Studies on the neurotoxicity of 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) in SH-SY5Y cells

We have studied the hypothesis that 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) is neurotoxic. Salsolinol induced a significant time and dose related inhibition of 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazoyl blue (MTT) reduction, and increased lactate dehydrogenase release (LDH) release from human SH-SY5Y neuroblastoma cells, at concentrations within the range of 1-methyl-4-phenylpyridinium (MPP+) cytotoxicity, in vitro. Cytotoxicity was not inhibited by the addition of antioxidants, monoamine oxidase inhibitors or imipramine. In confluent monolayers, salsolinol stimulated catecholamine uptake with EC50 values of 17 muM and 11 muM, for noradrenaline and dopamine, respectively. Conversely, at concentrations above 100 muM, salsolinol inhibited the uptake of noradrenaline and dopamine, with IC50 values of 411 muM and 379 muM, respectively. The inhibition of catecholamine uptake corresponded to the increase displacement of [3H]nisoxetine from the uptake 1 site by salsolinol, as the Ki (353 muM) for displacement was similar to the IC50 (411 and 379 muM) for uptake. Salsolinol stimulated catecholamine uptake does not involve the uptake recognition site, or elevation of cAMP, cGMP, or inhibition of protein kinase C. Salsolinol also inhibited both carbachol (1 mM) and K+ (100 mM, Na+ adjusted) evoked released of noradrenaline from SH-SY5Y cells, with IC50 values of 500 muM and 120 muM, respectively. In conclusion, salsolinol appears to be cytotoxic to SH-SY5Y cells, via a mechanism that does not require uptake 1, bioactivation by monoamine oxidase, or membrane based free radical damage. The effects of salsolinol on catecholamine uptake, and the mechanism of toxicity require further investigation.

Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity

The loss of dopamine in idiopathic or animal models of Parkinson's disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic-globus pallidus complex in generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABAA receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic-globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity. © 2006 IBRO.

Fluorescent probe:complexation of Fe3+ with the myo-inositol 1,2,3-trisphosphate motif

Natural myo-inositol phosphate antioxidants containing the 1,2,3-trisphosphate motif bind Fe3+ in the unstable penta-axial conformation.

Conformational analysis of the natural iron chelator myo-inositol 1,2,3-trisphosphate using a pyrene-based fluorescent mimic

myo-Inositol phosphates possessing the 1,2,3-trisphosphate motif share the remarkable ability to completely inhibit iron-catalysed hydroxyl radical formation. The simplest derivative, myo-inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], has been proposed as an intracellular iron chelator involved in iron transport. The binding conformation of Ins(1,2,3)P3 is considered to be important to complex Fe3+ in a 'safe' manner. Here, a pyrene-based fluorescent probe, 4,6-bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-bispyrenoyl Ins(1,2,3,5)P4], has been synthesised and used to monitor the conformation of the 1,2,3-trisphosphate motif using excimer fluorescence emission. Ring-flip of the cyclohexane chair to the penta-axial conformation occurs upon association with Fe3+, evident from excimer fluorescence induced by π-π stacking of the pyrene reporter groups, accompanied by excimer formation by excitation at 351 nm. This effect is unique amongst biologically relevant metal cations, except for Ca 2+ cations exceeding a 1:1 molar ratio. In addition, the thermodynamic constants for the interaction of the fluorescent probe with Fe3+ have been determined. The complexes formed between Fe 3+ and 4,6-bispyrenoyl Ins(1,2,3,5)P4 display similar stability to those formed with Ins(1,2,3)P3, indicating that the fluorescent probe acts as a good model for the 1,2,3-trisphosphate motif. This is further supported by the antioxidant properties of 4,6-bispyrenoyl Ins(1,2,3,5)P4, which closely resemble those obtained for Ins(1,2,3)P3. The data presented confirms that Fe3+ binds tightly to the unstable penta-axial conformation of myo-inositol phosphates possessing the 1,2,3-trisphosphate motif. © 2010 The Royal Society of Chemistry.

Crystal structure of 1-benzylsulfonyl-1,2,3,4-tetrahydroquinoline

Peer reviewed

Tab. 1+2+3: Selected principal soil properties in the oil exploitation region of KomiArcticOil (Usinsk) in the Russian tundra

Oil polluted and not oil polluted soils (crude oil hydrocarbons contents: 20-92500 mg/kg dry soil mass) under natural grass and forest vegetation and in a bog in the Russian tundra were compared in their principal soil ecological parameters, the oil content and the microbial indicators. CFE biomass-C, dehydrogenase and arylsulfatase activity were enhanced with the occurrence of crude oil. Using these parameters for purposes of controlling remediation and recultivation success it is not possible to distinguish bctween promotion of microbial activity by oil carbon or soil organic carbon (SOC). For this reason we think that these parameters are not appropriate to indicate a soil damage by an oil impact. In contrast the metabolie quotient (qC02), calculated as the ratio between soil basal respiration and the SIR biomass-C was adequate to indicate a high crude oil contamination in soil. Also, the ß-glucosidase activity (parameter ß-GL/SOC) was correlated negatively with oil in soil. The indication of a soil damage by using the stress parameter qCO, or the specific enzyme activities (activity/SOC) minimizes the promotion effect of the recent SOC content on microbial parameters. Both biomass methods (SIR, CFE) have technical problems in application for crude oil-contaminated and subarctic soils. CFE does not reflect the low C_mic level of the cold tundra soils. We recommend to test every method for its suitability before any data collection in series as well as application for cold soils and the application of ecophysiological ratios as R_mic/C_mic, C_mic/SOC or enzymatic activity/SOC instead of absolute data.

Varianzanalysen - Prüfen der Voraussetzungen und nichtparametrische Methoden sowie praktische Anwendungen mit R und SPSS. Version 1.1 (2.3.2015)

Die Voraussetzunen der parametrischen 1- und mehrfaktoriellen Varianzanalyse, mit und ohne Messwiederholungen, werden besprochen. Ferner werden eine Reihe von alternativen Verfahren vorgestellt, insbesondere einige nichtparametrische, darunter RT (rank transform), INT (inverse normal transform), ART (aligned rank transform), Puri & Sen (L statistic), van der Waerden und Akritas & Brunner (ATS anova type statistic), die sich auf die parametrische Varianzanalyse zurückführen lassen, sowie dichotome und ordinale logistische Regression. Hierzu werden Lösungen mit R und SPSS ausführlich gezeigt.

1-2-3 VOTE : How To Use South Carolina’s Voting System

This paper describes, with pictures, how to use voting machines and how to cast your vote.

Sílica gel organofuncionalizada com 4-amino-5-(4-piridil) 4H-1,2,4-triazol-3-tiol (aptt): Propriedades adsortivas e eletroanalíticas

Pós-graduação em Ciência dos Materiais - FEIS

Ms. Ff. Mus. 1323 - Am 2 post Epiphan. : Sehet an die Exempel der Alten, und pp. ; C. A. T. B. , 1 cornettino, 3 tromboni, 2 violini, 2 hautbois se piace, 1 viola, violoncello et organo.

von Telemann. [Textverf.: Gottfried Simonis]

The ν2, 2ν2, 3ν2, ν4 and ν2+ν4 bands of 15NH3

The ir absorption of gaseous 15NH3 between 510 and 3040 cm−1 was recorded with a resolution of 0.06 cm−1. The ν2, 2ν2, 3ν2, ν4, and ν2 + ν4 bands were measured and analyzed on the basis of the vibration-rotation Hamiltonian developed by V. Špirko, J. M. R. Stone, and D. Papoušek (J. Mol. Spectrosc. 60, 159–178 (1976)). A set of effective molecular parameters for the ν2 = 1, 2, 3 states was derived, which reproduced the transition frequencies within the accuracy of the experimental measurements. For ν4 and ν2 + ν4 bands the standard deviation of the calculated spectrum is about four times larger than the measurements accuracy: a similar result was found for ν4 in 14NH3 by Š. Urban et al. (J. Mol. Spectrosc. 79, 455–495 (1980)). This result suggests that the present treatment takes into account only the most significant part of the rovibration interaction in the doubly degenerate vibrational states of ammonia.

Copper(II)-catalyzed [2,3]-sigmatropic rearrangement of N-methyltetrahydropyridinium ylids

A ring-contractive and highly diastereoselective [2,3]-sigmatropic rearrangement occurs when N-methyl-1,2,3,6-tetrahydropyridine is treated with sub-stoichiometric amounts of copper or rhodium salts, in the presence of ethyl diazoacetate, giving ethyl cis-N-methyl-3-ethenyl proline (4).