Influence of rate of administration on the mechanism behind propofol induced loss of consciousness.

BACKGROUND: Propofol effect-site time course models included in TCI systems have been under discussion. We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model: yielding different plasmatic concentrations, loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site. METHODOLOGY: ASA III patients were randomized in two groups: rapid induction (RI) received TCI of propofol effect-site (CeCALC) 5.4 µg/mL (modified Marsh model), and slow induction (SI) propofol infusion of 10 mg/kg/hour. A neurologist, blinded to induction method, performed neurological assessments using the FOUR score until the loss of consciousness (LOC). At LOC, the presence of brain stem reflexes, EEG index (PSI) and infusion time/mass of drug were registered. Fisher's exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofo models at LOC time. RESULTS: 16 patients divided in two groups were included. All patient in SI had brainstem reflexes free at LOC. In the RI, all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score (brain stem reflexes unaffected; P < .001). CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk/Pd models. CONCLUSIONS: Depending of the infusion rate, propofol CeCALC at LOC calculated by different Pk/Pd models could be the source of confuse data to be used to guide the state of general anesthesia.

Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol / Influence of rate of administration on the mechanism behind propofol induced loss of consciousness

Antecedentes: Se han debatido los modelos de curso temporal del sitio de efecto del propofol. Nosotros supusimos que la tasa de administración es un gran factor contributivo que afecta a la construcción de un modelo de sitio de efecto útil: elaborando distintas concentraciones plasmáticas, la pérdida de consciencia puede producirse debido a diferentes mecanismos más complejos que el sitio del efecto farmacológico. Metodología: Se aleatorizaron pacientes ASAI-II en dos grupos: el grupo de inducción rápida (IR) recibió TCI de sitio de efecto de propofol (CeCALC) 5,4μg/ml (modelo Marsh modificado) y el grupo de inducción lenta (IL) recibió una infusión de propofol de 10mg/kg/h. Un neurólogo, a quien se ocultó el método de inducción, realizó las evaluaciones neurológicas utilizando la escala FOUR hasta lograr la pérdida de consciencia (LOC). Una vez lograda, se registraron la presencia de reflejos troncoencefálicos, el índice EEG (PSI) y el tiempo de infusión/masa del fármaco. Se realizó la prueba exacta de Fisher para describir las diferencias entre los reflejos troncoencefálicos y los componentes respiratorios de la escala FOUR, así como CeCALC para los 4 modelos de propofol en el momento de la LOC. Resultados: Se incluyeron 16 pacientes, divididos en dos grupos. Todos los pacientes del grupo IL tuvieron reflejos troncoencefálicos libres en LOC. En el grupo IR, en todos los pacientes se suprimieron los reflejos troncoencefálicos, y un paciente obtuvo 4 puntos B y R en la escala FOUR (reflejos troncoencefálicos no afectados; p<0,001). CeCALC en el momento de LOC fue contradictorio en ambos grupos, utilizando 4 modelos Pk/Pd diferentes. Conclusiones: Dependiendo de la tasa de infusión, CeCALC de propofol en el momento de la LOC, calculado mediante modelos Pk/Pd diferentes, podría ser la fuente de datos de confusión a utilizar para guiar el estado de la anestesia general.(AU)

Background: Propofol effect-site time course models included in TCI systems have been under discussion.We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model: yielding different plasmatic concentrations, loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site. Methodology: ASA I-II patients were randomized in two groups: rapid induction (RI) received TCI of propofol effect-site (CeCALC) 5.4μg/mL (modified Marsh model), and slow induction (SI) propofol infusion of 10mg/kg/hour. A neurologist, blinded to induction method, performed neurological assessments using the FOUR score until the loss of consciousness (LOC). At LOC, the presence of brain stem reflexes, EEG index (PSI) and infusion time/mass of drug were registered. Fisher's exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofol models at LOC time. Results: 16 patients divided in two groups were included. All patient in SI had brainstem reflexes free at LOC. In the RI, all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score (brain stem reflexes unaffected; P<.001). CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk/Pd models. Conclusions: Depending of the infusion rate, propofol CeCALC at LOC calculated by different Pk/Pd models could be the source of confuse data to be used to guide the state of general anesthesia.(AU)

Influence of rate of administration on the mechanism behind propofol induced loss of consciousness. / Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol.

BACKGROUND: Propofol effect-site time course models included in TCI systems have been under discussion. We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model: yielding different plasmatic concentrations, loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site. METHODOLOGY: ASA I-II patients were randomized in two groups: rapid induction (RI) received TCI of propofol effect-site (CeCALC) 5.4µg/mL (modified Marsh model), and slow induction (SI) propofol infusion of 10mg/kg/hour. A neurologist, blinded to induction method, performed neurological assessments using the FOUR score until the loss of consciousness (LOC). At LOC, the presence of brain stem reflexes, EEG index (PSI) and infusion time/mass of drug were registered. Fisher's exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofol models at LOC time. RESULTS: 16 patients divided in two groups were included. All patient in SI had brainstem reflexes free at LOC. In the RI, all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score (brain stem reflexes unaffected; P<.001). CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk/Pd models. CONCLUSIONS: Depending of the infusion rate, propofol CeCALC at LOC calculated by different Pk/Pd models could be the source of confuse data to be used to guide the state of general anesthesia.

Is it always necessary to perform an axillary lymph node dissection after neoadjuvant chemotherapy for breast cancer?

INTRODUCTION: Recent prospective studies support the feasibility of performing sentinel lymph node biopsy following neoadjuvant chemotherapy in initially fine-needle aspiration cytology or ultrasound-guided biopsy-proven node-positive breast cancer. The main aid is to identify preoperative features that help us predict a complete axillary response to neoadjuvant chemotherapy in these patients and thus select the candidates for sentinel lymph node biopsy post-neoadjuvant chemotherapy to avoid unnecessary axillary lymphadenectomy. MATERIALS AND METHODS: A retrospective observational study with a total of 150 patients, biopsy-proven node-positive breast cancer who underwent neoadjuvant chemotherapy followed by breast surgery and axillary lymphadenectomy were included and retrospectively analysed. A predictive model was generated by a multivariate logistic regression analysis for pathological complete response-dependent variable. RESULTS: The response of the primary lesion to neoadjuvant chemotherapy according to post-treatment magnetic resonance imaging, Her2/neu overexpression and a low estrogen receptor expression are associated with a higher rate of nodal pathologically complete response. The multivariant model generated a receiver operating characteristic curve with an area under the curve of 0.79 and a confidence interval of 0.72-0.87 at a 95% level of significance. CONCLUSIONS: This model could be a helpful tool for the surgeon to help in predicting which cases have a higher likelihood of achieving a pathologically complete response and therefore selecting those who may benefit from a post-neoadjuvant chemotherapy sentinel lymph node biopsy and avoid unnecessary axillary lymphadenectomy.

Detection of Teschovirus type 13 from two swine herds exhibiting nervous clinical signs in growing pigs.

Recently, the number of clinical reports of growing pigs showing neurological signs possibly related to viral infections has increased. The objective of this report was to describe two outbreaks of an atypical condition observed in 6- to 7-week-old pigs with a morbidity of 20% and a fatality rate of 60% in two unrelated farms of the same company. During the acute phase of the disease, fever, sudden death, neurological signs, ear necrosis and occasional corneal opacity were observed. Histopathological examination revealed interstitial pneumonia, lymphoid depletion and lymphocytic vasculitis in different organs and mild polioencephalomyelitis suggesting a potential viral infection. Possible aetiologies such as exogenous intoxications, salt intoxication, mineral deficiencies/intoxications (Se, Cu, Cd and Zn), oedema disease and mycotoxicosis were ruled out through the diagnostic process. No clinically relevant bacteria could be consistently isolated from affected animals, and the presence of the common swine viruses was ruled out by PCR or RT-PCR. Porcine Teschovirus serotype 13 was the only virus detected by RT-PCR within central nervous system (CNS) of acutely affected pigs. This is the first description of PTV serotype 13 within the CNS of clinically affected pigs.

Litiasis urinaria y su relación con el consumo de aguas duras en la comuna de Maipú / Urinary lithiasis and its relation to the consumption of hard water in the Maipu Borough

INTRODUCCIÓN: La litiasis urinaria es una patología frecuente, que afecta principalmente a adultos en edad productiva, y que en el último tiempo ha presentado un aumento en la incidencia global. Cerca del 80 % de los cálculos se componen mayoritariamente de calcio. Existe controversia en la literatura sobre el rol que podría tener el consumo de aguas con altos índices de dureza y el riesgo de padecer litiasis. El objetivo de este estudio es identificar una posible asociación entre dureza de agua para consumos e incidencia de litiasis urinaria en la poblacion de Maipú. MATERIALES Y METODOS: Se incluyen en el estudio todos los pacientes atendidos por urólogos en forma ambulatoria electiva en el Hospital El Carmen de Maipú, por diagnóstico de litiasis urinaria, en los años 2015 y 2016, que residen en la comuna. Se georreferenciaron de acuerdo a sus direcciones en los distintos sectores de distribución de agua potable.Se realizó análisis fisicoquímico de muestras de agua extraídas de cada sector para determinar su dureza. Se estudiaron a través del índice de correlación de Pearson las posibles asociaciones entre dureza del agua e incidencia de litiasis. RESULTADOS: La dureza promedio del agua de Maipú es de 484 mg/L de CaCO3, valor que se encuentra por sobre el promedio regional y nacional. La incidencia anual de litiasis en la poblacion estudiada fue de 4,4 casos/10.000 habitantes, valor similar al promedio nacional. El índice de correlación de Pearson entre dureza de agua e incidencia anual fue de -0,51. CONCLUSIONES: No fue posible establecer una relación causal entre dureza de agua e incidencia de litiasis en la población estudiada. Se sugiere avanzar en esta misma línea con estudios futuros de casos y controles.AU

INTRODUCTION: Urinary lithiasis is a frequent pathology, which mainly affects adults in a productive age, and which-in recent times- has increased in terms of global incidence. About 80 % of the stones are composed mainly of calcium.There is controversy in literature addressing the possible relation amongst water consumption with high hardnessindexes and the risk of lithiasis. The objective of this study is to identify a possible association between water hardnessfor consumption and urinary lithiasis incidence in the Maipu population. MATERIALS AND METHODS: All patients assisted by urologists on an elective ambulatory basis, at the El Carmen Hospital in Maipú, diagnosed with urinary lithiasis, in the years 2015 and 2016, and who reside in the Borough have been included in the study. They were georeferenced according to their address in the different drinking water distribution areas. Physiochemical analysis of water samples extracted from each sector was carried out to determine its hardness. The possible associations between hardness of water and incidence of lithiasis were studied through the Pearson correlation index. RESULTS: The average water hardness in Maipu is 484 mg / L of CaCO3, a value that is above the regional and national average. The annual incidence of lithiasis in the studied population was 4.4 cases / 10,000 inhabitants, a value that is similar to the national average. The Pearson correlation index between water hardness and annual incidence was -0.51. CONCLUSIONS: It was not possible to establish a causal relation between water hardness and incidence of lithiasis in the studied population. It is suggested to advance in this same line with future case and control studies.

Cross-reactions in specific Brachyspira spp. PCR assays caused by "Brachyspira hampsonii" isolates: implications for detection.

An emerging novel spirochete in swine, provisionally designated "Brachyspira hampsonii," has been detected worldwide. It has been associated with swine dysentery and cannot be differentiated from B. hyodysenteriae, the classical etiologic agent of this disease, using standard phenotypic methods. We evaluated cross-reactions of "B. hampsonii" isolates recovered from avian species in some of the currently available species-specific polymerase chain reaction (PCR) assays for the identification of swine Brachyspira species. Ten avian "B. hampsonii" isolates recovered from wild waterfowl were used. No false-positive results were recorded with a B. pilosicoli-specific PCR based on the amplification of a fragment of the 16S rRNA gene. However, the percentage of false-positive results varied, with a range of 10-80%, in the evaluated B. hyodysenteriae-specific assays based on the amplification of the 23S rRNA, nox, and tlyA genes. Similarly, results of the B. intermedia-specific PCR assays yielded poor specificity, with up to 80% of the "B. hampsonii" isolates tested giving false-positive results. Finally, 2 "B. hampsonii" avian isolates yielded a positive result in a B. innocens- and B. murdochii-specific PCR. This result should be interpreted very cautiously as these 2 isolates could represent a recombinant genotype.

C-reactive protein, haptoglobin and Pig-Major acute phase protein profiles of pigs infected experimentally by different isolates of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) is the etiologic agent of PRRS, one of the most important diseases in swine worldwide. In the present work, the effects of different PRRSV strains were tested on a piglet experimental model to study the induced acute phase response. For this purpose, pigs (n=15 for each group) were intranasally inoculated with one of five PRRSV strains (isolates EU10, 12, 17, 18 from genotype 1 and isolate JA-142 from genotype 2). The acute phase response was monitored by measuring acute phase proteins (APPs). Specifically, the serum concentration of haptoglobin (Hp), C-reactive protein (CRP) and Pig-Major Acute Protein (Pig-MAP) was determined at 0, 3, 6, 9, 12, 15, 18 and 21 days p.i. Clinical signs and growth performance were also monitored during the experiment. All animals became viremic after inoculation during the study period. The APP response was heterogeneous and dependent on the strain, being strains EU10, EU 18 and JA-142 those that induced the highest response and the strongest clinical signs. In general, Hp was the most sensitive biomarker for PRRSV infection, CRP behaved as moderate and Pig-MAP was the less responsive during the course of PRRSV experimental infection. Hp and CRP were significantly discriminatory between infected and control pigs, but not Pig-MAP.

Porcine epidemic diarrhoea: new insights into an old disease.

Porcine epidemic diarrhea (PED) is an enteric disease in swine caused by an alphacoronavirus. It affects swine of all ages causing acute diarrhoea and can lead to severe dehydration and death in suckling piglets. Being recognized for the first time in Europe and Asia during the seventies and the eighties, respectively, it has remained a relevant cause of diarrhea outbreaks in Asia for years and to the present. It has become a major concern in swine production since 2013 when the virus was detected for first time in the USA and in other American countries causing a high number of pig deaths and significant economic losses. The present review aims at approaching the reader to the state of the art of PED giving answer to some of the most recent questions which have arisen related to this disease.

Playing games with the brain: The possible link between anesthesia and Alzheimer's disease revisited / Jugando con el cerebro: revisión del posible vínculo entre la anestesia y el Alzheimer

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Cistectomía radical por cáncer vesical en un hospital docente-asistencial: análisis de resultados perioperatorios / Radical cystectomy for bladder cancer in a state teaching hospital: analysis of perioperative outcomes

Introduction: A number of patients have been studied after undergoing Radical Cystectomy (RC) for bladder cancer, to review prognostic factors and analyze perioperative outcomes. A contemporary benchmark was established for future comparisons. Material and Methods: Retrospective study of 46 patients that underwent RC for bladder cancer between July 2003 and September 2012, assessing demographic characteristics, comorbidities, anesthetic risk and clinical status, interval between transurethral resection (TUR) and cystectomy, operative times, bleeding and transfusions, surgical technique, nutritional management, pathologic findings, hospital stay and complications. Complications were detailed by type and frequency and classified as early (within 30 days) or late. In addition, we used the Clavien-Dindo classification for reporting postoperative complications. Mortality rates at 30, 60 and 90 days after cystectomy were estimated. Results: Average patient age was 70 years (49-88) and mean ASA classification was 2.7. The average between TUR and cystectomy was 68.2 days (median = 57.5 days). Mean operative time for cutaneous ureterostomy was 194 minutes, 320 for ileal conduit and 342 for neobladder. 60.8 percent had pathological stage major than pT2 and 41 percent had nodal involvement. There were 19.5 percent of positive margins. The 23.9 percent had Clavien-Dindo postoperative complications grade 3 or 4. The 90-day global mortality was 17.3 percent. Conclusions: CR was associated with a high morbidity and mortality, which seems to be explained by an advanced stage of the disease and the high presence of poor prognostic factors.

Objetivos: Estudiamos una serie de pacientes sometidos a cistectomía radical (CR) por cáncer vesical para examinar factores pronósticos y analizar los resultados perioperatorios, estableciendo así un punto de referencia para futuras evaluaciones. Material y Método: Estudio retrospectivo de 46 pacientes sometidos a CR por cáncer vesical entre julio de 2003 y septiembre de 2012, evaluando características demográficas, comorbilidades, riesgo anestésico y condición clínica, lapso entre la resección transuretral (RTU) y la cistectomía, tiempos operatorios, sangrado y transfusiones, técnica quirúrgica utilizada, manejo nutricional, resultados anatomopatológicos, estada hospitalaria y complicaciones. Estas últimas fueron detalladas según tipo y frecuencia y catalogadas como precoces (durante los primeros 30 días) o tardías. Además, se utilizó la clasificación de Clavien-Dindo para reportar las complicaciones postoperatorias. Se estimaron las tasas de mortalidad a 30, 60 y 90 días post cistectomía. Resultados: El promedio de edad fue 70 años (49-88) y la media de la clasificación ASA fue 2,7. El promedio entre la RTU y la cistectomía fue 68,2 días. Los tiempos operatorios promedio fueron de 194 min la ureterostomía cutánea, 320 el conducto ileal y 342 la neovejiga. Un 60,8 por ciento tenía un pT > 2 y un 41 por ciento compromiso ganglionar. Hubo 19,5 por ciento de márgenes positivos. Un 23,9 por ciento tuvo complicaciones grado 3 ó 4 según Clavien-Dindo. La mortalidad global a 90 días fue 17,3 por ciento. Conclusiones: la CR se asoció a una elevada morbimortalidad, lo que parece explicarse por un estado avanzado de la enfermedad y por la alta presencia de factores de mal pronóstico.

Análisis de supervivencia en pacientes sometidos a cistectomía radical por cáncer vesical en un Hospital docente-asistencial / Analysis of survival in patients undergoing radical cystectomy forbladder cancer in a teaching Hospital

Examinar factores pronósticos y analizar la supervivencia en pacientes sometidos a cistectomía radical (CR) por cáncer vesical. MATERIAL Y MÉTODO: estudio de cohortes retrospectivo de 46 pacientes sometidos a CR por cáncer vesical entre julio de 2003 y septiembre de 2012, considerándose como variable dependiente la supervivencia y como variables independientes: las características demográficas, comorbilidades, riesgo anestésico, condición clínica, lapso entre la RTU y la cistectomía, derivación urinaria utilizada, resultados anatomopatológicos y complicaciones postoperatorias. Se analizó la supervivencia mediante Kaplan-Meier, elaborando curvas que fueron comparadas mediante el método de Mantel-Cox. Se efectuó un análisis de supervivencia a 2 años de la cistectomía, mediante regresión logística binaria multivariante. RESULTADOS: La media de la supervivencia global fue 31,8 meses (mediana = 12 meses) y la de la específica 38,2 meses (mediana = 16). La supervivencia global fue mayor en enfermos menores de 70 años, con función renal o albuminemia normales, ASA <3 y en quienes se elaboró una neovejiga. La supervivencia específica fue mayor en los pacientes con estadio tumoral (pT) <3, densidad ganglionar <20 por ciento, margen quirúrgico negativo, sin compromiso ganglionar o masa residual (R0) y en los sometidos a linfadenectomía. Los factores de riesgo para fallecer dentro de los primeros 2 años fueron edad sobre 69 años, ASA >2, pT >2 (OR 25), compromiso ganglionar, metástasis a distancia, masa residual y margen positivo. CONCLUSION: La infiltración local, la afectación ganglionar y una edad mayor a 69 años fueron los tres factores de riesgo más determinantes de un peor pronóstico.

To review prognostic factors and analyze the survival of patients treated with radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Retrospective cohort study of 46 patients underwent RC for bladder cancer between July 2003 and September 2012 was carried out, considering survival as the dependent variable and as independent variables the following: demographic characteristics, comorbidities, anesthetic risk, clinical condition, delay between transurethral resection (TUR) and cystectomy, urinary diversion performed, pathologic findings, and postoperative complications. A survival analysis using the Kaplan-Meier method was performed; as a result curves were obtained and compared using the Mantel-Cox test. A multivariate binary logistic regression was performed, and prognostic factors of survival at 2 years of cystectomy were evaluated. RESULTS: The median overall survival was 31.8 months (median 12 months) and specific overall survival was 38.2 months (median = 16). Overall survival was higher in patients younger than 70 years, with normal renal function and normal albumin, ASA minor than 3 and in those that a neobladder was developed. Specific survival was higher in patients with tumor stage (pT) <3, node density <20 percent, negative surgical margins, without lymph node involvement or residual mass (R0) and in those underwent to lymphadenectomy. Risk factors for death within the first 2 years were: age over 69 years, ASA> 2, pT> 2 (OR 25), nodal involvement, distant metastases, residual mass and positive margins. CONCLUSIONS: Local infiltration, lymph node involvement and age over 69 years were the three most crucial risk factors for a worse prognosis.

MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis.

BACKGROUND: Renal cell tumours (RCTs) are clinically, morphologically and genetically heterogeneous. Accurate identification of renal cell carcinomas (RCCs) and its discrimination from normal tissue and benign tumours is mandatory. We, thus, aimed to define a panel of microRNAs that might aid in the diagnostic workup of RCTs. METHODS: Fresh-frozen tissues from 120 RCTs (clear-cell RCC, papillary RCC, chromophobe RCC (chRCC) and oncocytomas: 30 cases each), 10 normal renal tissues and 60 cases of ex-vivo fine-needle aspiration biopsies from RCTs (15 of each subtype validation set) were collected. Expression levels of miR-21, miR-141, miR-155, miR-183 and miR-200b were assessed by quantitative reverse transcription-PCR. Receiver operator characteristic curves were constructed and the areas under the curve were calculated to assess diagnostic performance. Disease-specific survival curves and a Cox regression model comprising all significant variables were computed. RESULTS: Renal cell tumours displayed significantly lower expression levels of miR-21, miR-141 and miR-200b compared with that of normal tissues, and expression levels of all miRs differed significantly between malignant and benign RCTs. Expression analysis of miR-141 or miR-200b accurately distinguished RCTs from normal renal tissues, oncocytoma from RCC and chRCC from oncocytoma. The diagnostic performance was confirmed in the validation set. Interestingly, miR-21, miR-141 and miR-155 expression levels showed prognostic significance in a univariate analysis. CONCLUSION: The miR-141 or miR-200b panel accurately distinguishes RCC from normal kidney and oncocytoma in tissue samples, discriminating from normal kidney and oncocytoma, whereas miR-21, miR-141 and miR-155 convey prognostic information. This approach is feasible in fine-needle aspiration biopsies and might provide an ancillary tool for routine diagnosis.

Antibacterial activity and mode of action of a commercial citrus fruit extract.

AIMS: This study addresses the antibacterial activity and mechanism of action of BIOLL(+®), a commercial extract obtained from citrus fruits. METHODS AND RESULTS: Strong activities with minimum inhibitory concentrations (MIC) ranging from 10 ppm (for some Brachyspira hyodysenteriae strains) to 80 ppm (for various Salmonella enterica and Escherichia coli strains) were observed. Membrane integrity tests and Fourier transform infrared (FT-IR) spectroscopic analyses were performed to shed light on the effects caused on molecular structure and composition. Physical effects, with formation of pores and leakage of intracellular components, and chemical effects, which were dependent on the bacterial species, were evident on cellular envelopes. Whereas for S. enterica and E. coli, changes were focused on the carboxylic group of membrane fatty acids, for B. hyodysenteriae, the main effects were found in polysaccharides and carbohydrates of the cell wall. CONCLUSIONS: The great antibacterial activity shown by BIOLL(+®) and its proposed dual physico-chemical mode of action, with species-specific cellular targets, show its attractiveness as an alternative to antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic resistance is becoming a serious problem. Our study characterizes a novel antimicrobial extract, which could represent an alternative to antibiotics for treatment or prevention of bacterial infectious diseases.

Repeat-enriched proteins are related to host cell invasion and immune evasion in parasitic protozoa.

Proteins containing repetitive amino acid domains are widespread in all life forms. In parasitic organisms, proteins containing repeats play important roles such as cell adhesion and invasion and immune evasion. Therefore, extracellular and intracellular parasites are expected to be under different selective pressures regarding the repetitive content in their genomes. Here, we investigated whether there is a bias in the repetitive content found in the predicted proteomes of 6 exclusively extracellular and 17 obligate intracellular protozoan parasites, as well as 4 free-living protists. We also attempted to correlate the results with the distinct ecological niches they occupy and with distinct protein functions. We found that intracellular parasites have higher repetitive content in their proteomes than do extracellular parasites and free-living protists. In intracellular parasites, these repetitive proteins are located mainly at the parasite surface or are secreted and are enriched in amino acids known to be part of N- and O-glycosylation sites. Furthermore, in intracellular parasites, the developmental stages that are able to invade host cells express a higher proportion of proteins with perfect repeats relative to other life cycle stages, and these proteins have molecular functions associated with cell invasion. In contrast, in extracellular parasites, degenerate repetitive motifs are enriched in proteins that are likely to play roles in evading host immune response. Altogether, our results support the hypothesis that both the ability to invade host cells and to escape the host immune response may have shaped the expansion and maintenance of perfect and degenerate repeats in the genomes of intra- and extracellular parasites.

Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer.

BACKGROUND: Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly promising novel target in breast cancer. However, the expression of PARP-1 protein in breast cancer and its associations with outcome are yet poorly characterized. PATIENTS AND METHODS: Quantitative expression of PARP-1 protein was assayed by a specific immunohistochemical signal intensity scanning assay in a range of normal to malignant breast lesions, including a series of patients (N = 330) with operable breast cancer to correlate with clinicopathological factors and long-term outcome. RESULTS: PARP-1 was overexpressed in about a third of ductal carcinoma in situ and infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P = 0.01), estrogen-negative tumors (P < 0.001) and triple-negative phenotype (P < 0.001). The hazard ratio (HR) for death in patients with PARP-1 overexpressing tumors was 7.24 (95% CI; 3.56-14.75). In a multivariate analysis, PARP-1 overexpression was an independent prognostic factor for both disease-free (HR 10.05; 95% CI 5.42-10.66) and overall survival (HR 1.82; 95% CI 1.32-2.52). CONCLUSIONS: Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.