The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

Neuroprotective treatments in Parkinson's disease (PD) have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms) include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R), although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS), reactive nitrogen species (RNS), apoptosis, inflammation, and trophic factors including GDNF and BDNF

Stable oxygen and carbon isotopes of carbonates in lake sediments as a paleoflood proxy

Lake sediments are increasingly explored as reliable paleoflood archives. In addition to established flood proxies including detrital layer thickness, chemical composition, and grain size, we explore stable oxygen and carbon isotope data as paleoflood proxies for lakes in catchments with carbonate bedrock geology. In a case study from Lake Mondsee (Austria), we integrate high-resolution sediment trapping at a proximal and a distal location and stable isotope analyses of varved lake sediments to investigate flood-triggered detrital sediment flux. First, we demonstrate a relation between runoff, detrital sediment flux, and isotope values in the sediment trap record covering the period 2011–2013 CE including 22 events with daily (hourly) peak runoff ranging from 10 (24) m3 s−1 to 79 (110) m3 s−1. The three- to ten-fold lower flood-triggered detrital sediment deposition in the distal trap is well reflected by attenuated peaks in the stable isotope values of trapped sediments. Next, we show that all nine flood-triggered detrital layers deposited in a sediment record from 1988 to 2013 have elevated isotope values compared with endogenic calcite. In addition, even two runoff events that did not cause the deposition of visible detrital layers are distinguished by higher isotope values. Empirical thresholds in the isotope data allow estimation of magnitudes of the majority of floods, although in some cases flood magnitudes are overestimated because local effects can result in too-high isotope values. Hence we present a proof of concept for stable isotopes as reliable tool for reconstructing flood frequency and, although with some limitations, even for flood magnitudes

Classification and stability of simple homoclinic cycles in R^5

The paper presents a complete study of simple homoclinic cycles in R^5. We find all symmetry groups Gamma such that a Gamma-equivariant dynamical system in R^5 can possess a simple homoclinic cycle. We introduce a classification of simple homoclinic cycles in R^n based on the action of the system symmetry group. For systems in R^5, we list all classes of simple homoclinic cycles. For each class, we derive necessary and sufficient conditions for asymptotic stability and fragmentary asymptotic stability in terms of eigenvalues of linearisation near the steady state involved in the cycle. For any action of the groups Gamma which can give rise to a simple homoclinic cycle, we list classes to which the respective homoclinic cycles belong, thus determining conditions for asymptotic stability of these cycles.Comment: 34 pp., 4 tables, 30 references. Submitted to Nonlinearit

Early psychiatric morbidity in a Brazilian sample of acute ischemic stroke patients

OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians

Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells

The roles of CYP lipid-metabolizing pathways in endothelial cells are poorly understood. Human endothelial cells expressed CYP2J2 and soluble epoxide hydrolase (sEH) mRNA and protein. The TLR-4 agonist LPS (1 μg/ml; 24 h) induced CYP2J2 but not sEH mRNA and protein. LC–MS/MS analysis of the stable commonly used human endothelial cell line EA.Hy926 showed active epoxygenase and epoxide hydrolase activity: with arachidonic acid (stable epoxide products 5,6-DHET, and 14,15-DHET), linoleic acid (9,10-EPOME and 12,13-EPOME and their stable epoxide hydrolase products 9,10-DHOME and 12,13-DHOME), docosahexaenoic acid (stable epoxide hydrolase product 19,20-DiHDPA) and eicosapentaenoic acid (stable epoxide hydrolase product 17,18-DHET) being formed. Inhibition of epoxygenases using either SKF525A or MS-PPOH induced TNFα release, but did not affect LPS, IL-1β, or phorbol-12-myristate-13-acetate (PMA)-induced TNFα release. In contrast, inhibition of soluble epoxide hydrolase by AUDA or TPPU inhibited basal, LPS, IL-1β and PMA induced TNFα release, and LPS-induced NFκB p65 nuclear translocation. In conclusion, human endothelial cells contain a TLR-4 regulated epoxygenase CYP2J2 and metabolize linoleic acid > eicosapentaenoic acid > arachidonic acid > docosahexaenoic acid to products with anti-inflammatory activity

Breakthrough in purification of fossil pollen for dating of sediments by a new large-particle on-chip sorter

Particle sorting is a fundamental method in various fields of medical and biological research. However, existing sorting applications are not capable for high-throughput sorting of large-size (>100 micrometers) particles. Here, we present a novel on-chip sorting method using traveling vortices generated by on-demand microjet flows, which locally exceed laminar flow condition, allowing for high-throughput sorting (5 kilohertz) with a record-wide sorting area of 520 micrometers. Using an activation system based on fluorescence detection, the method successfully sorted 160-micrometer microbeads and purified fossil pollen (maximum dimension around 170 micrometers) from lake sediments. Radiocarbon dates of sorting-derived fossil pollen concentrates proved accurate, demonstrating the method’s ability to enhance building chronologies for paleoenvironmental records from sedimentary archives. The method is capable to cover urgent needs for high-throughput large-particle sorting in genomics, metabolomics, and regenerative medicine and opens up new opportunities for the use of pollen and other microfossils in geochronology, paleoecology, and paleoclimatology

CO adsorption on neutral iridium clusters

The adsorption of carbon monoxide on neutral iridium clusters in the size range of n = 3 to 21 atoms is investigated with infrared multiple photon dissociation spectroscopy. For each cluster size only a single v(CO) band is present with frequencies in the range between 1962 cm-1 (n = 8) and 1985 cm-1 (n = 18) which can be attributed to an atop binding geometry. This behaviour is compared to the CO binding geometries on clusters of other group 9 and 10 transition metals as well as to that on extended surfaces. The preference of Ir for atop binding is rationalized by relativistic effects on the electronic structure of the later 5d metals

Homogeneous and heterogenised new gold C-scorpionate complexes as catalysts for cyclohexane oxidation

Gold(III) complexes of type [AuCl2{eta(2)-RC(R'pz)(3)}]Cl [R = R' = H (1), R = CH2OH, R' = H (2) and R = H, R' = 3,5-Me-2(3), pz = pyrazol-1-yl] were supported on carbon materials (activated carbon, carbon xerogel and carbon nanotubes) and used for the oxidation of cyclohexane to cyclohexanol and cyclohexanone, with aqueous H2O2, under mild conditions