פרסומים

Crystal growth of calcium hydrogenphosphate dihydrate (DCPD), in the presence of polyaspartic acid or calcium phytate (system A), as well as nucleation and growth of octacalcium phosphate (OCP), in the presence of poly-L-lysine, poly-L-glutamic acid or polystyrene sulfonate (system B) were investigated. In system A crystn. of DCPD was inhibited and the crystal growth morphol. was specifically modified by preferential interaction of the resp. additive with the dominant (010) crystal face. In system B crystals were formed via precursor phase(s) and polyelectrolytes exhibited dual action, at low concns. inducing and at high concns. inhibiting nucleation of the cryst. phase. Crystal/additive interactions controlling growth were nonspecific and resulted in smaller crystals with rounded edges, but with the same basic orientation as in the controls. [on SciFinder(R)]

Off-centered top-seeded solution growth (TSSG) method is demonstrated as an effective and simple way to generate controlled composition modulation in potassium lithium tantalate niobate (KLTN) single crystals. The changes in concentration were measured by differential interference contrast (DIC) microscopy. Large length with periodic modulations ranging from 1 to 5 mum in period was grown along a KLTN sample with period dispersion lower than 2%. (C) 2004 Elsevier B.V. All rights reserved.

OBJECTIVE: Although there are several animal models of epilepsy, the extrapolation of antiepileptic drug (AEDs) performance to epileptic patients from anticonvulsant activity results in animals is not straightforward. Consequently, the aim of this work was to perform a correlation analysis between therapeutic daily doses (D) and average steady-state plasma concentrations (Css,av) of AEDs and their activity in common anticonvulsant animal models. METHODS: AED activity in anticonvulsant animal models was expressed as maximal electroshock seizure (MES) test ED50 values in mice and rats and ED50 values in audiogenic seizure-susceptible mice (AGS ED50). Data were examined, by use of linear and logarithmic approaches, for an association between Css,av (mg/L or micromol/L) and D (mg or mmol) for each AED in epileptic patients as the dependent variable (Y) and its MES ED50 in mice and rats and AGS ED50 in mice (mg/kg or micromol/kg) as the independent variable (X). RESULTS: Linear correlation analyses between Css,av (mg/L) and ED50 (mg/kg) for 11 AEDs gave the following correlation coefficients (R2): 0.68 (mice, MES); 0.73 (rat, MES); 0.64 (AGS). Switching the units from milligrams to micromoles improved the correlation significantly and gave the following R2 values: 0.88 (mice, MES); 0.90 (rat, MES); 0.76 (AGS). The linear correlation between Css,av and ED50 was better than that between D and ED50. CONCLUSIONS: The results of this analysis suggest that the relationship between Css,av and ED50 is useful in predicting target concentration ranges in humans. The Y intercepts of the Css,av-versus-ED50 and D-versus- ED50 plots were similar in all three animal models and ranged between 12 and 17 mg/L and between 570 and 890 mg, respectively, indicating that for all AEDs analyzed except valproic acid and ethosuximide, the therapeutic plasma concentration is in the range 10-20 mg/L.

We report an intriguing empirical observation. The relationship between corruption and output depends on the economy's degree of openness: in open economies, corruption and GNP per capita are strongly negatively correlated; but in closed economies, there is no relationship at all. This stylized fact is robust to a variety of different empirical specifications. In particular, the same basic pattern persists if we use alternative measures of openness, if we focus on different time periods, if we restrict the sample to include only highly corrupt countries, if we restrict attention to specific geographic areas or to poor countries, and if we allow for the possible endogeneity of both the corruption and openness measures. We find that the extent to which corruption affects output is determined primarily by the degree of financial openness. The difference between closed and open economies is mainly due to the different effect of corruption on capital accumulation. We present a model, consistent with these findings, in which the main channel through which corruption affects output is capital drain.

DNA can be delivered into the cell nucleus either using physical means or specific carriers that carry the genes into the cells for gene expression). Various carriers for delivering genes have been investigated which can be divided into two main groups: viral carriers where the DNA to be delivered is inserted into a virus, and cationic molecular carriers that form electrostatic interactions with DNA). Successful gene therapy depends on the efficient delivery of genetic materials into the cells nucleus and its effective expression within these cells). Although at present the in vivo expression levels of synthetic molecular gene vectors are lower than for viral vectors and gene expression is transient, these vehicles are likely to present several advantages including safety, low-immunogenicity, capacity to deliver large genes and large-scale production at low-cost). The two leading classes of synthetic gene delivery systems that have been mostly investigated are cationic lipids and cationic polymers). This review discusses recent developments in viral vectors, physical means and molecular gene carriers). The last part focuses on our recent studies in developing a new series of biodegradable polycations for in vitro and in vivo gene transfection).

This paper studies the role of business cycles in the phenomenon of increasing government-spending/GDP ratios in the OECD countries. An empirical framework that includes both long-run and cyclical considerations in the determination of government spending is applied to panel data covering 1975–1998. The main finding is that the prolonged rise in the spending/GDP ratio is partially explained by cyclical upward ratcheting due to asymmetric fiscal behavior: the ratio increases during recessions and is only partially reduced in expansions. The long-run ratcheting effect is estimated as approximately 2% of GDP. Also analyzed are the cyclical changes in the composition of government spending (government consumption, transfers and subsidies, and capital expenditure), as well as a possible link between cyclical ratcheting and government weakness.

Collagen matrices can be used as non-viral biocompatible gene carriers for localized implantable gene therapy. Collagen matrices embedding pDNA with enhanced binding through condensing agent linkage to the matrix or to the pDNA have been formulated, and characterized in various systems. pDNA and condensed pDNA were released intact from the matrices within 1-2 days. In vitro transfection with collagen matrices containing pDNA (luciferase encoding), pDNA in liposome (LIP), and pDNA with polyethylenimine (PEI) resulted in significantly higher expression levels in comparison to naked pDNA. pDNA-LIP matrices exhibited a dose response transfection of NIH 3T3, 293, MDA-MB-231 and smooth muscle cells (SMCs) in cell cultures. Subdermal implantations of collagen-polylysine-pDNA matrices in rats resulted in significantly higher gene expression levels in comparison to non-condensed pDNA matrices. Perivascular treatment with pDNA matrix and of naked pDNA solution in balloon-injured rat carotid arteries resulted in significant expression. In conclusion, a facile method for embedding cationic formulations of pDNA in collagen matrices was developed. These bioactive matrices seem to be suitable for tissue engineering and local gene therapy strategies.

PURPOSE: To assess the corneal iontophoretic delivery of gentamicin by drug-loaded hydrogel probe, and to determine the resultant ocular disposition and elimination of the drug from the cornea and anterior chamber. METHODS: Corneal iontophoresis of gentamicin sulfate was studied in healthy white rabbits by using drug-loaded disposable hydroxyethyl methacrylate (HEMA) hydrogel disk probes and a portable mini-ion device designed in the authors' laboratory. The iontophoretic treatment was performed with a current intensity of 1 mA for 60 seconds only. Three control groups were used: mock iontophoresis (no current) for 60 seconds, topical eye drops of fortified gentamicin (1.4%) every 5 minutes for 1 hour, and subconjunctival injection of 0.25 mL of 40 mg/mL gentamicin solution. The animals in the iontophoretic experimental groups were killed at predetermined time points. The gentamicin concentrations in the cornea and aqueous humor were assayed with a fluorescence polarization immunoassay. Analysis of the gentamicin eye pharmacokinetics was performed with a modeling approach. RESULTS: Peak gentamicin concentrations in the cornea (363.1 +/- 127.3 microg/g) and in the aqueous humor (29.4 +/- 17.4 microg/mL) were reached at 0 and 2 hours after the iontophoretic treatment, respectively. The peak gentamicin concentrations after a single iontophoresis treatment were 12 to 15 times higher than those obtained after gentamicin injection or after topical eye drop instillation, and much higher than in mock iontophoresis. The concentration versus time profile of gentamicin in the cornea and the anterior chamber after iontophoresis was appropriately described by applying a two-compartment pharmacokinetic model. CONCLUSIONS: A short iontophoretic treatment using gentamicin-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior segments of the eye and maintaining therapeutic drug levels in the cornea for more than 8 hours.