Excretion of biliary compounds during intrauterine life

In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.     

Recurrent malignant pilomatrixoma invading the cranial cavity: Improved local control with adjuvant radiation

We report the case of a 41‐year‐old mentally retarded male with recurrent pilomatrix carcinoma of the occipital region which invaded the occipital bone, left cerebellum and left temporal lobe. At his initial presentation the patient had a craniotomy and subtotal excision of the lesion with positive margins. He received no adjuvant therapy. After an early intracranial recurrence he had subtotal debulking and was referred for external beam radiotherapy. At 27 months follow‐up after adjuvant external beam radiotherapy the intracranial component has not progressed and the patient remains clinically well.     

Synthesis and bioacceptability of fluorinated surfactants derived from F-alkylated tertiary amines

Two methods for synthesizing tertiary F-alkylated amines are reported. The more general method allows the access in 56–87% yields to various N,N-dialkyl F-alkyl amines. These amines are key intermediates leading in 52–96% yields to several families of surfactants, including zwitterionic and cationic derivatives and amine oxides, potentially useful in the formulation of fluorocarbon emulsions for diagnostic and therapeutic uses. The toxicity of the new surfactants and the influence of the polar head were assessed: the long chain compounds (8, 9 and 10) were found to be toxic for cell cultures and the zwitterionic compounds (7b and 8) have a LD₅₀ < 250 mg·kg bw⁻¹ in mice. The hemolysis test highlights the influence of the polar head: the zwitterionic compounds (7 and 8) were found to be non-hemolytic even at remarkably high concentrations (100 g l⁻¹ for 8), whereas the cationic compounds 9 are highly hemolytic even at very low concentrations (0.05 g l⁻¹).     

K-Ⅱ和U-50488H对κ阿片受体亲和力的比较

3,4-二氯-N-甲基-N-[反式-2-(1-△³-吡咯啉基)环己基]苯乙酰胺(K-Ⅱ)是新合成的U-50488H类似物,其对小鼠的镇痛效应和对离体兔输精管的抑制作用均比U-50488H强。本文用放射受体结合试验方法对这两种化合物在富含x阿片受体的豚鼠小脑和大脑皮层前叶上的亲和力进行了比较,并求出这两种化合物的Ki值.结果表明K-Ⅱ对k阿片受体的亲和力比U-50488H强6～42倍。K-Ⅱ对阿片受体亚型选择性比较研究正在进行中。