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.

Decreased Susceptibility to Diet-Induced Atherosclerosis in Human Apolipoprotein A-II Transgenic Mice

Abstract: Studies performed in vivo have been controversial regarding the implication of human apolipoprotein (apo)A-II in the atherogenic process. Expression of human apoA-II in transgenic mice fed a chow diet leads to (1) a bimodal distribution of high density lipoprotein (HDL) size as in humans, (2) a reduction in total cholesterol concentration that is mainly due to a reduction in non-HDL cholesterol level, and (3) a dramatic reduction in mouse endogenous apoA-I and apoA-II. After 20 weeks on an atherogenic diet, transgenic mice had reduced total cholesterol concentrations because of a reduction in cholesterol associated with all lipoprotein classes. Endogenous apoA-I and apoA-II were also dramatically decreased in transgenic mice. The mean area of atherosclerotic lesions was drastically decreased in transgenic mice (-44%, P=0.0027) compared with control mice. The amount of aortic surface covered by lesions was positively correlated with very low density lipoprotein cholesterol (P<0.01) and intermediate density lipoprotein cholesterol levels (P<0.05). Transgenic mice were protected against the development of atherosclerosis despite a marked decrease in HDL cholesterol and apoA-I concentrations. This protection may be related to the marked reduction in circulating low density lipoprotein (very low density and intermediate density lipoprotein) levels in transgenic mice.

Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

Abstract: The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase I inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg−1 day−1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg−1 day−1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg−1 day−1 given on days 0–4, days 7–11, days 21–25 and days 28–32 (total dose, 200 mg kg−1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg−1 day−1 on days 0–4 and days 28–32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg−1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4–0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01–0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies. Int. J. Cancer 73:156–163, 1997. © 1997 Wiley-Liss, Inc.

Structure-activity relationships of a series of anti-inflammatory benzisoselenazolones (BISAs).

Abstract: Ebselen (2-phenyl1,2-benzisoselenazol-3(2H)-one) was discovered as a selenoorganic compound with anti-inflammatory activity which catalytically reduces hydroperoxides in the presence of thiols with a similar mechanism to that of endogenous glutathione peroxidase (GSH-Px) [1-3]. The compound has an unusual spectrum of antiinflammatory activity, being only weakly active in classical tests, such as carrageenan paw oedema and adjuvant arthritis and an effective inhibitor of novel experimental models, such as cobra venom factor (CVF) paw oedema and glucose oxidase monoarthritis [4]. In an attempt to increase the potency in comparison to ebselen, we have now tested a series of benzisoselenazolones (BISAs) and their respective benzisothiazolones in in vitro and in vivo tests. Adjuvant arthrit& was assessed by paw volume measurement of the noninjected paw in male HanWistar rats (n = 10-20) on days 10, 14, 17 and 21 after injection of Freund's complete adjuvant. Compounds (in 1% MHC, p.o.) were given daily on days 0 -17 or 10-17.