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1.
Rev Med Liege ; 74(11): 563-565, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31729843

RESUMO

The thyroid gland is usually resistant to infections due to its anatomy. However, suppurative thyroiditis could be found in immunocompromised patients or those with previous thyroid diseases. We report a case of thyroid abscess secondary to Salmonella enteritidis infection in an immunocompetent patient. We were not able to establish the source of infection. Clinical improvement was achieved under antibiotic treatment without complications. Early diagnosis is important as thyroid abcess may be a life threatening condition.


La thyroïde est une glande endocrine généralement résistante aux infections en raison de sa localisation et présentation anatomique. Cependant, une thyroïdite suppurée est susceptible de survenir chez des patients immunodéprimés ou ayant déjà présenté un dysfonctionnement thyroïdien. Nous rapportons un cas d'abcès thyroïdien consécutif à une infection à Salmonella enteritidis chez un patient immunocompétent. Nous n'avons pas pu établir la source de l'infection. Une amélioration clinique a été obtenue sous traitement antibiotique sans complications. Un diagnostic précoce est essentiel afin d'éviter toutes complications graves mettant en jeu le pronostic vital.


Assuntos
Infecções por Salmonella , Tireoidite Supurativa , Abscesso , Humanos , Infecções por Salmonella/diagnóstico , Salmonella enteritidis , Tireoidite Supurativa/diagnóstico
2.
Rev Med Chil ; 146(5): 670-674, 2018 May.
Artigo em Espanhol | MEDLINE | ID: mdl-30148932

RESUMO

There is an increased incidence of hematological malignancies, particularly non-Hodgkin lymphoma (NHL) in systemic lupus erythematosus (SLE). In contrast, the concurrence with Multiple Myeloma (MM) is very rare, and the possible pathogenetic mechanisms underlying this association remain unclear. We report two patients who developed MM 15 and four years after being diagnosed as having SLE.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico
3.
Int J Obes (Lond) ; 39(2): 279-87, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24675715

RESUMO

BACKGROUND: Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care. METHODS: We used liquid and gas chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD. RESULTS: Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased ß-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare. CONCLUSION: Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.


Assuntos
Ácidos Cetoglutáricos/sangue , Metaboloma , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade Mórbida/sangue , Biomarcadores/sangue , Cromatografia Líquida , Progressão da Doença , Humanos , Metabolismo dos Lipídeos , Espectrometria de Massas , Metabolômica/métodos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Valor Preditivo dos Testes
4.
Anal Bioanal Chem ; 404(10): 3081-90, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23064706

RESUMO

Sample preparation is an important step for the determination of phenolic compounds in biological samples. Different extraction methods have been tested to determine phenolic compounds and their metabolites in plasma by nano-liquid chromatography coupled to electrospray ionisation-time-of-flight mass spectrometry (nanoLC-ESI-TOF-MS). The sample treatment optimisation was performed using commercial foetal bovine serum spiked with representative phenolic standards, namely naringenin, luteolin, verbascoside, apigenin, rutin, syringic acid and catechin. Different protein-precipitation conditions were evaluated as well as enzymatic digestion with trypsin and solid-phase extraction using different phases such as C-18, ABN and ENV+, working at different pH values. The optimum extraction procedure consisted of a previous protein-precipitation step using HCl 200 mmol/L in methanol for 2.5 h at 50 °C followed by a solid-phase extraction using C-18 cartridges at pH 2.5. This procedure was finally applied to the plasma of rats overfed with a phenolic-rich Lippia citriodora extract. These samples were analysed by nanoLC-ESI-TOF-MS, enabling the identification of five compounds previously found in the administered L. citriodora extract and one metabolite.


Assuntos
Fenóis/sangue , Fenóis/isolamento & purificação , Extração em Fase Sólida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Bovinos , Cromatografia Líquida/métodos , Masculino , Fenóis/análise , Fenóis/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/sangue , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Ratos , Ratos Wistar , Verbenaceae/química
5.
Environ Monit Assess ; 184(9): 5613-21, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21922174

RESUMO

The objective of the present study was to monitor the levels of organochlorine pesticides HCB; α-, ß-, γ-HCH; pp'DDE; op'DDT; and pp'DDT in blood serum of Veracruz, Mexico inhabitants. Organochlorine pesticides were analyzed in 150 blood serum samples that constituted that which remained after clinical analyses, using gas chromatography-electron-capture detection (GC-ECD). The results were expressed as milligrams per kilogram on fat basis and micrograms per liter on wet weight. Only the following pesticides were detected: p,p'-DDE was the major organochlorine component, detected in 100% of samples at mean 15.8 mg/kg and 8.4 µg/L; p,p'-DDT was presented in 41.3.% of monitored samples at mean 3.1 mg/kg and 1.4 µg/L; ß-HCH was found in 48.6% of the samples at mean 4.9 mg/kg and 2.7 µg/L; op'DDT was determined to be in only 3.3% of monitored samples at mean 2.7 mg/kg and 1.4 µg/L. The pooled samples divided according to sex showed significant differences of ß-HCH and pp'DDE concentrations in females. The samples grouped according to age presented the third tertile as more contaminated in both sexes, indicating age as a positively associated factor with serum organochlorine pesticide levels in Veracruz inhabitants.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Exposição Ambiental/análise , Feminino , Hexaclorobenzeno/sangue , Hexaclorocicloexano/sangue , Humanos , Masculino , México , Pessoa de Meia-Idade , Adulto Jovem
6.
Bull Environ Contam Toxicol ; 86(3): 289-93, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21290101

RESUMO

The objective of the present study was to determine levels and calculate ratios of copartition coefficients among organochlorine pesticides ß-HCH, pp'DDE, op'DDT and pp'DDT in maternal adipose tissue, maternal blood serum and umbilical blood serum of mother-infant pairs from Veracruz, Mexico. Organochlorine pesticides were analyzed in 70 binomials: maternal adipose tissue, maternal serum and umbilical cord serum samples, using gas chromatography with electron capture detection (GC-ECD). The results were expressed as mg/kg on fat basis. p,p'-DDE was the major organochlorine component, detected in every maternal adipose tissue (0.770 mg/kg), maternal serum sample (5.8 mg/kg on fat basis) and umbilical cord blood sample (6.9 mg/kg on fat basis). p,p'-DDT was detected at 0.101 mg/kg, 2.2 mg/kg and 5.9 mg/kg respectively, according to the order given above. ß-HCH was detected at 0.027 mg/kg, 4.2 mg/kg and 28.0 mg/kg respectively. op'DDT was detected only in maternal adipose tissue at 0.011 mg/kg. The copartition coefficients among samples identify significant increases in concentrations from adipose tissue to maternal blood serum and to umbilical blood serum. The increase indicated that maternal adipose tissue released organochlorine pesticides to blood serum and that they are carried over to umbilical cord blood.


Assuntos
Tecido Adiposo/metabolismo , Sangue Fetal/metabolismo , Hidrocarbonetos Clorados/metabolismo , Exposição Materna/estatística & dados numéricos , Praguicidas/metabolismo , Adulto , DDT/sangue , DDT/metabolismo , Diclorodifenil Dicloroetileno/sangue , Diclorodifenil Dicloroetileno/metabolismo , Monitoramento Ambiental , Poluentes Ambientais/sangue , Poluentes Ambientais/metabolismo , Feminino , Hexaclorocicloexano/sangue , Hexaclorocicloexano/metabolismo , Humanos , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue
7.
Acta Neurol Scand ; 122(3): 202-8, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20199521

RESUMO

OBJECTIVE: This open-label extension evaluated the long-term efficacy and tolerability of rufinamide in patients with Lennox-Gastaut syndrome (LGS) who had previously completed a 12-week double-blind study. MATERIALS AND METHODS: In total, 124 patients (aged 4-37 years), receiving 1-3 concomitant antiepileptic drugs, were treated with rufinamide approximately 25-60 mg/kg/day. Efficacy was assessed by seizure frequency; tolerability by adverse events (AEs) and laboratory tests. RESULTS: Overall, patients were treated with rufinamide for a median (range) of 432 (10-1149) days. Reductions in seizure frequency were observed throughout the study; during the last 12 months of treatment, 41.0% and 47.9% of patients had > or = 50% reduction in total and tonic-atonic seizure frequency, respectively. The most common AEs were vomiting (30.6%) and pyrexia (25.8%). CONCLUSIONS: In this open-label extension, rufinamide appeared to be an effective long-term adjunctive therapy for the treatment of LGS-associated seizures in children and young adults.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Triazóis/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Método Duplo-Cego , Avaliação de Medicamentos , Quimioterapia Combinada/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Resultado do Tratamento , Adulto Jovem
8.
Arch Environ Contam Toxicol ; 58(1): 230-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19468667

RESUMO

Since the discovery of insecticide properties of DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) and HCH (hexachlorocyclohexane), they have provided great benefits to humans in sanitary actions to combat the spread of infection-borne disease vectors. Public Health Programs in Mexico used DDT and HCH until 1999 as the insecticides of choice to control disease-transmitting organisms. Because of their persistence and accumulative properties, organochlorine pesticides bioconcentrate in lipids of the human body, reflecting the rate of environmental exposure. Eighty human abdominal adipose tissue samples from Veracruz and 80 samples from Puebla were analyzed and the obtained results were compared among both populations. The results from Veracruz showed higher contamination levels (mg/kg on lipid base) compared to Puebla: beta-HCH, 0.072 vs. 0.029; pp'DDE (Dichlorodiphenyldichloroethylene), 2.364 vs. 0.726; op'DDT, 0.022 vs. 0.025; pp'DDT, 0.192 vs. 0.061; and Sigma-DDT, 2.589 vs. 0.806. The population from Veracruz and from Puebla divided by sex, origin, and cause of death presented no statistical differences. The comparison between sexes (women and men groups) at Veracruz and Puebla indicated significantly higher levels in Veracruz and statistical significant differences. Calculating possible risks (odds ratios, OR), pp'DDE (OR = 5.04) and op'DDT (OR = 2.93) revealed significantly higher risk for the Veracruz population. The study indicated prolonged DDT exposure of Mexicans caused by the past sanitary use and persistence of its residues in soils and air.


Assuntos
Tecido Adiposo/química , DDT/análise , Hexaclorocicloexano/análise , Resíduos de Praguicidas/análise , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade
9.
Phytochem Anal ; 21(4): 307-13, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20039337

RESUMO

INTRODUCTION: Cistus ladanifer is an aromatic shrub that is widespread in the Mediterranean region. The labdanum exudate is used in the fragrance industry and has been characterised. However, there is not enough information about the phenolic content of the raw plant, the aerial part of it being a very rich source of bioactive compounds. OBJECTIVE: Characterisation of the bioactive compounds of the raw plant and its aerial parts. METHODOLOGY: High-performance liquid chromatography with diode array and electrospray ionisation mass spectrometric detection was used to carry out the comprehensive characterisation of a Cistus ladanifer shrub aqueous extract. Two different MS techniques were coupled to HPLC: time-of-flight mass spectrometry and tandem mass spectrometry. RESULTS: Many well-known compounds present in Cistus ladanifer were characterised, such as flavonoids, phenolic acids, ellagitanins, hexahydroxydiphenoyl and derivatives, and other compounds. CONCLUSION: The method described simultaneously separated a wide range of phenolic compounds and the proposed characterisation of the major compounds of this extract was carried out. It is important to highlight that, to our knowledge, this is the first time that a Cistus ladanifer aqueous extract from the raw plant has been characterised.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cistus/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Fenóis/química
10.
Acta Ortop Mex ; 34(4): 254-260, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-33535285

RESUMO

The compendium of disorders that affect the normal growth or function of the thorax will cause Thoracic Insufficiency Syndrome (TIS). TIS is defined as the inability of the chest to sustain normal breathing and/or lung growth. The etiology of the syndrome may be secondary to spinal deformities, global deformities of the chest, neuromuscular dysfunction or the combination of any these. Its manifestation is based on a history that highlights respiratory symptoms, a physical examination that demonstrates chest deformity, abnormal radiographic findings and/or computed tomography of the chest, accompanied by alterations in lung function or other studies of respiratory function. This syndrome must be treated with haste since it progressively worsens with the aggravation of the underlying condition(s) which is unfavorable to the irreversible physiological changes of the lung that occur during development, and are directly related to the respiratory insufficiencies. The vertical expandable prosthetic titanium rib (VEPTR) was developed as a treatment procedure that aims to restore the volume and function of the thorax with the purpose of enabling thoracic growth during the development of the child or adolescent. The treatment targets the components of the rib cage as a unit, in order to prevent or treat respiratory insufficiencies. Its indications include children with early development scoliosis who are prone to develop SIT. The proposed procedure entails a high incidence of complications and conflicting results that limit its efficacy as a treatment, which is why it is a subject of great controversy in the medical literature.


Los procesos que afecten el crecimiento normal o la función del tórax causarán el síndrome de insuficiencia torácica (SIT). Éste se define como la incapacidad del tórax de sostener una respiración normal y/o crecimiento pulmonar. La etiología del síndrome puede ser secundaria a deformidades de la columna, deformidades globales del tórax, disfunción neuromuscular o la combinación de éstas. Su manifestación se basa en un historial que resalta síntomas respiratorios, un examen físico que demuestra deformidad del tórax, hallazgos anormales radiográficos y/o tomografía computarizada del pecho, acompañados de alteración en la función pulmonar o de otros estudios de la función respiratoria. Este síndrome debe ser tratado con premura debido a que progresivamente empeora con el agravamiento de la condición subyacente, lo que resulta irreversiblemente desfavorable en los cambios fisiológicos del pulmón y se relaciona con insuficiencia respiratoria durante el desarrollo. El tratamiento expansor de costilla conocido en inglés como vertical expandable prosthetic titanium rib (VEPTR) propone restaurar el volumen y la función torácica con el propósito de permitir el crecimiento del tórax a través del desarrollo del paciente. El tratamiento se dirige a los componentes de la caja torácica como una unidad, con el fin de prevenir o tratar la insuficiencia respiratoria. Sus indicaciones incluyen niños con escoliosis de desarrollo temprano que sean propensos a desarrollar el SIT. El procedimiento propuesto conlleva una alta incidencia de complicaciones y resultados conflictivos que limitan su eficacia como tratamiento, por lo que es un tema de gran controversia en la literatura médica.


Assuntos
Insuficiência Respiratória , Escoliose , Adolescente , Criança , Humanos , Próteses e Implantes , Costelas , Titânio , Resultado do Tratamento
11.
Sci Total Environ ; 703: 134526, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767312

RESUMO

Air pollution is a public health concern. Polycyclic aromatic hydrocarbons (PAH) are ubiquitous atmospheric pollutants contained in the atmospheric aerosol. PAH in particulate matter with diameters ≤2.5 µm (PM2.5) represent a human health risk due to their toxic properties. In this study, PAH in PM2.5 at a receptor site of Mexico City during the dry cold season were determined. The most abundant PAH (median, 10-90th percentile, pg m-3) were benzo[ghi]perylene (467, 291-697), followed by pyrene (427, 218-642). A decrease around 40% in the carcinogenic PAH onto PM2.5 was calculated with respect to the same PAH measured a decade ago, at the same receptor site, despite of increase in vehicle fleet. The PAH decrease trend agrees with the decrease trend of CO, NO and NO2, released into the air by similar emission sources than PAH. Control emissions strategies implemented by local and federal authorities are discussed. PAH analyses were carried out by non-real-time and real-time methods. The PAH non-real-time method involved PM2.5 sampling, sample treatment and gas chromatography-mass spectrometry analysis. The PAH real-time method involved the use of a photoelectric aerosol sensor (PAS). The PAH determination by non-real time method was selective and efficient, with recoveries between 75 ±â€¯14% and 98 ±â€¯26%. By combining non-real-time and real-time methodologies, multivariate regression models were obtained based on PAS response, NO2 and wind speed to estimate PAH in PM2.5 at low-cost (r2 = 0.59 to r2 = 0.89). Fossil fuel combustion from vehicles was the major source around the sampling site. Diagnostic ratios (DR) based on retene, chrysene, and triphenylene, suggested biomass burning emission sources. Photo-oxidation in sunny months was observed based on benzo[a]pyrene, benzo[ghi]perylene, benz[a]anthracene, indeno[1,2,3-cd]pyrene and black carbon. The correlation analyses suggested transport of PM2.5, O3, BC and SO2 to the sampling site, and local emissions of PAH, NO and CO.

12.
Clin Transl Oncol ; 22(7): 1078-1085, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31679126

RESUMO

PURPOSE: Neoadjuvant chemotherapy (NACT) is employed in patients with breast cancer (BC) with the aim of reducing tumor burden and improving surgical outcomes. We evaluated the levels of energy metabolites pre- and post-radiotherapy (RT) in breast cancer (BC) patients who previously received NACT and investigated the alterations of these metabolites in relation to the patient achieving a pathologic complete response to NACT. MATERIALS AND METHODS: We included 37 BC patients who were treated with NACT following surgery and analyzed the concentrations of energy balance-related metabolites using targeted metabolomics before and one month after the end of RT. The control group was composed of 44 healthy women. RESULTS: Pre-radiotherapy, patients had significant decreases in the plasma levels of 12 metabolites. RT corrected these alterations and the improvement was superior in patients with a pathologic complete response. CONCLUSION: Our results highlight the importance of metabolism in the outcomes of patients with BC.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Metabolismo Energético , Mastectomia , Radioterapia Adjuvante , Radioterapia Conformacional , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Excisão de Linfonodo , Mastectomia Segmentar , Metabolômica , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Estudos Prospectivos , Biópsia de Linfonodo Sentinela , Trastuzumab/administração & dosagem , Adulto Jovem
13.
Hum Mutat ; 30(1): 12-21, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18634022

RESUMO

The functional consequences of missense variants are often difficult to predict. This becomes especially relevant when DNA sequence changes are used to determine a diagnosis or prognosis. To analyze the consequences of 12 missense variants in patients with mild forms of ataxia-telangiectasia (A-T), we employed site-directed mutagenesis of ataxia-telangiectasia mutated (ATM) cDNA followed by stable transfections into a single A-T cell line to isolate the effects of each allele on the cellular phenotype. After induction of the transfected cells with CdCl2, we monitored for successful ATM transcription and subsequently assessed: 1) intracellular ATM protein levels; 2) ionizing radiation (IR)-induced ATM kinase activity; and 3) cellular radiosensitivity. We then calculated SIFT and PolyPhen scores for the missense changes. Nine variants produced little or no correction of the A-T cellular phenotype and were interpreted to be ATM mutations; SIFT/PolyPhen scores supported this. Three variants corrected the cellular phenotype, suggesting that they represented benign variants or polymorphisms. SIFT and PolyPhen scores supported the functional analyses for one of these variants (c.1709T>C); the other two were predicted to be "not tolerated" (c.6188G>A and c.6325T>G) and were classified as "operationally neutral." Genotype/phenotype relationships were compared: three deleterious missense variants were associated with an increased risk of cancer (c.6679C>T, c.7271T>G, and c.8494C>T). In situ mutagenesis represents an effective experimental approach for distinguishing deleterious missense mutations from benign or operationally neutral missense variants.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Mutação de Sentido Incorreto , Neoplasias/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/metabolismo , Biologia Computacional , Proteínas de Ligação a DNA/metabolismo , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Mutagênese Sítio-Dirigida , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Risco , Transfecção , Proteínas Supressoras de Tumor/metabolismo
14.
J Phys Chem A ; 113(9): 1858-63, 2009 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-19209882

RESUMO

A procedure is described for the theoretical study of chemical reactions in solution by means of molecular dynamics simulation, with solute-solvent interaction potentials derived from ab initio quantum calculations. We apply the procedure to the case of neutral hydrogen isocyanate hydrolysis, HNCO + 2 H(2)O --> H(2)NCOOH + H(2)O, in aqueous solution, via the assisted-concerted mechanisms and the two-water model. We used the solvent as a reaction coordinate and the free-energy curves for the calculation of the properties related to the reaction mechanisms, with a particular focus on the reaction and activation energies. The results showed that the mechanism with two water molecules attacking the C=N bond is preferred to the mechanism with three waters forming a ring of eight members. In addition, the aqueous medium significantly reduces the activation barrier (DeltaG(double dagger) = 13.9 kcal/mol) and makes the process more exothermic (DeltaG = -11.1 kcal/mol) relative to the gas-phase reaction, increasing the rate constant of the process to k = 4.25 x 10(5) s(-1).


Assuntos
Cianatos/química , Simulação de Dinâmica Molecular , Água/química , Algoritmos , Carbamatos , Hidrólise , Estrutura Molecular , Teoria Quântica , Soluções , Termodinâmica
15.
J Toxicol Environ Health A ; 72(15-16): 974-85, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19672766

RESUMO

The Colombian amphibian fauna is among the richest known in the world, with about 20 species of salamanders (order Caudata), 35 of the limbless caecilians (order Gymnophiona), and more than 700 species of frogs and toads (order Anura) recorded from localities within the country. The potential effects of exposure to glyphosate on amphibians arising from production of illegal crops (coca) were examined. The analysis was based on (1) behavior and ecology of species and (2) proximities of actual museum records to localities in which illegal crops are being grown and the subset of those that have been sprayed with glyphosate. Based on data on the location of amphibians collected in Colombia, records were obtained for 193 species (28% of the national diversity) of frogs and toads found in localities within 10 km of areas where coca is grown. Further analyses with ARC MAP software allowed for measurement of the direct distance separating collection locations for frogs, known coca fields, and areas where aerial spraying was being conducted. Records in or near coca fields included data for 11 of 13 families of frogs and toads known to be present in Colombia. Only Ceratophryidae and Pipidae were not reported from these locations and appear not to be at risk. For eight species (Dendrobates truncatus, Craugastor raniformis, Pristimantis gaigeae, Smilisca phaeota, Elachistocleis ovale, Hypsiboas crepitans, Trachycephalus venulosus, and Pseudis paradoxa) selected to represent several habitat preferences and life-cycle strategies, large areas of their distributions lie outside coca production regions and their populations as a whole are at low risk. For a limited number of species that barely enter Colombian territory, the consequences of coca production may be more serious and may have placed several species of frogs at risk. These include Ameerega bilingua, Dendropsophus bifurcus, Pristimantis colomai, P. degener, P. diadematus, P. quaquaversus, P. variabilis, and Trachycephalus jordani. Other species may also be at risk but exact numbers are unknown since few investigations were undertaken in these areas during the past 30 yr. The main ranges for these species were assumed to be in Ecuador.


Assuntos
Agricultura , Anuros/fisiologia , Desfolhantes Químicos/toxicidade , Controle de Medicamentos e Entorpecentes/métodos , Poluentes Ambientais/toxicidade , Glicina/análogos & derivados , Adjuvantes Farmacêuticos/análise , Adjuvantes Farmacêuticos/toxicidade , Aeronaves , Animais , Colômbia , Desfolhantes Químicos/análise , Combinação de Medicamentos , Ecossistema , Monitoramento Ambiental , Poluentes Ambientais/análise , Glicina/análise , Glicina/toxicidade , Estágios do Ciclo de Vida/efeitos dos fármacos , Estágios do Ciclo de Vida/fisiologia , Medição de Risco , Tensoativos/análise , Tensoativos/toxicidade , Glifosato
16.
Bull Environ Contam Toxicol ; 83(6): 869-73, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19551328

RESUMO

Breast milk is considered the most important route in the elimination of deposited organochlorine pesticides in a mother's body. The equilibrium of organochlorine pesticides in the human body considers the elements of internal transport processes, the equilibrium pattern between pesticides and tissue fat contents, and the mobilization of lipids and lipoproteins among body parts. The aim of this study was to determine organochlorine pesticide levels in breast milk samples from the 4th to the 30th day of lactation and the trend in their concentration time so as to forecast the time tendency of residue levels and the pesticide excretion pattern. Milk samples were taken from forty participants and analyzed by GLC-ECD. The organochlorine pesticide residues determined in the breast milk samples during lactation decreased: ß-HCH from 0.095 to 0.066 mg/kg, pp'DDE from 1.807 to 1.423 mg/kg and pp'DDT from 0.528 to 0.405 mg/kg, at the characteristic rate for each compound. The obtained results compared with the calculated fits of forecasts were parallel and did not exhibit significant differences. The newborn baby exposed during lactation had organochlorine pesticide residues whose levels decreased permanently. The levels depended not only on the breast milk nutrition, but also on the total environmental exposures which included air pollution as a significant contamination source.


Assuntos
DDT/metabolismo , Diclorodifenil Dicloroetileno/metabolismo , Poluentes Ambientais/metabolismo , Hexaclorocicloexano/metabolismo , Leite Humano/metabolismo , Praguicidas/metabolismo , Monitoramento Ambiental , Feminino , Humanos , Exposição Materna/estatística & dados numéricos
17.
Oncogene ; 37(7): 963-970, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29059169

RESUMO

The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carbono/metabolismo , Neoplasias do Colo/tratamento farmacológico , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genoma Humano , Metformina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Biomarcadores Tumorais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Complexo I de Transporte de Elétrons/metabolismo , Feminino , Seguimentos , Humanos , Hipoglicemiantes/farmacologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Células Tumorais Cultivadas
18.
Hum Exp Toxicol ; 26(9): 715-22, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17984142

RESUMO

Genotoxicity caused by tobacco smoke was assessed in peripheral blood lymphocytes of smokers living in Mexico City by determining sister chromatid exchange (SCE), cell proliferation kinetics (CPK), replication index (RI) and mitotic index (MI). Nicotine levels, and its major metabolite cotinine, were also estimated in urine samples using gas-chromatography-mass spectrometry to quantify smoking intensity. The outcome of the analysis and the comparison of the 77-smoker group with a non-smoking control group showed that moderate and heavy smokers exhibited significant differences (P < 0.001 and P < 0.05, respectively) in CPK, with an underlying delay in the cellular cycle; similarly, RI was significantly different in these groups (P < 0.001 and P < 0.0001, respectively). There were significant correlations (P < 0.05) between age and number of years the subject had been smoking, as well as between RI and nicotine and cotinine levels and between CPK (M1, M2 and M3) and nicotine and cotinine levels. Smokers were classified for the analysis according to the nicotine levels (it is in relation to number of cigarettes smoked per day) found in urine (ng/mL) as: light (10-250), moderate (251-850) and heavy (851-4110). Significant differences in CPK were found (P < 0.05) between moderate and heavy smokers and non-smokers. Significant differences in RI were found between moderate (P < 0.001) and heavy smokers (P < 0.0001) and non-smokers, but not for the light smoking group. MI was determined in 57 of the smokers, whereas SCE frequency was only recorded in 34 smokers. Both parameters yielded no significant differences, nor correlations with any of the assessed variables. In conclusion, cytokinetic and cytostatic effects were mainly detected in heavy and moderate smokers. Cell cycle delay and RI decrease were found in all ;healthy' smokers. The nicotine and cotinine exposure (causing oxidative damage to DNA) may have implications in the decrease in cell replication due to direct damage to DNA and/or a decrease in the DNA repair mechanisms. Alternatively, nicotine and cotinine may possibly induce apoptosis.


Assuntos
Proliferação de Células/efeitos dos fármacos , Cotinina/toxicidade , Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Troca de Cromátide Irmã/efeitos dos fármacos , Fumar/efeitos adversos , Adulto , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Cotinina/urina , Dano ao DNA , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Cinética , Linfócitos/patologia , Masculino , México , Pessoa de Meia-Idade , Índice Mitótico , Nicotina/urina , Agonistas Nicotínicos/urina , Estresse Oxidativo/efeitos dos fármacos , Fumar/urina
19.
Rev Neurol ; 43(10): 577-83, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17099848

RESUMO

INTRODUCTION: There is a high prevalence of sleep disorders in Parkinson's disease (PD). AIMS. To assess some basic metric attributes of the SCOPA-Sleep scale, a measure for PD patients; secondary objective: to check the impact caused by the sleep disorder on the health-related quality of life (HRQoL) of patients and their caregivers. SUBJECTS AND METHODS: 68 PD patients and their main caregivers; measures: Hoehn and Yahr staging, SCOPA-Motor, Clinical Impression of Severity Index (CISI-PD), PDSS, Hospital Anxiety and Depression Scale, SCOPA-Psychosocial, and EuroQoL. Carers filled in a PDSS questionnaire about patient sleep and HRQoL measures (SF-36, EuroQoL). SCOPA-Sleep acceptability, scaling assumptions, internal consistency, construct validity and precision were determined. RESULTS: SCOPA-Sleep acceptability and scaling assumptions resulted satisfactory, although the nocturnal sleep subescale (SC-Ns) showed a mild ceiling effect (22.1%) and a defective convergent validity was found for daytime sleepiness (SC-Ds) item 6. Internal consistency also was satisfactory for both scales (alpha = 0.84 and 0.75, respectively). The correlation between SC-Ns and PDSS was high (rs = -0.70), as it was between SC-Ns and PDSS questionnaire by caregiver (rs = -0.53). The corresponding coefficients with the SC-Ds gained lower values (rs = -0.41 y -0.50). Standard error of measurement was 1.45 for the SC-Ns and 1.76 for the SC-Ds. Both, patient and caregiver HRQoL showed a loose association with the sleep measures. CONCLUSION: SCOPA-Sleep is a feasible, consistent, and useful scale for assessment of sleep disorder in PD patients. A weak association between sleep disorder and HRQoL was found.


Assuntos
Doença de Parkinson/complicações , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia , Inquéritos e Questionários , Idoso , Idoso de 80 Anos ou mais , Cuidadores , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida
20.
J Chromatogr A ; 1477: 100-107, 2016 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-27894697

RESUMO

New clean technologies are needed to determine concentration of organic pollutants without generating more pollution. A method to extract Persistent Organic Pollutants (POPs) from airborne particulate matter was developed using a novel technology recently patented called ultrasound assisted extraction micro-scale cell (UAE-MSC). This technology extracts, filters, collects the sample, and evaporates the solvent, on-line. No sample transfer is needed. The cell minimizes sample manipulation, solvent consumption, waste generation, time, and energy; fulfilling most of the analytical green chemistry protocol. The methodology was optimized applying a centred 23 factorial experimental design. Optimum conditions were used to validate and determine concentration of 16 organochlorine pesticides (OCls) and 6 polybrominated diphenyl ethers (PBDEs). The best conditions achieved were 2 extractions with 5mL (each) of dichloromethane over 5min (each) at 60°C and 80% ultrasound potency. POPs were determined by gas chromatography/mass spectrometry in negative chemical ionization (GC/MS-NCI). Analytical method validation was carried out on airborne particles spiked with POPs at seven concentration levels between 0.5 and 26.9pgm-3. This procedure was done by triplicate (N=21). Recovery, ranged between 65.5±2.3% and 107.5±3.0% for OCls and between 79.1±6.5% and 105.2±3.8% for PBDEs. Linearity (r2) was ≥0.94 for all compounds. Method detection limits, ranged from 0.5 to 2.7pgm-3, while limits of quantification (LOQ), ranged from 1.7 to 9.0pgm-3. A Bias from -18.6% to 9% for PBDEs was observed in the Standard Reference Material (SRM) 2787. SRM 2787 did not contain OCls. OCls recoveries were equivalent by UAE-MSC and Soxhlet methods UAE-MSC optimized extraction conditions reduced 30 times less solvent and decreased the extraction time from several hours to ten minutes, respect to Soxhlet. UAE-MSC was applied to 15 samples of particles less than 2.5µm (PM2.5) from three seasons (warm dry, rainy, and cold dry) collected in five sites around Mexico City. OCls (4,4'-DDE and endrin aldehyde) concentrations ranged from

Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos/análise , Material Particulado/análise , Ultrassom/métodos , Calibragem , Éteres Difenil Halogenados/análise , México , Reprodutibilidade dos Testes , Estações do Ano , Solventes
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