YC-1 potentiates the antiplatelet effect of hydrogen peroxide via sensitization of soluble guanylate cyclase.

In the present study, we showed that 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, could potentiate H2O2-induced inhibition of platelet aggregation and increase of platelet cGMP levels. The synergistic effect of YC-1 and H2O2 on platelet aggregation and increases of cGMP were almost completely prevented by catalase and a selective soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or partially attenuated by the hydroxyl radical scavenger mannitol. In contrast, superoxide dismutase failed to influence H2O2/YC-1-induced inhibition of aggregation. Furthermore, YC-1 could enhance the activation of soluble guanylate cyclase caused by FeSO4/H2O2 and, this effect was prevented markedly by mannitol. These results suggest that YC-1 may enhance the antiaggregatory effect of H2O2 via the sensitization of platelet soluble guanylate cyclase. In addition, this phenomenon is, at least in part, dependent on H2O2-derived hydroxyl radical.     

Aggregation inhibitory activity of minor acetophenones from Paeonia species

Two minor acetophenones, 2,5-dihydroxy-4-methoxy-acetophenone (2) and 2,5-dihydroxy-4-methylacetophenone (7) from Paeonia species were found to selectively inhibit the aggregation of rabbit platelets induced by arachidonic acid. They were more potent than the major compound, paeonol (1), and 7 also inhibited the formation of TXA2 and PGD2 from arachidonic acid.     

Production of ginkgolides and bilobalide by Ginkgo biloba plants and tissue cultures

The accumulation of the terpenes ginkgolides and bilobalide in Ginkgo biloba was reported in plants as well as in plant cell cultures. Several hundred plants cultivated under controlled conditions in the field have been analyzed for their terpene production over many years. Cross-pollination experiments were performed with mature trees and the terpene content of the progeny was analyzed. The age of the tree is the main factor influencing the terpene content of the leaves as the level always decreases dramatically between young and old trees. 80 cell culture strains have been established and ginkgolides analyzed by GC/MS. These cell cultures reveal very low amounts of terpenes (1 microgram g-1 D.W. or less). On the contrary, isolated in vitro root cultures accumulate terpenes at the same concentration as the young plant leaves (4 mg g-1 D.W.). Attempts to obtain rapid growing roots or even hairy-roots did not succeed but the possibility to transform Ginkgo cell strains has been demonstrated.     

Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine

Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use. Received: 11 January 1999 / Final version: 25 March 1999     

Doppler sonographic detection of reverse twin-twin transfusion after intrauterine death of the donor

We report a "stuck" twin, in which a reverse blood shunt from the recipient to the donor was detected by Doppler sonography after death of the donor. This acute reverse transfusion caused intrauterine fetal distress and severe neonatal anemia of the surviving recipient. We believe that acute hemodynamic change after death of one fetus, in addition to causing a derangement in coagulation, causes immediate danger or subsequent organ damage for the surviving co-twin.     

Critical reassessment of second-look exploratory laparotomy for epithelial ovarian carcinoma. Minimal diagnostic and therapeutic value in patients with persistent cancer.

From 1979 to 1984, 88 women with epithelial ovarian cancer were treated with surgery and chemotherapy, achieved a clinical complete response, and then had "second-look" exploratory laparotomy to assess the pathologic status of their disease. Persistent cancer was found in 50 (57%) patients: 34 of 50 (68%) had gross tumor, which was larger than 2 cm in 12 (24%) and smaller than 2 cm in 22 (44%), and 16 (32%) had microscopic disease. Salvage therapy was as follows for these patients: whole abdominal irradiation, 29 (58%); chemotherapy, 17 (34%); intraperitoneal chromic phosphate, 1 (2%); and no further therapy, 3 (6%). With a follow-up time of 4 to 8 years, 7 (14%) patients are alive without evidence of cancer, 7 (14%) are alive with disease, 35 (70%) are dead of disease, and 1 (2%) has died of treatment complications. At 5 years, the relapse-free rate was 18% and the survival rate was 25%. Seventy-two parameters of suspected prognostic significance and 64 potential sites of tumor involvement were correlated with survival in a univariate analysis. The factors favorably affecting survival included the following: lower grade; microscopic tumor versus gross disease at second-look laparotomy; removal of the uterus; removal of the omentum; pelvic and paraaortic lymph node biopsy; negative results of a right diaphragm biopsy; and radiation therapy at Stanford University Medical Center, Stanford, California. There was no survival advantage for whole abdomen irradiation compared with chemotherapy or for the patients who had their disease successfully debulked at second-look laparotomy. The above factors and others were evaluated by multivariate regression. The best model (P = 0.000004) for predicting survival included largest tumor mass (P = 0.0002), operative blood loss (P = 0.002), perioperative blood transfusion (P = 0.003), and grade (P = 0.004). The detection of persistent ovarian cancer by second-look exploratory laparotomy should identify a subgroup of patients whose conditions can be salvaged by a second-line therapy. Unfortunately, that subgroup is small (8%) and an effective salvage therapy remains to be identified.     

Treatment of glomerulonephritis in the elderly

With the increasing use of renal biopsy in the elderly, glomerulonephritis is now known to be a common finding. Whereas membranous glomerulonephritis and minimal change disease are common in younger and older adults, primary amyloidosis and crescentic glomerulonephritis are more common in the elderly. Other glomerulonephritides such as focal segmental glomerulosclerosis or IgA nephropathy are very uncommon in the elderly. Because of the serious consequences of the nephrotic syndrome and acute and chronic renal failure in the elderly, aggressive treatment with immunosuppression should not be withheld. Caution should always be taken because of the presumed greater morbidity and mortality from such treatment in the elderly.     

高强度体外聚焦超声热疗治疗局部晚期胰腺癌的多中心临床研究

目的：探讨临床单用HIFU治疗局部晚期胰腺癌(local advanced pancreatic carcinoma，APC)的可能性。方法：4个中心共41例患者入选进行非随机病例对照研究，其中HIFU组24例，单用HIFU治疗；对照组17例，接受HIFU及吉西他滨综合治疗。比较两组的疗效、治疗费用及安全性，采用Cox回归分析进一步确定吉西他滨化疗对生存期的影响。结果：HIFU组临床受益率、平均生存期与对照组相似，分别为66．7％比76．5％(P=10．740)和141．5天比176．5天(P=0．3510)；而治疗费用较低，为20500元比51805元(P=0．000)；安全性更高。Cox回归分析显示仅体力状态、HIFU次数及临床受益进入方程(P=0．000)，化疗对生存期无影响。结论：单用HIFU治疗APC，其疗效等同于HIFU和吉西他滨的综合治疗，但较综合治疗经济、安全。推测可以单独应用HIFU治疗局部晚期胰腺癌．值得临床进一步验证。     

青岛地区消化性溃疡1963例胃镜分析

目的　了解青岛地区消化性溃疡的发病学特点。方法　分析 1996年～ 2 0 0 3年间我院经胃镜检查诊断为消化性溃疡的病例。结果　在 13478例行胃镜检查患者中检出消化性溃疡 196 3例 (14 5 6 % ) ,其中十二指肠溃疡 135 2例(6 8 87% ) ,胃溃疡 5 5 7例 (2 8 38% ) ,复合性溃疡 5 4例 (2 75 % ) ;溃疡患者男性 15 34例 ,女性 4 2 9例 ,男女之比为 3 5 8∶1。十二指肠溃疡好发年龄段为 2 0～ 4 0岁 ,平均年龄 39 7岁 ,胃溃疡好发年龄段为 4 0～ 6 0岁 ,平均年龄 4 7 2岁。消化性溃疡检出率较高的月份为 12月和 3月。结论　十二指肠溃疡发病率高于胃溃疡。溃疡发病男性明显高于女性 ,且好发于天气寒冷和气温易变的季节     

榼藤子水溶性提取物的体外抗肿瘤作用

目的观察榼藤子水溶性提取物对3种不同肿瘤细胞株的抑制作用。方法采用噻唑蓝染色法(MTT法),肿瘤细胞株选用人类慢性髓性白血病细胞株(K562)、人类淋巴瘤细胞株(U937)和人早幼粒白血病细胞株(HL60),检测A值,计算抑瘤率。结果榼藤子水溶性提取物对K562、U937、HL60有较强的抑制作用,且呈一定的浓度依赖性,半数生长抑制剂量(IC50)均<20μg·ml-1。结论榼藤子水溶性提取物体外实验具有显著的抗肿瘤活性。