Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess

Summary Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminatedCandida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.     

Radioprotective effects of Sipunculus nudus L. polysaccharide combined with WR-2721, rhIL-11 and rhG-CSF on radiation-injured mice

This study investigated the radioprotective effect of Sipunculus nudus L. polysaccharide (SNP) in combination with WR-2721, rhIL-11 and rhG-CSF on irradiated mice. A total of 70 Imprinting Control Region (ICR) mice were divided into seven groups: the control group, the model group and five administration groups. All groups, except the control group, were exposed to a 5 Gy ⁶⁰Co γ-ray beam. Blood parameters [including white blood cell (WBC), red blood cell (RBC) and platelet counts and hemoglobin level] were assessed three days before irradiation, and the on the 3rd, 7th and 14th days after irradiation. Spleen, thymus and testicular indices, DNA contents of bone marrow cells, bone marrow nucleated cells, sperm counts, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and estradiol levels in the serum were assessed on the 14th day after irradiation. The combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF exerted synergistic recovery effects on peripheral blood WBC, RBC and platelet counts and hemoglobin levels in irradiated mice, and synergistic promotion effects on spleen, thymus, testicle, bone marrow nucleated cells and sperm counts in irradiated mice. The synergistic administration increased the serum SOD activities and serum testosterone content of irradiated mice, but synergy decreased the content of serum MDA and estradiol in irradiated mice. These results suggest that the combined administration of SNP, WR-2721, rhIL-11 and rhG-CSF should increase the efficacy of these drugs for acute radiation sickness, protect immunity, hematopoiesis and the reproductive organs of irradiated-damaged mice, and improve oxidation resistance in the body.     

重组人粒细胞集落刺激因子在大鼠局灶性脑缺血中的抗炎作用

目的 探讨重组人粒细胞集落刺激因子(rhG-CSF)在大鼠局灶性脑缺血中的抗炎作用.方法 用线栓法建立大鼠大脑中动脉缺血-再灌注(MCAO/R)模型,观察rhG-CSF对神经功能缺损评分的影响;用半定最逆转录-聚合酶链式反应(RT-PCR)方法 测定脑缺血区白细胞介素(IL)-1βamRNA和肿瘤坏死因子(TNF)-α mRNA的表达.结果 与对照组相比,rhG-CSF治疗绀大鼠的神经功能缺损评分明显降低,脑缺血区IL-1βmRNA和TNF-αmRNA表达降低.结论 rhG-CSF可降低IL-1βmRNA和TNF-αmRNA表达,在缺血-再灌注损伤中有抗炎作用.     

儿童恶性肿瘤化疗后小剂量短疗程国产rhG-CSF的应用

目的:观察小剂量短疗程重组人粒细胞集落刺激因子(rhG-CSF)对化疗儿童白细胞(WBC)下降的防治作用.方法:34例恶性肿瘤化疗儿童,采取自身交叉对照的方法,每例同方案化疗3个疗程.其中一个疗程不用rhG-CSF作为对照组;一个疗程化疗结束后48小时起给予小剂量短疗程rhC-CSF 3～5μg/kg·d,皮下注射,连用5天,为治疗1组;另一个疗程化疗结束后,WBC＜4×109/L时给予同样疗程和剂量的rhG-CSF作为治疗2组.比较各组间WBC及中性粒细胞(ANC)的变化,并观察不良反应.结果:治疗1组和治疗2组WBC下降(＜4×109/L)、ANC下降(＜2×109/L)持续的天数均低于对照组,但治疗1组的疗效优于治疗2组.WBC和ANC下降的最低值治疗1组高于对照组(P＜0.05),而治疗2组与对照组相比无差异.结论:小剂量短疗程国产rhG-CSF的早期应用可以缩短WBC、ANC下降的持续时间及减轻其下降程度,缩短化疗间歇,提高化疗效果.     

rhG-CSF增加脑缺血周边区脑源性神经营养因子的表达

目的　 观察重组人粒细胞集落刺激因子 (rhG CSF)是否能改善局灶性脑缺血大鼠的神经功能 ,以及其对脑缺血周边区脑源性神经营养因子 (BDNF)表达的影响。方法　线栓法复制大鼠大脑中动脉梗死模型 ,皮下给予rhG CSF ,10 μg/ (kg .d) ,连续 5d。进行神经功能评分并采用免疫组织化学法观察脑组织中BDNF的表达。进行nestin和BDNF的免疫双标染色。结果　 手术 7,14 ,2 1d干预组的神经功能缺损评分分别为 4 .0 0± 0 .89,3.83±1.17,3.5 0± 1.38,对照组分别为 5 .5 0± 1.38,5 .83± 1.4 7,5 .6 6± 1.6 3,干预组明显低于对照组 ,差别有显著性 (P<0 .0 5 )。干预组梗死边缘区的BDNF免疫阳性细胞数较对照组明显增加 (P <0 .0 5 )。梗死边缘区可见nestin和BDNF双阳性细胞。结论　粒细胞集落刺激因子可增加脑缺血之后梗死边缘区BDNF的表达和改善神经功能     

Bioactive components on immuno-enhancement effects in the traditional Chinese medicine Shenqi Fuzheng Injection based on relevance analysis between chemical HPLC fingerprints and in vivo biological effects

Ethnopharmacological relevance

Shenqi Fuzheng Injection (SFI) is an injectable traditional Chinese herbal formula comprised of two Chinese herbs, Radix codonopsis and Radix astragali, which were commonly used to improve immune functions against chronic diseases in an integrative and holistic way in China and other East Asian countries for thousands of years.

Materials and methods

This present study was designed to explore the bioactive components on immuno-enhancement effects in SFI using the relevance analysis between chemical fingerprints and biological effects in vivo. According to a four-factor, nine-level uniform design, SFI samples were prepared with different proportions of the four portions separated from SFI via high speed counter current chromatography (HSCCC). SFI samples were assessed with high performance liquid chromatography (HPLC) for 23 identified components. For the immunosuppressed murine experiments, biological effects in vivo were evaluated on spleen index (E1), peripheral white blood cell counts (E2), bone marrow cell counts (E3), splenic lymphocyte proliferation (E4), splenic natural killer cell activity (E5), peritoneal macrophage phagocytosis (E6) and the amount of interleukin-2 (E7). Based on the hypothesis that biological effects in vivo varied with differences in components, multivariate relevance analysis, including gray relational analysis (GRA), multi-linear regression analysis (MLRA) and principal component analysis (PCA), were performed to evaluate the contribution of each identified component.

Results

The results indicated that the bioactive components of SFI on immuno-enhancement activities were calycosin-7-O-β-d-glucopyranoside (P9), isomucronulatol-7,2′-di-O-glucoside (P11), biochanin-7-glucoside (P12), 9,10-dimethoxypterocarpan-3-O-xylosylglucoside (P15) and astragaloside IV (P20), which might have positive effects on spleen index (E1), splenic lymphocyte proliferation (E4), splenic natural killer cell activity (E5), peritoneal macrophage phagocytosis (E6) and the amount of interleukin-2 (E7), while 5-hydroxymethyl-furaldehyde (P5) and lobetyolin (P13) might have negative effects on E1, E4, E5, E6 and E7. Finally, the bioactive HPLC fingerprint of SFI based on its bioactive components on immuno-enhancement effects was established for quality control of SFI.

Conclusions

In summary, this study provided a perspective to explore the bioactive components in a traditional Chinese herbal formula with a series of HPLC and animal experiments, which would be helpful to improve quality control and inspire further clinical studies of traditional Chinese medicines.     

维生素D3联合rhG-CSF对糖尿病小鼠眼部结构的保护作用

目的:探讨维生素D3(VD3)联合rhG-CSF对实验性糖尿病(diabetes mellitus,DM)小鼠眼部结构损伤的作用。方法:健康C57BL/6小鼠22只,体质量20~25g,随机分为联合治疗实验组、DM对照组,并设健康对照。用20g/L链脲佐菌素(streptozotocin,STZ)ip,制备实验性DM模型,实验组小鼠制模后14d行VD35mg/kg ip,1次/wk;制模后28d行20μg/kg rhG-CSF sc,1次/d,连续注射5d。两组每周进行血糖监测和眼底镜观察。每周各组随机摘取3只眼球,常规病理制片后镜下观察眼球各部分结构,利用病理图像分析系统测量中央角膜、视乳头旁1PD处脉络膜厚度和视网膜神经上皮层的厚度。结果:DM小鼠7d角膜中央出现明显水肿,21d达高峰后逐渐减轻,经联合治疗后小鼠角膜厚度一直呈现减少趋势,水肿情况比DM对照组有明显缓解,接近健康小鼠平均值。DM小鼠7d角膜上皮厚度明显增加,21d达高峰后逐渐下降,到35d后DM对照组角膜上皮厚度持续下降,萎缩明显,联合治疗组的角膜上皮厚度接近正常(P>0.05)。DM小鼠7d脉络膜厚度降低,开始萎缩,逐渐加剧,联合治疗组在28d后脉络膜厚度明显增加,到49d时与正常小鼠无差异,两组DM小鼠的视网膜神经上皮层厚度均呈逐渐下降趋势,联合治疗组的下降趋势略缓和。结论:VD3联合rhG-CSF治疗能有效缓解小鼠DM角膜水肿,改善角膜上皮萎缩,有效缓解并改善脉络膜萎缩,对视网膜神经上皮层萎缩也有一定的保护作用。     

rhG-CSF穴位注射治疗化疗后粒细胞减少的临床研究

目的　研究基因重组人粒细胞集落刺激因子 (rhG CSF)穴位注射对肿瘤化学治疗所致的白细胞 (WBC)和中性粒细胞 (ANC)减少的影响。方法　将 6 0例进行随机分为穴位注射组和皮下注射组 ,两组分别有消化道恶性肿瘤、非小细胞肺癌、乳腺癌各 10例。化疗 2 4小时后应用rhG CSF 15 0 μg ,连用 5天 ;穴位注射组采用穴位注射 ,皮下注射组采用皮下注射。观察白细胞和中性粒细胞绝对数的动态变化。结果　对照组 1例消化道恶性肿瘤因故出组 ,其余 5 9例在rhG CSF的剂量为 15 0 μg时 ,穴位注射组与皮下注射组比较 ,ANC最低值、ANC减少的持续时间、ANC减少程度和ANC平均值变化曲线均无明显差异。但在各种不良反应方面亦基本相似。结论　rhG CSF剂量为 15 0 μg/天时 ,穴位注射并不比皮下注射在对抗骨髓抑制方面更具优势。     

rhG-CSF动员对异基因造血干细胞移植供者外周血CD4~+ T细胞S1P_1表达的影响

CD4+ T细胞主要通过其表面的S1P1受体与外界的第一信使1磷酸鞘氨醇(S1P)相互作用调节免疫功能。本研究旨在探讨重组人粒细胞集落刺激因子(rhG-CSF)动员对异基因造血干细胞移植(allo-HSCT)供者外周血CD4+ T细胞S1P1表达的影响。17例allo-HSCT供者于rhG-CSF动员前及动员后第4天采集外周血,使用磁珠分选法纯化CD4+ T细胞,提取微量RNA,用实时定量PCR法检测S1P1的表达。结果显示,rhG-CSF动员前后CD4+ T细胞均表达S1P1,且动员后S1P1在CD4+ T细胞中的表达明显低于动员前。结论:rhG-CSF动员使allo-HSCT供者外周血CD4+ T细胞S1P1的表达明显下调。     

重组人粒细胞集落刺激因子对阿糖胞苷诱导HL-60细胞凋亡的影响

为了研究重组人粒细胞集落刺激因子（rhG-CSF）对阿糖胞苷（Ara-C）诱导HL-60细胞凋亡的影响,体外培养HL-60细胞,加入rhG-CSF和（或）Ara-C,瑞氏染色观察细胞形态变化,吖啶橙/溴化乙锭双染色观察细胞凋亡情况,MTT实验检测细胞增殖活性.结果表明：加入rhG-CSF后Ara-C诱导的HL-60细胞的凋亡率升高（P＜0.01）,而MTT实验的OD值降低（P＜0.01）.结论：rhG-CSF有诱导HL-60细胞凋亡的作用,rhG-CSF可以促进Ara-c诱导HL-60细胞凋亡的作用.