RESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.
Assuntos
Carcinoma Ductal Pancreático/epidemiologia , Biologia Computacional , Neoplasias Pancreáticas/epidemiologia , Análise de Sistemas , Biologia de Sistemas , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Estudos de Casos e Controles , Análise por Conglomerados , Comorbidade , Bases de Dados Genéticas , Europa (Continente)/epidemiologia , Análise Fatorial , Humanos , Modelos Logísticos , Análise Multivariada , Razão de Chances , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Análise de Componente Principal , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Condensation and boiling are phase transitions highly relevant to industry, geology, and atmospheric science. These phase transitions are initiated by the nucleation of a drop in a supersaturated vapor and of a bubble in an overstretched liquid, respectively. The surface tension between both phases, liquid and vapor, is a key parameter in the development of such nucleation stage. Whereas the surface tension can be readily measured for a flat interface, there are technical and conceptual limitations to obtain it for the curved interface of the nucleus. On the technical side, it is quite difficult to observe a critical nucleus in experiments. From a conceptual point of view, the interfacial free energy depends on the choice of the dividing surface, being the surface of tension the one relevant for nucleation. We bypass the technical limitation by performing simulations of a Lennard-Jones fluid where we equilibrate critical nuclei (both drops and bubbles). Regarding the conceptual hurdle, we find the relevant cluster size by searching the radius that correctly predicts nucleation rates and nucleation free energy barriers when combined with Classical Nucleation Theory. With such definition of the cluster size we find the same value of the surface tension for drops and bubbles of a given radius. Thus, condensation and boiling can be viewed as two sides of the same coin. Finally, we combine the data coming from drops and bubbles to obtain, via two different routes, estimates of the Tolman length, a parameter that allows describing the curvature dependence of the surface tension in a theoretical framework.
RESUMO
Simulations are widely used to study nucleation in first order phase transitions due to the fact that they have access to the relevant length and time scales. However, simulations face the problem that nucleation is an activated process. Therefore, rare event simulation techniques are needed to promote the formation of the critical nucleus. The Seeding method, where the simulations are started with the nucleus already formed, has proven quite useful in efficiently providing estimates of the nucleation rate for a wide range of orders of magnitude. So far, Seeding has been employed in the NPT ensemble, where the nucleus either grows or redissolves. Thus, several trajectories have to be run in order to find the thermodynamic conditions that make the seeded nucleus critical. Moreover, the nucleus lifetime is short and the statistics for obtaining its properties is consequently poor. To deal with these shortcomings we extend the Seeding method to the NVT ensemble. We focus on the problem of bubble nucleation in a metastable Lennard Jones fluid. We show that, in the NVT ensemble, it is possible to equilibrate and stabilise critical bubbles for a long time. The nucleation rate inferred from NVT-Seeding is fully consistent with that coming from NPT-Seeding. The former is quite suitable to obtain the nucleation rate along isotherms, whereas the latter is preferable if the dependence of the rate with temperature at constant pressure is required. Care should be taken with finite size effects when using NVT-Seeding. Further work is required to extend NVT seeding to other sorts of phase transitions.
RESUMO
We investigate vapor homogeneous nucleation in a superheated Lennard-Jones liquid with computer simulations. Special simulation techniques are required to address this study since the nucleation of a critical vapor bubble-one that has an equal chance to grow or shrink-in a moderately superheated liquid is a rare event. We use the Seeding method, which combines Classical Nucleation Theory with computer simulations of a liquid containing a vapor bubble to provide bubble nucleation rates in a wide temperature range. Seeding has been successfully applied to investigate the nucleation of crystals in supercooled fluids, and here we apply it to the liquid-to-vapor transition. We find that the Seeding method provides nucleation rates that are consistent with independent calculations not based on the assumptions of Classical Nucleation Theory. Different criteria to determine the radius of the critical bubble give different rate values. The accuracy of each criterion depends of the degree of superheating. Moreover, seeding simulations show that the surface tension depends on pressure for a given temperature. Therefore, using Classical Nucleation Theory with the coexistence surface tension does not provide good estimates of the nucleation rate.
RESUMO
Colorectal cancer is one of the most prevalent cancers in developed countries. However, the genetic factors influencing its appearance remain far from being fully characterized. Recently, a G>A functional transition mapping the 3' untranslated region of the CXCL12 gene (rs1801157) has been found to be under-represented among rectal cancer patients when compared to colon cancer patients from a Swedish series. Here we present the results from an independent analysis of CXCL12 rs1801157 in a larger CRC series of Spanish origin in order to analyse the robustness of this association within a different European population. No significant difference was observed between controls and colon or rectal cancer patients. We were also unable to find a correlation between rs1801157 and different prognostic markers such as metastasis development or disease-free survival time. The epidemiologic data involving CXCL12 rs1801157 in colorectal cancer risk are discussed.
Assuntos
Regiões 3' não Traduzidas/genética , Quimiocina CXCL12/genética , Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/genética , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/genética , Valores de Referência , Análise de SobrevidaRESUMO
Los ganglioneuromas son tumores benignos del sistema nervioso simpático, con origen en las células de la cresta neural. Forman parte del grupo de tumores neurogénicos, segundo en frecuencia en la clasificación de tumores retrorrectales. Describimos el caso de una mujer de 71 años que presenta una lesión en el espacio retrorrectal izquierdo de unos 45 X 21 X 56mm con una biopsia guiada por TC preoperatoria que descarta malignidad. Se decide exéresis de la tumoración a través de un abordaje posterior, realizando una incisión parasacrococcígea izquierda. El estudio anatomopatológico de la pieza quirúrgica describe un ganglioneuroma con bordes de resección libres. Los tumores de localización retrorrectal son infrecuentes y a pesar de no ser sintomáticos, se recomienda su exéresis. Por tanto, un correcto estudio preoperatorio para una estrategia quirúrgica adecuada es esencial. La RMN es el método diagnóstico de elección y fundamental para elegir el abordaje quirúrgico. De manera general, lesiones con límite superior por encima de S3 o con invasión locorregional de estructuras pelvianas, requerirían un aborde abdominal o en ocasiones combinado. Por tanto, una amplia exéresis del tumor es el pilar fundamental del tratamiento. La recurrencia postoperatoria y la trasformación maligna, aunque están descritas en la literatura hasta la fecha, son extraordinarias
Ganglioneuromas are benign lesions arising from sympathetic ganglion cells. They are in the neurogenic group, second in frequency in retrorectal tumors clasification. We present a case of a 71-year-old woman who presented a lesion in the left retrorectal space around 45 X 21 X 56 mm with a preoperative CT-guided biopsy that ruled out malignancy. The tumor was excised through a posterior approach, using a left parasacrococcygeal incision. Postoperative histopathologic study confirmed the lesion as a ganglioneuroma. Retrorectal tumors are uncommon and may be incidental, but their excision is recommended. Therefore, a correct preoperative study is essential. Pelvic MRI is the best imaging modality and aids surgical planning. In general, lesions with an upper limit above S3 or with locoregional invasion of pelvic structures would require an abdominal or combined approach. Therefore, a complete excision of the tumor is the mainstay of the treatment. Postoperative recurrence and malignant transformation, although described in the literature, are extraordinary
Assuntos
Humanos , Feminino , Idoso , Ganglioneuroma/cirurgia , Neoplasias Retais/cirurgia , Ganglioneuroma/patologia , Neoplasias Retais/patologia , Resultado do Tratamento , Biópsia/métodos , Espectroscopia de Ressonância Magnética/métodosRESUMO
The synthesis of four lipids containing the hemithioindigo chromophore as part of the fatty acid is described. Heck reaction of bromophenyl thioacetate esters with acrylonitrile, followed by reduction, ester hydrolysis, and Friedel--Craft acylation--cyclization gave a substituted thioindoxyl that condensed with an alkoxy benzaldehyde to produce the hemithioindigo. "Solventless" nitrile hydrolysis followed by mixed anhydride coupling of the acid with glycerophosphocholine produced lipids bearing two hemithioindigo chromophores. The photochemistry of various hemithioindigo derivatives was studied to confirm the expected photoisomerization in both homogeneous organic solution, and in vesicle bilayer membranes. Characteristic changes in the UV--visible spectra are consistent with fully reversible Z--E photoisomerization. Chromatographic separation of the Z and E isomers of a compound containing a single hemithioindigo chromophore confirmed the spectroscopic analysis and provided a quantitative analysis of the compositions of Z--E isomer mixtures.
Assuntos
Lipídeos/química , Cromatografia Líquida de Alta Pressão , Indicadores e Reagentes , Isomerismo , Lipídeos/síntese química , Espectroscopia de Ressonância Magnética , Membranas Artificiais , Fotoquímica , Espectrofotometria UltravioletaRESUMO
In this study we investigated the effects of the branched chain alpha-ketoacids accumulating in maple syrup urine disease (MSUD) on the concentrations of the high molecular weight neurofilament subunit (NF-H) associated with the cytoskeletal fraction of the cerebral cortex of 12-day-old rats. Cortical slices were incubated with alpha-ketoisocaproic acid (KIC), alpha-keto beta-methylvaleric acid (KMV) and alpha-ketoisovaleric acid (KIV) at concentrations ranging from 0.5 to 1.0 mM. The cytoskeletal fraction was extracted and the immunoreactivity for phosphorylated and total NF-H was analyzed by immunoblotting. The in vitro 32P incorporation into NF-H was also determined. Results showed that treatment of tissue slices induced with KMV increased Triton-insoluble phosphorylated NF-H immunoreactivity, with no alteration in total NF-H immunoreactivity. Furthermore, KIC treatment drastically increased the total amount of NF-H, whereas KIV did not change either phosphorylated or total NF-H immunoreactivity. KMV also increased the in vitro 32P incorporation into NF-H, confirming the highly phosphorylated NF-H levels detected in the immunoblot. These findings demonstrate that KIC and KMV alter the dynamic regulation of NF-H assembly in the cytoskeletal fraction. Therefore we may suggest that cytoskeletal disorganization may be one of the factors associated with the neurodegeneration characteristic of MSUD disease.
Assuntos
Córtex Cerebral/metabolismo , Cetoácidos/metabolismo , Doença da Urina de Xarope de Bordo/metabolismo , Degeneração Neural/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neurônios/metabolismo , Animais , Animais Recém-Nascidos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Relação Dose-Resposta a Droga , Hemiterpenos , Imuno-Histoquímica , Cetoácidos/farmacologia , Doença da Urina de Xarope de Bordo/patologia , Doença da Urina de Xarope de Bordo/fisiopatologia , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Proteínas de Neurofilamentos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Wistar , Frações SubcelularesRESUMO
The metal ions Zn(2+), Co(2+), and La(3+) strongly catalyze the methanolysis of the activated amides acetylimidazole (1) and its ligand-exchange-inert Co(III) complex, (NH(3))(5)Co(III)-AcIm (2). Studies of the kinetics of methanolysis are performed with pH measurement and control, and the metal ions are soluble in the medium throughout the pH regions where ionization of the M(x+)(CH(3)OH)(y) occurs. Zn(2+) and Co(2+) act as Lewis acids toward 1, catalyzing attack of external methoxide on a 1:M(2+) complex at values only 100-fold lower than the diffusion limit, the k(OR) values being 5.6 x 10(7) M(-1) s(-1) and 2.5 x 10(7) M(-1) s(-1), while that for CH(3)O(-) attack on 2 is 4.69 x 10(7) M(-1) s(-1). Since neither Zn(2+) nor Co(2+) promotes the methanolysis of 2, these metals appear to be acting through transient binding to the distal N of 1, which activates the C=O of the complex to external CH(3)O(-) attack. La(3+) catalyzes the methanolysis of both 1 and 2, which occurs by a mechanism that is fundamentally different from that exhibited by Zn(2+) and Co(2+) in that the active species appears to be a bis-methoxy-bridged dimer (La(3+))(2)(CH(3)O(-))(2)(CH(3)OH)(x)() that interacts directly with the C=O unit of the substrate.
Assuntos
Amidas/metabolismo , Metais/farmacologia , Catálise , Cátions Bivalentes/farmacologia , Cobalto/farmacologia , Hidrólise , Cinética , Lantânio/farmacologia , Metanol/metabolismo , Zinco/farmacologiaRESUMO
Propionic and methylmalonic acidemias are inherited neurometabolic disorders biochemically characterized by tissue accumulation of propionic (PA) and methylmalonic (MMA) acids, respectively. Neurofilaments (NF) are important cytoskeletal proteins and phosphorylation/dephosphorylation of NF is important to stabilize the cytoskeleton. We investigated the effects of PA and MMA on the high molecular weight neurofilament subunit associated with the cytoskeletal fraction of rat cerebral cortex along development. Cortical slices from 9- to 60-day-old rats were incubated with 2.5 mM PA or MMA. The cytoskeletal fraction was extracted and the immunoreactivity for phosphorylated or total NF-H was analyzed by immunoblotting using specific antibodies. Results showed that treatment of tissue slices with the acids induced an increased Triton-insoluble phosphorylated NF-H immunoreactivity in up to 17-day-old rats. Furthermore, treatments significantly increased the total amount of NF-H in 12-day-old rats. These findings indicate that PA and MMA alter the dynamic regulation of NF-H assembly in the cytoskeletal fraction.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Ácido Metilmalônico/farmacologia , Proteínas de Neurofilamentos/metabolismo , Propionatos/farmacologia , Animais , Western Blotting , Córtex Cerebral/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Técnicas In Vitro , Peso Molecular , Fosforilação , Ratos , Ratos WistarRESUMO
Se realiza un estudio comparativo y descriptivo con el objetivo de determinar la morbimortalidad por cardiopatía isquémica en ambos sexos, en el servicio de Cardiología del Hospital Provincial Docente Dr. Agostinho Neto, en el período comprendido desde enero de 2003 hasta septiembre de 2006. Se revisa la base de datos computarizada de dicho servicio. Se analizan datos de 907 pacientes, 471 mujeres y 436 hombres. Se determinan variables tales como: factores de riesgo asociados a esta enfermedad, letalidad y análisis de los resultados del tratamiento trombolítico. Se concluye que la mayor incidencia de la cardiopatía isquémica se encuentra en las féminas mayores de 60 años. La incidencia de la angina de pecho es mayor en las mujeres, mientras que en los hombres predomina el infarto. La mortalidad por infarto es similar en ambos sexos. El equiparamiento de las mortalidades de las mujeres pudiera explicarse por una avanzada edad al ingreso y una frecuencia mayor de diabetes mellitus. Las pacientes no trombolisadas son evidentemente menos beneficiadas que los hombres (AU)
Assuntos
Humanos , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/mortalidade , MulheresAssuntos
Serviços de Saúde Escolar , Adolescente , Adulto , Criança , Chile , Feminino , Humanos , Masculino , Pais , Serviços de Saúde Escolar/organização & administração , EnsinoAssuntos
Atitude , Psicologia do Adolescente , Puberdade , Adolescente , Chile , Feminino , Humanos , Relações Interpessoais , Masculino , Relações Pais-Filho , Inquéritos e QuestionáriosAssuntos
Transtornos do Comportamento Infantil/epidemiologia , Delinquência Juvenil , Adolescente , Alcoolismo/epidemiologia , Criança , Transtornos do Comportamento Infantil/etiologia , Criança Institucionalizada , Chile , Feminino , Humanos , Deficiências da Aprendizagem/epidemiologia , Masculino , Relações Pais-Filho , Fatores Sexuais , Comportamento Sexual , Fatores SocioeconômicosAssuntos
Assistência Integral à Saúde , Planejamento em Saúde , Adolescente , Criança , Chile , Estudos de Avaliação como Assunto , Feminino , Humanos , MasculinoAssuntos
Amicacina/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Canamicina/análogos & derivados , Serratia marcescens/efeitos dos fármacos , Adolescente , Adulto , Idoso , Amicacina/efeitos adversos , Infecções Bacterianas/microbiologia , Pré-Escolar , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Resistência Microbiana a Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Serratia marcescens/isolamento & purificaçãoAssuntos
Nocardiose , Pneumonia/etiologia , Adulto , Feminino , Humanos , Nocardia asteroides , Pneumonia/patologiaRESUMO
Se aislaron 24 hongos a partir de 8 muestras de tierra, mediante el método de dilución sobre agar y se determinó la viabilidad de 225 hongos del cepario del Instituto de Investigaciones Fármaco Bioquímicas (IIFB) encontrándose viable el 81,7 por ciento. De las 208 colonias de hongos evaluadas, el 28,5 por ciento presentaron actividad antimicrobiana en medio sólido. Por su actividad antimicrobiana de amplio espectro fueron seleccionados 7 hongos por duplicado en condiciones de iluminación, pH y concentración de glucosa controladas. La cepa productora de antibióticos, Aspergillus sp, fue seleccionado para estudios cinéticos en cultivo batch (100ml), detectándose actividad contra Staphylococcus aureus (50ul/ml) y Escherichia coli (200ul/ml). Posteriormente, se realizaron cultivos a 1,000 ml en fermentador con agitación controlando el pH, la producción de antibiótico y la concentración de glucosa en el medio. Una vez filtrado el sobrenadante, fue sometido a una cromatografía en columna con la resina HP21 lipofílica, deluida con mezclas de agua y metanol para su purificación, resultando activa la fracción obtenida con metanol al 80 por ciento, contra S. aureus (25ul/ml) y E. coli (2000ul/ml)