Effect of chronic ethanol administration on the uptake and degradation of asialoglycoproteins by the perfused rat liver

We have shown previously reduced binding, internalization, degradation and receptor-ligand dissociation during receptor-mediated endocytosis (RME) of 125I-asialoorosomucoid (ASOR) by hepatocytes isolated from rats fed ethanol for 4-6 weeks. In the present study, we investigated the effect of ethanol feeding on RME by using the intact perfused liver as a model. Male, Sprague-Dawley rats were fed a liquid diet containing either ethanol (36% of calories) or isocaloric carbohydrate. Receptor-mediated endocytosis of 125I-ASOR was then examined over a time course of perfusion. In all cases, clearance of the labeled glycoprotein was followed by a slower but steady appearance of acid-soluble products in the medium. Ethanol-fed animals had a significantly (P less than 0.01) slower rate of clearance of the labeled ligand from the circulating perfusate than did control animals. Impairment of ASOR surface binding and degradation in ethanol-fed animals was also demonstrated in this model. When we examined the subcellular distribution of labeled ligand after various times of perfusion, we found that in control livers, a shift of radiolabeled ligand from the subcellular fractions containing endosomes and plasma membranes to fractions containing lysosomes occurred, while significantly less ligand was shifted to the lysosomes of ethanol-treated rats. These results show that ethanol administration inhibits RME of ASOR in the isolated perfused liver model, thus confirming our earlier reported defects in isolated hepatocytes. In addition, transport of ligand along the intracellular RME pathway was also shown to be altered by ethanol treatment as indicated by the impaired movement of ASOR from the endosomal to the lysosomal compartment.     

华蟾蜍毒素对离体豚鼠输精管的作用

华蟾蜍毒素(华蟾素)使离体豚鼠输精管产生剂量依赖性收缩反应,利血平化豚鼠输精管及冷藏输精管对华蟾素反应减弱。给酚妥拉明、维拉帕米后,输精管对华蟾素反应均受抑制,溴苄胺可使反应潜伏期缩短。结果提示华蟾素收缩输精管反应可能与其促进肾上腺素能神经末稍NA释放有关。     

Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.