Synthesis of two biologically active fluorescent probes of thymopentin

This study reports on the synthesis of two fluorescent analogues of thymopentin (TP-5; Arg-Lys-Asp-Val-Tyr). A fluorescein isothiocyanate labeled analogue (FITC-TP-5) and a stilbene isothiocyanate labeled analogue (SITS-TP-5) were extensively purified by ion-exchange and gel filtration chromatography. Characterization of the coupling site through amino acid analysis, dansylation and N-terminal cleavage of the fluorescent amino acid yielded results which indicated that both were mono-labeled analogues derivatized at the N-terminal. These analogues were shown to be TP-5-like in nature by their ability to induce the expression of the Thy 1.2 surface marker on nude mouse prothymocytes in both in vivo and in vitro assays. In addition, these analogues were able to inhibit the specific binding of radiolabeled TP-5 to human lymphocytes. Initial studies describing the interaction of FITC-TP-5 with human lymphocytes are shown.     

肝细胞癌SCT表现和相关基因表达的初步研究

目的　探讨肝细胞癌细胞中nm2 3 H1基因和C erbB 2基因的表达和其与SCT表现的关系。方法　对 3 6例经手术病理证实且行螺旋CT动、静脉双期增强扫描的肝细胞癌病例 ,观察其SCT表现特征 ,如包膜、子灶、门静脉癌栓、肝门淋巴结转移、肿瘤的大小和强化特征。用免疫组织化学的方法检测癌组织中nm2 3 H1基因和C erbB 2基因的表达情况。结果　肝细胞癌细胞中 ,nm2 3 H1阳性 2 1例 ,阳性率为 5 8.3 % ,转移高危组 (子灶、门脉癌栓、肝门淋巴结转移 )nm2 3 H1基因的表达低于转移低危组 (P <0 .0 5 ) ;C erbB 2基因阳性 2 2例 ,阳性率为 71.1% ,C erbB 2基因的表达在中等大小肝癌组表达高于小肝癌组和大肝癌组 (P <0 .0 5 )。结论　肝细胞癌的SCT表现与nm2 3 H1和C erbB 2基因的表达有一定关系     

ASSOCIATION OF PLASMA HOMOCYSTEINE LEVEL AND N^5,N^10—METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM WITH CEREBRAL INFARCTION

OBJECTIVE: To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level. METHODS: The plasma Hcy level was measured by capillary electrophoresis-ultraviolet detection and the gene polymorphism of N5,N10-methylenetetrahydrofolate reductase (MTHFR) was studied with PCR-RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy control. RESULTS: The plasma Hcy level of the patients (19.3 +/- 6.0 micromol/L) was markedly higher than that of the controls (13.7 +/- 5.4 micromol/L) (t = 4.16, P < 0.001). There are 3 genotypes, C/C, C/T and T/T, about base-variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls. CONCLUSIONS: The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C-->T mutation at locus 677 of MTHFR gene.     

Synthesis of deramciclane* labeled with tritium in various positions

[(1R)‐endo]‐(+)‐3‐bromocamphor was dehalogenated with tritium gas to [3‐³H]camphor and via [3‐³H]phenylborneol converted to [3‐³H]deramciclane isolated as the fumarate salt (specific activity 51.8 GBq/mmol). This three step synthesis from [3‐³H]camphor gave an overall yield of 22%. Benzyloxy‐acetic acid methyl ester was reduced with sodium‐borotritide to 2‐benzyloxy‐ethanol‐[1‐³H], and through a four step procedure was converted to 2‐dimethylaminoethyl‐[2‐³H] chloride. The latter was condensed with the sodium derivative of 2‐phenylborneol giving rise to [2‐dimethylamino‐[2‐³H]ethoxy]deramciclane isolated as the fumarate (specific activity 8.177 GBq/mmol). This six step synthesis from [³H]NaBH₄ gave an overall yield of 6%. Copyright © 2005 John Wiley & Sons, Ltd.     

Pharmacokinetics, metabolism and renal excretion of sulfatroxazole and its 5-hydroxy- and N4-acetyl-metabolites in man

Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes.     

3-(3-吡啶基)-6-芳基-7H-1,2,4-三唑并[3,4-b][1,3,4]噻二嗪的合成与波谱表征

目的：研究分子中含吡啶基的有多个杂环的化合物系列的波谱表征，方法：由烟酸出发，经多步反应，制得有吡啶基的均三唑并噻二嗪化合物，并进行红外，核磁共振氢谱与碳谱测试。结果：得到原料，中间体和产物的红外光谱图，产物的核磁共振氢谱与碳谱图。结论：标题化合物红外光谱1600cm^-1处多有C＝N伸缩振动峰，1250cm^-左右有N－N＝C伸缩振动峰，700cm^-1有C－S－C弯曲振动峰；噻二嗪亚甲基氢的化学位移δ值约为4．46，吡啶基四个氢原子化学位移约为9．3、8．9、8．7、8．0，噻二嗪亚甲基碳化学位移为23。     

rhGM—CSF对小鼠口腔粘膜损伤的防治作用

目的：观察rhGM-CSF对TMX致实验性小鼠口腔粘膜损伤的疗效。方法：按随机分组原则将501只昆明种小白鼠分成8组，分别在相应时间给予不同药物（MTX，CF或rhGM-CSF）的处理因素，于第1－10天光镜下观察小鼠口腔粘膜的病理改变和积分情况。结果：IDMTX致口腔粘膜损伤病变率（45％－63％）和积分率（19．4％－56％）较其它组高，且死亡率很低（小于5％）；IDMTX＋GM0（或GM2）组的口腔粘膜损伤病变率（30．53％和30．99％）和积分率（19．47％和17．25％）比IDMTX组（55．56％和36．31％）明显减少，且溃疡严重程度较轻，二者相差显著（P＜0．01）。结论：IDMTX致小鼠口腔粘膜损伤模型可以用于粘膜损伤的研究；rhGM-CSF可以减少MTX致小鼠口腔粘膜损伤，并促进粘膜损伤恢复。     

De-novo expression of vascular ecto-5′-nucleotidase and down-regulation of glomerular ecto-ATPase in experimental chronic renal transplant failure

Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF.     

组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1.0 and 60.0% in 5-FC group, 0.5±0.8 and 13.3% in 5-FC thermotherapy group, with statistical difference among the 3 groups (F=25.898, χ2=5.208, 19.548, 5.168, P<0.05). The mean apoptotic indexes of tumor cells of the 3 groups were 4.6%, 9.9% and 17.4%, respectively. Vacuolar degeneration, cell necrosis, cytolysis and apoptotic bodies were mostly observed in the 5-FC thermotherapy group. The expression of CD gene in tumor tissue was detected in all the groups. Conclusion Tissue specific CD/5-FC thermotherapy has inhibitory effects on the hepatic metastasis of LoVo cells transfected with CD gene.     

Proton magnetic resonance spectroscopy in childhood brainstem lesions

Background Diagnosis of brainstem lesions in children based on magnetic resonance imaging alone is a challenging problem. Magnetic resonance spectroscopy (MRS) is a noninvasive technique for spatial characterization of biochemical markers in tissues and gives information regarding cell membrane proliferation, neuronal damage, and energy metabolism. Methods We measured the concentrations of biochemical markers in five children with brainstem lesions and evaluated their potential diagnostic significance. Images and spectra were acquired on a 1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g., choline), creatine, phosphocreatine, lactate, and lipids were measured within lesions located at the brainstem using Point-resolved spectroscopy sequences. Results Diagnosis based on localized proton spectroscopy included brainstem glioma, brainstem encephalitis, demyelination, dysmyelination secondary to neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In all but one patient, diagnosis was confirmed by biopsy or by clinical follow-up. Conclusions This small sample of patients suggests that MRS is important in the differential diagnosis between proliferative and nonproliferative lesions in patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have a rather misdiagnosis role.