可逆性胆碱酯酶抑制剂的研究:2-氧化-1,3,2-二氧磷杂环己烷类化合物的合成

本文报道2-氧化-1,3,2-二氧磷杂环己烷类衍生物的合成,希望寻找效果较好的可逆性胆碱酯酶抑制剂。初步药理实验证明,所合成的大部分化合物具有一定的抑制乙酰胆碱酯酶的作用,且毒性较低。通过对中间体Ⅱ进行质谱分析,发现该类化合物中大部分存在M-57碎片离子峰,利用高分辨质谱和亚稳离子测定,确定了该碎片离子的生成过程。     

乏氧诱导因子-1α在非小细胞肺癌中的表达研究

Objective: To explore the expression level and its clinical significance of hypoxia inducible factor 1α (HIF-1α) in non-small lung cancer. Methods: The expression of HIF-1α was detected in 68 human non-small lung cancer samples by immunohistochemistry. Results: (1) Thirty-nine (57.35%) out of the 68 human non-small lung cancer samples was positive for HIF-1α; (2) The positive rate of HIF-1α in adenocarcinoma and squamous carcinoma was 54.76% (23/42) and 61.54% (16/26) respectively. No significant difference was found between adenocarcinoma and squamous carcinoma of non-small lung cancer in the expression of HIF-1α (P>0.05). The positive rate of HIF-1α in middle-high differentiation was 74.28% (26/35), significantly higher than in low differentiation (39.39%, 13/33) (P<0.05); (3) The positive expression of HIF-1α was not correlated to the sexes, ages, tumor stage and lymph node status. Conclusion: The expression of HIF-1α is higher in non-small lung cancer and is correlated to differentiation.     

Analysis of a decreased Na+ conductance by tumor necrosis factor in identified neurons of Aplysia kurodai.

The ionic mechanisms of the effect of extracellularly ejected recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on the membrane of identified neurons R9 and R10 of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion substitution techniques. Micropressure-ejected rhTNF caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at it resting potential level (-60 mV) and reejecting rhTNF-alpha with the same dose produced a slow outward current [Io (TNF)] associated with a decrease in input membrane conductance. Io (TNF) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of Io (TNF) was approximately +10 mV. Ion substitution and pharmacological experiments suggest that Io (TNF) in identified neurons R9 and R10 of A. kurodai is due to a decreased Na+ conductance but not due to an activation of the Na(+)-K+ pump. Our results demonstrate that the immunomodulator TNF can act directly on the nervous system as well as on the immune system.     

Variability in hand surface representations in areas 3b and 1 in adult owl and squirrel monkeys

Detailed microelectrode maps of the hand representation were derived in cortical areas 3b and 1 from a series of normal adult owl and squirrel monkeys. While overlap relationships were maintained, and all maps were internally topographic, many map features varied significantly when examined in detail. Variable features of the hand representations among different monkeys included a) the overall shapes and sizes of hand surface representations; b) the actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces, which commonly varied severalfold in area 3b and manyfold in area 1; c) the topographic relationships among skin surface representations, with skin surfaces that were represented adjacently in some monkeys represented in locations many hundreds of microns apart in others; d) the internal orderliness of representations; e) the completeness of representations of the dorsal hand surfaces; and f) the skin surfaces represented along the borders of the hand representation. Owl monkey maps were, in general, internally more strictly topographic than squirrel monkey maps. In both species, area 3b was more strictly topographic and less variable than was area 1. The degree of individual variability revealed in these experiments is difficult to reconcile with the hypothesis that details of cortical maps are ontogenetically specified during a period in early life. Instead, we propose that differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands. This conclusion is consistent with earlier studies of the consequences of peripheral nerve transection and digital amputation, which revealed that cortical maps are dynamically maintained and are alterable as a function of use or nerve injury in these monkeys (Merzenich et al., '83a,b, '84a; Merzenich, '86; Jenkins et al., '84; Jenkins and Merzenich, '87).     

NJ-1型医用引流装置的设计与应用

我们自行设计ＮＪ - 1型医用引流装置 ,见图 1。1　产品引流装置结构本引流装置共分 3个部分 ,第 1部分为引流瓶体的上方连接管 ,长 6 0ｃｍ ,一端接瓶体上端 ,另一端接病人的导尿管 ,上方连接管有一个三通开关 ,目的供留取尿标本和膀胱冲洗。第 2部分为瓶体 ,总容量为 5 0 0ｍｌ,分粗细两段 ,细段容量 5 0ｍｌ,按正常人排尿 1～ 2ｍｌ/ (ｋｇ体重·ｈ)计算 ,能留取一个小的尿量 ,基本满足临床要求。第 3部分为瓶体下方连接管 ,安有一个二通开关 ,开关下的引流管可与 3Ｌ塑料袋或一般尿袋连接。本引流装置可根据临床需要定时放尿 ,避免传统…     

益肾化浊注射液对慢性肾功能衰竭大鼠残余肾中细胞因子含量的影响

通过观察益肾化浊注射液对5／6肾切除大鼠残余肾中细胞因子含量的影响，益肾化浊注射液延缓慢性肾功能衰竭（CRF）模型大鼠肾功能减退的作用机理。结果显示：益肾化浊注射液可以降低5／6肾切在鼠血清肌,尿素氮（P＜0．01），下调肾组织中白细胞介素－1（IL－1）（P＜0．05），白细胞介素－8（IL－8）（P＜0．05）及肿瘤坏死因子（TNF）（P＜0．05）的总体水平，说明益肾化浊注射液可以通过下调5／6肾切除大鼠残余肾中相关细胞因子含量，抑制促炎细胞因子对肾脏的损害，从而延缓CRF的进展。     

Heparin effect on ionised calcium concentration

The effect of heparin on plasma ionised calcium was studied by adding it in increasing amounts to whole blood from 10 normal subjects. There was no significant change in ionised calcium from the addition of 1 U/ml but a significant fall of 0.02 mmol/1 when 2 U/ml were added and a progressive further fall with increasing concentrations. Heparin from three different manufacturers produced similar results. The effect of heparinisation in vivo was studied during regular haemodialysis on 10 patients with chronic renal failure. Following intravenous injection of 10000 U of heparin there was a consistent and significant fall averaging 0.03 mmol/l.     

Effect of prostaglandin E1 on graft function of kidneys from living related donors

Prostaglandin E₁ (PGE₁) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 µg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE₁ (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 ± 12.8 ml/min compared with 40.3 ± 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-β-d -glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B₂ (TxB₂) in group A was higher than in group B, but not significantly (5.1 ± 3.0 ng/day and 2.8 ± 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE₁ improves graft function in kidneys from living related donors.     

Spermidine/Spermine N-Acetyltransferase, a New Biochemical Marker for Epithelial Proliferation in Rat Bladder

We examined the activity of spermidine/spermine N ¹-acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N -butyl- N -(4–hydroxybutyI)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis.     

Testicular amplificaion and impaired transmission of human butyrylcholinesterase cDNA in transgenic mice

Gene amplification occurs frequently in tumour tissues yet is,in general, non-inheritable. To study the molecular mechanismsconferring this restraint, we created transgenic mice carryinga human butyrylcholinesterase (BCHE) coding sequence, previouslyfound to be amplified in a father and son. Blot hybridizationof tail DNA samples revealed somatic transgene amplificationswith variable restriction patterns and intensities, suggestingthe occurrence of independent amplification events, in 31% (11/35)of mice from the FII generation but in only 3.5% (2/58) of theFII and FIV generations. In contrast, >10-fold amplificationsof the BCHE transgene and the endogenous acetylcholinesteraseand c-raf genes appeared in both testis and epididymis DNA from>80% of FIII mice. Drastic, selective reductions in testisBCHEmRNA but not in actin mRNA were detected by the PCR amplificationof testis cDNA from the transgenic mice, and apparently resultedin the limited transmission of amplified genes. The testicularamplification of the BCHE transgene may potentially representa general phenomenon with clinical implications in human infertility.