Oxidation of serotonin by superoxide radical: implications to neurodegenerative brain disorders

Many new lines of evidence implicate both superoxide anion radical (O2*-) and biogenic amine neurotransmitters in the pathological mechanisms that underlie neuronal damage caused by methamphetamine (MA), glutamate-mediated oxidative toxicity, ischemia-reperfusion, and other neurodegenerative brain disorders. In this investigation the oxidation of 5-hydroxytryptamine (5-HT, serotonin) by an O2*--generating system (xanthine/xanthine oxidase) in buffered aqueous solution at pH 7.4 has been studied. The major product of the O2*--mediated oxidation of 5-HT is tryptamine-4,5-dione (T-4, 5-D). However, O2*- and H2O2, cogenerated by the xanthine oxidase-mediated oxidation of xanthine to uric acid, together react with trace levels of iron that contaminate buffer constituents to give a chemically ill-defined oxo-iron species. This species mediates the oxidation of 5-HT to a C(4)-centered carbocation intermediate that reacts with 5-HT to give 5,5'-dihydroxy-4, 4'-bitryptamine (4,4'-D) and with uric acid to give 9-[3-(2-aminoethyl)-5-hydroxy-1H-indol-4-yl]-2,6,8-triketo-1H,3H, 7H-purine (7) as the major products. These products differ from those formed in the HO*-mediated oxidation of 5-HT under similar conditions. When the reaction is carried out in the presence of the intraneuronal nucleophile glutathione (GSH), T-4,5-D is scavenged to give 7-(S-glutathionyl)tryptamine-4,5-dione, whereas the putative carbocation intermediate is scavenged to give 4-(S-glutathionyl)-5-hydroxytryptamine. T-4,5-D also reacts with the sulfhydryl residues of a model protein, alcohol dehydrogenase, and inhibits its activity. Previous investigators have proposed that T-4, 5-D is a serotonergic neurotoxin. This raises the possibility that T-4,5-D and perhaps other putative intraneuronal metabolites formed by the O2*-/H2O2/oxo-iron-mediated oxidations of 5-HT might be endotoxins that contribute to neurodegeneration in brain regions innervated by serotonergic neurons caused by MA, ischemia-reperfusion, and other neurodegenerative brain disorders.     

241Am removal by DTPA vs. occurrence of skeletal malignancy

PURPOSE: The distribution of hyaluronan (HA) and the cellular response after photokeratitis induced by different ultraviolet (UV) wavelengths in the rabbit cornea was examined to help understand the mechanism of corneal injury and repair after UV damage. HA is a high molecular weight disaccharide polymer capable of binding considerable amounts of water. It is not normally found in the rabbit corneal stroma. The production of HA represents a generalized corneal response to injury. METHODS: Twenty-four albino rabbit corneas were exposed to 270, 290, and 310 nm of UV radiant energy in 8-nm full wavebands in doses producing biomicroscopically significant keratitis (three corneal thresholds for keratitis (Hc): 0.016 J/cm2 for 270 nm, 0.04 J/cm2 for 290 nm, and 0.14 J/cm2 for 310 nm) and in subkeratitis doses (0.7 Hc: 0.004 J/cm2 for 270 nm, 0.008 J/cm2 for 290 nm, and 0.03 J/cm2 for 310 nm). The rabbits exposed to 270 and 290 nm of UV radiation were sacrificed 3 days after exposure. The rabbits exposed to 310 nm of UV radiation were sacrificed 3, 7, and 14 days after exposure, respectively. The corneal tissue specimens were double stained and examined morphologically and histochemically for HA by light microscopy. RESULTS: Evaluation of corneas exposed to 270 and 290 nm of UV radiant energy in both subkeratitis and keratitis doses and those corneas exposed to 310 nm of radiant energy in subkeratitis dose showed neither stromal changes nor production of HA by corneal cells. Corneas exposed to 310 nm of UV radiant energy in keratitis dose at 3 days after exposure showed disappearance of keratocytes in entire thickness of central cornea. Cells bordering this damaged area were staining for HA. By 7 days after exposure almost the whole damaged area, except one fourth of anterior stroma, was repopulated by new keratocytes staining positive for HA. The corneal structures became normal and HA almost completely disappeared 14 days after exposure. CONCLUSIONS: A keratitis dose of 310 nm of UV light irradiation is needed to cause keratocyte damage. A keratitis dose of the shorter wavelengths does not cause keratocyte cell damage at the light microscopic level. The keratocyte production of HA appears to be a sign of cell readiness to repopulate the damaged stroma devoid of keratocytes.     

Ethnic conflict: Global challenges and psychological perspectives.

Introduces a special section on ethnic conflict in 5 different parts of the world. This section analyzes psychological dimensions of particular conflicts and promotes thinking about the possible contributions psychology can make in the research, practice, and policy domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Critical evaluation of histogram densitometry of Feulgen-stained normal human lymphocyte nuclei

By means of a Vickers M85 microdensitometer, combined with a histogram unit, the distribution of the coloured product of the Feulgen reaction in single nuclei of human lymphocytes was examined by taking the fraction of each nucleus occupied by DNA at different concentrations. Tchacarof's index of homogeneity, derived from these fractions, was found to rise with the mean nuclear DNA concentration, and the calculated linear relation between the index and the concentration was found, in a preliminary experiment, to be independent of the degree of flattening of the nuclei. Further analysis, of the contribution of more and less densely packed areas to differences in mean intranuclear DNA concentration, showed that these differences depended on differences in both denser and less dense areas. The effects of hydrolysis on homogeneity were controlled by the use of Tchacarof's index. The procedure for using the Vickers M86 microdensitometer, with histogram unit, for analyses such as those reported here was developed to become established critically.     

Duplication of the midface

Facial duplication is one of the rarest forms of craniofacial anomalies. Only a few cases have been reported and described in the literature. We describe here two cases of midfacial duplication, one in a male and the other in a female. Both were examined clinically and radiologically including computed tomographic scanning, with three-dimensional computer reconstruction in the second patient. A histopathological examination was also carried out in both patients for the removed abnormal masses. The embryology of the face, together with the morphopathogenesis and the surgical management and outcome of the two patients, is discussed in detail.     

The Use of Synchronous Demodulation for the Measurement of Eye Movements by Means of an Ocular Magnetic Search Coil

This paper describes an eye position monitoring system that can be built using inexpensive components for the demodulator. It uses a two-frequency (f and 2f) technique which provides excellent channel separation with a miinimum of adjustment and wide dynamic signal range. Phasing errors produce no crosstalk effects for a pure sine-wave signal. It should be noted that this system will also work as a single-frequency two-phase system, merely by changing the driver unit.