The position of mefloquine as a 21st century malaria chemoprophylaxis

BACKGROUND: Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis. METHODS: A literature search to update the status of mefloquine as a malaria chemoprophylaxis. RESULTS: Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerarability of mefloquine and the use of this medication by groups at high risk of malaria. DISCUSSION: Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors. CONCLUSION: The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline

Chitosan Aerogel Beads as a Heterogeneous Organocatalyst for the Asymmetric Aldol Reaction in the Presence of Water: an Assessment of the Effect of Additives

The catalytic properties of chitosan aerogel for the direct asymmetric aldol reaction in water assisted by various surfac- tants and acid co-catalysts have been evaluated by em- ploying a range of donor and acceptor systems. A beneficial effect on both the yields and enantioselectivities was observed, and the combination of surfactants and acid co-catalysts has proven particularly useful in the case of heterocyclic ketone donors

Scintigraphic study of the lymphatic drainage of the anterior chamber of the mouse eye and its pathophysiological implications

Pendant de nombreuses années, le réseau lymphatique intraoculaire et notamment le drainage de l'humeur aqueuse par ce réseau ont été considérés comme inexistants. Notre étude démontre de fac¸on dynamique et in vivo la présence d'un drainage lymphatique de l'oeil de souris. Cela a été permis grâce à la lymphoscintigraphie après injection de nanomolécules de sulfure de rhénium marquées au technétium 99 m en chambre antérieure de l'oeil de souris. Les acquisitions ont été faites par un tomographe à émission monophotonique expérimental dédié au petit animal. L'hypothèse d'une voie de drainage " uvéolymphatique ", présente dans le corps ciliaire, qui contribuerait à l'écoulement de l'humeur aqueuse a été confortée par les récents progrès de la microbiologie (découverte de marqueurs spécifiques de l'endothélium lymphatique) et de l'imagerie. Cette voie de drainage ouvre des perspectives nouvelles : le développement de techniques de visualisation et de quantification de ce flux lymphatique in viv

Magnons coherent transmission and heat transport at ultrathin insulating ferromagnetic nanojunctions

A model calculation is presented for the magnons coherent transmission and corresponding heat transport at insulating magnetic nanojunctions. The system consists of a ferromagnetically ordered ultrathin insulating junction between two semi-infinite ferromagnetically ordered leads with ideally flat crystal interfaces. The ground state of the system is depicted by an exchange Hamiltonian neglecting smaller dipolar and anisotropy terms. The spin dynamics are analyzed using the equations of motion for the spin precession displacements, valid in the limit of low temperatures compared to an order-disorder transition temperature characteristic of the system. The coherent transmission and reflection spectra at the nanojunction boundary are calculated in the Landauer-Buttiker formalism using the matching theory, for all the magnons in the lead bulk, at arbitrary angles of incidence on the boundary, and for variable temperatures. The model calculations yield the thermal conductivity κm due to the magnons coherent transmission between the two leads maintained at slightly different temperatures. The model is general, and is applied in particular to the Fe/Gd/Fe system to calculate the coherent transmission of magnons and their thermal conductivity at the junction boundary, for different thicknesses of the Gd junction and its corresponding magnetic order. The calculated results elucidate the comparison between the heat transport from magnons with that in parallel channels from electrons and phonons, at the nanojunction boundary

Small molecule blockers of the Alzheimer Aβ calcium channel potently protect neurons from Aβ cytotoxicity

Alzheimer's disease (AD) is a common, chronic neurodegenerative disease that is thought to be caused by the neurotoxic effect of the Amyloid beta peptides (Aβ). We have hypothesized that the intrinsic Aβ calcium channel activity of the oligomeric Aβ polymer may be responsible for the neurotoxic properties of Aβ, and that Aβ channel blockers may be candidate AD therapeutics. As a consequence of a rational search paradigm based on the model structure of the Aβ channel, we have identified two compounds of interest: MRS2481 and an enatiomeric species, MRS2485. These are amphiphilic pyridinium salts that both potently block the Aβ channel and protect neurons from Aβ toxicity. Both block the Aβ channel with similar potency (≈500 nM) and efficacy (100%). However, we find that inhibition by MRS2481 is easily reversible, whereas inhibition by MRS2485 is virtually irreversible. We suggest that both species deserve consideration as candidates for Alzheimer's disease drug discovery