Safe Cytotoxic Drug Preparation Using Closed-system Transfer Device: Technical and Practical Evaluation of a New Device (Vialshield/Texium) Comparatively to a Reference One (Phaseal).

Closed-system transfer devices enhance the drug handlers' protection against hazardous drugs exposure by prohibiting the escape of liquid or vapor from the system. PhaSeal (Becton Dickinson), a reference closed-system transfer device, includes a vial protector with an expansion chamber, and an injector with an enclosed needle. VialShield (CareFusion) is another more recent closed-system transfer device including an expansion-chamber and a non-return valve, designed to be used in association with Texium (CareFusion), a closed, needle-free male luer with its preassembled syringe.

Soluble CD146 boosts therapeutic effect of endothelial progenitors through proteolytic processing of short CD146 isoform.

Aims: Endothelial colony-forming cells (ECFC) constitute an endothelial progenitor fraction with a promising interest for the treatment of ischaemic cardiovascular diseases. As soluble CD146 (sCD146) is a new factor promoting angiogenesis, we examined whether sCD146 priming could improve the therapeutic potential of ECFC and defined the involved mechanism.

Methods And Results: We investigated the effects of sCD146 priming on regenerative properties of ECFC in vivo.

Single photon emission computed tomography imaging of cerebral blood flow, blood-brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats.

Background: Cerebral ischemia is a leading cause of disability worldwide and no other effective therapy has been validated to date than intravenous thrombolysis. In this context, many preclinical models have been developed and recent advances in preclinical imaging represent promising tools. Thus, we proposed here to characterize in vivo time profiles of cerebral blood flow, blood-brain barrier disruption and apoptosis following a transient middle cerebral artery occlusion in rats using SPECT/CT imaging.

Stability of a highly concentrated solution of epirubicin for conventional transcatheter arterial chemoembolization.

Introduction: Epirubicin is widely used for conventional transcatheter arterial chemoembolization (cTACE) in patients with hepatocellular-carcinoma. However, there is no data about its stability in solution at concentration higher than 2 mg/L, yet needed when mixing it with a standard volume of Lipiodol(®) to produce an efficient water-in-oil emulsion. The aim of this study was therefore to evaluate the stability of a highly concentrated solution of epirubicin for cTACE and verify whether epirubicin solution could be prepared in advance.

[Pertinence of Off-label Prescriptions of Innovating and Expensive Drugs in a University Hospital].

Objectives: Pertinence of off-label prescriptions of innovative and expensive drugs needs a strict scientific appraisal to prevent adverse reaction risks and financial drift.

Methods: Pertinence of such prescriptions has been analyzed in a University Hospital by bibliometric methods. Scientific publications issued from this clinical activity have been also evaluated.

Visual compatibility of defibrotide with selected drugs during simulated Y-site administration.

Purpose: The visual compatibility of a solution of defibrotide (the only drug recommended for treatment and prophylaxis of hepatic venoocclusive disease) with solutions of various drugs commonly administered in bone marrow transplant procedures was studied.

Methods: Solutions of 43 drug products in concentrations typically used in clinical practice were evaluated in 1:1 mixtures with defibrotide solution in glass tubes kept at room temperature. The evaluated products included antiinfectious, corticoid, sedative, analgesic, and cardiovascular agents widely used for hematopoietic stem cell transplantation and other marrow transplant procedures; in most cases, test solutions were prepared via dilution in or reconstitution with sterile water, 0.

Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity.

Introduction: Recent data on newborn animals exposed to anesthetics have raised safety concerns regarding anesthesia practices in young children. Indeed, studies on rodents have demonstrated a widespread increase in brain apoptosis shortly after exposure to sevoflurane, followed by long-term neurologic impairment. In this context, we aimed to evaluate the protective effect of rh-EPO, a potent neuroprotective agent, in rat pups exposed to sevoflurane.

Aseptic simulation test for cytotoxic drug production in isolators.

Purpose: The results of a media-fill test (MFT) study to validate processes for cytotoxic drug preparation inside and outside aseptic compounding isolators are presented.

Methods: Using an MFT protocol adapted to institution-specific production conditions, the pharmacy team at a hospital in France performed a series of tests to verify the efficacy of decontamination and sterile compounding procedures, as required by French compendial standards, while assessing the performance of its team of 12 isolator operators; all operators were tested on three occasions, producing 10 MFT samples per test for a total of 30 samples per operator. The team also tested alternative compounding systems (i.

Cisplatin dose adjustment in patients with renal impairment, which recommendations should we follow?

Background: Nephrotoxicity is the dose-limiting side effect of cisplatin justifying the assessment of renal function for dose adjustment.

Objective: To determine whether appropriate dose adjustment is made in patients with renal impairment using the Cockcroft-Gault (CG) or the abbreviated Modification of Diet in Renal Disease (aMDRD) formulas to estimate the glomerular filtration rate (GFR).

Setting: The study was conducted in a 1,000-bed university hospital.

Therapeutic benefit of a combined strategy using erythropoietin and endothelial progenitor cells after transient focal cerebral ischemia in rats.

Objective: Many studies have demonstrated beneficial effects of either erythropoietin (EPO) or endothelial progenitor cell (EPC) treatment in cerebral ischemia. To improve post-ischemic tissue repair, we investigated the effect of systemic administration of endothelial colony-forming cells (ECFCs), considered as relevant endothelial progenitors due to their specific vasculogenic activity, in the presence or absence of EPO, on functional recovery, apoptosis, angiogenesis, and neurogenesis in a transient focal cerebral ischemia model in the adult rat.

Design: Experimental study.

[Amyotrophic lateral sclerosis: update on etiological treatment].

Amyotrophic lateral sclerosis is a rare neurodegenerative disease. It is characterized by motoneurons progressive degeneration. Associated with a paralysis of the legs, arms and the respiratory muscles, its evolution is lethal.

[Gene therapy in Parkinson disease: a promising future treatment?].

Parkinson disease is a neurodegenerative pathology with high incidence. Current treatments ease the symptoms but don't stop the development of the disease and aren't without any major side effects. Although this pathology is not specifically caused by genetic abnormalities, the involvement of numerous proteins in the pathophysiological process enables us to give an interest to gene therapy.

Population pharmacokinetics analysis of mycophenolic acid in adult kidney transplant patients with chronic graft dysfunction.

The aim of this study is to develop a population pharmacokinetic model for total and free mycophenolic acid (MPA) in adult kidney transplant patients with chronic graft dysfunction to understand the contribution of potentially relevant covariates to the inter- and the intraindividual variability of MPA in these patients. Twenty patients received mycophenolate mofetil orally up to 1 g twice daily were enrolled in this prospective pharmacokinetic study. Two hundred twenty-nine total and 257 free concentration-time points were determined using reversed-phase high-performance liquid chromatography/ultraviolet at 21 days and 6 months after initiation of mycophenolate mofetil therapy.

Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke.

Endothelial progenitor cells (EPCs) seem to be a promising option to treat patients with ischemic diseases. Here, we investigated the effects of late outgrowth EPCs, or endothelial colony-forming cells (ECFCs), a recently defined homogeneous subtype of EPCs, in a rat model of transient middle cerebral artery occlusion (MCAO). Either vehicle or 4.

[Interests in angiogenesis inhibitor drugs approved for the treatment of cancers].

New blood vessel formation (angiogenesis) is fundamental to the process of tumor. Vascular Endothelial Growth Factors (VEGF) and their receptors are considered to be ones of the most important regulators of angiogenesis and new key targets for anti-cancer treatment. Three angiogenesis inhibitors are approved in France for patients with various malignancies.

CD146 short isoform increases the proangiogenic potential of endothelial progenitor cells in vitro and in vivo.

Rationale: CD146, a transmembrane immunoglobulin mainly expressed at the intercellular junction of endothelial cells, is involved in cell-cell cohesion, paracellular permeability, monocyte transmigration and angiogenesis. CD146 exists as 2 isoforms, short (sh) and long (lg), but which isoform is involved remains undefined.

Objective: The recently described role of CD146 in angiogenesis prompted us to investigate which isoform was involved in this process in human late endothelial progenitors (EPCs), with the objective of increasing their proangiogenic potential.

Soluble CD146 displays angiogenic properties and promotes neovascularization in experimental hind-limb ischemia.

CD146, an endothelial molecule involved in permeability and monocyte transmigration, has recently been reported to promote vessel growth. As CD146 is also detectable as a soluble form (sCD146), we hypothesized that sCD146 could stimulate angiogenesis. Experiments of Matrigel plugs in vivo showed that sCD146 displayed chemotactic activity on endogenous endothelial cells, and exogenously injected late endothelial progenitor cells (EPCs).

Chocolate intake associated with failed labeling of (99m)Tc red blood cells.

Unlabelled: Red blood cells (RBC) labeled in vivo with (99m)Tc-pertechnetate are used worldwide in nuclear medicine departments.

Methods: Here, we present a case of (99m)Tc-RBC labeling failure associated with chocolate intake in a 25-y-old woman, resulting in uninterpretable images. Because of this clinical observation, we performed in vitro RBC labeling on blood samples from volunteers after they consumed chocolate.

Sevoflurane preconditioning against focal cerebral ischemia: inhibition of apoptosis in the face of transient improvement of neurological outcome.

Background: Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia.

Early anesthetic preconditioning in mixed cortical neuronal-glial cell cultures subjected to oxygen-glucose deprivation: the role of adenosine triphosphate dependent potassium channels and reactive oxygen species in sevoflurane-induced neuroprotection.

Background: The purpose of the present study, on mixed cortical neuronal-glial cell cultures subjected to transient oxygen-glucose deprivation (OGD) was: i) to compare the neuroprotection afforded by sevoflurane added either before (preconditioning) or during (direct neuroprotection) the OGD and ii) to explore the possible involvement of adenosine triphosphate-sensitive potassium (KATP) channels and intracellular reactive oxygen species (ROS) levels in the mechanism of the early preconditioning effect of sevoflurane.

Methods: Mature mixed cortical neuronal-glial cell cultures were exposed to 90-min OGD in an anaerobic chamber followed by reoxygenation. Sevoflurane (0.

Exposure of medical personnel to radiation during radionuclide therapy practices.

Objectives: Radioisotopes that emit beta radiation are used for the treatment of hepatocellular carcinoma, of arthritic patients (radiosynovectomy) and treatment of bone metastases with, respectively, I-labelled lipiodol, colloidal citrate of Y or and Sm-labelled EDTMP. Radiation energy of these radioisotopes that emit beta or beta and gamma radiation (from 300 to 2000 keV) leads to an increase in radiation dose received by nuclear medicine staff. In this paper we focused on clinical and laboratory staff exposure during these types of metabolic radiation therapies.

Sevoflurane protects rat mixed cerebrocortical neuronal-glial cell cultures against transient oxygen-glucose deprivation: involvement of glutamate uptake and reactive oxygen species.

Background: The purpose of this study was to clarify the role of glutamate and reactive oxygen species in sevoflurane-mediated neuroprotection on an in vitro model of ischemia-reoxygenation.

Methods: Mature mixed cerebrocortical neuronal-glial cell cultures, treated or not with increasing concentrations of sevoflurane, were exposed to 90 min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber followed by reoxygenation. Cell death was quantified by lactate dehydrogenase release into the media and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium by mitochondrial succinate dehydrogenase.

The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?

EAAC1/EAAT3 is a transporter of glutamate (Glu) present at the post-synaptic neuronal element, in opposition to the two other main transporters, GLAST/EAAT1 and GLT1/EAAT2, expressed at the excitatory amino acid (EAA) synapse by surrounding astrocytes. Although, in the adult, EAAC1/EAAT3 exhibits a rather low expression level and is considered to make a minor contribution to Glu removal from the synapse, its early expression during brain development, before the astrocytes are functional, suggests that such a neuronal transporter is involved in the developmental effects of EAA and, possibly, in the biosynthesis and trophic role of GABA, which is excitatory in nature in different brain regions during the earlier stages of brain development. This neuronal Glu transporter is considered to have a dual action as it is apparently involved in the neuronal uptake of cysteine, which acts as a key substrate for the synthesis of glutathione, a major anti-oxidant, because the neurones do not express the Xc(-) transport system in the mature brain.