Parvovirus-associated cerebellar hypoplasia and hydrocephalus in day old broiler chickens.

Cerebellar hypoplasia and hydrocephalus were identified in day old broiler chickens showing nervous signs, impaired mobility, and diarrhea. At postmortem examination, brains of chickens were misshapen and cerebellums were smaller than normal. Microscopically, cerebellar folia were reduced in size and irregularly shaped, and the ventricles were widely distended. Affected cerebellums had focal areas along the base of folia where the internal granular cell layer had been lost, and Purkinje cells were disorganized and located within the molecular layer. Parvovirus DNA was detected by polymerase chain reaction in three of nine brains with oligonucleotide primers designed for amplification of chicken and turkey parvoviruses. On the basis of phylogenetic analyses, the detected virus was most closely related to chicken parvoviruses. These findings suggest that a chicken parvovirus might cause a neurologic disease of young chickens characterized by cerebellar hypoplasia and hydrocephalus; however, its role as the cause of the disease remains to be confirmed.

Iron complexes of the cardioprotective agent dexrazoxane (ICRF-187) and its desmethyl derivative, ICRF-154: solid state structure, solution thermodynamics, and DNA cleavage activity.

This study investigates the solution thermodynamics of the iron complexes of dexrazoxane (ICRF-187, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane), [Fe(ADR-925)](+/0), and its desmethyl derivative ICRF-154, [Fe(ICRF-247)H2O](+/0). The solid state structure of [Fe(ICRF-247)H2O]+ is also reported. [Fe(ICRF-247)H2O]Br x 0.5NaBr x H2O crystallizes in the P42(1)2 space group with Z = 4, a = 14.9851(8), b = 14.9851(8), c = 8.0825(9) A and R = 0.03(2) for 1839 reflections and exhibits a pentagonal bipyramidal geometry with a labile water molecule occupying the seventh coordination site. Potentiometric titrations (FeL = 8.5 mM, 0.1 M NaNO3, 25 degrees C) reveal stable monomeric complexes (log Kf = 18.2 +/- 0.1, [Fe(ADR-925)]+, and 17.4 +/- 0.1, [Fe(ICRF-247)H2O]+) exist in solution at relatively low pH. Upon addition of base, the iron-bound water is deprotonated; the pKa values for [Fe(ICRF-247)H2O]+ and [Fe(ADR-925)]+ are 5.63 +/- 0.07 and 5.84 +/- 0.07, respectively. At higher pH both complexes undergo mu-oxo dimerization characterized by log Kd values of 2.68 +/- 0.07 for [Fe(ICRF-247)H2O]+ and 2.23 +/- 0.07 for [Fe(ADR-925)]+. In the presence of an oxidant and reductant, both [Fe(ICRF-247)H2O]+ and [Fe(ADR-925)]+ produce hydroxyl radicals that cleave pBR322 plasmid DNA at pH 7 in a metal complex concentration-dependent manner. At low metal complex concentrations (approximately 10(-5) M) where the monomeric form predominates, cleavage by both FeICRF complexes is efficient while at higher concentrations (approximately 5 x 10(-4) M) DNA cleavage is hindered. This change in reactivity is in part accounted for by dimer formation.

Fe-EDTA-Bisamide and Fe-ADR-925, The Iron-Bound Hydrolysis Product of the Cardioprotective Agent Dexrazoxane, Cleave DNA Via the Hydroxyl Radical.

Use of the antitumor drug doxorubicin is limited by cardiomyopathic side-effects which are believed to be due to iron-mediated hydroxyl radical generation. Dexrazoxane reduces this cardiotoxicity, possibly by removal of iron from doxorubicin by the EDTA-like hydrolysis product of dexrazoxane, ADR-925. However, EDTA-diimides like dexrazoxane, previously used as antitumor agents, are themselves carcinogenic, and recent studies have found that Fe-ADR-925 can also promote hydroxyl radical production. This study demonstrates that, like Fe-EDTA, Fe-ADR-925 and a related desmethyl complex can cleave plasmid DNA under Fenton conditions, and suggests by radical scavenger study that this cleavage is probably via the hydroxyl radical. Differences in DNA cleavage dependence upon concentrations of Fe-EDTA, Fe-ADR-925 and Fe-EDTA-bisamide can be explained by differences in the solution chemistry of the complexes.

Directed hydroxyl radical probing of 16S rRNA using Fe(II) tethered to ribosomal protein S4.

Localized hydroxyl radical probing has been used to explore the rRNA neighborhood around a unique position in the structure of the Escherichia coli 30S ribosomal subunit. Fe(II) was attached to ribosomal protein S4 at Cys-31 via the reagent 1-(p-bromoacetamidobenzyl)-EDTA. [Fe-Cys31]S4 was then complexed with 16S rRNA or incorporated into active 30S ribosomal subunits by in vitro reconstitution with 16S rRNA and a mixture of the remaining 30S subunit proteins. Hydroxyl radicals generated from the tethered Fe resulted in cleavage of the 16S rRNA chain in two localized regions of its 5' domain. One region spans positions 419-432 and is close to the multihelix junction previously placed at the RNA binding site of S4 by chemical and enzymatic protection (footprinting) and crosslinking studies. A second site of directed cleavage includes nucleotides 297-303, which overlap a site that is protected from chemical modification by protein S16, a near neighbor of S4 in the ribosome. These results provide useful information about the three-dimensional organization of 16S rRNA and indicate that these two regions of its 5' domain are in close spatial proximity to Cys-31 of protein S4.

Structure of aqua[N,N'-ethylenebis(N-carbamoylmethylglycinato)]copper(II) dihydrate.

The structure consists of a copper(II) cation octahedrally coordinated to the polyaminocarboxylate ligand through five ligating atoms: one N atom of the ethylenediamine ring, two carboxylate O atoms and a molecule of water form a square plane, while one amide O and the other ethylenediamine-ring N atom are above and below the plane. The latter two atoms display tetragonal distortion. Eight intermolecular hydrogen bonds involve H, N and O atoms of the complex as well as the two water molecules of crystallization.