[New insights in the pathogenesis of pulmonary arterial hypertension]. / Nouveau regard sur la physiopathologie de l'hypertension artérielle pulmonaire.

Pulmonary arterial hypertension (PAH) is a severe and incurable cardiopulmonary disorder. Research from the past 10 years illustrates the complex and multifactorial aspects of PAH pathophysiology. Furthermore, latest advances in the field have led to a better understanding of the key components underlying this inadequate accumulation of pulmonary vascular cells within the pulmonary arterial walls, leading to pulmonary vascular remodelling. Among the underlying molecular and cellular mechanisms, pulmonary endothelial dysfunction, alterations of the inter-cell communications within the pulmonary arterial walls as well as defects of the inflammatory component and the loss of BMPRII activity play critical roles in the pathogenesis of the disease.

[Quality control of hospital preparations: results concerning capsules production in a child hospital]. / Contrôle qualité des préparations hospitalières: bilan de la production de gélules d'un hôpital pédiatrique.

In France, lack of paediatric drugs leads pharmacies to produce many hospital preparations in order to meet prescribers'needs. To ensure the quality of these preparations, the pharmacy department of the Armand Trousseau Child Hospital set up a quality control system of its capsules. It integrates both European Pharmacopeia's requirements (Mass and Content uniformity test) and more strict internal quality specifications. They include exactitude of the average content compared to the awaited content, coefficient of variation of the contents and, "modified" content uniformity test. These criteria and the percentage of nonconformity are used as indicators to assure quality follow-up of the preparations. We reviewed quality control records for five hospital preparations produced over the last three years. We highlighted that lower dosage showed a higher percentage of nonconformity compared to higher dosage. Type of active ingredients was a key factors too (1,0% and 14.8% of non conform batches for ursodesoxycholic acid and for morphine hydrochloride respectively). Analysis showed that the essential character of content test because mass test is not predictive of the conformity of the batch. Content test was the main criterion to judge batches conformity. Thus, it will be generalized to all our preparations. These study results helped us to implement new procedures to assure an ongoing improvement of our practices of preparation.

[Development of an intravesial oxybutynin chloride solution: from formulation to quality control]. / Développement d'une solution de chlorhydrate d'oxybutynine pour instillation vésicale: de la formulation au contrôle qualité.

Intravesical oxybutynin chloride has demonstrated its efficacy in children with neurogenic bladder and urinary incontinence refractory to oral anticholinergic agents. We developed a 205 microg/ml oxybutynin chloride solution in accordance with the specifications of the European Pharmacopeae. To guarantee quality, we assessed and validated formulation, the preparation process, and packaging. The solution was obtained by disolving oxybutynin chloride in 0.9% saline and sterile filtration. The solution was then packaged in syringes. Physical properies for intravesical instillation were met: pH 5.76 +/- 0.03, osmolality 281 mosmol/kg. The unit dose package guarantees sterility of the solution until use. The medication is given by adapting the syringe on the Luer Lock exteremity of the urinary catheter. The solution remains stable up to one month at 4 degrees C.

Role of iron in tumor cell protection from the pro-apoptotic effect of nitric oxide.

F2The host defense against tumor cells is in part based upon the production of nitric oxide (NO) by activated macrophages. However, carcinogenesis may involve mechanisms that protect tumor cells from NO-mediated apoptosis. In the present study, we have assessed the effects of exogenous NO on the proliferation and survival of human liver (AKN-1), lung (A549), skin (HaCat), and pancreatic (Capan-2) tumor cell lines, compared with normal skin-derived epithelial cell cultures. Except to the HaCat cell line, all of the other human epithelioid cells were sensitive to the antiproliferation effect of S-nitroso-N-acetyl-penicillamine or Deta NONOate, whereas tumor cells had low if any response to sodium nitroprusside. Growth inhibition with exogenous NO correlated with increased apoptosis, but was not mediated by cyclic GMP, peroxynitrite generation, or poly(ADP-ribose) polymerase modulation, all of which involved in NO-mediated growth inhibition of normal skin-derived epithelial cell cultures. The simultaneous addition of iron-containing compounds protected tumor cells from NO-mediated growth inhibition and apoptosis. Intracellular iron quantification indicated that, as deferoxamine, exogenous NO significantly decreased intracellular ferric iron levels in tumor cells. Together, the current study reveals that intracellular iron elevation rescues tumor cells from NO-mediated iron depletion and subsequent growth inhibition and apoptosis.