RESUMO
BACKGROUND: The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. PATIENTS AND METHODS: The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. RESULTS: With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile remained unchanged since the previous analysis. CONCLUSIONS: Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Terapia Neoadjuvante/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Fluoruracila/administração & dosagem , Intervalo Livre de Doença , Quimiorradioterapia/métodos , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Quimioterapia Adjuvante/métodos , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Camptotecina/uso terapêuticoRESUMO
Polyphenols are plant food microconstituents that are widely distributed in the human diet, with fruits and fruit-derived products as one of the main dietary sources. Epidemiological studies have shown an inverse relationship between the intake of different classes of polyphenols and the risk of myocardial infarction or cardiovascular disease (CVD) mortality. These compounds have been associated with the promotion of cardiovascular health as evidenced by clinical studies reporting beneficial effects of polyphenol-rich fruit consumption on intermediate markers of cardiovascular diseases. Additionally, animal and in vitro studies have indicated positive roles of polyphenols in preventing dysfunctions associated with the development of cardiovascular diseases. However, the mechanisms of action underlying their beneficial effects appear complex and are not fully understood. This review aims to provide an update on the nutrigenomic effects of different groups of polyphenols from fruits and especially focuses on their cardiovascular protective effects in cell and animal studies.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Frutas/química , Nutrigenômica , Polifenóis/administração & dosagem , Animais , Linhagem Celular , Dieta , Flavanonas , Flavonoides , Expressão Gênica , Promoção da Saúde , Células Endoteliais da Veia Umbilical Humana , HumanosRESUMO
Intake of anthocyanin-rich foods has been associated with a reduced risk of cardiovascular diseases. We recently reported that a nutritional supplementation with a bilberry anthocyanin-rich extract (BE) attenuates atherosclerotic lesion development in apolipoprotein E-deficient (apoEâ»/â») mice. However, the mechanism(s) of their preventive action are not completely understood. Anthocyanins may alter mRNA levels of genes related to atherosclerosis in cultured macrophages and endothelial cells, but in vivo studies remain scarce. The aim of the present study was to explore the in vivo mechanisms of action of the same bilberry extract, administered by supplementation at a nutritional level, in the aorta of apo Eâ»/â» mice using a global transcriptomic approach. This study focused on the early stage of atherosclerosis development for better assessment of BE action on initiation mechanisms of this pathology. After a two week period, plasma lipid and antioxidant capacity were evaluated and the global genomic analysis was carried out using pangenomic microarrays. BE supplementation significantly improved hypercholesterolemia whereas the plasmatic antioxidant status remained unchanged. Nutrigenomic analysis identified 1261 genes which expression was modulated by BE in the aorta. Bioinformatic analysis revealed that these genes are implicated in different cellular processes such as oxidative stress, inflammation, transendothelial migration and angiogenesis, processes associated with atherosclerosis development/protection. Some of the most significantly down-regulated genes included genes coding for AOX1, CYP2E1 or TXNIP implicated in the regulation of oxidative stress, JAM-A coding for adhesion molecules or VEGFR2 implicate in regulation of angiogenesis. Other genes were up-regulated, such as CRB3, CLDN14 or CDH4 potentially associated with increased cell-cell adhesion and decreased paracellular permeability. These results provide a global integrated view of the mechanisms involved in the preventive action of bilberry anthocyanin-rich extract against atherosclerosis.
Assuntos
Antocianinas/farmacologia , Apolipoproteínas E/deficiência , Aterosclerose/genética , Suplementos Nutricionais , Extratos Vegetais/farmacologia , Vaccinium myrtillus/química , Aldeído Oxidase/genética , Aldeído Oxidase/metabolismo , Animais , Antioxidantes/farmacologia , Aorta/metabolismo , Aorta/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Caderinas/genética , Caderinas/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Claudinas/genética , Claudinas/metabolismo , Biologia Computacional , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Regulação para Baixo , Frutas/química , Regulação da Expressão Gênica de Plantas , Lipídeos/sangue , Masculino , Glicoproteínas de Membrana , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Estresse Oxidativo/genética , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Regulação para CimaRESUMO
Visceral leishmaniasis is one of the world's most neglected diseases. Over 90% of the 500,000 annual new cases occur in only five countries: India, Nepal, Bangladesh, Sudan and North-Eastern Brazil, but the disease remains endemic in Southern Europe. We report a case of visceral leishmaniasis in an immunocompetent serviceman after a seven-day stay in the Marseilles region of South-Eastern France. This case is intended to alert clinicians to the possibility of visceral leishmaniasis in patients who develop a febrile illness after returning from travel in Southern European countries.
Assuntos
Leishmaniose Visceral/diagnóstico , Viagem , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Febre/parasitologia , Hepatomegalia/parasitologia , Humanos , Imunocompetência , Leishmaniose Visceral/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Militares , Pancitopenia/parasitologia , Esplenomegalia/parasitologiaRESUMO
The aim of this study was to evaluate the impact of urban air pollution, assessed through reliable indicators of exposure, on asthma and allergies in schoolchildren. A validated dispersion model combining data on traffic conditions, topography, meteorology and background pollution was used to relate 3-yrs averaged concentrations of major urban pollutants at the sites of schools to skin prick tests, exercise-induced asthma and reported asthma and allergies in 6,683 children (9-11 yrs) attending 108 schools randomly selected in six French communities. For the 4,907 children who had resided at their current address for the past 3 yrs, asthma (exercise induced, past year and lifetime) was significantly positively associated with benzene, SO(2), particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen oxides (NO(x)) and CO. In the same children, eczema (lifetime and past year) was significantly positively associated with benzene, PM(10), NO(2), NO(x) and CO, lifetime allergic rhinitis with PM(10) and sensitisation to pollens with benzene and PM(10). Among the 2,213 children residing at their current address since birth, the associations persisted for lifetime asthma with benzene (adjusted OR per interquartile range (95% CI) 1.3 (1.0-1.9)) and PM(10 )(1.4 (1.0-2.0)), and for sensitisation to pollens with volatile organic compounds (1.3 (1.0-1.9)) and PM(10) (1.2 (1.0-1.9)). Accurately modelled urban air pollution was associated with some measures of childhood asthma and allergies.
Assuntos
Poluição do Ar/efeitos adversos , Asma/epidemiologia , Exposição Ambiental , Hipersensibilidade/epidemiologia , Saúde da População Urbana/estatística & dados numéricos , Asma/induzido quimicamente , Benzeno/efeitos adversos , Monóxido de Carbono/efeitos adversos , Criança , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Hipersensibilidade/etiologia , Masculino , Óxidos de Nitrogênio/efeitos adversos , Material Particulado/efeitos adversos , Pólen/efeitos adversos , Rinite Alérgica Sazonal/etiologia , Dióxido de Enxofre/efeitos adversos , Emissões de Veículos , Compostos Orgânicos Voláteis/efeitos adversosRESUMO
Pyomyositis is a primitive infection of the skeletal muscle usually caused by Staphylococcus aureus in tropical areas, and associated with immunodeficiency. We report a 49-year-old immunocompetent woman, living in a temperate climate presenting with a pyomyositis of adductor muscles caused by Escherichia coli. Diagnosis was obtained with magnetic resonance imaging (MRI). Disease course was uneventful after surgical debridement and antibiotics. This case report highlights the usefulness of MRI in the diagnosis of pyomyositis.
Assuntos
Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/diagnóstico , Escherichia coli/isolamento & purificação , Imunocompetência , Músculo Esquelético/microbiologia , Piomiosite/diagnóstico , Piomiosite/microbiologia , Antibacterianos/uso terapêutico , Clima , Desbridamento , Infecções por Escherichia coli/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Piomiosite/terapia , Coxa da Perna , Resultado do TratamentoRESUMO
BACKGROUND: Prognostic factors for pure mucinous carcinomas of the breast are controversial; data on DNA ploidy and S-phase fraction (SPF) are lacking. We examined the relation of these parameters with histological features and patient survival. METHODS: DNA flow cytometry was performed on 69 fresh or frozen pure mucinous carcinomas samples. Results were interpreted according to patient survival. RESULTS: Tumor size exceeded 2 cm in 40.5% of cases. Lymph nodes were involved in 11.5% of cases and never when tumor size was less than 2 cm. Aneuploidy was only observed in one-quarter of the tumors. Very few tumors had a high-SPF or a high histological grade (7.2% of all cases). These two parameters were of prognostic value respectively for disease-free (P=0.035) and overall survival (0.050). Patients with tumors>2 cm had shorter overall survival than patients with tumors≤2 cm (P=0.028). Disease-free and overall survivals were not influenced by nodal status and hormone receptors (HRs) status. Patients with aneuploid tumors had shorter disease-free survival than patients with diploid tumors (P=0.031). The combination of tumor size and DNA ploidy was strongly predictive of survival (P<10(-3)): six patients with large aneuploid tumors had a poor outcome (1-year overall survival 16.7%). CONCLUSION: We identified a subset of patients with a poor prognosis, namely those with large aneuploid tumors. This study confirms the good prognosis of pure mucinous carcinomas, particularly when tumor is less than 2 cm (corresponding to cases without lymph nodes involvement), thus challenging the need for axillary nodal examination.
Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias da Mama/patologia , DNA/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/mortalidade , Adulto , Idoso , Aneuploidia , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , DNA/metabolismo , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Carga TumoralRESUMO
INTRODUCTION: After having increased for some time, the prevalence of allergic diseases may have reached a plateau. During this increase, considerable concomitant changes in air pollution have occurred. Photo-oxidant air pollution, related to traffic, has become preponderant. The implication of air pollution in the epidemic of allergies is still debated. BACKGROUND: Experimental studies have suggested that the effect of air pollutants, including particulates and ozone, on the worsening and even the induction of allergies is biologically plausible. In addition, epidemiological studies have shown a short term impact of the peaks of air pollution on exacerbations of asthma. On the other hand, the results of epidemiological studies dealing with the long-term effects of chronic exposure to air pollution on the prevalence of allergies are less consistent. VIEWPOINTS: The implementation of new-born cohorts, the use of dispersion models to improve exposure assessment and the study of gene-environment correlations, should increase our knowledge of the role of traffic-related air pollutants in the development of allergies and identify subjects more sensitive to their effects. CONCLUSIONS: Some traffic-related air pollutants may have played a more important role in the increase in the prevalence of allergies than was assumed from the first epidemiological studies.
Assuntos
Poluição do Ar/efeitos adversos , Hipersensibilidade Respiratória/etiologia , Exposição Ambiental/efeitos adversos , Humanos , Hipersensibilidade Respiratória/epidemiologia , Fatores de TempoRESUMO
Acute ischemic stroke is a leading cause of death and severe disability in industrialised countries and also in many developing countries. An excessive amount of free radicals is generated during cerebral ischemia, which significantly contributes to brain damage. Therefore, an increasing interest has been devoted to the potential benefits of antioxidant compounds in ischemic stroke patients. In this review, we examined the most relevant observational studies concerning the relationship between dietary antioxidants and ischemic stroke as well as clinical trials investigating the effects of single or multiple antioxidant supplementation in the prevention or treatment of acute ischemic stroke. Furthermore, we reviewed the most promising antioxidant compounds, i.e. dehydroascorbic acid, alpha-tocotrienol, gamma-tocopherol, flavonoids, resveratrol and gingko biloba, tested in animal models of acute ischemic stroke. Finally, we carefully evaluated the reasons for the discrepancy between experimental and clinical studies, and provided recommendations to improve the translation of the results obtained in animal models to patients with acute ischemic stroke.
Assuntos
Antioxidantes/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/dietoterapia , Dieta , Acidente Vascular Cerebral/dietoterapia , Acidente Vascular Cerebral/etiologia , Animais , Ácido Ascórbico/uso terapêutico , Encéfalo/patologia , Isquemia Encefálica/prevenção & controle , Frutas , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Risco , Acidente Vascular Cerebral/prevenção & controle , Verduras , Vitamina A/uso terapêutico , Vitamina E/uso terapêuticoRESUMO
Amatoxin poisoning constitutes the main cause of death due to mushroom intoxication in Europe. This one was initially reported for the ingestion of Amanita phalloides with frequently fatal outcome. Prognosis of amatoxin poisoning initialy depends on the acute deshydratation and secondarily of the liver failure. Emergency liver transplantation is sometimes necessary. With the knowledge of mushroom, most of them involved other species which can often be linked to edible mushroom. We report a collective intoxication by Lepiota brunneoincarnata.
Assuntos
Intoxicação Alimentar por Cogumelos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intoxicação Alimentar por Cogumelos/diagnóstico , Intoxicação Alimentar por Cogumelos/terapiaRESUMO
The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/prevenção & controle , Remodelação Óssea/efeitos dos fármacos , Hesperidina/farmacologia , Hipolipemiantes/farmacologia , Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Fatores Etários , Aminoácidos/urina , Animais , Fenômenos Biomecânicos , Composição Corporal , Conservadores da Densidade Óssea/sangue , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/fisiopatologia , Reabsorção Óssea/prevenção & controle , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Fêmur/fisiopatologia , Hesperidina/sangue , Hesperidina/uso terapêutico , Hipolipemiantes/sangue , Hipolipemiantes/uso terapêutico , Osteocalcina/sangue , Osteoporose/etiologia , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Ratos , Ratos Wistar , Triglicerídeos/sangue , Útero/efeitos dos fármacos , Útero/patologiaRESUMO
Cushing's syndrome is rare and remains a challenge to diagnose. Particularly difficult are the differentiation between Cushing's syndrome and Pseudo-Cushing's states and between the two forms of ACTH dependent Cushing's: Cushing's disease and ectopic ACTH syndrome. We report the case of a patient diagnosed with a metastatic small cells lung carcinoma associated with ectopic ACTH-syndrome. Hypokalaemia was a clue to diagnosis. We focus on critical questions addressing diagnosis and differential diagnosis of Cushing's syndrome and we explain the mechanism of hypokalaemia.
Assuntos
Síndrome de ACTH Ectópico/sangue , Carcinoma de Células Pequenas/diagnóstico , Síndrome de Cushing/diagnóstico , Hipopotassemia/sangue , Neoplasias Pulmonares/diagnóstico , Síndrome de ACTH Ectópico/etiologia , Adulto , Análise Química do Sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/patologia , Síndrome de Cushing/sangue , Diagnóstico Diferencial , Feminino , Humanos , Hipopotassemia/etiologia , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Metástase NeoplásicaRESUMO
Plant extracts rich in polyphenols (PERP) could represent interesting alternative antioxidants but their use in ruminants needs further investigation since the antioxidant capacity of PERP could be altered by digestive processes. The aim of the study was to investigate the bioavailability and the antioxidant capacity of four PERP (rosemary; grape; citrus; marigold) in ruminants made highly susceptible to lipoperoxidation by a continuous linseed oil infusion (4 % DM) in the duodenum. The PERP were given, as a single acute dose (10 % DM), directly into the rumen of sheep (n 5) and blood was then collected every 3 h over a period of 30 h. Grape was particularly efficient to enhance the plasma total antioxidant status (P < 0.05). Moreover, many new polyphenols were detected in the plasma and the identification of epicatechin in the grape group suggested that, contrary to monogastrics, ruminants can benefit from the antioxidant effect of polymeric proanthocyanidins. Finally, the four PERP tested, and more especially marigold, significantly reduced plasma susceptibility to liperoxidation (mean increase of lag phase: +5.9 min, P < 0.02; mean reduction of oxidation rate: - 1.7 A234/min, P < 0.01). In conclusion, the digestive processes in ruminants do not inhibit the antioxidant properties of PERP in vivo and are beneficial by improving the biological effect of polymeric proanthocyanidins. Further experiments are now necessary to determine the optimum dose of administration and to characterize the bioactive molecules.
Assuntos
Antioxidantes/farmacocinética , Flavonoides/farmacocinética , Peroxidação de Lipídeos/efeitos dos fármacos , Fenóis/farmacocinética , Extratos Vegetais/farmacocinética , Ração Animal , Animais , Disponibilidade Biológica , Estresse Oxidativo , Polifenóis , Ovinos , Carneiro Doméstico , Resultado do TratamentoRESUMO
Flavanones, the main polyphenols of citrus fruits, are thought to contribute to the protective effects of these fruits against cardiovascular diseases and cancer. The metabolism of naringin (naringenin 7-O-neohesperidoside) is studied here in healthy (sham-operated, ShO) and tumor-bearing (TuB) rats. The tumor was induced by implanting Yoshida's sarcoma in hindlimb. Both groups received for 7 days a semi-synthetic diet containing 0.5% naringin in per feeding conditions. Flavanones were analyzed in plasma, liver, kidney and urine by tandem mass spectrometry. Naringenin conjugates (essentially glucuronides) accounted for up to 98% of the total flavanones in plasma. Low amounts of hesperetin (4'-O-methyl naringénine) and isosakuranetin (3'-hydroxy-4'-O-methylnaringenin) were also detected in all biological samples and accounted for 2% of the total flavanones in plasma. They were largely present as aglycones. The in vivo hydroxylation of flavanones is described here for the first time. Total concentrations of naringenin metabolites reached 17.3+/-2.7 microM in plasma 6 hours after the beginning of the meal in healthy rats and only 10.6+/-1.3 microM in TuB rats. The nature of metabolites was similar in both healthy and TuB rats and in plasma, tissues and urine. The lower concentration of flavanones in the TuB rats suggests that disease and more particularly cancer, may affect the bioavailability of flavonoids.
Assuntos
Flavanonas/metabolismo , Neoplasias Experimentais/metabolismo , Animais , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: As more and more postmenopausal women are taking soy isoflavone supplementation for relieving menopausal symptoms, we investigated the impact of chronic exposure on their bioavailability, with focus on achievable plasma concentrations and potential stimulation of the capacity to produce equol. SUBJECTS: A total of 12 Caucasian postmenopausal women. INTERVENTION: Volunteers ingested 100 mg isoflavones/day (aglycone equivalents, in cereal bars and yoghurts) for 1 month. Plasma concentrations of metabolites at 2, 4, 6, 8, 10, 12 and 24 h postdose, as well as urinary excretion in fractions over 36 h were compared between days 1 and 30. RESULTS: Similar plasma kinetic curves were obtained at day 1 and day 30 for genistein and daidzein. Maximum plasma concentrations were 1.68+/-0.68 micromol/l on day 1 compared to 2.27+/-0.76 micromol/l on day 30 for daidzein (P=0.056), and 3.88+/-1.50 micromol/l on day 1 compared to 5.30+/-2.38 micromol/l on day 30 for genistein (P=0.091). Urinary excretion of daidzein and genistein did not differ significantly between days 1 and 30. Maximum plasma concentration of equol increased significantly from 0.31+/-0.27 to 0.99+/-0.51 micromol/l for equol-producer volunteers (P=0.046). However, the seven volunteers who were classified as non-equol producers on day 1 did not acquire the ability to produce equol after 1-month exposure. CONCLUSIONS: Chronic exposure to isoflavones in postmenopausal women resulted in plasma concentrations as high as 2.5-5 micromol/l of each isoflavone, but did not induce the ability to produce equol.
Assuntos
Glycine max/química , Isoflavonas/farmacocinética , Pós-Menopausa/efeitos dos fármacos , Administração Oral , Idoso , Área Sob a Curva , Disponibilidade Biológica , Suplementos Nutricionais , Equol , Feminino , Genisteína/sangue , Genisteína/urina , Humanos , Isoflavonas/administração & dosagem , Isoflavonas/biossíntese , Isoflavonas/sangue , Isoflavonas/urina , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pós-Menopausa/urina , Fatores de TempoRESUMO
BACKGROUND: After ingestion of a complex meal containing foods and beverages of plant origin, different polyphenols are likely to be simultaneously present in the intestine. However, almost nothing is known about their interactions and possible consequences on their bioavailability. AIM OF THE STUDY: The present study deals with the intestinal absorption and splanchnic metabolism of three polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the small intestine alone or in combination, at different doses (15 and 120 microM). METHODS: The fate of polyphenols in the small intestine was studied using a rat in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile and plasma by HPLC. RESULTS: Whatever the perfused dose, the efficiency of the net transfer towards the enterocyte was similar for the three polyphenols and not significantly modified by any association between these molecules. However, FA largely differed from the two flavonoids by its low intestinal secretion of conjugates. When perfused at 15 microM, the secretion of conjugates back to the lumen represented 6.2% of the net transfer into the enterocytes for FA compared to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal conjugation and secretion of conjugates back to the gut lumen varied with the dose of flavonoids: saturation of conjugation was observed for the highest dose or when a high dose of a second flavonoid was perfused simultaneously. Intensity of the biliary secretion substantially differed among tested polyphenols: 7.7% of the net transfer for FA vs 50% for genistein or hesperetin. The extent of the enterohepatic cycling of these polyphenols was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine. CONCLUSION: Genistein and hesperetin appeared less available than FA for peripheral tissues because of a high intestinal and biliary secretion of their conjugates. Moreover, data suggest that a high polyphenol intake may improve their bioavailability due to saturation of the intestinal secretion of conjugates.
Assuntos
Flavonoides/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/metabolismo , Fígado/metabolismo , Fenóis/farmacocinética , Animais , Ductos Biliares/metabolismo , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacocinética , Relação Dose-Resposta a Droga , Flavonoides/química , Genisteína/química , Genisteína/farmacocinética , Hesperidina/química , Hesperidina/farmacocinética , Masculino , Estrutura Molecular , Perfusão , Fenóis/química , Polifenóis , Ratos , Ratos WistarRESUMO
BACKGROUND: The impact of air pollution on asthma and allergies still remains a debate. OBJECTIVE: Our cross-sectional study was intended to analyse the associations between long-term exposure to background air pollution and atopic and respiratory outcomes in a large population-based sample of schoolchildren. METHODS: Six thousand six hundred and seventy-two children aged 9-11 years recruited from 108 randomly schools in six French cities underwent a clinical examination including a skin prick test (SPT) to common allergens, exercise-induced bronchial reactivity (EIB) and skin examination for flexural dermatitis. The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis was assessed by a standardized health questionnaire completed by the parents. Three-year-averaged concentrations of air pollutants (NO2, SO2, PM10 and O3) were calculated at children' schools using measurements of background monitoring stations. RESULTS: After adjusting for confounders, EIB, lifetime asthma and lifetime AR were found to be positively related to an increase in the exposure to SO2, PM10 and O3. The adjusted odds ratios (aOR) per increase of 5 microg/m3 of SO2 was 1.39 (95% confidence interval (CI)=1.15-1.66) for EIB and 1.19 (1.00-1.41) for lifetime asthma. The aOR for lifetime AR per increase of 10 microg/m3 of PM10 was 1.32 (CI=1.04-1.68). Moreover, SPT positivity was associated with O3 (aOR=1.34; CI=1.24-1.46). Associations with past year symptoms were consistent, even if not always statistically significant. Results persisted in long-term resident (current address for at least 8 years) children. However, no consistent positive association was found with NO2. CONCLUSIONS: A moderate increase in long-term exposure to background ambient air pollution was associated with an increased prevalence of respiratory and atopic indicators in children.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Hipersensibilidade Imediata/etiologia , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Asma/epidemiologia , Asma/etiologia , Hiper-Reatividade Brônquica/epidemiologia , Hiper-Reatividade Brônquica/etiologia , Criança , Estudos Transversais , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Feminino , França/epidemiologia , Humanos , Masculino , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Ozônio/efeitos adversos , Ozônio/análise , Prevalência , Rinite/epidemiologia , Rinite/etiologia , Instituições Acadêmicas , Testes Cutâneos/métodos , Dióxido de Enxofre/efeitos adversos , Dióxido de Enxofre/análise , Emissões de Veículos/efeitos adversos , Emissões de Veículos/análiseRESUMO
BACKGROUND: Food allergy (FA) is an important health problem. However, epidemiological studies at the population level are scarce. We assessed the prevalence of FA and its associations with respiratory manifestations among schoolchildren. METHODS: A total of 6672 schoolchildren aged 9-11 years recruited from 108 randomly chosen schools in six French cities underwent a clinical examination including skin prick test (SPT) to common food and aeroallergens and the standardized protocol of the run test to assess exercise-induced bronchial hyper-responsiveness (EIB). Asthma, allergic rhinitis (AR) and clinical symptoms of FA were determined using a standardized questionnaire completed by parents. RESULTS: About 2.1% of the children reported symptoms of FA, 1.9% were sensitized to food allergens, and 0.1% had SP-tested FA. The AR was more prevalent than asthma (20.0% lifetime, 11.9% past year vs 9.8%, 8.7% respectively). Reported FA, food sensitization and SP-tested FA were all positively associated with asthma and AR (P < 0.001). These associations persisted also for FA not manifesting as respiratory symptoms (P < 0.001). Asthma and AR remained significantly associated with reported symptoms of FA and allergic sensitization to food allergens after adjustment for confounders as well as for sensitization to aeroallergens. No relationship existed between EIB (9.0%) and FA. CONCLUSION: The relationships between FA and asthma and AR could be totally explained neither by the existence of respiratory manifestations of FA nor by sensitization to aeroallergens. The FA might intervene differently in asthma and AR.
Assuntos
Asma/complicações , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/epidemiologia , Rinite/complicações , Criança , Feminino , França/epidemiologia , Humanos , Masculino , PrevalênciaRESUMO
Endometrial stromal sarcoma is a rare malignant uterine tumor. We report 4 cases of low-grade endometrial stromal sarcoma, corresponding to the form with a mitotic index at less than 10 mitoses per 10 high power fields (HPF), from which we carried out a review of the literature and defined the potential interest of hormone therapy and chemotherapy by etoposide. Generally diagnosed in pre-menopause, the main clinical signs, which are not very specific, are metrorrhagia and pelvic pain. The etiologic diagnosis is established from the pathology analysis. Intravascular extension, which is observed in nearly 50% of patients, should evoke the disease. The initial treatment is mainly based open surgery, generally total hysterectomy with annexectomy. There is no effective adjuvant treatment. The potential of reccurences remains around 50% with a 34-month median. Several therapeutic options are possible after recurrence but no standard treatment has been established. We are mainly interested in three medical options but the surgery remains an alternative of choice. Chemotherapy by oral etoposide offers easy administration, good compliance and acceptable toxicity with median 20-month remission in 3 patients before progression. Hormone therapy with progestogens (hormone receptor expression of the tumor is 71% for estrogens and 95% for progesterone) is widely studied in the literature with a 46% response rate and 46% rate of disease stabilization. Hormone therapy with an anti-aromatase appears to be a promising treatment according to the bibliographic references on this subject. Overall, prognosis of low-grade endometrial sarcoma is relatively good with 100% survival at 5 years. The progression pattern is slow, requiring regular and prolonged surveillance.