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1.
Rev. odontol. UNESP (Online) ; 45(2): 85-89, mar.-abr. 2016. ilus
Artigo em Português | LILACS, BBO - Odontologia | ID: lil-780067

RESUMO

Introdução: A avaliação microbiológica em produtos de higiene pessoal constitui uma etapa importante no que se refere à segurança do usuário e à qualidade do produto, visto que a carga microbiana elevada pode acarretar problemas de saúde, especialmente em pessoas imunocomprometidas. Objetivo: Verificar o cumprimento das exigências acerca da qualidade microbiológica de cremes e géis dentais adquiridos comercialmente. Material e método: Realizou-se a contagem de bactérias e fungos viáveis totais e pesquisa dos patógenos E. coli, Salmonella sp., S. aureus e P. aeruginosa em 21 amostras. Resultado: Das amostras analisadas, 52,0% apresentaram crescimento microbiano e 28,6% e 0,21% apresentaram contaminação fúngica e bacteriana, respectivamente, acima dos limites descritos na Farmacopeia Brasileira para preparações de uso tópico (máximo permitido 2 × 102 UFC/g de bactérias e 2 × 101 UFC/g de fungos). Nenhuma amostra apresentou os patógenos pesquisados E. coli, Salmonella sp., S. aureus e P. aeruginosa. Conclusão: Estes resultados indicam que muitos produtos disponíveis no mercado apresentam qualidade inadequada, demonstrando falhas no controle de qualidade. Para prevenir esta situação, faz-se necessária fiscalização rigorosa e adoção de medidas regulamentadoras e educacionais aliadas ao seguimento das Boas Práticas de Fabricação pelas indústrias fabricantes.


Introduction: Microbiological evaluation in personal care products is important to guarantee user safety and product quality since microbial contamination elicits health problems especially in immunocompromised patients. Objective: To verify the compliance with the requirements regarding the microbiological quality of creams and dental gels acquired commercially. Material and method: Microbiological contamination was performed through total bacterial and fungal viable count and research of E. coli, Salmonella sp., S. aureus and P. aeruginosa in twenty-one samples. Result: 52.0% of sample presented microbial growth, and 28.6% and 0.21% presented fungal and bacterial contamination, respectively, exceeding the limits described in Brazilian Pharmacopoeia for topical preparations (maximum allowable 2 × 102 CFU / g of bacteria and 2 × 101 CFU / g yeast). None of the researched pathogens E. coli, Salmonella sp., S. aureus and P. aeruginosa were found. Conclusion: These results indicate that many products available in the market present inadequate quality, demonstrating quality control failures. Rigorous inspection and adoption of regulatory and educational measures aligned with the compliance of Good Manufacturing Practices by manufactures are needed to prevent this situation.


Assuntos
Higiene Bucal , Controle de Qualidade , Cremes Dentais , Contaminação de Medicamentos , Controle de Infecções Dentárias , Dentifrícios , Pseudomonas , Salmonella , Streptococcus , Escherichia coli
2.
Artigo em Português | Coleciona SUS | ID: biblio-945787

RESUMO

O Programa Mais Médicos faz parte de um amplo processo de melhoria do atendimento do Sistema Único de Saúde(SUS), que prevê investimentos em hospitais e unidades de saúde, levando médicos para regiões com escassez eausência de profissionais. Essa medida é apenas uma série de tantas outras que visam ao aprimoramento da formação médica e à resolução da carência de profissionais em regiões menos favorecidas. Este artigo apresenta umacontextualização do programa, bem como pretende a compreensão de seus instrumentos normativos, aspectos relevantes e finalidades. É uma pesquisa de cunho bibliográfico, com revisão na literatura a respeito do tema. Constatou-se que o programa objetiva resolver a disparidade entre os estados brasileiros, no que diz respeito ao índice de médicos/mil habitantes, refletindo na melhoria da atenção básica de saúde. Conclui-se que a convocação de médicos para a atuação em municípios que apresentam maior vulnerabilidade social, tem a finalidade de garantir mais saúde para todo o Brasil, bem como a expansão de vagas de medicina e de residência médica, possibilitando o aprimoramento profissional dos envolvidos.


More Physicians Program is part of a broader process of improving the care of the Unified Health System (SUS), whichforesees investments in hospitals and health units, leading doctors to areas with shortages and lack of professionals,noting that this measure is only a host of many others aimed at improving medical training and the resolution of theshortage of professionals in underprivileged areas. This article seeks to contextualize the program as well asunderstanding its normative instruments relevant aspects and purposes. It is a survey of bibliographic nature, withreview of the literature on the subject, divided into two chapters. It was found that the program aims to address thedisparity between the Brazilian states, with regard to the number of doctors / thousand, reflecting the improvement ofprimary health care. We conclude that the call for medical operations in municipalities with higher social vulnerability,aims to ensure better health for all over Brazil, as well as the expansion of places of Medicine and residency, enablingthe professional development of those involved.


Assuntos
Atenção Primária à Saúde , Médicos de Atenção Primária/provisão & distribuição , Brasil , Programas Nacionais de Saúde
3.
Rev. bras. cancerol ; 61(4): 335-341, out./dez. 2015.
Artigo em Português | LILACS | ID: biblio-847040

RESUMO

Introdução: Os enfermeiros são os profissionais com maior contato com os pacientes oncológicos na atenção básica. A hipótese deste estudo é que existam lacunas de conhecimento desses profissionais sobre as particularidades no tratamento dos pacientes oncológicos. Objetivo: Identificar o nível de conhecimento de enfermeiros atuantes na Estratégia Saúde da Família (ESF), sobre os cuidados com o paciente oncológico durante o tratamento quimioterápico. Método: Estudo transversal, prospectivo, quantitativo, desenvolvido com 15 enfermeiros atuantes das ESF de três municípios do Norte do Estado do Rio Grande do Sul. Os dados foram coletados no mês de novembro de 2014, por meio da aplicação de questionário semiestruturado. Resultados: O nível geral de conhecimento foi classificado como escore regular. Apenas um entrevistado acertou 89% das questões, os demais não ultrapassaram o total de 67% das questões. O município Y obteve o maior número de acertos entre os participantes do estudo e também foi o único em que os enfermeiros eram 100% concursados e com o maior nível de formação profissional na população do estudo. Pode-se atribuir o melhor desempenho nas respostas ao maior nível de exigência na contratação dos enfermeiros. Conclusão: Existem lacunas no conhecimento dos enfermeiros para o atendimento aos pacientes portadores de neoplasias. Tal fator é limitante da prática profissional. É necessário investir nas capacitações e educação continuada para atingir um maior nível de conhecimento e, consequentemente, maior qualidade na atenção prestada aos pacientes oncológicos.


Introduction: Nurses are the professionals who have the greatest contact with cancer patients in primary care. Our hypothesis is that there are knowledge gaps about the particulars of the treatment of cancer patients in these professionals. Objective: To identify the level of knowledge of nurses working in the Family Health Strategy (FHS), on the care of cancer patients during chemotherapy. Method: Transversal, prospective study of quantitative nature, developed with 15 nurses working in Family Health Strategies of three municipalities in the north of the Rio Grande do Sul State. Data were collected in November 2014, by applying a semi structured questionnaire online. Results: The general level of knowledge was classified as regular. Only one respondent scored on 89% of the issues, and the others did not exceed the total of 67% of the questions. Y county had the highest number of correct responses of the study participants and was also the only one where nurses were gazetted and 100% with the highest level of training among the study population. You can assign the best performance in the answers to the most demanding level in the recruitment of nurses. Conclusion: There are gaps in the knowledge of nurses in caring for patients with cancer. This factor is limiting professional practice. We must invest in training and continuing education to achieve a higher level of knowledge and consequently, higher quality care provided to cancer patients.


Introducción: Los profecionales en enfermería tienen un mayor contacto con los pacientes de cáncer en la atención primaria. La hipótesis de este estúdio es que existen lagunas en los conocimientos de estos profesionales sobre las particularidads en el tratamento en pacientes con cáncer. Objetivo: Identificar el nivel de conocimiento de los profecionales en enfermería que trabajan en la Estrategia de Salud de la Familia (ESF), en el cuidado de los pacientes con cáncer durante la quimioterapia. Método: Estudio transversal, prospectivo de carácter cuantitativo, desarrollado con 15 enfermeros que trabajan con Estrategia de Salud de la Familia en tres municipios del norte del Estado Rio Grande do Sul los datos fueron recolectados en noviembre de 2014, mediante la aplicación semiestructurada de un cuestionario en línea. Resultados: El nivel general de conocimientos fue clasificado con un puntaje regular. Sólo uno de los encuestados alcanzó el 89% de los temas, los demás no superó el total de 67% de las preguntas. El municipio Y obtuvo el mayor número de aciertos entre los participantes del estudio y también fue el único donde los profesionales eran 100%, concursados y con el mayor nivel de formación profesional entre la población del estudio. Puede asignar el mejor rendimiento en las respuestas a un mayor nivel de exigencia en la contratación de personal de enfermería. Conclusión: Hay lagunas en el conocimiento de los profesionales de enfermería para el cuidado de pacientes portadores de neoplasias. Este factor está limitando la práctica profesional. Es necesario invertir en la capacitación y educación continua para lograr un mayor nivel de conocimiento y, en consecuencia, una atención de mayor calidad que se ofrece a los pacientes de cáncer.


Assuntos
Humanos , Masculino , Feminino , Enfermagem Oncológica , Enfermeiras de Saúde da Família , Estudos Transversais , Tratamento Farmacológico/enfermagem , Capacitação de Recursos Humanos em Saúde , Cuidados de Enfermagem
4.
Toxicol Lett ; 229(1): 178-89, 2014 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-24968061

RESUMO

Abuse of synthetic drugs is widespread among young people worldwide. In this context, piperazine derived drugs recently appeared in the recreational drug market. Clinical studies and case-reports describe sympathomimetic effects including hypertension, tachycardia, and increased heart rate. Our aim was to investigate the cytotoxicity of N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(4-methoxyphenyl) piperazine (MeOPP), and 1-(3,4-methylenedioxybenzyl) piperazine (MDBP) in the H9c2 rat cardiac cell line. Complete cytotoxicity curves were obtained at a 0-20 mM concentration range after 24 h incubations with each drug. The EC50 values (µM) were 343.9, 59.6, 570.1, and 702.5 for BZP, TFMPP, MeOPP, and MDBP, respectively. There was no change in oxidative stress markers. However, a decrease in total GSH content was noted for MDBP, probably due to metabolic conjugation reactions. All drugs caused significant decreases in intracellular ATP, accompanied by increased intracellular calcium levels and a decrease in mitochondrial membrane potential that seems to involve the mitochondrial permeability transition pore. The cell death mode revealed early apoptotic cells and high number of cells undergoing secondary necrosis. Among the tested drugs, TFMPP seems to be the most potent cytotoxic compound. Overall, piperazine designer drugs are potentially cardiotoxic and support concerns on risks associated with the intake of these drugs.


Assuntos
Drogas Desenhadas/toxicidade , Mitocôndrias Cardíacas/patologia , Mioblastos Cardíacos/patologia , Piperazinas/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes , Metabolismo Energético/efeitos dos fármacos , Citometria de Fluxo , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Mioblastos Cardíacos/efeitos dos fármacos , Necrose/patologia , Vermelho Neutro , Ratos , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sais de Tetrazólio , Tiazóis
5.
Basic Clin Pharmacol Toxicol ; 114(3): 254-62, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24119282

RESUMO

Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury.


Assuntos
Antineoplásicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doenças Hematológicas/induzido quimicamente , Mitoxantrona/toxicidade , Animais , Antineoplásicos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Leucócitos/patologia , Masculino , Testes para Micronúcleos , Mitoxantrona/administração & dosagem , Ratos , Ratos Wistar , Fatores de Tempo , Testes de Toxicidade Subcrônica
6.
Cardiovasc Toxicol ; 14(1): 30-40, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24096626

RESUMO

Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early MTX cardiac toxic effects, while the other was euthanized on day 48 (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac mitochondria isolated from 4 adult untreated rats were also used to evaluate in vitro the MTX (10 nM, 100 nM, and 1 µM) direct effects upon mitochondria functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a reduction in relative body weight gain in both treated groups with no significant changes in water and food intake. Decreased levels of plasma total creatine kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of lactate were seen in MTX48. Increased cardiac relative mass and microscopic changes were evident in both treated groups. Considering mitochondrial effects, for the first time, it was evidenced that MTX induced an increase in the complex IV and complex V activities in MTX22 group, while a decrease in the complex V activity was accompanied by the reduction in ATP content in the MTX48 rats. No alterations in mitochondria transmembrane potential were found in isolated mitochondria from MTX48 rats or in isolated mitochondria directly incubated with MTX. This study highlights the relevance of the cumulative MTX-induced in vivo mitochondriopathy to the MTX cardiotoxicity.


Assuntos
Antineoplásicos/toxicidade , Metabolismo Energético/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitoxantrona/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Biomarcadores/sangue , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Cardiopatias/metabolismo , Cardiopatias/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Ratos Wistar , Fatores de Tempo , Aumento de Peso/efeitos dos fármacos
7.
Cardiovasc Toxicol ; 13(4): 413-25, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24046265

RESUMO

Mitoxantrone (MTX) is a chemotherapeutic agent that emerged as an alternative to anthracycline therapy. However, MTX also causes late cardiotoxicity, being oxidative stress and mitochondrial-impaired function proposed as possible mechanisms. This work aimed to investigate the relevance of these mechanisms to the MTX toxicity in H9c2 cells, using therapeutic concentrations. The observed cytotoxicity of MTX was time and concentration dependent in both lactate dehydrogenase leakage assay and MTT reduction assay. Two therapeutic concentrations (100 nM and 1 µM) and three time points were selected (24, 48, and 96 h) for further studies. Both MTX concentrations caused a significant increase in caspase-3 activity, which was not prevented by inhibiting MTX CYP450-metabolism. Significant decreases were observed in the total and reduced glutathione levels only in MTX 100 nM at 96 h; however, neither alterations in oxidized glutathione nor increases in the malondialdehyde levels were observed at any time or concentrations tested. On the other hand, changes in the intracellular ATP levels, mitochondrial membrane potential, and intracellular calcium levels were observed in both concentrations and all time tested. Noteworthy, decreased levels of ATP-synthase expression and activity and increases in the reactive species generation were observed at 96 h in both working concentrations. However, the radical scavenger N-acetylcysteine or the mitochondrial function enhancer L-carnitine did not prevent MTX cytotoxicity. Thus, this work evidenced the early MTX-induced energetic crisis as a possible key factor in the cell injury.


Assuntos
Antineoplásicos/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Mitoxantrona/administração & dosagem , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Metabolismo Energético/fisiologia , Ratos , Fatores de Tempo
8.
Arch Toxicol ; 87(10): 1809-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23545721

RESUMO

Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18 % patients. The metabolic profile of MTX was assessed after incubation of 100 µM MTX with hepatic S9 fraction isolated from rats. The presence of MTX and its metabolites was also assessed in vivo through the analysis of liver and heart extracts of MTX-treated rats. The cytotoxic effects of MTX and MTX metabolites were evaluated in the H9c2 cells after 24-h incubation with MTX alone and MTX + metabolites. The influence of CYP450- and CYP2E1-mediated metabolism for the cytotoxicity of MTX was assessed after 96-h incubation with MTX (100 nM and 1 µM) in the presence/absence of CYP450 or CYP2E1 inhibitors. After 4-h incubation in supplemented S9 fraction, the MTX content was 35 % lower and 5 metabolites were identified: an acetoxy ester derivative (never described before), two glutathione conjugates, a monocarboxylic acid derivative, and the naphtoquinoxaline, the later commonly related to MTX pharmacological effects. The presence of MTX and naphtoquinoxaline metabolite was evidenced in vivo in liver and heart of MTX-treated rats. The cytotoxicity caused by MTX + metabolites was higher than that observed in the H9c2 cells incubated with non-metabolized MTX group. The co-incubation of MTX with CYP450 and CYP2E1 inhibitors partially prevented the cytotoxicity observed in the MTX groups incubated with H9c2 cells, highlighting that the metabolism of MTX is relevant for its undesirable effects. The naphtoquinoxaline metabolite is described in heart and liver in vivo, highlighting that this metabolite accumulates in these tissues. It was demonstrated that MTX P450-mediated metabolism contributed to MTX toxicity.


Assuntos
Antineoplásicos/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Cardiopatias/induzido quimicamente , Mitoxantrona/metabolismo , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Coração/efeitos dos fármacos , Cardiopatias/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mitoxantrona/administração & dosagem , Mitoxantrona/toxicidade , Ratos , Ratos Wistar , Fatores de Tempo , Distribuição Tecidual
9.
Curr Clin Pharmacol ; 8(4): 350-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23342978

RESUMO

Amphetamine-like drugs are sympathomimetic agents with marked central and peripheral stimulant properties. Despite the street illegal drugs such as amphetamine and ecstasy, some amphetamine-like compounds are also legally marketed under medical prescription in the treatment of attention deficit-hyperactivity disorder (methylphenidate) and obesity/overweight (fenproporex and diethylpropione). However, similar with what happens with their illicit analogues, therapeutic amphetamine-like drugs also share important toxicological risks. Although methylphenidate is considered the first choice in the treatment of attention deficit-hyperactivity disorder, its high popularity among teenagers and children is raising concern in the medical community. Regarding weight-loss purposes, the use of amphetamine-like compounds are very controversial, though. Thus, the present review will address pharmacokinetic, pharmacodynamic, and toxicological aspects of amphetamine-like compounds used with therapeutic aims.


Assuntos
Anfetaminas/farmacologia , Depressores do Apetite/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Adolescente , Anfetaminas/efeitos adversos , Anfetaminas/farmacocinética , Animais , Depressores do Apetite/efeitos adversos , Depressores do Apetite/farmacocinética , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/farmacocinética , Criança , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/farmacocinética , Drogas Ilícitas/farmacologia , Obesidade/tratamento farmacológico
10.
Genet Mol Biol ; 35(3): 599-602, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23055798

RESUMO

Certain mutations in BRCA1 and BRCA2 genes are frequent in the Ashkenazi Jewish population. Several factors contribute to this increased frequency, including consanguineous marriages and an event known as a "bottleneck", which occurred in the past and caused a drastic reduction in the genetic variability of this population. Several studies were performed over the years in an attempt to elucidate the role of BRCA1 and BRCA2 genes in susceptibility to breast cancer. The aim of this study was to estimate the carrier frequency of certain common mutations in the BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) genes in an Ashkenazi Jewish population from Porto Alegre, Brazil. Molecular analyses were done by PCR followed by RFLP (ACRS). The carrier frequencies for BRCA1 185delAG and 5382insC were 0.78 and 0 respectively, and 0.4 for the BRCA2 6174deT mutation. These findings are similar to those of some prior studies but differ from others, possibly due to excluding individuals with a personal or family history of cancer. Our sample was drawn from the community group and included individuals with or without a family or personal history of cancer. Furthermore, increased dispersion among Ashkenazi subpopulations may be the result of strong genetic drift and/or admixture. It is therefore necessary to consider the effects of local admixture on the mismatch distributions of various Jewish populations.

13.
Food Chem Toxicol ; 49(1): 8-16, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21075161

RESUMO

Synephrine is cited as 'the active component' of plants and dietary supplements used in weight loss. It became one of the most popular stimulants present in weight-loss products after the US Food and Drug Administration had interdicted the use of ephedrine-containing dietary supplements. Synephrine is also a trace amine that can be found in vertebrates and invertebrates. Synephrine acts on several adrenergic and serotonergic receptors and its activity on trace-amine-associated receptors has long been discussed. Synephrine exists in three different positional isomers; however, only p- and m-synephrine have been described in weight-loss products. The alleged effectiveness of synephrine-containing supplements is attributed to the thermogenic effects arising from synephrine's adrenergic stimulation. The growing use of synephrine has raised concerns since it has been accompanied by reports of adverse effects. Cardiac adverse events, including hypertension, tachyarrhythmia, variant angina, cardiac arrest, QT prolongation, ventricular fibrillation, myocardial infarction, and sudden death, have been the most common adverse effects associated with synephrine intake. The mechanisms involved in synephrine-induced cardiotoxicity are still unknown since studies related to its safety are scarce. This review will address general aspects concerning the pharmacology of synephrine, but will focus on the efficacy and toxicity aspects related to the use of synephrine in weight-loss.


Assuntos
Sinefrina/administração & dosagem , Redução de Peso/efeitos dos fármacos , Citrus/química , Humanos , Relação Estrutura-Atividade , Sinefrina/farmacologia , Sinefrina/toxicidade
14.
Arch Toxicol ; 85(8): 929-39, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21140131

RESUMO

Synephrine is a natural compound, frequently added to ephedra-free dietary supplements for weight-loss, due to its effects as a nonspecific adrenergic agonist. Though only p-synephrine has been documented in plants, the presence of m-synephrine has also been reported in weight-loss products. The use of synephrine in dietary supplements was accompanied by reports of adverse effects, especially at the cardiovascular level. It is well known that the imbalance in cardiac glutathione levels can increase the risk of cardiomyopathy. The present work aimed to study the role of organic cation-mediated transport of m- and p-synephrine and the possibility that p- and m-synephrine induce intracellular changes in glutathione levels in calcium-tolerant freshly isolated cardiomyocytes from adult rat. After a 3 h incubation with 1 mM p- or m-synephrine, the intracellular content of synephrine was measured by gas chromatography/ion trap-mass spectrometry (GC/IT-MS); cell viability and intracellular glutathione levels were also determined. To evaluate the potential protective effects of antioxidants against the adverse effects elicited by m-synephrine, cells were pre-incubated for 30 min with Tiron (100 µM) or N-acetyl-cysteine (NAC) (1 mM). To assess the influence of α(1)-adrenoceptors activation in glutathione depletion, a study with prazosin (100 nM) was also performed. The results obtained provide evidence that organic cation transporters OCT3 and OCT1 play a major role in m- and p-synephrine-mediated transport into the cardiomyocytes. The importance of these transporters seems similar for both isomers, although p-synephrine enters more into the cardiomyocytes. Furthermore, only m-synephrine induced intracellular total glutathione (GSHt) and reduced glutathione (GSH) depletion. NAC and Tiron were able to counteract the m-synephrine-induced GSH and GSHt decrease. On the other hand, the incubation with prazosin was not able to change m-synephrine-induced glutathione depletion showing that this effect is independent of α(1)-adrenoceptor stimulation. In conclusion, both positional isomers require OCT3 and OCT1-mediated transport to enter into the cardiomyocytes; however, the hydroxyl group in the p-position favours the OCT-mediated transport into cardiomyocytes. Furthermore, the structural isomerization of synephrine influences its toxicological profile since only m-synephrine caused GSH depletion.


Assuntos
Agonistas alfa-Adrenérgicos/toxicidade , Glutationa/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Sinefrina/toxicidade , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Acetilcisteína/farmacologia , Agonistas alfa-Adrenérgicos/química , Agonistas alfa-Adrenérgicos/farmacocinética , Animais , Antioxidantes/farmacologia , Transporte Biológico , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/deficiência , Masculino , Miócitos Cardíacos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Sinefrina/química , Sinefrina/farmacocinética
15.
J Pharm Biomed Anal ; 52(5): 721-6, 2010 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-20303689

RESUMO

After the FDA's ban of ephedrine-containing supplements, Citrus aurantium appeared as an alternative to ephedra in herbal weight loss products. Synephrine, the most abundant active component of C. aurantium, exists in three different structural or positional isomeric forms (ortho-o-, meta-m-, and para-p-). Dietary supplements contain m- and p-synephrine, both alpha-adrenergic agonists,while the m-isoform is the most potent at alpha(1)-adrenoreceptors. In spite of the pharmacokinetic and toxicological interest in the study of these compounds, adequate methods for their quantification in biological samples are yet to be developed. Thus, in the present study, a sensitive gas chromatography-ion trap mass spectrometry (GC/IT-MS) method was developed and validated for the simultaneous quantitation of m- and p-synephrine in a cellular matrix after solid phase extraction (SPE). The validation of the method was performed through the evaluation of the following parameters: selectivity, linearity, specificity, precision, accuracy, limit of detection, limit of quantification, and recovery. The method's applicability was studied in two different biological matrices by evaluating p- and m-synephrine uptake in Caco-2 cells and also in freshly isolated cardiomyocytes from adult rat. The developed GC/IT-MS method was shown to be selective, accurate, precise, and valid for simultaneous determination of p- and m-synephrine in biological samples.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Sinefrina/análise , Animais , Células CACO-2 , Humanos , Limite de Detecção , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sinefrina/farmacocinética
16.
Mol Med Rep ; 2(5): 793-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21475903

RESUMO

Breast cancer is the most common neoplasia as well as the main cause of cancer-related death among women, experiencing a 0.5% increase in incidence per year. The disease results from a series of mutations in the DNA development and repair genes. Approximately 50% of human carcinomas present mutations in the TP53 gene. Polymorphisms of TP53 include codon 72 containing either arginine (CGC) or proline (CCC). Such polymorphisms may be involved in the susceptibility and predisposition to cancer, presenting a widely variable ethnic and geographic distribution. The arginine homozygous genotype seems to be a significant risk factor for breast cancer. The purpose of this study was to determine the frequency of the R72P polymorphism of the TP53 gene in patients with invasive ductal breast cancer from southern Brazil, where this type of cancer has a high incidence, as well as its association with breast carcinoma and clinicopathological characteristics. Seventy-six patients suffering from invasive ductal breast cancer and 80 controls were analyzed, and samples were evaluated by PCR followed by restriction enzyme digestion. No statistical differences in terms of the genotype frequency (P=0.707) or the arginine and proline allele frequencies (P=0.469) involving codon 72 were found in patients compared to controls. Thus, statistical analysis did not suggest any association between the R72P polymorphism of the TP53 gene and invasive ductal carcinoma in the population studied. Additionally, no significant association with the clinicopathological characteristics presented by the breast carcinoma patients was found.

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