The Antioxidant Role of Xanthurenic Acid in the Aedes aegypti Midgut during Digestion of a Blood Meal

In the midgut of the mosquito Aedes aegypti, a vector of dengue and yellow fever, an intense release of heme and iron takes place during the digestion of a blood meal. Here, we demonstrated via chromatography, light absorption and mass spectrometry that xanthurenic acid (XA), a product of the oxidative metabolism of tryptophan, is produced in the digestive apparatus after the ingestion of a blood meal and reaches milimolar levels after 24 h, the period of maximal digestive activity. XA formation does not occur in the White Eye (WE) strain, which lacks kynurenine hydroxylase and accumulates kynurenic acid. The formation of XA can be diminished by feeding the insect with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl] benzenesulfonamide (Ro-61-8048), an inhibitor of XA biosynthesis. Moreover, XA inhibits the phospholipid oxidation induced by heme or iron. A major fraction of this antioxidant activity is due to the capacity of XA to bind both heme and iron, which occurs at a slightly alkaline pH (7.5-8.0), a condition found in the insect midgut. The midgut epithelial cells of the WE mosquito has a marked increase in occurrence of cell death, which is reversed to levels similar to the wild type mosquitoes by feeding the insects with blood supplemented with XA, confirming the protective role of this molecule. Collectively, these results suggest a new role for XA as a heme and iron chelator that provides protection as an antioxidant and may help these animals adapt to a blood feeding habit

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies

Study of the deformation-driving vd5/2 orbital in 6728Ni39 using one-neutron transfer reactions

Abstract The ν g 9 / 2 , d 5 / 2 , s 1 / 2 orbitals are assumed to be responsible for the swift onset of collectivity observed in the region below 68Ni. Especially the single-particle energies and strengths of these orbitals are of importance. We studied such properties in the nearby 67Ni nucleus, by performing a ( d , p ) -experiment in inverse kinematics employing a post-accelerated radioactive ion beam (RIB) at the REX-ISOLDE facility. The experiment was performed at an energy of 2.95 MeV/u using a combination of the T-REX particle detectors, the Miniball γ-detection array and a newly-developed delayed-correlation technique as to investigate μs-isomers. Angular distributions of the ground state and multiple excited states in 67Ni were obtained and compared with DWBA cross-section calculations, leading to the identification of positive-parity states with substantial ν g 9 / 2 (1007 keV) and ν d 5 / 2 (2207 keV and 3277 keV) single-particle strengths up to an excitation energy of 5.8 MeV. 50% of the ν d 5 / 2 single-particle strength relative to the ν g 9 / 2 -orbital is concentrated in and shared between the first two observed 5 / 2 + levels. A comparison with extended Shell Model calculations and equivalent (3He, d) studies in the region around 9040Zr50 highlights similarities for the strength of the negative-parity pf and positive-parity g 9 / 2 state, but differences are observed for the d 5 / 2 single-particle strength