Therapeutic drug monitoring of intravenous anti-tuberculous therapy: management of an 8-month-old child with tuberculous meningitis.

Tuberculous meningitis (TBM) is now uncommon in high-income countries. It is the most severe form of extrapulmonary tuberculosis with high rates of mortality and morbidity if diagnosis and treatment are delayed. An 8-month-old girl with TBM who was treated with high-dose intravenous anti-tuberculous drugs (ATD) is reported. Therapeutic drug monitoring (TDM) of isoniazid and rifampicin was undertaken by measuring serial drug concentrations in serum and cerebrospinal fluid (CSF). There was rapid eradication of Mycobacterium tuberculosis from the CSF with a good clinical outcome and no adverse effects. Using high-dose regimens of intravenous ATD to treat TBM is an important option in order to obtain sufficient CSF diffusion. When available, TDM and a multidisciplinary approach are essential for efficient therapeutic management.

Structural properties of POPC monolayers under lateral compression: computer simulations analysis.

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a lipid comprising a saturated and an unsaturated acyl chain, belongs to the class of glycerophosphatidylcholines, major lipids in eukaryotic cell membranes. To get insight into the structural properties of this lipid within monolayers as membrane models, we performed molecular dynamics (MD) simulations of POPC monolayers under compression at the air/water interface. MD simulations were carried out at 300 K and at different surface pressures using the all-atom general Amber force field (GAFF). A good agreement was found between the simulated data and experimental isotherms. At surface pressures greater than 15 mN/m, two orientations of the head groups clearly appear: one nearly parallel to the monolayer interface and another one pointing toward the water. On the basis of the analysis of headgroup dihedral angles, we propose that the conformational variations around the bonds connecting the phosphorus atom to the adjacent oxygens are involved in these two orientations of the headgroup. The glycerol group orientation is characterized by a large distribution centered around 50° with respect to the monolayer normal. The acyl chains are predominantly in trans configuration from 7.5 to 43 mN/m surface pressures. Moreover, the calculated order parameter profiles of both chains suggest an independent behavior of the saturated and unsaturated chains that could be correlated with the formation of chain-type clusters observed along the simulated trajectories.

In silico platform for xenobiotics ADME-T pharmacological properties modeling and prediction. Part I: Beyond the reduction of animal model use.

There is an urgent need for efficient in silico ADME-T prediction tools for the selection of potent therapeutic drugs as well as the elimination of toxic compounds. This is particularly important in view of the high costs and ethical issues inherent to the use of animal models for drugs filtering. To achieve this mission, not only does the accuracy of in silico tools need to be improved, but also new experts in the field with skills in theoretical chemistry, clinical and fundamental biology have to be trained. Similarly, clinical biologists committed to the obligation of means and legally responsible for the results they generate could establish a legal framework that defines legal responsibilities when performing in silico predictions.