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Carbon film resistor electrode for amperometric determination of acetaminophen in pharmaceutical formulations

Felix, Fabiana S.; Brett, Christopher M.A.; Angnes, Lúcio
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
ENG
Relevância na Pesquisa
37.23%
Flow injection analysis (FIA) with amperometric detection was employed for acetaminophen quantification in pharmaceutical formulations using a carbon film resistor electrode. This sensor exhibited sharp and reproducible current peaks for acetaminophen without chemical modification of its surface. A wide linear working range (8.0 × 10-7 to 5.0 × 10-4 mol L-1) in phosphate buffer solution as well as high sensitivity (0.143 A mol-1 L cm-2) and low submicromolar detection limit (1.36 × 10-7 mol L-1) were achieved. The repeatability (R.S.D. for 10 successive injections of 5.0 × 10-6 and 5.0 × 10-5 mol L-1 acetaminophen solutions) was 3.1 and 1.3%, respectively, without any memory effect between injections. The new procedure was applied to the analyses of commercial pharmaceutical products and the results were in good agreement with those obtained utilizing a spectrophotometric method. Consequently, this amperometric method has been shown to be very suitable for quality control analyses and other applications with similar requirements.; http://www.sciencedirect.com/science/article/B6TGX-4MSHT96-1/1/a5eb87f817e43c4bd0120021afa851f3

Effects of short-term acetaminophen and celecoxib treatment on orthodontic tooth movement and neuronal activation in rat

STABILE, A. C.; STUANI, M. B. S.; LEITE-PANISSI, C. R. A.; ROCHA, M. J. A.
Fonte: PERGAMON-ELSEVIER SCIENCE LTD Publicador: PERGAMON-ELSEVIER SCIENCE LTD
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.3%
Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for pain relief in orthodontics, but clinical studies reported that they may reduce tooth movement (TM). By other side, TM seems to activate brain structures related to nociception, but the effects of NSAIDs in this activation have not been studied yet. We analyzed the effect of short-term treatment with acetaminophen or celecoxib in the separation of rat upper incisors, as well as in neuronal activation of the spinal trigeminal nucleus, following tooth movement. Thirty rats (400-420 g) were pretreated through oral gavage (1 ml/dose)with acetaminophen (200 mg/kg), celecoxib (50 mg/kg) or vehicle (carboxymethylcellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance for TM. In controls, this appliance was immediately removed after its introduction. Rats received ground food, and every 12 h, one of the drugs or vehicle. After 48 h, they were anesthetized, maxilla was radiographed, and were perfused with 4% paraformaldehyde. Brains were further processed for Fos immunohistochemistry. TM induced incisor distalization (p < 0.05) and neuronal activation of the spinal trigeminal nucleus. Treatment with both drugs did not affect tooth movement, but reduced c-fos expression in the caudalis subnucleus. No changes in c-fos expression were seen in the oralis and interpolaris subnuclei. We conclude that neither celecoxib nor acetaminophen seems to affect tooth movement...

Efeitos microscópicos do ácido acetilsalicílico (aspirina) e do acetaminofeno (tylenol) na movimentação dentária induzida e nas reabsorções radiculares associadas; Microscopic effects of Acetylsalicylic Acid (Aspirin) and Acetaminophen (Tylenol) on induced dental movement and root resorption associated

Maldonado, Vanessa Bernardini
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 02/10/2009 PT
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37.23%
Este estudo objetivou analisar a influência do ácido acetilsalicílico e do acetaminofeno na movimentação dentária induzida e nas reabsorções radiculares associadas do ponto de vista celular e tecidual ao microscópio óptico. Os grupos experimentais constituíram-se de 18 ratos com administração de soro fisiológico; 36 ratos, com ácido acetilsalicílico e os outros 36 com acetaminfeno. Os animais foram subdividos de acordo com o tempo de tratamento movimentação dentária induzida: 5, 7 e 9 dias. O aparelho para a movimentação ortodôntica foi o preconizado por Heller e Nanda e modificado por Martins-Ortiz. As drogas foram submetidas em períodos curtos e longos. Aplicou-se análise microscópica histomorfométrica quantitativa na raiz distovestibular do primeiro molar superior esquerdo do rato. Esta análise foi dividida em duas etapas: quantificação do percentual de áreas hialinas no ligamento periodontal e quantificação do percentual de reabsorção radicular no lado de pressão. Os resultados do teste t de Student nos permitiram as seguintes constatações: 1) a administração de ácido acetilsalicílico (AAS) e do acetaminofeno (ACT) comparado ao controle, tanto na forma longa quanto curta, não alterou os percentuais de áreas hialinas e reabsorções radiculares nos três períodos de tempo avaliados; 2) a administração de AAS longa comparado ao AAS - curta e ACT - longa comparado ao ACT - curta...

Desenvolvimento e validação de um método analítico para determinação dos fármacos Diclofenaco, Nimesulida e Paracetamol em águas superficiais da cidade de São Carlos-SP; Development and validation of analytical method for determining the drug diclofenac, nimesulide and acetaminophen in surface waters from São Carlos

Vicente, Gustavo Henrique Lourenço
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 21/10/2011 PT
Relevância na Pesquisa
37.23%
Residuos de fármacos estão presentes em diversas matrizes ambientais e estudos focados na determinação destes tem ganhado grande importância nos últimos anos, devido ao aumento do consumo de medicamentos pela população. A questão do controle de resíduos de compostos farmacologicamente ativos no meio ambiente aquático foi reconhecida como uma das questões emergentes na Química Ambiental, e tem-se dado maior importância visto que os fármacos são encontrados em matrizes em estudos em concentrações de μgL-1 e ngL-1. Nesta pesquisa estudou-se três fármacos antiflamatórios que são amplamente consumidos pela população: diclofenaco, nimesulida e paracetamol. O método analítico foi desenvolvido e validado para a determinação destes fármacos em amostras de águas superficiais da cidade de São Carlos (SP). Inicialmente foi feita a validação do método proposto segundo a Resolução DOQ-CGCRE-008 do INMETRO. Os limites de detecção, e de quantificação e inferior de quantificação do método para a determinação do diclofenaco, nimesulida e paracetamol, foram, respectivamente, 0,5; 1,1 e 1,1 μgL-1. A linearidade, desvio-padrão relativo, exatidão e recuperação média para o diclofenaco foram, respectivamente...

Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats; Transplante de hepatócitos recém-isolados em um modelo de hepatotoxicidade induzida por acetaminofeno em ratos

Rodrigues, Daniela; Silveira, Themis Reverbel da; Matte, Ursula da Silveira; Study Group on Experimental Hepatology
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
Relevância na Pesquisa
37.23%
Context - Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. Objective - The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. Methods - Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x107 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. Results - Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. Conclusion - These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.; Contexto - O transplante de hepatócitos é uma modalidade terapêutica atrativa para doenças hepáticas como alternativa ao transplante hepático ortotópico. Objetivo - Investigar a factibilidade do uso de hepatócitos frescos isolados de ratos em um modelo de hepatotoxicidade induzida por paracetamol. Métodos - Hepatócitos foram isolados de ratos Wistar machos e transplantados 24 horas após a administração de paracetamol em receptores fêmeas. As ratas receberam 1x107 hepatócitos ou tampão salina fosfato pela veia porta ou no baço e foram sacrificadas após 48 horas. Resultados - Os níveis de alanina aminotransferase medidos durante o experimento não diferiram entre os grupos em nenhum momento. Análises moleculares e histológicas demonstraram a presença de hepatócitos no fígado dos animais transplantados pelo baço ou pela veia porta. Conclusão - Os dados indicam a factibilidade e eficácia do transplante de hepatócitos no fígado ou baço em um modelo de hepatotoxicidade leve induzida por paracetamol.

Studies of the Electrochemical Degradation of Acetaminophen Using a Real-Time Biomimetic Sensor

Quintino de Oliveira, Mariana Calora; Tanaka, Auro Atsushi; Roberto de Vasconce los Lanza, Marcos; Taboada Sotomayor, Maria Del Pilar
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artigo de Revista Científica Formato: 2616-2621
ENG
Relevância na Pesquisa
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 08/00303-5; Processo FAPESP: 07/08314-3; Processo FAPESP: 08/05899-3; Real-time monitoring of the electrochemical degradation of acetaminophen was performed using a biomimetic sensor coupled to a flow injection analysis (FIA) system. Degradation of the drug was carried out at constant current density (24 to 180 mAcm(-2)) in an electrolyte consisting of 0.1 molL(-1) K(2)SO(4)/5.0 x 10(-4) molL(-1) FeSO(4)center dot 7H(2)O. Two commercial DSA anodes (DSA-Cl(2) and DSA-O(2)) were compared. The degradation process was monitored online using an amperometric sensor based on the biomimetic catalyst iron(III) tetrapyridinoporphyrazine (FeTPyPz), coupled to the degradation cell. The optimized FIA detection system employed the electrolyte solution as carrier, a flow rate of 1.25 mLmin(-1) and an injected sample volume of 75 mu L. The real-time data obtained showed, as expected, that acetaminophen degradation followed pseudo-first order kinetics, with the DSA-Cl(2) anode showing a higher efficiency according to the calculated apparent rate constant values. The advantage of the proposed on-line system is that a larger number of points can be monitored in a shorter time compared to other off-line methods...

Efeito da quercetina nas atividades fosfatasicas e seu efeito protetor na hepatotoxicidade induzida pelo acetaminofeno em camundongos; Effects of quercetin on phosphatases activities and its protective effects on acetaminophen-induced hepatotoxicity in mice

Camila de Andrade Camargo
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 16/02/2007 PT
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37.49%
Os flavonóides são fitocompostos polifenólicos, caracterizados quimicamente como heterosídeos flavônicos. Apresentam diversas atividades biológicas devido às suas propriedades antioxidantes e habilidades em modular a atividade de diversas enzimas ou receptores celulares, tornando-os responsáveis pelo efeito protetor contra doenças relacionadas ao sistema cardiovascular; certas formas de câncer e doenças de fotossensibilidade e envelhecimento. As fosfatases ácidas, enzimas que hidrolisam ésteres fosfatos em meio ácido, encontram-se amplamente distribuídas no organismo. Estas enzimas são importantes no catabolismo de diversas substâncias, acreditando-se que a alteração da atividade destas enzimas esteja relacionada com modificações induzidas por drogas e por várias doenças. As transaminases são enzimas hepáticas cujo nível aumenta quando há lesão das células hepáticas (hepatócitos) provocada por qualquer tipo de agressão, como vírus, consumo excessivo de álcool ou drogas. O acetaminofeno é uma droga frequentemente usada como analgésico e antipirético. O dano hepático causado pelo uso frequente ou exagerado do acetaminofeno é comum hoje em dia. A manutenção correta dos sistemas metabólicos hepáticos é de grande importância para a manutenção da saúde. Desta forma...

Carbon-based materials prepared from pine gasification residues for acetaminophen adsorption

Galhetas, M.; Mestre, A. S.; Pinto, Moisés L.; Gulyurtlu, Ibrahim; Lopes, M. Helena; Carvalho, A. P.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2014 ENG
Relevância na Pesquisa
37.36%
Fly ash, a residue produced frompine gasification,was used as precursor of carbon-basedmaterials assayed in acetaminophen adsorption. Materials prepared by activation with K2CO3, presented high porosity development (ABET 1200m2 g1) and samples calcined at 900 C presented high volumes of large micropores and mesopores. Kinetic and equilibrium acetaminophen adsorption data showed that the process obeys to the pseudo-second order kinetic equation and Langmuir model, respectively. The rate of acetaminophen adsorption depends of the presence of larger micropores. For the lab-made samplesmonolayer adsorption capacities attained values similar to those of commercial carbons. The influence of themicropore size distribution of the carbons in the acetaminophen adsorption process justified the lower adsorption affinities of the lab-made carbons. The importance of pores of a specific dimension (0.7 nm) to enhance the affinity of the molecule towards the carbon surfacewas demonstrated. The increase of temperature lead to highermonolayer adsorption capacities, most likely due to the easier accessibility of the acetaminophen species to the narrowest micropores.

Chars from gasification of coal and pine activated with K2CO3: Acetaminophen and caffeine adsorption from aqueous solutions

Galhetas, M.; Mestre, A. S.; Pinto, Moisés L.; Gulyurtlu, Ibrahim; Lopes, M. Helena; Carvalho, A. P.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //2014 ENG
Relevância na Pesquisa
37.12%
The high carbon contents and low toxicity levels of chars from coal and pine gasification provide an incentive to consider their use as precursors of porous carbons obtained by chemical activation with K2CO3. Given the chars characteristics, previous demineralization and thermal treatments were made, but no improvement on the solids properties was observed. The highest porosity development was obtained with the biomass derived char (Pi). This char sample produced porous materials with preparation yields near 50% along with high porosity development (ABET 1500 m2 g1). For calcinations at 800 C, the control of the experimental conditions allowed the preparation of samples with a micropore system formed almost exclusively by larger micropores. A mesopore network was developed only for samples calcined at 900 C. Kinetic and equilibrium acetaminophen and caffeine adsorption data, showed that the processes obey to a pseudo-second order kinetic equation and to the Langmuir model, respectively. The results of sample Pi/1:3/800/2 outperformed those of the commercial carbons. Acetaminophen adsorption process was ruled by the micropore size distribution of the carbons. The caffeine monolayer capacities suggest a very efficient packing of this molecule in samples presenting monomodal micropore size distribution. The surface chemistry seems to be the determinant factor that controls the affinity of caffeine towards the carbons.

Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

Rodrigues,Daniela; Silveira,Themis Reverbel Da; Matte,Ursula
Fonte: Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia - IBEPEGE ; Colégio Brasileiro de Cirurgia Digestiva - CBCD ; Sociedade Brasileira de Motilidade Digestiva - SBMD ; Federação Brasileira de Gastroenterologia - FBG; Sociedade Brasileira de Hepatologia - SBH; Sociedade Brasileira de Endoscopia Digestiva - SOBED Publicador: Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia - IBEPEGE ; Colégio Brasileiro de Cirurgia Digestiva - CBCD ; Sociedade Brasileira de Motilidade Digestiva - SBMD ; Federação Brasileira de Gastroenterologia - FBG; Sociedade Brasileira de Hepatologia - SBH; Sociedade Brasileira de Endoscopia Digestiva - SOBED
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2012 EN
Relevância na Pesquisa
37.23%
CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7) hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.

Gastric emptying in rats with acetaminophen-induced hepatitis

Hessel,G.; Collares,E.F.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/1998 EN
Relevância na Pesquisa
37.36%
The objective of this work was to study the gastric emptying (GE) of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise) was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each). Group I was fed a sucrose diet throughout the experiment (66 h) while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each). Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg). Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 µg/ml) than in group IB (87 µg/ml). The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values). The correlation between gastric retention and AST levels was significant (P<0.05) for group IIB for the three test meals: r = 0.73...

Simultaneous voltammetric determination of acetaminophen and caffeine at a graphite and polyurethane screen-printed composite electrode

Saciloto,Thalita R.; Cervini,Priscila; Cavalheiro,Éder T. G.
Fonte: Sociedade Brasileira de Química Publicador: Sociedade Brasileira de Química
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2013 EN
Relevância na Pesquisa
37.3%
A selective electrochemical method was developed for the individual or simultaneous determination of acetaminophen and caffeine in phosphate buffer pH 6.0 on graphite and polyurethane screen-printed composite electrode (EIGPU) using Differential Pulse Voltammetry (DPV). The oxidation peaks of acetaminophen and the caffeine appeared at 0.3 V and 1.3 V(vs. pseudo-Ag/AgCl), respectively, showing the possibility of simultaneous determination of both analytes, at the EIGPU, besides the individual determination. Analytical curves for the simultaneous determination showed a linear response for both compounds. The acetaminophen presented a linear region in the concentration range 1.00 - 40.0 µmol L-1 with detection limit of 0.84 µmol L-1, and the caffeine presented a linear region, in the concentration range 4.00 - 200 µmol L-1 with detection limit of 1.6 µmol L-1. The proposed method was applied in the simultaneous determination of acetaminophen and caffeine in three pharmaceutical formulations, with results similar to those obtained using a HPLC method, at 95% confidence level (Student t-Test).

Dipyrone and acetaminophen: correct dosing by parents?

Alves,João Guilherme Bezerra; Cardoso Neto,Fortunato José; Almeida,Camila Dornelas Câmara; Almeida,Natalia Dornelas Câmara
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2007 EN
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37.47%
CONTEXT AND OBJECTIVE: Several studies in developed countries have documented that a significant percentage of children are given inappropriate doses of acetaminophen and ibuprofen. The objective of this paper was to investigate parents’ accuracy in giving dipyrone and acetaminophen to their children, in a poor region. DESIGN AND SETTING: Cross-sectional study at the pediatric emergency department of Instituto Materno-Infantil Prof. Fernando Figueira, a teaching hospital in Pernambuco. METHODS: The inclusion criteria were age between 3 and 36 months, main complaint of fever and at least one dose of dipyrone or acetaminophen given to the child during the 24 hours preceding their arrival at the emergency department. The mothers were asked for demographic information and about the antipyretic doses given, which were compared with the recommended dosage. RESULTS: Among the 200 patients studied, 117 received dipyrone and 83 received acetaminophen. Overall, 75 % received an incorrect dose of antipyretic. Of the patients who received dipyrone, 105 (89.7%) were given an incorrect dose; 16 (15.2%) received too little dipyrone, and 89 (84.8%) received too much. Of the patients who received acetaminophen, 45 (54.2%) were given an incorrect dose; 38 (84.4%) received too little acetaminophen...

TRPM2 channels mediate acetaminophen-induced liver damage

Kheradpezhouh, E.; Ma, L.; Morphett, A.; Barritt, G.J.; Rychkov, G.Y.
Fonte: National Academy of Sciences of the United States of America Publicador: National Academy of Sciences of the United States of America
Tipo: Artigo de Revista Científica
Publicado em //2014 EN
Relevância na Pesquisa
37.51%
Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca(2+) homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca(2+) rise. Here we report that the channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice...

Entwicklung eines Modells des Paracetamol-induzierten akuten Leberversagens und Vergleich von Leberersatzverfahren am Schwein; Development of a model of Acetaminophen-induced acute liver failure and comparison of liver replacement systems in pigs

Rubitschek, Sofia
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
Relevância na Pesquisa
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Paracetamol (PCM) ist ein weit verbreitetes Antipyretikum und Analgetikum, von dem seit Jahren bekannt ist, dass es bei Überdosierung lebertoxisch wirkt und zu einem ALV, schlimmstenfalls bis zum Tode führen kann. Trotz großer Bemühungen war es bislang nicht möglich, die genauen Zusammenhänge der Toxizität zu klären, was eine zuverlässige Prognose des Krankheitsverlaufs bei einer Überdosierung erschwert. Nicht unbeteiligt hieran ist der Mangel an suffizienten Großtiermodellen, die es sowohl erlauben, Krankheitsbild und Behandlung mit der klinischen Situation zu vergleichen, als auch genauere Einblicke in die Initiation der Toxizität zu gewähren. Aus diesem Grund wurde in dieser Arbeit der Versuch unternommen, ein aussagekräftiges Tiermodell hinsichtlich des PCM- induzierten akuten Leberversagens (ALV) zu entwickeln, um daran artifizielle Leberersatzverfahren (LEV) klinisch auf ihre Relevanz hin untersuchen zu können. Zur Etablierung eines Tiermodells wurde bei 28 Schweinen mit der Gabe eines initialen Bolus und anschließender stündlicher Erhaltungsdosis von PCM unter maximaler intensivmedizinischer Überwachung ein ALV induziert. Nach Eintritt des LV wurden an den blockrandomisierten Studientieren ihrer Gruppenzugehörigkeit entsprechend die unterschiedlichen Dialyseverfahren geprüft. Zu jeder Zeit wurden Vital- und Blutparameter aufgezeichnet bzw. bestimmt und regelmäßig Keilbiopsien der Leber entnommen. Im Rahmen dieser Arbeit ist es gelungen...

Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro

Lima,Renilton Aires; Cândido,Eduardo Batista; Melo,Flávia Perrim de; Piedade,Josiane Barbosa; Vidigal,Paula Vieira Teixeira; Silva,Luciana Maria; Silva Filho,Agnaldo Lopes da
Fonte: Federação Brasileira das Sociedades de Ginecologia e Obstetrícia Publicador: Federação Brasileira das Sociedades de Ginecologia e Obstetrícia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2015 EN
Relevância na Pesquisa
37.3%
PURPOSES: To determine the basic expression of ABC transporters in an epithelial ovarian cancer cell line, and to investigate whether low concentrations of acetaminophen and ibuprofen inhibited the growth of this cell line in vitro. METHODS: TOV-21 G cells were exposed to different concentrations of acetaminophen (1.5 to 15 μg/mL) and ibuprofen (2.0 to 20 μg/mL) for 24 to 48 hours. The cellular growth was assessed using a cell viability assay. Cellular morphology was determined by fluorescence microscopy. The gene expression profile of ABC transporters was determined by assessing a panel including 42 genes of the ABC transporter superfamily. RESULTS: We observed a significant decrease in TOV-21 G cell growth after exposure to 15 μg/mL of acetaminophen for 24 (p=0.02) and 48 hours (p=0.01), or to 20 μg/mL of ibuprofen for 48 hours (p=0.04). Assessing the morphology of TOV-21 G cells did not reveal evidence of extensive apoptosis. TOV-21 G cells had a reduced expression of the genes ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 within the ABC transporter superfamily. CONCLUSIONS: This study provides in vitro evidence of inhibitory effects of growth in therapeutic concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally...

Effect of copaiba oil in hepatic damage induced by acetaminophen in rats

Teixeira,Renan Kleber Costa; Yamaki,Vitor Nagai; Yasojima,Edson Yuzur; Brito,Marcus Vinicius Henriques
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2013 EN
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37.47%
PURPOSE: To investigate the effects of copaiba oil on the hepatic damage induced by paracetamol. METHODS: Thirty six rats were distributed into six study groups (N=6): control group, that didn't receive the acetaminophen; Acetaminophen Group, that only received the acetaminophen; Prophylactic Copaiba Group 1, that received copaiba oil two hours before the acetaminophen; Prophylactic Copaiba Group 7, that received copaiba oil seven days, once by day, before the acetaminophen; Therapy Copaiba Group, that received the copaiba oil two hours afther the acetaminophen; and N-Acetyl-Cysteine Group, , that received the N-Acetyl-Cysteine two hours afther the acetaminophen. Euthanasia was performed after 24 hours. The serum levels of AST, ALT, alkaline phosphatase, GT, total bilirubin, direct bilirubin and indirect bilirubin and histological analisis were analized. RESULTS: The prophylactic copaiba group 7, therapy copaiba group and N-Acetyl-Cysteine Group showed amounts of AST and ALT similar to the control group; and the prophylactic copaiba group 1 showed similar levels to the acetaminophen group. There was no significant difference between the groups regarding the amount of alkaline phosphatase and GT (p>0.05). The therapy copaiba group showed the highest levels of bilirubin and was statistically different from the other groups (p<0.01) and this increased the costs of direct bilirubin. Regarding histopathology...

Microsomal oxidative damage promoted by acetaminophen metabolism

Aracena, Paula; Rojas Sepúlveda, Daniel; López Valladares, Miguel; Peredo Silva, Liliana; Letelier Muñoz, María Eugenia
Fonte: PERGAMON-ELSEVIER SCIENCE LTD. Publicador: PERGAMON-ELSEVIER SCIENCE LTD.
Tipo: Artículo de revista
EN
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37.4%
Artículo de publicación ISI; Adverse reactions of acetaminophen have been associated to oxidative stress, which may be elicited by reactive oxygen species (ROS) and/or production of the metabolite NAPQI. Both phenomena would arise through the activity of liver cytochrome P450 (CYP450) system, but their contribution to this oxidative stress is yet to be clarified. A NADPH oxidase activity has been proposed in rat liver microsomes. This activity may be due to the presence of NAD(P)H oxidase (NOX) isoforms in liver endoplasmic reticulum. Both NOX and the CYP450 system activities can catalyze ROS generation using NADPH as a cofactor. Therefore, acetaminophen biotransformation, which requires NADPH, may promote ROS generation through either activity or both. To discriminate between these possibilities, rat liver microsomes were incubated with acetaminophen and NADPH in the presence or absence of specific inhibitors. Incubation with NADPH and acetaminophen elicited lipid peroxidation and decreased thiol content and glutathione- S-transferase (GST) activity. The NOX inhibitors apocynin and plumbagin prevented all these phenomena but the decrease in thiol content. In contrast, this decrease was completely prevented by the specific CYP450 system inhibitor SKF-525A. These data suggest that ROS generation following incubation of microsomes with acetaminophen and NADPH appears to be mainly caused by a NOX activity. In light of these data...

Preferential solvation of acetaminophen in ethanol + water solvent mixtures according to the inverse Kirkwood-Buff integrals method

Delgado,Daniel Ricardo; Peña,Maria Angeles; Martínez,Feming
Fonte: Revista Colombiana de Ciencias Químico - Farmacéuticas Publicador: Revista Colombiana de Ciencias Químico - Farmacéuticas
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2013 EN
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The preferential solvation parameters, i.e., the differences between the local mole fraction of solvents around the solute and those for the bulk co-solvent mixtures in solutions of acetaminophen in ethanol + water binary mixtures were derived from their thermodynamic properties by means of the inverse Kirkwood-Buff integrals (IKBI) method. It is found that acetaminophen is sensitive to solvation effects, so the preferential solvation parameter δxE,A, is negative in water-rich and ethanol-rich mixtures but positive in co-solvent compositions from 0.24 to 0.73 in mole fraction of ethanol. It is conjecturable that in water-rich mixtures the hydrophobic hydration around the aromatic ring and methyl group present in the drug plays a relevant role in the solvation. The more solvation by ethanol in mixtures of similar co-solvent compositions could be due mainly to polarity effects. Finally, the preference of this drug for water in ethanol-rich mixtures could be explained in terms of the bigger acidic behavior of water molecules interacting with the hydrogen-acceptor groups present in acetaminophen such as the carbonyl group.

Simultaneous Determination of Acetaminophen, Pamabrom and Pyrilamine Maleate in Pharmaceutical Formulations Using Stability Indicating HPLC Assay Method

Saleem,Atif; Anwar,Shahid; Hussain,Talib; Ahmad,Rehan; Mustafa,Ghulam; Ashfaq,Muhammad
Fonte: Sociedad Química de México A.C. Publicador: Sociedad Química de México A.C.
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2015 EN
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37.23%
A simple, specific and accurate stability indicating RP-HPLC method was developed for the determination of acetaminophen, pamabrom and pyrilamine maleate simultaneously in pharmaceutical dosage forms. Successful separation of all the components was enacted within 10 min using C18 column with mobile phase of methanol and acidified water (pH 1.8) in the ratio of (27: 73 v/v respectively). Flow rate of the mobile phase was 1.5 mL/min with detection at 300 nm. The method was validated in accordance with ICH guidelines. Response was a linear function of concentration over the range of 50- 150 μg/mL for acetaminophen, 2.5-7.5 μg/mL for pamabrom and 1.5-4.5 μg/mL for pyrilamine maleate. The method resulted in excellent separation of all the analytes along with their stress induced degradation products with acceptable peak tailing and good resolution. It is therefore can be applied successfully for simultaneous determination of acetaminophen, pamabrom and pyrilamine maleate in pharmaceutical formulations and their stability studies.