Medicinal Chemistry: A Teacher's and Worker's Perspective

This personal commentary aims at offering a description of the origin, purpose, and methods of medicinal chemistry, and a delineation of its fields of activity in connection with related sciences. Directions of future development of medicinal chemistry as a science are suggested

The quenched generating functional for hadronic weak interactions

The ultraviolet behaviour of the generating functional for hadronic weak interactions with $|\Delta S| =1, 2$ is investigated to one loop for a generic number of flavours and in the quenched approximation. New quenched chiral logarithms generated by the weak interactions can be accounted for via a redefinition of the weak mass term in the $\Delta S=\pm 1$ weak effective Lagrangian at leading order. Finally, we illustrate how chiral logarithms are modified by the quenched approximation in $K\to\pi\pi$ matrix elements with $\Delta I=1/2$ and 3/2.Comment: LATTICE98(matrixelement), 3 page

A 0-dimensional counter-example to rooting?

We provide an example of a 0-dimensional field theory where rooting does not work.Comment: 3 pages; Physics Letters B (2010

Results from a Non-Perturbative Renormalization of Lattice Operators

We propose a general renormalization method, which avoids completely the use of lattice perturbation theory. We present the results from its numerical applications to two-fermion operators on a $16^3 \times 32$ lattice, at $\beta=6.0$.Comment: 3 pages postscript file. Contribution to Lattice '9

Non-Perturbative Renormalisation and Kaon Physics

A general review is presented on the problem of non perturbative computation of the $K\to\pi\pi$ transition amplitude.Comment: 8 pages, Latex, uses espcrc2.sty, Talk given at LATTICE9

Non-perturbative renormalization in kaon decays

We discuss the application of the MPSTV non-perturbative method \cite{NPM} to the operators relevant to kaon decays. This enables us to reappraise the long-standing question of the $\Delta I=1/2$ rule, which involves power-divergent subtractions that cannot be evaluated in perturbation theory. We also study the mixing with dimension-six operators and discuss its implications to the chiral behaviour of the $B_K$ parameter.Comment: Talk presented at LATTICE96(improvement), LaTeX 3 pages, uses espcrc2, 2 postscript figure

Quantitative Structure-Permeation Relationships (QSPeRs) to Predict Skin Permeation: A Critical Evaluation

Purpose. Development of reliable mathematical models to predict skin permeability remains a challenging objective. This article examines some of the existing algorithms and critically evaluates their statistical relevance. Methods. Complete statistics were recalculated for a number of published models using a stepwise multiple regression procedure. The predictivity of the models was obtained by cross-validation using a "leave-one-out” deletion pattern. The relative contribution of each independent variable to the models was calculated by a standardization procedure. Results. The heterogeneity of the data in terms of skin origin and experimental conditions has been shown to contribute to the residual variance in existing models. Furthermore, rigorous statistics demonstrate that some published models are based on nonsignificant parameters. As such, they afford misleading mechanistic insight and will lead to over-interpretation of the data. Conclusions. The large number of published models reflects the need for predictive tools in cutaneous drug delivery and toxicology. However, such models are more reliable when confined within well-defined chemical classes, and their applicability is often limited by the narrow property space of the set of permeants under stud

The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube

Aims: To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers. Methods: In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, $${\text{AUC}}_{0 - \infty }$$ , t½, ke, tmax) were compared statistically, and Cmax, $${\text{AUC}}_{0 - \infty }$$ and tmax were analyzed for bioequivalence. Results: A statistically significant difference was seen in the $${\text{AUC}}_{0 - \infty }$$ of bromazepam, with nasogastric administration decreasing availability by about 25%: AUCOR = 2501 ng mL−1 h; AUCNT = 1855ng mL−1 h (p  0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUCOR = 37μg mL−1 h; AUCNT = 41μg mL−1 h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28). Conclusion: The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drug

Molecular Factors Influencing Retention on Immobilized Artificial Membranes (IAM) Compared to Partitioning in Liposomes and n -Octanol

Purpose. To assess the effect of molecular factors influencing retention on immobilized artificial membrane (IAM) high-performance liquid chromatography columns compared to liposomal partitioning and traditional n-octanol/water partition coefficients. Methods. IAM capacity factors were measured at pH 7.0 on an IAM.PC.DD2 stationary phase. Liposomal partitioning at pH 7.0 and n-octanol/water partition coefficients were measured using the pH metric method. Partitioning in egg-phosphatidylcholine (PhC) liposomes was also measured by equilibrium dialysis for a series of β-blockers. Results. For the ionized β-blockers, potentiometry and equilibrium dialysis yielded consistent partitioning data. For relatively large bases, IAM retention correlated well with PhC liposome partitioning, hydrophobic forces being mainly involved. For more hydrophilic compounds and for heterogeneous solutes, in contrast, the balance between electrostatic and hydrophobic interactions was not the same in the two systems. Hydrogen bonding, an important factor in liposomes partitioning, played only a minor role in IAM retention. Conclusions. Partitioning in immobilized artificial membranes depends on size, hydrophobicity, and charge. When hydrophobic interactions dominate retention, IAM capacity factors are well correlated with liposomal partitioning. On the contary, for hydrophilic solutes, the two systems do not yield the same information and are not interchangeabl