Caracterización clínica, citoquímica y microbiológica de pacientes cirróticos con peritonitis bacteriana en la Fundación Cardioinfantil

Introducción: La peritonitis bacteriana espontanea es la infección más frecuente en pacientes cirróticos causado generalmente por Escherichia coli. Existen factores de riesgo relacionados con la aparición y recurrencia de infección peritoneal por lo que la implementación de estrategias tempranas y preventivas podría impactar en la disminución de la morbimortalidad. Metodología: Estudio descriptivo, serie de casos, se efectuó la búsqueda de los resultados del estudio citoquímico de líquidos ascíticos de pacientes entre los años 2009 y 2013, seleccionando aquellos compatibles con infección y que correspondieran a sujetos cirróticos, para posteriormente realizar la recolección de datos clínicos y paraclínicos con el fin de conformar la base de datos y finalizar con su respectivo análisis. Resultados: El alcohol es la principal causa de cirrosis en pacientes infectados; el principal microorganismo aislado fue Escherichia coli, documentando un 78% de cultivos negativos, 20% más que lo reportado por la literatura. La ampicilina sulbactam fue el antibiótico de elección en el 65% de los casos, de estos el 61% continuaron sin requerir cambio del mismo. Discusión: El presente estudio confirma al alcohol como principal etiología de cirrosis en nuestro país y a la Escherichia coli multisensible como principal agente. Debido al bajo porcentaje de cambios que requirió la ampicilina sulbactam durante el ajuste de la terapia se puede sugerir a este antibiotico dentro del manejo, sin embargo se require de estudios complementarios para comparar su efectividad en relación con cefalosporinas de tercera generación. De igual forma debe priorizarse la toma de cultivos en botellas de hemocultivos para aumentar la cantidad de aislamientos y optimizar el tratamiento antibiótico guiado de acuerdo al microorganismo obtenido.

Adherencia a antibioterapia prequirúrgica en intervenciones torácicas y abdominales en el Hospital Universitario San Jorge, de Pereira

Objetivos: determinar la adherencia al protocolo de antibioterapia prequirúrgica en pacientessometidos a cirugías torácicas y abdominales del Hospital Universitario San Jorge, de Pereira.Materiales y métodos: estudio descriptivo observacional que recogió información de todos lospacientes intervenidos quirúrgicamente entre el 1 de abril y el 31 de junio de 2010. La informaciónse tomó de historias clínicas considerando las variables edad, sexo, tipo de intervención quirúrgica,hora, día de la semana, antimicrobianos empleados comparados con los recomendados porlas guías institucionales. El análisis se hizo mediante SPSS 19.0 para Windows. Resultados: sehicieron 211 cirugías, con predominio de hombres (52,6%) y edad promedio de 45,2 ± 19,9 años.La adherencia a guías de profilaxis antibiótica prequirúrgica fue de 44,5% de los procedimientos.Las variables sexo masculino (OR: 2,2; IC 95%: 1,220-4,063, p=0,009), cirugía de urgencias (OR:2,1; IC 95%: 1,136-3,889, p=0,018) y fines de semana (OR: 2,3; IC 95%: 1,090-5,255, p=0,03)se asociaron de manera estadísticamente significativa con falta de adherencia. Conclusiones: seidentificó una baja adherencia a las guías de antibioterapia prequirúrgica, asociada con cirugíasde urgencia y de fines de semana. Se debe intervenir con educación y realimentación el equipohumano que trabaja en estas condiciones para mejorar el cumplimiento de las guías.

Desenlaces de las infecciones respiratorias en la unidad de cuidado intensivo de la fundación neumologica colombiana

Las infecciones asociadas a ventilación mecánica (VM) son frecuentes en la unidad de cuidado intensivo (UCI). Existen dos infecciones: neumonía (NAV) y traqueobronquitis (TAV). NAV genera impacto negativo en los desenlaces de los pacientes al aumentar la morbilidad, mortalidad y los tiempos en UCI y VM, pero no se conoce el impacto de TAV. El objetivo de este estudio fue identificar si hay diferencias entre NAV y TAV. Materiales y métodos: Se realizó un estudio de cohortes entre 2009 y 2013 en la UCI de la Fundación Neumológica Colombiana. De los pacientes con NAV y TAV se obtuvieron datos demográficos, epidemiológicos, microbiológicos y desenlaces como tiempos de estancia en UCI, VM y de hospitalización y mortalidad. Se compararon estadísticamente mediante t de Student y Chi2 para datos normales y prueba de Mann-Whitney para datos no normales. Resultados: Los pacientes con NAV y TAV fueron similares en la condición de ingreso a UCI. Al diagnóstico de la infección hubo diferencias significativas entre grupos en la oxigenación y tiempo de estancia hospitalaria, en UCI y VM. La microbiología fue con predominio de gérmenes Gram negativos y presencia de multirresistencia en el 52.5% de casos, sin diferencias significativas entre grupos. En los desenlaces, se observó diferencias en los tiempos totales de estancia en UCI, hospitalización y VM, pero sin diferencia en ellos después del diagnóstico. No hubo diferencias significativas en mortalidad. Conclusiones: NAV y TAV son similares en el impacto sobre la evolución de los pacientes en cuanto a morbilidad, estancias y mortalidad.

Perfil de resistencia microbiológico en ciudados intensivos adultos en la fundación Santa Fe de Bogotá año 2014

Se realizó un estudio descriptivo, retrospectivo; se usó la base de datos de los aislamientos microbiológicos documentados en las UCI de la Fundación Santa fe de Bogotá para el año 2014. La prevalencia de bacterias resistentes en los aislamientos de la FSFB no es baja, por lo que se requiere una terapia empírica acertada acorde con la flora local. Se requieren estudios analíticos para evaluar factores asociados al desarrollo de gérmenes multi resistentes y mortalidad por sepsis

Caracterização das infecções do trato urinário de origem microbiana - casuística de um hospital veterinário em Lisboa

As infecções do trato urinário (ITU’s) são doenças infecciosas frequentes na prática clínica veterinária, sendo fundamental uma correta antibioterapia, principalmente pelo crescente desenvolvimento de resistências bacterianas aos antibióticos. Realizou-se um estudo retrospectivo, englobando 86 animais admitidos no Hospital Veterinário do Restelo, submetidos a urocultura, com o objetivo de caracterizar as ITU’s microbianas neste hospital, avaliando a sua epidemiologia e susceptibilidade antibiótica das bactérias isoladas. Da totalidade das uroculturas realizadas (n=86), 28 foram positivas, 18 em canídeos e 10 em felídeos, sem predisposição racial, mais em fêmeas nos canídeos e em machos nos felídeos. A idade média dos animais com ITU foi 8 anos nos canídeos e 10 anos nos felídeos. Todas as ITU´s foram monobacterianas, sendo o microorganismo mais frequentemente isolado a Escherichia coli. Verificou-se multirresistência em 10 das 28 bactérias isoladas. A gentamicina foi o antibiótico com melhor perfil de sensibilidade global e o que apresentou mais resistências foi a tetraciclina. O antibiótico mais prescrito de forma empírica foi a enrofloxacina. Este estudo, especialmente se realizado de forma periódica, poderá ser um contributo para a elaboração de guias institucionais de antibioterapia adequada e minimização do aparecimento de resistências bacterianas.

Caracterização das infeções do trato urinário de origem microbiana : casuística de um Hospital Veterinário de Lisboa

As infeções do trato urinário (ITU’s) são doenças infeciosas frequentes na prática clínica veterinária, sendo fundamental uma correta antibioterapia, principalmente pelo crescente desenvolvimento de resistências bacterianas aos antibióticos. Realizou-se um estudo retrospetivo, englobando 86 animais admitidos no Hospital Veterinário do Restelo, submetidos a urocultura, com o objetivo de caracterizar as ITU’s microbianas neste hospital, avaliando a sua epidemiologia e suscetibilidade antibiótica das bactérias isoladas. Da totalidade das uroculturas realizadas (n=86), 28 foram positivas, 18 em canídeos e 10 em felídeos, sem predisposição racial, mais em fêmeas nos canídeos e em machos nos felídeos. A idade média dos animais com ITU foi 8 anos nos canídeos e 10 anos nos felídeos. Todas as ITU´s foram monobacterianas, sendo o microorganismo mais frequentemente isolado a Escherichia coli. Verificou-se multirresistência em 10 das 28 bactérias isoladas. A gentamicina foi o antibiótico com melhor perfil de sensibilidade global e o que apresentou mais resistências foi a tetraciclina. O antibiótico mais prescrito de forma empírica foi a enrofloxacina. Este estudo,especialmente se realizado de forma periódica, poderá ser um contributo para a elaboração de guias institucionais de antibioterapia adequada e minimização do aparecimento de resistências bacterianas.

Dietary-based gut flora modulation against Clostridium difficile onset

Clostridium difficile infection is a frequent complication of antibiotic therapy in hospitalised patients, which today is attracting more attention than ever and has led to its classification as a 'superbug'. Disruption of the composition of the intestinal microflora following antibiotic treatment is an important prerequisite for overgrowth of C. difficile and the subsequent development of an infection. Treatment options for antibiotic-associated diarrhoea and C. difficile-induced colitis include administration of specific antibiotics (e.g. vancomycin), which often leads to high relapse rates. More importantly, both the rate and severity of C. difficile-associated diseases are increasing, with new epidemic strains of C. difficile often implicated. For the prevention and treatment of antibiotic-associated diarrhoea and C. difficile infection, several probiotic bacteria such as selected strains of lactobacilli (especially Lactobacillus rhamnosus GG), Bifidobacterium longum, and Enterococcus faecium and the non-pathogenic yeast Saccharomyces boulardii have been used. Controlled trials indicate a benefit of S. boulardii and L. rhamnosus GG as therapeutic agents when used as adjuncts to antibiotics. However, the need for more well designed controlled trials with probiotics is explicit.

Human microbiota in health and disease

Each human body plays host to a microbial population which is both numerically vast (at around 1014 microbial cells) and phenomenally diverse (over 1,000 species). The majority of the microbial species in the gut have not been cultured but the application of culture-independent approaches for high throughput diversity and functionality analysis has allowed characterisation of the diverse microbial phylotypes present in health and disease. Studies in monozygotic twins, showing that these retain highly similar microbiota decades after birth and initial colonisation, are strongly indicative that diversity of the microbiome is host-specific and affected by the genotype. Microbial diversity in the human body is reflected in both richness and evenness. Diversity increases steeply from birth reaching its highest point in early adulthood, before declining in older age. However, in healthy subjects there appears to be a core of microbial phylotypes which remains relatively stable over time. Studies of individuals from diverse geopraphies suggest that clusters of intestinal bacterial groups tend to occur together, constituting ‘enterotypes’. So variation in intestinal microbiota is stratified rather than continuous and there may be a limited number of host/microbial states which respond differently to environmental influences. Exploration of enterotypes and functional groups may provide biomarkers for disease and insights into the potential for new treatments based on manipulation of the microbiome. In health, the microbiota interact with host defences and exist in harmonious homeostasis which can then be disturbed by invading organisms or when ‘carpet bombing’ by antibiotics occurs. In a portion of individuals with infections, the disease will resolve itself without the need for antibiotics and microbial homeostasis with the host’s defences is restored. The administration of probiotics (live microorganisms which when administered in adequate amounts confer a health benefit on the host) represents an artificial way to enhance or stimulate these natural processes. The study of innate mechanisms of antimicrobial defence on the skin, including the production of numerous antimicrobial peptides (AMPs), has shown an important role for skin commensal organisms. These organisms may produce AMPs, and also amplify the innate immune responses to pathogens by activating signalling pathways and processing host produced AMPs. Research continues into how to enhance and manipulate the role of commensal organisms on the skin. The challenges of skin infection (including diseases caused by multiply resistant organisms) and infestations remain considerable. The potential to re-colonise the skin to replace or reduce pathogens, and exploring the relationship between microbiota elsewhere and skin diseases are among a growing list of research targets. Lactobacillus species are among the best known ‘beneficial’ bacterial members of the human microbiota. Of the approximately 120 species known, about 15 are known to occur in the human vagina. These organisms have multiple properties, including the production of lactic acid, hydrogen peroxide and bacteriocins, which render the vagina inhospitable to potential pathogens. Depletion of the of the normal Lactobacillus population and overgrowth of vaginal anaerobes, accompanied by the loss of normal vaginal acidity can lead to bacterial vaginosis – the commonest cause of abnormal vaginal discharge in women. Some vaginal anaerobes are associated with the formation of vaginal biofilms which serve to act as a reservoir of organisms which persists after standard antibiotic therapy of bacterial vaginosis and may help to account for the characteristically high relapse rate in the condition. Administration of Lactobacillus species both vaginally and orally have shown beneficial effects in the treatment of bacterial vaginosis and such treatments have an excellent overall safety record. Candida albicans is a frequent coloniser of human skin and mucosal membranes, and is a normal part of the microbiota in the mouth, gut and vagina. Nevertheless Candida albicans is the most common fungal pathogen worldwide and is a leading cause of serious and often fatal nosocomial infections. What turns this organism from a commensal to a pathogen is a combination of increasing virulence in the organism and predisposing host factors that compromise immunity. There has been considerable research into the use of probiotic Lactobacillus spp. in vaginal candidiasis. Studies in reconstituted human epithelium and monolayer cell cultures have shown that L. rhamnosus GG can protect mucosa from damage caused by Candida albicans, and enhance the immune responses of mucosal surfaces. Such findings offer the promise that the use of such probiotic bacteria could provide new options for antifungal therapy. Studies of changes of the human intestinal microbiota in health and disease are complicated by its size and diversity. The Alimentary Pharmabiotic Centre in Cork (Republic of Ireland) has the mission to ‘mine microbes for mankind’ and its work illustrates the potential benefits of understanding the gut microbiota. Work undertaken at the centre includes: mapping changes in the microbiota with age; studies of the interaction between the microbiota and the gut; potential interactions between the gut microbiota and the central nervous system; the potential for probiotics to act as anti-infectives including through the production of bacteriocins; and the characterisation of interactions between gut microbiota and bile acids which have important roles as signalling molecules and in immunity. The important disease entity where the role of the gut microbiota appears to be central is the Irritable Bowel Syndrome (IBS). IBS patients show evidence of immune activation, impaired gut barrier function and abnormal gut microbiota. Studies with probiotics have shown that these organisms can exert anti-inflammatory effects in inflammatory bowel disease and may strengthen the gut barrier in IBS of the diarrhoea-predominant type. Formal randomised trials of probiotics in IBS show mixed results with limited benefit for some but not all. Studies confirm that administered probiotics can survive and temporarily colonise the gut. They can also stimulate the numbers of other lactic acid bacilli in the gut, and reduce the numbers of pathogens. However consuming live organisms is not the only way to influence gut microbiota. Dietary prebiotics are selectively fermented ingredients that can change the composition and/or activity of the gastrointestinal microbiota in beneficial ways. Dietary components that reach the colon, and are available to influence the microbiota include poorly digestible carbohydrates, such as non-starch polysaccharides, resistant starch, non-digestible oligosaccharides (NDOs) and polyphenols. Mixtures of probiotic and prebiotic ingredients that can selectively stimulate growth or activity of health promoting bacteria have been termed ‘synbiotics’. All of these approaches can influence gut microbial ecology, mainly to increase bifidobacteria and lactobacilli, but metagenomic approaches may reveal wider effects. Characterising how these changes produce physiological benefits may enable broader use of these tactics in health and disease in the future. The current status of probiotic products commercially available worldwide is less than ideal. Prevalent problems include misidentification of ingredient organisms and poor viability of probiotic microorganisms leading to inadequate shelf life. On occasions these problems mean that some commercially available products cannot be considered to meet the definition of a probiotic product. Given the potential benefits of manipulating the human microbiota for beneficial effects, there is a clear need for improved regulation of probiotics. The potential importance of the human microbiota cannot be overstated. ‘We feed our microbes, they talk to us and we benefit. We just have to understand and then exploit this.’ (Willem de Vos).

A retrospective study of zygomatico-orbital complex and/or zygomatic arch fractures over a 71-month period

Background/Aim: The aim of this retrospective study was to evaluate the epidemiology, treatment, and complications of zygomatico-orbital complex (ZOC) and/or zygomatic arch (ZA) fractures either associated with other facial fractures or not over a 71-month period. Material and methods: This survey was performed in three hospitals of Ribeirao Preto in Sao Paulo, Brazil, from August 2002 to July 2008. The records of 1575 patients with facial trauma were reviewed. There were 140 cases of ZOC and ZA fractures either associated with other facial fractures or not. Data regarding gender, age, race, addictions, day of trauma, etiology, signs and symptoms, oral hygiene condition, day of initial evaluation, hospital admission, day of surgery, surgery approach, pattern of fractures, treatment performed, post-operative antibiotic therapy, day of hospital discharge, and post-operative complications were collected. The data were subjected to descriptive statistical analyses. Results: The most frequent fractures affected Caucasian men and occurred during the fourth decade of life. The most frequent etiology was traffic accident, and symptoms and signs included pain and edema. Type I fractures were the main injury observed, and the treatment of choice was always rigid internal fixation. Post-operative antibiotic therapy was solely employed when there was an indication. Complications were observed in 13.1% of the cases. Conclusions: The treatment protocol yielded suitable post-operative results and also showed success rates comparable to published data around the world.

Research on Candida dubliniensis in a Brazilian yeast collection obtained from cardiac transplant, tuberculosis, and HIV-positive patients, and evaluation of phenotypic tests using agar screening methods

The aim of this study was to research Candida dubliniensis among isolates present in a Brazilian yeast collection and to evaluate the main phenotypic methods for discrimination between C. albicans and C. dubliniensis from oral cavity. A total of 200 isolates, presumptively identified as C. albicans or C. dubliniensis obtained from heart transplant patients under immunosuppressive therapy, tuberculosis patients under antibiotic therapy, HIV-positive patients under antiretroviral therapy, and healthy subjects, were analyzed using the following phenotypic tests: formation and structural arrangement of chlamydospores on corn meal agar, casein agar, tobacco agar, and sunflower seed agar; growth at 45 degrees C; and germ tube formation. All strains were analyzed by polymerase chain reaction (PCR). In a preliminary screen for C. dubliniensis, 48 of the 200 isolates on corn meal agar, 30 of the 200 on casein agar, 16 of the 200 on tobacco agar, and 15 of the 200 on sunflower seed agar produced chlamydoconidia; 27 of the 200 isolates showed no or poor growth at 45 degrees C. All isolates were positive for germ tube formation. These isolates were considered suggestive of C. dubliniensis. All of them were subjected to PCR analysis using C. dubliniensis-specific primers. C. dubliniensis isolates were not found. C. dubliniensis isolates were not recovered in this study done with immunocompromised patients. Sunflower seed agar was the medium with the smallest number of isolates of C. albicans suggestive of C. dubliniensis. None of the phenotypic methods was 100% effective for discrimination between C. albicans and C. dubliniensis. (C) 2011 Elsevier Inc. All rights reserved.

Interactions of mast cell degranulating peptides with model membranes: A comparative biophysical study

In the last decade, there has been renewed interest in biologically active peptides in fields like allergy, autoimmume diseases and antibiotic therapy. Mast cell degranulating peptides mimic G-protein receptors, showing different activity levels even among homologous peptides. Another important feature is their ability to interact directly with membrane phospholipids, in a fast and concentration-dependent way. The mechanism of action of peptide HR1 on model membranes was investigated comparatively to other mast cell degranulating peptides (Mastoparan, Eumenitin and Anoplin) to evidence the features that modulate their selectivity. Using vesicle leakage, single-channel recordings and zeta-potential measurements, we demonstrated that HR1 preferentially binds to anionic bilayers, accumulates, folds, and at very low concentrations, is able to insert and create membrane spanning ion-selective pores. We discuss the ion selectivity character of the pores based on the neutralization or screening of the peptides charges by the bilayer head group charges or dipoles. (C) 2009 Elsevier Inc. All rights reserved.

O exame direto do lavado broncoalveolar para o diagnóstico precoce de pneumonia nosocomial : um modelo experimental em ratos

A pneumonia nosocomial é a principal causa de infecção nosocomial em unidades de tratamento intensivo e possui alta morbi/mortalidade. A incidência cumulativa varia, conforme os autores, entre limites amplos desde 8% até 51%, dependendo do tipo de paciente e do uso de instrumentação das vias respiratórias. Nos casos específicos das pneumonias de má resolução e da pneumonia associada à ventilação mecânica, o diagnóstico é problemático devido à ausência de uma padronização definitiva, decorrente não só da grande variabilidade fisiopatológica como também da pouca acurácia dos critérios clínicos, microbiológicos e radiológicos. Estes fatos ensejaram a utilização progressiva de técnicas invasivas sofisticadas para coleta de amostras respiratórias endobrônquicas. Entretanto, a validação dessas técnicas para uso sistemático depende ainda de estudos que avaliem não só o seu custo/benefício em cenários clínicos diversos como também a comparação de seu desempenho para o diagnóstico com um padrão-ouro histopatológico. Além disso, o rendimento das técnicas invasivas é freqüentemente limitado quando são aplicadas em pacientes sob antibioticoterapia, que constituem a maioria dos casos em unidades de cuidados intensivos. A otimização desses testes, discutindo suas indicações e avaliando sua capacidade técnica para a confirmação ou exclusão de pneumonia, é justificada pela necessidade da instituição precoce e correta do tratamento, pois disto resulta menor mortalidade, redução de custos e permanência no hospital. Entre os testes que podem auxiliar no diagnóstico encontra-se o exame direto do lavado broncoalveolar, que proporciona resultados precoces e úteis para a tomada de decisão, mas não suficientemente testados em diferentes situações clínicas ou experimentais. Com o objetivo de avaliar o rendimento diagnóstico do exame direto precoce e das culturas quantitativas obtido por lavado broncoalveolar, estudou-se sua utilização em um modelo experimental de pneumonia provocada através de inoculação bacteriana intrabrônquica em ratos. O estudo comparou a acurácia do exame direto e dos exames culturais em três grupos de animais: Grupo A com pneumonia pneumocócica (37 animais); Grupo P com pneumonia por P. aeruginosa (26 animais) e Grupo B controle (10 animais), utilizando a histopatologia dos pulmões como teste de referência para o diagnóstico. Os Grupos A e P foram ainda randomizados em dois subgrupos cada, para tratamento ou não com antibióticos, usando penicilina no grupo pneumococo e amicacina no grupo Pseudomonas. Como resultado, observou-se que nos animais com pneumonia e ausência de antibióticos a pesquisa de bactéria fagocitada (BIC) no exame direto mostrou um rendimento elevado para o diagnóstico, sendo superior ao das culturas quantitativas. No grupo com pneumonia pneumocócica a BIC mostrou: S:94,4% a 100%, E:100%, VPP:100% e VPN:100%; e as culturas quantitativas mostraram: S:77,8%, E:100%, VPP:100%, VPN:40%. Nos com pneumonia por Pseudomonas a BIC obteve: S: 69%, E:100%; VPP:100% e VPN:71,4%); e as culturas quantitativas mostraram valores muito baixos: S:28,6%, E:100%, VPP:100% e VPN:50%). Nos animais com pneumonia pneumocócica sob tratamento antibiótico havia uma queda acentuada de sensibilidade das culturas quantitativas (S:21%) e, em menor grau da BIC (S:57,9%), mas sem perda da especificidade de ambos os exames. Ao contrário, nos animais com pneumonias por Pseudomonas sob tratamento não havia alteração no rendimento dos dois exames, cujos resultados foram semelhantes aos dos animais sem tratamento. Não havia diferenças de leitura da BIC para o diagnóstico, contando a sua positividade em macrófagos ou em neutrófilos infectados. A avaliação global dos casos estudados, reunindo todos os grupos (tratados e não-tratados) em ambos os modelos de pneumonia, mostrou que a acurácia do exame direto, representado pela pesquisa da BIC, foi superior (66%) ao das culturas quantitativas (53%). As conclusões principais do estudo foram: 1) o exame direto do lavado broncoalveolar (LBA) mostrou-se um teste útil e de alto rendimento para o diagnóstico de pneumonia quando realizado na ausência de antibióticos; 2) o LBA feito na vigência de antibióticos efetivos para a pneumonia perde mais de 50% de sua acurácia, mas não é afetado quando o antibiótico for ineficaz ou houver resistência ao mesmo; 3) a pesquisa de BIC no LBA é um exame de resultado precoce, de alta especificidade e com melhor rendimento do que as culturas quantitativas.

Estudo do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Dermatose responsiva à biotina em cão

Os transtornos da pele e dos pelos são parte importante na prática clínica de pequenos animais. Numerosos fatores nutricionais afetam a homeostase, a qualidade e o aspecto da pelagem. As vitaminas do complexo B incluem compostos hidrossolúveis necessários como coenzimas em diversas funções celulares envolvidas no metabolismo energético e na síntese tecidual. A biotina, em especial, é necessária nas reações de carboxilação, participando da síntese de ácidos graxos, aminoácidos e purinas pelo tecido epitelial. Uma cadela com quadro de cistite recorrente e tumor venéreo transmissível foi tratada com antibioticoterapia prolongada e quimioterapia. Após alguns meses de tratamento, foram observadas lesões no plano nasal e nos coxins plantar e palmar, caracterizadas por hiperceratose, espessamento, fissuras, sangramento e inflamação. O paciente recebeu suplementação de 15mg de biotina por via oral (equivalente a 1,4mg kg-1 de peso corporal), uma vez por dia, durante 60 dias, havendo importante regressão das lesões. Sugere-se que, sob antibioticoterapia e doença, a síntese intestinal de biotina possa não ter sido suficiente, sendo necessária sua suplementação.

Comparison of lung tissue concentrations of nebulized ceftazidime in ventilated piglets: ultrasonic versus vibrating plate nebulizers

Objective: To compare the efficiency of an Aeroneb Pro vibrating plate and an Atomisor MegaHertz ultrasonic nebulizer for providing ceftazidime distal lung deposition.Design: In vitro experiments. One gram of cetazidime was nebulized in respiratory circuits and mass median aerodynamic diameter of particles generated by ultrasonic and vibrating plate nebulizers was compared using a laser velocimeter. In vivo experiments. Lung tissue concentrations and extrapulmonary depositions were measured in ten anesthetized ventilated piglets with healthy lungs that received 1 g of ceftazidime by nebulization with either an ultrasonic (n = 5), or a vibrating plate (n = 5) nebulizer.Setting: A two-bed Experimental Intensive Care Unit of a University School of Medicine.Intervention: Following sacrifice, 5 subpleural specimens were sampled in dependent and nondependent lung regions for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography.Measurements and results: Mass median aerodynamic diameters generated by both nebulizers were similar with more than 95% of the particles between 0.5 and 5 mu m. Lung tissue concentrations were 553 +/- 123 [95% confidence interval: 514-638] mu g g(-1) using ultrasonic nebulizer, and 452 +/- 172 [95% confidence interval: 376-528] mu g g(-1) using vibrating plate nebulizers (NS). Extrapulmonary depositions were, respectively, of 38 +/- 5% (ultrasonic) and 34 +/- 4% (vibrating plate) (NS).Conclusions: Vibrating plate nebulizer is comparable to ultrasonic nebulizers for ceftazidime nebulization. It may represent a new attractive technology for inhaled antibiotic therapy.