Non-contact scanning probe technique for electric field measurements based on nanowire field-effect transistor.

We report on the new active tip for scanning probe microscopy allowing the simultaneous measurements of surface topography and its potential profile. We designed and fabricated a field-effect transistor with nanowire channel located on the apex of silicon-on-insulator small chip. The field-effect transistor with nanowire channel was selected due to its extremely high electric field sensitivity even at room temperature. We developed the scanning probe operated in the tuning fork regime and demonstrated its reasonable spatial and field resolution. The proposed device can be a unique tool for high-sensitive, high-resolution, non-destructive potential profile mapping of nanoscale objects in physics, biology and material science. We discuss the ways to optimize the sensor charge sensitivity to the theoretical limit which is 10-3e/Hz-1/2 at room temperature.

Nanoimprint lithography using vertically aligned carbon nanostructures as stamps.

Nanoimprint lithography using vertically aligned carbon nanostructures as stamps is reported. The functionality of the stamp is demonstrated through lift-off and etch-back processes after pattern replication. The imprint process is robust and the stamp structures survived more than 50 consecutive imprints. In this paper we demonstrate this for feature sizes ranging from 80 nm to 200 microm where the aspect ratio of the individual nanostructures surpasses 1:5 with a pitch down to 100 nm. This demonstration opens up the possibility of utilizing vertically grown carbon nanostructures for manufacturing extremely high aspect ratio and small pitch stamps for nanoimprint lithography.

Study of the bioequivalence of two controlled-release formulations of morphine.

The management and treatment of chronic pain in cancer patients is a clear priority for practitioners regularly confronted by the situation. This investigation was carried out to evaluate the bioavailability of a recent sustained-release (SR) formulation of morphine sulphate (30 mg), Skenan, consisted of capsules, relative to a recognized product, Moscontin which is a matrix tablet SR form. The bioavailability was carried out on 12 healthy male volunteers who received a single dose (30 mg) of the test (T) and the recognized (R) products in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 24 hours. Morphine and its main metabolites (i.e. glucuronides M6G and M3G) were assayed by high-performance liquid chromatography using a ion-pair formation. Data were analyzed by a noncompartmental method and were compared by ANOVA method and, each subject taken as his own control, by the Wilcoxon T test. Mean bioavailability of the T formulation was greater than that of R. The parametric confidence intervals (90%) of the mean values of the pharmacokinetics characteristics for T:R ratio were in each case without the bioequivalence acceptable ranges of 0.8-1.25 and 0.70-1.43 respectively for AUCs (i.e. AUCo-->24h and AUCo-->infinity) and Cmax, while confidence intervals symmetric of Westlake (CIW90%) was invariably greater than 20%, i.e. 62.8, 71.1 and 39.3% respectively. Further, the test formulation was not found bioequivalent to the reference formulation by Schuirmann's 2 one-sided t-test. These results justify the conclusion of the non-bioequivalence of the two forms at the unit dose of 30 mg. This information must be considered above all as a dosage adjustment tool enabling use of the two forms by application of a correction factor of the order of 15% when prescribing Skenan in comparison with Moscontin. Assessment is needed of the possible clinical consequences of this finding.

[Pharmacokinetics of clofibrate in jaundiced newborn infants at term]. / Pharmacocinétique du clofibrate chez le nouveau-né à terme ictérique.

BACKGROUND: Clofibrate (CFB) has been proposed to increase elimination of bilirubin in neonates with hyperbilirubinemia. Nevertheless, its disposition, at this age, remains unknown. The aim of this work was to characterize pharmacokinetics of an oil formulation of CFB in neonates at term with jaundice. PATIENTS AND METHODS: Two groups (G1 and G2) of eight neonates, presenting with jaundice, entered an open, non randomized and comparative study. Five blood samples were collected over 50 hours following a single oral administration of 100 mg/kg or 50 mg/kg CFB, respectively, in G1 and G2. Serum concentrations of both CFB and clofibric acid (CFA) were measured by HPLC and the pharmacokinetic analysis was made by a non-compartmental method. Data were compared to those obtained in adults receiving 2 g dose of CFB. RESULTS: Tolerance to the treatment was excellent. Pharmacokinetic profiles were similar in both groups of infants. There was a slow and prolonged formation of CFA whose serum concentrations remained high 50 hours after drug administration. Non-hydrolyzed CFB was found in the blood of three neonates. Elimination of CFA was prolonged corresponding to a terminal half-life (t1/2m) often above 100 hours and sometimes incalculable. MRTo-->50 (h) was similar in both groups (ie 26.2 +/- 2.0 vs 25.5 +/- 1.3, respectively). The decrease of t1/2m was related to the decrease of the clearance of CFA. CONCLUSIONS: The decrease in CFB's metabolism in newborns is probably the result of at least two concurrent phenomenons: partial hydrolysis of CFA, especially at high doses, and decrease in the hepatic capacity to conjugate the active metabolite. A single oral administration of 50 mg/kg CFB seems to be a suitable schedule.

Disposition of ornidazole and its metabolites during pregnancy.

The disposition of ornidazole and its two major hydroxylated metabolites was studied in five pregnant women (gestational ages 25 5/7 to 38 4/7 weeks) with either chorioamnionitis or pyelonephritis treated with ceftriaxone 2 g, tobramycin 3 mg/kg body weight and ornidazole 1 g all administered once-daily. Two series of blood samples were obtained, the first on the first day of treatment and the second at steady-state on day 5. Local and systemic tolerability of ornidazole was excellent and patients showed complete remission without premature delivery. There was no evidence of ornidazole accumulation, and the pharmacokinetic parameters were very similar to those seen in healthy subjects. The dosage regimen of ornidazole therefore requires no adjustment during pregnancy. Trough concentrations of ornidazole measured at 24 h post dose were above the MIC of sensitive organisms. Children born to the trial patients showed normal initial development and their growth was normal.

[Pharmacological treatment of ectopic pregnancy]. / Le traitement pharmacologique des grossesses ectopiques.

The incidence of ectopic pregnancies (EP), has increased significantly in the past 20 years. Conservative tubal surgery has long been the treatment of choice. However, non-surgical treatment of EP has recently become an alternative to surgery. This pharmacological approach uses chiefly methotrexate but attempts have been reported using prostaglandins, actinomycin D, potassium chloride, mifepristone and anti-hCG monoclonal antibodies. Early diagnosis and close follow-up of EP by methods including transabdominal and transvaginal ultrasound examination and serial measurements of hCG allow to choose the more appropriate treatment of EP. The present article gives an overview of the pathophysiology of EP, followed by a review of the various pharmacological treatments available. This review is centered on methotrexate as the best known drug in this indication. Published data on local and general tolerance, efficacy and pharmacokinetics are reviewed. A pretherapeutic assessment score using six criteria is also discussed, the objective of which is to better define the surgical and non-surgical indications. The non-surgical treatment of EP can provide a safe and effective alternative to surgical treatment. However, further studies are needed to assess the effects of these pharmacological treatments on both fertility and risk of recurrence of EP.

Ceftriaxone distribution and protein binding between maternal blood and milk postpartum.

OBJECTIVE: To study postpartum distribution and protein binding of ceftriaxone (CTX) between maternal blood and milk and to discuss risk factors and possible impact for the neonate. DATA SOURCES: Reference articles and books are identified in the text. DATA SYNTHESIS: CTX distribution and protein binding between maternal blood and milk postpartum were studied in a patient at term presenting with acute pyelonephritis caused by Escherichia coli. The antibiotic therapy prescribed pending bacteriology results consisted of CTX 2 g/d, ornidazole 1 g/d, and tobramycin 3 mg/kg/d. Pharmacokinetics of total CTX were studied after the first 2-g infusion. At plateau (i.e., two days after delivery; seventh infusion), pharmacokinetics and milk distribution of total and free CTX also were studied. No accumulation of CTX was noted in the plasma at plateau. When high dosages of CTX are used (approximately 2 g), its penetration into the milk is important (i.e., protein binding capacity is overwhelmed). No notable adverse reactions occurred in mother or child. Thus, an important diffusion into the milk (4.4 percent of the dose) appears not to be clinically important. Our knowledge of both metabolism and milk distribution of drugs with high protein binding (> or = 95 percent) and an acid characteristic should be expanded to better understand their use during both the pregnancy and postpartum periods. Finally, the child of the patient described here has normal initial growth and development at the present time. CONCLUSIONS: Caution should be taken when drugs such as CTX, which have both high protein binding (> or = 95 percent) and an acid characteristic are administered to breastfeeding women. Drugs of this type should be systematically investigated to better understand their use during pregnancy and postpartum.