Selectivity control in Pt-catalyzed cinnamaldehyde hydrogenation

Chemoselectivity is a cornerstone of catalysis, permitting the targeted modification of specific functional groups within complex starting materials. Here we elucidate key structural and electronic factors controlling the liquid phase hydrogenation of cinnamaldehyde and related benzylic aldehydes over Pt nanoparticles. Mechanistic insight from kinetic mapping reveals cinnamaldehyde hydrogenation is structure-insensitive over metallic platinum, proceeding with a common Turnover Frequency independent of precursor, particle size or support architecture. In contrast, selectivity to the desired cinnamyl alcohol product is highly structure sensitive, with large nanoparticles and high hydrogen pressures favoring C=O over C=C hydrogenation, attributed to molecular surface crowding and suppression of sterically-demanding adsorption modes. In situ vibrational spectroscopies highlight the role of support polarity in enhancing C=O hydrogenation (through cinnamaldehyde reorientation), a general phenomenon extending to alkyl-substituted benzaldehydes. Tuning nanoparticle size and support polarity affords a flexible means to control the chemoselective hydrogenation of aromatic aldehydes

Safety of topical methimazole for the treatment of melasma. Transdermal absorption, the effect on thyroid function and cutaneous adverse effects

Methimazole is an oral antithyroid compound that exhibits a skin-depigmenting effect when used topically. However, the effect of topical methimazole on thyroid function has not been reported. This study was aimed at assessing the safety of topical methimazole used to treat pigmented lesions, without affecting thyroid hormones due to systemic delivery. The pharmacokinetics of methimazole, either applied in the form of a 5% topical formulation to facial skin or taken orally in the form of a 5-mg tablet by 6 volunteers, were determined. In addition, the effect of long-term topical applications of 5% methimazole on the function of the thyroid gland in 20 patients with epidermal melasma was determined following 6 weeks of once-daily application. Cutaneous adverse effects of topical methimazole were determined. From 15 min up to 24 h after application, methimazole was undetectable in the serum of the individuals receiving single topical methimazole dosing. Methimazole, however, was detected in serum after 15 min of oral administration and remained detectable in serum up to 24 h after administration. Long-term topical methimazole applications in melasma patients did not induce any significant changes in serum TSH, free thyroxine and free triiodothyronine levels. Topical methimazole was well tolerated by the patients and did not induce any significant cutaneous side effects. Present data together with the previously shown non-cytotoxic and non-mutagenic characteristics of methimazole indicate that this agent could be considered as a safe skin-depigmenting compound for topical treatment of skin hyperpigmentary disorders in humans

Patients' preferences of cutaneous leishmaniasis treatment outcomes: Findings from an international qualitative study

Background: Cutaneous leishmaniasis (CL) is a disease that often affects exposed skin areas and may heal leaving lifelong scars. Patients’ expectations from treatment are rarely considered in drug development for CL. An initiative aiming to address shortcomings in clinical trial design and conduct for CL treatments involving the researchers’ community is on-going. This manuscript presents patient-preferred outcomes for CL and an assessment on how to consider these in the conduct of future trials. Methodology/Principal findings: We report preferred treatment outcomes by 74 patients with confirmed CL in endemic regions of Brazil, Burkina Faso, Colombia, Iran, Morocco, Peru and Tunisia during individual in-depth interviews. Beyond outcomes customarily considered in trials (such as lesion appearance and adverse events), patients talked about a large number of outcomes related to quality of life, such as pain, scar formation, and others affecting their work and daily activities. They also reported fears around getting rid of the parasite, disease recurrence, and possible sequelae. Conclusions/Significance: The study results provide a rich insight into important outcomes for CL treatments, as well as related topics, from the perspective of a diverse patient population. Among the outcomes identified, we argue that those related to quality of life as well as recurrence should be included to a greater extent for assessment in clinical trials, and discuss the suitability of measurement instruments such as the Dermatology Quality of Life Index (DLQI). Interviews also point out the potential need to address concerns related to parasitological cure or scar formation, such as social stigmatization and disability. In addition, patients should be given information in order to clarify reported misconceptions. This study therefore suggests a methodology for consulting CL patients on outcomes as elements of clinical trial design, and how to incorporate these outcomes in trials. It also discusses how reported outcomes could be addressed in clinical care.</br

An international qualitative study exploring patients’ experiences of cutaneous leishmaniasis: study set-up and protocol

Lack of investments in drug development, lack of standardisation of clinical trials and the complexity of disease presentations contribute to the current lack of effective, safe and adapted treatments for cutaneous leishmaniasis (CL). One aspect concerns outcomes affecting patients' quality of life (QoL): these are hardly assessed in trials, despite potential functional and/or aesthetic impairment caused by CL, which typically affects disadvantaged and vulnerable people living in rural areas. Here, we describe the approach used to bring perspectives of patients with CL into designing and assessing treatments.This international qualitative study uses interviews with patients to explore their experiences with CL to (1) elicit outcomes and eligibility criteria for clinical trials important to them and (2) to better understand their needs and views about the disease and their requirements and expectations from treatment. Here, we describe the set-up of this collaborative study and the protocol. Data collection is ongoing.The protocol includes study design, preparation, conduct and analysis of individual interviews with approximately 80 patients in seven countries (Burkina Faso, Brazil, two sites in Colombia, Iran, Morocco, Peru and Tunisia) where CL is prevalent. Principal investigators and sites were selected through an open call, and two workshops were organised for protocol development and training in conduct and analysis of qualitative health research. Patient recruitment aims at covering a maximum variation of experiences. Transcripts will be analysed to identify outcomes and eligibility criteria as well as further topics that are expected to emerge from the interviews, such as direct and indirect costs related to CL, its psychological impact, preferred modes of drug administration and traditional treatments.The study received ethical approval by the responsible committees of each of the participating institutions. Findings will be disseminated through publication in peer-reviewed journals, scientific meetings and to participants and their communities