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1.
Phys Chem Chem Phys ; 18(4): 2292-6, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26700139

RESUMO

Iridium oxide based electrodes are among the most promising candidates for electrocatalyzing the oxygen evolution reaction, making it imperative to understand their chemical/electronic structure. However, the complexity of iridium oxide's electronic structure makes it particularly difficult to experimentally determine the chemical state of the active surface species. To achieve an accurate understanding of the electronic structure of iridium oxide surfaces, we have combined synchrotron-based X-ray photoemission and absorption spectroscopies with ab initio calculations. Our investigation reveals a pre-edge feature in the O K-edge of highly catalytically active X-ray amorphous iridium oxides that we have identified as O 2p hole states forming in conjunction with Ir(III). These electronic defects in the near-surface region of the anionic and cationic framework are likely critical for the enhanced activity of amorphous iridium oxides relative to their crystalline counterparts.

2.
Phys Chem Chem Phys ; 17(38): 25073-89, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26345450

RESUMO

The oxidation of copper catalysts during ethylene epoxidation was characterized using in situ photoemission spectroscopy and electron microscopy. Gas chromatography, proton-transfer reaction mass spectrometry and electron-ionization mass spectrometry were used to characterize the catalytic properties of the oxidized copper. We find that copper corrodes during epoxidation in a 1 : 1 mixture of oxygen and ethylene. The catalyst corrosion passes through several stages, beginning with the formation of an O-terminated surface, followed by the formation of Cu2O scale and eventually a CuO scale. The oxidized catalyst exhibits measurable activity for ethylene epoxidation, but with a low selectivity of <3%. Tests on pure Cu2O and CuO powders confirm that the oxides intrinsically exhibit partial-oxidation activity. Cu2O was found to form acetaldehyde and ethylene epoxide in roughly equal amounts (1.0% and 1.2% respectively), while CuO was found to form much less ethyl aldehyde than ethylene epoxide (0.1% and 1.0%, respectively). Metallic copper catalysts were examined in extreme dilute-O2 epoxidation conditions to try and keep the catalyst from oxidizing during the reaction. It was found that in feed of 1 part O2 to 2500 parts C2H4 (PO2 = 1.2 × 10(-4) mbar) the copper surface becomes O-terminated. The O-terminated surface was found to exhibit partial-oxidation selectivity similar to that of Cu2O. With increasing O2 concentration (>8/2500) Cu2O forms and eventually covers the surface.

3.
Orthod Craniofac Res ; 18 Suppl 2: 56-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26567856

RESUMO

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Atenção à Saúde , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Fala , Reino Unido
4.
Orthod Craniofac Res ; 18 Suppl 2: 14-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26567852

RESUMO

OBJECTIVES: To compare facial appearance and dento-alveolar relationship outcomes from the CSAG (1998) and CCUK (2013) studies. SETTING AND SAMPLE POPULATION: Five-year-olds born with non-syndromic unilateral cleft lip and palate. Those in the original CSAG were treated in a dispersed model of care with low-volume operators. Those in CCUK were treated in a more centralized, high-volume operator model. MATERIALS AND METHODS: We compared facial appearance using frontal view photographs (252 CCUK, 239 CSAG) and dental relationships using study models (198 CCUK, 223 CSAG). Facial appearance was scored by a panel of six assessors using a standardized and validated outcome tool. Dento-alveolar relationships were scored by two assessors using the 5-Year-Olds' Index. Ordinal regression was used to compare results between surveys. RESULTS: Excellent or good facial appearance was seen in 36.2% of CCUK compared with 31.9% in CSAG. In CCUK, 21.6% were rated as having poor or very poor facial appearance compared with 27.6% in CSAG. The percentage rated as having excellent or good dento-alveolar relationships was 53.0% in CCUK compared with 29.6% in CSAG. In CCUK, 19.2% were rated as having poor or very poor dento-alveolar relationships compared to 36.3% in CSAG. The odds ratios for improved outcome in CCUK compared to CSAG were 1.43 (95% CI 1.03, 1.97) for facial appearance and 2.29 (95% CI 1.47, 3.55) for dento-alveolar relationships. CONCLUSIONS: Facial and dento-alveolar outcomes were better in CCUK children compared to those in CSAG.


Assuntos
Transplante Ósseo , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Pré-Escolar , Face , Feminino , Humanos , Masculino , Resultado do Tratamento
5.
J Chem Phys ; 141(2): 024503, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25028023

RESUMO

Bulk metallic glasses (BMGs) are characterized by a number of remarkable physical and mechanical properties. Unfortunately, these same materials are often intrinsically brittle, which limits their utility. Consequently, considerable effort has been expended searching for correlations between the phenomenologically complex mechanical properties of metallic glasses and more basic properties, such correlations might provide insight into the structure and bonding controlling the deformation properties of BMGs. While conducting such a search, we uncovered a weak correlation between a BMG's work function and its susceptibility to brittle behavior. We argue that the basis for this correlation is a consequence of a component of the work function - the surface dipole - and a fundamental bond property related to the shape of the charge density at a bond critical point. Together these observations suggest that simple first principle calculations might be useful in the search for tougher BMGs.

6.
Intern Med J ; 43(5): 507-12, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23176301

RESUMO

BACKGROUND/AIMS: Recent data show great benefit from beta adrenergic blocking drug (ß-blocker) use in heart failure and has resulted in increased use of these established agents. Older data caution against their use in patients with reversible airways disease because of risks of bronchoconstriction. Anecdotally, we noted a difference in willingness to prescribe ß-blockers by cardiologists and respiratory physicians, especially for patients with coexisting airways disease. We sought to test this difference. METHODS: Nine clinical scenarios were created, tested and emailed to all members of the Cardiac and Thoracic societies of Australasia. Scenarios combined varying degrees of benefit and risk (bronchoconstriction). An inducement to return questionnaires was applied. RESULTS: Cardiologists and respiratory physicians were similarly willing to prescribe ß-blockers for patients at little risk of bronchoconstriction, irrespective of potential benefit. Cardiologists were more willing to prescribe ß-blockers than respiratory physicians for patients at greater risk of bronchoconstriction, particularly when the potential therapeutic benefit was greater. CONCLUSIONS: Our perception that cardiologists were more willing to prescribe ß-blockers than respiratory physicians was confirmed. This probably results from a difference in focus (namely focus on benefit by cardiologists vs focus on risk by respiratory physicians), although other factors including awareness of limitations of pulmonary function testing by respiratory physicians may have been involved. Until better tests are available (that discriminate between patients who are likely to suffer bronchoconstriction from those who are not), it is likely that this difference between the specialties will remain.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Cardiologia/métodos , Coleta de Dados/métodos , Prescrições de Medicamentos , Médicos , Pneumologia/métodos , Australásia , Comportamento de Escolha , Humanos , Médicos/psicologia
7.
Intern Med J ; 42(3): 311-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20298510

RESUMO

BACKGROUND: Cigarette smoking prevalence has been declining over decades in Western countries especially in higher socioeconomic groups. Employees of Australian hospitals span the socioeconomic spectrum, but there are few data on smoking prevalence from these workplaces. Because smoking is a health hazard, some argue that it should be banned on hospital premises, but employees' opinions appear not to have been widely canvassed. Cigarette smoking is a particular problem in hospitals because of the need for prolonged abstinence by immobile patients and the stressors that accompany life-and-death events for patients and/or relatives. The Queen Elizabeth Hospital has had a Stop Smoking Service for >10 years, but how smoking prevalence has changed and how it compares with similar hospitals is unknown. AIMS: The aims of this study were (i) to determine smoking prevalence by employees of The Queen Elizabeth Hospital and to compare this with employees of other hospitals and (ii) to ascertain employees' perspectives regarding smoking on hospital grounds. METHODS: Single page questionnaires were forwarded to employees of four South Australian/Northern Territory hospitals enquiring about smoking status, employment category, views about smoking on hospital premises, etc. Responses were voluntary. RESULTS: Response rates were 39-59%. Smoking prevalence has steadily declined at The Queen Elizabeth Hospital and is now 8.4%. Prevalence at comparator hospitals was approximately double this value. Most staff thought the visibility of smoking was problematic, but support for providing smoking area/s was greater than for a hospital-wide ban. CONCLUSIONS: The ongoing decline in smoking prevalence at The Queen Elizabeth Hospital is probably the result of the Staff Stop Smoking Service.


Assuntos
Hospitais de Ensino/estatística & dados numéricos , Recursos Humanos em Hospital/psicologia , Abandono do Hábito de Fumar , Fumar/epidemiologia , Adulto , Atitude do Pessoal de Saúde , Feminino , Hospitais Urbanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Recursos Humanos em Hospital/estatística & dados numéricos , Prevalência , Austrália do Sul/epidemiologia , Inquéritos e Questionários
8.
Intern Med J ; 42(3): 317-22, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20298509

RESUMO

BACKGROUND: A period of hospitalisation is perhaps the longest period of enforced 'temporary abstinence' smokers have to endure and hence many crave during their admission. Cravings may result in patients' smoking on hospital premises. Nicotine replacement may reduce cravings, decrease smoking on hospital grounds and increase interest in quitting post-discharge. AIM: The aim of this study was to compare the efficacy of two nicotine formulations in controlling inpatient cravings and enthusiasm for quitting post-discharge. METHODS: Inpatients who were smokers were randomised to nicotine patch or inhaler on alternating days. Patients selected their preferred formulation, which was then used for the duration of the hospital stay. Craving control and formulation preference were assessed by visual analogue scales (VAS), and interest in quitting on a 3-point scale. Abstinence was confirmed by exhaled breath CO monitoring. RESULTS: Patches were preferred by 64% of the 367 subjects. Fewer patients went outside to smoke after either formulation (37% before, 5% after enrolment). Cravings were reduced by both nicotine formulations (mean VAS score fell from 7.5 to 1.7). Interest in quitting post-discharge increased. Estimated mean exposure to nicotine was 5 mg/day (inhaler), 15 mg/day (transdermal patch) compared with 30 mg/day (cigarettes) before hospitalisation. CONCLUSIONS: Many smokers crave and some smoke outside during a hospital admission. While the patch was the preferred formulation of nicotine replacement therapy, both were effective in reducing cravings, increasing motivation for quitting post-discharge and improving Hospital 'image' by reducing smoking on campus. Nicotine replacement therapy should be made available to inpatients in all hospitals and other places of enforced prolonged abstinence.


Assuntos
Promoção da Saúde/organização & administração , Hospitais de Ensino/organização & administração , Pacientes Internados/psicologia , Motivação , Nicotina/uso terapêutico , Abandono do Hábito de Fumar , Tabagismo/tratamento farmacológico , Administração Cutânea , Administração por Inalação , Tosse/etiologia , Sonhos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Satisfação Pessoal , Prurido/induzido quimicamente , Inquéritos e Questionários , Dispositivos para o Abandono do Uso de Tabaco
9.
Intern Med J ; 42(2): 154-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21299782

RESUMO

BACKGROUND: Cigarette smoking remains a health issue despite declining prevalence in Australia. The burden of tobacco-related morbidity affects hospitals, particularly those in lower socioeconomic areas where prevalence is highest. AIM: We have shown that nicotine replacement therapy (NRT) use during hospitalization increases motivation to quit post-discharge. We postulated that subjects using the nicotine patch post-discharge, in comparison to the inhaler, would have higher rates of abstinence at 12 months after discharge. The aim was to compare the efficacy of the nicotine patch or inhaler formulation for cessation post-discharge, following use during admission. METHODS: Post-discharge, subjects chose their preferred formulation (patch or inhaler) based on their experience with NRT during admission. Tailored, medium-intensity support was provided with subsidized NRT during outpatient visits. Subjects were followed for 12 months. Exhaled breath CO confirmed non-smoking. RESULTS: Of 123 subjects enrolled, 37 elected to use the inhaler, 50 the patch and 36 no NRT. At 12 months continuous abstinence rates were 38%, 38% and 25% respectively. DISCUSSION: This study built upon the 'teachable moment' provided by hospitalization and the inpatient use of NRT, encouraging cessation post-discharge. Both NRT formulations provided similar 12 month cessation rates, and were superior to those achieved by subjects electing not to use NRT. Although the patch was the most popular formulation, the inhaler provided an equally efficacious alternative which addressed other facets of cigarette addiction. Subjects electing not to use NRT were less successful. Continuous abstinence rates were equivalent to community-based studies using NRT. We recommend a similar programme to other hospitals.


Assuntos
Admissão do Paciente/tendências , Alta do Paciente/tendências , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Dispositivos para o Abandono do Uso de Tabaco/estatística & dados numéricos , Dispositivos para o Abandono do Uso de Tabaco/tendências , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Fumar/epidemiologia , Fatores de Tempo
10.
Intern Med J ; 40(1): 52-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20575164

RESUMO

BACKGROUND: Digoxin remains a commonly prescribed medication for the treatment of congestive cardiac failure or atrial tachyarrhythmias. Its utility is offset by its narrow therapeutic index requiring regular blood concentration monitoring. Recent evidence suggests that a lower therapeutic range (0.5- 0.8 mg/L, or 0.6-1.0 nmol/L) is associated with reduced mortality in patients with congestive cardiac failure. Therapeutic drug monitoring for digoxin is carried out by immunoassays that are well established in routine clinical practice. Laboratories using different immunoassays may be involved in monitoring individual patients throughout the protracted course of therapy. These results should be concordant to ensure consistent dose individualization and optimum clinical management. We have investigated the discordance in digoxin measurements involving five different laboratories across the Adelaide metropolitan area. METHODS: Aliquots from routine digoxin samples (n = 261) were analysed by accredited laboratories using commercially available immunoassays. RESULTS: The results showed that 119 (46%) of 261 samples were so varied that a different clinical outcome was indicated when reviewed by the treating physician. The differences between the highest and lowest readings from any one sample were also substantial, with 45% of the measurements exceeding 0.3 microg/L. CONCLUSIONS: Our study shows the considerable variation in the routine monitoring of digoxin. This makes therapeutic drug monitoring difficult to interpret and complicates clinical management when treating physicians are endeavouring to avoid toxicity and optimize dosing. These results raise a significant concern for the quality of therapeutic drug monitoring of digoxin and have direct repercussions on patient care.


Assuntos
Técnicas de Laboratório Clínico/normas , Digoxina/sangue , Monitoramento de Medicamentos/normas , Papel do Médico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Técnicas de Laboratório Clínico/métodos , Digoxina/uso terapêutico , Monitoramento de Medicamentos/métodos , Humanos , Patologia Clínica/métodos , Patologia Clínica/normas , Resultado do Tratamento
11.
Nat Chem ; 10(10): 1008-1015, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30150725

RESUMO

Alloying provides a means by which to tune a metal catalyst's electronic structure and thus tailor its performance; however, mean-field behaviour in metals imposes limits. To access unprecedented catalytic behaviour, materials must exhibit emergent properties that are not simply interpolations of the constituent components' properties. Here we show an emergent electronic structure in single-atom alloys, whereby weak wavefunction mixing between minority and majority elements results in a free-atom-like electronic structure on the minority element. This unusual electronic structure alters the minority element's adsorption properties such that the bonding with adsorbates resembles the bonding in molecular metal complexes. We demonstrate this phenomenon with AgCu alloys, dilute in Cu, where the Cu d states are nearly unperturbed from their free-atom state. In situ electron spectroscopy demonstrates that this unusual electronic structure persists in reaction conditions and exhibits a 0.1 eV smaller activation barrier than bulk Cu in methanol reforming. Theory predicts that several other dilute alloys exhibit this phenomenon, which offers a design approach that may lead to alloys with unprecedented catalytic properties.

12.
J Phys Chem B ; 110(42): 21152-60, 2006 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-17048939

RESUMO

The growth and annealing behavior of ultrathin Au films on Pd{111} were monitored with scanning tunneling microscopy (STM) and medium energy ion scattering (MEIS). The adsorption of acetic acid on both clean and deliberately carbon-contaminated bimetallic surfaces was investigated with reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD). We report that the surface chemistry of acetic acid is strongly modified by the presence of Au in the bimetallic surface which acts both to stabilize adsorbed acetate and to decrease the tendency of acetic acid to decompose on adsorption to produce adsorbed carbon. The adsorption of acetic acid at 300 K is found to cause measurable segregation of Pd to the surface for all surface compositions tested.

13.
Biochim Biophys Acta ; 452(2): 597-607, 1976 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-188467

RESUMO

GMP synthetase (xanthosine-5'-phosphate: ammonia ligase (AMP-forming), EC 6.3.4.1) from Ehrlich ascites cells was found to be subject to multiple inhibition by its reaction product, PPi, and some analogs of adenosine. PPi and the nucleoside (N) inhibitors were also capable of individually inhibiting this enzyme. Under no conditions did the inhibition appear to be irreversible or "pseudoinactivating" in nature. The individual inhibition by PPi was competitive with respect to ATP (KI = 0.42 mM). Conversely, in the absence of PPi, the binding of N was noncompetitive with ATP, but shifted to a competitive pattern when PPi was present. Furthermore, with the inhibitors in concert, there was an apparent lowering of the KI values for both inhibitors. This data was consistent with either PPi functioning to tighten the binding of N at a noncatalytic site (positive cooperativity) or with PPi actually opening a second binding site for N in addition to the non-catalytic site. Although this study did not distinguish which of these events was occurring, it did reveal that the intensity of the effect of PPi appeared to be constant. That is, for various N inhibitors with a range of independently determined KI values from 26 to 1650 muM, the ratio of their KI values determined in the absence of PPi to the values determined in the presence of PPi was always 38 +/- 1.


Assuntos
Carcinoma de Ehrlich/enzimologia , Difosfatos/farmacologia , Ligases/antagonistas & inibidores , Ribonucleosídeos/farmacologia , Amônia , Animais , Nucleotídeos de Guanina/biossíntese , Cinética , Matemática , Camundongos , Fosfatos/farmacologia , Relação Estrutura-Atividade
14.
Biochim Biophys Acta ; 1330(2): 233-47, 1997 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-9408177

RESUMO

Sarcoplasmic reticulum (SR) membranes purified from young adult (4-6 months) and aged (26-28 months) Fischer 344 male rat skeletal muscle were compared with respect to the functional and structural properties of the Ca-ATPase and its associated lipids. While we find no age-related alterations in (1) expression levels of Ca-ATPase protein, and (2) calcium transport and ATPase activities, the Ca-ATPase isolated from aged muscle exhibits more rapid inactivation during mild (37 degrees C) heat treatment relative to that from young muscle. Saturation-transfer EPR measurements of maleimide spin-labeled Ca-ATPase and parallel measurements of fatty acyl chain dynamics demonstrate that, accompanying heat inactivation, the Ca-ATPase from aged skeletal muscle more readily undergoes self-association to form inactive oligomeric species without initial age-related differences in association state of the protein. Neither age nor heat inactivation results in differences in acyl chain dynamics of the bilayer including those lipids at the lipid-protein interface. Initial rates of tryptic digestion associated with the Ca-ATPase in SR isolated from aged muscle are 16(+/- 2)% higher relative to that from young muscle. indicating more solvent exposure of a portion of the cytoplasmic domain. During heat inactivation these structural differences are amplified as a result of immediate and rapid further unfolding of the Ca-ATPase isolated from aged muscle relative to the delayed unfolding of the Ca-ATPase isolated from young muscle. Thus age-related alterations in the solvent exposure of cytoplasmic peptides of the Ca-ATPase are likely to be critical to the loss of conformational and functional stability.


Assuntos
Envelhecimento/metabolismo , ATPases Transportadoras de Cálcio/química , Retículo Sarcoplasmático/enzimologia , Animais , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Membrana Celular/ultraestrutura , Espectroscopia de Ressonância de Spin Eletrônica , Temperatura Alta , Masculino , Lipídeos de Membrana/metabolismo , Estrutura Terciária de Proteína , Ratos , Ratos Endogâmicos F344 , Retículo Sarcoplasmático/ultraestrutura
15.
Clin Pharmacokinet ; 32(5): 357-67, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9160170

RESUMO

Since its discovery in 1970, and introduction into clinical practice in 1978, cyclosporin has become the most important immunosuppressive drug used to prevent organ transplant rejection. This has been achieved by virtue of the improved graft survival rates and adverse effect profiles in patients when compared with that of the older agents. Cyclosporin is substantially more expensive (both to provide and to monitor) however, and the magnitude of these costs may preclude its use, particularly where the transplant recipient is required to pay. Cyclosporin has a complex pharmacokinetic profile with poor absorption, extensive metabolism to more than 30 metabolites and considerable inter- and intrapatient variability. Many transplant centres routinely use drugs ("cyclosporin-sparing agents') to allow a reduction in the dosage of cyclosporin while maintaining therapeutic blood cyclosporin concentrations. The use of a second drug to affect the pharmacokinetic profile of a primary drug is not new, but the use of cyclosporin-sparing agents is a departure from previous practices in that this coprescription is primarily for economic reasons. The decision to use these agents (and the choice of agent) is based upon economic and other factors including the extent of the cyclosporin-sparing effect, the potential for additional therapeutic benefit and/or adverse effects. The coprescription of cyclosporin-sparing agents is ethically more acceptable where the transplant recipient is the economic beneficiary but where the savings accrue to a third party it is more difficult. Benefits to the community at large must be balanced against the risk of adverse effects to the patient. The use of cyclosporin-sparing agents may reduce compliance and hence, jeopardise transplant and/or recipient outcomes. The transplant recipient must be informed about the reasons for their use and advised to consult an experienced physician or pharmacist before altering the established drug regimen.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Ciclosporina/administração & dosagem , Diltiazem/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Cetoconazol/uso terapêutico , Transplante de Órgãos , Austrália , Ciclosporina/economia , Ciclosporina/farmacocinética , Citocromo P-450 CYP3A , Inibidores das Enzimas do Citocromo P-450 , Diltiazem/economia , Sinergismo Farmacológico , Inibidores Enzimáticos/economia , Rejeição de Enxerto/economia , Humanos , Imunossupressores/economia , Imunossupressores/farmacocinética , Cetoconazol/economia , Nova Zelândia , Transplante de Órgãos/economia , Oxirredutases N-Desmetilantes/antagonistas & inibidores
16.
Biochem Pharmacol ; 31(23): 3891-7, 1982 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-7159467

RESUMO

GMP reductase was highly purified from promastigotes of Leishmania donovani by chromatography on a single DEAE-cellulose column. Bimodal substrate saturation curves resulted in a 1/v versus 1/[GMP] plot that curved downward above 40 microM GMP. The kinetic constants were, therefore, obtained with GMP below this concentration. The K'm for GMP was 21 microM at pH 6.9. The enzyme was very sensitive to activation by GTP. At 20 microM GMP, a maximum of 600% activation occurred at 100 microM GTP. Half-maximal activation occurred at 8 microM GTP. GTP at 100 microM did not affect the K'm for GMP but did increase its V'max by 7-fold. Xanthosine monophosphate (XMP) and IMP analogs served equally well as competitive inhibitors versus GMP. The inhibition by the analogs and the activation by GTP were mutually antagonistic processes. The inhibition by the IMP analogs, allopurinol nucleotide and thiopurinol nucleotide is of chemotherapeutic interest because these compounds were shown previously to be produced in Leishmania from the anti-leishmanial agents allopurinol and thiopurinol. These nucleotides were 100- and 20-fold, respectively, more potent inhibitors of GMP reductase from L. donovani than of the corresponding enzyme from human erythrocytes.


Assuntos
Leishmania/enzimologia , NADH NADPH Oxirredutases/antagonistas & inibidores , Nucleotídeos/uso terapêutico , Animais , Ativação Enzimática/efeitos dos fármacos , GMP Redutase , Guanosina Trifosfato/farmacologia , Cinética , Leishmania/efeitos dos fármacos , Nucleotídeos/síntese química
17.
Biochem Pharmacol ; 32(17): 2505-9, 1983 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-6351865

RESUMO

Adenosine deaminase (ADA) was partially purified from several sources using affinity chromatography. These enzymes have the capacity to catalyze the deamination of 2,6-diamino-9-(2-hydroxyethoxymethyl)purine (A134U) to form the antiviral agent acyclovir [9-(2-hydroxyethoxymethyl)guanine]. Their relative substrate efficiencies (Vmax/Km) with A134U (standardized to adenosine = 100) were: dog ADA, 0.092; human ADA, 0.015-0.029; rat ADA, 0.025; calf ADA, 0.016; and Escherichia coli ADA, 0.0003. In addition to having the lowest efficiency with A134U, the bacterial ADA was also distinguished by its lack of binding of the mammalian ADA inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine and by its weak binding to the 9-(p-aminobenzyl)adenine-agarose affinity column. Four minor metabolites of A134U and acyclovir have been reported to be produced in the rat. These compounds are oxidized on either the C-8 position of the ring or the terminal carbon of the side chain. Neither acyclovir nor any of these metabolites produced significant inhibition of calf intestine ADA. The oxidized metabolites containing an N-6 amino group were extremely slow substrates of this enzyme.


Assuntos
Aciclovir/análogos & derivados , Aciclovir/metabolismo , Adenosina Desaminase/metabolismo , Nucleosídeo Desaminases/metabolismo , Adenosina Desaminase/isolamento & purificação , Animais , Cães , Eritrócitos/enzimologia , Escherichia coli/enzimologia , Humanos , Intestino Delgado/enzimologia , Cinética , Ratos , Especificidade da Espécie , Espectrofotometria Ultravioleta , Especificidade por Substrato
18.
Biochem Pharmacol ; 33(10): 1611-7, 1984 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-6732835

RESUMO

Formycin B 5'-monophosphate (Form B-MP) and allopurinol riboside 5'-monophosphate ( HPPR -MP) are isomers of IMP that are metabolically produced when Leishmania spp. are incubated with the antileishmanial agents formycin B and allopurinol or allopurinol riboside. The interactions of Form B-MP with succino -AMP synthetase and GMP reductase from both leishmanial and mammalian sources were compared with the data of earlier studies with HPPR -MP. Both analogs could substitute for IMP as a substrate for succino -AMP synthetase isolated from Leishmania donovani. The V'max values of Form B-MP and HPPR -MP were about 1% of the V'max of IMP. Only Form B-MP (and not HPPR -MP) could serve as an alternative substrate for mammalian succino -AMP synthetase. The V'max of Form B-MP was 40% that of IMP. The corresponding analogs of AMP, ADP and ATP were produced when Formycin B was incubated with mouse L cells. The Formycin A residue was incorporated into the cellular RNA. The amount of Formycin A-TP produced (relative to ATP) in mouse L cells was considerably less than that produced in Leishmania spp. Both Form B-MP and HPPR -MP were inhibitors of partially purified GMP reductase from L. donovani. The binding of Form B-MP and HPPR -MP to human GMP reductase was 40- and 100-fold weaker, respectively, than the binding to leishmanial GMP reductase. Pretreatment of promastigotes of L. donovani with either allopurinol or Formycin B resulted in greater than 95% reduction of the incorporation of the radiolabel from [14C]xanthine into ATP and greater than 80% reduction of the incorporation of the label into GTP. The HPPR -MP and Form B-MP present in these cells may have inhibited the leishmanial succino -AMP synthetase and GMP reductase. The analogs had little or no effect on the pool sizes of ATP and GTP of either mouse L cells or L. donovani.


Assuntos
Adenilossuccinato Sintase , Alopurinol/análogos & derivados , Antibióticos Antineoplásicos/metabolismo , Antiprotozoários/metabolismo , Formicinas/metabolismo , Leishmania/enzimologia , Ligases , NADH NADPH Oxirredutases/antagonistas & inibidores , Ribonucleosídeos/metabolismo , Ribonucleotídeos/metabolismo , Alopurinol/metabolismo , Aminação , Animais , Antiprotozoários/farmacologia , Formicinas/toxicidade , GMP Redutase , Humanos , Inosina Monofosfato/metabolismo , Cinética , Células L/metabolismo
19.
J Appl Physiol (1985) ; 71(1): 16-22, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1917738

RESUMO

The energy expenditures (EE) of 23 adult male Marines were measured during a strenuous 11-day cold-weather field exercise at 2,200- to 2,550-m elevation by both doubly labeled water (2H2 18O, DLW) and intake balance methods. The DLW EE calculations were corrected for changes in baseline isotopic abundances in a control group that did not receive 2H2 18O. Intake balance EE was estimated from the change in body energy stores and food intake. Body energy-store changes were calculated from anthropometric [-1,574 +/- 144 (SE) kcal/day] and isotope dilution (-1,872 +/- 293 kcal/day) measurements made before and after the field exercise. The subjects kept daily logbook records of ration consumption (3,132 +/- 165 kcal/day). Mean DLW EE (4,919 +/- 190 kcal/day) did not differ significantly from intake balance EE estimated from food intake and either anthropometric (4,705 +/- 181 kcal/day) or isotope dilution (5,004 +/- 240 kcal/day) estimates of the change in body energy stores. The DLW method can be used with at least the same degree of confidence as the intake balance method to measure the EE of active free-living humans.


Assuntos
Água Corporal/metabolismo , Metabolismo Energético , Exercício Físico , Adulto , Deutério , Alimentos , Humanos , Isótopos de Oxigênio , Saliva/metabolismo
20.
Brain Res ; 585(1-2): 196-204, 1992 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-1355002

RESUMO

Horseradish peroxidase (HRP) was injected, bilaterally, into the rat masseter muscle, subsequent to an intramuscular or intraperitoneal injection of one of five dopamine antagonists (chlorpromazine and haloperidol as the D1 and D2 receptor antagonist, SCH 23390 as the specific D1 receptor antagonist, sulpiride and domperidone as the specific D2 receptor antagonist). Control rats received an injection of a corresponding vehicle solution. After a survival period of 16 h, the brainstem was cut into 60 microns cryosections and processed with the TMB technique. The amount of retrogradely transported HRP was quantitatively measured in terms of the amount of HRP reaction product present in the motoneuron by the method which we have developed using an image processing system combined with a light microscope and a TV camera. Chlorpromazine, haloperidol, SCH 23390 and sulpiride significantly raised the quantity of retrograde transport of HRP. On the contrary, domperidone which can not penetrate the blood-brain barrier showed no significant change in the amount of the retrograde transport. In addition, an intravenous injection of chlorpromazine (8 mg/kg) was found to increase the amplitude of monosynaptic masseteric reflex EMG activity evoked by stimulations of the mesencephalic trigeminal nucleus. These results suggest that a possible regulatory system involving the dopamine receptor in the uptake and retrograde transport of HRP from axon terminals to cell bodies of the masseteric motoneuron exists in higher order neurons which make synaptic contact with the motoneuron.


Assuntos
Dopaminérgicos/farmacologia , Antagonistas de Dopamina , Peroxidase do Rábano Silvestre/farmacocinética , Músculo Masseter/inervação , Neurônios Motores/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Contagem de Células , Clorpromazina/farmacologia , Relação Dose-Resposta a Droga , Eletromiografia , Injeções Intravenosas , Masculino , Músculo Masseter/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Reflexo/efeitos dos fármacos , Núcleos do Trigêmeo/citologia , Núcleos do Trigêmeo/metabolismo
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