Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson’s disease?

In Parkinson’s disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7 days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30 days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia

Trochosira polychaeta: a colonial diatom from the late Cretaceous exhibiting two contrasting chain-linking mechanisms and a wide range of preservation

The fossil species Trochosira polychaeta Strelnikova, exhibits a wide range of preservational states that has led to contrasting interpretations with regard to its resting stage or vegetative cell status. Within shallow-buried, well preserved diatomites from the Alpha Ridge of the Arctic Ocean, a continuum of dissolution effects are documented and a vegetative cell status is clearly indicated. The chains are formed by a central linking process but complex marginal structures also constitute a complementary linking mechanism. The double linkage may have supported the integrity of the colonial chains and provided a mechanism for enhanced nutrient uptake. The presence of two distinct types of linking might also represent a stage in a transition from the Cretaceous when central linking structures were common, through the Cenozoic to the modern with more common linking through marginal structures

Photosynthetic potential of planets in 3 : 2 spin-orbit resonances

Photosynthetic life requires sufficient photosynthetically active radiation (PAR) to metabolise. On Earth, plant behaviour, physiology and metabolism are sculpted around the night-day cycle by an endogenous biological circadian clock. The evolution of life was influenced by the Earth-Sun orbital dynamic, which generates the photo-environment incident on the planetary surface. In this work the unusual photo-environment of an Earth-like planet (ELP) in 3:2 spin orbit resonance is explored. Photo-environments on the ELP are longitudinally differentiated, in addition to differentiations relating to latitude and depth (for aquatic organisms) which are familiar on Earth. The light environment on such a planet could be compatible with Earth's photosynthetic life although the threat of atmospheric freeze-out and prolonged periods of darkness would present significant challenges. We emphasise the relationship between the evolution of life on a planetary body with its orbital dynamics.Comment: 18 pages, 17 figures, accepted for publication in the International Journal of Astrobiolog