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Value of indium-111 tropolonate autologous granulocyte scintigraphy in the assessment of inflammatory bowel disease.

Indium-111 autologous leucocyte scanning is a non-invasive and reliable technique for the detection of abdominal abscesses. In the past decade several papers have been published concerning the use of this technique in the assessment of inflammatory bowel disease (IBD) with variable results. We conducted a prospective study of 62 patients with IBD attending the Leiden University Hospital, to assess the diagnostic value of indium-111 tropolonate autologous granulocyte scanning. Fifty-one patients had Crohn's disease (CD) (30 with involvement of the small bowel, 18 the colon only, and 3 patients had both localizations), and 11 had ulcerative colitis (UC). Twenty-one of 26 patients with evidence of active disease of the small intestine had a true-positive scan (sensitivity, 80%). However, accurate assessment of localization and extent of disease were often difficult. The other five patients had a false-negative scan. Seven patients had a true-negative scan. No false-positive scans were found. Thus, the diagnostic accuracy for small-intestinal Crohn's disease was 85%. In contrast, of 32 patients with colonic disease (CD and UC), 26 had a true-positive scan corresponding in localization and extent with standard investigations, 3 patients had a false-negative scan (sensitivity, 90%), and 3 had a true-negative scan (diagnostic accuracy, 91%). The patients' acceptability of this procedure was definitely superior to that for radiology and endoscopy. In conclusion, this technique has a definite place in evaluating localization and extent of active colonic disease and in severely ill patients in whom invasive techniques are contraindicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

In vivo kinetics of canine leukocytes labeled with technetium-99m HM-PAO and indium-111 tropolonate.

Two weeks after the introduction of osteomyelitis in three dogs, autologous leukocytes were dual-labeled with both [99mTc]HM-PAO and [111In]tropolonate, and reinjected. Blood sampling and imaging were then performed. Two weeks later, the same dogs received simultaneous injections of singly-labeled [99mTc]WBC and [111In]WBC for comparison. For both studies, blood samples were drawn over 6 hr to determine the respective blood clearance half-time (TB) and % recovery (%R0) of cell-bound radioactivity. There were no significant differences in the average TB results of the 99mTc and 111In groups, either within or between the dual- and singly-labeled studies. The %R0 of singly-labeled [99mTc]WBC was about half that of the other groups (p less than 0.01); however, this difference was attributed to the dissimilar radiochemical purity of the [99mTc]HM-PAO reagents. Region of interest analysis of the 6 and 24 hr images revealed no significant differences between either cell label in the relative or absolute in vivo uptake at known sites of osteomyelitis, noninfected surgery, and normal bone marrow.

Animals↗

Clinical comparison of indium-111 acetylacetone and indium-111 tropolone granulocytes.

This clinical study compares the efficacy of two 111In white blood cells preparations. Seventy-six patients were imaged after an injection of granulocytes (GRAN) isolated on a Ficoll-Hypaque gradient and labeled with [111In]acetylacetone (ACAC) in saline; 105 patients were imaged after an injection of GRAN isolated on a metrizamide-plasma gradient and labeled with [111In]tropolone (TROP) in plasma. Early (2-4 hr), intermediate (4-6 hr), and delayed (24 hr) images were obtained. The specificity was quite high (94-100%) in both preparations and no statistical differences could be found. The sensitivity for ACAC-GRAN for the early, intermediate, and delayed images were 39%, 63%, and 64%, respectively; for TROP-GRAN it was 80%, 89%, and 92%, respectively. In all cases the TROP-GRAN images were significantly more sensitive than the ACAC-GRAN images obtained at the same time after injection (p less than 0.001 for early and delayed images, 0.01 less than p less than 0.025 for intermediate images). For ACAC-GRAN the intermediate and delayed images were significantly more sensitive than the early images, while no significant difference could be found for TROP-GRAN. In a blinded experiment, the ability of TROP-GRAN to demonstrate a lesion was compared to that of ACAC-GRAN. TROP-GRAN demonstrated the lesions better than ACAC-GRAN, both in the early and late images (p less than 0.001). TROP-GRAN visualization scores at 4-6 hr equaled those obtained 24 hr after injection. In conclusion, GRAN separated and labeled in plasma with TROP are superior to those separated and labeled in saline with ACAC in three ways: higher visualization scores, earlier visualization of the lesion, and greater sensitivity.

Adolescent↗

The importance of the phenyl-tropolone 'aS' configuration in colchicine's binding to tubulin.

Measuring ellipticities of (+/-)-colchicine and (+/-)-deacetamidocolchicine in the presence of tubulin afforded net positive CD bands with maxima at 340 nm resulting from reduction of the negative ellipticities upon binding of (-) enantiomers to the protein. Results of optical studies together with earlier NMR conformational analysis of these molecules substantiate the hypothesis that colchicinoids bind to tubulin with the phenyl-tropolone moiety in the 'aS' configuration. Natural colchicine which binds to tubulin, therefore, should be referred to as (-)-(aS,7S)-colchicine.

Animals↗

Quantum tunneling in the midrange vibrational fundamentals of tropolone.

The Fourier transform infrared spectrum of tropolone(OH) vapor in the 1175-1700 cm(-1) region is reported at 0.0025 and 0.10 cm(-1) spectral resolutions. The 12 vibrational fundamentals in this region of rapidly rising vibrational state density are dominated by mixtures of the CC, CO, CCH, and COH internal coordinates. Estimates based on the measurement of sharp Q branch peaks are reported for 11 of the spectral doublet component separations DS(v) = |Delta(v) +/- Delta(0)|. Delta(0) = 0.974 cm(-1) is the known zero-point splitting, and three a(1) modes show tunneling splittings Delta(v) approximately Delta(0), four b(2) modes show splittings Delta(v) approximately 0.90Delta(0), and the remaining four modes show splittings Delta(v) falling 5-14% from Delta(0.) Significantly, the splitting for the nominal COH bending mode nu(8) (a(1)) is small, that is, 10% from Delta(0). Many of the vibrational excited states demonstrate strong anharmonic behavior, but there are only mild perturbations on the tautomerization mechanism driving Delta(0). The data suggest, especially for the higher frequency a(1) fundamentals, the onset of selective intramolecular vibrational energy redistribution processes that are fast on the time scale of the tautomerization process. These appear to delocalize and smooth out the topographical modifications of the zero-point potential energy surface that are anticipated to follow absorption of the nu(v) photon. Further, the spectra show the propensity for the Delta(v) splittings of b(2) and other complex vibrations to be damped relative to Delta(0).

Journal Article↗

Epolones: novel sesquiterpene-tropolones from fungus OS-F69284 that induce erythropoietin in human cells.

In the course of our screening for small molecule modulators of erythropoietin gene expression, two novel sesquiterpene tropolones and pycnidone were isolated from a culture of OS-F69284 (ATCC 74390). Their structures were elucidated by extensive 1H and 13C NMR spectroscopic studies and chemical reactions. These compounds induced erythropoietin gene expression 5-fold at a concentration of 1-1.6 microM.

Carbohydrate Sequence↗

Polarization spectroscopy of gaseous tropolone in a strong electric field.

We report studies of polarization spectroscopy of gaseous tropolone in a strong electric field using resonantly enhanced multiphoton ionization. The electric field induces localization of the tunneling proton between the two equivalent oxygen atoms. As a result, the C2v symmetry of the molecular frame is broken, and the parity selection rule is violated. The field induced transitions are type A with transition dipoles perpendicular to those under field free conditions. The polarization ratios, i.e., the ratios of the overall excitation yield under different polarizations of the resonant laser, thus deviate from those of a pure type B transition. In a field of 60 kV/cm, the experimental polarization ratio implies an essentially equal mixture of type B and type A transitions. Moreover, the induced transitions overlap with the two field-free subbands, and the resulting intensity ratios between the two subbands demonstrate dependence on the applied electric field. These observations can be qualitatively modeled using a quantum mechanical approach by assuming a two level system. A puzzling result is the magnitude of the transition dipole of the induced transition, which is proven to be essentially linearly dependent on the applied electric field.

Journal Article↗

The all-Cartesian reaction plane Hamiltonian: formulation and application to the H-atom transfer in tropolone.

In this work we present an all-Cartesian reaction surface approach, where the large amplitude coordinates span the so-called reaction plane, that is, the unique plane defined by the two minima and the saddle-point structure of an isomerization reaction. Orthogonal modes are treated within harmonic approximation which gives the total Hamiltonian an almost separable form that is suitable for multidimensional quantum dynamics calculations. The reaction plane Hamiltonian is constructed for the H-atom transfer in tropolone as an example for a system with an intramolecular O...H-O hydrogen bond. We find ground-state tunneling splittings of 3.5 and 0.16 cm(-1) for the normal and deuterated species, respectively. We calculated infrared-absorption spectra for a four-dimensional model focusing on the low-frequency region. Here, we identify a reaction mode which is closely connected to the tautomerization that is reflected in the increase of tunneling splitting to 18 cm(-1) upon excitation.

Journal Article↗

Tropolone.

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Tropolone↗

Platelet viability (aggregation, migration, recovery) after radiolabelling from hypercholesterolemics using various tracers (oxine, oxine-sulphate, tropolone, MPO).

Earlier results indicated a diminished labelling efficiency and recovery negatively linked to actual cholesterol and lipoprotein values in hyperlipoproteinemics. This study was designed to examine whether other alternative tracers exhibit similar results and to study the influence on platelet viability in the presence or absence of PGI2. We demonstrate that no substantial difference occurs between the four tracers concerning labelling efficiency and recovery in normo- and hypercholesterolemics. Cholesterol severely affects the labelling parameters for all the tracers to a comparable extent. The absolute platelet function varies considerably, however, the percent changes in normo- and hypercholesterolemics seen before and after the labelling procedure do not differ significantly. PGI2 improves recovery in general, however, without affecting labelling efficiency or in vitro viability testing. As prolonged incubation further increases labelling efficiency, the presence and extent of hyperlipoproteinemia should be known in order to avoid poor labeling and viability and subsequently poor clinical results.

Adult↗