Die Anwendung von humanisierten Anti-Immunoglobulin-E-Antikörpern

Omalizumab is a humanized monoclonal anti-IgE antibody developed for the treatment of allergic diseases. It has demonstrated good efficacy in patients with intermittent and persisting allergic rhinitis and in patients with moderate-to-severe allergic asthma. Omalizumab results in a marked lowering of free IgE in serum and down-regulation of IgE receptors on circulating basophils. In addition, it reduces the inflow of eosinophils into nasal and bronchial tissue and the number of IgE-positive mast cells in the bronchial mucosa. Omalizumab treatment has also been shown to be associated with down-regulation of IgE receptors on circulating dendritic cells, suggesting that blocking IgE may also inhibit chronic aspects of allergic inflammation involving T cell-activation. Patients’ clinical symptoms are attenuated and their quality of life improved by anti-IgE treatment with omalizumab; other medications effective in symptomatic treatment are therefore less necessary. Omalizumab’s broad spectrum of efficacy emphasizes the central role of IgE in the allergic-inflammatory cascade. Further areas of applications in ENT medicine could be anticipated in other IgE-related illnesses, such as allergic rhinitis, food allergies, laryingitis and chronic allergy-related rhinosinusitis.     

Insulin receptor substrate-1 is over-expressed in glycogenotic but not in amphophilic preneoplastic hepatic foci induced in rats by N-nitrosomorpholine and dehydroepiandrosterone.

Insulin receptor substrate-1 (IRS-1) is over-expressed in preneoplastic glycogenotic hepatic foci (GSF) and is gradually down-regulated during progression of these lesions, via mixed cell foci (MCF), to the basophilic neoplastic phenotype. The aim of the present study was to investigate the effect of dehydroepiandrosterone (DHEA), a weak hepatocarcinogen and tumour enhancer, on IRS-1 expression. Hepatocellular lesions were induced by N-nitrosomorpholine followed by DHEA. Under these conditions, many glycogen-poor amphophilic (APF) and intermediate cell foci (ICF) appear, in addition to GSF and MCF. IRS-1 was over-expressed in 215 out of 295 GSF, in 50 out of 53 MCF and in a glycogen-rich mixed cell adenoma. IRS-1 expression was not shown in 147 APF, 51 ICF and 5 amphophilic hepatocellular adenomas, and 3 out of 5 hepatocellular carcinomas showed a weak IRS-1 expression. The results suggest a close association of IRS-1 over-expression with the glycogenotic hepatocellular phenotype. The modulation and enhancement of tumour progression by DHEA is associated with a shift from glycogenosis to amphophilia and basophilia, and a down-regulation of IRS-1 expression.     

取样胶囊吸取胃液的模拟实验分析与研究

取样胶囊主要是吸取人体消化道内的消化液进行研究,本文以胃液为例,对取样胶囊吸取消化液进行探讨,分析在取样胶囊的研究中选取何种吸附材料最合适．首先对胃液成分进行分析,然后配置模拟胃液,选取六种不同吸附材料进行了吸附实验,并按实验结果绘制了不同的吸附曲线．由实验结果,对各种材料的吸附量、吸附稳定性和可靠性等进行了对比分析,同时还对取样机构模型设计的简单化因素进行分析．最后得出结论,认为德制胶棉在各个因素上都有明显的优势,适宜作为取样胶囊中的吸附材料．     

Lipid profiles in Polish adolescents from high- and low-risk families: tracking unfavourable lipid levels over a one-year period

In a country with a high cardiovascular mortality rate, lipid profiles were studied in 929 adolescents (440 from affected and 489 from non-affected families for cardiovascular disease and hypercholesterolaemia). In 334 children with elevated or borderline total cholesterol level, lipid profiles were re-measured after a 1-y period. In boys from affected families, in contrast to boys from non-affected families, significantly higher total cholesterol levels (4.36 +/- 0.81 vs 4.19 +/- 0.78 mmol/L, p < 0.05) and LDL-C level (2.1 +/- 0.72 vs 1.89 +/- 0.79 mmol/L, p < 0.05) and significantly lower HDL-cholesterol levels (1.81 +/- 0.34 vs 1.93 +/- 0.38 mmol/L, p < 0.05) were found. The odds ratio for being in the most unfavourable decile for LDL-cholesterol was significantly higher for girls from affected families (2.17, p = 0.02). A relatively high HDL-C level as well as a favourable TC/HDL-C ratio was demonstrated in all groups, being lowest in boys from affected families. A significant correlation was found between baseline lipids and their values re-measured after 1 y. It is concluded that (1) adolescents with a positive family history are at increased risk for unfavourable lipid profile, (2) adolescents with elevated total cholesterol and LDL-cholesterol levels remain hypercholesterolaemic after a 1-y period and are therefore candidates for further biochemical and clinical monitoring, and (3) children with elevated total cholesterol may not be at high risk for cardiovascular disease owing to the favourable TC/HDL-C ratio. The study results do not indicate that general cholesterol screening in Polish adolescents is necessary, as the proportion of children with elevated LDL-cholesterol is relatively low.     

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.     

Chronic treatment with antidepressants decreases the number of [3H]SCH 23390 binding sites in the rat striatum and limbic system

Binding of [3H]SCH 23390 to dopamine D-1 receptors and of [3H]spiperone to D-2 sites was measured in identical membrane preparations of the striatum and limbic system of rats treated chronically (twice daily, for two weeks) with antidepressants. Chronic administration of imipramine, amitriptyline, mianserin, citalopram, bupropion, iprindole and electroconvulsive shocks, but not benztropine or cyproheptadine (non-antidepressants) decreased the number of [3H]SCH 23390 binding sites, while no change in the parameters of [3H]spiperone binding was observed. The serotonin2 receptor antagonist ketanserin when added to the incubation medium had no effect on [3H]SCH 23390 binding to D-1 sites. The results suggest that D-1 receptor subsensitivity is a component of the therapeutic effect of antidepressants.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.