Investigation of the antinociceptive efficacy and relative potency of extended duration injectable 3-acylmorphine-6-sulfate prodrugs in rats

This investigation was designed to examine the antinociceptive activity in rats of 3-O-acyl prodrugs of M6S relative to the parent drug, after intravenous and intramuscular injection, using the tail flick latency test of antinociception. M6S, 3-acetylmorphine-6-sulfate (3AcM6S), 3-propionylmorphine-6-sulfate (3PrM6S), 3-butanoylmorphine-6-sulfate (3BuM6S) and 3-heptanoylmorphine-6-sulfate (3HpM6S) were administered by the IV route in a dose of 4.10 mu mol/kg. Relatively high levels of antinociception (>40% Maximum Possible Effect) were achieved following administration of M6S, 3AcM6S and 3PrM6S, whereas insignificant antinociception (<20%MPE) was achieved following administration of 3BuM6S or 3HpM6S. Although the mean duration of action for 3AcM6S (6 h) was longer than for M6S or 3PrM6S (4 h), the mean area (+/- S.E.M.) under the degree of antinociception versus time curve (AUG) for 3AcM6S (151.6 +/- 6.9%MPE h) was not significantly different (p <0.05) from that for M6S (120.8 +/- 32.7%MPE h) or for 3PrM6S (106.0 +/- 21.3%MPE h). The mean ED50 (range) doses for M6S, 3AcM6S and 3PrM6S were calculated to be 4.16 (3.61-4.48), 4.32 (3.55-5.09) and 4.54 (4.21-4.79) mu mol/kg, respectively. Preliminary studies were conducted on potential long-acting formulations containing 8 x ED50 doses of M6S and the 3-acetyl and 3-propionyl esters suspended in soybean oil. These showed that 3PrM6S gave a greater AUC (mean + S.E.M.) (1087.4 +/- 97.4%MPE h) and longer duration of action (20 h) than did M6S (613.1 +/- 155.9%MPE h; 10 h duration) or 3AcM6S (379.3 + 114.2%MPE h: 8 h duration). Further studies are needed to more fully investigate these findings. (C) 1998 Elsevier Science B.V. All rights reserved.

Apparent insensitivity of the hotplate latency test for detection of antinociception following intraperitoneal, intravenous or intracerebroventricular M6G administration to rats

Although morphine-6-glucuronide (M6G) has been shown to be analgesically active, the relative involvement of spinal and supraspinal structures in mediating M6G's pain-relieving effects following central and systemic administration to rats is unclear. As the tail flick and hotplate latency tests are reported to quantify antinociception mediated primarily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative apparent levels of antinociception (expressed as percentage maximum possible effect, % MPE) achieved after M6G or morphine administration. Following i.v. or i.p. M6G (1.9-5.4 mu mol) dosing or i.p. morphine (10 mu mol) dosing, high levels of antinociception (>50% MPE) were achieved using the tail flick test whereas base-line levels of antinociception were observed 30 sec later in the same rats using the hotplate test. By contrast, antinociception evoked by i.v. morphine (10 mu mol) exceeded 50% MPE using both the hotplate and tail flick tests although the apparent potency was approximately 2.5 times greater using the tail flick test. After i.c.v. dosing, M6G (0.22-3.3 nmol) was significantly (P < .05) more potent when assessed using the tail flick compared with the hotplate test. Taken together, these data strongly indicate that following central and systemic administration, M6G's antinociceptive effects are mediated primarily by spinal structures whereas both spinal and supraspinal mechanisms contribute to systemic morphine's antinociceptive effects.

Efficacy and safety of iodopovidone pleurodesis in malignant pleural effusions

Background and objective: Pleurodesis is one of the best methods of controlling malignant pleural effusions (MPE), a distressing complication of metastatic disease. In recent studies of a wide range of pleural diseases, iodopovidone was used as a sclerosing agent for pleurodesis and demonstrated good results with low morbidity. The aim of this study was to evaluate the efficacy and safety of iodopovidone pleurodesis in MPE. Methods: A retrospective analysis was performed on patients with MPE who underwent pleurodesis at our institution between 2005 and 2008. All patients underwent instillation of 20 mL of 10% iodopovidone, 80 mL of normal saline and 2 mg/kg of lidocaine through a chest tube, which was clamped for 2 h. The tube was removed when the daily output of fluid was < 200 mL. Data on the requirement for additional pleural procedures, adverse events and survival were collected. Results: Sixty-one pleurodesis procedures were performed in 54 patients. No procedure-related mortality was observed. Adverse events occurred after 11 (18%) pleurodesis procedures. The most frequent complication was mild thoracic pain that occurred immediately after 10 (16.4%) procedures, and one patient developed pleural empyema that was treated with drainage and antibiotics. A success rate of 98.4% was observed. Except for the patient who developed pleural empyema, none of the other patients had recurrences of pleural fluid or required additional pleural procedures during the follow-up period (mean of 5.6 months). Conclusions: Iodopovidone pleurodesis was successful and was associated with only a few minor complications. It appears to be a good option for the management of recurrent MPE.

Carbohydrates Concentration in leaves of potato plants affected by nitrogen fertilization rates

ABSTRACT At poor conditions of nitrogen (N) in the soil, potato plants may accumulate starch in leaves and be indicative of N nutritional stress. The objective of this work was to determine the effects of N rates (0, 50, 100, 200 and 300 kg ha-1 of N) on the concentrations of carbohydrates (total soluble sugars-TSS, reducing sugars-RS, non-reducing sugars-NRS and starch) in the fourth leaf (FL) of two potato cultivars (Asterix and Atlantic) and their critical levels (CL) associated to the N fertilization rate necessary to obtain the maximum physical (MPE) and economic (MEE) efficiency of tubers. A randomized block design with four replications was used in both experiments. On day 21 after plant emergence, four FL were collected from four plants. Potatoes plants fertilized with low rates of N accumulated less TSS in leaves than those properly fertilized. The opposite occurred with content of starch. The cultivars showed similar responses to five doses of N in relation to contents of starch and TSS. However, the response to the increase in doses of N for RS, NRS and Starch/NRS is cultivar-specific. The correlations between contents of RS, NRS and Starch/NRS with the starch and TSS were dependent on the potato cultivar.

Formação de estratégia nas micro e pequenas empresas: um estudo no centro-oeste mineiro

Muito se tem dito e escrito sobre as peculiaridades da administração estratégica nas micro e pequenas empresas (MPE). Pouco, entretanto, tem sido feito em termos de trabalho empírico, de cunho quantitativo, quando comparado com o volume de pesquisa que trata de grandes empresas. Nesse sentido, o presente artigo buscou explorar o processo de formação de estratégias nessas empresas, descrevendo seus principais aspectos e, principalmente, verificando se há características desse processo que podem ser associadas a níveis de desempenho acima (e/ou abaixo) da média. Para tanto, utilizou-se a análise de regressão linear múltipla para entender as relações existentes entre as variáveis do processo de formação da estratégia consideradas no estudo e o desempenho; e, ainda, a análise discriminante para determinar os indicadores que diferenciam os grupos de empresas com desempenho acima e abaixo da média. Os resultados apontaram uma tendência à utilização de processos de formação de estratégia deliberados e formais. Por outro lado, reconhecemos também, uma tendência de inovação e mudança. O desempenho acima da média das micro e pequenas empresas, ao que parece, é resultado de uma receita balanceada desses dois ingredientes.

Gestão de capital de giro: contribuição para as micro e pequenas empresas no Brasil

Este artigo trata da importância das questões de capital de giro na gestão das micro e pequenas empresas (MPE) no Brasil. Apresenta-se uma revisão dos conceitos de capital de giro e da importância das MPE no Brasil, além de uma discussão sobre a relevância de uma gestão financeira de curto prazo eficiente para o sucesso de um empreendimento de pequeno porte. Com características bem definidas, as micro e pequenas empresas são responsáveis pela geração da maior parte dos empregos formais no Brasil; apesar disso, ainda não contam com uma estrutura formal de apoio de crédito. O trabalho aponta como fator relevante para o sucesso das micro e pequenas empresas ter um bom gerenciamento do capital de giro. O mau gerenciamento desse fator contribui para o alto índice de mortalidade dessas empresas. Para que o administrador de capital de giro tenha êxito, é importante que haja um forte entrelaçamento com a administração estratégica, para uma solução definitiva do problema, isto é, que consista numa recuperação de lucratividade da empresa e as consequentes recomposições de seu fluxo de caixa, fazendo com que as micro e pequenas empresas consigam chegar à fase de maturidade.

Impacto da reforma de financiamento de hospitais de ensino no Brasil

OBJETIVO: Avaliar o impacto da reforma de financiamento na produtividade de hospitais de ensino. MÉTODOS: A partir do Sistema de Informações dos Hospitais Universitários Federais, foram construídas fronteiras de eficiência e produtividade em 2003 e 2006 com técnicas de programação linear, por meio de análise envoltória de dados, considerando retornos variáveis de escala e orientação a input. Calculou-se o Índice de Malmquist para identificar mudanças de desempenho ao longo dos anos quanto à eficiência técnica (razão entre os escores de eficiência em tempos distintos) e eficiência tecnológica (deslocamento da fronteira no período considerado). RESULTADOS: Houve aumento do aporte financeiro em 51% e da eficiência técnica dos hospitais de ensino (de 11, passaram a ser 17 na fronteira empírica de eficiência), o mesmo não ocorrendo com a fronteira tecnológica. O uso de análise envoltória de dados estabeleceu os benchmarks para as unidades ineficientes (antes e depois da reforma) e os escores de eficiência mostraram uma possível correlação entre a eficiência técnica encontrada e a intensidade e dedicação de ensino. CONCLUSÕES: A reforma permitiu o desenvolvimento de melhorias gerenciais, mas é necessário maior tempo de acompanhamento para observar mudanças mais efetivas do modelo de financiamento.

Power law and entropy analysis of catastrophic phenomena

Catastrophic events, such as wars and terrorist attacks, tornadoes and hurricanes, earthquakes, tsunamis, floods and landslides, are always accompanied by a large number of casualties. The size distribution of these casualties has separately been shown to follow approximate power law (PL) distributions. In this paper, we analyze the statistical distributions of the number of victims of catastrophic phenomena, in particular, terrorism, and find double PL behavior. This means that the data sets are better approximated by two PLs instead of a single one. We plot the PL parameters, corresponding to several events, and observe an interesting pattern in the charts, where the lines that connect each pair of points defining the double PLs are almost parallel to each other. A complementary data analysis is performed by means of the computation of the entropy. The results reveal relationships hidden in the data that may trigger a future comprehensive explanation of this type of phenomena.

Systems of Navier-Stokes equations on cantor sets

We present systems of Navier-Stokes equations on Cantor sets, which are described by the local fractional vector calculus. It is shown that the results for Navier-Stokes equations in a fractal bounded domain are efficient and accurate for describing fluid flow in fractal media.