Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol

Aims Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect charges in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers. to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption. Methods Healthy male subjects (n = 12) received intravenously infused 2500 mg sinistrin (glomerular filtration) and 440 mg p-aminohippuric acid (PAH; anion secretion), and orally administered 100 mg fluconazole (reabsorption) and 15 mg rac-pindolol (cation secretion). The potential interaction between these markers was investigated in a pharmacokinetic study where markers (M) or fluconazole (F) were administered alone or together (M + F). Validated analytical methods were used to measure plasma and urine concentrations in order to quantify the renal handling of each marker. Plasma protein binding of fluconazole was measured by ultrafiltration. All subjects had an estimated creatinine clearance within the normal range. The renal clearance of each marker (Mean +/- s.d.) was calculated as the ratio of the amount excreted in urine and thearea-under-the-concentration-time curve. Statistical comparisons were made using a paired t-test and 95% confidence intervals were reported. Results The renal clearances of sinistrin (M: 119 +/- 31 ml min(-1); M + F: 130 +/- 40 ml min(-1); P = 0.32), PAH (M: 469 +/- 145 ml min(-1); M + F: 467 +/- 146 ml min(-1); P = 0.95), R-pindolol (M: 204 +/- 41 ml min(-1); M + F: 190 +/- 41 ml min(-1); P = 0.39; n = 11), S-pindolol (M: 225 +/- 55 ml min(-1); M + F: 209 +/- 60 ml min(-1); P = 0.27; n = 11) and fluconazole (F: 14.9 +/-3.8 ml min(-1); M + F: 13.6 +/- 3.4 ml min(-1); P = 0.16) were similar when the markers or fluconazole were administered alone (M or F) or as a cocktail (M + F). Conclusions This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes call be used to simultaneously investigate pathways of renal drug elimination.

Glass transition in Australian honeys

Differential scanning calorimetry (DSC) was used to study the glass transition in 10 Australian honeys by scanning at 10 degrees Cmin(-1) from -130 to 50 degreesC after annealing at -50 degreesC. The honeys had moisture contents 14.9 to 18.0%, seven were from Eucalyptus species. The glass transition temperatures (T-g) ranged from -46 degrees to -38 degreesC and were significantly (p

Controlled partial mine ventiliation recirculation trial at Mount Isa Mines

The ventilation and cooling of deep, hot mines present particular problems in Australia as a consequence of the surface climate, the size of the underground voids, the degree of mechanization and the cost of power in remote areas. A preliminary investigation of the effects of controlled partial recirculation of air was conducted in Mount Isa Mines' Deep Copper section. Gas and dust concentrations were measured in the exhaust air of the major working section to assess the potential for recirculating exhaust air to the intake airways to reduce the cost of providing an acceptable working environment in the deep parts of the mine. Studies were undertaken of airborne dust deposition in vertical airways and the efficiency of usage of the ventilation air in diluting contaminants. It was established that 45% of the respirable dust was deposited in a 130-m vertical raise and 60% of the air supplied to the section could be reused or recirculated. The first major field trial of a controlled partial recirculation system in Australia was undertaken in the light of these results and demonstrated excellent potential for significant reduction in ventilation costs. Gas and dust contaminant levels were well below the threshold limit values during the trial. It is concluded that controlled partial recirculation can be a practical, effective and safe aid to normal ventilation practice in Australian deep, hot mines.

Developmental changes in hyperpolarization-activated currents I-h and I-K(IR) in isolated rat intracardiac neurons

The hyperpolarization-activated nonselective cation current, I-h, was investigated in neonatal and adult rat intracardiac neurons. I-h was observed in all neurons studied and displayed slow time-dependent rectification. I-h was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of I-h was approximately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as compared with adult (-2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of I-h was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, I-K(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. I-K(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of -0.6 pA/pF at -130 mV. I-K(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I-K(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of I-K(IR). I-K(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in I-h may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.

Phylogeography of the pipefish, Urocampus carinirostris, suggests secondary intergradation of ancient lineages

We assayed the pattern of mitoehondrial DNA evolution in the live bearing, seagrass specialist pipefish, Urocampus carinirostris, in eastern Australia. These life history attributes were predicted to result in strong phylogeographic structure in U. carinirostris. Phylogenetic analysis of cytochrome b sequences detected two monophyletic mtDNA clades that differed by 8.69% sequence divergence - a large level of intraspecific divergence for a marine fish. The geographical distribution of clades was non-random and resembled clinal secondary intergradation over a 130-km stretch of coastline. Contrary to phylogeographic predictions, this large phylogeographic break does not occur across a traditionally recognised biogeographic boundary. Analyses of historical demography suggested that individuals belonging to the most widespread clade underwent a population expansion from a small refuge population during the Pleistocene.

Routine ultrasound screening in diabetic pregnancies

Objectives To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. Methods A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. Results During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Peri-conceptional hemoglobin A 1 c of more than 9% was associated with a high prevalence of major anomalies (14311000). Women who had fetuses with major anomalies bad a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m(2); P < 0.001). Conclusion The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly, worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.

Beyond hearing aid fitting: improving communication for older adults

Many older adults with hearing impairment continue to have substantial communication difficulties after being fitted with hearing aids, and many do not choose to wear hearing aids. Two group communication education programs aimed at such older people are described. The 'Keep on Talking' program has a health promotion focus, and is aimed at maintaining communication for older adults living in the community. An experimental group (n=120) attended the program, and a control group (n=130) received a communication assessment but no intervention. Significant improvements were found in the experimental participants in terms of knowledge about communication changes with age and about strategies to maintain communication skills. At the follow-up evaluation at 1 year, 45% of the experimental group, compared to 10% of the control group, had acted to improve their communication skills. The 'Active Communication Education' program focuses on the development of problem-solving strategies to improve communication in everyday life situations. Preliminary outcomes have been assessed on a small scale (n=14) to date. It is concluded that communication programs represent an important adjunct to, or supplement for, the traditional approach that focuses on hearing aid fitting.

Dissolution of sucrose crystals in the anhydrous sorbitol melt

The dissolution of a sugar (sucrose as a model) with higher melting point was studied in a molten food polyol (sorbitol as a model) with lower melting point, both in anhydrous state. A DSC and optical examination revealed the dissolution of anhydrous sucrose crystals (mp 192 degreesC) in anhydrous sorbitol (mp 99 degreesC) liquid melt. The sucrose-sorbitol crystal mixtures at the proportions of 10, 30, 60, 100 and 150 g of sucrose per 100 g of sorbitol were heat scanned in a DSC to above melting endotherm of sorbitol but well below the onset temperature of melting of sucrose at three different temperatures 110, 130 and 150 degreesC. The heat scanning modes used were with or without isothermal holding. The dissolution of sucrose in the sorbitol liquid melt was manifested by an increase in the glass transition temperature of the melt and corresponding decrease in endothermic melting enthalpy of sucrose. At given experimental conditions, as high as 25 and 85% of sucrose dissolved in the sorbitol melt during 1 h of isothermal holding at 110 and 150 degreesC, respectively. Optical microscopic observation also clearly showed the reduction in the size of sucrose crystals in sorbitol melt during the isothermal holding at those temperatures. (C) 2003 Elsevier Science Ltd. All rights reserved.

Sistema Ponto Focal: gerenciamento eletr??nico de informa????es sobre exig??ncias t??cnicas

O Inmetro ?? o ponto focal para o Acordo sobre Barreiras T??cnicas ao Com??rcio (TBT), como representante do Brasil na Organiza????o Mundial do Com??rcio (OMC). O exerc??cio dessa atividade propiciou ac??mulo de informa????es sobre exig??ncias t??cnicas, necess??rias para inser????o dos produtos industriais brasileiros nos mercados externos. A otimiza????o do uso dessas informa????es demandou o desenvolvimento de um sistema de gest??o de informa????o. Para tanto, desenvolveu-se o Sistema Ponto Focal, que ?? uma ferramenta de dissemina????o personalizada e proativa de informa????es sobre barreiras t??cnicas ??s exporta????es para o setor empresarial. Trata-se de um instrumento que auxilia o exportador no aprimoramento cont??nuo da qualidade e competitividade do produto brasileiro no mundo globalizado

Programa de capacita????o em coopera????o t??cnica internacional (PCCTI projeto)

Este projeto visa ?? elabora????o de um programa piloto de capacita????o para servidores p??blicos ou outros agentes que desempenham atividades de interesse p??blico na ??rea de Coopera????o T??cnica Internacional. Tem por objetivo central criar condi????es para desenvolver um Programa Piloto de Capacita????o em Coopera????o T??cnica Internacional, que poder?? ser ofertado regularmente pela ENAP. Para o desenho deste programa piloto, foram levantadas informa????es a partir de uma pesquisa de levantamento de perfil e mapeamento de compet??ncias (participa????o de 130 profissionais), bem como uma oficina de identifica????o de compet??ncias (participa????o de 60 profissionais). A partir da an??lise de seus resultados, decidiu-se pela formula????o do referido programa de capacita????o, que contemplar?? duas frentes de atua????o: i) a elabora????o de cursos de capacita????o, abordando conte??dos relativos ?? coopera????o t??cnica internacional, gest??o e habilidades relacionais e interpessoais; e ii) a implementa????o de um espa??o de retroalimenta????o e di??logo, tanto por meio de encontros presenciais como de um ambiente virtual de aprendizagem

Relat??rio da oficina de mapeamento de compet??ncias

Este relat??rio apresenta os principais resultados da Oficina de Mapeamento de Compet??ncias, realizado no Minist??rio das Rela????es Exteriores, Bras??lia no dia 7 de Abril de 2010. Esta atividade est?? inserida no Programa de Capacita????o em Gest??o de Coopera????o T??cnica Internacional, estabelecido entre a Escola Nacional de Administra????o P??blica, ENAP, a Ag??ncia de Coopera????o Internacional do Minist??rio das Rela????es Internacionais, ABC, e a Ag??ncia de Coopera????o T??cnica da Rep??blica Federal de Alemanha, GTZ. Este projeto conjunto visa a elabora????o de um programa de capacita????o para profissionais que trabalham na Coopera????o T??cnica Internacional, ou profissionais envolvidos com projetos espec??ficos neste ??mbito. Este encontro foi precedido por uma pesquisa de levantamento de perfil e mapeamento de compet??ncias de profissionais atualmente envolvidos na coopera????o t??cnica internacional do Brasil. Este pesquisa contou com a participa????o de 130 profissionais e apontou importantes informa????es para o desenho desta atividade

Disciplina 4.10: aspectos fiscais: receita e necessidade de financiamento do governo central

Hist??rico recente da pol??tica fiscal do Brasil. Receita: conceitua????o da receita p??blica (administrada, pr??pria, vinculada; da previd??ncia, etc); vis??o geral da gest??o das receitas p??blicas (SOF, STN, SRF e Unidades Or??ament??rias); metodologia de proje????o das receitas; manual dos modelos de proje????o. Necessidade de Financiamento do Governo Central. Breve hist??rico da pol??tica fiscal recente no Brasil. Regime de metas de super??vit prim??rio e estabiliza????o d??vida/PIB. Fundamentos legais (Lei de Responsabilidade Fiscal). Processo Or??ament??rio ??? elabora????o: macro etapas na elabora????o do or??amento; conceitos de resultado fiscal (prim??rio, nominal e operacional); principais agregados de receita e despesa para fins de apura????o de resultado; aspectos legais e institucionais. Processo Or??ament??rio ??? execu????o: a limita????o de empenho conforme a Lei de Responsabilidade Fiscal

Caf?? com debate: tecnologias da informa????o, gest??o e comunica????o no setor p??blico

Essa edi????o do Caf?? com Debate com o tema ???Tecnologias da informa????o, gest??o e comunica????o no setor p??blico??? marcou um ??ndice de comparecimento recorde com 130 participantes, entre servidores, dirigentes e t??cnicos da administra????o p??blica federal. O encontro focou-se em estrat??gias de integra????o e sistematiza????o de informa????es para planejamento, execu????o e monitoramento de pol??ticas p??blicas. Tamb??m foi destacada pelos convidados a inova????o assegurada pelos dois instrumentos, no campo da transpar??ncia e da presta????o de contas ?? sociedade, dos processos de gest??o governamental

Os controles

O texto explora a quest??o dos controles administrativos na It??lia, tanto no que se refere aos controles internos quanto no que se refere aos controles externos. O autor aponta a debilidade dos controles internos, em particular no tocante aos controles de gest??o, e analisa o tipo mais difundido de controle externo na ordena????o italiana, os controles preventivos de legitimidade, que na sua opini??o deveriam ser substitu??dos pelos controles sucessivos sobre a atividade ou sobre a gest??o administrativas. O texto fala ainda da evolu????o das rela????es entre o Tribunal de Contas e o Parlamento, das tend??ncias recentes de transforma????o na ??rea de controle, incluindo aspectos relativos ?? reforma constitucional e ?? Uni??o Europ??ia, e das novidades legislativas surgidas em 1993 e 1994.

Idades e crescimento da cioba, Ocyururs chrysurus, da Costa Central do Brasil

A idade e o crescimento da cioba da costa central do Brasil foram estudados a partir de leituras de otólitos obtidos em amostragens mensais de desembarques comerciais, realizados nas cidades de Vitória e Vila Velha, entre os anos de 1998 e 1999. Através da análise do incremento marginal, foi verificada a formação anual de uma zona translúcida a partir do final do outono e durante o inverno. Foram observadas ciobas de 2 a 19 anos. Os comprimentos furcais (CF) médios retrocalculados variaram de 108 mm para idade 1 a 524 mm para idade 19. A equação de Von Bertalanffy ajustada aos CF médios retrocalculados foi CFt = 567,1 (1 - e -0.130 (t + 0.773)). A relação comprimento peso foi P = 2,68x10-5CF2.914, onde P = peso total em gramas. O crescimento é lento, com os incrementos anuais em peso aumentando gradativamente até atingir o máximo de 164 g entre as idades 7 e 8 anos. Os resultados deste trabalho indicam que a cioba tem longa expectativa de vida e baixas taxas de crescimento somático, características das espécies mais sensíveis à exploração pesqueira.