Endothelial heterogeneity and plasticity

Angiogenesis - Vascular endothelial cells are highly plastic and show great phenotypic heterogeneity. In recent years, emerging technologies have identified a range of novel endothelial phenotypes...     

Beitr?ge zu einer anatomischen Monographie von Xenopus laevis (Daud.)

Ohne ZusammenfassungMit 15 Textabbildungen.     

二阶导数光谱法测定酮洛芬体外经皮渗透量

为进一步探讨酮洛芬透皮给药的可行性,用二阶导数光谱法测定酮洛芬体外经皮渗透量。结果表明,本法可排除皮下组织的干扰,能准确测定药物体外渗透量,且操作简便、快速。平均回收率为99.00%±1.51%。     

钾通道开放剂的抗过敏作用及其机制

用多种抗变态反应实验方法,研究钾通道开放剂米诺地尔(Min)与二氮嗪(Dia)的抗过敏作用,并探讨其作用机制。结果表明,Min能抑制大鼠同种被动皮肤过敏反应,拮抗5-HT引起的大鼠皮肤血管通透性增高。Dia和Min均能抑制豚鼠离体回肠平滑肌的过敏性收缩,Dia并能抑制A₂₃₁₈₇和化合物48/80诱发的肥大细胞释放组胺。因此钾通道开放剂Min与Dia具有抗过敏作用,作用的主要机理是抑制肥大细胞外Ca²⁺内流和细胞内贮存钙的释放,从而抑制组胺的释放,此可能与药物开放钾通道的作用有关。     

估算肾功能不全的心衰患者血清地高辛总浓度和地高辛样免疫活性物质浓度

用超滤荧光极化免疫分析法测定血清地高辛游离浓度，结合其游离百分率，估算了１２位伴有肾功能不全的慢性心衰患者血清地高辛总浓度和地高辛样免疫活性物质（ＤＬＩＳ）浓度。结果表明，患者的血清实测地高辛游离浓度为０．７９±０．４８ｎｍｏｌ·Ｌ－１；实测地高辛总浓度为１．３１±０．８０ｎｍｏｌ·Ｌ－１，明显高于计算的地高辛总浓度（１．０５±０．６４ｎｍｏｌ·Ｌ－１），Ｐ＜０．０１。计算的ＤＬＩＳ浓度为０．２７±０．１９ｎｍｏｌ·Ｌ－１，该结果与用Ｄａｓｇｕｐｔａ等新近报道的计算方法获得的数据（０．２９±０．２２ｎｍｏｌ·Ｌ－１）一致（Ｐ＞０．０５）。     

Structurally diverse amphiphiles exhibit biphasic modulation of GABAA receptors: similarities and differences with neurosteroid actions

Background and purpose:

Some neurosteroids, notably 3α-hydroxysteroids, positively modulate GABA_A receptors, but sulphated steroids negatively modulate these receptors. Recently, other lipophilic amphiphiles have been suggested to positively modulate GABA receptors. We examined whether there was similarity among the actions of these agents and the mechanisms of neurosteroids. Significant similarity would affect theories about the specificity of steroid actions.

Experimental approach:

Xenopus laevis oocytes were challenged with Triton X-100, octyl-β-glucoside, capsaicin, docosahexaenoic acid and sodium dodecyl sulphate (SDS), along with different GABA concentrations.

Key results:

These compounds have both positive and negative effects on GABA currents, which can be accentuated according to the degree of receptor activation. A low GABA concentration (1 µM) promoted potentiation and a high concentration (20 µM) promoted inhibition of current, except for SDS that inhibited function even at low GABA concentrations. Amphiphile inhibition was characterized by enhanced apparent desensitization and by weak voltage dependence, similar to pregnenolone sulphate antagonism. We then tested amphiphile effects on mutated receptor subunits that are insensitive to negative (α1V256S) and positive (α1Q241L or α1N407A/Y410F) steroid modulation. Negative regulation by amphiphiles was nearly abolished in α1V256S-mutated receptors, but potentiation was unaffected. In α1Q241L- or α1N407A/Y410F-mutated receptors, potentiation by amphiphiles remained intact.

Conclusions and implications:

Structurally diverse amphiphiles have antagonist actions at GABA_A receptors very similar to those of sulphated neurosteroids, while the potentiating mechanisms of these amphiphiles are distinct from those of neurosteroid-positive modulators. Thus, such antagonism at GABA_A receptors does not have a clear pharmacophore requirement.     

Comparison of the metabolism of testosterone undecanoate and testosterone in the gastrointestinal wall of the rat in vitro and in vivo

The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat. The major metabolite first appearing during incubation of TU with the small intestine is T. Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.     

Diffusion-derived parameters in lesions,peri-lesion and normal-appearing white matter in multiple sclerosis using tensor,kurtosis and fixel-based analysis

Neuronal damage is the primary cause of long-term disability of multiple sclerosis (MS) patients. Assessment of axonal integrity from diffusion MRI parameters might enable better disease characterisation. 16 diffusion derived measurements from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and fixel-based analysis (FBA) in lesions, peri-lesion and normal appearing white matter were investigated. Diffusion MRI scans of 11 MS patients were processed to generate DTI, DKI, and FBA images. Fractional anisotropy (FA) and fibre density (FD) were used to assess axonal integrity across brain regions. Subsequently, 359 lesions were identified, and lesion and peri-lesion segmentation was performed using structural T₁w, T₂w, T₂w-FLAIR, and T₁w post-contrast MRI. The segmentations were then used to extract 16 diffusion MRI parameters from lesion, peri-lesion, and contralateral normal appearing white matter (NAWM). The measurements for axonal integrity, DTI-FA, DKI-FA, FBA-FD, produced similar results. All diffusion MRI parameters were affected in lesions as compared to NAWM (p < 0.001), confirming loss of axonal integrity in lesions. In peri-lesions, most parameters, except FBA-FD, were also significantly different from NAWM, although the effect size was smaller than in lesions. The reduction in axonal integrity in peri-lesions, despite unaffected fibre density estimates, suggests an effect of Wallerian degeneration.