Reduction-triggered delivery using nucleoside-lipid based carriers possessing a cleavable PEG coating.

A new non-ionic nucleoside based lipid (DOU-SS-PEG(2000), 5'-PEG(2000)-2',3'-dioleoyluridine) featuring uridine (U) as nucleoside and 2',3'-dioleyl (DO), as lipid moieties and a poly(ethylene glycol) (PEG) thiolytic cleavable spacer for in vitro delivery of drugs is described. The PEG detachable nucleotide lipid (DOU-SS-PEG(2000)) was prepared via a convergent synthesis starting from HS-PEG-OMe and uridine. The reduction-triggered delivery using the PEG detachable nucleoside lipid DOU-SS-PEG(2000) was evaluated on both liposomal and micellar objects.

Cationic nucleoside lipids derived from universal bases: A rational approach for siRNA transfection.

Cationic nucleoside lipids (CNLs) derived from 5-nitroindole and 4-nitroimidazole bases were prepared from d-ribose by using a straightforward chemical synthesis. TEM experiments indicate that these amphiphilic molecules self-assemble to form supramolecular organizations in aqueous solutions. Electrophoresis and standard ethidium bromide (EB) fluorescence displacement assay shows that CNLs are able to bind siRNA.

Glycosyl-nucleoside-lipid based supramolecular assembly as a nanostructured material with nucleic acid delivery capabilities.

A glycosyl-nucleoside-lipid self-assembles to give highly organized structures such as fibers and nanotubes, which can stabilize hydrogels; carbohydrate moieties provide a suitable environment to deliver nucleic acids into human cells.

The effect of charge-reversal amphiphile spacer composition on DNA and siRNA delivery.

A series of charge-reversal amphiphiles with different spacers separating the headgroup from the hydrophobic chains are described for delivery of DNA and siRNA. Among them, the amphiphiles possessing a glycine spacer (e.g.

Identification of novel truncated androgen receptor (AR) mutants including unreported pre-mRNA splicing variants in the 22Rv1 hormone-refractory prostate cancer (PCa) cell line.

Advanced prostate cancer (PCa) has emerged as a public health concern due to population aging. Although androgen deprivation has proven efficacy in this condition, most advanced PCa patients will have to face failure of androgen deprivation as a treatment. Mutations in the androgen receptor (AR) from tumor cells have been shown to induce androgen independency both in PCa cell lines and in the clinic.

Anionic nucleotide--lipids for in vitro DNA transfection.

A family of new anionic nucleotide based lipids featuring thymidine-3'-monophosphate as nucleotide and 1,2-diacyl-sn-glycerol as lipid moiety for in vitro delivery of nucleic acids is described. The nucleotide lipids were prepared in three steps starting from 1,2-diacyl-sn-glycerols and 2'-deoxythymidine-3'-phosphoramidite. Gel electrophoresis experiments show that nucleotide-based lipid-DNA complexes are observed at Ca(2+) concentration higher than 1 mM.

Upper gastrointestinal symptoms in patients treated with nonsteroidal anti-inflammatory drugs: prevalence and impact--the COMPLAINS study.

Objectives: To investigate the prevalence and type of upper gastrointestinal symptoms during nonsteroidal anti-inflammatory drug (NSAID) therapy, the impact of these symptoms on daily life and adherence to treatment and the concordance between physicians' and patients' assessments.

Methods: A sample of 1000 French rheumatologists was invited to participate in the study, of which 630 accepted. Participating physicians enrolled all patients above 18 years of age seen during a 1-week period who had been receiving daily NSAID treatment for at least 3 days (n = 8269).

Glycosyl-nucleoside lipids as low-molecular-weight gelators.

A family of new glycosyl-nucleoside lipids (GNLs) that were prepared using a convenient "double click" chemistry route is described. Physicochemical studies (surface tension measurements, gelation properties, and transmission electron microscopy) indicate that these amphiphiles spontaneously assemble into supramolecular structures including fibers, vesicles, hydrogels, and organogels. GNLs possess unique gelation properties both in water and chloroform.

Cationic nucleoside lipids based on a 3-nitropyrrole universal base for siRNA delivery.

Cationic nucleoside lipids based on a 3-nitropyrrole universal base were prepared from D-ribose using a straightforward chemical synthesis. Several studies including DLS, TEM, and ethidium bromide (EthBr) assay demonstrated that these amphiphilic molecules form supramolecular organizations of nanometer size in aqueous solutions and are able to bind nucleic acids. siRNA knockdown experiments were performed with these nucleolipids, and we observed protein knockdown activity similar to the siPORT NeoFX positive control.

Sensitive liposomes encoded with oligonucleotide amphiphiles: a biocompatible switch.

DNA-tagged liposomes made of DOPC specifically bind to a fluorescently labelled complementary ss-DNA with virtually no influence from the lipid bilayer despite the absence of a linker; depending on an external stimulus, either physical (temperature) or chemical (competitive complementary ON sequences), the liposomes switch between an on and off fluorescent state depending on the location of the probe either at the surface or in the bulk.

Real time imaging of supramolecular assembly formation via programmed nucleolipid recognition.

Supramolecular assembly formation resulting from molecular recognition between complementary nucleolipids has been visualized in real time at the micrometer scale.

Lipid-conjugated oligonucleotides via "click chemistry" efficiently inhibit hepatitis C virus translation.

Conjugation of a lipid moiety via "click chemistry" potentiates the cellular uptake of oligonucleotides and allows their intracellular delivery. These nontoxic lipid conjugates efficiently inhibit hepatitis C virus internal ribosome entry site (IRES)-mediated translation in human hepatic Huh7 cells. The biological activity of the lipid-conjugated oligonucleotides is not affected by the presence of serum.

Two-dimensional self-assembly and complementary base-pairing between amphiphile nucleotides on graphite.

2D supramolecular structures on HOPG by self-assembly of physisorbed amphiphile nucleotides have been successfully imaged by high resolution STM. The organization of the systems depends on the nature of nucleic bases. In the case of the thymidine derivative a head-to-tail self-assembly is observed, whereas the amphiphile adenosine affords head-to-head nanostructures.

Nucleoside, nucleotide and oligonucleotide based amphiphiles: a successful marriage of nucleic acids with lipids.

Amphiphilic molecules based on nucleosides, nucleotides and oligonucleotides are finding more and more biotechnological applications. This Perspective highlights their synthesis, supramolecular organization as well as their applications in the field of biotechnology.

A new helper phospholipid for gene delivery.

Enhanced gene transfection activity is observed when using a new helper lipid with DOTAP, compared to DOPE.

Amphiphilic copolymer for delivery of xenobiotics: in vivo studies in a freshwater invertebrate, a Mesostominae flatworm.

The synthesis of an amphiphilic polymethacrylate copolymer containing cholesterol hydrophobic moieties and rhodamine as a fluorescent probe, the formation of microspheres, and the uptake of these microspheres in an invertebrate are reported. The cholesterol-derived methacryloyl monomer, which was prepared via a one-step synthesis, was copolymerized with methacrylic acid and methacryloxyethyl thiocarbamoyl rhodamine B in the presence of AIBN as initiator. The obtained dye-labeled copolymer was characterized by (1)H NMR and UV-vis spectroscopy.

Lipophilic peptides for gene delivery.

DNA transfections are widely performed in research laboratories and in vivo gene delivery holds the promise for curing many diseases. The synthetic carriers or vectors for DNA are typically cationic lipids. However, in biology, the recognition of nucleic acids by proteins involves both electrostatic and stacking contributions.

Management of gastro-esophageal reflux disease in primary care. Results from an observational study of 2,474 patients (AO).

Objective: The aim of the present study was to describe the management of gastro-esophageal reflux disease (GERD) by primary care physicians (PCPs).

Methods: This prospective survey was conducted in patients with suspected or previously diagnosed GERD. PCPs completed questionnaires at first consultation (M0) and at a 3-month follow-up visit (M3).

Nucleoside phosphocholine amphiphile for in vitro DNA transfection.

A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfection efficacy and low cytotoxicity is described. TEM, ethidium bromide displacement assays, agarose gel electrophoresis and SAXS studies support the formation of lipoplexes for the transfection of CHO cells.

Self-assembled microspheres from f-block elements and nucleoamphiphiles.

Hollow microspheres featuring a hybrid lipid-cation multilamellar shell are prepared by hydration of a nucleoside based amphiphile with an aqueous solution containing either actinide or lanthanide salts. The physico-chemical data collected clearly indicate that the formation of these microspheres is a consequence of the following concomitant stabilizing factors: (i) hydrophobic interactions, (ii) nucleobase dimer formation and (iii) phosphate/f-block element salt binding.

Cationic nucleoside lipids for gene delivery.

A novel uridine-based nucleo-lipid, DOTAU (N-[5'-(2',3'-dioleoyl)uridine]-N',N',N'-trimethylammonium tosylate) was prepared by using a convenient four-step synthetic pathway. From the preliminary physicochemical studies (quasielastic light scattering and light microscopy), this amphiphilic structure forms supramolecular organizations in aqueous solution. In addition, in the presence of nucleic acids, transmission electronic microscopy experiments (TEM) and small angle X-ray scattering (SAXS) reveal the formation of multilamellar structures similar to lipoplexes (cationic liposome-DNA complexes) with cationic lipids.

[Gastroesophageal reflux in the French general population: national survey of 8000 adults].

Objectives: To assess the population-based prevalence in France of gastroesophageal reflux disease (GERD) and to report its characteristics, consultation rate, modes of management, as well as patients' satisfaction.

Methods: This epidemiological quantitative mail survey sent to a sample of 8000 persons representative of the French adult population comprised 46 questions about GERD, its risk factors, management, last episode, and satisfaction with treatment. GERD was defined in accordance with the guidelines of the 1999 consensus conference as the existence of typical symptoms (heartburn, acid regurgitation) and frequent GERD as occurring at a frequency of at least once a week.

Nucleic acid complexing glycosyl nucleoside-based amphiphile.

A neutral amphiphile derived from uridine featuring two oleyl chains and one glucose for DNA binding was prepared using a convenient four-step synthetic route. The nucleic acid binding capabilities of this amphiphile were investigated by UV-vis, quasi-elastic light scattering (QELS), transmission electronic microscopy (TEM), gel electrophoresis, 31P NMR, IR, and circular dichroism (CD). Amphiphile-nucleic acid complex formation is a consequence of the amphiphilic character of the molecule, phosphate-sugar, and nucleobase-nucleobase interactions.

Supramolecular assemblies of DNA with neutral nucleoside amphiphiles.

A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show that the three distinct structural components of the amphiphile (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the formation of DNA-amphiphile supramolecular assemblies on a mica surface.

[Primary leiomyoma of the liver: a rare benign tumor].

Primary hepatic leiomyoma is a very rare tumor secondary to benign smooth muscle proliferation. The primary location in the liver is usually found in adult women. A 36-year-old woman with right upper quadrant abdominal pain had primary hepatic leiomyoma.