Sequential psychological testing during the course of autoimmune hyperthyroidism

Summary Although the psychological disturbances accompanying Graves' disease are well known, the time required for normalisation of these disturbances during antithyroid drug treatment is not known. Therefore sequential psychological testing during the course of Graves' disease was done. There are also contradictory results concerning the possible correlation of neurophysiological and psychological test results during the course of Graves' disease with thyroid hormone values. Finally, psychological disturbances have been proposed as possible etiologic factors in Graves' disease.In our study, a significant decrease in anxiety and irritability could be observed at the time euthyroidism was achieved. Self-evaluations of depressivity, activity, exhaustion, well-being, extraversion, introversion, and the ability to concentrate changed 1 or 2 months after euthyroidism was induced. Similar test results could be observed after induction of euthyroidism by antithyroid drugs and subtotal thyroid resection. Therefore the mode of therapy does not seem to influence the course of normalisation of psychological parameters.In contrast to other investigations there was hardly any correlation between thyroid hormone values and psychological test results or the ability to concentrate. Nontheless, patients with Graves' disease showing high scores for depression and anxiety exhibit abnormal peripheral helper/suppressor T-lymphocyte relations. Furthermore, patients suffering from Graves' disease tend to be more anxious than controls. It remains to be determined whether an increased susceptibility to psychological disturbances has led to these alterations of lymphocyte subsets in Graves' disease patients with severe depression and anxiety.Supported by SFB 258     

Effect of terbutaline and bambuterol on immediate-type allergic skin responses and mediator release in human skin

Background: Beta-2 agonists are potent inhibitors of mast cell degranulation in vitro. Intradermally injected they also inhibit mast cell activation in human skin in vivo. To what extent orally administered ₂-agonists inhibit mast cell degranulation and allergic skin responses in vivo in daily recommended doses remains unclear.Purpose: The main purpose was to study the effects of oral administered terbutaline and bambuterol on allergen- and codeine-induced histamine release and skin responses in intact human skin in vivo. In addition, control studies were carried out with intradermally injected terbutaline.Methods: Ten allergic subjects were randomized to receive bambuterol (10 mg tablets twice daily), terbutaline (7.5 mg controlled release tablets twice daily) and corresponding placebo for 5 days with a washout phase of 3 days between treatments in a double-blind, double-dummy, cross-over trial. The patients were studied at the fifth day of each regimen, i.e. at day 5, 13, and 21. Allergen- and codeine-induced histamine release was measured by microdialysis technique. Wheal and flare reactions to allergen, codeine, and histamine were measured planimetrically. Measurements were performed in the morning on day 5 on each regimen before medication and for additional 5 h after administration of the morning dose. In a separate series of experiments in another 10 allergic patients, 1–1,000 nM (0.05–50 pmoles) of terbutaline was injected intradermally for measurement of histamine release, prostaglandin D2 (PGD2) synthesis and skin responses.Results: Neither orally administered terbutaline nor bambuterol significantly reduced allergen- or codeine-induced histamine release. Flare reactions to allergen, codeine and histamine remained unaffected which was also the case for the majority of the wheal reactions. In comparison, intradermally injected terbutaline significantly reduced allergen-induced histamine release, PGD₂ synthesis, and skin reactions. Codeine-induced histamine release remained unaffected. Terbutaline significantly reduced flare reactions to codeine and histamine with no effect on wheal reactions.Conclusions: Terbutaline, in micromolar concentrations, was a potent inhibitor of immediate allergic skin reactions primarily due to inhibition of mast cell degranulation. However orally administered terbutaline, as the active drug itself or released from its pro-drug bambuterol, did not inhibit mast cell activation or allergic skin responses. Received 28 January 2003; returned for revision 7 March 2003; accepted by M. Parnham 29 April 2003     

Use of the iso-inertial force mass relationship in the prediction of dynamic human performance

The purpose of this investigation was to develop a new test of muscle function, termed the isoinertial force-mass relationship, and to determine its relationship to dynamic physical performance in comparison to an isometric test. A group of 13 trained subjects performed an isometric, and a series of iso-inertial maximal upper body tests, in a bench press movement at loads of 30%, 60%, 100% (concentric) and 100%, 130% and 150% (eccentric) of maximum. Vertical forces exerted throughout the movement were recorded by a force plate. In addition, the subjects performed the following three performance tests: a maximal bench press, a seated shotput, and two drop bench-press throws from a height of 0.25 m, with loads of 10 kg and 30% of maximum. Correlation analysis demonstrated that in each instance the iso-inertial force mass tests were the best predictors of performance (r=0.78–0.88) with both contraction type and mass specific effects apparent. Maximal isometric force and rate of force development were significantly related to some performance variables (r=0.22–0.78). However, for all the performance movements assessed, the iso-inertial test modality recorded the highest relationship to performance. The difference in the relationship between performance and iso-inertial and isometric test modalities was particularly evident in the light load dynamic performance of the seated shotput (r=0.86 vsr=0.38, respectively). These results are explained in part by the neural and mechanical differences between iso-inertial and isometric muscle actions and their respective specificity to dynamic physical performance.     

Interaction of nanobacteria with cultured mammalian cells

Nanobacteria were recently isolated from human blood and commercial fetal bovine serum (FBS) and were located in the -2 subgroup of proteobacteria based upon their 16S rRNA gene sequence. They can be cultured even in the absence of mammalian cells, and have extraordinary properties, like very slow growth rate and an impermeable cell wall, making their detection difficult by standard microbiological techniques. Since they are present in FBS, and thus in cell cultures, it is essential to clarify their effects on cultured mammalian cells. In this study, we show that four out of six nanobacterial isolates from different sera exerted a cytotoxic effect on 3T6 fibroblasts verified by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] viability assay, lactate dehygrogenase (LDH) release and by direct microscopy. The cytotoxic effect of nanobacteria was attenuated after they had been subcultured several times. The cytotoxic effect was similar with all tested murine and human fibroblastoid cell lines. Differential interference contrast and electron microscopy, and FITC staining with specific monoclonal antibodies indicated selective, possibly receptor-mediated adherence, followed by internalization and cytotoxicity in the 3T6 fibroblasts used as a model in these interaction studies. Thus, nanobacteria have a special way of invading mammalian cells: they trigger cells that are not normally phagocytic to engulf them. These organisms seem to be an important cause for cell vacuolization, poor thriving and unexpected cell lysis, problems frequently encountered in mammalian cell culture.     

Nano-C60 cytotoxicity is due to lipid peroxidation

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C₆₀, a fullerene aggregate that readily forms when pristine C₆₀ is added to water. Nano-C₆₀ was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses 50 ppb (LC₅₀=2–50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C₆₀ colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C₆₀ inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C₆₀ was completely prevented.     

Combined skin prick and patch testing enhances identification of peanut-allergic patients with atopic dermatitis

BACKGROUND: Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far. METHODS: APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts. RESULTS: Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age. CONCLUSIONS: Our data suggest that APTs with peanuts may represent a useful integration to standard testing modalities employed for the diagnosis of peanut allergy in AD patients.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

双特异性抗体对LAK细胞增殖和细胞毒作用影响的体外研究

将抗ＣＤ３与抗ＨＢｓ的单克隆抗体经化学偶联得到双特异性抗体，观察该双特异性抗体对ＬＡＫ细胞增殖和增强细胞毒性的作用。结果显示双特异性抗体显著提高ＬＡＫ细胞与２．２．１５细胞结合率；促进淋巴细胞增殖。１２５Ｉ－ＵｄＲ释放试验检测发现双特异性抗体增强ＬＡＫ细胞对２．２．１５细胞的细胞毒性且与抗体浓度呈正相关。进一步对抗体的特异性研究表明，加入双特异性抗体后ＬＡＫ细胞对２．２．１５细胞毒性作用显著高于对照组。     

GKT原理的模拟犯罪测试范式实验研究

目的:本实验旨在以实际犯罪较接近的实验场景验证GKT的测谎机制,并探讨其对罪犯以及其他嫌疑人的判定有效性。方法:以72名健康大学生为被试,让被试在模拟犯罪的背景下采用三种包含不同说谎和认知成分的回答方式进行测谎测试,采用Limestone测谎仪测量被试皮肤电反应。结果:回答方式与角色两因子在判定分数上的主效应均显著,交互作用不显著。结论:在模拟犯罪测试范式下,GKT模式中认知与说谎机制是共存的,其中认知成分不占主要地位,说谎成分占主要地位,GKT模式无法兼顾有效地判定"犯罪"和"知情无辜"角色,需进一步改进。     

Gentamicin susceptibility in Escherichia coli related to the genetic background: problems with breakpoints

In total, 120 Escherichia coli isolates positive for one of the gentamicin resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2')-I were tested for gentamicin susceptibility by the agar dilution method. Isolates positive for aac(3)-IV or ant(2')-I had an MIC distribution of 8-64 mg/L, whereas isolates positive for aac(3)-II had MICs of 32 to >512 mg/L, suggesting a relationship between the distribution of MICs and the specific GEN(R) mechanism. The MIC distribution, regardless of the GEN(R) mechanism, was 8 - >512 mg/L, which supports the clinical breakpoint of MIC >4 mg/L suggested by EUCAST and questions the breakpoint recommended by the CLSI (> or =16 mg/L).