Improvement of Charcot-Marie-Tooth Phenotype with a Nanocomplex Treatment in Two Transgenic Models of CMT1A.

Curcumin has been shown to exert beneficial effects in peripheral neuropathies. Despite its known biological activities, curcumin has unfavorable pharmacokinetics. Its instability has been linked to its failure in clinical trials of curcumin for the treatment of human pathologies. For this reason, we developed curcumin-loaded cyclodextrin/cellulose nanocrystals (NanoCur) to improve its pharmacokinetics. The present study aims to assess the potency of a low dose of NanoCur in 2 Charcot-Marie-Tooth disease type 1A (CMT1A) rodent models at different stages of the disease. The efficiency of NanoCur is also compared to that of Theracurmin (Thera), a commercially available curcumin formulation. The toxicity of a short-term and chronic exposure to the treatment is investigated both in vitro and in vivo, respectively. Furthermore, the entry route, the mechanism of action and the effect on the nerve phenotype are dissected in this study. Overall, the data support an improvement in sensorimotor functions, associated with amelioration in peripheral myelination in NanoCur-treated animals; an effect that was not evident in the Thera-treated group. That was combined with a high margin of safety both in vivo and in vitro. Furthermore, NanoCur appears to inhibit inflammatory pathways that normally include macrophage recruitment to the diseased nerve. This study shows that NanoCur shows therapeutic benefits with minimal systemic toxicity, suggesting that it is a potential therapeutic candidate for CMT1A and, possibly, for other neuropathies.

Quantitative phase restoration by direct inversion using the optical transfer function.

Quantitative phase recovery of phase objects is achieved by a direct inversion using the defocused weak object transfer function. The presented method is noniterative and is based on partially coherent principles. It also takes into account the optical properties of the system and gives the phase of the object directly. The proposed method is especially suitable for application to weak phase objects, such as live and unstained biological samples but, surprisingly, has also been shown to work with comparatively strong phase objects.

Analytical aspects of volatile substance abuse (VSA).

Through a case report, the authors illustrate the volatile substance abuse (VSA) toxicological investigation difficulties mainly due to evaporation of the compounds from postmortem samples and to the lack of reference data for interpretation. A 17-year-old man, student in a chemistry institute, was found dead with a plastic bag placed over his head. Several chemical substances were found in his belongings. Autopsy findings included serious pulmonary lesions and hemorrhagic digestive ulcerations. A large screening of drugs and toxic compounds and selective analyses for several classes of drugs of abuse were carried out in the autopsy samples. In particular, a headspace (HS), -gas chromatography/-mass spectrometry (GC/MS) technique was used to screen for volatile substances and metabolites in the biological samples and for residues of volatile substances on the surface of the plastic bag and in the chemicals found on the scene. The main analytical finding was the presence of alkanes (heptane, methyl-2-pentane, methyl-3-hexane, methylcyclohexane) in the gastric content. The literature data, VSA practices, long time-delay between death and autopsy, preservation conditions of the biological samples before analysis, and in-lab experiments on evaporation of volatile substances were considered to interpret this result. The present fatality was attributed to VSA with a gasoline-based stain remover like "eau écarlate," associated with a hypoxic recreation practice using a plastic bag.

Pharmacological exposure to ribavirin: a key player in the complex network of factors implicated in virological response and anaemia in hepatitis C treatment.

Ribavirin remains today a pivotal drug in the treatment of hepatitis C; in standard double therapy, as well as in triple combination with direct antiviral agents, ribavirin reduces relapse and can double the sustained virological response obtained with peginterferon alone or in association with direct antiviral agents. In the complex network of interacting factors determining sustained virological response independently of known predictive factors related to host and virus, two modern tools are emerging: polymorphisms in the IL28B gene and very early exposure to ribavirin. The use of a pharmacokinetic-pharmacodynamic model of early ribavirin exposure to adjust the dose individually would help promote a safer ribavirin use and improve sustained virological response. The variability of the influence of ribavirin exposure on anaemia is probably genetically determined; however, the low prevalence of the implicated protective alleles of the inosine triphosphate pyrophosphatase gene could explain their lack of influence on sustained virological response.