Suchergebnisse

After an alleged sorcery attack in Lima, an anthropologist investigates and realizes that her skepticism might not be enough to protect her against the attack's power.

8 pags., 6 figs. ; Purpose: The crystalline lens undergoes morphological and functional changes with age and may also play a role in eye emmetropisation. Both the geometry and the gradient index of refraction (GRIN) distribution contribute to the lens optical properties. We studied the lens GRIN in the guinea pig, a common animal model to study myopia. Methods: Lenses were extracted from guinea pigs (Cavia porcellus) at 18 days of age (n = 4, three monolaterally treated with negative lenses and one untreated) and 39 days of age (n = 4, all untreated). Treated eyes were myopic (−2.07 D on average) and untreated eyes hyperopic (+3.3 D), as revealed using streak retinoscopy in the live and cyclopeged animals. A custom 3D spectral domain optical coherence tomography (OCT) system (λ = 840 nm, Δλ = 50 nm) was used to image the enucleated crystalline lens at two orientations. Custom algorithms were used to estimate the lens shape and GRIN was modelled with four variables that were reconstructed using the OCT data and a minimisation algorithm. Ray tracing was used to calculate the optical power and spherical aberration assuming a homogeneous refractive index or the estimated GRIN. Results: Guinea pig lenses exhibited nearly parabolic GRIN profiles. When comparing the two age groups (18- and 39 day-old) there was a significant increase in the central thickness (from 3.61 to 3.74 mm), and in the refractive index of the surface (from 1.362 to 1.366) and the nucleus (from 1.443 to 1.454). The presence of GRIN shifted the spherical aberration (−4.1 µm on average) of the lens towards negative values. Conclusions: The guinea pig lens exhibits a GRIN profile with surface and nucleus refractive indices that increase slightly during the first days of life. GRIN plays a major role in the lens optical properties and should be incorporated into computational guinea pig eye models to study emmetropisation, myopia development and ageing. ; This work was supported by European Research Council (ERC) Grant Agreement ERC-2011-AdC- 294099; ERC under the European Union's Horizon 2020 research and innovation programme (H2020-MSCA COFUND-2015 FP-713694, MULTIPLY) and under grant agreement No 779960, IMCUSTOMEYE and No 675137 (MyFUun MSCA ITN); Spanish Government Grant FIS2017-84753-R; Hunter Medical Research Institute G1400967 and the University of Newcastle (FVG 1031537 and SSP).

The recent outbreaks of the Ebola virus (EBOV) in Africa have brought global visibility to the shortage of available therapeutic options to treat patients infected with this or closely related viruses. We have recently computationally identified three molecules which have all demonstrated statistically significant efficacy in the mouse model of infection with mouse adapted Ebola virus (ma-EBOV). One of these molecules is the antimalarial pyronaridine tetraphosphate (IC(50) range of 0.82–1.30 μM against three strains of EBOV and IC(50) range of 1.01–2.72 μM against two strains of Marburg virus (MARV)) which is an approved drug in the European Union and used in combination with artesunate. To date, no small molecule drugs have shown statistically significant efficacy in the guinea pig model of EBOV infection. Pharmacokinetics and range-finding studies in guinea pigs directed us to a single 300mg/kg or 600mg/kg oral dose of pyronaridine 1hr after infection. Pyronaridine resulted in statistically significant survival of 40% at 300mg/kg and protected from a lethal challenge with EBOV. In comparison, oral favipiravir (300 mg/kg dosed once a day) had 43.5% survival. All animals in the vehicle treatment group succumbed to disease by study day 12 (100% mortality). The in vitro metabolism and metabolite identification of pyronaridine and another of our EBOV active molecules, tilorone, suggested significant species differences which may account for the efficacy or lack thereof, respectively in guinea pig. In summary, our studies with pyronaridine demonstrates its utility for repurposing as an antiviral against EBOV and MARV.