Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel.

Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis.

Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections.

Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections.

Consensus and evidence-based medication review to optimize and potentially reduce psychotropic drug prescription in institutionalized dementia patients.

BACKGROUND: Dementia patients often show neuropsychiatric symptoms, known as behavioral and psychological symptoms of dementia (BPSD). These are a common motive for medical consultations, hospitalizations, and nursing home stays. Various studies have suggested that the high prevalence of psychotropic drug use to treat BPSD in institutionalized dementia patients may lead to impaired cognitive capacity, rigidity, somnolence, and other complications during the course of the illness. The aim of this study was to design a consensus-based intervention between care levels to optimize and potentially reduce prescription of psychotropic drugs in institutionalized patients with dementia and assess the changes occurring following its implementation. METHODS: Design: Prospective, quasi-experimental, pre/post intervention, multicenter study. SCOPE: 7 nursing homes associated with a single primary care team. INCLUSION CRITERIA: Institutionalized patients diagnosed with dementia and under treatment with 1 or more psychotropic drugs for at least 3 months. SAMPLE: 240 individuals; mean age, 87 years (SD: 6.795); 75% (180) women. INTERVENTION: Creation of evidence-based therapeutic guidelines for psychotropic drug use in the treatment of BPSD by consensus between reference professionals. Joint review (primary care and geriatric care nursing home professionals) of the medication based on the guidelines and focusing on individual patient needs. Primary variable: Number of psychotropic drugs used per patient. ASSESSMENT: Preintervention, immediate postintervention, and at 1 and 6 months. RESULTS: Overall, the number of psychotropic drugs prescribed was reduced by 28% (from 636 before to 458 after the intervention). The mean number of psychotropic drugs prescribed per patient decreased from 2.71 at baseline to 1.95 at 1 month postintervention and 2.01 at 6 months (p < 0.001 for both time points). Antipsychotics were the drug class showing the highest reduction rate (49.66%). Reintroduction of discontinued psychotropic drugs was 2% at 1 month following the intervention and 12% at 6 months. CONCLUSIONS: A consensus guidelines-based therapeutic intervention with a patient-centered medication review by a multidisciplinary team led to a reduction in prescription of psychotropic drugs in institutionalized dementia patients.

Lab on valve-multisyringe flow injection system (LOV-MSFIA) for fully automated uranium determination in environmental samples.

The hyphenation of lab-on-valve (LOV) and multisyringe flow analysis (MSFIA), coupled to a long path length liquid waveguide capillary cell (LWCC), allows the spectrophotometric determination of uranium in different types of environmental sample matrices, without any manual pre-treatment, and achieving high selectivity and sensitivity levels. On-line separation and preconcentration of uranium is carried out by means of UTEVA resin. The potential of the LOV-MSFIA makes possible the fully automation of the system by the in-line regeneration of the column. After elution, uranium(VI) is spectrophotometrically detected after reaction with arsenazo-III. The determination of levels of uranium present in environmental samples is required in order to establish an environmental control. Thus, we propose a rapid, cheap and fully automated method to determine uranium(VI) in environmental samples. The limit of detection reached is 1.9 ηg of uranium and depending on the preconcentrated volume; it results in ppt levels (10.3 ηg L(-1)). Different water sample matrices (seawater, well water, freshwater, tap water and mineral water) and a phosphogypsum sample (with natural uranium content) were satisfactorily analyzed.

Smart thorium and uranium determination exploiting renewable solid-phase extraction applied to environmental samples in a wide concentration range.

A smart fully automated system is proposed for determination of thorium and uranium in a wide concentration range, reaching environmental levels. The hyphenation of lab-on-valve (LOV) and multisyringe flow injection analysis (MSFIA), coupled to a long path length liquid waveguide capillary cell, allows the spectrophotometric determination of thorium and uranium in different types of environmental sample matrices achieving high selectivity and sensitivity levels. Online separation and preconcentration of thorium and uranium is carried out by means of Uranium and TEtraValents Actinides resin. The potential of the LOV-MSFIA makes possible the full automation of the system by the in-line regeneration of the column and its combination with a smart methodology is a step forward in automation. After elution, thorium(IV) and uranium(VI) are spectrophotometrically detected after reaction with arsenazo-III. We propose a rapid, inexpensive, and fully automated method to determine thorium(IV) and uranium(VI) in a wide concentration range (0-1,200 and 0-2,000 µg L(-1) Th and U, respectively). Limits of detection reached are 5.9 ηg L(-1) of uranium and 60 ηg L(-1) of thorium. Different water sample matrices (seawater, well water, freshwater, tap water, and mineral water), and a channel sediment reference material which contained thorium and uranium were satisfactorily analyzed with the proposed method.

Automated determination of uranium(VI) at ultra trace levels exploiting flow techniques and spectrophotometric detection using a liquid waveguide capillary cell.

Rapid and fully automated multisyringe flow-injection analysis (MSFIA) with a multi-pumping flow system (MPFS) coupled to a long path-length liquid waveguide capillary cell (LWCC) is proposed for the determination of uranium(VI) at ultra trace levels. On-line separation and pre-concentration of uranium is carried out by means of a TRU resin. After elution, uranium(VI) is spectrophotometrically detected after reaction with arsenazo-III. Combination of the MSFIA and MPFS techniques with the TRU-resin enables the analysis to be performed in a short time, using large sample volumes and achieving high selectivity and sensitivity levels. A detection limit of 12.6 ng L(-1) (ppt) is reached for a 100-mL sample volume. The versatility of the proposed method also enables pre-concentration of variable sample volumes, enabling application of the analysis to a wide concentration range. Reproducibility of better than 5% and a resin durability of 40 injections should be emphasized. The developed method was successfully applied to different types of environmental sample matrices with recoveries between 95 and 108%.

Positive operator valued measures and the quantum Monty Hall problem.

A quantum version of the Monty Hall problem, based upon the Positive Operator Valued Measures (POVM) formalism, is proposed. It is shown that basic normalization and symmetry arguments lead univocally to the associated POVM elements, and that the classical probabilities associated with the Monty Hall scenario are recovered for a natural choice of the measurement operators.

Sequential injection 90Sr determination in environmental samples using a wetting-film extraction method.

A sequential injection procedure involving a flow-reversal wetting-film extraction method for the determination of the radionuclide 90Sr has been developed. The methodology is based on the coating of the inner walls of an open tubular reactor with a film prepared from a 0.14 M 4,4'(5')-bis(tert-butylcyclohexano)-18-crown-6 (BCHC) solution in 1-octanol, which allows the selective isolation of strontium from the sample matrix. Selection of the optimum extractant diluent attending its physical properties, investigation of the extraction kinetics features, and choice of the proper elution procedure are discussed in detail in this paper. The noteworthy aspects of using a wetting-film phase instead of a solid-phase material described to date in the literature are the reduction of crown ether consumption and the simplification of both the operational sequence and the automation of the extractant-phase renewal between consecutive samples, which is of interest to avoid analyte carryover and reduction of the resin capacity factor caused by irreversible interferences. The proposed method has been successfully applied to different spiked environmental samples (water, milk, and soil), with 90Sr total activities ranging between 0.07 and 0.30 Bq, measured using a low-background proportional counter. The standard deviation of the automated analytical separation procedure is lower than 3% (n = 10), and the 90Sr isolation process under the studied conditions may be carried out with a yield up to 80%.