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2.
Clin Exp Obstet Gynecol ; 37(4): 283-6, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21355458

RESUMEN

OBJECTIVE: To identify clinical, physical, life quality and nutritional aspects of Brazilian women during menopausal transition and postmenopausal periods. METHODS: 115 women agreed to participate in the study. They were divided into two groups: GI--menopausal transition (n = 48) and GII--postmenopause (n = 67). The Kupperman-Blatt Menopausal Index (IMK) and Women's Health Questionnaire (WHQ), Food Frequency Questionnaire and functional capacity were used. All patients were examined and underwent clinical and gynecological examination. RESULTS: There was no significant difference in IMK, WHQ and functional capacity in either group. There was a higher caloric intake, especially in sugars, in postmenopause women than in menopausal transition women. Both groups presented reduced parameters in life quality and functional capacity. CONCLUSION: Our data suggests that there is no significant difference between women in menopausal transition and postmenopause, except in relation to the nutritional parameter. In both groups, the women presented low quality of life and reduced functional capacity.


Asunto(s)
Dieta , Menopausia/fisiología , Posmenopausia/fisiología , Calidad de Vida , Índice de Masa Corporal , Brasil , Sacarosa en la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Humanos , Estado Civil , Persona de Mediana Edad , Fenómenos Fisiológicos de la Nutrición
3.
Cancer Epidemiol Biomarkers Prev ; 3(2): 137-40, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8049634

RESUMEN

Coal tar-treated psoriasis patients were used as a model population to test a newly developed enzyme-linked immunosorbent assay (ELISA) for urinary excretion of benzo(a)pyrene and related polycyclic aromatic hydrocarbons (PAHs). The ability of the ELISA to detect exposure was also compared with that of two previously established biomonitoring methods, measurement of urinary 1-hydroxypyrene by high performance liquid chromatography with fluorescence detection and mutagenicity measured by the Salmonella typhimurium mutagenesis assay. Urine samples were collected from 57 patients and 53 untreated volunteers. Urinary excretion of PAH metabolites, measured by competitive ELISA with a monoclonal antibody (4D5), was elevated in patients (mean, 730 +/- 1370 mumol/mol creatinine) compared with untreated volunteers (110 +/- 90 mumol/mol creatinine; P < 0.0001). 1-Hydroxypyrene also was elevated in patients (mean, 547 +/- 928 mumol/mol creatinine) compared with volunteers (mean, 0.14 +/- 0.17 mumol/mol creatinine; P < 0.0001). Much larger differences between mean values in patients and volunteers were observed with the 1-hydroxypyrene assay compared with the PAH metabolite ELISA. No significant effect of smoking could be detected by either assay. Analysis by the Salmonella typhimurium mutagenesis assay indicated elevated mutagenicity in urine from patients (1410 +/- 2750 revertants/mmol creatinine) compared with volunteers (715 +/- 846 revertants/mmol creatinine; P = 0.072). In all subjects, there was a good correlation between the PAH metabolites and both 1-hydroxypyrene (r = 0.717; P < 0.0001) and urinary mutagenicity (r = 0.317; P = 0.004). These results suggest that the ELISA, which easily can be carried out on large numbers of samples, can be used for monitoring urinary excretion of PAHs in a high exposure population. Ongoing studies are designed to determine its applicability to lower exposure populations.


Asunto(s)
Alquitrán/efectos adversos , Pruebas de Mutagenicidad , Mutágenos/farmacocinética , Compuestos Policíclicos/farmacocinética , Psoriasis/tratamiento farmacológico , Pirenos/farmacocinética , Administración Tópica , Adulto , Cromatografía Líquida de Alta Presión , Alquitrán/administración & dosificación , Alquitrán/farmacocinética , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia PUVA , Psoriasis/orina , Salmonella typhimurium
4.
Cancer Lett ; 129(2): 131-8, 1998 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-9719453

RESUMEN

The tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen in mice, rats and Syrian golden hamsters and a suspected human lung carcinogen. We have reported earlier that structural analogs of the naturally occurring pulmonary toxin 4-ipomeanol (IPO) were non toxic up to 50 micromol/mouse. Because these analogs are in part structurally similar to NNK, they are expected to compete for the same enzymes and/or reactive sites within DNA. Both NNK and IPO are primarily metabolized by cytochrome P450 enzymes in the Clara cells of the lung but also in the liver. We describe here the optimal conditions for the study of NNK metabolism in human liver microsomes and our investigation of four non-toxic IPO analogs as potential inhibitors of NNK activation. The IPO analogs studied were 4-hydroxy-1-phenyl-1-octanone (4-HPO), 1,4-diphenyl-4-hydroxy-1-butanone (DPHB), 4-hydroxy-1-phenylpentane (HPPentane) and amyl benzene (AB). When added to microsomal incubations of human liver cells at a concentration of 100 microM, all of these compounds were strong inhibitors of NNK activation, decreasing the total alpha-hydroxylation of NNK, which is the main pathway of activation, by 60-70% and preventing N-oxidation by 78-86%.


Asunto(s)
Microsomas Hepáticos/metabolismo , Nitrosaminas/metabolismo , Terpenos/farmacología , Antineoplásicos , Biomarcadores/análisis , Biotransformación/efectos de los fármacos , Butanonas/metabolismo , Butanonas/farmacología , Humanos , Hidroxilación/efectos de los fármacos , Cetonas/farmacocinética , Cetonas/farmacología , Microsomas Hepáticos/efectos de los fármacos , Pentanos/farmacología , Piridinas/metabolismo
5.
Chem Biol Interact ; 103(3): 153-66, 1997 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-9134006

RESUMEN

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco specific carcinogen believed to be a causative agent for human lung cancer. To exert its carcinogenic potential, NNK must be metabolically activated, by alpha-hydroxylation, at either the methyl or methylene carbons adjacent to the N-nitroso group. We recently reported the presence of a glucuronide conjugate of 4-(hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (alpha-hydroxymethylNNK-Gluc) in the urine of Phenobarbital (PB) treated rats, and in the media of PB induced hepatocytes incubated with NNK. PB induces the alpha-hydroxylation of NNK, which generates the aglycon, as well as several UDP-glucuronosyl transferases. In the study presented here, we compared the metabolism of NNK to alpha-hydroxymethylNNK-Gluc by PB induced, 3-methylcholanthrene (3-MC) induced and control rat hepatocytes. Media was analyzed for the products of alpha-hydroxylation, N-oxidation and glucuronidation by radioflow HPLC. PB induced both N-oxidation and alpha-hydroxylation of NNK. 3-MC did not induce N-oxidation but induced alpha-hydroxylation more than 10-fold. alpha-HydroxymethylNNK-Gluc was not detected (< 0.05% total metabolites) when control hepatocytes were incubated with 1 to 100 microM NNK. When 3-MC and PB induced hepatocytes were incubated with 1-100 microM NNK alpha-hydroxymethylNNK-Gluc, expressed as the average percent of metabolites, accounted for 0.725 +/- 0.27 and 1.35 +/- 0.24% (+/-S.D.) of the NNK metabolites, respectively. The percent of NNK metabolized to alpha-hydroxymethylNNK-Gluc is small. But this glucuronide is potentially important in NNK carcinogenesis, since its formation results in the direct conjugation of an active metabolite responsible for DNA adduct formation. When PB induced rats were injected with NNK the level of NNK hemoglobin adducts, which can serve as surrogates for DNA adducts, decreased 50% compared to control rats administered NNK. Hepatic microsomal metabolism increased 2-fold and urinary alpha-hydroxymethylNNK-Gluc increased more than 10-fold in PB treated rats. One explanation for the decrease in NNK hemoglobin adducts may be a PB induced increase in the glucuronidation of alpha-hydroxymethylNNK, the metabolite responsible for adduct formation.


Asunto(s)
Carcinógenos/metabolismo , Glucuronatos/metabolismo , Hígado/metabolismo , Metilcolantreno/farmacología , Nitrosaminas/metabolismo , Fenobarbital/farmacología , Animales , Biotransformación , Células Cultivadas , Hemoglobinas/metabolismo , Hidroxilación , Inactivación Metabólica , Hígado/citología , Masculino , Microsomas Hepáticos/metabolismo , Oxidación-Reducción , Ratas , Ratas Endogámicas F344
6.
Sao Paulo Med J ; 115(2): 1403-5, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9460301

RESUMEN

The ACTH test has been used to confirm the diagnosis of adrenal insufficiency and the classic and the non-classic adrenal hyperplasia due to the 3-HSD, 21 OH e 110H deficiencies. This article reviews the historical aspects of the use of ACTH in the diagnosis of hirsutism and points out its mains indications. In spite of new biological molecular advances in the diagnosis of adrenal enzymatic deficiencies, the use of the ACTH test can help the physician to predict both genothipus and fenothipus in populations with hyperandrogenic manifestations due to non-classical or late-onset congenital adrenal hyperplasia.


Asunto(s)
Hormona Adrenocorticotrópica , Hirsutismo/diagnóstico , Humanos , Sistema Hipófiso-Suprarrenal/enzimología
7.
Rev. bras. plantas med ; 14(2): 327-334, 2012. ilus, tab
Artículo en Portugués | LILACS | ID: lil-650674

RESUMEN

Diabetes é alvo interessante para a busca de novos métodos de tratamento com a possibilidade de uso de várias espécies de plantas medicinais. Este trabalho objetivou descrever a prevalência do uso de plantas medicinais consideradas hipoglicemiantes por pacientes diabéticos em Vitória de Santo Antão. O estudo foi do tipo descritivo transversal realizado com 158 pacientes diabéticos atendidos pelo programa HIPERDIA nos PSF's da cidade entre julho de 2009 a maio de 2010, com a coleta de dados realizada por meio de formulário estruturado. Entre os entrevistados, 36% relatavam uso de plantas medicinais consideradas hipoglicemiantes. Foram citadas 35 plantas diferentes pertencentes à 24 famílias, sendo as mais freqüentes: Asteraceae (12,5%) e Myrtaceae (9,37%). A planta medicinal mais prevalente foi a pata de vaca (Bauhinia sp), com 16,8%, seguida por azeitona roxa (Syzygium jambolanum DC.) e insulina (Cissus sicyoides L.). A maioria dos indivíduos (58%) cultivava a planta medicinal que usavam e, entre aqueles que adquiriam, a principal fonte foi a de raizeiros (28,16%).


Diabetes is an attractive target to search for new methods of treatment, with the possibility of using several medicinal plant species. This study aimed to describe the prevalence of the use of medicinal plants considered hypoglycemic for diabetic patients from Vitoria de Santo Antão-Pernambuco State, Brazil. This was a transversal descriptive study conducted with 158 diabetic patients enrolled in the program HIPERDIA at the PSF's of this city, between July 2009 and May 2010 with data collected by means of structured form. Among interviewees, 36% reported the use of medicinal plants considered hypoglycemic. A total of 35 different plants belonging to 24 families were cited and the most frequent species were: Asteraceae (12.5%) and Myrtaceae (9.37%). The most prevalent medicinal plant was "pata-de-vaca" (Bahuinia sp.), with 16.8%, followed by "azeitona roxa" (Syzygium jambolanum DC.) and "insulina" (Cissus sicyoides L.). Most individuals (58%) cultivated the medicinal plant they used, and for those who acquired them, the main source was "raizeiros" [people similar to healers but who only sell medicinal plants] (28.16%).


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Plantas Medicinales/efectos adversos , Diabetes Mellitus/patología , Hipoglucemiantes/administración & dosificación , Fitoterapia/métodos
8.
J Toxicol Clin Toxicol ; 38(6): 631-6, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11185970

RESUMEN

OBJECTIVE: A simple reversed-phase high performance liquid chromatography method with a variable wavelength detection has been developed for determining the commonly used tricyclic antidepressant drugs in plasma. METHODS: The assay procedure involves a liquid-liquid extraction with an initial extraction into hexane:ethyl acetate after basification of the homogenate. The column used was a Supelco Hypersil 5 microm, 150 x 3.2 mm. The mobile phase was acetonitrile, methanol, and phosphate buffer (0.01M, pH 7.4) at 12:3:5 ratio (v/v/v). RESULTS: The recoveries ranged from 89 to 108% and the day-to-day precision was 1.1 to 13% CV depending on the compound. The method is sensitive to 15 ng/mL and linear to 400 ng/mL with a 25 microL injection. CONCLUSION: This method is simple, sensitive, precise, inexpensive, and is currently used in our laboratory for therapeutic monitoring of tricyclics. The data generated by this method were within the range outlined by the College of American Pathologists.


Asunto(s)
Antidepresivos Tricíclicos/sangre , Cromatografía Líquida de Alta Presión/métodos , Humanos , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
9.
Chem Res Toxicol ; 8(5): 772-9, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7548761

RESUMEN

In the rat, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lung tumors independent of the route of administration. To exert its carcinogenic potential, NNK must be metabolically activated. Like most nitrosamines NNK is activated by alpha-hydroxylation. The striking tissue specificity of tumor induction by nitrosamines has been primarily attributed to the efficient alpha-hydroxylation of a particular nitrosamine by its target tissue. Two other factors which may contribute to this are the following: the relative capacity of different tissues to detoxify the alpha-hydroxynitrosamine and the preferential uptake of the active metabolite by the target tissue. In the present study we report the characterization of the O-glucuronide of 4-((hydroxymethyl)nitrosamino)-1-(3-pyridyl)-1-butanone (alpha-hydroxymethylNNK-Gluc). The formation of this glucuronide could either serve as a detoxification pathway or provide a stable transport form of the alpha-hydroxylated metabolite. In addition, the metabolism of NNK to a glucuronide of the alpha-hydroxynitrosamine provides the first definitive evidence for the formation of alpha-hydroxymethylNNK. alpha-HydroxymethylNNK-Gluc was present in the urine of rats treated with phenobarbital (PB) and NNK. It was also formed by hepatocytes from PB-treated rats, accounting for 4% of the total metabolites in the media following incubation with 1 microM NNK. The data that support the identity of this metabolite as alpha-hydroxymethylNNK-Gluc are as follows. (1) Incubation of this metabolite with beta-glucuronidase resulted in the quantitative release of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), the decomposition product of alpha-hydroxymethylNNK.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Carcinógenos/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Glucuronatos/metabolismo , Nitrosaminas/metabolismo , Fenobarbital/farmacología , Acetilación , Animales , Biotransformación , Células Cultivadas , Cromatografía Líquida de Alta Presión , Glucuronidasa/metabolismo , Hígado/citología , Masculino , Fenobarbital/metabolismo , Ratas , Ratas Endogámicas F344 , Espectrometría de Masa de Ion Secundario
10.
Drug Metab Dispos ; 25(2): 154-62, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9029045

RESUMEN

We compared the metabolism in human hepatic microsomes of three tobacco smoke carcinogens believed to be involved in the induction of cancer in humans: benzo[a]pyrene (BaP),4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonomicotine (NNN). The metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK, was also investigated. Although the metabolism of some of these compounds by human enzymes or tissue preparations has been previously examined in some studies, they have never been compared in the same human hepatic samples. Moreover, there have been no previous reports of NNAL metabolism by human tissues or enzymes. The tritium-labeled carcinogens (3 microM) were incubated with 10 different human hepatic microsomal preparations and cofactors for 10-20 min, and the products were analyzed by radioflow HPLC. NNN was the best substrate for oxidative metabolism, with the 5'-hydroxylation pathway being the predominant one observed (mean +/- SD = 31 +/- 17 pmol/min/mg protein). alpha-Hydroxylation of NNK by the methylene and methyl hydroxylation metabolic activation pathways was the next fastest reaction, with rates of 3.1 +/- 1.9 and 3.3 +/- 1.1 pmol/min/mg protein, respectively. Metabolism of BaP resulted in the formation of dihydrodiols and phenols; trans-7,8-dihydro-7,8-dihydroxy-BaP, its major proximate carcinogen, was formed at a rate of 1.1 +/- 0.61 pmol/min/mg protein. alpha-Hydroxylation of NNAL proceeded at a rate of 0.53 +/- 0.26 pmol/min/mg protein. The results of this study demonstrate that human hepatic microsomes metabolize all of these tobacco carcinogens resulting in a substantial stream of electrophilic intermediates capable of binding to DNA. The relative rates of oxidative metabolism to electrophiles or their precursors were NNN > NNK > BaP > NNAL. Correlation studies indicated involvement of cytochrome P4502A6 in the 5'-hydroxylation of NNN and cytochrome P4503A4 in the alpha-methylene hydroxylation and pyridine-N-oxidation of NNK and NNAL. The results of this study provide the first data on the comparative metabolism of these important carcinogens in human hepatic microsomes.


Asunto(s)
Benzo(a)pireno/metabolismo , Carcinógenos/metabolismo , Microsomas Hepáticos/metabolismo , Nitrosaminas/metabolismo , Biotransformación , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Plantas Tóxicas , Nicotiana/química
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