Expression of Antiangiogenic Prolactin Fragments in the Placentas of Women with Pregnancy Induced Hypertension

It has been reported that prolactin (PRL) is cleaved to 14 or 16 kDa fragments by cathepsin D in vitro and in vivo, and that such fragments exhibit antiangiogenic and proapoptotic properties. The aim of this study was to investigate the relationship between pregnancy induced hypertension (PIH) and the placental expression of antiangiogenic PRL fragments and cathepsin D. Placental expression of PRL fragments and cathepsin D was evaluated by Western blot analysis in a group of 9 pregnant women consisting of 5 normal pregnancies and 4 severe PIH cases. Antiangiogenic PRL fragments were detected in 4 placental samples from all PIH cases but not detected in those from normal pregnancies (p0.05). The expression of cathepsin D in PIH placentas was significantly lower than that in those without PIH (p0.05), while the placental expression of procathepsin D was significantly greater in PIH cases than in the normal pregnancies (p0.05). These data suggest that antiangiogenic PRL fragments in the placenta may be present only in PIH cases, and that PRL fragments in the placenta might be implicated in the pathophysiology of PIH

Circulating levels of ciliary neurotrophic factor in normal pregnancy and preeclampsia

Ciliary neurotrophic factor (CNTF) has been shown to decrease food intake in mouse models of obesity and to improve insulin sensitivity. It is well known that tight regulation of glucose metabolism is essential for successful gestational outcomes (e.g. fetal growth), and that abnormal insulin resistance is associated with preeclampsia (PE). To investigate the possibility that CNTF might be involved in the regulation of insulin resistance during pregnancy, circulating levels of CNTF were assessed in non-pregnant, normal pregnant, postpartum, and pregnant women with PE. Sera from healthy non-pregnant women (n10), pregnant women (n30:1st trimester;n10, 2nd trimester n10;3rd trimester;n10), postpartum women (n10), and patients with PE (n11) were studied with Western blotting. Circulating CNTF was detected by Western blotting, and the levels of CNTF in pregnant women were decreased as compared with those in non-pregnant women, and tended to decrease as pregnancy progressed. A significant decrease was found in PE as compared with normal pregnancy. Circulating CNTF might be associated with physiological and abnormal insulin resistance during pregnancy.</p

A Japanese, Multicenter, Open-label, Phase 3 Study to Investigate the Safety and Efficacy of Gadobutrol for Contrast-enhanced MR Imaging of the Central Nervous System

Purpose: Gadobutrol 1.0 M is macrocyclic gadolinium-based contrast agent for magnetic resonance imaging (MRI). This multicenter, open-label, phase 3 study aimed to investigate the efficacy and safety of gadobutrol-enhanced versus unenhanced MRI in the visualization and diagnosis of central nervous system (CNS) lesions in Japanese patients.Methods: A total of 223 patients referred for contrast-enhanced MRI of the CNS underwent unenhanced and gadobutrol-enhanced (0.1 mmol/kg body weight) MRI. The unenhanced and combined (unenhanced and enhanced) images were evaluated by three independent readers in a blinded manner for degree of contrast enhancement, border delineation, internal morphology, and number of detected lesions (primary variables), and for primary diagnosis and diagnostic confidence. Final clinical diagnoses were established by an independent truth committee consisting of two neurosurgeons. Sensitivity, specificity, and accuracy were calculated for the detection of malignancy and the preciseness of diagnoses (secondary variables) by comparing the results obtained by the blinded readers and the truth committee.Results: Gadobutrol enhancement significantly improved three visualization parameters in MR images: contrast enhancement, border delineation, and internal morphology (P < 0.0001). Non-inferiority was achieved for mean number of lesions detected. Gadobutrol-enhanced imaging provided significant improvements in sensitivity and accuracy for the detection of malignant disease with no loss in specificity, and also improvements in accuracy of exact match diagnosis and diagnostic confidence. Drug-related adverse events were reported in 6 out of 223 patients (2.7%); all were non-serious.Conclusion: Gadobutrol is an effective and well-tolerated contrast agent for MR imaging of the CNS

A novel approach for the endothelialization of xenogeneic decellularized vascular tissues by human cells utilizing surface modification and dynamic culture

Decellularized xenogeneic vascular grafts can be used in revascularization surgeries. We have developed decellularization methods using high hydrostatic pressure (HHP), which preserves the extracellular structure. Here, we attempted ex vivo endothelialization of HHP-decellularized xenogeneic tissues using human endothelial cells (ECs) to prevent clot formation against human blood. Slices of porcine aortic endothelium were decellularized using HHP and coated with gelatin. Human umbilical vein ECs were directly seeded and cultured under dynamic flow or static conditions for 14 days. Dynamic flow cultures tend to demonstrate higher cell coverage. We then coated the tissues with the E8 fragment of human laminin-411 (hL411), which has high affinity for ECs, and found that Dynamic/hL411showed high area coverage, almost reaching 100% (Dynamic/Gelatin vs Dynamic/hL411; 58.7 ± 11.4 vs 97.5 ± 1.9%, P = 0.0017). Immunostaining revealed sufficient endothelial cell coverage as a single cell layer in Dynamic/hL411. A clot formation assay using human whole blood showed low clot formation in Dynamic/hL411, almost similar to that in the negative control, polytetrafluoroethylene. Surface modification of HHP-decellularized xenogeneic endothelial tissues combined with dynamic culture achieved sufficient ex vivo endothelialization along with prevention of clot formation, indicating their potential for clinical use as vascular grafts in the future

Deformation of Palladium Plates by a Small Stress during Hydrogen Absorption and Desorption

We observed an unexpected bending of a horizontally held palladium plate at 150$^{\circ}$C under a small external shearing stress. The deformation was fastest at the nominal composition of PdH$_{{\rm 0.1-0.2}}$, which is in the $\alpha+\beta$ phase. We also observed that a plate warped back and forth during a cycle of absorption and desoprtion of hydrogen when it was hung vertically, which does not have a reasonable explanation.Comment: 12 pages, 11 figure

Fetal topographical anatomy of the female urethra and descending vagina: a histological study of the early human fetal urethra

Background: Which parts of the male urethra correspond to the female urethra? To resolve this question, we need to understand fetal topographical changes in the urethra, its external sphincter and vagina. The vagina joins the mid-course of the primitive urethra and, later "descends" to the vaginal vestibulum. Methods: We examined histological sections of 14 female and 4 male mid-term fetuses. Results: The inferior end of the vagina was consistently embedded in the posterior wall of the urethra at 9-12 weeks. The supero-inferior level of the vaginal merging was lower in larger fetuses. Thus, the sequential variation in levels appeared to reflect the process of vaginal descent. However, in spite of penetration of the vaginal end into the posterior urethral wall, we found no sign of destruction of the urethral wall after vaginal descent in the low-merging types. Before vaginal descent, the female external sphincter extended posterolaterally around the urethra. Conclusion: The vaginal descent is classically regarded as a relative topographical change, but it is likely to be a result of elongation of the proximal urethra in the superior side of the vaginal merging. Conversely, the distal urethra is likely to be incorporated into the vaginal vestibulum by 15 weeks. During these processes, most of the female external sphincter seems to be expelled from the original anterior position into the vestibular wall as the urethrovaginal sphincter. The adult female urethra seems to correspond to the male prostatic urethra superior to the prostatic colliculus.Depto. de Anatomía y EmbriologíaFac. de MedicinaTRUEpu