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1.
Recent Pat Anticancer Drug Discov ; 19(2): 137-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36788702

RESUMO

BACKGROUND: Cannabis use for tumor treatment has been explored in several areas, and its potential for tumor remission is currently being studied after the discovery of the endogenous cannabinoid. OBJECTIVE: The study aimed to conduct a critical patent review to identify and explore the latest advances and therapeutic strategies using Cannabis to treat cancer. METHODS: The research was carried out in the free and online database Espacenet, using the descriptors "cancer" and "Cannabis or cannabidiol" in the title or abstract. A total of 95 patents were identified for preliminary evaluation in the database. Six duplicate patents were excluded, 12 referring to traditional Chinese medicine and 36 with a title in disagreement with the scope of this review. In addition the final selection involved 21 patents that were in line with the objective of the study. RESULTS: As observed in the reading of patents, the interest of pharmaceutical industries and researchers and the development of new products to fight cancer have increased in recent years. The main cannabinoids present in the patents are tetrahydrocannabinol, cannabidiol, and hemp. Moreover, the patents were classified and the main applicant countries were the United States followed by Japan, with a higher filing rate in 2019 and, mainly by the industry. CONCLUSION: In conclusion we can say that, the importance of parliamentary approval in the cultivation and investments that, in addition to bringing innovation to the industrial sector, enriches research in the area, contributing to the creation of new medicines.


Assuntos
Canabidiol , Canabinoides , Cannabis , Neoplasias , Humanos , Estados Unidos , Canabidiol/uso terapêutico , Patentes como Assunto , Canabinoides/uso terapêutico , Neoplasias/tratamento farmacológico
2.
Pharmaceutics ; 15(7)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37513968

RESUMO

Voriconazole is a triazole antifungal used empirically for the treatment of complicated meningitis associated with Cryptococcus neoformans. Biopsy studies show that the drug exhibits adequate brain penetration although levels of cerebral spinal fluid (CSF) are highly variable. Considering that CSF is one of the main surrogates for CNS exposure, the present work proposed the building of a population pharmacokinetic modeling (popPK) model able to describing the exposure achieved by voriconazole in the plasma, interstitial cerebral fluid and CSF of healthy and infected rats. The developed popPK model was described by four compartments, including total plasma, free brain and total CSF concentrations. The following PK parameters were determined: Km = 4.76 mg/L, Vmax = 1.06 mg/h, Q1 = 2.69 L, Qin = 0.81 h-1 and Qout = 0.63 h-1. Infection was a covariate in the Michaelis-Menten constant (Km) and intercompartmental clearance from the brain tissue compartment to central compartment (Qout). Simulations performed with the popPK model to determine the probability of reaching the therapeutic target of fAUC > MIC showed that VRC has sufficient tissue exposure in the interstitial fluid and in the CSF for the treatment of fungal infections in these tissues at prevalent minimum inhibitory concentrations.

3.
Future Microbiol ; 17: 1421-1432, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36169343

RESUMO

Drugs used to fight fungal infections may cause toxic or adverse drug interactions. For this reason, there is an increase in the development of natural, semisynthetic and synthetic antifungal peptides. This study aimed to perform a patent review to identify the advances in peptides to treat fungal infections. In a preliminary assessment, 597 patents were identified from the database. Then, duplicated patents (62) and those with titles in disagreement with the scope of this review (196) were excluded. Then, six patents were not in English or Spanish. Following the screening, 288 patents were outside the focus of this review, according to their abstract and description. The final selection covered 45 patents.


Currently, medications used to treat fungal infections may interact negatively with other drugs or be hazardous to the host. Scientists have been looking for novel, safe and efficient antifungal drugs since the enhancement of fungal resistance. Antimicrobial peptides, as opposed to traditional antibiotics, offer a variety of antibacterial activity against bacteria, fungi, parasites, viruses and cancer cells. The production of isolated natural, semisynthetic and synthetic antifungal peptides has increased. As a result, patents are a reliable and up-to-date source of innovation. As a result, their content analysis provides crucial information for identifying trends in new medications and targeted treatment plans.


Assuntos
Antifúngicos , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/microbiologia , Peptídeos/farmacologia , Peptídeos/uso terapêutico
4.
Pharmaceutics ; 15(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36678714

RESUMO

Diabetes mellitus (DM) is a metabolic syndrome that can be considered a growing health problem in the world. High blood glucose levels are one of the most notable clinical signs. Currently, new therapeutic alternatives have been tackled from clinicians' and scientists' points of view. Natural products are considered a promising source, due to the huge diversity of metabolites with pharmaceutical applications. Therefore, this review aimed to uncover the latest advances in this field as a potential alternative to the current therapeutic strategies for the treatment of DM. This purpose is achieved after a patent review, using the Espacenet database of the European Patent Office (EPO) (2016-2022). Final screening allowed us to investigate 19 patents, their components, and several technology strategies in DM. Plants, seaweeds, fungi, and minerals were used as raw materials in the patents. Additionally, metabolites such as tannins, organic acids, polyphenols, terpenes, and flavonoids were found to be related to the potential activity in DM. Moreover, the cellular transportation of active ingredients and solid forms with special drug delivery profiles is also considered a pharmaceutical technology strategy that can improve their safety and efficacy. From this perspective, natural products can be a promissory source to obtain new drugs for DM therapy.

5.
Braz J Microbiol ; 52(4): 1967-1979, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34337679

RESUMO

OBJECTIVES: The aim of this study was to investigate the effect of daptomycin against methicillin-resistant staphylococci (MRSA and MRSE) bacteremia using computer modeling. METHODS: A pharmacokinetic/pharmacodynamic (PK/PD) modeling strategy to explain the data from an in vitro dynamic model employing time-kill curves for MRSA and MRSE was proposed. Bacterial killing was followed over time by determining viable counts and the resulting time-kill data was analyzed. Monte Carlo simulations were performed using pharmacokinetic parameters and pharmacodynamic data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. Simulations were conducted to assess the reduction in the number of colony-forming units (CFU)/mL for 18 days of treatment with daptomycin at doses of 6, 8, and 10 mg/kg/24 h or 48 h with variations in creatinine clearance (CLCR): 15-29 mL/min/1.73 m2, 30-49 mL/min/1.73 m2, 50-100 mL/min/1.73 m2, as well as for defining the probability of reaching the target fAUC/MIC = 80 in the same dose and clearance range. A PK/PD model with saturation in the number of bacteria in vitro, growth delay, and bacterial death, as well as Hill's factor, was used to describe the data for both MRSA and MRSE. RESULTS: Monte Carlo simulations showed that for MRSA there was a reduction > 2 log CFU/mL with doses ≥ 6 mg/kg/day in 75th percentile of the simulated population after 18 days of treatment with daptomycin, whereas for MRSE this reduction was observed in 95th percentile of the population. CONCLUSIONS: The presented in vitro PK/PD model and associated modeling approach were able to characterize the time-kill kinetics of MRSA and MRSE. Our study based on PTAs suggests that doses ≥ 6 mg/kg/day of daptomycin should be used to treat bacteremia caused by MRSA and MRSE in patients with CLCR of 15-29 mL/min/1.73 m2. For patients with CLCR ≥ 50 mL/min/1.73 m2, it would be necessary to employ a dose of 10 mg/kg/day to treat complicated bacteremias.


Assuntos
Bacteriemia , Daptomicina , Staphylococcus aureus Resistente à Meticilina , Método de Monte Carlo , Infecções Estafilocócicas , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Daptomicina/farmacocinética , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico
6.
Arq. neuropsiquiatr ; 79(8): 732-742, Aug. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1339229

RESUMO

ABSTRACT Background: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. Objective: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. Methods: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. Results: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. Conclusion: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.


RESUMO Antecedentes: Insônia é um distúrbio do sono caracterizado por dificuldade de iniciar e manter o sono, afetando diferentes faixas etárias. Atualmente, a melatonina é utilizada no tratamento de insônia em crianças, adultos e idosos. Objetivo: Avaliar a eficácia da melatonina nos distúrbios do sono, posologia e potenciais efeitos adversos, bem como a regulamentação vigente no Brasil. Métodos: Trata-se de uma revisão integrativa, os artigos foram identificados nas bases de dados Cochrane Library, Medline (Pubmed) e Science Direct, totalizando 25 artigos, e foram selecionados três materiais disponíveis no site da Sociedade Brasileira de Endocrinologia e Metabologia e Agência Nacional de Vigilância Sanitária, publicados entre 2015 e 2020. Resultados: Verificou-se na maioria dos artigos selecionados que a melatonina reduz a latência do sono. Quanto as dosagens de melatonina identificou-se variação em cada faixa etária, para crianças de 0,5 a 3mg; adolescentes de 3 a 5mg; adultos de 1 a 5mg e idosos 1 mg a 6 mg demostraram serem eficazes. Em doses habituais os efeitos colaterais são leves. No Brasil, não foi identificado medicamento registrado e regulamentação vigente sobre o uso e comercialização de melatonina. Conclusão: A utilização da melatonina é uma alternativa que pode ser utilizada em distúrbios do sono. De acordo com as evidências encontradas, não demonstrou toxicidade ou efeitos colaterais severos, nem dependência mesmo em doses elevadas, sendo, portanto, segura para tratamento de pacientes desde crianças a idosos que sofrem de distúrbios do sono.


Assuntos
Humanos , Criança , Adolescente , Adulto , Idoso , Transtornos do Sono-Vigília/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Melatonina/uso terapêutico , Sono , Brasil
7.
Acta Sci Pol Technol Aliment ; 20(3): 325-336, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34304550

RESUMO

BACKGROUND: The use of natural plant antioxidants has been an alternative approach to synthetic antioxidants for food applications. This study investigated the antioxidant properties of the leaves of Curcuma longa L. against the oxidation of soybean oil using leaf extracts obtained from seven different types of organic solvents and compared to the action of efficient synthetic antioxidants which are widely used and low cost but with toxicity risk. The application of natural alternatives from sources still little studied is a proposal and the extraction of compounds with high antioxidant capacity may vary according to the type of solvent, its mixture, its polarity and other factors that burden or harm the health of the consumer. METHODS: The leaf extracts were sanitized, dried, and obtained for solvent selection. The quantification of total phenolic compounds (TPC) and antioxidants was performed by using different combinations and proportions of solvents: water (100%), ethanol (100%), methanol (100%), ethanol/water (70%:30%), methanol/water (70%:30%), methanol/acetic acid (99.5%:0.5%), and acetone/water/acetic acid (70%:28:2%). The solvent selected was the one that extracted the highest content of phenolic and antioxidant compounds (using the free radical DPPH scavenging method and FRAP assay). It used an accelerated storage test and experimental design to assess oxidative stability (using peroxide index (PI), thiobarbituric acid reactive substances (TBARS), dienes (DC) and triple conjugates (TC) and statistical analysis). RESULTS: The ethanol/water solvent was efficient in the extraction of TPC (2422 mg GAE 100 g-1). The mixture of solvents extracted an average of 23.65% more TPC when compared to the single solvents. Regarding the antioxidant capacity, the ethanol/water solvent showed 1847 mg TE 100 g-1 using the DPPH and 217 µmol of FeSO4 100 g-1 using the FRAP assays. In addition, the oxidation of soybean oil was delayed by the accelerated storage test showing equivalent results to BHT at 0.02% for the values of PI, TBARS and DC/TC. CONCLUSIONS: The E/W extract showed the highest yield in the extraction of phenolic compounds and is a safe solvent for food. The addition of Curcuma longa L. leaf extract to soybean oil caused reductions in PI, TBARS, CD and CT values. The leaf extract of C. longa L. is considered to be a good alternative to synthetic antioxidants against the oxidative degradation of soybean oil.


Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Óleo de Soja , Antioxidantes/análise , Curcuma/química , Etanol , Humanos , Oxirredução , Fenóis/análise , Extratos Vegetais/química , Folhas de Planta , Solventes , Glycine max , Substâncias Reativas com Ácido Tiobarbitúrico , Água
8.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 13: 995-1000, jan.-dez. 2021. tab
Artigo em Inglês, Português | BDENF, LILACS | ID: biblio-1254998

RESUMO

Objetivo: desenvolver atividades a fim de facilitar a reinserção social e no mercado de trabalho de dependentes químicos residentes da comunidade terapêutica Fazenda Paraíso, um centro de recuperação de toxicômanose alcoólatras do noroeste do estado do Rio Grande do Sul. Método: trata-se de um estudo de abordagem qualiquantitativa, com caráter descritivo. Quinze internos com idade entre 16 e 49 anos participaram de oficinas com cunho teórico/prático ministradas por docentes e acadêmicos do curso de graduação de Farmácia. Resultados: a maioria dos participantes estava com idade acima dos 30 anos, e 80% tinham somente formação em educação básica. Constatou-se que o emprego é capaz de gerar estabilidade financeira, além de proporcionar dignidade e trazer reconhecimento por parte da sociedade, sendo então importante para o toxicômano. Conclusão: o profissional farmacêutico pode ser um grande aliado na reinserção do dependente químico na sociedade, seja pela ministração de oficinas ou palestras de educação em saúde


Objective: to develop activities that facilitate social and labor market reintegration of drug addicts residing in Fazenda Paraíso, a drug and alcohol rehabilitation center in the northwest of Rio Grande do Sul, Brazil. Methods: this qualitative/quantitative study of descriptive character included 15 interns aged 16 to 49 years who participated in workshops of theoretical/practical nature taught by educators of the Pharmacy graduation course. Results: most participants were over 30 years old, and 80% had only basic education. Employment was shown to allow for financial stability, as well as to provide dignity and recognition by society, and it is considered important for drug addicts. Conclusion: pharmacy professionals can be great allies in the reintegration of drug addicts in society by providing workshops or lectures on health education


Objetivo: desarrollar actividades para facilitar la reinserción social y laboral de los toxicómanos que residen en la comunidad terapêutica Fazenda Paraíso, un centro para la recuperación de toxicómanos y alcohólicos en el noroeste del estado de Rio Grande do Sul. Método: estudio cualitativo y cuantitativo con carácter descriptivo. 15 pasantes de entre 16 y 49 años participaron en talleres teórico-prácticos impartidos por profesores y académicos del curso de graduación de Farmacia. Resultados: la mayoría de los participantes tenían más de 30 años, y el 80% solo tenían la educación básica. Se observó que el empleo es capaz de generar estabilidad financiera, además de proporcionar dignidad y reconocimiento por parte de la sociedad, lo cual es importante para el toxicómano. Conclusión: el profesional farmacéutico puede ayudar en la reintegración del toxicómano en la sociedad, por medio de la impartición de cursos o conferencias sobre la educación para la salud


Assuntos
Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Readaptação ao Emprego/métodos , Centros de Tratamento de Abuso de Substâncias , Educação Profissionalizante/métodos , Usuários de Drogas/educação , Alcoólicos/educação , Farmacêuticos , Relações Profissional-Paciente , Educação em Saúde , Inquéritos e Questionários , Escolaridade
9.
Rev. bras. geriatr. gerontol. (Online) ; 23(4): e200165, 2020. tab
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1156054

RESUMO

Resumo Objetivo verificar a prevalência da utilização de medicamentos potencialmente inapropriados e polifarmácia pela pessoa idosa. Método estudo observacional, com recorte transversal, analítico, quantitativo, de base populacional em uma associação de aposentados. Os dados foram coletados a partir de questionário estruturado, criado pelos próprios pesquisadores e aplicado em domicílio a uma amostra de 203 pessoas idosas. Resultados a idade média dos participantes foi de 73,1+8,13 anos (IC90%: 72,2-74,0), variando de 60 a 95 anos. A maioria declarou-se casado 54,2% (n=110/203), com ensino fundamental 71,4% (n=145/203), e renda familiar entre 2 e 4 salários mínimos 49,3% (n=100/203). As comorbidades mais encontradas foram: hipertensão arterial sistêmica 67,5% (n=137/203), artrite/artrose 30,5% (n=62/203), osteoporose 20,2% (n=41/203), entre outras. Quanto ao uso de medicamentos contínuos e eventuais, constatou-se uma mediana de 6 medicamentos utilizados pelos participantes, sendo 1 o número mínimo e 18 o número máximo. Houve polifarmácia em 64,5% (n=131/203) dos idosos e o uso de medicamentos potencialmente inapropriados em 78,8% (n=160/203). Quanto à utilização de polifarmácia, foi verificado associação significativa com: sexo feminino (p=0,004); e ter baixa escolaridade (p=0,017), e estado civil solteiro (0,027). Conclusão no âmbito da farmacoepidemiologia, o conhecimento dos fatores associados à utilização de medicamentos, como os identificados neste estudo, pode ser útil para alertar os prescritores e demais profissionais da saúde quanto à importância de identificar e monitorar os grupos mais vulneráveis, como por exemplo, as pessoas idosas.


Abstract Objective to verify the prevalence of the use of potentially inappropriate medications and polypharmacy by old people. Methods observational, cross-sectional, analytical, quantitative, population-based study in a retirees association. The data were collected from a questionnaire structured and created by the researchers and applied to the household. The association has 2,902 associates and underwent a stratified proportional sampling by gender, delimiting a sample of 203 old people, being 129 women and 76 men. Results the mean age of study participants was 73.1+8.13 years (90%CI:72.2-74.0), ranging from 60 to 95 years. The majority declared being married 110 (54.2%), with elementary education 145 (71.4%) and family income between 2 and 4 minimum wages 100 (49.3%). The most frequent comorbidities were: diabetes mellitus 33 (16.26%), systemic arterial hypertension 137 (67.49%), hypercholesterolemia 24 (11.8%), arthritis/arthrosis 62 (30.54%), osteoporosis 41 (20.2%), depression 27 (13.3%), among others with non-significant values. When analyzing the use of continuous and occasional medications, a median of 6 drugs used by participants was found, with 1 being the minimum number and 18 being the maximum number. The use of polypharmacy was identified in 131 (64.5%) old people and the use of potentially inappropriate medications in 160 (78.8%). Regarding the use of polypharmacy, a significant association was found with: female gender (p=0.004); and having low education (p=0.017), and single marital status (0.027). Conclusions in the context of pharmacoepidemiology, knowledge of the factors associated with the use of medicines may be useful to alert health professionals to the importance of identifying and monitoring the most vulnerable groups of old people in order to avoid the use of potentially inappropriate medications for the age group.

10.
Acta toxicol. argent ; 26(3): 104-112, Dec. 2018. ilus, tab
Artigo em Português | LILACS | ID: biblio-1001122

RESUMO

Anualmente milhões de agricultores são intoxicados no mundo, e destes, mais de 20 mil morrem em consequência da exposição a agrotóxicos. Intoxicações por organofosforados (OF) e carbamatos (CAR) representam as maiores ameaças à saúde dos trabalhadores rurais. Os OF e CAR atuam na inibição da enzima colinesterase, sendo assim a inibição desta mostra-se um excelente indicador da severidade da intoxicação. O objetivo deste estudo foi analisar o impacto do uso de OF e CAR em trabalhadores rurais na cidade de Mato Queimado/RS. Foi realizado um estudo transversal, prospectivo e experimental. Investigaramse 27 trabalhadores rurais expostos. Foram realizadas coletas sanguíneas e dados epidemiográficos nos meses de fevereiro e março de 2014. A atividade da colinesterase foi determinada através do método bioquímico cinético colorimétrico. A faixa etária média dos participantes foi 34,6 anos (± 8,5). A forma de contato mais prevalente foi a aplicação do produto (88,9%). O tempo médio de exposição foi de 10,7 anos. 70,4% relataram usar equipamentos de proteção individual (EPI), sendo mais frequente o uso de máscara (55,5%). A média dos valores de colinesterase para foi de 3244,45 U/I (± 345,8), níveis estes abaixo dos de referência. Através dos resultados obtidos nesta pesquisa torna-se imprescindível a utilização de meios de monitoramento biológico dos trabalhadores rurais na finalidade de prevenção e promoção da saúde.


Annually millions of rural workers are intoxicated in the world, and of these, more than 20,000 die as a result of exposure to pesticides. Intoxication by insecticides organophosphate (OF) and carbamates (CAR) represent the greatest threats to the health of rural workers. OF CAR and act on the inhibition of cholinesterase enzyme, thus inhibition of this proves to be an excellent indicator of the severity of the intoxication. The objective of this study was to analyze the impact of using OF CAR and in rural workers in the city of Mato Queimado/RS. A cross-sectional, prospective and experimental study was conducted. Twenty-three rural workers exposed were investigated. Sample collection and data demographic were conducted in February and March 2014. The cholinesterase activity was determined by biochemical kinetic colorimetric method. The average age of participants was 34.6 years (± 8.5). The most prevalent form of contact is via the application of the product (88.9%). The mean duration of exposure was 10.7 years. Still, 70.4% reported using personal protective equipment (PPE), more frequent use of mask (55.5%). The average values for cholinesterase was 3244.45 U/l (± 345.8) levels below those of the reference. The results obtained in this study are essential to use biological monitoring means of rural workers in purpose of prevention and health promotion.


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Trabalhadores Rurais , Carbamatos/intoxicação , Carbamatos/sangue , Exposição Ocupacional/estatística & dados numéricos , Intoxicação por Organofosfatos/sangue , Brasil/epidemiologia , Inibidores da Colinesterase/sangue , Colinesterases/sangue , Agroquímicos/intoxicação
11.
Artigo em Inglês | MEDLINE | ID: mdl-28483963

RESUMO

To make advances in the treatment of cryptococcal meningitis, it is crucial to know a given drug's free fraction that reaches the biophase. In the present study, we applied microdialysis (µD) as a tool to determine the free levels reached by voriconazole (VRC) in the brains of healthy and Cryptococcus neoformans-infected rats. The infection was induced by the intravenous (i.v.) administration of 1 × 105 CFU of yeast. The dose administered was 5 mg/kg (of body weight) of VRC, given i.v. Plasma and microdialysate samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LC-UV methods. The free brain/free plasma ratio (fT) and population pharmacokinetic (popPK) analyses were performed to evaluate the impact of infection on PK parameters of the drug. The brain penetration ratio showed an increase on brain exposure in infected animals (fThealthy = 0.85 versus fTinfected = 1.86). The structural PK model with two compartments and Michaelis-Menten (MM) elimination describes the VRC concentration-time profile in plasma and tissue simultaneously. The covariate infection was included in volume of distribution in the peripheral compartment in healthy animals (V2) and maximum rate of metabolism (VM ). The levels reached in infected tissues were higher than the values described for MIC of VRC for Cryptococccus neoformans (0.03 to 0.5 µg ml-1), indicating its great potential to treat meningitis associated with C. neoformans.


Assuntos
Encéfalo/metabolismo , Voriconazol/farmacocinética , Voriconazol/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/patogenicidade , Masculino , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/metabolismo , Microdiálise , Ratos , Ratos Wistar
12.
J Med Food ; 14(10): 1159-66, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21548805

RESUMO

Herbal drugs have been used since ancient times to treat a wide range of diseases. Morinda citrifolia Linn (popularly known as "Noni") has been used in folk medicine by Polynesians for over 2,000 years. It is reported to have a broad range of therapeutic effects, including effects against headache, fever, arthritis, gingivitis, respiratory disorders, infections, tuberculosis, and diabetes. The aim of this study was to investigate the antioxidant, anti-inflammatory, antinociceptive, and antibacterial properties of the aqueous extract from M. citrifolia leaves (AEMC). Antioxidant activity was observed against lipid peroxidation, nitric oxide, and hydroxyl radicals. The antinociceptive effect of AEMC was observed in the acetic acid-induced writhing test at the higher dose. Moreover, AEMC significantly reduced the leukocyte migration in doses of 200 and 400 mg/kg and showed mild antibacterial activity. Together, the results suggest that properties of M. citrifolia leaf extract should be explored further in order to achieve newer tools for managing painful and inflammation conditions, including those related to oxidant states.


Assuntos
Analgésicos/farmacologia , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Morinda/química , Extratos Vegetais/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão , Radical Hidroxila/farmacologia , Leucócitos/citologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Medicina Tradicional , Camundongos , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Fenol/farmacologia , Folhas de Planta/química , Tiobarbitúricos/análise , Tiobarbitúricos/metabolismo
13.
Rev. Soc. Bras. Med. Trop ; 43(5): 575-579, set.-out. 2010. ilus, tab
Artigo em Português | LILACS | ID: lil-564298

RESUMO

INTRODUÇÃO: A candidíase vaginal é uma condição que afeta um grande número de mulheres em idade fértil. Candida albicans é a espécie mais frequentemente isolada de secreção vaginal, entretanto, outras espécies mais resistentes às drogas antifúngicas podem ser isoladas de amostras clínicas vaginais. MÉTODOS: Foram identificadas as espécies de 30 isolados vaginais de Candida sp por PCR utilizando o primer universal ITS4 e primers espécie-específicos para C. albicans, C. glabrata, C. tropicalis e C. krusei. A sensibilidade destes isolados frente à anfotericina B, fluconazol e voriconazol foi determinada pelo método de macrodiluição M27-A2 do CLSI. RESULTADOS: Através dos ensaios de PCR, 28 isolados foram caracterizados como C. albicans e 2 isolados apresentaram amplificação para os primers específicos de C. albicans e C. glabrata. A concentração inibitória mínima para anfotericina B variou de 0,03µg/mL a 0,25µg/mL, para o fluconazol de 0,125µg/mL a 16µg/mL e para o voriconazol de 0,03µg/mL a 0,25µg/mL. CONCLUSÕES: A identificação de Candida ao nível de espécie através de ensaios de PCR deve ser relevante para o gerenciamento clínico destas infecções.


INTRODUCTION: Vaginal candidiasis is a condition that affects innumerous fertile women. Candida albicans is the most frequently isolated species from vaginal discharge; however, other different species that are more resistant to antifungal drugs can be identified in vaginal clinical samples. METHODS: The species of 30 vaginal Candida isolates was identified by PCR using the universal ITS4 primer and species-specific primers for C. albicans, C. glabrata, C. tropicalis and C. krusei. The sensitivity pattern to amphotericin B, fluconazole and voriconazole was assessed using the CLSI M27-A2 macrodilution method. RESULTS: The PCR assay revealed 28 C. albicans and 2 samples showed amplification for C. albicans and C. glabrata primers. The minimum inhibitory concentration for amphotericin B ranged from 0.03µg/mL to 0.25µg/mL, for fluconazole from 0.125µg/ml to 16µg/mL and for voriconazole from 0.03µg/mL to 0.25µg/m. CONCLUSIONS: Identification at Candida species level by PCR assay could be relevant for clinical management of these infections.


Assuntos
Feminino , Humanos , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase Vulvovaginal/microbiologia , Anfotericina B/farmacologia , Candida/genética , Candida/isolamento & purificação , DNA Fúngico/análise , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Pirimidinas/farmacologia , Triazóis/farmacologia
14.
Rev. Soc. Bras. Med. Trop ; 42(5): 556-560, Sept.-Oct. 2009. ilus, tab
Artigo em Português | LILACS | ID: lil-532513

RESUMO

Neste estudo estimou-se a distribuição e prevalência de β-lactamases de espectro estendido pertencentes às famílias TEM, SHV e CTX-M entre amostras de Escherichia coli e Klebsiella spp. no Hospital Universitário de Santa Maria, Rio Grande do Sul. Durante 14 meses, 90 microrganismos foram selecionados como prováveis produtores de ESBL. Os isolados foram submetidos a testes fenotípicos confirmatórios para a presença de ESBL. A seguir, os tipos de ESBLs presentes em cada microrganismo foram determinados através da pesquisa dos respectivos genes através da reação em cadeia da polimerase. Empregando-se o método do disco combinado, a presença de ESBLs foi confirmada em 55 (61,1 por cento) amostras; quando o método do duplo disco foi utilizado, 57 (63,3 por cento) amostras foramprodutoras de ESBLs. Com base na PCR, as ESBLs do tipo TEM e SHV foram mais presentes em Klebsiella pneumoniae enquanto que ESBL do tipo CTX-M foram mais presentes em Klebsiella oxytoca.


In this study, the distribution and prevalence of extended-spectrum β-lactamases belonging to the TEM, SHV and CTX-M families were estimated among samples of Escherichia coli and Klebsiella spp. at the university hospital of Santa Maria, Rio Grande do Sul. Over a 14-month period, 90 microorganisms were selected as likely ESBL producers. The isolates were subjected to confirmatory phenotype tests for the presence of ESBL. Through investigating the respective genes using the polymerase chain reaction, the ESBL types present in each microorganism were then determined. Fifty-five samples (61.1 percent) were confirmed as ESBL-positive by means of the combined disc method, and 57 (63.3 percent) were found to be ESBL producers by means of the double disc method. From the polymerase chain reaction, ESBLs of TEM and SHV types were more frequently present in Klebsiella pneumoniae, while ESBL of CTX-M type was more frequently present in Klebsiella oxytoca.


Assuntos
Humanos , Escherichia coli/enzimologia , Klebsiella/enzimologia , beta-Lactamases/genética , Cefalosporinas/farmacologia , DNA Bacteriano/análise , Escherichia coli/efeitos dos fármacos , Hospitais Universitários , Klebsiella/classificação , Testes de Sensibilidade Microbiana , Fenótipo , Reação em Cadeia da Polimerase , Prevalência , beta-Lactamases/análise
15.
Arq. bras. cardiol ; 79(3): 285-291, Sept. 2002. tab
Artigo em Inglês | LILACS | ID: lil-321669

RESUMO

OBJECTIVE: Lupus anticoagulant and anticardiolipin antibodies (aCL) have been associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), but their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies (aPL) and echocardiographic abnormalities in patients with SLE. METHODS: A total of 70 consecutive patients and 42 control subjects underwent M-mode, 2-dimensional and Doppler echocardiography and tests for lupus anticoagulant, aCL IgG, IgM, and IgA. Lupus anticoagulant was assayed with the dilute Russell viper venom time, and aCL IgG, IgM, and IgA were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Lupus anticoagulant showed a prevalence of 10 percent. As a whole, aCL had a prevalence of 44.3 percent and aPL had a prevalence of 50 percent. Patients with echocardiographic abnormalities had a prevalence of 54.3 percent and showed a trend towards an association with aCL IgG (P=0.06). The presence of pulmonary hypertension (PH) was significantly associated with aCL IgG (p=0.02). CONCLUSION: aCL IgG was significantly associated with PH and showed a strong trend towards an association with echocardiographic abnormalities taken together. These findings suggest a role for aCL IgG in the development of lupus cardiovascular disease


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos , Ecocardiografia , Cardiopatias , Lúpus Eritematoso Sistêmico , Anticorpos Anticardiolipina , Estudos de Casos e Controles , Ecocardiografia Doppler , Ecocardiografia Tridimensional , Ensaio de Imunoadsorção Enzimática , Cardiopatias , Concentração de Íons de Hidrogênio , Imunoglobulinas , Inibidor de Coagulação do Lúpus , Lúpus Eritematoso Sistêmico
16.
An. Fac. Med. Univ. Fed. Pernamb ; 38(1): 12-5, 1993. ilus
Artigo em Português | LILACS | ID: lil-227900

RESUMO

O presente trabalho tem como objetivo apresentar nossa experiência com a "istmoplastia sem enxerto". No período compreendido entre 01.08.91 e 13.07.92, seis pacientes portadores de coarctaçäo de aorta foram operados por esta técnica. A idade variou de três meses a seis anos (média= 24 meses) e o peso de 2.800grs a 19.600grs (média = 9.000grs.)Quatro pacientes possuíam uma coarctaçäo anular e os outros dois segmentar. A aorta bem liberada, e a regiäo coarctada incisada longitudinalmente sendo entÝo suturada transversalmente sem a utilizaçäo de material protético. Näo evidenciamos gradientes e a anastomose apresentou um excelente aspecto cirúrgico. Um paciente foi a óbito e os demais apresentaram boa evoluçäo pós-operatória, com a normalizaçäo dos pulsos nos membros inferiores. O ecocardiograma foi realizado em todos pacientes e apenas um tinha um gradiente de 10mm/Hg. Os autores discutem a técnica, suas indicaçöes, compara com as demais técnicas e considera este procedimento a operaçäo de escolha para tratamento da coarctaçäo levando-se em consideraçäo o completo alívio da área coarctada sem a utilizaçäo de enxerto e a näo mobilizaçäo ou ligadura da artéria subclávia


Assuntos
Humanos , Masculino , Feminino , Lactente , Cardiopatias Congênitas/cirurgia , Coartação Aórtica/cirurgia , Procedimentos Cirúrgicos Operatórios , Ligadura , Cirurgia Torácica
17.
Rev. bras. cir. cardiovasc ; 7(3): 165-73, jul.-set. 1992. tab
Artigo em Português | LILACS | ID: lil-164363

RESUMO

Os autores relatam a presente experiência clínica do programa NE-Tx, que é integrado por quatro diferentes Centros, bem como suas peculiaridades regionais. Foi idealizado um programa com baixo custo e integraçao regional. Na investigaçao pré-operatória, foi valorizado o nível social e intelectual do receptor e sua relaçao com os familiares. A busca de órgao à distância foi suprimida, com o deslocamento do receptor até o local da disponibilidade do órgao. No pás-operatório nao se utilizou dosagem sérica de ciclosporina, tendo os pacientes sido controlados com monitorizaçao seriada da funçao renal. Com essa estratégia, foram operados 7 pacientes, no período compreendido entre 19.7.86 e 1.11.91., em três diferentes Centros Integrados. Todos eram do sexo masculino e a idade variou de 17 a 50 anos. Três (42,8 por cento) pacientes eram portadores de miocardiopatia chagásica, 2 (28,5 por cento) de miocardiopatia idiopática, 1 (14,3 por cento) de miocardiopatia hipertrófica e 1 (14,3 por cento) de miocardiopatia reumática. Três (42,8 por cento) pacientes vieram de Centros diferentes: 1 de Natal para Recife, 1 de Maceió para Aracajú e um terceiro de Aracajú para Maceió. Dois (28,6 por cento) pacientes faleceram: um no período de pós-operatório imediato, de maneira ignorada e outro no pós-operatório tardio, devido a crise de rejeiçao. A mortalidade imediata foi de 14,3 por cento e a tardia de 14,3 por cento. Os restantes 5 (71,4 por cento) pacientes encontram-se evoluindo bem, tendo o follow-up variado de 2 a 48 meses. A incidência de infecçao, rejeiçao e demais problemas relacionados com o pás-operatório tardio é superponível com outros Centros. O programa mostrou-se eficiente, prático, compatível com nossa realidade e reproduz resultados de outras experiências.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Adolescente , Cardiomiopatias/cirurgia , Transplante de Coração , Brasil , Rejeição de Enxerto , Complicações Pós-Operatórias , Estudos Retrospectivos , Doadores de Tecidos
18.
Rev. paul. enferm ; 11(1): 35-40, jan.-abr.1992. ilus
Artigo em Português | LILACS, BDENF | ID: lil-139473

RESUMO

Os enfermeiros docentes do Curso de Auxiliar de Enfermagem do Centro de Formaçäo e Aperfeiçoamento em Ciências da Saúde do Instituto do Coraçäo (InCor) relatam a experiência da simulaçäo como uma estratégia de ensino inovadora e descrevem sua aplicaçäo no sistema cardiorespiratório. A participaçäo ativa dos alunos e a eficácia do processo ensino-aprendizagem tem sido observada.


Assuntos
Materiais de Ensino , Sistema Cardiovascular/anatomia & histologia , Assistentes de Enfermagem/educação , Educação em Enfermagem/métodos , Exercício de Simulação
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