高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats

The effect of bile on the development of 1,2-dimethylhydrazine (DMH)-induced colon cancer was studied in male Wistar rats. Experimental operative models were created, in which in Group 1, the half intestinal tract, the ileum, and the right side of colon were released from bile. In Group 2, both sides of the colon contained bile. The sham operated animals formed Group 3. These techniques changed the concentration of bile acid in different parts of the colon, and the daily total fecal bile acid excretion as well. After DMH treatment, the relationship between these changes of bile acid level and the development of colon cancer was studied. Significantly more tumors than in the control group were found if the daily total bile acid level and the bile acid concentration in the left side of the colon were increased. Our findings show an unambiguous connection between the fecal bile acid level and the incidence of DMH-induced colon cancer.     

Long-term treatment of central Cushing's syndrome with rosiglitazone.

CONTEXT: Central Cushing's syndrome is not always curable by surgery or radiation of the pituitary. Medical treatment is often not possible or effective. Some studies revealed beneficial effects of the PPARgamma (Peroxisome-Proliferator-Activator- Receptor-gamma)-agonist rosiglitazone (RG) in in vitro studies, animal models and short term clinical studies. OBJECTIVE: of this study was to observe the long-term effects of RG-treatment on cortisol- and ACTH -secretion, clinical outcomes and morphological changes of the pituitary in patients with persistent ACTH-overproduction despite previous operation and radiation. DESIGN, SETTING AND PATIENTS: 14 patients with persistent central ACTH -production were included and monitored over a period up to 12 months. RG was administered daily and increased to a maximum dosage of 24 mg daily, according to the response of ACTH and cortisol secretion. ACTH and cortisol were measured at least every 4 weeks during RG treatment. RESULTS: Patients were treated between 4 and 12 months with RG (mean 6.8 months). Compared to baseline, ACTH- and cortisol levels dropped significantly (p<0.01) after 12, 16, 20, 24 and 28 weeks but thereafter rose again during the study period, despite continuous RG- treatment and dose increase up to the maximum dosage. This was paralleled by reocurrence of clinical symptoms. MRI-scans were performed in 6 patients because of persisting visible adenoma, but showed no morphological changes. CONCLUSION: RG seems not to be a long-term treatment option for patients with persistent central ACTH-evcess. Though, in order to reduce perioperative complications, short term treatment of patients could be an alternative.     

The UTX gene escapes X inactivation in mice and humans

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.      

Possibilities of sterility therapy in a patient with a premature menopause due to an X-chromosomal anomaly - a case report

Our report concerns a patient with a climacterium praecox and an X-chromosomal anomaly (86% 46, XX; 7% 47, XXX; 7% 45, X0) desiring to give birth. She conceived once after down-regulation of the gonadotrophins by means of a cyclical hormone replacement therapy followed by gonadotrophin stimulation, as well as a second time under down-regulation with a GnRH-analogue and gonadotrophin stimulation. On the basis of the case report and of the literature, a possible interval therapy in such a patient, especially one even with increasing ovarian insufficiency, will be portrayed and discussed.     

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.      

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.