Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.     

Polysialylated Neural Cell Adhesion is Involved in Target-induced Morphological Differentiation of Arcuate Dopaminergic Neurons

We have previously shown that the morphological and biochemical maturation of developing rat hypothalamic dopaminergic neurons is accelerated when they are cocultivated with pituitary intermediate lobe cells, one of their targets. Only two subsets of hypothalamic dopaminergic neurons (arcuate, A12, and periventricular, A14, nuclei) may project to the pars intermedia. In order to determine whether the two populations are equally responsive to coculture conditions, we microdissected the hypothalamus of 17-day-old rat fetuses in two fragments containing cell bodies from the A12 and from the A14 regions, prepared neuronal cultures from both portions and incubated them separately with intermediate lobe cells. The presence of intermediate lobe cells increased tyrosine hydroxylase levels in both dopaminergic neuron subsets, but morphological differentiation was accelerated in dopaminergic neurons originating in the arcuate nucleus only. We then investigated whether physical contact between developing arcuate neurons and their target cells was a prerequisite of the morphological effect by interposing a semipermeable membrane between cultivated neurons and intermediate lobe cells in transwell culture dishes. The morphological effect was no longer observed under transwell coculture conditions, pointing to the involvement of membrane-bound molecules. Accordingly, the stimulating effect of coculture on arcuate dopaminergic neurons was completely abolished by the removal of polysialic acid on neural cell adhesion molecules by endoneuraminidase N treatment. Thus, maturation of A12 and A14 dopaminergic neurons exhibits differential susceptibility to intermediate lobe target cells, and polysialylated-NCAM is required for the contact-dependent effect.     

L’endoscople d’urgence: les structures,les techniques,le personnel et les statuts

Acta Endoscopica - L’urgence en endoscopie est une situation toujours difficile, qu’elle soit au lit du malade s’il est intransportable, ou au bloc d’endoscopie. Elle...     

Solitary ileocolic arteriovenous malformation: spongostan and silk therapeutic embolisation.

A debilitated patient with liver cirrhosis and poor haemostasis had a severe lower gastrointestinal haemorrhage. A superior mesenteric arteriogram revealed an early persistent and promiment draining vein in the ileocolic artery. Two fragments of Spongostan and silk were used to embolise the bleeding artery and the haemorhage ceased immediately. No infarction of the embolised area was observed and the bleeding was controlled.     

Corticosteroids for multiple sclerosis: II. Application for disease-modifying effects

Physicians who treat multiple sclerosis (MS) face the challenge of patients exhibiting ongoing disease activity, including exacerbations, loss of functional capabilities, intellectual decline, and radiologic progression, despite being on a disease-modifying agent (DMA). After searching for factors that might at least in part explain these changes—such as nonadherent drug-taking behavior, or the presence of interfer-on-neutralizing antibodies—some providers may ultimately decide to switch the patient to another DMA. In most circumstances, patients likely derive only partial effects from these agents, even in the absence of compromising factors. Thus, a number of factors must be considered in order to intensify the treatment regimen in response to disease progression. In the context of an inadequate treatment response to a DMA, some clinicians will convert the patient to an alternative therapy, and others will instead use a second agent in combination with the first (the so-called platform agent). In the first of this two-part series, we explored the use of anti-inflammatory CS and ACTH to treat MS exacerbations. Although we underscored the limited availability of evidence-based studies to support specific regimens for this purpose, there is an even greater paucity of data to support the routine use of these agents in order to achieve chronic disease-modifying effects in those who continue to deteriorate clinically, radiographically, or both. Without doubt, a number of factors influence the formulation of combination treatment plan for MS. Nevertheless, we will focus on the rationale and practical schemes that can be considered for using corticosteroids (CS) (and perhaps even ACTH) in an attempt to modify various domains of ongoing disease activity.     

Hypertension following renal transplantation in children

The files of 334 consecutive cadaver kidney (CK) and of 27 living related (LR) transplantations (T) in children and adolescents performed from 1973 to 1984 have been reviewed. Following cadaver transplantation, 52 patients (15%) never had hypertension (HT), 41 patients (12%) had only initial HT up to 6 months after transplantation and 18 other patients (5%) exhibited transient HT episodes while on high-dose steroid therapy. Finally, 209 patients (62%) had HT for periods longer than 6 months and 16 patients (5%) until death or graft failure within the first 3 months. Chronic graft rejection was the major cause of HT, but other factors either isolated or in association were also present. Renal artery stenosis (RAS) was diagnosed in 43 cases (13%) 2–17 months post-transplantation; 10 of these were operated upon (5 successfully) and 9 underwent transluminal angioplasty with a single success. Nine cases of RAS resolved spontaneously. HT was attributed to the host kidney in 10 cases (3%) and to recurrence of primary renal disease in 9 (3%). HT observed after CKT was sometimes severe and difficult to control. Acute complications from HT were recorded in 35 cases, with 6 deaths and 2 severe neurological sequelae. Among 25 LRT, 11 cases (40%) had no HT 13 (48%) had HT for longer than 6 months. In this group, no case of RAS was observed and only one complication (without sequelae) was noted. In conclusion, HT is a frequent and sometimes severe complication post-transplantation in children and adolescents.     

Synthesis and characterisation of novel nanospheres made from amphiphilic perfluoroalkylthio-beta-cyclodextrins.

This work describes the synthesis of new amphiphilic perfluorohexyl- and perfluorooctyl-propanethio-beta-cyclodextrins and the comparison of the ability of these molecules and alkyl analogue, nonanethio-beta-cyclodextrin to form nanospheres. Nanospheres were prepared using nanoprecipitation method (perfluoroalkylthio-beta-cyclodextrin in THF [0.11 x 10(-3)M], stirring rate 700rpm, addition of aqueous phase at 64 degrees C into organic phase at 50 degrees C). They were characterised by Photon Correlation Spectroscopy (PCS) and by electron microscopy (SEM and cryo-TEM). The nanospheres prepared from these new beta-cyclodextrin derivatives have an average size of 260nm, and appear to be spherical in cryo-TEM images. Whereas alkyl analogue forms polydisperse aggregates with sizes in the range 60-350nm.