Application of median-effect in quantitative analysis of antitumor drugs in vitro

Objective: To analyze quantitatively the synergistic and antagonistic effects of combined oxymatrine (OMT) and 5-fluorouracil (5-GU) on a cell line of human liver cancer (HepG2) with median-effect principle in vitro. Methods: The median-effect principle and MTT method were used in the quantitative analysis of effects of the two drugs. Results: Cytotoxic activity of the individual drugs enhanced as drug concentration increased. As fa=0.41, a CI equal to 1 indicated additivity; fa<0.41, a CI less than 1 indicated synergy; and fa>0.41, a CI greater than 1 indicated antagonism. The sequence of administration did not influence the cytotoxic activity of the combined antitumor drugs. The ratio of drug concentration was a factor that can influence the killing effect. Conclusion: The combined drugs interaction (CI<1) was synergistic at lower concentration and antagonistic at higher concentration. The ratio of drug concentration is a factor that can influence the killing effect. Biography: HE Song(1965–), male, doctor of medicine, associate professor, Chongqing Medical University, majors in gastroenterology.     

Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale.A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery.It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825     

5-Hydroxytryptamine increases excitability of CA1 hippocampal pyramidal cells.

In the presence of spiperone to block the 5-HT1A-mediated inhibition of pyramidal cell activity, 5-hydroxytryptamine (serotonin, 5-HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippocampal slices were used to identify the ionic mechanism and to characterize the 5-HT receptor mediating this excitatory response to 5-HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1A hyperpolarization. Since spiperone also has high affinity for 5-HT2 receptors, any response mediated by 5-HT2 receptors would also be blocked. Bath perfusion of the slice with 5-HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) to initiate spike firing. The 5-HT2,1C-selective agonist DOI mimicked this effect of 5-HT, and the 5-HT2,1C antagonist ketanserin (1 microM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (sAHP) or the amplitude of evoked inhibitory postsynaptic potentials (IPSPs). The increase in rectification and EPSP amplitude by 5-HT occurred even in the presence of the 5-HT4-selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5-HT. We conclude that 5-HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5-HT1C receptor.     

Soluble CD14 but not interleukin-6 is a new marker for clinical activity in atopic dermatitis

Summary Levels of soluble IL-2 receptors, IL-6, soluble CD23, soluble CD14 and ECP (eosinophilic cationic protein) were measured as markers of T-cell, B-cell, monocyte and eosinophilic leucocyte activation in 26 patients with atopic dermatitis (AD) on admission to (A) and at discharge from (D) the Department of Dermatology in Zurich. The serum levels of sIL-2R, IL-6, sCD23, sCD14 and ECP were significantly elevated in AD patients in comparison with the normal values of healthy donors. A significant decrease in sIL-2R (p=0.0093) and in sCD14 (p=0.0134) levels was demonstrated between A and D, correlating with the improvement in the skin intensity score (SIS). In addition, a significant correlation of the sCD14 levels and the SIS at A was demonstrated (p=0.0415). These results also incriminate monocytes in the pathogenesis of AD, indicating that, besides sIL-2R and ECP, SCD14 could also be a possible marker for the disease activity.     

糖尿病肾脏胶原非酶糖化与氨基胍阿斯匹林的治疗作用

本实验系统观察了ＳＴＺ所致糖尿病鼠在１、３、６个月后肾脏组织胶原发生非酶糖化的情况，及氨基胍、阿斯匹林对肾脏胶原非酶糖化的阻断作用。结果表明：各病程糖尿病动物肾组织的胶原含量和非酶糖化早期产物（５－ＨＭＦ）及胶原相联荧光值均明显高于正常对照。氨基胍能够减弱糖尿病动物肾组织胶原含量的增加和荧光产物的生成，但对５－ＨＭＦ含量无影响。阿斯匹林未显示出对胶原非酶糖化的影响。     

Poor co-ordination in 5 year olds: A screening test for use in schools

A simple standardized screening test (South Australian Motor Co-ordination Screening Test, SAM Test) was developed to screen for poor co-ordination in 5 year olds; This SAM Test, which can be used by teachers, nurses and doctors, has explicit pass/fail criteria and has classified correctly 90% of children. The McCarthy Motor Scales, which are time consuming and limited to use by psychologists, were used to categorize 60 poorly co-ordinated and 60 normal children. The 120 children thus selected were tested on 19 items covering gross and fine motor skills. Statistical analysis to determine which items best discriminated between the two groups found the following five gross motor items to be most effective: one leg balancing, hopping, heel-toe walking on line, jumping Over ribbon and dropping ball and catching.     

Identification of human chorionic gonadotropin (HCG) secreting cells and other cell types using antibody to HCG and a new monoclonal antibody (mABlu-5) in cultures of human placental villi

Summary We have identified cells which secrete human chorionic gonadotropin (HCG) of cultures if first trimester placental villi. As a first step, we identified epithelial cells using a new monoclonal antibody. We then added HCG antibodies to the cultured cells. We found that syncytiotrophoblast (and not cytotrophoblast), Hofbauer cells and some mesenchymal cells stained with HCG antibodies.     

Kringle 5的真核植物细胞穿梭表达载体的构建

目的：构建含有目的基因kring5的真核植物细胞穿酸表达载体。方法：应用RT－PCR方法，从正常人肝脏组织中获得kringle5基因，测序后，再通过DNA重组技术，将kringle5基因片段克隆到真核植物细胞表达载体pBI121和pCAMBIA3301上。结果：得到的kringle5基因序列测定结果与文献相符，重组载体pB1k5和pC33k5经酶切鉴定正确，含有植物高效表达CaMV35S启动子。结论：重组载体pB1k5和pC33k5不仅可以在大肠杆菌中稳定复制，而且可以在植物细胞中表达。