Marie Socha

Synthesis and characterization of S-nitrosoglutathione-oligosaccharide-chitosan as a nitric oxide donor

Objectives: The aim of this work is to synthesize a novel stable and biodegradable nitric oxide (NO) donor polymer based on a chitosan backbone. This polymer needed to be linked to glutathione (GSH), which was nitrosated in a second step. This polymer has been developed as an NO delivery platform that could be further evaluated for an oral delivery in Crohn’s disease. Methods: The new polymer (named S-nitrosoglutathione-oligosaccharide-chitosan or SNOC) was obtained using a two-step procedure involving the linkage of GSH to chitosan via an amidine reaction followed by a post-nitrosation with NaNO2. The GSH linkage was assessed using NMR, FTIR and an Ellman’s test, whereas the final NO amount was determined by the Griess and Saville method. Results: Polymers with different numbers of NO groups were obtained (159.04 ± 64.16 µmol/g of polymer for SNOC G1 and 525.08 ± 151.35 µmol/g of polymer for SNOC G2) depending on the procedure used for production. When tested in an Ussing chamber, SNOC G2 had a sustained release of NO and nitrites for at least 6 h. Conclusion: We believe that this type of polymer is adapted for the development of various formulations, including microparticles.

Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines

Abstract S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S-nitrosoglutathione-alginate, SNA) by cross-linking alginate with S-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn’s disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO2). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman’s method, and the amount of NO abducted on the polymer was calculated using the Griess–Saville method. An ex vivo model (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 ± 21 μmol/g for SNA F1 and 468 ± 23 μmol/g for SNA F2) depending on the procedure used for nitrosation. In the ex vivo studies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 μM.

The antitumor effects of an arsthinol–cyclodextrin complex in a heterotopic mouse model of glioma

In this paper, we examined arsthinol-cyclodextrin complexes, which display an anticancer activity. The association constants were 17,502±522 M(-1) for hydroxypropyl-β-cyclodextrin and 12,038±10,168 M(-1) for randomized methylated β-cyclodextrin. (1)H NMR experiments in solution also confirmed the formation of these complexes and demonstrated an insertion of the arsthinol (STB) with its dithiarsolane extremity into the wide rim of the hydroxypropyl-β-cyclodextrin cavity. Complexed arsthinol was more effective than arsenic trioxide (As2O3) and melarsoprol on the U87 MG cell line. Importantly, in the in vivo study, we observed significant antitumor activity against heterotopic xenografts after i.p. administration and did not see any signs of toxicity. This remains to be verified using an orthotopic model.

Unilateral mydriasis due to scopolamine patch

Case We report the case of a patient who presented with unilateral mydriasis after a scopolamine patch application. The specific clinical context (cancer) reported here may have led to the misinterpretation of the etiology of mydriasis. Conclusion Our case description warns against diagnostic mistakes related to this side effect and highlights the advantages of pilocarpine test in the differential diagnosis of unilateral mydriasis.

Inappropriate drug combinations in adult versus geriatric patients in a psychiatric setting

Introduction The objective of this study was to assess the reliability of drug–drug interaction software in monitoring prescriptions in psychiatric settings. Method A 1 day cross sectional analysis of the ongoing drug regimens in the inpatient population was carried out. Results This study showed a relatively high prevalence of hazardous or contraindicated drug combinations (approximately 15%). Three major categories of interactions were found: (1) those requiring diagnostic tests; (2) those requiring dosage adjustments, an appropriate drug choice or pharmacological class; and (3) those whose risk–benefit ratio was positive in the treatment indication. Discussion The findings demonstrate that without access to biological test results and indications, the most prevalent interactions cannot be validated by the pharmacist. These results suggest that the availability of these data is essential, and that interactions with prescribers should be facilitated in order to increase the quality of clinical pharmacy in psychiatry.

Assessing and making safe the medicine use pathway in paediatrics

Based on an assessment of adverse events in a follow-up care and rehabilitation unit in paediatrics, audits were carried out of the medicine use pathway. The evaluation grid taken from this study today serves as a basis for the audits carried out on the medicine use pathway on a national level.

À propos d’un cas d’hypersalivation secondaire à la substitution d’un traitement chronique par clonazépam

Les cas d’hypersalivation rapportes avec le clonazepam sont generalement lies a des expositions chroniques et/ou des augmentations posologiques. Nous rapportons ici un cas atypique ou une hypersalivation est apparue suite a une diminution de posologie d’un traitement par clonazepam lors d’un switch vers le diazepam. Cette substitution a ete realisee suite a l’evolution reglementaire recente sur les prescriptions de clonazepam per os. Le cas presente est discute en termes d’imputabilite de la molecule dans l’apparition de l’evenement indesirable et de la pertinence du choix d’une substitution comparativement a un sevrage au clonazepam.