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1.
PeerJ ; 11: e16340, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047029

RESUMO

Xylose is the second most abundant carbohydrate in nature, mostly present in lignocellulosic material, and representing an appealing feedstock for molecule manufacturing through biotechnological routes. However, Saccharomyces cerevisiae-a microbial cell widely used industrially for ethanol production-is unable to assimilate this sugar. Hence, in a world with raising environmental awareness, the efficient fermentation of pentoses is a crucial bottleneck to producing biofuels from renewable biomass resources. In this context, advances in the genetic mapping of S. cerevisiae have contributed to noteworthy progress in the understanding of xylose metabolism in yeast, as well as the identification of gene targets that enable the development of tailored strains for cellulosic ethanol production. Accordingly, this review focuses on the main strategies employed to understand the network of genes that are directly or indirectly related to this phenotype, and their respective contributions to xylose consumption in S. cerevisiae, especially for ethanol production. Altogether, the information in this work summarizes the most recent and relevant results from scientific investigations that endowed S. cerevisiae with an outstanding capability for commercial ethanol production from xylose.


Assuntos
Saccharomyces cerevisiae , Xilose , Saccharomyces cerevisiae/genética , Xilose/genética , Engenharia Metabólica/métodos , Fermentação , Etanol/metabolismo
2.
J Genet Eng Biotechnol ; 20(1): 80, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35612634

RESUMO

BACKGROUND: Sugarcane hemicellulosic material is a compelling source of usually neglected xylose that could figure as feedstock to produce chemical building blocks of high economic value, such as xylitol. In this context, Saccharomyces cerevisiae strains typically used in the Brazilian bioethanol industry are a robust chassis for genetic engineering, given their robustness towards harsh operational conditions and outstanding fermentation performance. Nevertheless, there are no reports on the use of these strains for xylitol production using sugarcane hydrolysate. RESULTS: Potential single-guided RNA off-targets were analyzed in two preeminent industrial strains (PE-2 and SA-1), providing a database of 5'-NGG 20 nucleotide sequences and guidelines for the fast and cost-effective CRISPR editing of such strains. After genomic integration of a NADPH-preferring xylose reductase (XR), FMYX (SA-1 hoΔ::xyl1) and CENPKX (CEN.PK-122 hoΔ::xyl1) were tested in varying cultivation conditions for xylitol productivity to infer influence of the genetic background. Near-theoretical yields were achieved for all strains; however, the industrial consistently outperformed the laboratory strain. Batch fermentation of raw sugarcane straw hydrolysate with remaining solid particles represented a challenge for xylose metabolization, and 3.65 ± 0.16 g/L xylitol titer was achieved by FMYX. Finally, quantification of NADPH - cofactor implied in XR activity - revealed that FMYX has 33% more available cofactors than CENPKX. CONCLUSIONS: Although widely used in several S. cerevisiae strains, this is the first report of CRISPR-Cas9 editing major yeast of the Brazilian bioethanol industry. Fermentative assays of xylose consumption revealed that NADPH availability is closely related to mutant strains' performance. We also pioneer the use of sugarcane straw as a substrate for xylitol production. Finally, we demonstrate how industrial background SA-1 is a compelling chassis for the second-generation industry, given its inhibitor tolerance and better redox environment that may favor production of reduced sugars.

3.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 3): 4226-4231, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36742517

RESUMO

Tinnitus is a symptom whose pathophysiology remains still unclear. Its diagnosis and treatment is complicated, due to its subjectivity. The generation of tinnitus is commonly linked with the impaired functioning of the outer hair cells (OHC) inside the cochlea. Distortion product otoacoustic emissions (DPOAEs) are the objective test used to assess their activity. This study investigates the cochlear outer hair cell function in patients with tinnitus and normal hearing using DPOAEs. We performed a prospective study of the cochlear function in normal hearing patients complaining of tinnitus by analysing DPOAEs amplitude and signal/noise (S/N) ratio. We gathered a sample of 21 ears from adults that attended to the ENT Department complaining of tinnitus with normal hearing. We compared their results with a control group of 21 ears, with the same demographic characteristics, presenting normal hearing but without tinnitus in order to exclude the influence of age in DPOAEs results. A decreased mean of S/N levels in DPOAEs was found in tinnitus and normal hearing group comparing with control group, although these differences were not statistically significant (p > 0.05). Based on the results, OHC dysfunction is not necessary to experience tinnitus. The majority of the patients that present OHC dysfunction do not present a tinnitus at the moment. Other mechanisms in auditory pathway may be evaluated in the tinnitus development.

4.
Methods Mol Biol ; 2282: 417-442, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928588

RESUMO

The field of RNAi therapeutics has quickly adapted to the treatment of ocular diseases. Although the eye provides a unique system for the delivery of siRNAs, its complex structure and composition fostered the development of novel strategies for efficient gene silencing in the target compartment. Moreover, anterior and posterior segments differ in their multiple drug barriers and clearance mechanisms. This chapter summarizes the recent achievements in terms of routes of administration, chemical modifications, and delivery systems for siRNAs that specifically apply to eye disorders. Methods employed for siRNA detection/quantitation in ocular tissues are also described, together with safety concerns that need to be addressed to fulfill regulatory requirements of new drug approval. Even though RNAi therapies for ocular diseases have not yet translated into patient care, we document herein the rising number of candidate drugs currently under preclinical or clinical development.


Assuntos
Oftalmopatias/terapia , Olho/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Terapêutica com RNAi , Animais , Disponibilidade Biológica , Oftalmopatias/genética , Oftalmopatias/metabolismo , Técnicas de Transferência de Genes , Humanos , RNA Interferente Pequeno/metabolismo , Distribuição Tecidual
5.
Ear Nose Throat J ; 100(10_suppl): 1031S-1037S, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32551964

RESUMO

OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is an increasing health problem, the diagnosis of which is generally delayed due to long waiting lists for the tests used to identify it. Therefore, tools that help on classifying patients at higher risk of suffering this syndrome have been developed. METHODS: One hundred ninety-three consecutive patients, with and without OSAS, filled in the Spanish version of the STOP-Bang questionnaire in Hospital Universitario de Torrejón (Spain). Polysomnographies were performed to diagnose the presence and severity of the OSAS. Statistics analysis of the demographic characteristics of the sample and the questionnaire results was performed. RESULTS: Most patients were male (73%) and the mean age was 50.4 years (ranging from 19-77 years). Cronbach α coefficient in the sample was 0.8072. A statistically significant difference was noted in the questionnaire scores between patients with OSAS and those without the syndrome. CONCLUSIONS: The Spanish version of the STOP-Bang questionnaire possess a good internal consistency that allows us to rely on it as a screening tool for patients with OSAS. In our sample, a difference in the questionnaire score was appreciated between patients with and without the syndrome, which strongly supports the utility of the questionnaire for its purpose.


Assuntos
Programas de Rastreamento/normas , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários/normas , Feminino , Humanos , Idioma , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Polissonografia , Reprodutibilidade dos Testes , Espanha , Traduções
6.
Eur Arch Otorhinolaryngol ; 278(1): 173-179, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32839861

RESUMO

OBJECTIVES: To determine the usefulness of the smoothed cepstral peak prominence (CPPS) in sustained vowel as objective measure of dysphonia. STUDY DESIGN: This is a retrospective cohort study. 49 patients presenting a vocal cord motility impairment between 2012 and 2018 were included. METHODS: Classical acoustic parameters, including jitter, shimmer and NHR, as well as the CPPS were obtained for each patient with a vocal cord motility impairment confirmed by means of a fiberoptic laryngoscopy. We calculated the S/E ratio of each patient to establish the glottal efficiency. An independent sample t test and a Pearson correlation test were used to compare data. RESULTS: Patients presenting a vocal cord motility impairment present abnormal values of the CPPS. Those patients presenting a vocal cord paralysis present lower values of those presenting a vocal cord paresis, with statistically significant difference (P < 0.005). CPPS and the S/E ratio present a moderate negative correlation (- 0.29). CONCLUSIONS: Subjects with a vocal cord motility impairment present abnormal values for CPPS and those values are lower, the greater the motility impairment is. Therefore, CPPS presents as an objective, measurable and reproducible acoustic parameter of dysphonia that will improve the evaluation of patients presenting vocal pathologies.


Assuntos
Disfonia , Prega Vocal , Acústica , Disfonia/diagnóstico , Humanos , Estudos Retrospectivos , Acústica da Fala , Qualidade da Voz
9.
Int J Pediatr Otorhinolaryngol ; 125: 164-167, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326733

RESUMO

Castleman's disease is a very rare entity in pediatric population and its presentation in the neck is scarcely described in the literature. We present the case of a 10-year-old-girl with an expanding neck mass over several months causing dysphagia and dyspnea. Surgical excision of the mass was performed and the analysis revealed unicentric Castleman's Disease. This is the second largest reported case of neck pediatric CD in the literature, and it presented with a symptomatology that differs from the other cases described. This fact highlights the need to include CD in the differential diagnosis of pediatric neck masses.


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/diagnóstico , Transtornos de Deglutição/etiologia , Dispneia/etiologia , Criança , Transtornos de Deglutição/diagnóstico , Diagnóstico Diferencial , Dispneia/diagnóstico , Feminino , Humanos , Pescoço/cirurgia
10.
J Voice ; 33(1): 27-32, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29056313

RESUMO

OBJECTIVE: Vocal changes are frequent following a surgical procedure to the thyroid gland. Even though they are a recognized morbidity, their bases are yet to be defined as well as their effect on vocal parameters. This study investigates the objective and subjective changes that occur after the surgery. STUDY DESIGN: This study is a prospective analysis of consecutive cases. SETTING: This study was conducted in a single-center tertiary care facility. SUBJECTS AND METHODS: Patients programmed for any thyroid procedure in Hospital Universitario Ramón y Cajal were enrolled consecutively to perform the vocal analysis before and after the surgery from April 2014 to April 2016. Patients were divided according to the vocal fold motility, and their vocal and aerodynamic parameters were obtained by means of electroglottography and phonatory aerodynamic system. Patients filled in the 10-item Voice Handicap Index (VHI-10) questionnaire. Statistical analysis was performed comparing vocal and aerodynamic parameters and quality of life before and after the surgery. RESULTS: 218 patients met inclusion criteria and completed the protocol. A total of 86.6% of the sample showed no vocal motility impairment, whereas the rest of the patients showed a paresis or a paralysis. Maximum phonatory time and VHI-10 questionnaire showed a statistically significant difference (P < 0.05) between groups. No differences were assessed regarding other vocal parameters. CONCLUSIONS: Efforts are still needed to understand the groundings and magnitude of the vocal changes after a thyroid surgery.


Assuntos
Fonação , Complicações Pós-Operatórias/epidemiologia , Tireoidectomia/efeitos adversos , Paralisia das Pregas Vocais/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Espanha/epidemiologia , Doenças da Glândula Tireoide/cirurgia , Paralisia das Pregas Vocais/etiologia
11.
Rev. esp. nutr. comunitaria ; 24(1): 0-0, ene.-mar. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-181502

RESUMO

Fundamentos: El campo profesional Nutrición Comunitaria es reconocido por su relación con una necesidad social de coadyuvar en la solución de los problemas de alimentación y nutrición, existen evidencias de su escaso desarrollo en la formación y mercado laboral, el objetivo del presente estudio fue conocer su importancia en los planes de estudio de la licenciatura en nutrición, así como el interés de los estudiantes por realizar estudios de posgrado en este campo. Métodos: Estudio transversal, la muestra se conformó de dos universidades, una pública y una privada de: Argentina, Uruguay, Paraguay, Chile, México y Perú. Se encuestó a estudiantes del primero y último año y se entrevistó al director y dos profesores de cada licenciatura. Para el análisis se utilizó Excel y SPSS. Resultados: El campo profesional de mayor interés para realizar estudios de posgrado fue Nutrición Clínica, seguido de Nutrición Comunitaria, situación semejante se presentó en la importancia de cada campo en los planes de estudio. No se encontraron diferencias a valores de P≤0.05, entre los estudiantes del primero y último año. Conclusiones: Aunque la Nutrición Comunitaria se ubicó en segundo nivel de importancia, con base en la situación epidemiológica, se considera conveniente impulsar un mayor desarrollo en la licenciatura y ofertar más oportunidades de estudios de posgrado


Background: Community Nutrition professional field is recognized by its relationby a social need to contributein the solution of food-supply and nutrition problems, there exist evidences of scanty development in the student formation and labor market area, for the aim of the present study was to know about its importance in the study plans of the nutrition degree, as well as the interest of the students to realice postgraduate studies. Methods: Transversal study, the sample was conformed of two universities of each country, a private and a public one from: Argentina, Uruguay, Paraguay, Chile, Mexico and Peru. Students were polled of firstly and last year and one interviewed the director and two teachers of every program, for the analysis we used Excel and SPSS. Results: The professional field of major interest to realize postgraduate studies was Clinic Nutrition, followed by Community Nutrition, a similar situation appeared in the importance of every field in the study plans. There was not differences to values of P≤0.05 among the students of the firstly and last year. Conclusions: Though the Community Nutrition was located in the second level of importance, with base in the epidemiological situation, it is considered suitable to stimulate a major development in the master and to offer more opportunities of postgraduate studies


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Ciências da Nutrição/educação , Centros Comunitários de Saúde/tendências , Estudantes de Ciências da Saúde/estatística & dados numéricos , América Latina , Nutrição dos Grupos Vulneráveis , Agentes Comunitários de Saúde/tendências , Programas de Pós-Graduação em Saúde , Capacitação Profissional , Escolha da Profissão , Estudos Transversais , Inquéritos e Questionários/estatística & dados numéricos
12.
Rev. MED ; 25(2): 78-95, jul.-dic. 2017. graf
Artigo em Espanhol | LILACS | ID: biblio-977037

RESUMO

RESUMEN Introducción: Actualmente a pesar de las estrategias de vacunación a nivel mundial, B. pertussis se ha convertido en un problema de salud pública, sigue siendo una de las enfermedades menos prevenibles por vacunación en todo el mundo, aún en países desarrollados con amplia cobertura de vacunación. Objetivo: Describir los principales mecanismos de virulencia asociados a la infección mediante los cuales la bacteria logra evadir la respuesta inmune, además de dar a conocer un panorama actual del estado de inmunización contra la tos ferina y la problemática de su reemergencia a nivel mundial. Métodos: Se realizó una revisión mediante búsqueda electrónica de literatura; entre las estrategias de búsqueda se destaca el empleo de las bases de datos como PubMed, ScienceDirect, SciELO, Redalyc; y búsqueda en portales de salud; sobre aspectos generales de la enfermedad y su agente causal, además de últimas actualizaciones sobre el tema. Resultados: Como lo confirman recientes estudios, el incremento del riesgo de infección por B. pertussis sigue presentándose en adolescentes y adultos debido a la disminución en la respuesta inmune inducida por la vacunación y la infección natural, por ende, la información actual indica que está reemergiendo la tos ferina en todo el mundo, situación que es necesario conocer para un oportuno diagnóstico y tratamiento. Conclusiones: Análisis de la literatura demuestra la necesidad de ampliar el uso de técnicas moleculares; llevar a cabo la modificación de los programas de vacunación, con la administración de dosis de refuerzo entre adolescentes y adultos; además programas de monitoreo epidemiológico eficaces de recolección de casos con tos ferina y sistemas adecuados de notificación para lograr la reducción equitativa y sustentable de la morbilidad y mortalidad de ésta enfermedad.


ABSTRACT Introduction: Currently despite vaccination strategies worldwide, B. pertussis has become a public health problem, it remains one of the least vaccine preventable diseases in the world, even in developed countries with extensive coverage of vaccination. Objective: To describe the main mechanisms of virulence associated with the infection through which the bacterium manages to evade the immune response, as well as to present a current picture of the state of immunization against pertussis and the problem of its reemergence worldwide. Methods: Electronic literature search was performed; among the search strategies we highlight the use of databases such as PubMed, ScienceDirect, SciELO, Redalyc; and search in health portals; on general aspects of the disease and its causal agent, in addition to the latest updates on the subject. Results: As confirmed by recent studies, the increased risk of B. pertussis infection continues to occur in adolescents and adult's due to the decrease in the immune response induced by vaccination and natural infection, therefore, current information indicates that reemerging whooping cough around the world, a situation that is necessary to know for a timely diagnosis and treatment. Conclusions: Analysis of the literature demonstrates the need to expand the use of molecular techniques; to carry out the modification of the vaccination programs, with the administration of doses of reinforcement between adolescents and adults; In addition to effective epidemiological monitoring programs for the collection of pertussis cases and adequate notification systems to achieve an equitable and sustainable reduction in the morbidity and mortality of this disease.


RESUMO Introdução: Atualmente, apesar das estratégias de vacinação em todo o mundo, B. pertussis tornou-se um problema de saúde pública, continua a ser uma das doenças menos evitáveis pela vacina no mundo, mesmo em países desenvolvidos com ampla cobertura de vacinação. Objetivo: Descrever os principais mecanismos de virulência associados à infecção através dos quais a bactéria consegue evadir a resposta imune, bem como apresentar uma imagem atual do estado da imunização contra a tosse convulsa e o problema da ressurgência em todo o mundo. Métodos: Pesquisa eletrônica de literatura foi realizadantre as estratégias de Investigação, destacamos o uso de bancos de dados como PubMed, ScienceDirect, SciELO, Redalyc; e investigação em portais de saúde; sobre aspectos gerais da doença e seu agente causal, além das atualizações mais recentes sobre o assunto. Resultados: Conforme confirmado por estudos recentes, o aumento do risco de infecção por B. pertussis continua a ocorrer em adolescentes e adultos devido à diminuição da resposta imune induzida por vacinação e infecção natural, portanto, informações atuais indicam que a ressurreição de tosse convulsa ao redor do mundo, uma situação que é necessário conhecer para um diagnóstico e tratamento oportunos. Conclusões: A análise da literatura demonstra a necessidade de ampliar o uso de técnicas moleculares; para realizar a modificação dos programas de vacinação, com a administração de doses de reforço entre adolescentes e adultos; além de programas efetivos de monitoramento epidemiológico para a coleta de casos de tosse convulsa e sistemas de notificação adequados para alcançar uma redução sustentável e equitativa na morbidade e mortalidade desta doença.


Assuntos
Humanos , Bordetella pertussis , Vacina contra Coqueluche , Coqueluche , Doenças Transmissíveis Emergentes
13.
Rev. MED ; 25(1): 87-101, ene.-jun. 2017. ilus
Artigo em Espanhol | LILACS | ID: biblio-896902

RESUMO

El alcohol es un tóxico que, actúa como depresor del sistema nervioso central (SNC). Sus efectos son consecuencia directa de su acción sobre las membranas celulares y sobre los neurotransmisores. Las neuronas son particularmente sensibles al efecto neurotóxico del Etanol (EtOH) y su exposición afecta la morfología neuronal, ya que en estudios recientes se ha observado una disminución en la longitud del árbol dendrítico. El EtOH también produce cambios en la expresión de las proteínas sinápticas, aumento del lumen del retículo endoplasmático, así como también, desorganización del aparato de Golgi y de las mitocondrias. Objetivos: Describir los efectos del Etanol a nivel celular y molecular en el Sistema Nervioso Central y su repercusión en la salud humana. Métodos: Se realizó una búsqueda de literatura en las siguientes bases de datos disponibles en web: PubMed, ScienceDirect, Jama Journal, Scielo y portales de salud, utilizando las palabras claves: "etanol y farmacología", "alcohol y toxicología", "neurotoxicidad y etanol". Resultados: De las bases consultadas se obtuvo un total de 120 referencias de las cuales se aceptaron solo 55 que resaltan los aspectos más relevantes de la fisiopatología de la intoxicación con etanol y ciertos aspectos a nivel molecular relacionados con los efectos sobre el SNC. Conclusiones: Los efectos del EtOH sobre el sistema nervioso pueden ser consecuencia de un consumo agudo y excesivo o secundario a un consumo crónico, en relación a un estado de adicción y dependencia al mismo. La toxicidad sobre el sistema nervioso es consecuencia directa de la agresión del etanol o por diferentes trastornos metabólicos ligados a la toxicidad del mismo sobre otros órganos. La neurotoxicidad del alcohol se debe a la activación del sistema inmunitario innato en el cerebro, que promueve compuestos inflamatorios que serían los responsables del daño de la morfología neuronal, además de la alteración neuroanatómica de la corteza.


Alcohol is a toxic that acts as a central nervous system (CNS) depressant. Its effects are a direct consequence of its action on cell membranes and on neurotransmitters. Neurons are particularly sensitive to the neurotoxic effect of Ethanol (EtOH) and their exposure affects neuronal morphology, since a reduction in the length of the dendritic tree has recently been observed. EtOH also causes changes in the expression of synaptic proteins, increased endoplasmic reticulum light, as well as disorganization of the Golgi apparatus and mitochondria. Objectives: To describe the effects of Ethanol at the cellular and molecular level in the Central Nervous System and its repercussion on human health. Methods: A literature search was conducted in the following databases available on the web: PubMed, ScienceDirect, Jama Journal, Scielo and health portals, using the keywords: "ethanol and pharmacology", "alcohol and toxicology", "Neurotoxicity and ethanol". Results: From the databases consulted, a total of 120 references were obtained, of which 55 are accepted, highlighting the most relevant pathophysiology of ethanol intoxication and the minimum number of molecular levels related to the effects on the CNS. Conclusions: The effects of EtOH on the nervous system can be a consequence of an acute and excessive consumption or secondary to a chronic consumption, in relation to a state of addiction and dependence to it. The toxicity on the nervous system is the direct consequence of the aggression of ethanol and the different metabolic disorders linked to the toxicity of the same on other organs. The neurotoxicity of alcohol is due to the activation of the immune system in the brain, which promotes inflammatory cascade that cause those responsible for neuron damage, in addition to neuroanalytic alteration of the cortex.


O álcool é um tóxico que atua como um depressor do sistema nervoso central (SNC). Seus efeitos são conseqüência direta de sua ação nas membranas celulares e nos neurotransmissores. Os neurônios são particularmente sensíveis ao efeito neurotóxico do Etanol (EtOH) e sua exposição afeta a morfologia neuronal, uma vez que uma redução no comprimento da árvore dendrítica foi recentemente observada. EtOH também provoca alterações na expressão de proteínas sinápticas, aumento da luz do retículo endoplasmático, bem como desorganização do aparelho de Golgi e das mitocôndrias. Objetivos: Descrever os efeitos do Etanol no nível celular e molecular no Sistema Nervoso Central e sua repercussão na saúde humana. Métodos: Uma investiga çao bibliográfica foi realizada nos seguintes bancos de dados disponíveis na web: PubMed, ScienceDirect, Jama Journal, Scielo E portais de saúde, usando as palavras-chave: "ethanol and pharmacology", "Álcool e toxicologia", "Neurotoxicidade e etanol". Resultados: partir dos bancos de dados consultados, foram obtidas 120 referências, das quais 55 são aceitas, destacando a fisiopatologia mais relevante da intoxicação por etanol e o número mínimo de níveis moleculares relacionados aos efeitos no SNC. Conclusões: Os efeitos do EtOH no sistema nervoso podem ser uma conseqüência de um consumo agudo e excessivo ou secundário a um consumo crônico, em relação a um estado de dependência e dependência. A toxicidade no sistema nervoso é a conseqüência direta da agressão do etanol e dos diferentes distúrbios metabólicos ligados à toxicidade do mesmo em outros órgãos. A neurotoxicidade do álcool deve-se à ativação do sistema imunológico no cérebro, que promove a cascata inflamatória que causa os responsáveis pelo dano neuronal, além da alteração neuroanalítica do córtex.


Assuntos
Humanos , Alcoolismo , Sinapses , Morte Celular , Síndromes Neurotóxicas
14.
Invest Ophthalmol Vis Sci ; 57(14): 6447-6454, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27893109

RESUMO

Purpose: To evaluate the efficacy and safety of SYL1001, a short interfering (si) RNA targeting the transient receptor potential cation channel subfamily V member 1 (TRPV1), for the treatment of dry eye disease (DED). Methods: This study combines a phase I and two phase II clinical trials to test different doses of SYL1001 in a total of 156 healthy subjects and patients with DED. After 10 days of treatment, the primary efficacy endpoints were the effect on (1) the scoring in the Visual Analogue Scale (VAS) and Ocular Surface Disease Index (OSDI) questionnaires, and (2) ocular tolerance evaluated by corneal fluorescein staining and conjunctival hyperemia. Secondary endpoints included the assessment of systemic and local tolerance. Results: Topical administration of SYL1001 1.125% once daily produced a significant decrease in VAS scores compared with placebo from day 4 until the end of treatment (change from baseline at day 10: -1.73 ± 0.32 vs. -0.91 ± 0.34; P = 0.013). For all treatments, OSDI scores were significantly reduced compared to their respective baseline values (P < 0.01), although no significant changes were detected between groups. Conjunctival hyperemia (quantified as normal or abnormal) significantly improved after instillation of SYL1001 1.125% compared with placebo (50% vs. 20%; P < 0.05). Excellent tolerability was reported, with no differences in the rates of occurrence of adverse events between groups. Conclusion: These trials achieved their primary endpoints of identifying the most effective dose of SYL1001 (1.125%). SYL1001 showed a large safety margin and may provide novel therapeutic opportunity for the relief of dry eye. (ClinicalTrials.gov numbers, NCT01438281, NCT01776658, and NCT02455999.).


Assuntos
Síndromes do Olho Seco/tratamento farmacológico , RNA Interferente Pequeno/administração & dosagem , Canais de Cátion TRPV/metabolismo , Lágrimas/metabolismo , Adolescente , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/metabolismo , Feminino , Humanos , Masculino , Soluções Oftálmicas/administração & dosagem , Estudos Prospectivos , Canais de Cátion TRPV/efeitos dos fármacos , Lágrimas/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
15.
Rev. MED ; 24(2): 88-99, jul.-dic. 2016. ilus
Artigo em Espanhol | LILACS | ID: biblio-957299

RESUMO

La neumoconiosis es caracterizada por el depósito nodular difuso de polvo en los pulmones como resultado de la exposición prolongada a polvo bituminoso o de antracita en los trabajadores de las minas de carbón. La neumoconiosis de los mineros del carbón también se denomina enfermedad del pulmón negro o antracosis. Un minero del carbón que padece o desarrolla una Antracosis puede presentar numerosos nódulos redondeados pulmonares en poco tiempo. Dichos nódulos aparecen en ocasiones en ausencia de una antracosis simple. A nivel histológico pueden parecerse a los nódulos reumatoides, pero tienen una zona periférica de inflamación aguda. Estos nódulos representan la respuesta inmunológica a la diátesis reumatoide asociada. En Colombia la minería es un factor estratégico a nivel económico para su desarrollo. Sin embargo, existen factores negativos derivados de ésta que giran en una carrera sin control ni reglas claras; esta actividad hace trámite en el territorio, arrastrando una estela de problemas sobre la sociedad, el ambiente, el bienestar y la salud de las personas.


Pneumoconiosis is characterized by diffuse nodular dust in the lungs as a result of prolonged exposure of workers in coal mines to bituminous dust or anthracite. Pneumoconiosis presented in coal miners is also called black lung disease lung. A coal miner who develops Anthracosis can present numerous pulmonary rounded nodules in a short time. These nodules appear sometimes in the absence of a simple anthracosis. Histologically they may look like resemble rheumatoid nodules, with the difference; they have a peripheral area of acute inflammation. These nodes represent the immune response associated to rheumatoid diathesis. In Colombia, mining is a strategy for economical development. However, there are negative factors arising rotating it in a race without control or clear rules; This activity is pending in the territory, dragging a trail of problems on society, the environment, welfare and People's health


A pneumoconiose é caracterizada por poeira nodular difusa nos pulmões como resultado da exposição prolongada a poeiras betuminosas ou antracite nas minas de carvão. Pneumoconiose de mineiros de carvão também chamado preto ou preto doença pulmonar pulmão. Um mineiro de carvão que sofre ou desenvolve uma antracose pode apresentar numerosos nódulos pulmonares arredondados em um curto espaço de tempo. Estes nódulos aparecem às vezes na ausência de uma antracose simples. Histologicamente podem assemelhar-se a nódulos reumatóides, mas têm uma área periférica de inflamação aguda. Esses nódulos representam a resposta imune associada à diátese reumatóide. A mineração na Colômbia é um fator estratégico economicamente para o desenvolvimento. No entanto, existem fatores negativos decorrent surgindo girando-o em uma corrida sem controle ou regras claras. Esta atividade está pendente no território, arrastando um rastro de problemas na sociedade, o meio ambiente, bem-estar e da saúde das pessoas.


Assuntos
Humanos , Masculino , Adulto , Pneumoconiose , Macrófagos Alveolares , Colômbia , Dispneia , Antracose
17.
Eur Arch Otorhinolaryngol ; 273(8): 2085-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26739302

RESUMO

Training in functional endoscopic sinus surgery (FESS) is an essential part of each ENT resident and it takes place on a very fragile area. This study focus on showing the learning curve of FESS, using an anatomical model such as the sheep's head. Four residents in our centre performed dissections. Each of these residents operated eight sheep's head. They performed an endoscopic septoplasty followed by maxillary antrostomy, total ethmoidectomy and frontal sinusotomy on every head. A staff member guided all procedures and checked for the appropriate dissection and complications occurred. Analysis was made upon the residents' performance of their first four septoplasties and eight nasal sides against their subsequent performance of the same. Final procedures presented better outcomes than the initial ones on every step of them. Results were measured by means of decrease of time (P < 0.0001) and complications, showing no major complications on the latest ones. Sheep's head is a suitable substitute for the cadaveric human head, to obtain the surgical skills needed for FESS procedures. Sheep's nasal cavity allows gaining dexterity and it is an easy model to obtain.


Assuntos
Internato e Residência , Curva de Aprendizado , Modelos Animais , Septo Nasal/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/educação , Seios Paranasais/cirurgia , Animais , Dissecação/educação , Endoscopia/educação , Endoscopia/métodos , Seio Etmoidal/cirurgia , Seio Frontal/cirurgia , Cabeça , Humanos , Masculino , Seio Maxilar/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Ovinos
18.
Clin Genitourin Cancer ; 13(6): 493-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26027772

RESUMO

Bladder cancer remains a frequent cancer worldwide, and most tumors are diagnosed at localized stages. Urothelial carcinoma (UC) accounts for 90% of bladder cancer cases. Sarcomatoid carcinoma (SaC) of the bladder is a rare variant (0.5% of total bladder cancers) characterized by 2 components based on histology; the epithelial and mesenchymal phenotypes, which can be easily differentiated by immunohistochemistry. SaC has similar epidemiologic features to UC but different behavior, aggressiveness, and prognosis. In this review, we summarize the main differences between UC bladder cancers and SaC subtypes. The therapeutic strategies used in SaC today do not differ much from those used for the urothelial variant. However, there is still no standard treatment--the result of a lack of clinical trials for the sarcomatoid variant. Further multicenter comparative studies are needed to devise a better treatment strategy for patients with this rare histologic tumor subtype.


Assuntos
Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Prognóstico , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapia
20.
Artigo em Inglês | MEDLINE | ID: mdl-18003261

RESUMO

We present and validate a quantitative, multidimensional image analysis protocol to assist in the early detection of lung cancer in minimal samples of bronchoalveolar lavage (BAL). To that end we stained BAL samples using Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms (FICTION). Our method allows preliminary immunophenotypic detection of rare cancerous candidate cells, followed by accurate three-dimensional analysis of genomic integrity, to confirm or refute the initial assessment. Our results show that our automated analysis can accurately assist a human expert in the diagnostic evaluation of BAL samples.


Assuntos
Algoritmos , Inteligência Artificial , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/patologia , Reconhecimento Automatizado de Padrão/métodos , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Tamanho da Amostra , Sensibilidade e Especificidade
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