采用RITQ综合评定婴儿气质的报告

采用Ｃａｒｅｙ的ＲＩＴＱ为４－８个月婴儿气质的测查工具，结合专人问卷与观察，对４００名婴儿的气质进行了综合评定，结果表明：九个气质因子的重测信度为０．７７－０．９０，多数气质因子间存在着显著的相关，相关系数为０．１０－０．５９。大、小婴儿活动水平、接近－退缩、适应及反应强度四个气质因子存在差异。气质类型与国外同龄婴儿及国内学前儿童的分布相接近。提示采用ＲＩＴＱ综合评定婴儿气质的信度和效度较好，可用于我国婴儿的气质测查及研究。     

围术期焦虑及干预

本文以自评、医师评定两种方式对腹部手术患者１０３例（除外精神科病史）进行围术期焦虑及干预的描述性研究。发现术前明显焦虑者占３０％，疑有焦虑者占３４％，无焦虑者占３６％。特质焦虑直接影响术前状态焦虑，疾病、手术因素影响术后焦虑，此时特质焦虑仍起作用。支持性心理治疗能降低术前焦虑，提高无并发症者满意程度，但对躯体预后无直接影响。另外，腹部手术患者入院时血皮质醇浓度高于正常人群。     

Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics,distribution, protection

Background and purpose:

Limited data on the brain penetration of potential stroke treatments have been cited as a major weakness contributing to numerous failed clinical trials. Thus, we tested whether interleukin-1 receptor antagonist (IL-1RA), established as a potent inhibitor of brain injury in animals and currently in clinical development, reaches the brain via a clinically relevant administration route, in experimental stroke.

Experimental approach:

Male, Sprague-Dawley rats [either naïve or exposed to middle cerebral artery occlusion (MCAo)] were given a single s.c. dose of IL-1RA (100 mg·kg⁻¹). The pharmacokinetic profile of IL-1RA was assessed in plasma and CSF up to 24 h post-administration. Brain tissue distribution of administered IL-1RA was assessed using immunohistochemistry. In a separate experiment, the neuroprotective effect of the single s.c. dose of IL-1RA in MCAo was assessed versus a placebo control group.

Key results:

A single s.c. dose of IL-1RA reduced damage caused by MCAo by 33%. This dose resulted in sustained, high concentrations in plasma and CSF, penetrated brain tissue exclusively in areas of blood–brain barrier breakdown and co-localized with morphologically viable neurones. CSF concentrations did not reflect massive parenchymal infiltration of IL-1RA in MCAo animals compared to naïve.

Conclusions and implications:

These data are the first to show that a potential treatment for stroke, IL-1RA, rapidly reaches salvageable brain tissue via an administration route that is clinically relevant. This allows confidence that IL-1RA, as a candidate for further clinical development, is able to confer its protective actions both peripherally and centrally.     

Prostanoid receptor antagonists: development strategies and therapeutic applications

Background and purpose:

Histamine H₃ receptor antagonists are currently being evaluated in clinical trials for a number of central nervous system disorders including narcolepsy. These agents can increase wakefulness (W) in cats and rodents following acute administration, but their effects after repeat dosing have not been reported previously.

Experimental approach:

EEG and EMG recordings were used to investigate the effects of acute and repeat administration of the novel H₃ antagonist GSK189254 on the sleep–wake cycle in wild-type (Ox+/+) and orexin knockout (Ox−/−) mice, the latter being genetically susceptible to narcoleptic episodes. In addition, we investigated H₃ and H₁ receptor expression in this model using radioligand binding and autoradiography.

Key results:

In Ox+/+ and Ox−/− mice, acute administration of GSK189254 (3 and 10 mg·kg⁻¹ p.o.) increased W and decreased slow wave and paradoxical sleep to a similar degree to modafinil (64 mg·kg⁻¹), while it reduced narcoleptic episodes in Ox−/− mice. After twice daily dosing for 8 days, the effect of GSK189254 (10 mg·kg⁻¹) on W in both Ox+/+ and Ox−/− mice was significantly reduced, while the effect on narcoleptic episodes in Ox−/− mice was significantly increased. Binding studies revealed no significant differences in H₃ or H₁ receptor expression between Ox+/+ and Ox−/− mice.

Conclusions and implications:

These studies provide further evidence to support the potential use of H₃ antagonists in the treatment of narcolepsy and excessive daytime sleepiness. Moreover, the differential effects observed on W and narcoleptic episodes following repeat dosing could have important implications in clinical studies.     

NS11021, a novel opener of large-conductance Ca2+-activated K+ channels,enhances erectile responses in rats

Background and purpose:

Large-conductance Ca²⁺-activated K⁺ channels (BK_Ca), located on the arterial and corporal smooth muscle, are potential targets for treatment of erectile dysfunction (ED). This study investigated whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5-yl)-phenyl]-thiourea), a novel opener of BK_Ca channels, relaxes erectile tissue in vitro and enhances erectile responses in intact rats. The effects were compared with sildenafil, an inhibitor of phosphodiesterase type 5.

Experimental approach:

Patch clamp was used to record whole cell current in rat isolated corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs). Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from rats and men, and simultaneous measurements of intracellular Ca²⁺ concentration ([Ca²⁺]_i) and tension were performed in intracavernous arteries. Erectile response was measured in anaesthetized rats.

Key results:

In patch clamp recordings, NS11021 increased currents sensitive to the selective BK_Ca channel blocker, iberiotoxin (IbTX) in SMCs, but did not modulate K⁺ current in HUVECs. NS11021 reduced [Ca²⁺]_i and tension in penile arteries. IbTX inhibited the vasorelaxation induced by NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not vehicle increased erectile responses in anaesthetized rats, an effect which was abolished after pretreatment with tetraethylammonium.

Conclusions and implications:

NS11021 leads to relaxation of both intracavernous arteries and corpus cavernosum strips primarily through opening of BK_Ca channels. It is also effective in facilitating erectile responses in anaesthetized rats. These results suggest a potential for use of BK_Ca openers in the treatment of ED.     

Gastroprotective effect of the aqueous leaf extract of Guiera senegalensis in Albino rats

ObjectiveTo evaluate the effect of aqueous leaf extract of Guiera senegalensis (G. senegalensis) on gastric mucosal damage using different ulcer models.MethodsConsidering the above claims, the present study was undertaken to validate the gastroprotective potential of the aqueous leaf extract of this plant against ethanol, water immersion and Aspirin induced ulcer models.ResultsThe leaf extract (50, 100 and 200 mg/kg, p.o.) significantly (P<0.05) decreased the ulcer index in all assays used.ConclusionsThe results obtained, provide strong evidence of antiulcer activity of the leaf extract of G. senegalensis and support the traditional uses of the plant for the treatment of ulcer.     

造血微环境决定脐血造血干/祖细胞的早期分裂行为

目的 在特定生长因子的培养体系中，观察模拟造血微环境及粘附因素对人类脐血造血干/祖细胞早期分裂行为影响。方法 （1）应用流式细胞仪（FACS）分选CD34^ CD38^-细胞；（2）细胞培养体系中应用干细胞支持性基质AFT024及单一粘附因素纤维结合素（Fn)。并观察其对细胞早期分裂行为的影响。结果 （1）在联合生长因子的条件下，人类脐血CD34^ CD38^-细胞早期分裂呈现固定比例的静止，慢分裂，快分裂以及不对称分裂状态；（2）未观察到单一粘附因子Fn对其早期分裂行为的影响；（3）干细胞支持性基质AFT024所模拟的体外造血微环境可促使脐血造血干/祖细胞广泛增殖并更多地进行不对称分裂。结论 （1）CD34^ CD38^-细胞群体具有异质性。由具有不同增殖行为的亚群组成，在体外培养早期存在不对称分裂；（2）体外模拟的骨髓微环境AFT024基质滋养层较细胞因子及单一粘附因素能够更好地支持造血干/祖细胞的增殖并保持其自我更新的特性。     

Effects of interleukin-2 on gene expression in human neutrophils

Recently, the interleukin-2 receptor (IL-2R) was shown to be present on human neutrophils, and IL-2-neutrophil interactions are believed to be important in both tumor rejection and increased susceptibility to bacterial infections. Furthermore, neutrophils have been shown to synthesize host defense proteins, such as cytokines. In this study, we analyzed the effects of IL-2 on the induction of de novo RNA and protein synthesis in this cell type. When cells were stimulated with IL- 2 alone, the level of incorporation of either [5-3H]-uridine or [35S]- methionine and [35S]-cysteine was similar to unstimulated cells. However, when cells were stimulated with the combination of a fixed concentration of granulocyte-macrophage colony-stimulating factor (GM- CSF), a dose-dependent effect of IL-2 was observed on the induction of both RNA and protein synthesis. In the presence of tumor necrosis factor-alpha or formyl-methionyl-leucyl-phenylalanine, however, IL-2 exerted no similar effect. Furthermore, the study of a large number of normal subjects (n = 55) showed reproducible categories of responders (low, intermediate, and high). The binding of IL-2 to the IL-2R complex on human neutrophils increased on GM-CSF-stimulated neutrophils compared with unstimulated cells. However, no increase in the level of expression of either the alpha or beta chains of this receptor complex was observed. This finding suggests that GM-CSF functionally activates the IL-2R, but does not regulate its level of expression. Finally, we found that human neutrophils constitutively express IL-2R gamma chain mRNA and thus have the potential to express the functional IL-2R complex. Our findings on IL-2-neutrophil interactions should lead to new avenues of research in understanding the responses of patients undergoing GM-CSF or IL-2 therapy.