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1.
Infect Immun ; 91(12): e0024523, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37916806

RESUMO

Virus-like particles (VLPs) are promising nanotools for the development of subunit vaccines due to high immunogenicity and safety. Herein, we explored the versatile and effective Tag/Catcher-AP205 capsid VLP (cVLP) vaccine platform to address the urgent need for the development of an effective and safe vaccine against gonorrhea. The benefits of this clinically validated cVLP platform include its ability to facilitate unidirectional, high-density display of complex/full-length antigens through an effective split-protein Tag/Catcher conjugation system. To assess this modular approach for making cVLP vaccines, we used a conserved surface lipoprotein, SliC, that contributes to the Neisseria gonorrhoeae defense against human lysozyme, as a model antigen. This protein was genetically fused at the N- or C-terminus to the small peptide Tag enabling their conjugation to AP205 cVLP, displaying the complementary Catcher. We determined that SliC with the N-terminal SpyTag, N-SliC, retained lysozyme-blocking activity and could be displayed at high density on cVLPs without causing aggregation. In mice, the N-SliC-VLP vaccines, adjuvanted with AddaVax or CpG, induced significantly higher antibody titers compared to controls. In contrast, similar vaccine formulations containing monomeric SliC were non-immunogenic. Accordingly, sera from N-SliC-VLP-immunized mice also had significantly higher human complement-dependent serum bactericidal activity. Furthermore, the N-SliC-VLP vaccines administered subcutaneously with an intranasal boost elicited systemic and vaginal IgG and IgA, whereas subcutaneous delivery alone failed to induce vaginal IgA. The N-SliC-VLP with CpG (10 µg/dose) induced the most significant increase in total serum IgG and IgG3 titers, vaginal IgG and IgA, and bactericidal antibodies.


Assuntos
Neisseria gonorrhoeae , Vacinas de Partículas Semelhantes a Vírus , Animais , Feminino , Humanos , Camundongos , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Capsídeo , Imunoglobulina A , Imunoglobulina G , Camundongos Endogâmicos BALB C , Muramidase , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/imunologia , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia
2.
ACS Appl Polym Mater ; 5(2): 1180-1190, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36817334

RESUMO

Hydrogels are commonly used materials in tissue engineering and organ-on-chip devices. This study investigated the nanomechanical properties of monolithic and multilayered poly(ethylene glycol) diacrylate (PEGDA) hydrogels manufactured using bulk polymerization and layer-by-layer projection lithography processes, respectively. An increase in the number of layers (or reduction in layer thickness) from 1 to 8 and further to 60 results in a reduction in the elastic modulus from 5.53 to 1.69 and further to 0.67 MPa, respectively. It was found that a decrease in the number of layers induces a lower creep index (CIT) in three-dimensional (3D) printed PEGDA hydrogels. This reduction is attributed to mesoscale imperfections that appear as pockets of voids at the interfaces of the multilayered hydrogels attributed to localized regions of unreacted prepolymers, resulting in variations in defect density in the samples examined. An increase in the degree of cross-linking introduced by a higher dosage of ultraviolet (UV) exposure leads to a higher elastic modulus. This implies that the elastic modulus and creep behavior of hydrogels are governed and influenced by the degree of cross-linking and defect density of the layers and interfaces. These findings can guide an optimal manufacturing pathway to obtain the desirable nanomechanical properties in 3D printed PEGDA hydrogels, critical for the performance of living cells and tissues, which can be engineered through control of the fabrication parameters.

3.
Rev. urug. cardiol ; 38(1): e301, 2023. ilus, tab
Artigo em Espanhol | BNUY, UY-BNMED, LILACS | ID: biblio-1442150

RESUMO

La amiloidosis cardíaca es una miocardiopatía restrictiva infiltrativa secundaria al depósito extracelular de amiloide. Las diferentes técnicas de imagen cardíaca permiten la evaluación de forma no invasiva. El ecocardiograma juega un rol central en la evaluación diagnóstica, pronóstica y ayuda a guiar el tratamiento. El objetivo de este artículo de revisión es describir las diferentes herramientas que nos brinda la ecocardiografía, poniendo énfasis en el strain por speckle tracking y describir su rol en el diagnóstico de esta patología.


Cardiac amyloidosis is an infiltrative restrictive cardiomyopathy secondary to extracellular amyloid deposition. Different cardiac imaging techniques allow noninvasive evaluation. Echocardiography plays a central role in diagnostic and prognostic evaluation and helps to guide treatment. The aim of this review is to describe the different tools provided by echocardiography, with emphasis on speckle tracking strain and to describe its role in the diagnosis of this pathology.


A amiloidose cardíaca é uma cardiomiopatia restritiva infiltrativa secundária ao depósito de amiloide extracelular. Diferentes técnicas de imagem cardíaca permitem fazer uma análise não invasiva. A ecocardiografia desempenha um papel central no diagnóstico e na avaliação prognóstica e ajuda a orientar o tratamento. O objetivo deste artigo de revisão é descrever as diferentes ferramentas proporcionadas pela ecocardiografia, com ênfase no strain por speckle tracking, e descrever o seu papel no diagnóstico desta patologia.


Assuntos
Ecocardiografia Doppler/métodos , Cardiopatias/diagnóstico por imagem , Amiloidose/diagnóstico por imagem , Prognóstico , Sensibilidade e Especificidade , Ecocardiografia Transesofagiana/métodos
4.
In. Huart Sottolano, Regina Natalia; Biafore, Federico. Imagen por resonancia magnética desde cero: manual para estudiantes y docentes. Montevideo, Oficina del Libro-FEFMUR, c2023. p.157-179, ilus.
Monografia em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1437725
6.
J Craniofac Surg ; 33(7): e680-e685, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35148530

RESUMO

ABSTRACT: Mandibular reconstruction is a challenging procedure, especially in cancer patients with defects that are greater than 6 cm. Free vascularized fibular flap is the gold standard treatment in these cases since it allows three-dimensional restoration of the lost segments after ablative surgery in addition to providing the possibility of a subsequent implant-supported rehabilitation improving the functional and aesthetic outcomes of the surgery.To obtain accurate results, preoperative planning must be done with detail. Approaches for the preoperative planning include both the conventional analog planning and the virtual planning that are valid alternatives in meeting the trans-surgical requirements.This study makes a comparative analysis of 2 clinical cases with a diagnosis of squamous cell carcinoma that were reconstructed using a vascularized fibular free flap. The first case was planned using the conventional analog method whereas the second case was planned using the virtual planning approach.The impact of virtual planning and conventional analog planning on preoperative planning time, ischemia period, and total surgical time is analyzed according to the experience obtained in the cases presented. In addition, the authors described the technique used for each planning method along with a literature review in which the results are contrasted and discussed.


Assuntos
Retalhos de Tecido Biológico , Reconstrução Mandibular , Transplante Ósseo , Estética Dentária , Fíbula/cirurgia , Humanos , Mandíbula/cirurgia , Reconstrução Mandibular/métodos , Duração da Cirurgia
7.
Int J Biol Macromol ; 168: 722-732, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33232700

RESUMO

Natural polymer-based hybrid nanocomposites have been proposed as one of the most promising tools for biomedical applications, including disease treatment and diagnosis procedures. Xyloglucan nanocapsules can simultaneously load magnetic iron oxide nanoparticles and bioactive for a specific tissue, reducing the processes of degradation and metabolic inactivation of molecules with biological activity. In this work, magnetic nanocapsules of xyloglucan loaded with hydrophilic sulfated quercetin (MNXQ_SO3) were successfully synthesized by inverse miniemulsion process through interfacial polymerization. The polymeric shell formation of nanocapsules was evidenced by Fourier Transform Infrared spectroscopy and Transmission Electron Microscopy. The ferrofluid (Fe3O4@PAAS) incorporated into the xyloglucan nanocapsules was synthesized by hydrothermal method, using polyacrylic acid sodium salt as coating. Dynamic Light Scattering technique confirmed the nanomeric dimensions (202.3 nm) and the good colloidal stability (-40.2 mV) of MNXQ_SO3. The saturation magnetization analyses pointed out the superparamagnetic behavior of Fe3O4@PAAS (48 emu/g) and MNXQ_SO3 (4.2 emu/g). MNXQ_SO3 was able to modify the release profile of sulfated quercetin (67%) when compared to the free bioactive (100%), exhibiting a release profile compatible with the zero-order kinetic model. The results showed that the development of MNXQ_SO3 presents a new perspective for biomedical applications, including studies of targeted drug delivery.


Assuntos
Glucanos/química , Quercetina/síntese química , Sulfetos/química , Xilanos/química , Sistemas de Liberação de Medicamentos , Difusão Dinâmica da Luz , Cinética , Nanopartículas de Magnetita , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Quercetina/química , Quercetina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Rev. urug. cardiol ; 36(3): e702, 2021. ilus
Artigo em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1367083

RESUMO

La hernia hiatal es una entidad relativamente frecuente y puede ser un hallazgo incidental en un estudio ecocardiográfico. Describimos el caso de una paciente con diagnóstico de masa en la aurícula izquierda (AI) sin clara etiología, a quien se le realiza el diagnóstico de hernia hiatal por resonancia magnética cardíaca (RMC) y luego se demuestra mediante ecocardiografía de contraste el contenido gástrico de la masa tras la ingestión de una bebida carbonatada, lo que permite de forma rápida y sencilla aclarar el diagnóstico.


Hiatal hernia is a relatively common entity, and may be an incidental finding in an echocardiographic study. We describe the case of a patient with a diagnosis of a mass in the left atrium with no clear etiology, in whom the diagnosis of hiatal hernia is made by cardiac magnetic resonance imaging and then demonstrated by contrast echocardiography the gastric content of the mass after the ingestion of a carbonated drink, which allows quickly and easily to clarify the diagnosis.


A hérnia de hiato é uma entidade relativamente comum, e pode ser um achado incidental em um estudo ecocardiográfico. Descrevemos o caso de um paciente com diagnóstico de massa em átrio esquerdo sem etiologia definida, em que o diagnóstico de hérnia de hiato é feito por ressonância magnética cardíaca e posteriormente demonstrado por ecocardiografia contrastada com uma bebida gaseificada, permitindo esclarecer de forma rápida e fácil o diagnóstico.


Assuntos
Humanos , Feminino , Idoso , Cardiopatias/diagnóstico por imagem , Hérnia Hiatal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tamponamento Cardíaco/diagnóstico por imagem , Ecocardiografia Doppler , Diagnóstico Diferencial , Imagem Multimodal , Água Carbonatada , Átrios do Coração/diagnóstico por imagem
9.
Vaccine ; 38(51): 8175-8184, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33162204

RESUMO

Bacterial surface lipoproteins are emerging as attractive vaccine candidates due to their biological importance and the feasibility of their large-scale production for vaccine manufacturing. The global prevalence of gonorrhea, resistance to antibiotics, and serious consequences to reproductive and neonatal health necessitate development of effective vaccines. Reverse vaccinology identified the surface-displayed L-methionine binding lipoprotein MetQ (NGO2139) and its homolog GNA1946 (NMB1946) as gonococcal and meningococcal vaccine candidates, respectively. Here, we assessed the suitability of MetQ for inclusion in a gonorrhea vaccine by examining MetQ conservation, its function inNeisseria gonorrhoeae (Ng) pathogenesis, and its ability to induce protective immune responses using a female murine model of lower genital tract infection. In-depth bioinformatics, phylogenetics and mapping the most prevalent Ng polymorphic amino acids to the GNA1946 crystal structure revealed remarkable MetQ conservation: ~97% Ng isolates worldwide possess a single MetQ variant. Mice immunized with rMetQ-CpG (n = 40), a vaccine containing a tag-free version of MetQ formulated with CpG, exhibited robust, antigen-specific antibody responses in serum and at the vaginal mucosae including IgA. Consistent with the activity of CpG as a Th1-stimulating adjuvant, the serum IgG1/IgG2a ratio of 0.38 suggested a Th1 bias. Combined data from two independent challenge experiments demonstrated that rMetQ-CpG immunized mice cleared infection faster than control animals (vehicle, p < 0.0001; CpG, p = 0.002) and had lower Ng burden (vehicle, p = 0.03; CpG, p < 0.0001). We conclude rMetQ-CpG induces a protective immune response that accelerates bacterial clearance from the murine lower genital tract and represents an attractive component of a gonorrhea subunit vaccine.


Assuntos
Gonorreia , Vacinas Meningocócicas , Animais , Vacinas Bacterianas/genética , Feminino , Gonorreia/prevenção & controle , Lipoproteínas/genética , Camundongos , Camundongos Endogâmicos BALB C , Neisseria gonorrhoeae/genética
10.
Front Microbiol ; 11: 607693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33519754

RESUMO

Codon usage bias (the preferential use of certain synonymous codons (optimal) over others is found at the organism level (intergenomic) within specific genomes (intragenomic) and even in certain genes. Whether it is the result of genetic drift due to GC/AT content and/or natural selection is a topic of intense debate. Preferential codons are mostly found in genes encoding highly-expressed proteins, while lowly-expressed proteins usually contain a high proportion of rare (lowly-represented) codons. While optimal codons are decoded by highly expressed tRNAs, rare codons are usually decoded by lowly-represented tRNAs. Whether rare codons play a role in controlling the expression of lowly- or temporarily-expressed proteins is an open question. In this work we approached this question using two strategies, either by replacing rare glycine codons with optimal counterparts in the gene that encodes the cell cycle protein Cdc13, or by overexpression the tRNA Gly that decodes rare codons from the fission yeast, Schizosaccharomyces pombe. While the replacement of synonymous codons severely affected cell growth, increasing tRNA levels affected the aggregation status of Cdc13 and cell division. These lead us to think that rare codons in lowly-expressed cyclin proteins are crucial for cell division, and that the overexpression of tRNA that decodes rare codons affects the expression of proteins containing these rare codons. These codons may be the result of the natural selection of codons in genes that encode lowly-expressed proteins.

11.
Int. j. odontostomatol. (Print) ; 13(1): 51-57, mar. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-990064

RESUMO

RESUMEN: El barro dentinario producido durante tratamiento endodóntico puede ser extruido hacia el tejido periradicular junto con el irrigante, produciendo inflamación y dolor postoperatorio. Comparar la cantidad de extrusión apical de barro dentinario e irrigante, producido durante la preparación químico-mecánica, por dos sistemas de instrumentación Rotatoria (Mtwo), y Reciprocante (Reciproc), complementado con irrigación pasiva o activa (Endoactivator). Cuarenta y ocho premolares (48) inferiores, fueron aleatoriamente distribuidos en cuatro grupos de estudio (n=12 dientes), (1) Rotatorio-pasiva, (2) Reciprocante-pasiva, (3) Rotatorio-activa y (4) Reciprocante-activa. Los conductos radiculares fueron instrumentados de acuerdo a las instrucciones del fabricante, e irrigados con hipoclorito de sodio al 5 %. El barro dentinario e irrigante extruido, fueron recolectados en tubos Eppendorf previamente pesados. Se calcularon los valores de extrusión de barro dentinario e irrigante para cada grupo. Los datos fueron analizados con el análisis de varianza ANOVA. En todos los grupos se produjo extrusión apical. No se encontraron diferencias estadísticamente significativas en la extrusión apical de barro dentinario, entre los grupos estudiados (P = 0,068), sin embargo, al analizar la extrusión de irrigantes, se evidenció diferencia estadísticamente significativa entre los grupos 1 y 4 (P< 0,05), entre los demás grupos no se observaron diferencias estadísticamente significativas. (P > 0,05). Bajo las condiciones de este estudio, los sistemas rotarios y reciprocante, extruyen sólido y líquido, siendo el sistema reciprocante el que produce mayor extrusión de líquido, tanto con irrigación activa como pasiva.


ABSTRACT: The smear layer produced during endodontic treatment can be extruded into the periradicular tissue together with the irrigant, producing inflammation and postoperative pain. The purpose of this in vitro study was to compare the amount of apical extrusion, produced during the endodontic preparations with two rotary instrumentation systems using passive and active irrigation. Forty-eight (48) mandibular premolars were randomly assigned to 4 groups (n = 12 teeth), (1) Rotatory - passive, (2) Reciprocating passive, (3) Rotatory-active, (4) Reciprocating- active. The root canals were instrumented according to the manufacturer's instructions and irrigated with 5 % sodium hypochlorite. Extruded debris and irrigant were collected in previously weighed Eppendorf tubes. The extrusion values were calculated for each group. The data were analyzed with the ANOVA analysis of variance. Results: Apical extrusion was produced in all groups. No statistically significant differences were found in the apical extrusion of smear layer, between the groups studied (P = 0.068), however, when analyzing the extrusion of irrigants, a statistically significant difference was evidenced between groups 1 and 4 (P <0.05). , among the other groups no statistically significant differences were observed. (P> 0.05). Under the conditions of this study, the reciprocating and rotary systems, extrude solid and liquid, being the reciprocating system the one that produces more extrusion of liquid, with both active and passive irrigation.


Assuntos
Humanos , Irrigantes do Canal Radicular , Camada de Esfregaço , Irrigação Terapêutica/instrumentação , Titânio/química , Dente Pré-Molar , Técnicas In Vitro , Análise de Variância , Níquel/química
13.
Front Immunol ; 9: 2793, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30564232

RESUMO

Expanding efforts to develop preventive gonorrhea vaccines is critical because of the serious health consequences combined with the prevalence and the dire possibility of untreatable gonorrhea. Reverse vaccinology, which includes genome and proteome mining, has proven successful in the discovery of vaccine candidates against many pathogenic bacteria. Here, we describe proteomic applications including comprehensive, quantitative proteomic platforms and immunoproteomics coupled with broad-ranging bioinformatics that have been applied for antigen mining to develop gonorrhea vaccine(s). We further focus on outlining the vaccine candidate decision tree, describe the structure-function of novel proteome-derived antigens as well as ways to gain insights into their roles in the cell envelope, and underscore new lessons learned about the fascinating biology of Neisseria gonorrhoeae.


Assuntos
Antígenos/imunologia , Vacinas Bacterianas/imunologia , Gonorreia/imunologia , Proteoma/imunologia , Animais , Membrana Celular/imunologia , Biologia Computacional/métodos , Humanos , Neisseria gonorrhoeae/imunologia , Proteômica/métodos , Relação Estrutura-Atividade
14.
Sci Rep ; 8(1): 14900, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297853

RESUMO

ß-lactam antibiotics, such as penicillin share a very unstable chemical structure. In water-based solutions, such as those used for clinical applications, the ß-lactam ring is readily opened due to a nucleophilic or electrophilic attack, leading to the loss of antimicrobial activity. Since the achievement and maintenance of optimum therapeutic levels of ß-lactam antibiotics is critical for the resolution of many infectious clinical situations, and to avoid antibiotic resistance generation, the design of new non-aqueous dosage forms is urgent. Recently, natural deep eutectic solvents (NADES) have emerged as alternative non-toxic and non-aqueous solvents for different biomedical applications. In this work, we formulated and characterized a NADES composed by betaine and urea (BU). Using this solvent, we evaluated the stability of clavulanic acid (CLV) and imipenem (IMP) and characterized their antimicrobial activities calculating the minimal inhibitory concentration. Characterization of BU solvent by infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR) indicated that the obtained solvent has a microstructure mainly based on hydrogen bonding interactions and water addition strongly affects its dynamic. The stability of ß-lactam antibiotic IMP and CLV using this solvent was increased by 7 fold and 2.5 fold respectively compared to water when analysed seven days after being dissolved. Microbiological assays showed that antibacterial activity at day seven was significantly decreased for both CLV and IMP when dissolved in water, while no change in their antibacterial properties was observed when antibiotics were dissolved in BU. The increased stability of IMP and CLV in BU may be related to the inert behaviour of the solvent and the higher dynamic restriction that helps antibiotics to maintain a more stable conformation. These data suggest the potential use of BU as a solvent to prevent degradation of ß-lactam antibiotics.


Assuntos
Antibacterianos/farmacologia , Solventes/química , beta-Lactamas/farmacologia , Betaína/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Ácido Clavulânico/farmacologia , Escherichia coli/efeitos dos fármacos , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Ureia/química , Vibração , Água/química
15.
Appl Radiat Isot ; 140: 238-246, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30071415

RESUMO

An onshore radiometric survey sampled in situ the isotopes U238, Th232, K40, and Rn222 to build maps of normalized values for each element containing negative and positive radiometric anomalies, which could associate with hydrocarbon deposits in the subsoil. The vertical migration of hydrocarbon, water or other gases would have generated the different isotope anomalies. In four 2D seismic sections of the study area, three on dip direction and another in strike direction, we interpreted unconformities, flooding surface, and maximum flooding surfaces, as well as Cretaceous tops. In structural contour maps made from aforementioned seismic sections, we observe structural highs and structures such as truncations of strata. These structures in-depth coincide with uranium, thorium, potassium and radon anomalies seen on the surface. This oil and gas exploration approach that integrates radiometric and emanometric integrated with seismic prospecting can help to reduce the risk in hydrocarbons projects (however, radiometric anomalies are not uniquely associated with hydrocarbons). This work shows a correlation between radiometric (uranium, thorium, and potassium) and emanometric (radon) data in the surface with structures in the subsurface suck like truncation, that could present hydrocarbon, however, on this sub-basin, there has not been found commercial hydrocarbon.

16.
Rev. Fac. Cienc. Méd. Univ. Cuenca ; 36(1): 9-16, Junio 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-998708

RESUMO

Mundialmente, el cáncer colo-rectal constituye la tercera neoplasia más común en hombres y la segunda en mujeres. Las vías de tumorogénesis, nos permite subclasificar a los pacientes y protocolizar tratamientos. Lainestabilidad microsatelital constituye una de estas vías; se presenta en un 15% a 20% en el carcinoma colo-rectal y su presencia se asocia a un mejor pronóstico. Objetivo:Determinar la frecuencia de inestabilidad microsatelital y su distribución de acuerdo a los factores pronósticos en biopsias de pacientes con cáncer colo-rectal atendidos en el Instituto del Cáncer SOLCA-Cuenca durante el periodo 2004-2014".Método:Es un estudio de tipo observacional, analítico. Se estudiaron 240 pacientes con cáncer colo-rectal, diagnosticados en Departamento de Patología del Instituto del Cáncer Solca Cuenca y que disponían de su material de biopsias en donde se realizaron las técnicas de inmunohistoquímica con 4 marcadores MLH1, MSH2, MSH6, PMS2. Resultados:El 37.9% correspondió a hombres y el 62.1% a mujeres. La media de edad fue 66.2 años. El 58.75% (n= 141) tuvieron localización en colon. Se observó falta de expresión proteica en un 24.2 % (58 pacientes). En cuanto a que proteínas, el 68.96% (40 casos) fueron MLH1/PMS2; 1.72 % (1 caso) MSH2/MSH6.De los casos que no expresaron las proteínas el 87.93% se localizaron en el colon; 79.3% fueron adenocarcinoma; 58.6% fueron grado moderado y 37.9% fueron etapa II. En el análisis bivariado se estableció asociación estadísticamente significativa entre la inestabilidad microsatelital con localización del tumor (OR 7 . 4 ; IC 3.2-17) y el grado de diferenciación (OR 2.8; IC 1.5- 5.4). Conclusiones: Se recomienda el uso protocolizado dentro del tratamiento del cáncer colo-rectal.


Worldwide, colorectal cancer is the third most common neoplasm in men and the second in women. Tumorigenesis pathways allow us to sub-classify patients and protocolize treatments. The microsatellite instability constitutes one of these pathways; it is present in a 15% to 20% in colorectal carcinoma; its presence is associated with a better prognosis.Objective:To determine the frequency of microsatellite instability and its distribution according to prognostic factors in biopsies of patients with colorectal cancer in the Solca-Cuenca Cancer Institute during the period 2004-2014. Method:It is an observational, analytical study. About 240 patients with colorectal cancer were studied, they were diagnosed in the Pathology Department of the Cuenca Cancer Institute and who had their biopsy material where the immunohistochemical techniques were performed with 4 markers MLH1, MSH2, MSH6, and PMS2.Results:The 37.9% corresponded to men and 62.1% to women. The average age was 66.2 years. The 58.75% (n = 141) had localization in the colon. A lack of protein expression was observed in 24.2% (58 patients). Regarding to proteins, 68.96% (40 cases) were MLH1 / PMS2; 1.72% (1 case) MSH2 / MSH6. About the cases that did not express the proteins, 87.93% were located in the colon; 79.3% were adenocarcinoma; 58.6% were moderate grade and 37.9% were stage II. In the bivariate analysis, a statistically significant association was established between microsatellite instability with tumor location (OR 7 . 4 , CI 3.2-17) and degree of differentiation (OR 2.8, CI 1.5- 5.4). Conclusions:The protocolized use is recommended within the treatment of colorectal cancer.


Assuntos
Humanos , Masculino , Feminino , Idoso , Neoplasias Colorretais , Instabilidade de Microssatélites , Carcinogênese , Prognóstico , Terapêutica , Imuno-Histoquímica
17.
J Antimicrob Chemother ; 73(6): 1611-1619, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29506074

RESUMO

Background: Klebsiella pneumoniae is an opportunistic pathogen and many strains are multidrug resistant. KPC is one of the most problematic resistance mechanisms, as it confers resistance to most ß-lactams, including carbapenems. A promising platform technology for treating infections caused by MDR pathogens is the nucleic acid-like synthetic oligomers that silence bacterial gene expression by an antisense mechanism. Objectives: To test a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) in a mouse model of K. pneumoniae infection. Methods: PPMOs were designed to target various essential genes of K. pneumoniae and screened in vitro against a panel of diverse strains. The most potent PPMOs were further tested for their bactericidal effects in broth cultures and in established biofilms. Finally, a PPMO was used to treat mice infected with a KPC-expressing strain. Results: The most potent PPMOs targeted acpP, rpmB and ftsZ and had MIC75s of 0.5, 4 and 4 µM, respectively. AcpP PPMOs were bactericidal at 1-2 × MIC and reduced viable cells and biofilm mass in established biofilms. In a mouse pneumonia model, therapeutic intranasal treatment with ∼30 mg/kg AcpP PPMO improved survival by 89% and reduced bacterial burden in the lung by ∼3 logs. Survival was proportional to the dose of AcpP PPMO. Delaying treatment by 2, 8 or 24 h post-infection improved survival compared with control groups treated with PBS or scrambled sequence (Scr) PPMOs. Conclusions: PPMOs have the potential to be effective therapeutic agents against KPC-expressing, MDR K. pneumoniae.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Klebsiella pneumoniae/efeitos dos fármacos , Morfolinos/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/genética , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Morfolinos/síntese química , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia
18.
Rev. urug. cardiol ; 32nov. 2017.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1509074

RESUMO

Historia clínica: paciente de 16 años, sexo masculino, sin antecedentes patológicos. Cuadro de dos semanas de evolución de fiebre hasta 41 ºC, sin otros fenómenos acompañantes. Del examen se destaca: hemorragias en astilla. Temperatura axilar 39 ºC. Cardiovascular: ritmo regular de 92 cpm, ruidos cardiacos normales, sin soplos. Resto del examen sin alteraciones. Pruebas complementarias: estudios paraclínicos: hemograma: hemoglobina 10 g/dl, leucocitos: 241.000/ml (neutrófilos: 90%), velocidad de eritrosedimentacion 120 s. Proteína C reactiva 214 mg/l. TAC tórax-abdómen-pelvis: infarto esplénico. Hemocultivos: Staphylococcus aureus meticilino resistente. ETT: masa hiperecogénica con movilidad independiente a nivel del ápex del VI, pediculada, plilobulada, de 22 por 10 mm. Evolución clínica: se realiza resección quirúrgica de la masa y tratamiento antibiótico con vancomicina y gentamicina, con buena evolución posoperatoria. El estudio patológico de la masa resecada fue compatible con una vegetación, y el cultivo de la misma desarrolló Staphylococcus aureus meticilino resistente. Diagnóstico: endocarditis infecciosa aguda primaria mural del ventrículo izquierdo. Discusión: presentamos un caso de endocarditis infecciosa primaria mural del ventrículo izquierdo en un paciente sin cardiopatía predisponente ni endocarditis valvular concomitante. Esta es una entidad infrecuente y existen pocos casos reportados. Habitualmente su diagnóstico es tardío, presentándose muchas veces con fenómenos embólicos al momento del diagnóstico. Son factores de riesgo la inmunodepresión, la adicción a drogas intravenosas y la cirugía reciente. La ecocardiografía precoz es una herramienta de suma importancia para su diagnóstico, ya sea transtorácica o transesofágica, mientras que el diagnóstico por resonancia nuclear magnética se realiza en aquellos casos en que la ecocardiografía no es concluyente. El germen más frecuentemente implicado es el Staphylococcus aureus. Dada la escasa evidencia, se plantea una conducta similar a la de la endocarditis infecciosa.

19.
Rev. urug. cardiol ; 32nov. 2017.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1509081

RESUMO

Historia clínica: paciente de 36 años de edad, sexo femenino, HTA de reciente diagnóstico. Asintomática. Del examen físico cardiovascular se destaca: R2 desdoblado. ECG: bloqueo incompleto de rama derecha. ETT: comunicación interauricular (CIA) tipo ostium secundum (OS). Dilatación de cavidades derechas. Qp/Qs: 1,6. Presión pulmonar sistólica 35 mmHg. Pruebas complementarias: se realiza ETE bidimensional (ETE2D) que evidencia CIA tipo OS con extensión anterior de 15 por 13 mm, con borde aórtico de 2 mm y presencia de buenos bordes en el resto de sus sectores. Septum impresiona firme, no aneurismático. ETE tridimensional (ETE3D) evidencia CIA de forma oval con eje mayor anteroposterior de 17 mm, en posición descrita, de 13 mm de eje menor y borde aórtico de 2,7 mm. Evolución clínica: se decide cierre transcatéter con dispositivo Amplatzer bajo anestesia general y monitoreo con ETE2D. Presión arteria pulmonar 26/7/13 mmHg. Por oximetría Qp/Qs 2,4. Por técnica de balón oclusor diámetro máximo de CIA de 17 mm. A pesar del borde aórtico subóptimo y tomando en consideración la buena calidad del resto de los bordes, la forma oval de orificio y el arco relativamente escaso del mismo en la topografía yuxta-aórtica, se decide proceder al implante, seleccionándose dispositivo no 19. Luego de desplegar ambos discos se corrobora posición con ecocardiografía. Se libera dispositivo luego de maniobra de Minnesota. Ecografía de control del dispositivo: mínimo shunt residual central, sin cabalgamiento sobre aorta. Diagnóstico: CIA OS con extensión anterior, con relevancia hemodinámica y anatomía favorable para cierre transcatéter. Discusión: el cierre percutáneo de CIA tipo OS es de elección cuando la anatomía lo permite. Las medidas exactas, forma, posición y relaciones anatómicas del defecto son imprescindibles. La vista "in face" del septum interauricular con ETE3D permite una valoración complementaria más precisa de su morfología. Presentamos un caso clínico en el que el ETE3D agregó información adicional a la aportada por el ETE2D, la cual fue determinante para planificar un exitoso procedimiento de cierre.

20.
Rev. Fac. Cienc. Méd. Univ. Cuenca ; 34(3): 33-40, Diciembre 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-999310

RESUMO

El diagnóstico anatomo-patológico de las enfermedades neoplásicas se realiza a través del estudio morfológico, ya sea por métodos citológicos o histopatológicos, complementados en casos necesarios, por otros procedimientos o técnicas adicionales. La diferenciación citológica entre células benignas y malignas en fluidos serosos y en biopsias por aspiración con aguja fina, es frecuentemente difícil en la práctica diaria. La técnica del bloque celular es importante para poder revelar células tumorales en muestras que han sido reportadas como negativas para malignidad por los métodos cito-lógicos convencionales, pues es una metodología que permite la utilización de la inmunohistoquímica. OBjETIVO: Análisis del valor diagnóstico de la técnica de bloque celular en fluidos corporales patológicos y de biopsias por aspiración con aguja fina, en el De-partamento de Patología del Instituto del Cáncer SOL-CA-Cuenca. Período junio 2007- marzo 2008. MÉTODOS: Estudio de tipo descriptivo correlacional entre citología convencional y bloque celular. Se incluye-ron 56 casos provenientes de líquidos de lavado perito-neal; líquido ascítico, pleural, intratumoral, biliar; BAAF de glándula mamaria, tiroides, ganglio, conducto vagi-nal; tumor pancreático; y de muestras fisiológicas como la orina; a los que se les realizó cito-centrifugación en el equipo de Cytospin y técnica de bloque celular. RESULTADOS: Con la técnica de Cytospin hubo casos no concluyentes para diagnóstico, mientras que con la técnica de bloque celular (BC) no se presentaron. Con la técnica de bloque celular se encontró en un 28.5% de casos neoplásicos malignos y con la citología con-vencional, en un 10.7%. Al 30.5% se le solicitó técnicas de inmunohistoquímica para definir el origen neoplási-co, siendo la mayoría procedentes del tracto gastroin-testinal y pulmonar. CONCLUSIONES: La técnica de bloque celular debe ser un procedimiento de rutina en la sección de citología. La utilidad de los bloques celulares se debe en parte a su sencillez, y por otro lado aporta especificidad, ya que permite valorar aspectos como la arquitectura de la muestra, y realizar técnicas de citoquímica e inmuno-histoquímica y presentan una calidad óptima para su interpretación.


Anatomy-pathological diagnosis of neoplastic diseases is performed through the morphological study, either by cytological or histopathological methods, which were supplemented in necessary cases by other procedures or additional techniques. The cytological differentiation between benign and malignant cells in serous fluids and in fine needle aspiration biopsies is often difficult in daily practice. The technique of the cell block is important to be able to reveal tumor cells in samples that have been reported as negative for malignancy by conventional cytological methods, since it is a methodology that allows the use of immunohistochemistry. OBjECTIVE: Analyze the diagnostic value of the cell block technique in pathological body fluids and fine needle aspiration biopsies in the Department of Pa-thology of the SOLCA-Cuenca Cancer Institute. Period June 2007 - March 2008.METhODS: It is a descriptive correlational study between conventional cytology and cell block. A total of 56 ca-ses from peritoneal lavage fluids were included; ascites fluid, pleural, intratumoral, biliary, BAAF of mammary gland, thyroid, ganglion, vaginal duct, pancreatic tu-mor and physiological samples such as urine; who were cyto-centrifuged in the Cytospin team and cell block technique. RESULTS: With the Cytospin technique there were in-conclusive cases for diagnosis, while with the cell block technique (CB) they were not present. The cell block technique was found in 28.5% of malignant neoplas-tic cases and with 10.7% in conventional cytology. The 30.5% were asked for immunohistochemical techniques to define the neoplastic origin, being the majority from the gastrointestinal and pulmonary tract.CONCLUSIONS: The cell block technique should be a routine procedure in the cytology section. The useful-ness of the cell blocks is due to its simplicity, and on the other hand it contributes specificity, since it allows eva-luating aspects such as the architecture of the sample, and performs techniques of cytochemistry and immu-nohistochemistry presenting an optimal quality for its in-terpretation.


Assuntos
Humanos , Masculino , Feminino , Líquidos Corporais , Técnicas e Procedimentos Diagnósticos , Diagnóstico , Patologia , Imuno-Histoquímica , Biologia Celular , Neoplasias
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