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Papers by Nathalie Hasler-Nguyen

Acta Pharmaceutica Hungarica

Background Topically applied non-steroidal anti-inflammatory drugs (NSAIDs) can produce clinicall... more Background Topically applied non-steroidal anti-inflammatory drugs (NSAIDs) can produce clinically effective drug concentrations at a peripheral site, but with low systemic concentrations and thus a lower risk of AEs. Various factors influence penetration and absorption of topical NSAIDs such as chemical properties of adjuvants included in the formulation and inter-individual variability in skin absorption. Modulating skin permeation is a pivotal factor in the development of new formulations as well as their posology and duration of therapeutic effect. Diclofenac diethylamine (DDEA) 1.16% gel (Voltaren® EmulgelTM [VEG 1%], Novartis Consumer Health, Nyon Switzerland) is used topically to relief pain and inflammation; it is applied to the affected site 3 or 4 times daily. We compared the in vitro skin permeation of VEG 1% with a new double-strength formulation of DDEA 2.32% [VEG 2%] including different doses of a permeation enhancer (PE) to assess the hypothesis of increased skin perm...

BMC Research Notes, 2012

Background: Rubbing a topical NSAID (non steroidal anti-inflammatory drug) on the skin may increa... more Background: Rubbing a topical NSAID (non steroidal anti-inflammatory drug) on the skin may increase local drug permeation, affecting its distribution to the site of pain and inflammation. The present study evaluates this hypothesis, by assessing in vitro the effect on skin permeation of applying diclofenac-dieythylamine 1.16% gel with or without rubbing. Methods: A single dose of 5 mg/cm 2 diclofenac-diethylamine 1.16% gel was applied on excised human skin mounted in Franz-type diffusion cells without or with rubbing for 45 s. Drug penetration into the skin layers was determined after 1 h using the tape stripping technique. In vitro cutaneous permeation into the receptor fluid of the diffusion chamber was measured up to 24 h. Skin electrical resistance was also recorded. Results: Application of diclofenac-diethylamine 1.16% gel with rubbing resulted to a 5-fold higher flux of diclofenac through the skin than when applied without rubbing at 8 h (P = 0.04). Skin rubbing for 45 s decreased by 2-fold skin electrical resistance when compared to the standard application. Application of diclofenac-diethylamine 1.16% gel with rubbing tended to result in higher accumulation in the stripped skin vs. the superficial skin layers when applied without rubbing (P = 0.2). Conclusion: These results suggest that rubbing may alter the superficial skin layer resulting in a transient faster initial diffusion of topically applied diclofenac through the stratum corneum into the deeper skin layer of the dermis to the tissue target.

BMC Dermatology, 2009

Background: Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin... more Background: Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm 2 of acyclovir 5% cream or penciclovir 1% cream. Methods: After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physicochemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips. Results: Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells. Conclusion: Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.

B and C) and freshly stimulated saliva after 60 min and 120 min of mastication (mean ± standard d... more B and C) and freshly stimulated saliva after 60 min and 120 min of mastication (mean ± standard deviation of 16 samples). Note: Bars with the same number of asterisks at the same time point are not statistically different. Gums A and B versus C or saliva, as well as C versus saliva, are significantly different (at p < 0.01) at 60 and 120 min.<b>Copyright information:</b>Taken from "tooth whitening effect of two medicated chewing gums compared to a whitening gum and saliva"http://www.biomedcentral.com/1472-6831/8/23BMC Oral Health 2008;8():23-23.Published online 11 Aug 2008PMCID:PMC2527295.

BMC Oral Health, 2008

Background Extrinsic staining of teeth may result from the deposition of a variety of pigments in... more Background Extrinsic staining of teeth may result from the deposition of a variety of pigments into or onto the tooth surface, which originate mainly from diet or from tobacco use. More recently, clinical studies have demonstrated the efficacy of some chewing gums in removing extrinsic tooth staining. The aim of this study was to assess the effectiveness of two nicotine medicated chewing gums (A and B) on stain removal in an in vitro experiment, when compared with a confectionary whitening chewing gum (C) and human saliva (D). Methods Bovine incisors were stained by alternating air exposure and immersion in a broth containing natural pigments such as coffee, tea and oral microorganisms for 10 days. Stained enamel samples were exposed to saliva alone or to the test chewing gums under conditions simulating human mastication. The coloration change of the enamel samples was measured using a spectrophotometer. Measurements were obtained for each specimen (average of three absorbances) us...

Phlebology, 2004

Objective: This study was undertaken to further elucidate the mechanism of action of the phleboto... more Objective: This study was undertaken to further elucidate the mechanism of action of the phlebotonic drug Venoruton®, which is a standardized mixture of hydroxyethylrutosides (HR). Methods: First, its oral absorption in rats was compared with that of hydroxyethylquercetins (HQ), which are the hydrolysed aglycones of HR. Second, the pharmacological activity of the major HR metabolites in humans, mono-3′-hydroxyethylquercetin (mono-3′HQ) and a mixture with mono-4′HQ, were further evaluated in vitro. Results: Time to reach the maximal plasma concentration of its marker metabolite mono-4′HQ was significantly shorter after HQ than after HR administration, with an eightfold higher maximal concentration. The rapid absorption of HQ and the increased plasma levels confirm the theory that rutosides need to be hydrolysed by the intestinal microflora prior to absorption. Mono-3′HQ and, even more so, the mixture with mono-4′HQ inhibited xanthine oxidase, an enzyme responsible for the formation o...

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2004

Nineteen coded chemicals were tested in an international collaborative study for their mutagenic ... more Nineteen coded chemicals were tested in an international collaborative study for their mutagenic activity. The assay system employed was the Ames II Mutagenicity Assay, using the tester strains TA98 and TAMix (TA7001-7006). The test compounds were selected from a published study with a large data set from the standard Ames plate-incorporation test. The following test compounds including matched pairs were investigated: cyclophoshamide, 2-naphthylamine, benzo(a)pyrene, pyrene, 2-acetylaminofluorene, 4,4 ′-methylene-bis(2-chloroaniline), 9,10-dimethylanthracene, anthracene, 4-nitroquinoline-N-oxide, diphenylnitrosamine, urethane, isopropyl-N(3-chlorophenyl)carbamate, benzidine, 3,3 ′-5,5 ′-tetramethylbenzidine, azoxybenzene, 3-aminotriazole, diethylstilbestrol, sucrose and methionine. The results of both assay systems were compared, and the inter-laboratory consistency of the Ames II test was assessed. Of the eight mutagens selected, six were correctly identified with the Ames II assay by all laboratories, one compound was judged positive by five of six investigators and one by four of six laboratories. All seven non-mutagenic samples were consistently negative in the Ames II assay. Of the four chemicals that gave inconsistent results in the traditional Ames test, three were uniformly classified as either positive or negative in the present study, whereas one compound gave equivocal results. A comparison of the test outcome of the different investigators resulted in an inter-laboratory consistency of 89.5%. Owing to the high concordance between the two test systems, and the low inter-laboratory variability in the Ames II assay results, the Ames II is an effective screening alternative to the standard Ames test, requiring less test material and labor.

BMC Pharmacology, 2009

Background Diclofenac is a nonsteroidal anti-inflammatory drug which is available as prescription... more Background Diclofenac is a nonsteroidal anti-inflammatory drug which is available as prescription (RX) and over-the-counter (OTC) medication for the systemic and topical treatment of painful and inflammatory conditions such as arthritis and back pain. This study was undertaken to investigate the distribution and retention of diclofenac and/or its metabolites in inflamed tissues, using the carrageenan-induced inflammation model and quantitative whole body autoradiography in rats. Methods [14C]diclofenac sodium was administrated as a single 2 mg/kg oral dose 1 h after injection of carrageenan into one front and one hind footpads and subcutaneously into the dorsum of the neck of rats. A control animal received saline injections. Three carrageenan-treated rats and one control rat were sacrificed at 1, 4, 8, and 24 h after [14C]diclofenac sodium administration (total of 4 rats/time point). The carcasses were immediately snap-frozen and prepared for cryosectioning. Lengthwise whole-body s...

Research article Oral health investigations of indigenous participants in remote settings: a meth... more Research article Oral health investigations of indigenous participants in remote settings: a methods paper describing the dental component of wave III of an Australian Aboriginal birth cohort study

L'invention concerne une source de δ-tocotrienol et/ou de tocopherol qui agit en synergie ave... more L'invention concerne une source de δ-tocotrienol et/ou de tocopherol qui agit en synergie avec une source antioxydante comportant des polyphenols afin de supprimer l'oxydation LDL dans le serum. La combinaison de ces deux sources antioxydantes offre une large gamme d'applications dans le traitement de conditions medicales dues a une generation de radicaux libres, incluant l'arteriosclerose et le cancer.