FK506对大鼠坐骨神经再生作用的实验研究

押目的对FK506促神经再生的作用及药物应用方法进行初步探讨。方法雄性SD大鼠60只,随机分成三组,切断双侧坐骨神经制成坐骨神经再生室模型。A组(对照组)再生室内注入生理盐水;B组(全身用药组)再生室内注入盐水,颈后皮下注射FK5061mg/kg,连续14天;C组(局部用药组)再生室内注入1μg/mlFK506。于术后一定时间内观察神经损伤局部的免疫反应熏检测腓肠肌湿重、组织形态学及图像分析、电生理学。结果B、C组神经损伤局部淋巴细胞浸润程度较A组轻微。6周时B组各测定结果明显优于A组;C组各指标好于A组,但不具有统计学意义。结论穴1雪全身应用FK506(1mg/kg)具有神经保护和神经营养作用,可加快神经功能的恢复。(2)局部应用FK506(1μg/ml)对早期损伤神经有一定的保护作用,但对神经再生的促进作用不确切。     

Cyclosporin A, an inhibitor of calcineurin, impairs memory formation in day-old chicks

Considerable evidence exists that changes in the phosphorylation state of neuronal proteins are correlated with learning and that inhibition of various protein kinases disrupts memory formation. Given the reversible nature of protein phosphorylation, a role for protein phosphatases in memory processing also seems likely. It has been shown recently that administration of the phosphatase inhibitor, okadaic acid, disrupts memory formation in day-old chicks, with retention deficits first appearing at approximately 40 min post-training [93]. In the present study the intracranial administration of the immunosuppressant cyclosporin A was also found to produce retention deficits in day-old chicks trained on a single-trial, passive-avoidance task, but the deficits were not significant until 85 min post-training. The difference could not be attributed to differences in the pharmacokinetics of the drugs. Since okadaic acid preferentially inhibits protein phosphatases 1 and 2A, while cyclosporin A is reported to inhibit only the Ca²⁺/calmodulin-dependent protein phosphatase, calcineurin, it is possible that different phosphatases may be involved in distinct stages of memory formation, as has been reported previously for protein kinases. The possibility that cyclosporin A may, in addition, act through inhibition of cyclophilin's peptidyl-prolyl-cis/trans- isomerase activity is also canvassed.     

Immunopharmacological profile of SR 31747: In vitro and in vivo studies on humoral and cellular responses

In our preceding paper, we demonstrated that both human and rat lymphocytes possess saturable high-affinity binding sites for the new sigma ligand SR 31747. Here we investigate the potential activity of this ligand on immune responses. In vitro, our study shows that SR 31747 exerts a concentration- and time-dependent inhibition of proliferative response to mitogens on mouse and human lymphocytes without affecting cell viability. This suppressive effect elicited by SR 31747 occurs over a concentration range which correlates with the pharmacological profile of the molecule in binding assays, strongly suggesting that SR 31747 acts through a receptor-mediated process. We showed that the SR 31747 effect, which was observed on purified T lymphocytes, affects a late event in the activation process which occurs after the G1 during the S phase of the cell cycle. Interestingly, no anti-proliferative effect was observed in a variety of tumor cell lines, supporting a specific effect limited to normal immune cells. In vivo, in mice, treatment with SR 31747 prevented both graft-versus-host disease and delayed-type hypersensitivity granuloma formation, while antibody response to sheep red blood cells was not affected. These results strongly suggest that the sigma-related receptor recognized by SR 31747 is very likely coupled to a biological function of lymphocytes.     

甾体-多肽缀合激素的合成及免疫抑制活性

尿毒素三肽UTP-A,UTP-B和UTP-C分别与氢化可的松缀合,得到4种缀合激素。与尿毒素三肽或氢化可的松相比,缀合激素可延长不同种属小鼠异位移植(Heterotopic transplatation)心肌的存活时间;与氢化可的松和尿毒素三肽的机械混合物相比,低浓度下缀合激素可增强对淋巴细胞增殖的抑制作用。表明缀合激素有一定的免疫抑制作用。     

Retrospective evaluation of the efficacy and safety of belatacept with thymoglobulin induction and maintenance everolimus: A single‐center clinical experience

Belatacept use has been constrained by higher rates of acute rejection. We hypothesized that belatacept with low‐dose rATG and initial mycophenolate maintenance with conversion to everolimus at 1 month post‐transplant ± corticosteroids would improve efficacy and maintain safety. Retrospective single‐center analysis of the first 44 low immunologic risk kidney transplant recipients treated with this regimen. The cohort was 59% male, mean age at transplant of 57 years. Diabetes was the most common cause of ESRD (39%). The mean 1‐year eGFR was 61.4 (SD 18.4) mL/min/1.73 m². There were five acute cellular rejections (11.4%) that occurred in patients who had changed from everolimus to mycophenolate mofetil due to side effects. Thirty‐two percent developed BK viremia and 12% developed CMV viremia. There were no cases of PTLD. A novel belatacept regimen with rATG induction and maintenance everolimus demonstrated a low acute rejection rate and maintained an excellent 1‐year eGFR.     

免疫抑制剂在大鼠坐骨神经损伤修复中的作用

目的探讨使用多种免疫抑制剂对大鼠坐骨神经损伤修复后神经轴突和髓鞘再生的影响。方法切断大鼠双侧坐骨神经,并予以端端吻合,分组分别联合给予不同时间的甲基强地松龙、CsA和FK506(B组术后使用2 d的甲基强地松龙20 mg·kg~(-1)·d~(-1);C组在B组的基础上,术后使用2周的FK506,剂量为1 mg·kg~(-1)·d~(-1);D组在B组的基础上,术后使用4周的FK506,剂量同C组;E组在B组的基础上,于术后使用2周的CsA,剂量为2 mg-kg~(-1)·d~(-1);F组在B组的基础上,于术后使用4周的CsA,剂量同E组),对照组(A组)不给药,于术后1、2、4周取材坐骨神经,分别进行苏木精-伊红染色、以及Nf和S100的免疫组织化学染色,并对染色结果进行分析、比较。结果从形态学观察,实验组较对照组神经吻合口远端的许旺细胞崩解不彻底,吻合口近端的神经轴突退变距离缩短,神经轴突生长速度更快,神经的再髓鞘化程度更高,早期即可见中央动脉形成。用药2周组与用药4周组在神经修复的组织学上无统计学意义(P>0.05)。对NF和S100进行图像分析和统计学处理后,提示用药组神经生长速度显著快于对照组(A组),而联合用药组(C、E组)的神经生长速度在2周内比单纯使用甲基强地松龙组(B组)更快。联合用药组(C、E组)S100阳性染色的数量在2周内显著高于对照组(A组)。结论免疫抑制剂的使用可以对神经吻合口远端的许旺细胞和神经吻合口近端的神经细胞起到一定的保护作用,短期用药就可以取得与长时间用药相似的效果。     

Immunosuppressant treatment for IgG4-related sclerosing cholangitis: A case report

BACKGROUNDImmunoglobulin G4-related disease (IgG4-RD) is a multi-system fibroin-flammatory disorder that can involve any organ, including the salivary glands, pancreas, and biliary tree. Treatment of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is similar to that for IgG4-RD, but progression is irreversible in some cases. We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARYA 63-year-old male presented with a prominent itching sensation and wholebody jaundice. He showed obstructive-pattern jaundice, an elevated IgG4 level, and infiltration of a large number of IgG4-positive cells in the ampulla of Vater. The imaging findings of intrahepatic duct (IHD) and common bile duct dilation, an elevated serum IgG4 level, and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria. We planned to treat the patient with high-dose glucocorticoid (GC), followed by cyclophosphamide pulse therapy. After treatment with high-dose GC and an immunosuppressant, imaging studies showed that IHD dilatation had completely resolved.CONCLUSIONPrompt diagnosis and appropriate treatment of IgG4-SC are important. Because there is a risk of relapse of IgG4-SC, the GC dose should be gradually reduced, and a maintenance immunosuppressant should be given.     

Long‐Term Lung Transplantation in Nonhuman Primates

Despite advances in surgical technique and clinical care, lung transplantation still remains a short‐term solution for the treatment of end‐stage lung disease. To date, there has been limited experience in experimental lung transplantation using nonhuman primate models. Therefore, we have endeavored to develop a long‐term, nonhuman primate model of orthotopic lung transplantation for the ultimate purpose of designing protocols to induce tolerance of lung grafts. Here, we report our initial results in developing this model and our observation that the nonhuman primate lung is particularly prone to rejection. This propensity toward rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2) a larger number of pre‐existing alloreactive memory T cells, leading to augmented deleterious immune responses. Our data show that triple‐drug immunosuppression mimicking clinical practice is not sufficient to prevent acute rejection in nonhuman primate lung transplantation. The addition of horse‐derived anti‐thymocyte globulin and a monoclonal antibody to the IL‐6 receptor allowed six out of six lung recipients to be free of rejection for over 120 days.     

天津市综合医疗机构在四种高危人群中开展结核病确诊相关检查现况调查

目的: 了解天津市综合医疗机构在单侧胸腔积液、咯血、拟应用免疫抑制剂和拟长期应用糖皮质激素住院患者中开展结核病确诊相关检查的现况。方法: 采用方便抽样法,选取天津市31家疑似结核病报告数量较大的综合医疗机构作为研究现场。每种高危人群先分别从每家医疗机构指定科室各抽取住院患者病案10份,共纳入1240份患者病案。查阅病案病程记录,提取符合高危人群定义的患者作为研究对象,最终纳入419例研究对象,其中单侧胸腔积液住院患者164例,咯血住院患者97例,拟应用免疫抑制剂住院患者86例,拟长期应用糖皮质激素住院患者72例。结果: 31家综合医疗机构以三级为主,占80.6%(25/31)。4种高危人群完成结核病确诊相关检查的比例为46.1%(193/419),单侧胸腔积液、咯血、拟应用免疫抑制剂和拟长期应用糖皮质激素住院患者完成检查的比例分别为57.3%(94/164)、52.6%(51/97)、29.1%(25/86)、31.9%(23/72)。涂片、培养、GeneXpert MTB/RIF、结核菌素皮肤试验(TST)、γ-干扰素释放试验(IGRA)和结核抗体检查比例分别为64.8%(125/193)、16.6%(32/193)、10.9%(21/193)、8.3%(16/193)、18.1%(35/193)和34.2%(66/193)。三级综合医疗机构IGRA检测比例为21.1%(35/66),高于二级综合医疗机构的0.0%(0/27),差异有统计学意义(χ²=6.954, P=0.005);结核抗体检测比例为31.3%(52/166),低于二级综合医疗机构的51.9%(14/27),差异有统计学意义(χ ²=4.348, P=0.049)。结论: 天津市综合医疗机构高危人群开展结核病确诊相关检查的比例较低,需进一步提高检查水平。     

边缘性脑炎1例报道

报告1例边缘性脑炎患者的临床特点、实验室检查、电生理和颅脑影像资料以及经免疫抑制剂治疗后的预后,并结合文献讨论边缘性脑炎可能是一种累及边缘系统的自身抗体介导的免疫性疾病,影像学检查以边缘系统受累为主,经免疫抑制剂治疗有一定疗效.