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1.
AIDS Res Hum Retroviruses ; 21(1): 68-81, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15665646

RESUMO

We used an external quality assurance (EQA) panel to assess laboratory competency and comparability when performing ELISPOT assays in support of human immunodeficiency virus type 1 (HIV-1) vaccine trials. Cell recovery, viability, and frequency of interferon-gamma (IFN-gamma)-secreting cells after antigen stimulation were obtained from 11 laboratories on a coded panel of 11 peripheral blood mononuclear cell samples. The median recovery and viability before plating for all samples were 35% and 86%, respectively, with notable interlaboratory and intrasample variability. Empirical as well as statistical analysis methods were used to define positive ELISPOT responses. Remarkable concordance between laboratories was obtained in defining a qualitative assessment of responder/nonresponder status to antigens, but the frequency of responding cells varied among the laboratories. This study highlights the need for better standardization of protocols and reagents to obtain reliable and reproducible data that may support immunogenicity studies, vaccine regulatory submissions, and licensure.


Assuntos
Vacinas contra a AIDS/imunologia , Ensaio de Imunoadsorção Enzimática , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Interferon gama/metabolismo , Laboratórios , Leucócitos Mononucleares/imunologia , Vacinas contra a AIDS/administração & dosagem , Ensaios Clínicos como Assunto , Humanos , Ativação Linfocitária , Controle de Qualidade , Reprodutibilidade dos Testes
2.
Am J Clin Nutr ; 76(5): 1126-37, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12399289

RESUMO

BACKGROUND: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers. OBJECTIVE: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women. DESIGN: Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h. RESULTS: We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different. CONCLUSIONS: A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones.


Assuntos
Glycine max/química , Isoflavonas/administração & dosagem , Isoflavonas/farmacocinética , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Idoso , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Genisteína/sangue , Genisteína/urina , Meia-Vida , Humanos , Isoflavonas/efeitos adversos , Isoflavonas/sangue , Isoflavonas/farmacologia , Isoflavonas/urina , Pessoa de Meia-Idade
3.
Am J Clin Nutr ; 77(4): 875-82, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12663286

RESUMO

BACKGROUND: Genistein may be useful in the prevention or treatment of prostate cancer; however, it causes genetic damage in cultured human cells. OBJECTIVE: The objective was to assess the potential genotoxicity of a purified soy unconjugated isoflavone mixture in men with prostate cancer. DESIGN: Twenty patients with prostate cancer were treated with 300 mg genistein/d for 28 d and then with 600 mg/d for another 56 d. In peripheral lymphocytes, DNA strand breaks were assessed as nuclear tail moment, chromosomal damage was assessed as micronucleus frequency (MF), and translocations of the MLL gene (11q23) were assessed by using fluorescence in situ hybridization. Values are also reported for 6 healthy men. The studies were performed under Investigational New Drug application no. 54 137 at a tertiary referral academic medical center. RESULTS: No changes in group average or individual nuclear tail moment and MF were observed. We observed a single elevated MF value in one subject that exceeded a clinical threshold set before we initiated the study. A significant decrease in average COMET tail moment was observed on day 28 relative to day 0. We detected no genistein-induced rearrangements of the MLL gene in the 3 subjects we studied with this technique. MF increased significantly in lymphocytes exposed in vitro to unconjugated genistein at concentrations > or = 100 micromol/L. Total genistein never exceeded a peak concentration of 27.1 micro mol/L, and unconjugated genistein never exceeded a peak concentration of 0.32 micromol/L. CONCLUSION: Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture.


Assuntos
Dano ao DNA/efeitos dos fármacos , Glycine max/química , Isoflavonas/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Proto-Oncogenes , Fatores de Transcrição , Adulto , Células Cultivadas , Ensaio Cometa , Proteínas de Ligação a DNA/genética , Deleção de Genes , Genisteína/efeitos adversos , Genisteína/sangue , Genisteína/uso terapêutico , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Isoflavonas/administração & dosagem , Isoflavonas/uso terapêutico , Linfócitos/química , Linfócitos/ultraestrutura , Masculino , Micronúcleos com Defeito Cromossômico/ultraestrutura , Proteína de Leucina Linfoide-Mieloide , Translocação Genética
4.
Med Wieku Rozwoj ; 16(3): 171-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23378394

RESUMO

Recently, scientific literature informed that metabolic conditions in pregnant women may be associated with increased risk for autism and other neurodevelopmental disorders in their offspring. In a cohort study of more than 1000 children between the ages of 2 and 5 years, those who had mothers classified as having "metabolic conditions" (which included diabetes, hypertension, and obesity) during pregnancy were at a significantly higher risk for developing an autism spectrum disorder (ASD) and neurodevelopmental delays. In addition, mothers with obesity were 1.6 times more likely to have a child with ASD and more than twice as likely to have a child with other developmental problems. In the United States, the prevalence of obesity among women of childbearing age is 34%. Moreover, with obesity rates rising steadily, these results appear to raise serious public health implications. The main objective of this Editorial is to propagate the health care improvement based on the translation research approach from basic behavioral sciences and relevant integrative neuroscience to pressing clinical issues that include an understanding of the etiology and assessment of disorders, and the assessment of functioning and development of innovative and culturally appropriate preventive treatment. Behavioral interventions for weight management in pregnancy may include the Transtheoretical Model (TTM) employed in obese pregnant women and then, the comparison with elements of the ecological model. A comparative effectiveness design is to test the effect of tailoring while including one of the most important predictors of screening-physician recommendation: after careful selection of analyzed behaviors from the TTM approach. However, there is also a risk that the evidence may not be conclusive for sustained weigh loss as a primary outcome of the proposed intervention, although the TTM in combination of physical activity and diet tended to produce significant results. Therefore, physicians might use the TTM to convince pregnant women to regulate weight and educate future parents on how to deal with autism at an early age of their children using watchful waiting management.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Obesidade/epidemiologia , Obesidade/prevenção & controle , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Ciências do Comportamento , Causalidade , Pré-Escolar , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Gravidez , Gravidez em Diabéticas/epidemiologia , Pesquisa Translacional Biomédica
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