标位点PSMA6(rs2277460),PSMA3(rs2348071),PSMC6(rs2295826,rs2295827)的基因型及等位基因频率。结果:SLE组及对照组中rs2277460(GG,GA、AA)基因型频率分别为97.22%,1.85%%,0.93%和96.5%,3.5%,0;rs2348071AA,AG,GG分别为30.56%、53.7%、15.74%和33.57%、50.35%、16.08%;rs2295826AA,AG,GG分别为75.93%、24.07%、0和69.23%、29.37%、1.4%;rs2295827CC、CT、TT分别为78.7%、19.45%、1.85%和76.22%、20.98%、2.8%,均无统计学差异(P0.05)。结论:PSMA6/PSMC6/PSMA3 SNPs可能与SLE的发病无关。     

Treatment of autoimmune disease by immunomodulation through extracorporeal elimination and intravenous immunoglobulin

If customary drug mediated immunosuppressive therapy leads to intolerable side effects or is inefficient, extracorporeal elimination and untargeted or targeted immunoglobin therapy modulating the immune response are taken into consideration for the treatment of patients with autoimmune diseases. Both elimination and immunoglobulin therapy, are not alternatives but appear to act complementary, if sequentially applied. Selective immunoadsorption is increasingly applied for extracorporeal elimination and is able to replace plasma exchange therapy. Both, hydrophobic interaction chromatography and affinity chromatography are effective in given clinical conditions. Therapeutic affinity chromatography appears to be superior to hydrophobic interaction chromatography, if an effective, rapid elimination of the disease promoting agent is desired. Experience with therapeutic chromatography collected in the past, indicates that a rapid elimination of immunoglobulins and the subsequent intravenous infusion of 7S immunoglobulin is superior to elimination or untargeted immunomodulation alone. These experimental approaches lead to an extension of the available treatment modalities. However, controlled trials rather than anecdotal reports are needed, to provide substantial information.     

Technical and clinical experience with protein A immunoadsorption columns

Protein A adsorption (Immunosorba, Excorim, Sweden) is a potent tool for the rapid removal of antibodies from the circulation. In comparison to conventional plasma exchange therapy, Protein A adsorption offers the advantage of processing large amounts of plasma, removing up to 87% of the initial level of IgG in one session without a clinically significant loss of fibrinogen. So far 61 treatments have been carried out in our department without serious side effects.     

大鼠发育第6天与第8天睾丸组织基因表达差异的分析

目的 检测大鼠精原干细胞早期发育过程中第6天与第8天睾丸组织的差异表达基因.方法 通过基因芯片技术,利用Roche-NimbleGen公司大鼠12×135K全基因组表达谱芯片分别与第6天和第8天睾丸组织的cDNA进行杂交.比较两个样品差异表达的基因.结果 差异表达基因700个,表达上调的基因共295个,表达下调的基因共405个.参与了1 407个基因功能分析条目;参与了46个生物学通路.结论 大鼠精原干细胞早期发育过程中,精原干细胞的发生与增殖是一个多基因参与、多因素作用和多阶段进展的过程.     

Effect of methylprednisolone, tirilazad mesylate and vitamin E on lipid peroxidation after experimental spinal cord injury

Effect of methylprednisolone (MP), tirilazad mesylate (TM) and vitamin E on lipid peroxidation (LP) was evaluated in an experimental model of spinal cord compression injury in anesthetized rats. Forty rats, divided randomly into four groups, were injured by compressing on the spinal cord at Th 3 for 1 min. Bolus injections of saline solution, MP (30 mg/kg bolus and 5.4 mg/kg/h), TM (10 mg/kg four times per day), or vitamin E (30 mg/ kg four times per day) were begun 1 h after the spinal cord injury (SCI). Twenty-four hours after treatment, the rats were killed, and malondialdehyde (MDA), a LP product, was measured in the spinal cord tissues. Rats treated with MP, TM and vitamin E had significantly decreased MDA levels (P<0.01) than rats in the control group. The lowest MDA levels were found in the TM group. These results suggest that MP, TM and vitamin E may have a protective effect against SCI in rats by its antioxidant effect.     

Late hepaticartery thrombosis after liver transplantation: which strategy? A single‐center retrospective study

The management of late hepatic artery thrombosis (LHAT) after liver transplantation (LT) is not codified. The objective of this study was to retrospectively evaluate outcomes after LHAT. All patients with HAT diagnosed 3 months or later after LT on computed tomography between 1993 and 2017 were included. Our policy was to apply a conservative management for asymptomatic or mild symptomatic patients and reserve retransplantation to symptomatic patients with diffuse cholangitis or liver abscess. A total of 56 patients were analyzed. LHAT diagnosis was made after a median interval of 48 months from LT (ranging from 3 to 368.3). At diagnosis, 28 (50%) patients were asymptomatic, 10 (17.8%) had mild symptoms (transient acute cholangitis), and 18 (32.1%) had severe complications. Asymptomatic patients experienced a 5‐year graft survival of 57% vs. 40% in those with mild symptoms and 11% in those with severe complications (P < 0.001). However, there was no difference in overall patient survival between groups. Our results suggest that conservative management of LHAT for asymptomatic patients or patients with mild complications is safe. Retransplantation should be reserved to patients with severe biliary complications.     

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.