Simultaneous determination of irinotecan (CPT-11) and SN-38 in tissue culture media and cancer cells by high performance liquid chromatography: Application to cellular metabolism and accumulation studies

A simple and sensitive HPLC method was developed to simultaneously determine CPT-11 and its major metabolite SN-38 in culture media and cell lysates. Camptothecin (CPT) was used as internal standard (I.S.). Compounds were eluted with acetonitrile–50 mM disodium hydrogen phosphate buffer containing 10 mM sodium 1-heptane-sulfonate, with the pH adjusted to 3.0 using 85% (w/v) orthophosphoric acid (27/73, v/v) by a Hyperclon ODS (C18) column (200 mm × 4.6 mm i.d.), with detection at excitation and emission wavelengths of 380 and 540 nm, respectively. The average extraction efficiencies were 96.9–108.3% for CPT-11 in culture media and 94.3–107.2% for CPT-11 in cell lysates; and 87.7–106.8% for SN-38 in culture media and 90.1–105.6% for SN-38 in cell lysates. Within- and between-day precision and accuracy varied from 0.1 to 10.3%. The limit of quantitation (precision and accuracy <20%) was 5.0 and 2.0 ng/ml for CPT-11 and 1.0 and 0.5 ng/ml for SN-38 in culture media and cell lysates, respectively. This method was successfully applied to quantitate the cellular accumulation and metabolism of CPT-11 and SN-38 in H4-II-E, a rat hepatoma cell line.

Simultaneous determination of the lactone and carboxylate forms of irintecan (CPT-11) and its actie metabolite SN-38 by high-performance liquid chromatography: Application to plasma pharmacokinetic studies in the rat.

Irinotecan (CPT-11) and its main metabolite SN-38 are potent anticancer derivatives of camptothecin (CPT), with active lactone and inactive carboxylate forms coexisting. A simple and sensitive HPLC method using the ion-pairing reagent tetrabutylammonium hydrogen sulfate (TBAHS) was developed to simultaneously determine all four analytes in rat plasma samples. Camptothecin (CPT) was used as internal standard. The mobile phase was 0.1 M potassium dihydrogen phosphate containing 0.01 M TBAHS (pH 6.4)–acetonitrile (75:25, v/v). Separation of the compounds was carried out on a Hypersil C18 column, monitored at 540 nm (excitation wavelength at 380 nm). All four compounds gave linear response as a function of concentration over 0.01–10 μM. The limit of quantitation in rat plasma was 0.01, 0.008, 0.005 and 0.005 μM for CPT-11 lactone, CPT-11 carboxylate, SN-38 lactone and SN-38 carboxylate, respectively. The method was successfully used in the study on the effect of coadministered thalidomide on the plasma pharmacokinetics of CPT-11 and SN-38 in rats. Coadministered thalidomide (100 mg/kg body weight by intraperitoneal injection) significantly increased the AUC_0–10h values of CPT-11 lactone and CPT-11 carboxylate by 32.6% and 30.3 %, respectively, (P < 0.01), but decreased the values by 19.2% and 32.4% for SN-38 lactone and carboxylate, respectively, (P < 0.05). Accordingly, the value of total body clearance (CL) of CPT-11 lactone was significantly lower in combination group compared to the control (1.329 versus 1.837 L/h/kg, P = 0.0002). Plasma t_1/2β values for SN-38 lactone and carboxylate were significantly (P < 0.01) smaller in rats with coadministered thalidomide, as compared to rats receiving CPT-11 alone. Further studies are needed to explore the underlying mechanisms for the observed kinetic interaction between CPT-11 and thalidomide.

Client identification and money laundering control : perspectives on the Financial Intelligence Centre Act 38 of 2001

The Financial Intelligence Centre Act 38 of 2001 (FICA) compels certain persons and institutions (defined as "accountable institutions'') to identify and verify the identity of a new client before any transaction may be concluded or any business relationship is established.1 Accountable institutions are listed in schedule ¹ to FICA and include banks, brokers, financial advisers, insurance companies, attorneys and estate agents. This duty to identify new clients came into effect on 30 June 2003. However, FICA also requires a similar procedure to be followed in respect of all current clients. Current clients are those with whom an accountable institution had business relationships on 30 June 2003.² After 30 June 2004 an institution may not conclude a transaction in the course of its business relationship with an unidentified current client, until it has established and verified that client's identity as prescribed. An institution that concludes any transaction in contravention of this prohibition, commits an offence and is liable to a fine not exceeding R10 million or to imprisonment of up to 15 years.³

The majority of accountable institutions and their clients failed to meet the June 2004 current client identification deadline.4 This failure posed serious economic and legal risks. With a few days to spare, the minister of finance granted a partial and temporary exemption in respect of these requirements. This article explores the statutory scheme for identification and re-identification of clients and some of the practical problems that were encountered. The June 2004 exemptions from these requirements are also considered and proposals for law reform are made.

The discussion of the FICA identification scheme necessitates the following brief overview of the international and South African money laundering control framework.

1 s 21(1) of FICA.
2 s 21(2) of FICA. See also s 82(2)(b).
3 s 46(2) of FICA read with s 68(1) of FICA.

Editorial : In Australian Journal of Communication, v.38 n.3

Edition of journal guest-edited by Martin Hirst (Deakin), Wayne Hope and Alan Cocker (AUT UNiversity). Papers collected from conference organised by Centre for Journalism, Media & Democracy (JMAD). Ten of the eleven articles here were originally presented to the Political Economy of Communication conference held at the Auckland University of Technology in September 2011. This international event was organised by Journalism, Media and Democracy (JMAD), a research centre co-founded by Martin Hirst and Wayne Hope in May 2010. The founding objectives were to foster individual research projects for members; develop opportunities for collaborative, funded research projects; and arrange interdisciplinary media conferences. In September 2010, JMAD launched an inaugural one-day conference: Media, Democracy and the Public Sphere. The success of this undertaking
encouraged the centre to plan for a second, two-day conference in 2011. The invited keynote speakers, Professors Graham Murdock, Dwayne Winseck, and Janet Wasko were, and are, distinguished scholars in the political economy of communication.
They have also given identity and purpose to their field within the annual International
Association of Communication Research (IAMCR) conference, which includes a longstanding political economy of communication section. Contributors to this section are featured in the book reviewed for this issue, Wasko, J., Murdock, G., & Sousa, H. (2011). The handbook of political economy of communications.

Corrigendum to “Least squares learning and the US treasury bill rate” [Econ. Syst. 38 (2014) 194–204]

Understanding how agents formulate their expectations about Fed behavior is important for market participants because they can potentially use this information to make more accurate estimates of stock and bond prices. Although it is commonly assumed that agents learn over time, there is scant empirical evidence in support of this assumption. Thus, in this paper we test if the forecast of the three month T-bill rate in the Survey of Professional Forecasters (SPF) is consistent with least squares learning when there are discrete shifts in monetary policy. We first derive the mean, variance and autocovariances of the forecast errors from a recursive least squares learning algorithm when there are breaks in the structure of the model. We then apply the Bai and Perron (1998) test for structural change to a forecasting model for the three month T-bill rate in order to identify changes in monetary policy. Having identified the policy regimes, we then estimate the implied biases in the interest rate forecasts within each regime. We find that when the forecast errors from the SPF are corrected for the biases due to shifts in policy, the forecasts are consistent with least squares learning.

Mighty Impressive: After 38 years as dean, vice president, dancer, and friend, Janice Kassman retires. But her legacy lives on

After 38 years, longtime dean Janice Kassman has retired. She leaves a legacy of accomplishment and countless Colby friends.

Desenvolvimento folicular de embriões de frangos de corte de diferentes genótipos expostos ao estresse térmico crônico

O objetivo do trabalho foi avaliar as alterações tegumentares (morfogênese da pena), em embriões de frangos de corte de linhagens de diferentes padrões de crescimento, obtidos de ovos incubados sob diferentes temperaturas. Os ovos foram obtidos de matrizes das linhagens Cobb 500 e ISA JA57, distribuídos proporcionalmente em três incubadoras. do primeiro (D1) ao sexto dia (D6) de incubação, utilizou-se uma temperatura padrão (37,8°C). A partir do sétimo dia (D7) e até o momento do nascimento aos 21 dias (D21), uma das incubadoras teve a temperatura reduzida para 36,8°C (fria) e uma outra alterada para 38,8°C (quente). A terceira incubadora foi mantida a 37,8°C (controle). O delineamento adotado foi o inteiramente casualizado, em esquema fatorial 3 x 2 (temperatura de incubação e linhagem). A temperatura de incubação e a linhagem não alteraram a densidade dos folículos da pena (número médio de folículos por área de 337,5µm²) nas regiões femural e dorsopélvica dos embriões até os 11 dias (D11). Entretanto, observou-se aumento na densidade folicular na região dorsal dos embriões aos 16 dias (D16) devido ao aumento da temperatura, permanecendo até o momento do nascimento. É possível oncluirque embriões incubados em temperatura acima da recomendada (38,8°C) apresentam uma maior densidade de folículos na região dorsopélvica. Apesar disso, a morfogênese dos folículos permaneceu inalterada.

Composição em ácidos graxos e qualidade da carne de tourinhos Nelore e Canchim alimentados com dietas à base de cana-de-açúcar e dois níveis de concentrado

O objetivo neste trabalho foi avaliar a composição de ácidos graxos e a qualidade do contrafilé (músculo Longissimus lumborum) de tourinhos das raças Nelore e Canchim. Os animais foram terminados em confinamento e alimentados com dietas contendo cana-de-açúcar e dois níveis de concentrado (40 e 60% na matéria seca). Os concentrados foram compostos de grãos de girassol, milho, farelo de soja, levedura seca de cana-de-açúcar, uréia e núcleo mineral. O delineamento experimental foi o inteiramente ao acaso, em esquema fatorial 2 × 2 (grupo genético × nível de concentrado). Não foram observadas diferenças nos teores de umidade, proteína e extrato etéreo da carne. Os animais da raça Nelore apresentaram maiores concentrações de ácido linoléico conjugado (0,52%), ácidos graxos insaturados (46,82%) e também relações mais elevadas de ácidos graxos insaturados:saturados (1,02) e monoinsaturados:saturados (0,86) em comparação aos tourinhos da raça Canchim. Os tourinhos da raça Canchim apresentaram maior intensidade das cores vermelha e amarela no contrafilé e maior luminosidade da gordura de cobertura. Houve interação para força de cisalhamento, que foi menor nos tourinhos Nelore alimentados com 40% de concentrado. Tourinhos da raça Nelore apresentam carne com melhor composição de ácidos graxos na gordura intramuscular do ponto de vista da saúde humana.

Lócus de controle e conceito de maternidade e paternidade em adolescentes

Locus of control is a construct that seeks to explain people's perceptions about the source of control of events, if the subject's own - internal - or belonging to some element outside of oneself - external. The location of individual s locus of control will suffer influence of their developmental period. During adolescence, individuals turn to the construction of their identity, and the structuring of sexual identity is a relevant part of this process, since the roles of males and females are the most important from the socio-cultural point of view. One of the roles that adolescents can take is the mother or father. We chose to head the adolescents who are not mothers and fathers, and question them about their concepts of parenthood. It is hypothesized that adolescents with internal locus of control will probably develop concepts of maternity and paternity in which they attach to themselves the responsibility for children. The aim of this study was to relate the locus of control s predominant dimension in adolescence and the way that these young people conceptualize parenthood. This is an exploratory analytical cross-sectional study accomplished with 400 adolescents from the classes of the sixth to ninth grade of high school at public schools in Natal / RN. We used as protocols: structured questionnaire involving sociodemographic questions and questions about the concept of parenthood, and the Multifactorial Scale of Locus of Control. Data were analyzed using descriptive and inferential statistics, with the aid of statistical package SPSS 18.0. The results regarding questions about the concept of maternity and paternity were analyzed using the analysis program often ALCESTE 4.7. The results showed that for boys and girls, maternity and paternity were characterized by the acquisition and assumption of responsibilities of adulthood. This concept is supported by the locus of control s classification of individuals, since most of the subjects of this study was characterized as individuals who tend to take responsibility for their life's events. For young people from lower classes (as the subjects of this research), the project of autonomy and social mobility is realized by the constitution of his own family and the ability to sustain it

SEABATHER'S ERUPTION: A CLINICAL and EPIDEMIOLOGICAL STUDY of 38 CASES IN SANTA CATARINA STATE, BRAZIL

Seabather's eruption (SBE) is an intensely itchy, papule-erythematous dermatitis that occurs predominantly in regions of the body covered by bathing costumes, after exposure to marine water. The planulae larvae of Linuche unguiculata scyphomedusae (thimble jellyfish) are the etiologic agent of the dermatitis, which is frequent in waters of Caribbean, Gulf of Mexico and Florida. The authors report 38 cases of SBE in the State of Santa Catarina (Southern region of Brazil), with emphasis on their clinical and epidemiological aspects, such as profile of victim, topography of the papules and conditions predisposing to the accident.

Effects of prolonged running performed at the intensity corresponding to the onset of blood lactate accumulation, on maximum isokinetic strength in active non-athletic individuals

OBJETIVO: O objetivo deste estudo foi analisar os efeitos da corrida contínua prolongada realizada na intensidade correspondente ao início do acúmulo do lactato no sangue (OBLA) sobre o torque máximo dos extensores do joelho analisado em diferentes tipos de contração e velocidade de movimento em indivíduos ativos. MÉTODO: Oito indivíduos do gênero masculino (23,4 ± 2,1 anos; 75,8 ± 8,7 kg; 171,1 ± 4,5 cm) participaram deste estudo. Primeiramente, os sujeitos realizaram um teste incremental até a exaustão voluntária para determinar a velocidade correspondente ao OBLA. Posteriormente, os sujeitos retornaram ao laboratório em duas ocasiões, separadas por pelo menos sete dias, para realizar 5 contrações isocinéticas máximas para os extensores do joelho em duas velocidades angulares (60 e 180º.s-1) sob as condições excêntrica (PTE) e concêntrica (PTC). Uma sessão foi realizada após um período de aquecimento padronizado (5 min a 50%VO2max). A outra sessão foi realizada após uma corrida contínua no OBLA até a exaustão voluntária. Essas sessões foram executadas em ordem randômica. RESULTADOS: Houve redução significante do PTC somente a 60º.s-1 (259,0 ± 46,4 e 244,0 ± 41,4 N.m). Entretanto, a redução do PTE foi significante a 60º.s-1 (337,3 ± 43,2 e 321,7 ± 60,0 N.m) e 180º.s-1 (346,1 ± 38,0 e 319,7 ± 43,6 N.m). As reduções relativas da força após o exercício de corrida foram significantemente diferentes entre os tipos de contração somente a 180º.s-1. CONCLUSÃO: Podemos concluir que, em indivíduos ativos, a redução no torque máximo após uma corrida contínua prolongada no OBLA pode ser dependente do tipo de contração e da velocidade angular.

High Prevalence of bla(CTX-M) Extended Spectrum Beta-Lactamase Genes in Klebsiella pneumoniae Isolates from a Tertiary Care Hospital: First report of bla(SHV-12), bla(SHV-31), bla(SHV-38), and bla(CTX-M-15) in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Discussion on the limit cycles of the Lev Ginzburg equation by M. Bellamy and R.E. Mickens, Journal of Sound and Vibration 308 (2007) 337-342

The authors M. Bellamy and R.E. Mickens in the article "Hopf bifurcation analysis of the Lev Ginzburg equation" published in Journal of Sound and Vibration 308 (2007) 337-342, claimed that this differential equation in the plane can exhibit a limit cycle. Here we prove that the Lev Ginzburg differential equation has no limit cycles. (C) 2012 Elsevier Ltd. All rights reserved.

Effect of antioxidant agents on bond strength of composite to bleached enamel with 38% hydrogen peroxide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Change in the ascorbic-acid content of acerolas (Malpighia-glabra L) as function of harvest maturation degree and storage-temperature

The content of ascorbic acid was assayed in acerolas harvested in three phases of maturation: green-yellow fruits (I); light red (II) and wine-coloured (III). Phase I and Phase II fruit were packed in aluminium sheets and stoppered flasks and stored in freezer (-10o.C) and in refrigerator (8o.C). Samples of 8 fruits from each experimental condiction were analysed for ascorbic acid determination by 2-chlorophenol indophenol discolouration method. The averages of 1.393,5 mg./100g. for Phase I sample, 1024,9 for Phase II and 756,5 for Phase III fruits, showed a statistically significative linear decreasing of the ascorbic acid content related with the maturation extent Phase I samples stored in freezing showed statitically significative decreasing of that vitamin at 408 hours of storage in both: aluminium sheet and stoppered flask package; in chilling temperature there was significative reduction of ascorbic acid content after 240 and 312 hours, respectively, for fruits packed in aluminium sheet and stopped flasks. Phase Il samples showed significative lost at 72 hours of storage when maintained in freezing temperature either, in aluminium sheet or in stoppered flasks: When stored in chilling temperature showed progressive lost of ascorbic acid in all measuring periods in every package. After 144 hours suffered deterioration suggested by colour changes.