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PubMed1997

The use of a multitracer technique for the studies of the uptake and retention of trace elements in rats.

The uptake by, and distribution and retention of radioactive isotopes in various organs of Wistar rats were examined using the multitracer technique. A hydrocholoric acid solution (pH 3) of a carrier-free radioactive multitracer was prepared from gold foil irradiated with a 14N beam of 135 MeV nucleon. The solution was administered orally to 12 7-week-old male rats. Urine and faeces were collected and each group of three rats was killed at 1, 2, 3 or 6 days after administration. The percentage of administered dose of the 17 elements, Mn, Co, Zn, As, Rb, Sr, Y, Eu, Gd, Er, Tm, Yb, Lu, W, Re, Ir and Pt in the organs blood and excreta were determined using gamma-ray spectrometry. Each element revealed its characteristic distribution among the different organs, including the blood. These results are discussed and compared with those of single-tracer experiments, and the advantages of the multitracer technique are presented.

Administration, Oral↗
PubMed1998

A longitudinal study of pulmonary involvement in primary Sjögren's syndrome: relationship between alveolitis and subsequent lung changes on high-resolution computed tomography.

Eighteen non-smoking women suffering from primary Sjögren's syndrome (pSS) with previously documented alveolitis were re-examined, clinically and by pulmonary function tests (PFT), bronchoalveolar lavage (BAL), chest X-ray and high-resolution computed tomography (HRCT) after a 2 yr follow-up period. Longitudinal evaluation revealed unchanged PFT. The final BAL study showed a normal differential count in six of 14 patients with initial lymphocyte alveolitis, and a persistent alveolar lymphocytosis in the remaining eight patients, associated with an increased percentage of neutrophils in one of them. In four patients with initial mixed alveolitis, the BAL cell profile was unchanged 2 yr later. Five of 18 patients (28%) had abnormal HRCT, represented by isolated septal/subpleural lines in three patients, ground-glass opacities with irregular pleural margins in one patient, and ground-glass opacities associated with septal/subpleural lines in another. All these patients had abnormal BAL results with an increased proportion of both neutrophils and lymphocytes. The presence of alveolar neutrophils was associated with a significantly (P=0.005) greater mean rate of reduction of carbon monoxide diffusing capacity (DLCO) -- more than four times the normal rate of loss of DLCO. Chest X-ray, repeated at the end of the 2 yr follow-up period, showed parenchymal abnormalities in only one patient who had evidence of fibrosis on HRCT. This study provides evidence that lung involvement is not an uncommon extraglandular manifestation of pSS and that a BAL neutrophilia may play an important role in the pathogenesis of pulmonary disease in this autoimmune disorder.

Adult↗
PubMed1981

[Is the intraoperative electrical stimulation test of Burge indispensable in order to ensure complete denervation in selective proximal vagotomy? (author's transl)].

The success of selective proximal vagotomy in the treatment of chronic duodenal ulcer is dependent on complete denervation of the proximal part of the stomach, as well as on the preservation of antral innervation. Inadequate nerve dissection results in therapeutic failure. The most frequent cause of recurrent ulcers is incomplete vagal denervation of the acid-secreting cells. Therefore, it would seem desirable to use an intraoperative test to check completeness of vagotomy, giving the surgeon the possibility of rectifying an inadequate nerve section still at the time of operation. Among several methods the electrical stimulation test described by Burge and Vane has gained general acceptance. However, the question of whether the intraoperative test actually improves the results of vagotomy remains equivocal. In an initial series of 39 vagotomies we ensured completeness of denervation by the electrical stimulation test. In a subsequent series of 44 operations vagotomy was performed without the test. The patients were re-examined one and again two years following operation (clinical evaluation, gastroscopy and/or X-ray examination). The results of this retrospective analysis using the classification of Visick showed no difference between the two series. Hence, we have no reason to suppose that omission of the intraoperative test will result in an increased number of incomplete vagotomies, provided the surgeon has gained his experience in this operative procedure by using the test to check his surgical technique, which thereby becomes standardized. Thereafter, the Burge test becomes dispensible.

Duodenal Ulcer↗
PubMed1996

Hot tub legionellosis.

Legionella pneumophila is the cause of Legionnaires' disease, and Pontiac fever, an influenza-like condition without pneumonia. We present a case of Pontiac fever after exposure to a hot tub contaminated with L pneumophila. A 37 y/o wf presented to the office with acute onset of sore throat, fever, headache, and myalgia. Patient was hospitalized 3 days later because of worsening shortness of air. Chest x-ray was normal. Patient was treated with 2 days of IV erythromycin and was discharged home on oral erythromycin. Her Legionella IFA was 1:16,384. Two days later, she developed chest tightness, pleuritic chest pain, and increasing shortness of air but did not have any cough or sputum production. She was re-hospitalized with a diagnosis of Pontiac fever and treated with IV erythromycin plus oral rifampin. A repeat chest x-ray remained normal. After a detailed epidemiologic history was obtained, it was noted that she became ill after using a hot tub, which her two children also used and they themselves developed a self limited illness. Water from the hot tub was positive for L pneumophila by DFA, culture, and PCR. Patient improved gradually with therapy and was discharged home. This report emphasizes the importance of a complete epidemiologic history in the diagnosis of respiratory infections. It also demonstrates that aquatic environment can be contaminated with Legionella and serve as a source of infection.

Adult↗
PubMed1998

Specificity of diastereomers of [99mTc]TRODAT-1 as dopamine transporter imaging agents.

Recently, we reported the first human study of [99mTc]TRODAT-1, technetium, 2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2- yl]methyl](2-mercaptoethyl)amino]ethyl]amino]-ethanethiolato(3-)-o xo- [1R-(exo-exo)]-, as an imaging agent of central nervous system (CNS) dopamine transporters. Due to the existence of several chiral centers on this molecule, upon the formation of [99mTc]TRODAT-1 complex (2) several diastereomers could be created. Two major diastereomers of [99mTc]TRODAT-1 (2), designated as peak A (2A) and peak B (2B), were separated by HPLC. Biodistribution of the purified diastereomers 2A,B was evaluated in rats. It appears that 2A displayed a higher lipophilicity than 2B (PC = 305 and 229, respectively), and a similar trend was observed for the initial brain uptake at 2 min postinjection (0.50% and 0.28% dose/organ for 2A,B, respectively). At 60 min post-iv-injection, the specific uptakes, as measured by [striatum - cerebellum]/cerebellum ([ST-CB]/CB) ratio, were 1.72 and 2.79 for 2A,B, respectively. The higher [ST-CB]/CB ratio observed for 2B was corroborated by the results of an in vitro binding assay. Higher binding affinity for dopamine transporters was observed for 3B (Ki = 13.87 and 8.42 nM for the analogous rhenium complexes 3A,B, respectively). The structure of the [99mTc]TRODAT-1 complexes was deduced using nonradioactive rhenium as a surrogate for radioactive technetium complex. Reacting free TRODAT-1 ligand with [Bu4N][ReOCl4] yielded two major complexes: Re-TRODAT-1A (3A) and Re-TRODAT-1B (3B) (corresponding with peaks A and B of [99mTc]TRODAT-1, respectively), whose structures were determined by X-ray analysis. The X-ray structures show that both complexes have a pseudo-square-pyramidal structure of [RevO]3+N2S2 core with oxygen occupying the apical position and the N-alkyl substitution in syn-configuration to the oxo-rhenium bond. In conclusion, TRODAT-1 formed at least two diastereomers after complexing with a metal(V)-oxo (M = 99mTc, Re) center core. The two isomers display different binding affinities toward dopamine transporters and distinct properties of localization in the striatum area of the brain where the transporters are located.

Animals↗
PubMed2004

The crucial role of the diphosphine heteroatom X in the stereochemistry and stabilization of the substitution-inert [M(N)(PXP)]2+ metal fragments (M = Tc, Re; PXP = diphosphine ligand).

The nature of the heteroatom X incorporated in the five-membered PXP-diphosphine bridging chain was found to play a primary unit role both in the overall stability and in the stereochemical arrangement of nitrido-containing [M(N)(PXP)](2+) metal fragments (M = Tc, Re). Thus, by mixing PXP ligands with labile [Re(N)Cl(4)](-) and Tc(N)Cl(2)(PPh(3))(2) nitrido precursors in CH(2)Cl(2)/MeOH mixtures, a series of neutral M(N)Cl(2)(PXP) complexes (M = Tc, 1-5; M = Re, 8, 9) was collected. In the resulting distorted octahedrons, PXP adopted facial or meridional coordination, and combination with halide co-ligands produced three different stereochemical arrangements, that is, fac,cis, mer,cis, and mer,trans, depending primarily on the nature of the diphosphine heteroatom X. When X = NH, mer,cis-Tc(N)Cl(2)(PNP1), 1, was the only isomer formed. Alternatively, when a tertiary amine nitrogen (X = NR; R = CH(3), CH(2)CH(2)OCH(3)) was introduced in the bridging chain, fac,cis-M(N)Cl(2)(PN(R)P) complexes (M = Tc, 2, 3; M = Re, 8f) were obtained. Isomerization into the mer,cis-Re(N)Cl(2)(PN(R)P), 8m, species was observed only in the case of rhenium when the tertiary amine group carried the less encumbering methyl substituent. fac,cis-Tc(N)Cl(2)(PSP), 4f, was isolated in the solid state when X = S, but a mixture of fac,cis-Tc(N)Cl(2)(PSP) and mer,trans-Tc(N)Cl(2)(PSP), 4m, isomers was found in equilibrium in the solution state. A similar equilibrium between fac,cis-M(N)Cl(2)(POP) (M = Tc, 5f; M = Re, 9f) and mer,trans-M(N)Cl(2)(POP) (M = Tc, 5m; M = Re, 9m) species was detected in POP-containing complexes. The molecular structure of all of these complexes was assessed by means of conventional physicochemical techniques including multinuclear NMR spectroscopy and X-ray diffraction analysis of representative mer,cis-Tc(N)Cl(2)(PN(H)P), 1, fac,cis-Tc(N)Cl(2)(PSP), 4f, and mer,cis-Re(N)Cl(2)(PN(Me)P), 8m, compounds.

Journal Article↗
PubMed2000

Variation of the antimicrobial activity of Pseudognaphalium vira vira (Asteraceae): isolation and X-ray structure of ent-3beta-hydroxy-16-kauren-19-oic acid.

The antimicrobial properties of the resinous exudate from twigs and leaves of a population of Pseudognaphalium vira vira were re-examined against five Gram positive bacteria. The observed decrease in the antimicrobial activity might reflect a change in the diterpenoid composition of the exudate. The title compound 2 was isolated in substantial amount, together with ent-16-kauren-19-oic acid (1), and its structure determined by X-ray diffraction analysis.

Anti-Bacterial Agents↗
PubMed2003

A cytochrome c oxidase proton pumping mechanism that excludes the O2 reduction site.

A redox-coupled conformational change in Asp51 of subunit I and a hydrogen-bond network connecting Asp51 with the matrix surface have been deduced from X-ray structures of bovine heart cytochrome c oxidase. This has provided evidence that Asp51 may play a role in the proton pumping process. However, the lack of complete conservation of a residue analogous to Asp51, the inclusion of a peptide bond in the hydrogen-bonding network and the lack of apparent involvement of the O2 reduction site have been used as arguments against the involvement of Asp51 in the mechanism of proton pumping. This minireview re-examines these arguments.

Animals↗
PubMed1988

A new calculation of the carcinogenic risk of obstetric X-raying.

The association between obstetric X-raying and childhood cancer was first identified by the Oxford Survey of Childhood Cancers in 1956. The present re-analysis exploits the case-control matching of the study while incorporating the effects of important risk determinants, notably year of birth, trimester of exposure and number of films exposed. The decline in risk over time is closely mirrored by the estimated decline in dose per film and, by constraining these two relationships to be parallel, time-invariant estimates of the extra risk per mGy are obtained. For example, it is now estimated that irradiating 10(6) foetuses with 1 mGy of X-rays would, in the absence of other causes of death, yield 175 extra cases of cancer and leukaemia in the first 15 years of life.

Adolescent↗
PubMed2000

Re(V) complexes with an open-chain quadridentate ligand containing two amine and two amido donors. Synthesis, characterization, and solution equilibria of Re2O3(dioxo-tetH4)2 and [ReO(H2O)(dioxo-tetH4)]Cl (dioxo-tetH6 = 1,4,8,11-tetraazaundecane-5,7-dione).

We are interested in identifying mononuclear cationic [M(V)=O]3+ (M = Tc, Re) complexes for radiopharmaceutical applications. The open-chain ligand, 1,4,8,11-tetraazaundecane-5,7-dione-(dioxo-tetH6) with two amine and two amide donors, was selected for investigation since the literature led us to expect that a five-coordinate [Re(V)=O(dioxo-tetH4)]+ cation would dominate. Instead, the neutral mu-oxo bridged dinuclear complex, Re2O3(dioxo-tetH4)2 (1), and a salt of the six-coordinate mononuclear cation, [ReO(H2O)(dioxo-tetH4)]+ (2), were isolated; the structure of each was determined by X-ray crystallography. The cation (2) is unusual because it has a trans-oxo/aqua core. Such aqua compounds are rarely isolated, and the Re-OH2 distance is relatively short (2.185 A). The cation has two pKa values, 4.1 and 8.7, determined with visible spectroscopy. Since the Re-OH2 bond is short, the coordinated water is likely to be acidic. Thus the two pKa's are assigned to the stepwise deprotonation of the water ligand to give a trans-oxo/hydroxo neutral form and a trans-dioxo anion. Although 1 was the first product isolated following ligand exchange of ReOCl3(Me2S)(OPPh3) with dioxo-tetH6 under neutral conditions, it probably formed from the hydroxo mononuclear complex. Under concentrated conditions (approximately 300 mM) the dinuclear complex deposited from solution, but the 1H NMR spectra of 2 (approximately 20 mM) were consistent with the presence of only monomeric forms in D2O, pH 3-12. 1H NMR experiments demonstrated that in DMSO-d6 2 converts to 1 upon addition of base, consistent with the proposal that two units of the hydroxo monomer condense to give the dinuclear form. In addition, all spectra of pure 1 dissolved in DMSO-d6 included extra low intensity signals that were characteristic of the monomer. Thus, although 1 is favored over the neutral monomer in DMSO-d6, the two complexes exist as a mixture of equilibrating forms. Our results do not support the previous findings for the Re(V) complex with a macrocyclic diamine-diamide ligand related to dioxo-tetH6. The data indicate that the ability of an amido group to donate electron density to a Re(V) center is moderately greater than the donating ability of a neutral amine group.

Amides↗
PubMed1990

Poly(ADP-ribose) metabolism in proliferating versus quiescent cells and its relationship to their radiation responses.

In the murine tumour cell lines 66 and 67 growing in vitro, quiescent (Q; unfed plateau-phase) cells are more sensitive to X-ray-induced cell killing than are proliferating (P) cells, while St4 cells (Q cells that have been re-fed and returned to 37 degrees C for 4h) are similar to P cells in radiosensitivity. We have been investigating parameters of poly(ADP-ribose) metabolism in order to determine whether such factors contribute to the variations in radiosensitivity of these growth states. These parameters were cellular NAD content, the activity of poly(ADP-ribose) transferase (ADPRT) in permeabilized cells and the activity of poly(ADP-ribose)-degrading enzymes. The results suggest that in line 66, but not 67, a reduced ability to regenerate NAD following irradiation was associated with the reduced survival of Q cells. However, neither the baseline activity of ADPRT nor the degree of stimulation of ADPRT by X-rays was found to correlate with survival, or with the induction and repair of DNA strand breaks. Stimulation of ADPRT by X-rays was dependent on dose and was greatest for a 2-min incubation with 3H-NAD. For a 2-min incubation the stimulation of ADPRT following a dose of 50 Gy was 7- and 10-fold in 66 and 67 P cells, respectively, versus 3-4-fold in Q cells. Detectable stimulation was observed in 66 P and Q cells for doses as low as 5 Gy. P and Q cells did not differ in the rate of degradation of the poly(ADP-ribose) polymers.

Animals↗