Large-Area Epitaxial Mott Insulating 1T-TaSe2 Monolayer on GaP(111)B.

Two-dimensional Mott materials have recently been reported in the dichalcogenide family with high potential for Mottronic applications. Nevertheless, their widespread use as a single or few layers is hampered by their limited device integration resulting from their growth on graphene, a metallic substrate. Here, we report on the fabrication of 1T-TaSe2 monolayers grown by molecular beam epitaxy on semiconducting gallium phosphide substrates. At the nanoscale, the charge density wave reconstruction and a moiré pattern resulting from the monolayer interaction with the substrate are observed by scanning tunneling microscopy. The fully open gap unveiled by tunneling spectroscopy, which can be further manipulated by the proximity of a metal tip, is confirmed by transport measurements from micrometric to millimetric scales, demonstrating a robust Mott insulating phase at up to 400 K.

Iuliacumite: A Novel Chemical Short-Range Order in a Two-Dimensional Wurtzite Single Monolayer InAs1-xSbx Shell on InAs Nanowires.

A chemical short-range order is found in single monolayer InAs1-xSbx shells, which inherit a wurtzite structure from the underlying InAs nanowire, instead of crystallizing in the energetically preferred zincblende structure. The chemical order is characterized by an anticorrelation ordering vector in the ⟨112̅0⟩ direction and arises from strong Sb-Sb repulsive interactions along the atomic chains in the ⟨112̅0⟩ direction.

A step further in the SATE mononucleotide prodrug approach.

Synthesis, in vitro anti-HIV activity, stability studies as well as potential for oral absorption of some novel phenyl S-acyl-2-thioethyl (SATE) phosphotriester derivatives of AZT (zidovudine; 3'-azido-2',3'- dideoxythymidine) are reported herein. These mononucleotide prodrugs (pronucleotides) are characterized by the presence of polar (amino or hydroxyl) functions on the SATE biolabile phosphate protections. Whereas pronucleotides incorporating an amino residue in the vicinity of the thioester functionality display low chemical stability, the introduction of one or two hydroxyl groups on the SATE moiety confers high resistance of the resulting prodrugs towards esterase hydrolysis. Thus, one of these pronucleotides, derivative 2, was able to cross a Caco-2 cell monolayer mainly in intact form, probing that its further development is warranted as a possible HIV-pronucleotide candidate.

Quantification of zidovudine and its monophosphate in cell extracts by on-line solid-phase extraction coupled to liquid chromatography.

A simple and rapid analytical method for the simultaneous quantification of zidovudine (AZT) and its monophosphate (AZTMP) in cell extracts has been developed using high-performance liquid chromatography (HPLC) with on-line solid-phase extraction and 2-aminoethyl-3'-azido-2',3'-dideoxythymidin-5'-yl phosphodiester sodium salt as internal standard (IS). The cell extract samples were directly injected on a short reversed-phase precolumn using an aqueous buffer containing an ion-pairing reagent as a mobile phase. Under these conditions, the analytes were retained on the precolumn whereas the proteins were discarded. The analytes were then transferred onto the analytical column by increasing the strength of the eluent. The calibration curve was linear over a concentration range of 0.5-100 microg/ml. Inter- and intra-day accuracy and precision results satisfied the accepted criteria for bioanalytical validation. This method was used to study the decomposition pathway of a model pronucleotide in an in vitro approach.

Diastereoisomeric resolution of a pronucleotide using solid phase extraction and high performance liquid chromatography: application to a stereoselective decomposition kinetic in cell extracts.

A stereospecific HPLC methodology has been developed for the diastereoisomeric resolution of a mononucleotide prodrug in cell extracts. This method involves the use of solid phase extraction on a C18 cartridge. Diastereoisomers and internal standard resolutions were performed on a cellulose based chiral column (Chiralcel OD-H) used in the normal phase mode. The method was validated in terms of specificity, recovery, linearity (diasteroisomers mixture concentration: 3-60 micromol L(-1)), precision and accuracy and detection limit (1.67 and 1.33 micromol L(-1) for first and second eluted diastereoisomer). This method was applied to the determination of the apparent rate constants of disappearance and half-lives of each stereoisomers. This permits to conclude to the stereoselectivity of the enzymatic activity involved in the decomposition pathway of 2.

Column selection and method development for the separation of nucleoside phosphotriester diastereoisomers, new potential anti-viral drugs. Application to cellular extract analysis.

Analytical HPLC methods using derivatized cellulose and amylose chiral stationary phases used in normal and reversed-phase modes were developed for the diastereoisomeric separation of mononucleotide prodrugs (pronucleotides) of 3'-azido-2',3'-dideoxythymidine (AZT). The resolutions were performed with two silica-based celluloses using normal and reversed-phase methodologies: Tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H and Chiracel OD-RH) and Tris-methylbenzoate (Chiralcel OJ and OJ-R). Two amyloses phases, Tris-3,5-dimethylphenylcarbamate (Chiralpak AD) and Tris-(S)-1-phenylethylcarbamate (Chiralpak AS), were used in normal-phase mode. Additionally, we developed separation using two stationary phases with immobilized cyclodextrins in reversed-phase and polar-organic modes. The mobile phase and the chiral stationary phase were varied to achieve the best resolution. Different types and concentration of aliphatic alcohols, acetonitrile or water in the mobile phase were also tested for the different separation modes. An optimal baseline separation (Rs > 1.5) was readily obtained with all silica-based celluloses and amyloses using a normal-phase methodology. The different columns gave complementary results in term of resolution. Limits of detection and quantification were 0.12-0.20 and 0.40-0.67 microm, respectively. This analytical method was applied in a preliminary study for the pronucleotide 2 quantification in cellular extract.

SATE pronucleotide approaches: an overview.

This review depicts in vitro and in vivo results obtained with nucleotide prodrugs (pronucleotides) bearing S-acyl-2-thioethyl (SATE) groups as esterase-labile phosphate protections. New developments are illustrated by the design of mononucleoside mixed phosphoester derivatives leading to the selective intracellular delivery of the corresponding 5'-mononucleotide through two different enzyme-mediated activation steps.

SATE (aryl) phosphotriester series. II. Stability studies and physicochemical parameters.

The stability of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-pivaloyl-2-thioethyl (tBuSATE) group and various aryl residues derived from L-tyrosine was evaluated in biological media. The results demonstrate that such compounds give rise to intracellular delivery of the parent mononucleotide through esterase and phosphodiesterase hydrolytic steps, successively.

[Chronic lupus erythematosus presenting as acneiform lesions]. / Lésions acnéiformes révélatrices d'un lupus érythémateux chronique.

BACKGROUND: Cutaneous manifestations of lupus erythematosus are numerous but usually permit easy diagnosis. However, there are atypical lesions that can mimic benign dermatologic disorders. We report on a patient with lesions of acne leading to the diagnosis of chronic lupus erythematosus, and who subsequently developed systemic lupus erythematosus. CASE REPORT: A 30-year-old woman presented with inflammatory lesions and comedos on the face. The eruption started after her last pregnancy and was refractory to local and general treatment. She also complained of arthralgia, Raynaud's phenomenon and diffuse alopecia. Cutaneous biopsy was characteristic of chronic lupus erythematosus. Immunofluorescence microscopy of lesional skin showed a lupus band deposit. Antinuclear antibodies were highly positive. The patient was successfully treated with chloroquine. Three years later, the patient presented with photodistributed eruption. Antinuclear antibodies were still positive and in addition anticardiolipin antibodies were found. Final diagnosis was systemic lupus erythematosus. DISCUSSION: Acneiform lesions are rarely reported in lupus erythematosus. Only three similar cases were reported in literature. Atypical and treatment-resistant eruptions should attract attention. Furthermore, the occurrence of systemic lupus in chronic lupus erythematosus is not an unfrequent phenomenon and the oestrogen-dependance of chronic lupus lesions may predict this association.

[Primitive cutaneous neuroendocrine carcinomas or Merkel's tumor. Clinical and therapeutic aspects in 22 patients]. / Carcinomes neuroendocrines cutanés primitifs ou tumeurs de Merkel. Aspects cliniques et thérapeutiques chez 22 malades.

INTRODUCTION: Primitive cutaneous neuroendocrine carcinoma (PCNC) is a rare tumor with poor prognosis. Surgery is the treatment of choice, but radiotherapy is taking a larger place in the management of these patients. METHODS: The files of 22 patients were studied retrospectively over a period of 14 years. RESULTS: The study included 17 women and 5 men with a mean age of 75.5 years. The localization of the tumor was the cephalic extremity in 12 cases. At the initial stage, the tumor in 3 of the 22 patients was of glandular or visceral localization. Thirteen stage I patients were treated surgically. Adjuvant radiotherapy was performed in 10 of these patients and only one relapsed (incomplete initial exeresis). The other three relapsed. Exclusive radiotherapy led to complete response in 4 patients who could not undergo surgery and in 2 with local relapses. Seven patients exhibited glandular involvement and 6 of them died (median 7 months) after the adenopathy had been discovered. DISCUSSION: Our series illustrates the clinical characteristics of this tumor of the elderly, which is predominantly cephalic and of rapid progression. From a therapeutic point of view, our results underline the benefit of radiotherapy as adjuvant to surgery. When surgery is impossible, and in the case of local relapse, radiotherapy gives good results.

Kinetics study of the biotransformation of an oligonucleotide prodrug in cells extract by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The fate of a dodecathymidine prodrug in cell extract was monitored by MALDI-TOF MS. This technique allows a facile identification and a relative quantification of metabolites produced. We showed that the relative peak intensities were similar to the relative metabolite proportions that permitted the determination of their half-lives. The oligonucleotide prodrug was fully metabolized to yield the T12 phosphorothioate likely through a carboxyesterase mediated mechanism.

Design of new mononucleotide prodrugs: aryl (SATE) phosphotriester derivatives.

Synthesis, biological activities and decomposition kinetics of novel phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-tButyl-2-thioethyl (tBuSATE) group and L-tyrosinyl residues are reported. All the derivatives appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments. The proposed decomposition process of these mixed phosphotriesters may involve successively an esterase and then a phosphodiesterase activation.

Direct MALDI-TOF MS analysis of oligonucleotides on solid support through a photolabile linker.

MALDI-TOF mass spectrometry was used to analyze oligonucleotides still anchored to long-chain alkylamine controlled-pore glass (LCAA-CPG) through a photolabile linker. This technique is useful to follow supported chemical reactions in real time and monitor by-products formation.

Rational design of a new series of pronucleotide.

A new pronucleotide series is described involving a two-step degradation process mediated by, respectively, carboxylesterase and phosphoramidase. Taking AZT as nucleosidyl moiety, it is shown that most of the compounds inhibit HIV replication in TK(-) cell line, which proves 5'-AZTMP delivery.

Inhibition of chitin synthetase from Saccharomyces cerevisiae by a new UDP-GlcNAc analogue.

The synthesis and biological evaluation of a new UDP-GlcNAc competitor (I), designed to mimic the transition state of the sugar donor in the enzymatic reaction catalysed by chitin synthetase, is described. Compound (I) was found to competitively inhibit chitin synthetase from Saccharomyces cerevisiae with respect to UDP-GlcNAc, but displayed minimal antifungal activity.

Kinetics study of the biotransformation of an oligonucleotide prodrug in cells extract by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.

The fate of a dodecathymidine prodrug in cell extract was monitored by MALDI-TOF MS. This technique allows a facile identification and a relative quantification of metabolites produced. We showed that the relative peak intensities were similar to the relative metabolite proportions that permitted the determination of their half-lives. We found a good fit between the calculated kinetics curves and the experimental points. The oligonucleotide prodrug was fully metabolized to yield the dodecathymidine phosphorothioate likely through a carboxyesterase mediated mechanism.

Synthesis of new (difluoromethylphosphono)azadisaccharides designed as bisubstrate analogue inhibitors for GlcNAc:beta-1,4 glycosyltransferases.

We report here the design, synthesis and antifungal evaluation of a new model of bisubstrate analogue inhibitor for glycosyltransferases. The synthetic strategy relies on the reductive amination between the aldehyde derived from an N-allylphosphono-pyrrolidine and an aminosugar.

[Ambulatory skin grafting in leg ulcers: a feasibility study of 34 patients]. / Greffe cutanée ambulatoire des ulcères de jambe: étude de faisabilité chez 34 malades.

OBJECTIVES: Despite the advent of modern dressings, management of leg ulcers remains a long costly process, particularly if no etiological treatment is possible. Autologous skin grafting is more and more widely used in this indication. The aim of this open single center noncomparative study was to analyze the feasibility of ambulatory procedures for skin grafting and the incidence of ambulatory care in a medical nursing clinic as an alternative to traditional hospitalization on total cost in this pathological condition. PATIENTS AND METHODS: Thirty-nine grafts were performed in 34 consecutive patients. No selection was made for etiology or duration of the leg ulcers. Three grafting techniques were used after debridement-cleansing: flap grafts for medium sized ulcers (29 cases), mesh grafts for large ulcers (6 cases) and patch grafts for small ulcers or ulcers with irregular contours (4 cases). The dressing was opened on day 5, nursing care was provided every 2 days and daily in case of infection. Percentage of healing was evaluated clinically on days 5, 15 and 30 then at months 3, 6 and 12. Photographs were taken. RESULTS: Four patients were lost to follow-up and one died. Among the 34 grafts assessed at 6 months, we obtained total healing in 56 p. 100, 75 p. 100 healing in 6 p. 100, 50 p. 100 healing in 9 p. 100 and failure in 29 p. 100. Healing rates were those expected for arterial ulcers and necrotic angiodermas. For venous leg ulcers, the rate of total healing was only 30 p. 100 at 6 months and 43 p. 100 at 1 year. Outcome depended on duration of the lesion and not on the type of skin graft or patient age. DISCUSSION: This prospective study reports outcome of ambulatory skin grafting in a large representative sample of patients with leg ulcers of various etiologies. The less favorable outcome for venous ulcers can be explained by the duration of the ulcerations and infection in these often neglected lesions. The risk of graft displacement, contact eczema, and infection must be recognized for early treatment. There were no cases with general complications. This ambulatory technique has the enormous advantage of limiting the risk of hospital-related problems in this elderly population and of reducing overall cost of care for leg ulcers, and finally of limiting the risk of recurrence by regular post-graft follow-up in a specialized center and by treatment of the causal disease.

Prooligonucleotide metabolism in a crude cell extract followed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.

Using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS) we studied the decomposition pathway of a prooligonucleotide during incubation in a crude cell extract. This study, involving no sample processing, except drop dailysis to remove salts, led us to identify more than thirty metabolites from several metabolic pathways.