High resolution real-time B-mode echotomography in the diagnosis of extracranial carotid lesions. Comparison with traditional angiography

Summary Tumour growth essentially requires fibrin formation and fibrinopeptide A (FPA) is liberated into the circulation on fibrin formation. In the present study, a possible elevation of serum FPA level was examined in patients with metastatic brain tumour. A significant elevation of serum FPA level was shown in all 6 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. It was extremely high in 2 patients with rapidly growing tumour. However, such a significant elevation was not shown in 3 cancer patients without brain metastasis or in 1 patient with a huge meningioma. This suggests the possibility that the presence of metastatic brain tumour could be detected by measuring FPA in blood drawn form the internal jugular vein. This also suggests the tendency that elevation of serum FPA is higher in patients with more rapidly growing tumour.Infusion of urokinase into the internal carotid artery resulted in an elevation of serum fibrinopeptide B (1)15–42 (FPB) in 5 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. This suggests that urokinase could induce fibrinolysis in the tumour tissue, though this remains in conclusive because of the lack of complete controls.     

Benzodiazepine ligands,nociception and ‘defeat’ analgesia in male mice

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5–30 mg/kg), midazolam (0.625–5 mg/kg), diazepam (0.5–4 mg/kg), Ro15-1788 (5–80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10–20 mg/kg) induced significant analgesia, an effect also observed with the -carboline derivatives FG7142 (5–20 mg/kg) and DMCM (1–2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tailflick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10–40 mg/kg) and by diazepam (0.5–2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5–20 mg/kg) nor midazolam (1.25–2.5 mg/kg) blocked defeat analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an inverse agonist-like manner at benzodiazepine sites.     

Prolongation of graft survival in allogeneic islet transplantation by (−) 15-deoxyspergualin in the rat

Summary The effect of 15-Deoxyspergualin, a novel drug which has been described to have anti-tumour activity, on allogeneic graft survival (Dark Agouti Lewis rats) after pancreatic islet transplantation was tested. A marked prolongation of graft survival could be shown using doses of 1.0, 2.5 and 5.0mg Deoxyspergualin/kg on day 0 until day +9 post transplantation. A maximum of 55.6 days (average) survival time was observed using 2.5mg/kg Deoxyspergualin compared to 5.2±0.6 days without immunosuppression. Using the chemiluminescence reaction of recipient monocytes after islet transplantation, a marked suppression of the monocyte system exceeding the treatment period could be observed. Since, in contrast to cyclosporin, B-cell toxicity could not be shown, the new drug seems to be a hopeful step towards successful allogeneic islet transplantation for treatment of diabetes.     

Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat

The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 g in 0.4 l) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 g in 0.5 l) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10^–5–10^–4 M in 0.2 l) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.     

On the convulsant action of Ro 5-4864 and the existence of a micromolar benzodiazepine binding site in rat brain

The benzodiazepine Ro 5-4864 (60 mg/kg) produced convulsions in mice that could be antagonised either by diazepam (2–4 mg/kg) or by Ro 15-1788 (10–20 mg/kg). In mice and rats subconvulsant doses of Ro 5-4864 were proconvulsant when combined with subconvulsant doses of picrotoxin or pentylenetetrazole. Ro 15-1788 antagonised the tonic convulsions triggered by the drug combinations when it was given at the same time as Ro 5-4864; this antagonism was not observed when the drugs were injected at different times. In contrast to a previous report, we could find no evidence that Ro 5-4864 antagonised seizures induced by electroshock. Using two different ligand-binding techniques, no evidence was seen for the existence in rat brain of the previously reported micromolar benzodiazepine receptor, a suggested site of action of Ro 5-4864.     

血清生长分化因子15水平与慢性淋巴细胞白血病发生风险的关联研究

目的 采用两样本孟德尔随机化研究方法探讨血清生长分化因子15(GDF15)水平与慢性淋巴细胞白血病(CLL)发生之间的关联。方法 基于欧洲人群血清GDF15和CLL的全基因组关联研究公开数据库,筛选与血清GDF15水平相关的遗传变异位点作为工具变量,采用逆方差加权法评估遗传学预测的血清GDF15浓度与CLL发生的关联,采用最大似然比法进行敏感性分析,采用MR-Egger回归探讨工具变量潜在多效性。结果 研究共纳入3个单核苷酸多态位点作为工具变量,逆方差加权法结果显示,血清GDF15水平与CLL发生风险之间存在负相关,GDF15浓度每升高一个标准差(SD),CLL发生风险降低33%(95%置信区间:2%～54%)(P=0.039)。敏感性分析得到了一致的结果。此外,MR-Egger回归未发现存在多效性。结论 本研究结果提示,在欧洲人群中,血清GDF15水平与CLL发生之间可能存在负相关,仍需大样本人群研究及体内外实验进一步阐明GDF15在CLL发生发展中的作用及其潜在生物学机制。     

Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity

Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.     

复发性口腔溃疡与血清TNF-α,TGF-β浓度关系的临床研究

目的 :研究复发性口腔溃疡与血清TNF α,TGF β浓度关系。方法 :选择复发性口腔溃疡患者 3 2例 ,采用ELISA检测其血清TNF α ,TGF β水平 ,并与正常成年人作对照。结果 :复发性口腔溃疡患者TNF α水平较正常组明显升高 (P <0 .0 1) ,TGF β水平与正常组相比 ,无显著统计学差异 (P >0 .0 5 )。结论 :复发性口腔溃疡的致病过程与细胞因子TNF α有关 ,与TGF β关系不密切     

p16、p15蛋白在小儿急性淋巴细胞白血病的表达及临床相关性研究

目的：探讨p16、p15蛋白在急性淋巴细胞白血病（ALL）发病中的意义。方法：对23例ALL细胞进行间接免疫荧光染色,用流式细胞仪检测细胞的荧光强度,间接反映p16、p15蛋白水平。结果：23例ALL患儿p16蛋白阴性10例,p15蛋白阴性8例,p16、p15蛋白均阴性6例。3例T－ALL中p16、p15蛋白皆阴性2例,13例Non T-ALL中,p16蛋白阴性6例,p15蛋白阴性5例。高白细胞组的p16、p15蛋白表达阳性率低于非高白细胞组,差异有显著意义（P＜0．05）,HR－ALL组p16、p15蛋白阳性表达低于SR－ALL组,差异有显著意义（P＜0．05）。结论：p16、p15蛋白参与了部分急性淋巴细胞白血病的发病,p15、p15蛋白阴性的患者可能预后不良。