Toward the optimal dose metric in continuous renal replacement therapy

Purpose: There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification. Methods: We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CWHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours. Results: Median daily treatment time was 1,413 min (1,260-1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863) (p<0.001). Urea mass removal rate was 13.0 +/- 7.6 mg/min. Both EKR (r(2)=0.250; p<0.001) and K-D (r(2)=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and K-D presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio. Conclusions: Effluent rate (ml/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as K-D. EKR also constitutes a good method for dose comparisons over time and across modalities.

Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

Background: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. Objective: We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10 mg/simvastatin 20 mg (E10/S20) with simvastatin 80 mg (S80). Methods and results: CAD patients (n = 83, 63 +/- 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 +/- 13% vs. 28 +/- 30%, p = 0.46), apo-B (18 +/- 17% vs. 22 +/- 15%, p = 0.22) and oxidized LDL (15 +/- 33% vs. 18 +/- 47%, p = 0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 +/- 43% vs. 8 +/- 33%, p = 0.02). Conclusions: These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4x less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of ultraviolet filters on skin superoxide dismutase activity in hairless mice after a single dose of ultraviolet radiation

Organic sunscreens may decrease their protective capability and also behave as photo-oxidants upon ultraviolet radiation (UVR) exposure. The present study investigated the effect of a cream gel formulation containing the UV filters benzophenone-3, octyl methoxycinnamate, and octyl salicylate on skin superoxide dismutase (SOD) after a single dose of UVR (2.87 J/cm(2)). The retention of these UV filters was first evaluated in vivo using hairless mice to guarantee the presence of the filters in the skin layers at the moment of irradiation. The in vivo effect of the UV filters on skin SOD was then assayed spectrophotometrically via the reduction of cytochrome c. The cream gel formulation promoted the penetration of the three UV filters into the epidermis and the dermis at one hour post-application. A significant decrease in SOD activity was observed in irradiated animals treated with sunscreen formulation. However, no effect on SOD activity in skin was observed by the isolated presence of the sunscreens, the formulation components, or the exposure to UVR. The sunscreens may have formed degradation products under UVR that may have either inhibited the enzyme or generated reactive species in the skin. (C) 2011 Elsevier B.V. All rights reserved.

Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2 mg/day, but does not enhance efficacy of haloperidol, 2 mg/day: Comparison with reference dose risperidone, 6 mg/day

Most atypical antipsychotic drugs (APDs), e. g. risperidone (RIS), produce more extensive blockade of brain serotonin (5-HT)(2A) than dopamine (DA) D-2 receptors. This distinguishes them from typical APDs, e.g. haloperidol (HAL). Our objective was to test the hypothesis that augmentation of low doses of RIS or HAL (2 mg/day) with pimavanserin (PIM), a selective 5-HT2A inverse agonist, to enhance 5-HT2A receptor blockade, can achieve efficacy comparable to RIS, 6 mg/day, but with lesser side effects. In a multi-center, randomized, double-blind, 6 week trial, 423 patients with chronic schizophrenia experiencing a recent exacerbation of psychotic symptoms were randomized to RIS2mg + placebo (RIS2PBO), RIS2mg + PIM20mg (RIS2PIM), RIS6mg + PBO (RIS6PBO), HAL2mg + PBO (HAL2PBO), or HAL2mg + PIM20mg (HAL2PIM). Improvement in psychopathology was measured by the PANSS and CGI-S. The reduction in PANSS Total Score with RIS2PIM at endpoint was significantly greater than RIS2PBO: -23.0 vs. -16.3 (p = 0.007), and not significantly different from the RIS6PBO group: -23.2 points. The percentage of patients with >= 20% improvement at day 15 in the RIS2PIM group was 62.3%, significantly greater than the RIS6PBO (42.1%; p = 0.01) and the RIS2PBO groups (37.7%; p = 0.002). Weight gain and hyperprolactinemia were greater in the RIS6PBO group than the RIS2PIM group but there was no difference in extrapyramidal side effects (EPS). HAL2PBO and HAL2PIM were not significantly different from each other in efficacy but HAL2PIM had less EPS at end point. Both HAL groups and RIS6PBO showed equal improvement in psychopathology at endpoint, indicating HAL 2 mg/day is effective to treat an acute exacerbation in chronic schizophrenia patients. In conclusion, a sub-effective RIS dose combined with PIM to enhance 5-HT2A receptor blockade provided faster onset of action, and at endpoint, equal efficacy and better safety, compared to standard dose RIS. These results support the conclusion that 5-HT2A receptor blockade is a key component of the action of some atypical APDs and can reduce EPS due to a typical APD. (C) 2012 Elsevier B.V. All rights reserved.

Dose and latency effects of leucine supplementation in modulating glucose homeostasis: opposite effects in healthy and glucocorticoid-induced insulin-resistance states

Dexamethasone (DEXA) is a potent immunosupressant and anti-inflammatory agent whose main side effects are muscle atrophy and insulin resistance in skeletal muscles. In this context, leucine supplementation may represent a way to limit the DEXA side effects. In this study, we have investigated the effects of a low and a high dose of leucine supplementation (via a bolus) on glucose homeostasis, muscle mass and muscle strength in energy-restricted and DEXA-treated rats. Since the leucine response may also be linked to the administration of this amino acid, we performed a second set of experiments with leucine given in bolus (via gavage) versus leucine given via drinking water. Leucine supplementation was found to produce positive effects (e. g., reduced insulin levels) only when administrated in low dosage, both via the bolus or via drinking water. However, under DEXA treatment, leucine administration was found to significantly influence this response, since leucine supplementation via drinking water clearly induced a diabetic state, whereas the same effect was not observed when supplied via the gavage.

Comparison of different dosimetric methods for red marrow absorbed dose calculation in thyroid cancer therapy

Several dosimetric methods have been proposed for estimating red marrow absorbed dose (RMAD) when radionuclide therapy is planned for differentiated thyroid cancer, although to date, there is no consensus as to whether dose calculation should be based on blood-activity concentration or not. Our purpose was to compare RMADs derived from methods that require collecting patients' blood samples versus those involving OLINDA/EXM software, thereby precluding this invasive procedure. This is a retrospective study that included 34 patients under treatment for metastatic thyroid disease. A deviation of 10 between RMADs was found, when comparing the doses from the most usual invasive dosimetric methods and those from OLINDA/EXM. No statistical difference between the methods was discovered, whereby the need for invasive procedures when calculating the dose is questioned. The use of OLINDA/EXM in clinical routine could possibly diminish data collection, thus giving rise to a simultaneous reduction in time and clinical costs, besides avoiding any kind of discomfort on the part of the patients involved.

Low-dose Enalapril Reduces Angiotensin II and Attenuates Diabetic-induced Cardiac and Autonomic Dysfunctions

Activation of renin-angiotensin system has been linked to cardiovascular and autonomic dysfunctions in diabetes. Experiments were performed to investigate the effects of angiotensin-converting enzyme inhibitor (ACEI), enalapril, on cardiac and autonomic functions in diabetic rats. Diabetes was induced by streptozotocin (50 mg/kg), and rats were treated with enalapril (1 mg.kg(-1).d(-1)). After 30 days, evaluations were performed in control, diabetic, and enalapril-treated groups. Cardiac function was evaluated by echocardiography and through cannulation of the left ventricle (at baseline and in response to volume overload). Heart rate and systolic blood pressure variabilities were evaluated in the time and frequency domains. Streptozotocin rats had left ventricular systolic and diastolic dysfunctions, expressed by reduced ejection fraction and increased isovolumic relaxation time. The ACEI prevented these changes, improved diastolic cardiac responses to volume overload and total power of heart rate variability, reduced the ACE1 activity and protein expression and cardiac angiotensin (Ang) II levels, and increased angiotensin-converting enzyme 2 activity, despite unchanged blood pressure. Correlations were obtained between Ang II content with systolic and diastolic functions and heart rate variability. These findings provide evidence that the low-dose ACEI prevents autonomic and cardiac dysfunctions induced by diabetes without changing blood pressure and associated with reduced cardiac Ang II and increased angiotensin-converting enzyme 2 activity.

Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

Background: Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance. Methods: The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Jurua valley in the Amazon region. Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008. Results: The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95% CI 0.20 - 0.58) for the P. falciparum malaria incidence rates, 0.67 (95% CI 0.50 - 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95% CI 0.41 - 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported. Conclusions: In the remote region of the Jurua valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria.

Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery

In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system.

Cancelamento de cirurgias de catarata em um hospital público de referência

OBJETIVO: Analisar a incidência e causas de cancelamento de cirurgias de catarata em um hospital público de referência. MÉTODOS: Trata-se de um estudo retrospectivo em que foram analisados o número de cancelamentos de facectomias durante o ano de 2009. Foram analisados sexo, idade, tipo de procedimento suspenso (facoemulsificação ou extração extracapsular do cristalino), tipo de anestesia, convênio (Sistema Único de Saúde ou convênio/particular) e motivo de suspensão da cirurgia (causas clínicas, institucionais ou pessoais). RESULTADOS: Foram agendadas no período 2.965 cirurgias de catarata, havendo 650 cancelamentos (21,92%). Dentre as principais razões para a suspensão do procedimento destacaram-se as causas clínicas (86,90%). Os meses de inverno apresentaram os maiores índices de suspensão de cirurgias de catarata. CONCLUSÃO: A taxa de cancelamento de cirurgia de catarata em serviços públicos parece ser a mesma que há 10 anos. A principal causa de suspensão deve-se por condições clínicas (hipertensão, diabetes, falta de exames, etc.).

Impacto dos modelos de referência e maturidade no gerenciamento de projetos: estudo exploratório em projetos de tecnologia da informação

Modelos de maturidade e modelos de referência em gerenciamento de projetos têm sido implantados de forma crescente na área de tecnologia da informação (TI). Este artigo tem por objetivo analisar o impacto do grau de maturidade organizacional em gerenciamento de projetos e o da adoção de modelos de referência no sucesso de projetos de TI. Foi adotada a abordagem de pesquisa quantitativa, com levantamento junto a 51 profissionais da área. Os resultados apontam para correlação positiva entre o grau de maturidade organizacional em gerenciamento de projetos e a satisfação das demandas dos stakeholders (principais interessados no projeto). Também foi constatada relação estatística positiva entre a adoção do PMBoK e o sucesso de projetos de TI, no que concerne ao atendimento dos requisitos e satisfação das demandas dos stakeholders.

Desempenho de métodos de estimativa da evapotranspiração de referência nas localidades de Frederico Westphalen e Palmeira das Missões, RS

A estimativa da evapotranspiração de referência (ETo), usada no balanço hídrico, possibilita quantificar o armazenamento de água no solo, auxiliando no manejo da irrigação. O objetivo do trabalho foi comparar métodos mais simples de estimativa da evapotranspiração de referência com o método Penman-Monteith (FAO), nas escalas diária e de 5, 10, 15 e 30 dias, e mensal, para os municípios de Frederico Westphalen e Palmeira das Missões, no RS. Os métodos avaliados tenderam a melhorar a eficiência com o aumento da escala temporal de estudo, mantendo o mesmo desempenho para ambas as localidades. Os maiores e menores valores de ETo ocorreram nos meses de dezembro e junho, respectivamente. A maioria dos métodos subestimou os valores de ETo. Em qualquer escala temporal, os métodos de Makking e da Radiação FAO24 podem substituir o modelo de Penman-Monteith.

Protocolo de Observação Comportamental - PROC: valores de referência para uma análise quantitativa

OBJETIVO: obter valores de referência para protocolo de observação comportamental (PROC) sobre o desenvolvimento de habilidades comunicativas e de esquemas simbólicos em crianças com desenvolvimento típico de linguagem. MÉTODO: foram avaliadas 44 crianças entre 24 e 47 meses de ambos os gêneros, selecionadas em escolas de educação infantil, por meio de triagem do desenvolvimento global Denver II e questionário com os pais. Todas as crianças foram filmadas durante 30 minutos em interação com um adulto em atividade envolvendo brinquedos. As gravações foram analisadas por meio do PROC. A análise estatística descreveu valores de média, mediana, valores mínimos e máximos. Foi utilizado o teste T de Student para comparação das idades. RESULTADOS: nas habilidades comunicativas, as crianças do estudo mostraram evolução com a idade (média para três e dois anos, respectivamente: 58,12 e 51,44), apesar de não ter sido encontrada diferença estatisticamente significante para as faixas etárias comparadas (p=0,486). Quanto ao item compreensão verbal, as crianças de três anos obtiveram melhor desempenho que as de dois (respectivas médias: 59,41 e 50,70), havendo diferença estatisticamente significante (p=0,0000020). Em relação ao item aspectos do desenvolvimento cognitivo, as crianças de três anos apresentaram melhor desempenho em comparação com as de dois (respectivas médias: 44,53 e 31,96), havendo diferença estatisticamente significante entre as pontuações obtidas (p=0,00364), mostrando que as crianças evoluem na hierarquia do simbolismo. CONCLUSÃO: a obtenção de valores de referência para o PROC veio combinar análise qualitativa e quantitativa, contribuindo, além do diagnóstico, para o acompanhamento objetivo de processos terapêuticos.

Os saberes dos professores-referência no ensino de contabilidade

O presente estudo tem como propósito avaliar os saberes predominantes nos docentes percebidos como professores-referência pelos alunos de um curso de Graduação em Ciências Contábeis de uma universidade pública brasileira. O estudo justifica-se pelas recentes e significativas mudanças no contexto da Contabilidade no Brasil. Para alcance desse propósito, estruturou-se uma pesquisa qualitativa, em que foram utilizadas as seguintes estratégias de pesquisa e técnicas de coleta de dados: (i) pesquisa bibliográfica em obras relevantes que tratam do tema; (ii) pesquisa documental nas avaliações dos professores feitas pela instituição; (iii) questionários aplicados aos alunos do último ano; (iv) grupo focal com parte do grupo de alunos respondentes dos questionários; e (v) entrevista semiestruturada com professores apontados pelos alunos como docentes de referência. Amparados pelas discussões tecidas acerca de saberes, competências e conhecimentos necessários à docência (Shulman, 1986; Garcia, 1992; Freire, 2000; Pimenta, 1998; Pimenta & Anastasiou, 2002; Gauthier, Martineau, Desbiens, Malo, & Simard, 1998; Tardif, 2003; Cunha, 2004; Masetto, 1998; Braslavsky, 1999; Perrenoud, 2000; Zabalza, 2006) e aqueles necessários ao ensino de contabilidade (Antonelli, Colauto, & Cunha, 2012; Miranda, 2011; Catapan, Colauto, & Sillas, 2011; Vasconcelos, 2010; Slomsky, 2009; Araujo & Santana, 2008; Celerino & Pereira, 2008; Andere & Araújo, 2008; Laffin, 2005), bem como pesquisas sobre professores exemplares (Young & Shaw, 1999; Lowman, 2007), verificaram-se os seguintes resultados: as disciplinas responsáveis pelas experiências mais significativas de aprendizagem, durante o curso, eram as percebidas como base do curso (Contabilidade Básica, Intermediária e Avançada) e que apresentavam maior aplicação prática. As razões principais para escolha dos docentes de referência foram: didática ou metodologia de ensino, atitudes e qualidades pessoais do professor. Além disso, verificou-se que os três saberes docentes que subsidiaram essas escolhas foram, nesta ordem: conhecimento didático, domínio do conteúdo e saberes experienciais. Esses resultados apontam para: a necessidade de preparação didática sistematizada para o exercício da docência; a necessidade de formação continuada, notadamente, stricto sensu, para melhor domínio do conteúdo que ensina; e a importância de o docente estar conectado com as práticas mercadológicas.

ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking

The effect of angiotensin II (ANG II) or arginine vasopressin (AVP) alone or plus atrial natriuretic peptide (ANP) on H+-ATPase subcellular vesicle trafficking was investigated in MDCK cells following intracellular pH (pHi) acidification by exposure to20 mMNH4Cl for 2 min in a Na+-free solution containing Schering 28080, conditions under which H+-AT-Pase is the only cell mechanism for pHi recovery. Using the acridine orange fluorescent probe (5mM) and confocal microscopy, the vesicle movement was quantified by determining, for each experimental group, the mean slope of the line indicating the changes in apical/basolateral fluorescence density ratio over time during the first 5.30 min of the pHi recovery period. Under the control conditions, the mean slope was 0.079 ± 0.0033 min-1 (14) and it increased significantly with ANG II [10-12 and 10-7 M, respectively to 0.322 ± 0.038 min-1 (13) and 0.578 ± 0.061 min-1 (12)] or AVP [10-12 and 10-6 M, respectively to 0.301 ± 0.018 min-1 (12) and 0.687 ± 0.049 min-1 (11)]. However, in presence of ANP (10-6 M, decreases cytosolic free calcium), dimethyl-BAPTA/AM (5 × 10-5 M, chelates intracellular calcium) or colchicine (10-5 M, 2-h preincubation; inhibits microtubule-dependent vesicular trafficking) alone or plus ANG II or AVP the mean slopes were similar to the control values, indicating that such agents blocked the stimulatory effect of ANG II or AVP on vesicle trafficking. The results suggest that the pathway responsible for the increase in cytosolic free calcium and the microtu-bule-dependent vesicular trafficking are involved in this hormonal stimulating effect. Whether cytosolic free calcium reduction represents an important direct mechanism for ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking, or is a side effect of other signaling pathways which will require additional studies.