Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine

Abstract: A prospective, randomized study was conducted to evaluate the role of vitamin B₁₂ and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4 + cell counts < 500/mm³ were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B₁₂ (1000 μg monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B₁₂ and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm³ and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B₁₂ or folate levels and development of myelosuppression. Vitamin B₁₂ and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.     

肺癌TIL的体外培养及其表型分析

应用APAAP法对15例肺癌TIL部分膜抗原的表达动态进行了免疫组化分析。结果显示:未经激活的TIL细胞,其膜抗原(CD~+3,CD~+4,CD~+8)的表达动态基本恒定,经IL-2激活的TIL细胞体外培养一段时期后,其CD~+3细胞数明显上升,同时CD~+8的表达逐渐减少,而CD~+4的表达在培养后期明显增多。     

Detection of cytoplasmic IL-1 beta in peripheral blood mononuclear cells from intensive care unit (ICU) patients.

Cytokines including IL-1 beta have been implicated in the pathophysiology of sepsis and the systemic inflammatory response. It is believed that certain critically ill patients may be 'primed' with respect to cytokine production, and that subsequent 'triggers' may cause exaggerated cytokine production in these patients with exacerbation of their clinical condition; however, no means of identifying 'primed' patients has been described. The presence of cytoplasmic IL-1 beta within peripheral blood mononuclear cells (PBMC) from patients in the ICU was investigated as a means of identifying 'primed' patients, using fluorescent antibody labelling and flow cytometry. The study revealed that PBMC from ICU patients had a different staining pattern for IL-1 beta than those from healthy subjects, and that PBMC from certain ICU patients did indeed stain strongly for IL-1 beta; however, the presence of these strongly staining cells was not associated with clinical condition or outcome. It is concluded that whilst it might be possible to identify 'primed' patients in the ICU using this technique, this is of no clinical value as a predictor of clinical course.     

Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

健康人血清叶酸和维生素B_(12)水平的测定

本文对14岁以下健康小儿171名,成人30名及初生儿脐带血30份进行了血清叶酸和维生素B_(12)含量测定,171名小儿于采血前均经补足叶酸和维生素B_(12)。结果:血清叶酸(nmol/L)的正常值低限,<4岁者为6.1,4～14岁为8.4,成人为5.0;血清维生素B_(12)(pmol/L)的正常值低限,<1岁为459,1岁～成人为107。     

A highly variable STR at the D12S391 locus

A total of 103 fragments in the STR D12S391 locus were sequenced. 24 different alleles were found which can be grouped into 12 allelic classes based on the total number of repeats. The structure of this compund STR consists of blocks of (AGAT) and (AGAC) repeats with a consensus structure (AGAT)_8–l7 (AGAC)_6–10 (AGAT)_0–1. Whereas shorter alleles only have (AGAT) repeats, > 225 bp alleles are more complex, having two motifs (AGAT) and (AGAC). Population data showed that this to be a highly polymorphic STR with a heterozygosity of 0.9. This fact together with its simple structure make this STR very suitable for forensic and genetic purposes.     

Gingival crevicular fluid IL-8: correlation with local IL-1β levels and patient estrogen status

Gingival crevicular fluid (GCF) IL-8 and IL-1,1β levels were determined by sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1β GCF levels, and between these cytokines and patient estrogen status were evaluated. IL-8 and IL-1β were detected more frequently and in higher amounts/30 s GCF sample in estrogen-deficient patients than in estrogensufficient patients. IL-8 and IL-1β GCF levels were significantly correlated. These lindings suggest that GCF IL-8 levels are associated with patient estrogen status and local IL-1β concentrations.     

IFN-γ,IL-4水平对血透患者外周血PBLC Fas,Bcl-2表达的影响

目的研究IFN-γ,IL-4水平对血透患者外周血淋巴细胞(PBLC)凋亡调控蛋白Fas,Bcl-2表达的影响.方法采用流式细胞术的间接免疫荧光素标记法和双抗体夹心ELISA法,分别检测30例HD患者PBLC Fas,Bcl-2的表达水平和血清IFN-γ,IL-4水平.结果H-D患者血清IFN-γ水平明显低于健康对照组,IL-4浓度显著高于对照组(P均＜0.01);其外周血PBLC的Fas表达水平明显高于健康对照组,而Bcl-2水平则明显低于健康对照组(P均＜0.01).经相关分析发现:Fas表达水平与血清IFN-γ水平呈负相关,而与血清IL-4水平呈正相关(P均＜0.01);Bcl-2表达水平与血清IFN-γ水平呈正相关,而与血清IL-4水平呈负相关(P均＜0.01).结论HD患者PBLC存在异常凋亡现象;并与Th1型细胞因子分泌低下,以及TTh2型细胞因子分泌增加之间有一定的相关性,上述改变可能在HD患者的免疫功能紊乱中起着重要作用.     

Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine which regulates immune responses and host defence mechanisms. IL-6 has been found to be increased in certain inflammatory conditions of the kidney, in which tubular epithelial cells play a pivotal role. Human renal tubular cells express IL-6. Until now no data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL-6 expression were available. METHODS: Proximal and distal tubular epithelial cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were stimulated with interleukin-1beta (IL-1beta; 25 U/ml), IL-1beta+ MPA (0.25-50 micro M) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using the Quantikine mRNA kit. RESULTS: After IL-1beta stimulation, a highly significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was detectable. IL-6 mRNA was upregulated by IL-1beta [1.57- (PTC) and 2.03-fold (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent manner. Incubation with the lowest MPA concentration had no effect on the stimulated upregulation, whereas all higher doses significantly decreased IL-6 expression. Dexamethasone significantly inhibited the cytokine-induced IL-6 protein release in PTC, but not in DTC. CONCLUSIONS: In this study we demonstrated for the first time an inhibitory effect of MPA on the stimulated IL-6 expression of renal tubular epithelial cells. In contrast to older data, which showed a synergistic upregulation of the expression of a CC-chemokine by a combination of cytokines and MPA, in the present study we could demonstrate an immunosuppressive effect of MPA on the expression of an important cytokine.     

慢性肾功能衰竭病人高同型半胱氨酸血症及其影响因素

目的 :研究慢性肾衰 (CRF)病人血浆同型半胱氨酸 (Hcy)水平及其影响因素。方法 :采用荧光偏振免疫分析法测定 16 0例CRF病人血浆总同型半胱氨酸 (tHcy)水平 ,同时用离子夺获分析法和微离子酶免疫分析法分别检测血浆叶酸(FA)和维生素B12 (VB12 )浓度。结果 :CRF病人血浆tHcy水平 (2 2 6 9± 12 16 ) μmol/ )明显高于正常对照组 (7 97±2 6 5 ) μmol/L ,CRF病人高同型半胱氨酸血症的发生率为 82 5 0 % ,其中血液透析组血浆tHcy水平 (2 4 13± 12 6 8μmol/L ,n =73)明显高于持续性非卧床腹膜透析 (CAPD)组 (16 4 3± 5 5 8μmol/L ,n =19)和非透析治疗组 (19 79± 10 5 7)μmol/L ,(n =6 8) ,但血浆FA和VB12 与正常对照组均无明显差别 (P >0 0 5 )。CRF病人血浆tHcy水平与血浆FA浓度均呈负相关关系 ,未经透析的CRF病人血浆tHcy水平与内生肌酐清除率和血浆FA水平呈负相关 ;透析治疗组血浆tHcy水平与血浆FA浓度呈负相关。血透 4h使血浆tHcy下降约 4 0 0 % ,透析后 2 0h回复到透析前水平的 76 0 %～86 0 % ,但在采用血仿膜和聚砜膜透析的病人之间 ,血浆tHcy水平无明显差异。结论 :CRF病人普遍存在高同型半胱氨酸血症 ,但没有明显的FA和VB12 缺乏 ,CRF时肾脏损害削弱了对Hcy的代谢或清除能力 ,