丙帕锗的制备及分析

目的 探索合成条件，制备体内活性和稳定性好的高聚物丙帕锗．并分析其结构确定目的物的正确性。方法 以GeO2为起始原料，磷酸二氢钠为还原剂,制备3-氧锗丙烯酸低分子量聚合物和高分子量3-氧锗丙烯酸(丙帕锗)，并进行元素、红外光谱、核磁共振和X-射线的分析。结果 高分子量聚合物生成，在320℃以下不分解，终产率为72．9％。结论 所采用的方法可行，合成的产品结构正确。     

Time-dependent changes in sensitivity to apomorphine and monoamine receptors following withdrawal from continuous cocaine administration in rats

The effects of withdrawal from continuous administration of cocaine on behavioral sensitivity to apomorphine and monoamine receptor density were examined in rats. Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine hydrochloride were implanted for 2 weeks. Apomorphine-induced stereotypy (0.5 mg/kg, SC) was examined in separate groups of rats either 4 hr or 7, 28, or 60 days after removal of the minipumps. Transient enhanced sensitivity to apomorphine-induced stereotypy occurred during the course of withdrawal. Animals withdrawn from cocaine for 4 hours did not differ from controls in their sensitivity to apomorphine, whereas animals withdrawn from cocaine for 7 days exhibited an increase in apomorphine-induced oral stereotypy relative to controls. However, the enhanced stereotypy response was no longer evident in animals withdrawn for 28–60 days. The animals were sacrificed after behavioral testing, and their brains were assayed for changes in monoamine receptor density in the frontal cortex, caudate-putamen, and nucleus accumbens. The density of ³H-SCH-23390-labeled D1 receptors was altered in all three regions examined in a time-dependent manner that paralleled the changes in behavioral sensitivity to apomorphine. There was a transient decrease in D1 receptor density that was evident by 7 days following withdrawal from continuous cocaine administration and was no longer evident 28 or 60 days posttreatment. There were no changes in ³H-spiroperidol-labeled D2 receptors, ¹²⁵-pindolol-labeled β-adrenergic receptors, or ³H-ketanserin-labeled 5-HT₂ receptors in any of the regions examined at both 4 hr and 7 days after termination of the cocaine infusion. These findings are discussed in terms of their relevance to developing pharmacologic treatments for withdrawal from cocaine. © 1994 Wiley-Liss, Inc.     

Therapeutic effects of liposomal adriamycin in combination with tumor necrosis factor-alpha.

Liposomes as drug carriers in cancer chemotherapy have attracted considerable interest. To enhance the therapeutic effect of Adriamycin entrapped in liposomes (Lip-ADM) on human solid tumors, we investigated the therapeutic effects of Lip-ADM in combination with recombinant human tumor necrosis factor-alpha (rTNF-alpha), which is known to have specific effects on tumor vasculature. rTNF-alpha or saline solution was injected intravenously into nude mice bearing a human colon cancer strain, HC-1, at 1 hour before intravenous administration of Lip-ADM. The significant therapeutic effect of Lip-ADM in combination with rTNF-alpha was demonstrated by the evaluation with tumor growth curve and the actual tumor weights, in comparison with groups of mice treated with saline solution, rTNF-alpha alone, or with a Lip-ADM after saline. Levels of Adriamycin in tumor tissue in the Lip-ADM in combination with rTNF-alpha-treated group were higher than those in Lip-ADM with saline solution-treated group.     

重组2型腺相关病毒-转化生长因子β3对实验性肝纤维化大鼠肝脏组织病理学和Ⅰ型胶原表达的影响

Objective To investgate the effects of TGF β 3 on rat hepatic fibrosis. Methods The TGF β 3 cDNA was cloned into rAAV2 vector. Rats were randomly divided into four groups: normal control group, model group, negative control group and TGF β 3 group. Hepatic fibrosis was induced by hypodermic injection of 40% CCI4. Recombinant AAV2-TGF β 3 viral particles were injected via the vena caudalis one week before CCh treatment. Rats were executed 8 weeks after CCI4 treatment, global histological change was observed after HE staining, the distribution of the collagen fibers was observed after masson staining, his-tochemistry was done to observe the expression of collagen Ⅰ; The positive area rate of the collagen fibers and the average optical rate of collagen Ⅰ were quantified. Results HE staining indicated that collagen fibers were reduced in the TGF β 3 group. Masson staining shown that the collagen fibers were distributed around the blood vessel, in the portal area and disse space. Compared to the model group (13.2%±2.2%) and negative control group (12.3%±1.5%), the collagen fibers in liver tissues of TGF β3 group (7.7% ± 1.5%) were significantly decreased (q = 9.456, P < 0.01; q = 8.217, P < 0.01). Histochemistry indicated that the collagen fibers of liver tissues of TGF 15 3 group (0.185±0.033) were significantly higher than those in the model group (0.252±0.042) and the negative control group (0.230±0.029), (q = 6.228, P < 0.01; q = 4.346, P < 0.01). Conclusion TGF β 3 alleviates the damage to hepatic cell and the level offibrosis in CCI4 treated rats and inhibits the expression of collagen Ⅰ.     

Effects of immobilization stress on hippocampal monoamine release: Modification by mivazerol, a new α2-adrenoceptor agonist

Mivazerol is a new and selective α₂-adrenoceptor agonist which has demonstrated anti-ischemic effects, both in animals and in patients with myocardial ischemia. In the present study, mivazerol was evaluated for its ability to inhibit the release of catecholamines and serotonin (5-HT) in the hippocampus of freely moving rats, and also was compared to clonidine. In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed. Intravenous administration of mivazerol (8.0 μg/kg) had no effect on basal outflow of norepinephrine (NE), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC). In contrast, clonidine (8.5 μg/kg, i.v.) attenuated the basal release of DOPAC, which has been proposed to reflect NE biosynthesis, suggesting that clonidine has an inhibitory effect on NE synthesis. In addition, both mivazerol and clonidine decreased the spontaneous release of 5-HT, which provided further evidence that α₂-adrenoceptors in the hippocampus modulate 5-HT. Sixty-min immobilization stress significantly increased the release of NE (177 ± 28%), DA (209 ± 46%) and DOPAC (337 ± 72%). Mivazerol (2.5, 8.0 and 25 μg/kg, i.v.) completely prevented the immobilization stress-induced enhancement of NE, DA and DOPAC, which was equi-effective to clonidine at a dose of 8.5 gmg/kg, i.v. These findings demonstrate that mivazerol has a profound modulatory effect on stress-induced neurotransmitter release in the hippocampus, at dose levels reported to protect against myocardial ischemia.     

Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy

In order to investigate the validity of the hypothesis that acid-soluble peptides (ASP) in urinary excreta can be applied as an index of the protein catabolism of the whole body, we measured the urinary excretion of ASP in 46 normal children and in 18 children with Duchenne muscular dystrophy (DMD), in which continuous breakdown of skeletal muscle protein is presumed. The mean value of ASP in the children with DMD was significantly higher than that in normal controls. The concentration of ASP was correlated with that of 3-methylhistidine (3MH), which has been proposed as an index of muscle breakdown. This finding indicates that urinary ASP reflects the catabolism of body proteins. No correlation was observed between the concentration of ASP and that of 1-methylhistidine (1MH), which is used as an objective index of meat and fish ingestion. After the administration of bestatin, an inhibitor of leucine aminopeptidase, for 9 months, the urinary ASP concentration of children with DMD increased markedly. This increase is thought to have been directly caused by the bestatin itself. Urinary ASP is therefore apparently a more conveniently applied index of protein catabolism than is urinary 3MH, which requires the application of several restrictions. However, it should not be applied when the effect of bestatin administration is evident.     

Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (beta 121----Gln) in a Batak Indonesian family

A Batak Indonesian from North Sumatra with hemoglobin (Hb) D Punjab (alpha 2 beta 2 121----Gln) and hemoglobin Constant Spring (Hb CoSp) is described. The 24-year-old man did not have clinical symptoms, and his hematological indices were normal. However, he had a persistent slight elevation of fetal hemoglobin level. His mother and his brother were heterozygous for Hb D Punjab; his father had Hb CoSp trait. A sister did not have any abnormal hemoglobin. To show the exact molecular defect leading to the synthesis of Hb CoSp in this family, genomic DNA from the father was analyzed by hybridization with synthetic oligonucleotides. Genomic DNA was digested with Sst I and Hind III producing a 1.05-kb fragment from the 3' end segment of the alpha 2-globin gene, including the termination codon. Two nonadecamers were synthesized to serve as probes: one, entirely homologous to the normal 3' end of alpha 2A-globin gene sequence, including the termination codon TAA, the other different from it by a replacement of the T in the termination codon TAA with C, changing it to CAA, the codon for the amino acid glutamine. DNA from normal controls gave a positive signal with the normal alpha 2TAA oligonucleotide probe but negative with the alpha 2 CAA probe. The father of propositus who had Hb CoSp trait gave a positive signal with the normal alpha 2TAA oligonucleotide probe as well as with the alpha 2CAA oligonucleotide probe, showing him to be heterozygous for the alpha 2CAA-globin gene. This result shows that the Hb CoSp in the Batak family is indeed due to a replacement of T by C in the TAA termination codon of the alpha 2-globin gene changing it to CAA the condon for glutamine. This explains the resulting readthrough of the untranslated sequence of the mRNA.     

Diffusion‐Weighted MRI in Creutzfeldt‐Jakob Disease: A Better Diagnostic Marker Than CSF Protein 14‐3‐3?

Two middle-aged patients presented with rapidly progressive dementia and ataxia, nonspecific electroencephalography findings, and negative cerebrospinal fluid (CSF) protein 14-3-3. Both patients underwent brain magnetic resonance imaging (MRI) scans that demonstrated abnormalities on diffusion-weighted imaging (DWI) sequences, and both were later confirmed to have Creutzfeldt-Jakob disease. (CJD) by tissue examination. Because a recent position paper from the American Academy of Neurology characterized CSF protein 14-3-3 as a gold standard for clinically diagnosing CJD, the authors reviewed studies of CJD in which DWI-MRI imaging and CSF protein 14-3-3 studies were both performed. Among 19 reported cases of CJD with DWI-MRI lesions, CSF protein 14-3-3 was negative in 6 cases and positive in 2 others. The authors' findings suggest that multifocal cortical and subcortical hyperintensities confined to gray matter regions in DWI-MRI may be a more useful noninvasive diagnostic marker for CJD than CSF protein 14-3-3. These observations provide a compelling rationale for a prospective comparative study.     

Effect of anti-interferon-γ and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse

SJL/J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA) developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-infeferonγ (IFN-γ) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-γ to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-γ. These findings support the notion that IL-2 is required for disease induction whereas IFN-γ plays a disease-limiting role early in the development of EAE.     

The 21-aminosteroid antioxidant, U74389F, prevents estradiol-induced depletion of hypothalamic β-endorphin in adult female rats

A single intramuscular injection of 2 mg estradiol valerate (EV) results in neuronal degeneration and β-endorphin depletion in the hypothalamic arcuate nucleus of adult female rats. We have hypothesized that peroxidase-positive astrocytes in this brain region oxidize estrogens and catecholestrogens to semiquinone radicals which mediate oxidative neuronal injury. In the present study, dietary administration of the potent antioxidant 21-aminosteroid, U-74389F, completely blocked EV-induced β-endorphin depletion in the hypothalami of adult female rats. Neither EV nor 21-aminosteroid treatment had any effect on hypothalamic concentrations of neuropeptide Y and Met-enkephalin, confirming that the estradiol lesion is fairly selective for the β-endorphin cell population. The present findings support the hypothesis that the toxic effect of estradiol on hypothalamic β-endorphin neurons is mediated by free radicals.