The cardioprotectant 3',4'-dihydroxyflavonol inhibits opening of the mitochondrial permeability transition pore after myocardial ischemia and reperfusion in rats.

The study aimed to determine the effect of 3',4'-dihydroxyflavonol (DiOHF) on mitochondrial function, in particular opening of the mitochondrial permeability transition pore (mPTP), respiratory function and reactive oxygen species (ROS) production, in isolated cardiac mitochondria after coronary artery occlusion and reperfusion in vivo. Opening of the mPTP, oxygen consumption and ROS production (assessed by measurement of H2O2) was determined in mitochondria isolated from normal hearts or from the ischemic zone of rat hearts subjected to 30min coronary artery occlusion and 15min reperfusion. Treatment of sham rats with DiOHF (10mgkg(-1) iv) significantly increased the concentration of Ca(2+) required to stimulate mPTP opening. This was accompanied by increased state 3 oxygen consumption and decreased H2O2 release. Ischemia and reperfusion (IR) significantly decreased the concentration of Ca(2+) required to stimulate mPTP opening, decreased state 3 oxygen consumption and increased H2O2 release, when pyruvate plus malate was provided as a substrate. Treatment with DiOHF prevented IR-induced changes in mPTP opening, state 3 oxygen consumption and H2O2 release so that there was no difference compared to sham. In isolated cardiac mitochondria from normal rats DiOHF had no effect on mPTP opening or on state 3 respiration but caused a small increase in state 4 respiration and decreased the respiratory control ratio. DiOHF, administered during ischemia just before reperfusion, inhibits mPTP opening and preserves mitochondrial function through a mechanism likely to be independent of its antioxidant activity or any direct effect on the mPTP.

Lack of effect of doxycycline on trough concentrations of protease inhibitors or non-nucleoside reverse transcriptase inhibitors in HIV-infected patients.

BACKGROUND: Many HIV-treated patients travel to malaria-infected zones, but very few data are available on potential interactions between antiretroviral and antimalarial drugs. METHOD: We performed a pharmacokinetic study on the interaction of doxycycline (100 mg/d) on 2 protease inhibitors (PIs), atazanavir and lopinavir, and 2 non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, given at usual daily doses in HIV-infected migrants native from sub-Saharan Africa included in the VIHVO ANRS-study before travelling to a sub-Saharan country. Antiretroviral trough plasma concentrations were measured at enrollment visit during the month preceding the travel before doxycycline introduction and on the week following the patients' return to France when they had been taking doxycycline for at least 15 days. Impact of doxycycline on antiretroviral concentrations was tested either with antiretroviral drugs separately or within the therapeutic classes (PI or NNRTI) in patients with an HIV RNA level <50 copies/mL at both visits and with good declared adherence. The Two One-Sided Test that was adapted to the Wilcoxon test was used to evidence the lack of interaction. Sixty-five patients receiving regimens containing atazanavir (n = 1), ritonavir-boosted atazanavir (n = 14), ritonavir-boosted lopinavir (n = 23), efavirenz (n = 17), nevirapine (n = 10) were included. RESULTS: Lack of pharmacokinetic interaction was statistically significant when tested by therapeutic class (PI, P = .02; NNRTI, P = .005) and was not demonstrated for each antiretroviral when tested separately. CONCLUSION: This study is the first to assess the interaction of doxycycline on PI and NNRTI. This lack of pharmacokinetic interaction supports the choice of doxycycline as the antimalarial drug in patients treated with PI or NNRTI.

Physicochemical stability study of a new Trimix formulation for treatment of erectile dysfunction.

Currently, severe erectile dysfunction can be treated by intracavernous injections of solutions containing three active ingredients: prostaglandin E1 (PGE1), papaverine and urapidil. Very few data exist on this mixture where phentolamine has been replaced by Urapidil because Phentolamine is not used for this indication in France. The aim of our study was to assess the stability of this formulation and to extend its expiration to permit preparation of batches. Three batches of the preparation containing 15µg/mL PGE1, 15mg/mL of papaverine and 2mg/mL urapidil were made aseptically and then packed in polypropylene syringes stored at 4°C. The physico-chemical stability has been tested as follows: HPLC stability-indicating method, visual observation, measurement of pH and osmolarity. We found that the limiting factor was PGE1 and we exceeded the threshold of 10% loss after 55 days. Replacement of Urapidil by Phentolamine seems to have a slight detrimental effect on stability. Nevertheless, these results allow us to consider the advance preparation of this formulation and provide quality treatment to these patients by avoiding too frequent visits to the hospital.

[Assessment of physicians' and nurses' knowledge and practices of aerosol therapy]. / Évaluation des connaissances et des pratiques de la nébulisation par les soignants.

INTRODUCTION: Aerosol therapy is an efficient, but complex procedure. National and international practice guidelines are regularly updated. However, only a few studies have assessed the application of guidelines by users. The aim of this study is to assess the knowledge and practices of physicians and nurses regarding these guidelines. METHODS: Two self-administered questionnaires were designed by a working team and presented to physicians and nurses of four university hospitals in Paris. A pharmacy resident collected and analyzed the data with the aid of an online survey website. RESULTS: A total of 481 physicians and nurses completed the questionnaires (33 % of physicians and 67 % of nurses). Only 241/480 physicians and nurses (50 %) knew that several intravenous drugs cannot be nebulized. Ninety-four of 422 (22 %) of them always choose oxygen as the driving gas and 239/311 nurses (77 %) think that single use nebulizers can be re-used for the same patient. CONCLUSIONS: This survey shows that many physicians and nurses lack knowledge and use inappropriate practices. Based on these results, a booklet has been designed by the working team. This booklet should help health professionals to harmonize practices across hospitals and to follow the guidelines correctly.

Study of effects of Bt maize (Zea mays) events on Lepidoptera Ostrinia nubilalis, Sesamia nonagrioidesin southwestern France.

Crops of maize (Zea mays L.) were conducted in southwestern France with GMO (Genetic Modified Organism) vs isogenetic varieties in order to verify the control of European Corn Borer (ECB) Ostrinia nubilalis (Hübner) and the Corn Stalk Borer (CBS) Sesamia nonagrioides (Lefevbre) by GMO in field conditions. The bioassays were carried out in 1998 and 1999 before moratorium, then in 2005. Experiments involved respectively 18, 12 and 19 fields cultivated with Furio/Furio cb (GMO), Cecilia/ Elgina (GMO) and PR33P66/PR33P67 (GMO) varieties. These transgenic events expressed Cry1A(b) protein (Bt maize). Plants were noted for insect infestation assessment (number of larvae in stalks and ears per plant). Statistical tests used t-test on couple of plots. Results showed a significant difference in the density of both ECB and CBS between control and the two transgenic events. The two transgenic events acted differently. The control of the two Bt events on the two pests were differentiated and discussed. These experiments underlined the importance of field evaluation for testing real effects of transgenic events on crop according the environmental context.

Detection, identification and geographical distribution of European corn borer larval parasitoids using molecular markers.

Biological control requires specific tools for the accurate detection and identification of natural enemies, and to detect unusual variations in their density, which may follow changes in agricultural practices. Here we have developed specific molecular markers to detect Lydella thompsoni (Herting) and Pseudoperichaeta nigrolineata (Walker) (Diptera: Tachinidae) within the European corn borer, Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae). Primers amplifying fragments of the mitochondrial COI gene were designed following alignment of comparable sequences for a range of parasitoid and host species. Each of the primer pairs proved to be species specific to a tachinid species, amplifying DNA fragments of 191 and 91 bp in length for L. thompsoni and P. nigrolineata, respectively. This DNA-based technique allowed molecular evaluation of parasitism in O. nubilalis natural populations. In order to study the geographical distribution of both species in France, O. nubilalis diapausing larvae in maize stalks were collected from 12 locations over the whole country. The molecular evaluation of parasitism was compared with the traditional method of maintaining O. nubilalis populations in controlled conditions before breaking off the diapause. The percentage parasitism found in both species of tachinids was higher--approximately three times--using the molecular method, suggesting an underestimation by the traditional rearing protocol. Tachinid parasitism on O. nubilalis was not significantly different between geographical areas (south, central and north France) for both species. This study shows that molecular methods are very promising for the correct detection and identification of tachinid parasitoids in natural field populations.