Rhône-Poulenc

About: Rhône-Poulenc is a based out in . It is known for research contribution in the topics: Alkyl & Catalysis. The organization has 8909 authors who have published 8934 publications receiving 182241 citations. The organization is also known as: Rhone-Poulenc.

Cationic lipid-mediated gene transfer: Analysis of cellular uptake and nuclear import of plasmid DNA

Abstract: Cationic lipids are widely used for gene transfer in vitro and show promise as vectors for in vivo gene therapy applications. However, there is limited understanding of the cellular mechanisms involved in nonviral gene transfer. We investigated two major steps that could be limiting barriers to cationic lipid-mediated gene transfer in vitro. We used a fluorescent plasmid to study the cellular uptake and the intracellular fate of lipoplexes during in vitro transfection of fibroblast cells and found that 100% of the cells take up lipoplexes. The intracellular staining observed with lipoplexes was clearly different from that obtained with endocytosed fluorescent dextran. This suggests that cells readily take up lipoplexes by a mechanism that could be different from endocytosis in our conditions. However, the escape of DNA from intracellular vesicles could be a major limiting barrier to gene transfer. Direct injection of plasmid DNA into the nucleus and cytoplasm of cells indicated that DNA traffic from the cytoplasm to the nucleus might be also an important limiting step.

Pharmacokinetic profile of nicorandil in humans: an overview.

Abstract: Nicorandil is rapidly and almost completely absorbed from the gastrointestinal tract. Nicorandil is not metabolized significantly by the liver during passage through the portal system (lack of first-pass effect). Thus, it easily enters the systemic blood flow, resulting in almost complete bioavailability (75-100%). The concomitant food intake decreases the rate of absorption of the drug, resulting in a delay of peak plasma concentration, but has little or no effect on maximal plasma concentration or total amount of absorbed nicorandil. After oral administration of a 5-, 10-, 20-, or 40-mg dose, there is a linear relationship between the doses and increases of maximum plasma concentrations and area under the curve, demonstrating that the pharmacokinetics of nicorandil are linear. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after continuous dosing (20 mg b.i.d.), probably due to its distribution and metabolism patterns. On average, the Cmax then is approximately 300 ng/ml, which is achieved rapidly within 30 min after drug intake. Nicorandil is bound weakly to human albumin and other plasma proteins (approximately 25%). After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0 L/kg body weight. Nicorandil is metabolized extensively, and the major route of elimination is the kidney: Less than 2% of the dose is excreted through the biliary route. As a consequence, the parent drug is excreted poorly in urine (very low renal clearance), whereas 2-nicotinamidoethanol, a pharmacologically inactive denitrated metabolite, is the major nicorandil-related compound excreted in urine. The nicotinamide/nicotinic acid biotransformation pathway contributes to the accumulation of nicorandil and 2-nicotinamidoethanol (denitrated metabolite) during repeated dosing because of the saturable merging of nicotinamide/nicotinic acid derivatives (from the nicorandil metabolism) into the NAD/NADP endogenous pool of coenzymes. The apparent elimination half-life is short (approximately 1 h), and total body clearance is close to 1.15 L/min, which is lower than the liver blood flow. Especially during repeated dosing, a slower elimination process appears that is related to only approximately 10% of the amount of nicorandil found in plasma. Most of the nicorandil metabolites are excreted during the 24-h period after dosing, with the remainder excreted more slowly (as nicotinamide derivatives). The pharmacokinetics of nicorandil are not altered significantly in elderly persons and in patients who have chronic renal impairment or liver insufficiency. Furthermore, its disposition profile is not modified when concomitant drugs such as drug-metabolizing enzyme inducers or inhibitors are given.(ABSTRACT TRUNCATED AT 400 WORDS)

Adeno-associated viral (AAV) liposomes and methods related thereto

Abstract: A composition for genetic manipulation which comprises a liposome comprised of lipid material, and adeno-associated viral (AAV) material. Typically, the AAV material is plasmid, and comprises a terminal repeat of the AAV genome. Methods are disclosed for introducing genetic material into cells by use of AAV liposomes. Accordingly, genetic material was introduced and integrated into stem cells, T cells, primary tumor cells, or tumor cell lines.

Compounds having antihypertensive and anti-ischemic properties

Abstract: This invention relates to adenosine derivatives and analogs which possess adenosine agonist activity and are useful as anti-hypertensive and anti-ischemic agents, to pharmaceutical compositions including such compounds, and to their use in treating hypertension and myocardial ischemia, and to methods and intermediates used in the preparation of such compounds.