Análise do efeito de polimorfismos não-sinônimos em genes de reparo de DNA da via BER na resposta inflamatória da meningite

In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis and also developed a system to enable the functional analysis of polymorphic proteins. Patients with bacterial meningitis (BM), aseptic meningitis (AM) and controls (non-infected) genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. The levels of NF-κB and c-Jun were measured in CSF by dot blot assays. A significant (P<0.05) increase in the frequency of APE1 148Glu allele in BM and AM patients was observed. A significant increase in the genotypes Asn/Asn in control group and Asn/Glu in BM group was also found. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent (P<0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group (P<0.05). The occurrence of combined SNPs increased significantly in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 148Glu allele or OGG1 326Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1Asn148Glu, OGG1Ser326Cys or PARP-1Val762Ala. Reductions in the levels ofIL-6, IL-1Ra, MCP-1/CCL2and IL-8/CXCL8 were observed in the presence of APE1148Glu allele in BM patients, however no differences were observed in the levels of NF-κB and c-Jun considering genotypes and analyzed groups. Using APE1 as model, a system to enable the analysis of cellular effects and functional characterization of polymorphic proteins was developed using strategies of cloning APE1 cDNA in pIRES2-EGFP vector, cellular transfection of the construction obtained, siRNA for endogenous APE1 and cellular cultures genotyping. In conclusion, we obtained evidences of an effect of SNPs in DNA repair genes on the regulation of immune response. This is a pioneering work in the field that shows association of BER variant enzymes with an infectious disease in human patients, suggesting that the SNPs analyzed may affect immune response and damage by oxidative stress level during brain infection. Considering these data, new approaches of functional characterization must be developed to better analysis and interactions of polymorphic proteins in response to this context

Diagnóstico de paratuberculosis bovina en vacas lecheras del cantón Mejía utilizando un ELISA indirecto

La Paratuberculosis Bovina (PTB) o enfermedad de Johne es una enfermedad infecciosa de curso crónico que afecta a rumiantes domésticos y salvajes. Su principal sintomatología clínica es la pérdida progresiva de peso y la presencia de diarrea crónica que produce desmejoramiento y finalmente la muerte del animal. El agente causal es una bacteria perteneciente al Orden Actinomicetales, Familia Mycobacteriaceae denominada Mycobacterium avium subespecie paratuberculosis (Map), del cual se conocen tres subgrupos diferentes de cepas y solo uno de estos ocasiona la enfermedad en el ganado bovino. El objetivo de esta investigación fue determinar la seroprevalencia de paratuberculosis bovina en varios predios de producción lechera ubicados diferentes parroquias del cantón Mejía utilizando como método de diagnóstico una prueba ELISA indirecta.

Chagas congénito de segunda generación en Uruguay: Primer caso sintomático descrito en el país

El Chagas congénito se produce cuando la embarazada infectada trasmite el parásito al feto, situación que puede suceder en cualquier estadio de la enfermedad y momento del embarazo. Es el único mecanismo de trasmisión presente actualmente en Uruguay, con una incidencia cercana al 4%. La mayoría de los neonatos infectados nacen asintomáticos y un 10% al 40% presentan síntomas que son indistinguibles de otras infecciones de trasmisión vertical. La prematurez, el bajo peso, la hepatoesplenomegalia y las alteraciones hematológicas son los síntomas más frecuentes. El diagnóstico representa un desafío en aquellos lugares del país en donde, si bien la enfermedad era considerada endémica, no se realiza actualmente el screening obligatorio de la embarazada. Se describe un lactante procedente de Paysandú, de medio socioeconómico deficitario, que fue pretérmino severo y que presentó al nacer alteraciones hematológicas de las tres series y hepatoesplenomegalia, lo cual motivó múltiples estudios. Sin embargo, no se sospechó la enfermedad hasta los 5 meses de vida, cuando volvió a ingresar por otra patología. Se confirmó la infección a los 9 meses mediante tres técnicas serológicas diferentes. Se indicó tratamiento con nifurtimox por 2 meses y a los 26 y 36 meses de vida presentó serología negativa. Consideramos importante tener alto índice de sospecha de la enfermedad en neonatos con signos de infección congénita y sin serología materna que la descarte. Es importante saber que el tratamiento antes del primer año de vida tiene una excelente respuesta y evita secuelas crónicas que pueden ser invalidantes en etapa adulta.

Artrite meningocócica primária na criança

A artrite é uma complicação conhecida da doença meningocócica. Contudo, a artrite meningocócica primária (AMP), na ausência de meningite ou manifestações de meningococemia aguda, é rara. Descreve-se o caso de uma criança do sexo masculino, 17 meses, saudável, com quadro de febre, recusa da marcha e limitação dos movimentos da anca esquerda. Sem instabilidade hemodinâmica, exantema ou sinais meníngeos. Analiticamente tinha elevação dos parâmetros inflamatórios. Foi isolada Neisseria meningitidis serotipo B no líquido articular e foi medicado com ceftriaxone, seguido de amoxicilina oral, com boa evolução clínica e analítica. Apresentamos este caso raro, salientando a importância do diagnóstico etiológico de artrite séptica na criança.

La influencia de un programa de actividad física sobre parámetros corporales y cardiovasculares en mujeres premenopáusicas

Durante el ciclo de la vida, la figura corporal de la mujer se modifica paulatinamente, pero al llegar la edad mediana, a consecuencia de la pérdida folicular de la función ovárica entre otros factores, se acentúan los cambios fisiológicos que pueden aumentar el riesgo para la salud y el bienestar. La androgenia, en asociación con la obesidad, aumenta el riesgo de padecer diabetes, hipertensión, dislipidemia, arterosclerosis, enfermedades cardiovasculares, colelitiasis, artrosis, artritis, carcinomas femeninos y otras patologías de la edad mediana. El ejercicio físico ha adquirido cada vez mayor importancia dentro de la terapéutica en el climaterio. Se han demostrado los efectos positivos del ejercicio sobre las enfermedades cardiovasculares y el mantenimiento del peso. Por todo ello, el estudio pretende conocer la influencia de un programa de actividad física de cinco meses de duración sobre factores de riesgo cardiovasculares como la hipertensión arterial y la composición corporal en mujeres premenopáusicas. Participaron 20 mujeres premenopáusicas, separadas en dos grupos de mujeres: menores de 35 años (n=10), y mayores de 35 años (n=10). Las valoraciones previas y al finalizar el programa fueron: valoración de la tensión arterial y de la composición corporal. Los resultados mostraron una reducción significativa en mayor medida en la tensión arterial diastólica y en la masa grasa en el grupo de mujeres mayores de 35 años premenopáusicas. Por ello, practicar un programa de ejercicio físico basado en el aeróbic, clases de step y tonificación con mancuernas, mejora factores de riesgo cardiovasculares como la hipertensión arterial y la composición corporal en mujeres adultas mayores de 35 años premenopáusicas.

Small clonal B-cell population in the bone marrow as a possible tool in the diagnosis of occult primary parotid lymphoma

Case Description: An 82-years old Hispanic woman with a past medical history significant for pulmonary thromboembolism on oral anticoagulation, rheumatoid arthritis, and hypertension developed a new onset thrombocytopenia. Clinical Findings: Small clonal B-cells populations (SCBP) also known as monoclonal B-cell lymphocytosis was found as part of the workup for an idiopathic thrombocytopenia and lead ultimately to the diagnosis of parotid primary follicular lymphoma coexisting with Warthin tumor involving the bone marrow in a small extent and oncocytic papilloma located in the maxillary sinus. Treatment and Outcome: Patient was treated with Rituximab monotherapy with improvement on her platelet count. Clinical relevance: Although it is unclear the role of this clonal cells, they may work as a possible diagnostic tool for occult lymphomas. Further prospective studies are needed to confirm this possible association.

Atritis gotosa como causa de pie de riesgo

INTRODUCCIÓN: La gota es una manifestación común de la artritis, cuya inflamación se debe al depóstido de cristales de uratao monosódico en articulaciones y tejidos blandos por un aumento de ácido úrico en sangre y su padecimiento muestra una relación creciente con la edad. OBJETIVOS: Analizar las características fisiopatológicas de la artritis gotosa en el pie así como justificar la repercusión negativa que tiene su padecimiento en la calidad de vida de la población basándose en la simple afectación del pie. METODOLOGÍA: Se realizó una revisión bibliográfica basada en la búsqueda en las bases de datos PubMed y Scopus empleando los descriptores "gout", "gouty arthritis", "foot", "healing", "ulcer" y "wound". Se filtraron los artículos publicados posteriormente al año 2010 en inglés y castellano. RESULTADOS: Los niveles altos de ácido úrico en úlceras están relacionados con su gravedad y la mala cicatrización. La artritis gotosa en el pie se manifiesta mayoritariamente en la 1ª AMTF, siendo esto más común en hombres (68,6%) que en mujeres (31,8%). La manifestación en el pie se da al inicio de la enfermedad en el 43-76% de los casos. Su repercusión a nivel biomecánico-postural da lugar a zonas de presión anormales en el pie pudiendo causar complicaciones secudndarias (por ejemplo úlceras). DISCUSIÓN/CONCLUSIONES: La gota se relaciona íntimamente con la obesidad, el envejecimiento, la diabetes, patologías vasculares y más enfermedades concomicantes que están muy ligadas a la aparición de úlceras y su infeccción. ÇEl pie se ve afectado tanto en su función articular como muscular en este tipo de pacientes y el calzado es una interveción eficaz para reducir la discapacidad, deterioro, dolor y mejorar la marcha. Tanto en esto último como en la curaión de las zonas ulceradas y en la prevención de la artritis gotosa, el podólogo juega un papel fundamental.

Efeito da salinidade, densidade de estocagem e da infecção hipodermal e necrose hematopoiética (IHHN) na imunidade do camarão Litopenaeus vannamei cultivados em fazendas do Rio Grande do Norte

The main problem faced by the shrimp industry are the infectious diseases. The hypodermal and hematopoietic necrosis infection (IHHN) is one of the major cause of disease in the cultured shrimp, Litopenaeus vannamei. Environmental changes involving water quality, oxygen concentration, salinity, temperature, stocking density, presence of pathogens, among others, triggering a stressing condition for the cultured shrimp, weakening them and allowing the outbreak of diseases. The stress on the animal leads to a change in the molecules immune response components, which can be used as indicators of shrimp health. Thus, the objective of the present study was to evaluate the effect of salinity, stocking density and IHHNV infection on the L. vannamei shrimp. The immune parameters used to check the shrimp health were the total hemocytes counts (THC), the agglutinating activity (AA) and the clotting time (CT) of the serum of shrimp. These parameters were analyzed in healthy and IHHNV-infected shrimp, grown in low (0-0.5 ), medium (19-24 ) and high (> 38 ) salinity, and extensive (7-12 cam.m-2), semi-intensive (15-25 cam.m-2) and intensive (33-45 cam.m -2) stocking density. The IHHNV infection rate was significantly higher in low salinity (P<0.005) and intensive density (P<0.005), both stressful conditions for L. vannamei. Low salinity significantly increased THC (P<0.05) and decreased and CT (P<0.05) in healthy and infected shrimp, but AA (P<0.05) significantly decreased in healthy shrimp at medium salinity. Culture intensification did not affect the THC, AA and CT of healthy and infected shrimp (P>0.05). The IHHNV infection did not affect any immune parameters of shrimp cultured at different salinities and stocking densities. It is necessary to emphasize that this study was conducted in shrimp grown in ponds, where several environmental factors are acting simultaneously. Thus, further studies are needed about the influence of other environmental factors on the immune parameters of shrimp cultured in pond

Atividade antimalárica de plantas medicinais da biorregião do Araripe-CE em modelo murino - Plasmodium berghei

Malaria, also popularly known as maleita , intermittent fever, paludism, impaludism, third fever or fourth fever, is an acute infectious febrile disease, which, in human beings, is caused by four species: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Malaria, one of the main infectious diseases in the world, is the most important parasitoses, with 250 million annual cases and more than 1 million deaths per year, mainly in children younger than live years of age. The prophylactic and therapeutic arsenal against malaria is quite restricted, since all the antimalarials currently in use have some limitation. Many plant species belonging to several families have been tested in vivo, using the murine experimental model Plasmodium berghei or in vitro against P. falciparum, and this search has been directed toward plants with antithermal, antimalarial or antiinflammatory properties used in popular Brazilian bolk medicine. Studies assessing the biological activity of medicinal plant essential oils have revealed activities of interest, such as insecticidal, spasmolytic and antiplasmodic action. It has also been scientifically established that around 60% of essential oils have antifungal properties and that 35% exhibit antibacterial properties. In our investigation, essential oils were obtained from the species Vanillosmopsis arborea, Lippia sidoides and Croton zethneri which are found in the bioregion of Araripe-Ceará. The chemical composition of these essential oils was partially characterized and the presence of monoterpenes and sesquiterpenes. The acute toxicity of these oils was assessed in healthy mice at different doses applied on a single day and on four consecutive days, and in vitro cytotoxicity in HeLa and Raw cell lines was determined at different concentrations. The in vivo tests obtained lethal dose values of 7,1 mg/Kg (doses administered on a single day) and 1,8 mg/Kg (doses administered over four days) for 50% of the animals. In the in vitro tests, the inhibitory concentration for 50% of cell growth in Hela cell lines was 588 μg/mL (essential oil from C. zethneri after 48 h), from 340-555 μg/mL (essential oil from L. sidoides, after 24 and 48 h). The essential oil from V. arborea showed no cytotoxicity and none of the essential oils were cytotoxic in Raw cell lines. These data suggest a moderate toxicity in the essential XVIII oils under study, a finding that does not impede their testing in in vivo antimalarial assays. Was shown the antimalarial activity of the essential oils in mice infected with P. berghei was assessed. The three species showed antimalarial activity from 36%-57% for the essential oil from the stem of V. arborea; from 32%-82% for the essential oil from the leaves of L. sidoides and from 40%-70% of reduction for the essential oil from the leaves of C. zethneri. This is the first study showing evidence of antimalarial activity with these species from northeast Brazil. Further studies to isolate the active ingredients of these oils are needed to determine if a single active ingredient accounts for the antimalarial activity or if a complex integration of all the compounds present occurs, a situation reflected in their biological activity

Interventions for reducing extinction risk in chytridiomycosis-threatened amphibians

Wildlife diseases pose an increasing threat to biodiversity and are a major management challenge. A striking example of this threat is the emergence of chytridiomycosis. Despite diagnosis of chytridiomycosis as an important driver of global amphibian declines 15 years ago, researchers have yet to devise effective large-scale management responses other than biosecurity measures to mitigate disease spread and the establishment of disease-free captive assurance colonies prior to or during disease outbreaks. We examined the development of management actions that can be implemented after an epidemic in surviving populations. We developed a conceptual framework with clear interventions to guide experimental management and applied research so that further extinctions of amphibian species threatened by chytridiomycosis might be prevented. Within our framework, there are 2 management approaches: reducing Batrachochytrium dendrobatidis (the fungus that causes chytridiomycosis) in the environment or on amphibians and increasing the capacity of populations to persist despite increased mortality from disease. The latter approach emphasizes that mitigation does not necessarily need to focus on reducing disease-associated mortality. We propose promising management actions that can be implemented and tested based on current knowledge and that include habitat manipulation, antifungal treatments, animal translocation, bioaugmentation, head starting, and selection for resistance. Case studies where these strategies are being implemented will demonstrate their potential to save critically endangered species.

Efecto de la cuña supinadora de retropié sobre la primera articulación metatarsofalángica

La mayoría de los trabajos que intentan determinar cómo influyen las intervenciones ortopédicas sobre el movimiento de FD de la 1ª AMTF se han realizado utilizando plantillas. Las características de las plantillas empleadas han sido variadas y los resultados que muestran estos estudios también son muy variados. Kilmartin encontró que la utilización de una ortesis elaborada con la metodología que describe Root disminuía el movimiento de FD de la 1ª AMTF. Estas variaciones fueron bajas y no mostraron significancia estadística. Munuera y col. utilizando plantillas termoconformadas en polipropileno no observaron cambios en el movimiento de FD de la 1ª AMTF inicialmente pero si en las valoraciones realizadas a los cinco meses de uso. Nawoczensky y col. encontraron cambios en torno a lo 3º que no mostraban significancia pero el análisis de regresión lineal mostro que los cambios observados en el movimiento de FP del primer metatarsiano explicaban el 60% de las variaciones del pico de máxima FD de la 1ª AMTF cuando se utilizaba una plantilla con estabilizaciones externas de antepie y retropié. Finalmente Rao y col mostraron que el uso de ortesis termoconformadas en sujetos con artritis reumatoide incrementaba el pico máximo de FD de la 1ª AMTF, aumentaba el movimiento de FP del primer metatarsiano y disminuían la eversión del retropié. Son muy pocos los trabajos donde se ha evaluado el efecto que tienen las cuñas de retropié sobre el movimiento de FD de la 1ª AMTF. Únicamente hemos encontrado tres trabajos. Uno realizado en estática por Harradine y col. que muestra como la colocación de cuñas pronadoras de retropié disminuye el movimiento de FD de la 1ª AMTF. Los otros están realizados en dinámica y muestran que la utilización de CSR no varía el movimiento de FD de la 1ª AMTF (Halstead y col.) o incluso que lo disminuyen durante la fase propulsiva de la marcha (Smith y col). No se han encontrado trabajos donde se valore específicamente como influyen las CSR sobre el grado de rigidez de la 1ª AMTF al movimiento de FD...

Diabetes Mellitus tipo 1 em Odontopediatria

A Diabetes Mellitus é conhecida por uma doença metabólica caracterizada por um défice na ação ou secreção da insulina, na qual a consequência direta é o aparecimento de hiperglicemia, isto é, o nível de glicose apresentar valores elevados (Kidambi, 2008; Silva-Sousa, 2003). A DM1, especificamente, é apresentada como uma doença que é resultado da destruição das células beta do pâncreas, desenvolvendo assim, um défice na produção de insulina (Raymond et al., 2001). As complicações orais da DM1 incluem xerostomia, doença periodontal (gengivite e periodontite), abcessos dentários, perda de dentes, lesões de tecidos moles e síndrome de ardência oral. A complicação oral mais frequente da DM1 nas crianças é o aumento da sensibilidade à doença periodontal. A doença periodontal é caracterizada como uma reação inflamatória infecciosa dos tecidos gengivais (gengivite) ou do suporte dos dentes, ou seja, ligamento periodontal, cemento e osso alveolar (periodontite), podendo induzir um certo grau de resistência à insulina. Ambas as doenças resultam da interação entre microorganismos periodontais patogénicos. A avaliação e influência do controlo da doença é expressa pelos valores médios de hemoglobina glicosada (Hba1c) na saúde oral nas crianças e adolescentes com DM1. Vários estudos demonstraram que o controlo glicémico teve uma influencia sobre a saúde oral de crianças e adolescentes com DM1. Assim uma avaliação oral, deve fazer parte de procedimentos de rotina no atendimento de crianças e adolescentes com DM1. O dentista deve ser parte da equipa multidisciplinar que auxilia os indivíduos com DM1. O tratamento precoce numa população infantil com DM1, pode diminuir a severidade da doença periodontal. O presente trabalho tem por objectivo realizar uma revisão bibliográfica sobre a importância do estudo em crianças e adolescentes portadores de DM1 e doenças da cavidade oral, nomeadamente, a periodontite, e respetivas implicações.

Enteropatógenos y antibióticos

La gastroenteritis infecciosa continúa siendo un problema de salud pública. La etiología bacteriana es la responsable de la mayoría de los casos graves. En nuestro país, Campylobacter y Salmonella son los géneros bacterianos más prevalentes, mientras que Yersinia y Shigella son mucho menos frecuentes. La mayoría de los casos suelen ser autolimitados y, en general, el tratamiento antibiótico no está indicado, salvo en pacientes con factores de riesgo de infección grave y en shigelosis. Ciprofloxacino, cefalosporinas de tercera generación, azitromicina, ampicilina, cotrimoxazol y doxiciclina son los fármacos más recomendados. El patrón de sensibilidad de las diferentes bacterias determina la elección del tratamiento antibiótico más adecuado. El objetivo de esta revisión es analizar la situación, las novedades y la evolución de la resistencia y la multirresistencia en estos 4 enteropatógenos.

Infective endocarditis: Absence of microbiological diagnosis is an independent predictor of inhospital mortality

Infective endocarditis (IE) is associated with high inhospital mortality. New microbiological diagnostic techniques have reduced the proportion of patients without etiological diagnosis, but in a significant number of patients the cause is still unknown. Our aim was to study the association of the absence of microbiological diagnosis with in-hospital prognosis. Prospective cohort of 2000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. Modified Duke criteria were used to diagnose patients with suspected IE. A total of 290 patients (14.8%) had negative blood cultures. Etiological diagnosis was achieved with other methods (polymerase chain reaction, serology and other cultures) in 121 (6.1%). Finally, there were 175 patients (8.8%) without microbiological diagnosis (Group A) and 1825 with diagnosis (Group B). In-hospital mortality occurred in 58 patients in Group A (33.1%) vs. 487 (26.7%) in Group B, p = 0.07. Patients in Group A had a lower risk profile than those in Group B, with less comorbidity (Charlson index 1.9 ± 2.0 vs. 2.3 ± 2.1, p = 0.03) and lower surgical risk (EuroSCORE 23.6 ± 21.8 vs. 29.6 ± 25.2, p = 0.02). However they presented heart failure more frequently (53% vs. 40%, p = 0.005). Multivariate analysis showed that the absence of microbiological diagnosis was an independent predictor of inhospital mortality (odds ratio 1.8, 95% Confidence Interval 1.1–2.9, p = 0.016). Approximately 9% of patients with IE had no microbiological diagnosis. Absence of microbiological diagnosis was an independent predictor of inhospital mortality.

Incidence and clinical impact of infective endocarditis after transcatheter aortic valve implantation

The aim of this study is to describe the characteristics of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). This study was performed using the GAMES database, a national prospective registry of consecutive patients with IE in 26 Spanish hospitals. Of the 739 cases of IE diagnosed during the study, 1.3% were post-TAVI IE, and these 10 cases, contributed by five centres, represented 1.1% of the 952 TAVIs performed. Mean age was 80 years. All valves were implanted transfemorally. IE appeared a median of 139 days after implantation. The mean age-adjusted Charlson comorbidity index was 5.45. Chronic kidney disease was frequent (five patients), as were atrial fibrillation (five patients), chronic obstructive pulmonary disease (four patients), and ischaemic heart disease (four patients). Six patients presented aortic valve involvement, and four only mitral valve involvement; the latter group had a higher percentage of prosthetic mitral valves (0% vs. 50%). Vegetations were found in seven cases, and four presented embolism. One patient underwent surgery. Five patients died during follow-up: two of these patients died during the admission in which the valve was implanted. Conclusions: IE is a rare but severe complication after TAVI which affects about 1% of patients and entails a relatively high mortality rate. IE occurred during the first year in nine of the 10 patients.