Brain tumour stem cells and neural stem cells: still explored by the same approach?

Brain tumour stem cells (BTSCs) are chiefly responsible for the in vivo long-term growth and recurrence of malignant gliomas and may be a potential treatment target. They resemble neural stem cells (NSCs), so their self-renewal and differentiation are currently investigated by the same methods used to study NSCs. There are, however, essential differences between these cell types: in many cases the marker expression pattern of BTSCs does not match the CD133(+)/NSE(-)/FAP(-) pattern of NSCs; BTSC tumourigenicity is independent of marker expression; and while attachment, serum-containing medium and withdrawal of mitogens (epidermal growth factor [EGF] and basic fibroblast growth factor [bFGF]) are essential to induce NSCs to differentiate, they do not affect BTSC tumourigenicity. Evidence implies that research on the renewal and differentiation of BTSCs should be orientated towards tumourigenicity and is essentially a pharmaceutical problem. Such an approach may contribute to the development of an accurate definition of BTSCs and to the search for selective differentiation-inducing drugs for BTSCs.     

Sonography in pathologies of scalp and hair

Disorders of the scalp often result in severe cosmetic interference with quality of life, creating the need for optimal medical surveillance. We tested the latest generation of ultrasound machines in patients with scalp pathology and prepared a cross-sectional library encompassing a wide assortment of conditions. Normative data on the sonographic anatomy of scalp and human hair, and important methodological considerations, are also included.     

Radiation exposure from CT in early childhood: a French large-scale multicentre study

Objectives

The increasing use of CT scans in the paediatric population raises the question of a possible health impact of ionising radiation exposure associated with CT scans. The aim of this study was to describe the pattern of CT use in early childhood.

Methods

In 14 major French paediatric radiology departments, children undergoing at least 1 CT scan before age 5, between 2000 and 2006, were included. For each examination, absorbed organ doses were calculated.

Results

43% of the 27 362 children in the cohort were aged less than 1 year during their first exposure, with 9% being aged less than 1 month. The mean number of examinations per child was 1.6 (range 1–43). The examinations included: head in 63% of the cases, chest in 21%, abdomen and pelvis in 8% and others in 8%. Brain and eye lenses received the highest cumulative doses from head examinations, with mean organ dose values of 22 mGy (maximum 1107 mGy) and 26 mGy (maximum 1392 mGy), respectively. The mean cumulative effective dose was 3.2 mSv (range 0.1–189 mSv).

Conclusion

CT scan exposure in childhood is responsible for relatively high doses to radiosensitive organs. The rather large dose range according to the protocols used requires their optimisation. The cohort follow-up will study the risk of long-term radiation-induced cancer.Exposure for medical purposes is the main source of artificial radiation. In France, it represents 40% of the annual exposure of the whole population [1]. These exposures are mostly in relation to radiodiagnosis, which is associated with low levels of ionising radiation (IR). Previously, it has been observed that pre-natal and childhood exposure to X-rays was associated with an increased risk of cancer [2-4]; however, this was not confirmed by a review based on more recent studies published since 1990 [5]. The doses that used to be involved in pre-natal and post-natal diagnostic exposures in the past were much higher than those reported nowadays, and no evidence of an increased risk of leukaemia has been observed. However, some specific procedures, such as CT, are associated with much higher radiation doses than conventional radiodiagnosis: CT accounts for only 5% of all X-ray examinations but represents between 40% and 67% of the total medical dose received by the population [6]. Over the last 20 years the ease and speed of image acquisition linked to technological developments has encouraged the proliferation of procedures and has led to increased doses to patients. These trends are also observed in paediatric diagnostic imaging, leading to an increase in the use of CT and, therefore, an increase in the level of exposure to IR in children. About 11% of CT scans are carried out in the paediatric population [7]. Assessment of cancer risk after childhood radiation exposure remains a concern regardless of the radioprotection used for children. Children actually present an increased radiosensitivity of certain tissues compared with that of adults, which, combined with a long life expectancy, could allow cancer to develop. A lack of adjustment of specific technical parameters during imaging has also been noted.The objective of this study was to build a cohort of children who attended the major French radiology departments very early in life, in order to describe the pattern of CT scan use in early childhood and to estimate doses associated with these examinations.     

Urethral Reconstruction Using Bone Marrow Mesenchymal Stem Cell– and Smooth Muscle Cell–Seeded Bladder Acellular Matrix

Background

Congenital or acquired abnormalities may lead to a urethral defect that often requires surgical reconstruction. The traditional methods often lead to complications, including urethrocutaneous fistulae and strictures. In this study, we proposed to construct a tissue-engineered sheet graft (TESG) using a bone marrow mesenchymal stem cell (BMSC)– and smooth muscle cell (SMC)–seeded bladder acellular matrix (BAM) for urethral reconstruction.

Methods

Rabbit BMSCs and SMCs were isolated, expanded, and identified in vitro before seeding into BAM as the experimental group, whereas BAM-only was the control group. The graft was used to construct TESG for implantation into the rabbit omentum for 2 weeks before urethral reconstruction. We divided 24 male rabbits into four experimental groups six each, and six other were the control group. Histological analysis was performed at 2 weeks, 4 weeks, 8 weeks, and 16 weeks postoperatively. Retrograde urethrography was performed at 16 weeks postoperatively.

Results

All experimental rabbits survived to they were humanly killed. At 8 weeks, there was no difference between the graft and the normal urethra with no severe shrinkage. At 8 and 16 weeks after TESG grafting in vivo, multilayer urothelium covered the graft, neovascularization was visible within the center of TESG, and organized smooth muscle bundles were present. Retrograde urethrography failed to demonstrate diverticula formation or urethral stricture. Three control rabbits died within 4 weeks postoperatively. Autopsy showed their urethras to be almost completely blocked whereas another three hosts displays urethral strictures.

Conclusion

A TESG was constructed using a BMSC- and SMC-seeded BAM for urethral reconstruction.     

Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1)

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-beta. To test this hypothesis we compared the regulation of TGF-beta in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-beta(1) production in transgenic animals and macrophages were the major site of TGF-beta(1) production and deposition in these tissues. IL-13 also activated TGF-beta(1) in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-beta-binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-beta(1) activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13-induced fibrosis was also significantly ameliorated by treatment with the TGF-beta antagonist soluble TGFbetaR-Fc (sTGFbetaR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-beta(1) in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9-dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-beta pathway.     

Pharmacokinetics of bis(t-butyl-SATE)-AZTMP, a bispivaloylthioethyl prodrug for intracellular delivery of zidovudine monophosphate, in mice

The pharmacokinetics of a bispivaloylthioethyl prodrug of zidovudine monophosphate (AZTMP), bis(t-butyl-SATE)-AZTMP, and intracellular conversion of the prodrug to AZTMP were characterized following intravenous (i.v.) and oral (p.o.) administration of the prodrug to mice. Concentrations of bis(t-butyl-SATE)-AZTMP, AZTMP and zidovudine (AZT) in blood, red blood cells, plasma, brain and lymph nodes were determined by HPLC. Following i.v. administration of bis(t-butyl-SATE)-AZTMP, concentrations of the prodrug declined rapidly with low levels of the prodrug detected until 4 h. Both bis(t-butyl-SATE)-AZTMP and AZTMP were detected in brain 3 min after dosing. AZTMP was found in both plasma and peripheral red blood cells, peaking at approximately 30 min and remaining detectable until 2 h. No AZTMP was detected in lymph nodes. Compared to the pharmacokinetics of AZT following its i.v. administration, i.v. administration of bis(t-butyl-SATE)-AZTMP produced lower peak concentrations of AZT in plasma, peripheral red blood cells, brain and lymph nodes. However, terminal half-lives of AZT were significantly prolonged following administration of the prodrug. Following p.o. administration of bis(t-butyl-SATE)-AZTMP, neither the prodrug nor AZTMP were detectable in whole blood. The conversion of AZT from bis(t-butyl-SATE)-AZTMP in plasma and peripheral red blood cells following p.o administration was 12.1% of that following i.v. administration of the prodrug. Bis(t-butyl-SATE)-AZTMP demonstrated promising potential for intracellular delivery of AZTMP. The prodrug also prolonged the retention of AZT in mice, and particularly increased delivery of AZT to the lymphatic and central nervous systems.