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1.
Inorg Chem ; 62(31): 12392-12402, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37478498

RESUMO

The influence of manganese modification on the spectroscopic features of manganese-doped CeO2 systems synthesized by the microwave-assisted hydrothermal route and their correlation with the presence of O defective structures were verified, focusing on their interaction with poisonous atmospheres. Raman and electron paramagnetic resonance studies confirmed the presence of defective clusters formed by dipoles and/or quadrupoles. The number of paramagnetic species was found to be inversely proportional to the doping concentration, resulting in an increase in the Mn2+ signal, likely due to the reduction of Mn3+ species after the interaction with CO. X-ray photoelectron spectroscopy data showed the pure system with 33% of its cerium species in the Ce3+ configuration, with an abrupt decrease to 19%, after the first modification with Mn, suggesting that 14% of the Ce3+ species are donating one electron to the Mn2+ ions, thus becoming nonparamagnetic Ce4+ species. On the contrary, 58% of the manganese species remain in the Mn2+ configuration with five unpaired electrons, corroborating the paramagnetic feature of the samples seen in the electron paramagnetic resonance study.

2.
Nutr Metab Cardiovasc Dis ; 24(3): 328-35, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24462043

RESUMO

BACKGROUND AND AIMS: Reduction of cardiovascular risk with high consumption of fish in diet is still a matter of debate, and concerns about heavy metal contamination have limited consumption of oily fish. We aimed to evaluate the effect of regular ingestion of white fish on cardiovascular risk factors in patients with metabolic syndrome. METHODS AND RESULTS: Multicenter randomized crossover clinical trial including 273 individuals with metabolic syndrome. An 8-week only-one dietary intervention: 100 g/d of white fish (Namibia hake) with advice on a healthy diet, compared with no fish or seafood with advice on a healthy diet. Outcomes were lipid profile, individual components of the metabolic syndrome, serum insulin concentrations, homeostasis model of insulin resistance, serum C-reactive protein and serum fatty acid levels. We found a significant lowering effect of the intervention with white fish on waist circumference (P < 0.001) and diastolic blood pressure (P = 0.014). A significant lowering effect was also shown after the dietary intervention with fish on serum LDL concentrations (P = 0.048), whereas no significant effects were found on serum HDL or triglyceride concentrations. A significant rise (P < 0.001) in serum EPA and DHA fatty acids was observed following white fish consumption. Overall adherence to the intervention was good and no adverse events were found. CONCLUSION: In individuals with metabolic syndrome, regular consumption of hake reduces LDL cholesterol concentrations, waist circumference and blood pressure components of the metabolic syndrome. CLINICAL TRIAL REGISTRY: White Fish for Cardiovascular Risk Factors in Patients with Metabolic Syndrome Study, Registered under ClinicalTrials.gov Identifier: NCT01758601.


Assuntos
Doenças Cardiovasculares/sangue , Carne , Síndrome Metabólica/sangue , Alimentos Marinhos , Idoso , Animais , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Ácidos Graxos/sangue , Feminino , Peixes , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/dietoterapia , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue , Circunferência da Cintura
3.
Food Chem ; 384: 132530, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35227997

RESUMO

A new, fast, simple, and effective ultrasound-assisted dispersive liquid-liquid microextraction procedure (UA-DLLME) for the gas chromatography-mass spectrometry (GC-MS) determination of malondialdehyde, acrolein, and 4-hydroxy-2-nonenal in beverages was successfully developed. 2,4-Dinitrophenylhydrazine derivatization was performed during extraction. An asymmetrical 3541//18 screening design and a central composite surface response design were used to investigate the influence of the most critical factors during the extraction process (ultrasound time and temperature, extraction and disperser solvents volumes, salt addition, and derivatization reagent concentration). According to FDA guidelines, the method was validated, achieving good linearities with r2 ≥ 0.9982, recoveries between 94.0 and 102.4%, and reproducibility with RSD lower than 4.5%. The method was applied to simultaneously determine the compounds in 60 different beverage samples, including beer, coffee, black tea, and fruit juices. The presence of secondary lipid oxidation products is demonstrated in beverages with a strong roasting process or oxidation.


Assuntos
Microextração em Fase Líquida , Acroleína/análise , Aldeídos , Bebidas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Limite de Detecção , Microextração em Fase Líquida/métodos , Malondialdeído/análise , Reprodutibilidade dos Testes
4.
Nat Commun ; 11(1): 5060, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033246

RESUMO

Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.


Assuntos
Sistemas CRISPR-Cas/genética , Neoplasias/genética , Fusão Oncogênica/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Doxorrubicina/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Deleção de Genes , Loci Gênicos , Instabilidade Genômica , Células HEK293 , Humanos , Íntrons/genética , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas de Fusão Oncogênica/genética , RNA Guia de Cinetoplastídeos/metabolismo , Reprodutibilidade dos Testes , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Rev Esp Quimioter ; 32(2): 178-182, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-30834736

RESUMO

OBJECTIVE: To describe the clinical-epidemiological characteristics of a series of suspected systemic adverse reactions registered with the 23 serotype pneumococcal polysaccharide vaccine (PNEUMOVAX23®). Calculate the cumulative incidence of the reaction and know if similar and/or compatible cases have been described in the scientific literature or in pharmacovigilance. METHODS: Observational and retrospective study realized between 01/12/2015 and 30/09/2017 in the Vaccines Unit of an autonomic reference hospital. We calculated the cumulative incidence of the adverse reaction for that vaccine. The common pharmacovigilance database (FEDRA) was consulted. RESULTS: Nine systemic adverse reactions were recorded (flushing + bronchospasm + SatO2<95%). The cumulative incidence was 1.036%. The outcome was recovered/resolved for everyone. No similar and/or compatible cases were found. CONCLUSIONS: The reactions described do not appear in the PNEUMOVAX23® data sheet. Epidemiologically, no causal relationship can be established between the symptoms and the variables studied. This study could be the basis for more detailed research that could modify the vaccine data sheet.


Assuntos
Espasmo Brônquico/induzido quimicamente , Espasmo Brônquico/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Rubor/induzido quimicamente , Rubor/epidemiologia , Vacinas Pneumocócicas/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
6.
J Chromatogr A ; 1548: 19-26, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29555360

RESUMO

A fast and effective method using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach which includes partitioned liquid-liquid extraction (PLLE) and dispersive solid phase extraction (dSPE) clean-up step for the determination of seven 3-monochloropropane-1,2-diol (3-MCPD) fatty acid diesters in vegetable oils is developed and validated according to the Food and Drug Administration (FDA) guidelines. Due to the complexity of the matrices, combination of silica based sorbents (Silica Strong Anion Exchange (Si-SAX), Supel™ QuE Z-Sep+ (Z-Sep+) and Primary Secondary Amine (PSA) were tested for lipid removal. The effect of several experimental factors on the efficiency of the extraction procedure was studied by a screening design 3422//16 and a response surface Doehlert design. The separation and determination was carried out by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The method provided suitable linearity (r2 > 0.9960), precision (relative standard deviation (RSD) lower than 10%) and accuracy, in terms of recovery. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 10 to 20 µg kg -1 and from 25 to 50 µg kg-1, respectively. The recoveries at three spiking levels of 100, 250, and 500 µg kg-1 were over the range of 71.4-122.9% with RSD lower than 13%. The method was successfully applied in edible oils and fatty food samples. The results provide valuable information to assess the risk of exposure to these foodborne contaminants.


Assuntos
Cromatografia Líquida/métodos , Ésteres/análise , Extração Líquido-Líquido/métodos , Óleos de Plantas/química , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , alfa-Cloridrina/análise , Limite de Detecção , Margarina/análise , Reprodutibilidade dos Testes
7.
J Endocrinol Invest ; 30(3): 224-9, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17505156

RESUMO

UNLABELLED: As hypopituitarism is frequent in patients who have suffered a traumatic brain injury (TBI) a hormonal check-up is necessary. However, the prevalence of TBI is so large that the number of potential candidates to be tested is difficult to manage, in particular for GH deficiency diagnosis that requires cumbersome and expensive dynamic tests. GHRH plus GH-releasing hexapeptide (GHRP-6) is a safe and effective test capable of segregating normal subjects from GH deficient patients. As the GHRH+GHRP-6 test induces GH peaks consistently in the first 30 min, the working hypothesis assessed in this study was whether a single determination of GH 30 min after stimulus could provide the same biochemical classification as the whole secretory curve. A total of 83 subjects who suffered TBI at least one year before the study were administered GHRH 1 mug/kg iv plus GHRP-6 1 mug/kg iv at 0 min, and blood samples were obtained at regular intervals. GH was determined in all samples. An excellent correlation was observed between GH values at 30 min and GH peaks (r=0.972, p<0.0001). When comparing the 30-min GH values against the peaks, the biochemical classification changed only in 5 out of 83 subjects from normal GH secretion to uncertain. CONCLUSIONS: The GHRH+GHRP-6 test is convenient, safe and in patients with TBI can be reduced to a single fixed GH determination 30 min after stimulus without losing diagnostic power.


Assuntos
Lesões Encefálicas/sangue , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento Humano/sangue , Hipopituitarismo/sangue , Hipopituitarismo/diagnóstico , Oligopeptídeos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Somatotrofos/metabolismo , Fatores de Tempo
8.
Int J Impot Res ; 18(4): 375-81, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16395325

RESUMO

Although erectile dysfunction (ED) has been considered a complication of other medical conditions, clinicians and researchers suggest that ED may serve as a clinical marker of vascular health. This retrospective claims study examined the prevalence of predefined comorbid conditions in men with ED (N=301 994) in the 12 months before and the 6 months following ED diagnosis. Consistent with previous research, comorbid conditions were prevalent among men with ED. Comorbid conditions were most often diagnosed before an ED diagnosis, although new diagnoses in the 6 months following an ED diagnosis were common and occured more frequently than new diagnoses in a matched sample of men without ED during the same period. Differences by age, region and insurance coverage for ED medications were also examined. Findings support previous research that suggests ED may serve as a marker for previously undetected comorbid conditions.


Assuntos
Disfunção Erétil/diagnóstico , Disfunção Erétil/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Bases de Dados Factuais , Disfunção Erétil/tratamento farmacológico , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Inibidores de Fosfodiesterase/economia , Inibidores de Fosfodiesterase/uso terapêutico , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Work ; 27(2): 143-51, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16971761

RESUMO

The factors that influence time missed from work among individuals diagnosed with multiple sclerosis were the focus of this study. Records of individuals who were employed and diagnosed with multiple sclerosis between the years 1999 and 2002 (N=284) were examined for details pertaining to their medical claims. Multivariate regressions, controlling for demographic characteristics, type of immunomodulatory medication, and overall severity of illness, were used in the examination of the total number of days missed from work for any reason and those missed due to absenteeism, short-term disability, or worker's compensation. Results indicate that lost work time is affected by severity of illness, and type of immunomodulatory therapy. Comparing individuals treated with the specific immunomodulator glatiramer acetate, interferon beta-1a (intramuscular), or interferon beta-1b, to those who did not receive multiple sclerosis medications of this type; only glatiramer acetate was associated with significantly fewer days missed from work for short term disability (18.24 fewer days, P<0.03), worker's compensation (29.50 fewer days, P<0.04) or any reason (53.70 fewer days, P< 0.003).


Assuntos
Absenteísmo , Adjuvantes Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/psicologia , Peptídeos/uso terapêutico , Adulto , Emprego , Feminino , Acetato de Glatiramer , Humanos , Interferon beta-1a , Interferon beta-1b , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
J Diabetes Complications ; 30(2): 212-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26689451

RESUMO

AIMS: Examine the association between obesity and glycemic control among patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). METHODS: Data from US physician electronic health records (Humedica®) from 2009-2011 were utilized. Patients were defined as having above-target glycemic control if they had an HbA1c ≥7% at any time during the study period. Multinomial logistic regressions were conducted separately for T1DM and T2DM patients, and examined associations between BMI categories and probability of having above-target glycemic control (≥7% and <8%, ≥8% and <9%, or ≥9%) while controlling for patient demographics, general health, comorbid conditions, and antihyperglycemic medication use. RESULTS: There were 14,028 T1DM and 248,567 T2DM patients; 47.8% of T1DM and 63.4% of T2DM were obese (BMI ≥30kg/m(2)). For T1DM, being overweight (BMI 25-<30), obese class I (30-<35), II (35-<40), or III (≥40) was associated with a significantly higher probability of having HbA1c≥8% and <9% or ≥9%, while being overweight was associated with a significantly higher probability of having HbA1c ≥7% and <8% compared to normal BMI (BMI≥18.5 and<25). For T2DM patients, being overweight, obese class I, II, or III was associated with a significantly higher probability of having HbA1c ≥7% and <8%, ≥8% and <9%, or ≥9%. CONCLUSIONS: For both T1DM and T2DM patients, there were positive and statistically significant associations between being overweight or obese and having suboptimal glycemic control. These findings quantify the associations between obesity and glycemic control, and highlight the potential importance of individual characteristics on glycemic control.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Obesidade/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Médicos , Estados Unidos/epidemiologia
12.
AJNR Am J Neuroradiol ; 37(1): 28-36, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26450533

RESUMO

BACKGROUND AND PURPOSE: Early assessment of treatment response is critical in patients with glioblastomas. A combination of DTI and DSC perfusion imaging parameters was evaluated to distinguish glioblastomas with true progression from mixed response and pseudoprogression. MATERIALS AND METHODS: Forty-one patients with glioblastomas exhibiting enhancing lesions within 6 months after completion of chemoradiation therapy were retrospectively studied. All patients underwent surgery after MR imaging and were histologically classified as having true progression (>75% tumor), mixed response (25%-75% tumor), or pseudoprogression (<25% tumor). Mean diffusivity, fractional anisotropy, linear anisotropy coefficient, planar anisotropy coefficient, spheric anisotropy coefficient, and maximum relative cerebral blood volume values were measured from the enhancing tissue. A multivariate logistic regression analysis was used to determine the best model for classification of true progression from mixed response or pseudoprogression. RESULTS: Significantly elevated maximum relative cerebral blood volume, fractional anisotropy, linear anisotropy coefficient, and planar anisotropy coefficient and decreased spheric anisotropy coefficient were observed in true progression compared with pseudoprogression (P < .05). There were also significant differences in maximum relative cerebral blood volume, fractional anisotropy, planar anisotropy coefficient, and spheric anisotropy coefficient measurements between mixed response and true progression groups. The best model to distinguish true progression from non-true progression (pseudoprogression and mixed) consisted of fractional anisotropy, linear anisotropy coefficient, and maximum relative cerebral blood volume, resulting in an area under the curve of 0.905. This model also differentiated true progression from mixed response with an area under the curve of 0.901. A combination of fractional anisotropy and maximum relative cerebral blood volume differentiated pseudoprogression from nonpseudoprogression (true progression and mixed) with an area under the curve of 0.807. CONCLUSIONS: DTI and DSC perfusion imaging can improve accuracy in assessing treatment response and may aid in individualized treatment of patients with glioblastomas.


Assuntos
Neoplasias Encefálicas/patologia , Imagem de Tensor de Difusão/métodos , Progressão da Doença , Glioblastoma/patologia , Imageamento por Ressonância Magnética/métodos , Idoso , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Feminino , Glioblastoma/terapia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
13.
Biochim Biophys Acta ; 1329(2): 269-77, 1997 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-9371418

RESUMO

It has been reported that cis-unsaturated free fatty acids (cis-FFA) block intracellular Ca2+ rise in EGFR T17 and GH3 cells by perturbing the generation of Ins(1,4,5)P3. In the present work, it was found that cis-FFA did not alter potassium-induced cell depolarization in GH3 cells, while blocking Ca2+ rise and GH secretion. Interestingly enough, saturated or trans-unsaturated FFA exert the opposite actions, i.e., they block cell depolarization without altering Ca2+ rise and hormone secretion. As depolarization activates GH3 cells via direct opening of Ca2+ channels with no generation of intracellular mediators, these results suggest that cis-FFA act by a direct perturbation of the Ca2+ channel opening.


Assuntos
Canais de Cálcio/fisiologia , Cálcio/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Ácidos Graxos Insaturados/farmacologia , Hormônio do Crescimento/metabolismo , Hipófise/fisiologia , Cloreto de Potássio/farmacologia , Animais , Canais de Cálcio/química , Canais de Cálcio/efeitos dos fármacos , Células Cultivadas , Etanol/farmacologia , Gramicidina/farmacologia , Cinética , Potenciais da Membrana/efeitos dos fármacos , Nimodipina/farmacologia , Ácido Oleico/farmacologia , Ácidos Oleicos , Hipófise/efeitos dos fármacos , Neoplasias Hipofisárias , Prolactina/metabolismo , Ratos , Ratos Sprague-Dawley , Ácidos Esteáricos/farmacologia , Estereoisomerismo , Células Tumorais Cultivadas
14.
J Clin Endocrinol Metab ; 82(9): 2849-55, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9284709

RESUMO

UNLABELLED: It is commonly accepted that at least in girls puberty starts when a minimum level of body mass or a certain amount of body fat are present. However the precise signal by which adipose stores inform the hypothalamus of the degree of energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. To understand whether leptin is the adipose tissue signal that allows puberty, 789 normal children of both sexes, age 5-15 yr, were transversally studied. Leptin levels, as well as gonadal and gonadotropins, levels, were analyzed in addition to the determination of auxological parameters. In an age-related analysis, leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9 micrograms/L) in parallel with body weight. Boys always had lower leptin levels than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first hormone to rise followed by FSH and later by LH and estradiol. A similar pattern occurred in boys, despite the fact that leptin dropped after 10 yr when testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2 = early puberty, and P3 = overt puberty, in girls the four hormones rose progressively from P1 to P3, but from P2 to P3 the present increment was greater for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH, and testosterone rose. The age-related changes were not caused by adiposity variations, because data did not change when subtracting values of children over 97% of standard deviation score of body mass index. IN CONCLUSION: 1) leptin appears to increase in both boys and girls before the appearance of other reproductive hormones related to puberty; 2) leptin levels in boys are always lower than in girls, although they increase with age until the age 10 yr; 3) leptin in boys declines about the time testosterone increases. Leptin may well be a permissive factor for the initiation of pubertal events.


Assuntos
Envelhecimento/sangue , Índice de Massa Corporal , Hormônios/sangue , Proteínas/análise , Puberdade/sangue , Caracteres Sexuais , Adolescente , Peso Corporal , Criança , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Leptina , Masculino , Hormônios Hipofisários/sangue , Valores de Referência
15.
J Clin Endocrinol Metab ; 83(6): 2149-55, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9626154

RESUMO

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean +/- SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 +/- 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9), whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6). In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Dexametasona/farmacologia , Estradiol/farmacologia , Omento , Proteínas/metabolismo , Colforsina/farmacologia , AMP Cíclico/metabolismo , Feminino , Glucocorticoides/farmacologia , Humanos , L-Lactato Desidrogenase/metabolismo , Leptina , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos
16.
J Endocrinol ; 170(2): 425-31, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11479138

RESUMO

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.


Assuntos
Tecido Adiposo/metabolismo , Colecalciferol/farmacologia , Leptina/metabolismo , Tretinoína/farmacologia , Tecido Adiposo/efeitos dos fármacos , Análise de Variância , Técnicas de Cultura , Depressão Química , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tri-Iodotironina/farmacologia
17.
J Endocrinol ; 160(3): 425-32, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10076188

RESUMO

Leptin, the product of the Ob gene, is a polypeptide hormone expressed in adipocytes which acts as a signalling factor from the adipose tissue to the central nervous system, regulating food intake and energy expenditure. It has been reported that circulating leptin levels are higher in women than in men, even after correction for body fat. This gender-based difference may be conditioned by differences in the levels of androgenic hormones. To explore this possibility, a systematic in vitro study with organ cultures from human omental adipose tissue, either stimulated or not with androgens (1 microM), was undertaken in samples obtained from surgery on 44 non-obese donors (21 women and 23 men). The assay was standardized in periods of 24 h, ending at 96 h, with no apparent tissue damage. Leptin results are expressed as the mean+/-s.e.m. of the integrated secretion into the medium, expressed as ng leptin/g tissue per 48 h. Spontaneous leptin secretion in samples from female donors (4149+/-301) was significantly higher (P<0.01) than that from male donors (2456+/-428). Testosterone did not exert any significant effect on in vitro leptin secretion in either gender (4856+/-366 in women, 3322+/-505 in men). Coincubation of adipose tissue with dihydrotestosterone (DHT) induced a significant (P<0.05) leptin decrease in samples taken from women (3119+/-322) but not in those taken from men (2042+/-430). Stanozolol, a non-aromatizable androgen, decreased (P<0.05) leptin secretion in female samples (2809+/-383) but not in male (1553+/-671). Dehydroepiandrosterone sulphate (DHEA-S) induced a significant (P<0.01) leptin decrease in female samples (2996+/-473), with no modifications in samples derived from males (1596+/-528). Exposure to androstenedione also resulted in a significant reduction (P<0.01) of leptin secretion in samples taken from women (2231+/-264), with no effect on male adipose tissue (1605+/-544). In conclusion, DHT, stanozolol, DHEA-S and androstenedione induced a significant inhibition of in vitro leptin secretion in samples from female donors, without affecting the secretion in samples from men. Testosterone was devoid of activity in either gender.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Androgênios/farmacologia , Proteínas/metabolismo , Androstenodiona/farmacologia , Técnicas de Cultura , Sulfato de Desidroepiandrosterona/farmacologia , Depressão Química , Di-Hidrotestosterona/farmacologia , Feminino , Humanos , Leptina , Masculino , Pessoa de Meia-Idade , Omento , Estanozolol/farmacologia , Testosterona/farmacologia
18.
Eur J Endocrinol ; 143(5): 711-4, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11078997

RESUMO

OBJECTIVE: Leptin is an adipocyte-secreted hormone acting as a signal to the central nervous system, where it regulates energy homeostasis and neuroendocrine processes. Leptin plasma levels are mainly regulated by the percentage of body fat, but are also controlled by several metabolic and nutritional variables. Data regarding leptin secretion suggest that it is gender regulated, and higher levels are present in women than men; however, the biological basis for this sex-related difference is unknown. To clarify those points, a systematic study with tissue cultures from human omental adipose tissue was performed. DESIGN AND METHODS: Surgically obtained samples from 137 patients (68 women, 69 men) were evaluated. The assay was standardized in periods of 24 h ending at 96 h. Each adipose tissue sample from a single donor was incubated in triplicate and leptin results expressed as the mean of the integrated secretion into the medium (nanograms of leptin/g tissue per time). RESULTS: Tissue adipose cultures showed a steady leptin secretion throughout the 96 h studied, with the peak of secretory activity reached at 48 h; afterwards, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in the 24 h and 48 h period, as well as the area under the curve analyzed in the 0-48 h period, showed a gender-based difference that was significantly (P<0. 05) higher in women than in men. When data of spontaneous leptin secretion were correlated with the body mass index (BMI) of the donors, no correlation was found. This suggests that in vivo leptin levels are dependent on the total amount of fat of the individual, but independent of the leptin secretory rate by the adipose tissue of the donor. CONCLUSIONS: Leptin secretion from omental adipose tissue in vitro is: (i) significantly higher in samples from women than in samples from men; and (ii) not correlated with the BMI, showing that in vitro leptin secretion is not related to the adiposity of the donor.


Assuntos
Tecido Adiposo/metabolismo , Índice de Massa Corporal , Leptina/metabolismo , Adulto , Idoso , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Omento , Caracteres Sexuais
19.
Eur J Endocrinol ; 137(6): 655-8, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9437232

RESUMO

Sex-based differences in serum leptin concentrations have been reported in adolescence and adulthood. To discover when such differences were generated, serum leptin concentrations were measured in umbilical cord blood from 46 healthy infants and in the mother's blood at delivery. Considering the respective body weights of the mothers and infants (68.5 +/- 1.3 kg and 3.3 +/- 0.0 kg), umbilical cord concentrations of leptin were disproportionately high in the infants (9.4 +/- 1.2 micrograms/l) compared with those in the mothers (18.7 +/- 1.3 micrograms/l). There was a wide variation in the infants leptin values (1.2 +/- 56.8 micrograms/l) that did not correlate with height, weight, cephalic circumference, or any other growth-related parameter. The most striking differences emerged when results were analysed by sex: umbilical cord concentrations of leptin in the girls (12.9 +/- 2.2 micrograms/l) were significantly (P < 0.01) greater than those in the boys (6.8 +/- 0.9 micrograms/l), although no differences in leptin concentrations were observed between the mothers who gave birth to a girl (19.5 +/- 2.2 micrograms/l) and those who gave birth to a boy (18.1 +/- 1.7 micrograms/l). The sex-based differences were not attributable to any growth-related differences between the sexes, except heavier placental weights in the girls (P < 0.007) than in the boys. These differences in leptin concentrations may reflect a sex-based difference in the regulation of leptin production by the fetal adipose tissue.


Assuntos
Sangue Fetal/química , Proteínas/análise , Adulto , Peso ao Nascer , Feminino , Humanos , Leptina , Masculino
20.
Pharmacoeconomics ; 18(6): 581-9, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11227396

RESUMO

OBJECTIVE: To examine the effect of abciximab treatment on intensive care length of stay for patients undergoing percutaneous coronary intervention (PCI). DESIGN AND SETTING: A retrospective study conducted in a naturalistic setting. METHODS: A 2-stage econometric model was used to control for the influence of possible selection bias across categories of patients and for both observable and unobservable factors correlated with each patient's treatment selection and length of stay in intensive care. Multivariate analysis was applied to control for a wide range of factors (patient demographics, insurance provider, health conditions, admission and discharge information, and hospital characteristics) that may influence intensive care length of stay. Retrospective data were obtained from HCIA's Clinical Pathways Database. PARTICIPANTS: Patients (n = 13,364) who were hospitalised in any of 87 hospitals across the US over the period from October 1, 1995 to December 1, 1996. RESULTS: After controlling for high-risk indications and selection bias, results indicated that administration of abciximab was associated with a significantly shorter length of stay in intensive care compared with not administering a GPIIb/IIIa inhibitor (0.45 fewer days; p < or = 0.0001). In a subgroup analysis of patients having an acute myocardial infarction (n = 4793), administration of abciximab was also associated with a significantly shorter intensive care stay (0.27 fewer days; p < 0.0001). CONCLUSION: Results of this study indicate that the administration of abciximab is associated with a reduction in the length of stay in intensive care. This reduction implies potential cost offsets for patients undergoing PCI who receive abciximab.


Assuntos
Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Fragmentos Fab das Imunoglobulinas/economia , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Abciximab , Idoso , Cuidados Críticos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Modelos Econométricos , Estudos Retrospectivos
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