Effect of culture parameters on the heat tolerance and inorganic polyphosphate accumulation by Lacticaseibacillus rhamnosus CRL1505, a multifunctional bacterium.

Lacticaseibacillus rhamnosus CRL1505 can be used in functional products as a probiotic powder (dried live cells) or as a postbiotic intracellular extract containing inorganic polyphosphate as a functional biopolymer. Thus, the aim of this work was to optimize the production of Lr-CRL1505 depending on the target of the functional product (probiotic or postbiotic). For this purpose, the effect of culture parameters (pH, growth phase) on cell viability, heat tolerance and polyphosphate accumulation by Lacticaseibacillus rhamnosus CRL1505 was evaluated. Fermentations at free pH produced less biomass (0.6 log units) than at controlled pH while the growth phase affected both polyphosphate accumulation and cell heat tolerance. Exponential phase cultures showed 4-15 times greater survival rate against heat shock and 49-62% increased polyphosphate level, compared with the stationary phase. Results obtained allowed setting the appropriate culture conditions for the production of this strain according to its potential application, i.e., as live probiotic cells in powder form or postbiotic. In the first case, running fermentations at pH 5.5 and harvesting the cells at the exponential phase are the best conditions for obtaining a high live biomass yield capable of overcoming heat stress. Whereas the postbiotic formulations production requires fermentations at free pH and harvesting the cells in exponential phase to increase the intracellular polyphosphate level as a first step.

Inorganic Additive Improves the Survival of the Probiotic Lacticaseibacillus rhamnosus CRL1505 During Spray Drying, Rehydration, and Storage.

In previous in vitro studies, an inorganic additive (MCM3) showed a thermo-protective effect on the cell viability of Lacticaseibacillus rhamnosus CRL1505 (Lr-CRL1505). In this work, cultures of this probiotic strain were spray dried at lab scale using two carriers: maltodextrin (powder MA) and maltodextrin plus MCM3 (powder MA/MCM3). The cell survival was higher in powder MA/MCM3 (72.8%) than in powder MA (42.8%). Different rehydration media, including the additive MCM3, and two temperatures (37 °C and 45 °C) were evaluated. The best results were obtained in cells rehydrated at 37 °C in MCM3. During the storage of the powders, the highest cell counts were observed in the MA/MCM3 powder. Our results demonstrated that the presence of MCM3 in the carrier and in reconstitution media benefits the spray drying process and the recovery of dehydrated cells. Thus, the use of this additive of inorganic nature and low cost represents a promising technological alternative.

Oral Vaccination with Hepatitis E Virus Capsid Protein and Immunobiotic Bacterium-Like Particles Induce Intestinal and Systemic Immunity in Mice.

The hepatitis E virus (HEV) genotype 3 (GT3) is an emergent pathogen in industrialized countries. It is transmitted zoonotically and may lead to chronic hepatitis in immunocompromised individuals. We evaluated if the major antigen of HEV, the capsid protein, can be used in combination with immunobiotic bacterium-like particles (IBLP) for oral vaccination in a mouse model. We have cloned and expressed the RGS-His5-tagged HEV GT3 capsid protein (ORF2) in E. coli and purified it by NiNTA. IBLP were obtained from two immunobiotic Lactobacillus rhamnosus strains acid- and heat-treated. ORF2 and the IBLP were orally administered to Balb/c mice. After three oral immunizations (14-day intervals), blood, intestinal fluid, Peyer´s patches, and spleen samples were drawn. IgA- and IgG-specific antibodies were determined by ELISA. Mononuclear cell populations from Peyer's patches and spleen were analyzed by flow cytometry, and the cytokine profiles were determined by ELISA to study cellular immunity. Orally administered recombinant ORF2 and IBLP from two L. rhamnosus strains (CRL1505 and IBL027) induced both antigen-specific humoral and cellular immune responses in mice. IBLP027 was more effective in inducing specific secretory IgA in the gut. IFN-γ, TNF-α, and IL-4 were produced by Peyer's plaques lymphocytes stimulated with ORF2 ex vivo suggesting a mixed Th1/Th2-type adaptive immune response in immunized mice. Oral vaccines are not invasive, do not need to be administered by specialized personal, and elicit both systemic and local immune responses at the port of entry. Here, we present an experimental oral vaccine for HEV GT3, which could be further developed for human and/or veterinary use.

Biofunctionalized silicon nitride platform for sensing applications.

Silicon nitride (SiNx) based biosensors have the potential to converge on the technological achievements of semiconductor microfabrication and biotechnology. Development of biofunctionalized SiNx surface and its integration with other devices will allow us to integrate the biosensing capability with probe control, data acquisition and data processing. Here we use the hydrogen plasma generated by inductively coupled plasma-reactive ion etching (ICP-RIE) technique to produce amino-functionality on the surface of SiNx which can then be readily used for biomolecule immobilization. ICP-RIE produces high-density hydrogen ions/radicals at low energy, which produces high-density amino group on the SiNx surface within a short duration of time and with minimal surface damage. In this work, we have demonstrated selective amination of SiNx surface as compared to Si surface. The as-activated SiNx surface can be readily biofunctionalized with both protein and oligonucleotide through covalent immobilization. N-5-azido-2-nitrobenzoyloxysuccinimide, a photoactivable amino reactive bifunctional crosslinker, was used and greater than 90% surface coverage was achieved for protein immobilization. In addition, ssDNA immobilization and hybridization with its complemented strand was shown. Thus, we demonstrate a uniform, reliable, fast and economical technique for creating biofunctionalized SiNx surface that can be used for developing compact high-sensitivity biosensors.

Lactobacillus rhamnosus CRL1505 nasal administration improves recovery of T-cell mediated immunity against pneumococcal infection in malnourished mice.

Immunobiotic lactic acid bacteria have become an interesting alternative for the prevention of respiratory infections. Previously, we demonstrated that the nasal administration of Lactobacillus rhamnosus CRL1505, during repletion of malnourished mice, resulted in diminished susceptibility to the challenge with the respiratory pathogen Streptococcus pneumoniae. Considering the known alterations induced by malnutrition on T lymphocytes and the importance of this cell population on the protection against respiratory pathogens, we aimed to study the effect of L. rhamnosus CRL1505 nasal administration on the recovery of T cell-mediated defences against pneumococcal infection in malnourished mice under nutritional recovery. Malnourished mice received a balanced conventional diet (BCD) for seven days or BCD for seven days with nasal L. rhamnosus CRL1505 supplementation during last two days of the treatment. After the treatments mice were infected with S. pneumoniae. Flow cytometry studies were carried out in bone marrow, thymus, spleen and lung to study T cells, and Th1/Th2 cytokine profiles were determined in broncho-alveolar lavages and serum. The administration of CRL1505 strain to malnourished mice under recovery reduced quantitative and qualitative alterations of CD4+ T cells in the bone marrow, thymus, spleen and lung induced by malnutrition. In addition, CRL1505 treatment augmented Th2-cytokines (interleukin 10 and 4) in respiratory and systemic compartments after pneumococcal infection. These results show that modulation of CD4+ T lymphocytes induced by L. rhamnosus CRL1505 has an important role in the beneficial effect induced by this strain on the recovery of malnourished mice. These data also indicate that nasally administered L. rhamnosus CRL1505 may represent a non-invasive alternative to modulate and improve the T cell-mediated immunity against respiratory pathogens in immunocompromised malnourished hosts.

Clostridium difficile in the ICU: Study of the incidence, recurrence, clinical characteristics and complications in a University Hospital / Clostridium difficile en UCI: estudio de la incidencia, recurrencias, características clínicas y complicaciones en un hospital universitario

OBJECTIVE: Although several studies have established the association between antibiotics and Clostridium difficile infection (CDI), there is a lack of epidemiological studies on the incidence of CDI in European Intensive Care Units outside the context of infection outbreaks. The present study describes the incidence, patient characteristics, complications, and recurrence rates of CDI in a Spanish ICU. DESIGN: A retrospective study was carried out. SETTING: A clinical---surgical ICU with 34 beds, a tertiary referral hospital with 1400 beds. PATIENTS: All patients over 18 years of age admitted to the ICU from January 2010 to December2011 with diarrhea for more than 48 h.INTERVENTIONS: None. Study variables: Underlying diseases, risk factors, fever, leukocyte count, complications, recurrence of infection. RESULTS: A total of 1936 adult patients were admitted. Seven patients acquired CDI (0.36%),representing an infection rate of 3.1 per 10,000 bed-days and a cumulative incidence rate of3.6 in two years. The mean age was 61 years. Six patients showed some degree of immunosuppression. The mean APACHE II score at ICU admission was 17 (IQR 13---24). Severe sepsis was reported in 5 cases of CDI, three of which presented shock and multiorgan dysfunction. Four patients presented recurrence of CDI during hospitalization. ICU admission was prolonged for a mean of 24 days (SD 17.8) after diagnosis. CONCLUSIONS: Less than 1% of the patients admitted to a clinical---surgical ICU in a large teaching institution in Spain developed CDI. However, a high risk of recurrence/complications was associated with prolonged ICU stay

OBJETIVO: El objetivo de este estudio es describir la incidencia, características de los pacientes, complicaciones y la recurrencia de infección por Clostridium difficile en una UCI de un hospital universitario en un período fuera de brote. DISEÑO: Serie de casos. Ámbito: UCI médico-quirúrgica de 34 camas en hospital de referencia de 1.400 camas. Pacientes o participantes: Todo paciente mayor de 18 años ingresado en la UCI desde enero de2010 hasta diciembre de 2011 que tuviese diarrea durante más de 48 h. INTERVENCIONES: Sin intervención. Variables de interés principales: Enfermedades de base, factores de riesgo, recurrencia de infección. RESULTADOS: Un total de 1.936 pacientes fueron ingresados en el periodo de estudio, de los cuales 177 presentaron diarrea durante más de 48 h y 7 cumplieron criterios de infección por Clostridium difficile (0,36%). Una tasa de infección de 3,1 pacientes por cada 10.000 camas/día y una incidencia acumulada de 3,6×1.000, en 2 años. La edad media fue de 61 años. Seis mostraron algún grado de inmunosupresión. La media del score APACHE II al ingreso fue de17. Cinco casos presentaron sepsis grave, 3 de los cuales tuvieron shock y disfunción multiorgánica. Un paciente de los 7 (14%) falleció. Cuatro pacientes sufrieron recurrencia durante la hospitalización (57%). La estancia media se prolongó 24 días (DE 17,8) después del diagnóstico. CONCLUSIONES: Menos del 1% de los pacientes hospitalizados en una UCI médico-quirúrgica desarrollaron infección por Clostridium difficile. Sin embargo, se asoció a un alto grado de recurrencia/complicaciones y a una larga estancia en la UCI

Pneumonia in immunocompetent patients: combination antibiotic therapy.

Pneumonia's burden is still important worldwide not only because of its high incidence and mortality, but also for the elevated costs related to it. Despite the concerted efforts to reduce the incidence of sepsis-related complications, they continue to represent a major human and economic burden. The cornerstone of sepsis management is early appropriate empiric broad spectrum antibiotics, resuscitation, and source control. The association between inappropriate use of antibiotics and increased mortality is the rationale for the use of empiric antibiotic combination therapy in critically ill patients. The aim of this manuscript was to discuss recent literature regarding the management of severe pneumonia, both community-acquired and hospital-acquired/ventilator-associated, in critically ill patients. Use of combination therapy is warranted in severe infections with shock; considerations should be made on the importance of optimal antibiotic administration and adverse reactions, thus providing guidance for a rational use of antibiotics.

Clostridium difficile in the ICU: study of the incidence, recurrence, clinical characteristics and complications in a university hospital.

OBJECTIVE: Although several studies have established the association between antibiotics and Clostridium difficile infection (CDI), there is a lack of epidemiological studies on the incidence of CDI in European Intensive Care Units outside the context of infection outbreaks. The present study describes the incidence, patient characteristics, complications, and recurrence rates of CDI in a Spanish ICU. DESIGN: A retrospective study was carried out. SETTING: A clinical-surgical ICU with 34 beds, a tertiary referral hospital with 1400 beds. PATIENTS: All patients over 18 years of age admitted to the ICU from January 2010 to December 2011 with diarrhea for more than 48 h. INTERVENTIONS: None. STUDY VARIABLES: Underlying diseases, risk factors, fever, leukocyte count, complications, recurrence of infection. RESULTS: A total of 1936 adult patients were admitted. Seven patients acquired CDI (0.36%), representing an infection rate of 3.1 per 10,000 bed-days and a cumulative incidence rate of 3.6 in two years. The mean age was 61 years. Six patients showed some degree of immunosuppression. The mean APACHE II score at ICU admission was 17 (IQR 13-24). Severe sepsis was reported in 5 cases of CDI, three of which presented shock and multiorgan dysfunction. Four patients presented recurrence of CDI during hospitalization. ICU admission was prolonged for a mean of 24 days (SD 17.8) after diagnosis. CONCLUSIONS: Less than 1% of the patients admitted to a clinical-surgical ICU in a large teaching institution in Spain developed CDI. However, a high risk of recurrence/complications was associated with prolonged ICU stay.

Potentiality of standardized extract and isolated flavonoids from Zuccagnia punctata for the treatment of respiratory infections by Streptococcus pneumoniae: in vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuccagnia punctata Cav. (Fabaceae) is a monotypic species distributed in western Argentina and is traditionally used for the treatment of bacterial and fungal infections. The aim of this study was to demonstrated the antibacterial activity of the Zuccagnia punctata standardized extract and the structurally related non-methoxylated flavonoids with similar pattern of substitution and differences in ring C present in this plant species: 7-hydroxyflavanone (HF), 2',4'-dihydroxychalcone (DHC) and 3,7-dihydroxyflavone (DHF), against Streptococcus pneumoniae clinical isolates using in vitro and in vivo models. MATERIALS AND METHODS: MIC values of natural products were determined by agar macrodilution method. In vivo activities were investigated in a Streptococcus pneumoniae infection model in mice. Lung and blood samples were obtained for bacterial cell counts. The serum was used by biochemical analysis (alanine transaminase, aspartate transaminase, urea and creatinine) in order to evaluate the toxicity of natural products. RESULTS: All samples showed antimicrobial activity in vitro with MIC values between 50 and 500µg/ml. Zuccagnia punctata extract (1mg/mice) and HF (1mg/mice) significantly reduced the number of viable Streptococcus pneumoniae in lung (p<0.01) while lower quantities has not effect. Therefore, the present study has shown that intake once or twice a day of 1mg of Zuccagnia punctata extract or HF for seven days did not result in toxicity. CONCLUSIONS: Our results showed that Zuccagnia punctata extract as well as one of its isolated flavonoids, 7-hydroxyflavanone, could be useful for the development of a novel respiratory infections treatment.

Aerobic and strength training reduces adiposity in overweight Latina adolescents.

PURPOSE: To date, no study has examined the synergistic effects of a nutrition and combination of aerobic and strength training (CAST) on both adiposity and metabolic parameters in overweight Latina adolescent females. The goal was to assess if a 16-wk nutrition plus CAST pilot study had stronger effects on reducing adiposity and on improving glucose/insulin indices compared with control (C), nutrition only (N), and a nutrition plus strength training (N + ST) groups. METHODS: In a 16-wk randomized trial, 41 overweight Latina girls (15.2 +/- 1.1 yr) were randomly assigned to C (n = 7), N (n = 10), N + ST (n = 9), or N + CAST (n = 15). All intervention groups received modified carbohydrate nutrition classes (once a week), whereas the N + ST also received strength training (twice a week) and the N + CAST received a combination of strength and aerobic training (twice a week). The following were measured before and after intervention: strength by one repetition maximum, physical activity by the 7-d accelerometry and the 3-d physical activity recall, dietary intake by 3-d records, body composition by dual-energy x-ray absorptiometry (DEXA), glucose/insulin indices by oral glucose tolerance test, and intravenous glucose tolerance test with minimal modeling. Across intervention group, effects were tested using ANCOVA with post hoc pairwise comparisons. RESULTS: There were significant overall intervention effects for all adiposity measures (weight, body mass index [BMI], BMI z-scores, and DEXA total body fat), with a decrease of 3% in the N + CAST group compared with a 3% increase in the N + ST group (P < or = 0.05). There was also an intervention effect for fasting glucose with the N group increasing by 3% and the N + CAST group decreasing by 4% (P < or = 0.05). CONCLUSION: The CAST was more effective than nutrition alone or nutrition plus strength training for reducing multiple adiposity outcomes and fasting glucose in overweight Latina girls. However, further research investigating and identifying intervention approaches that improve both adiposity and insulin indices, particularly in high-risk populations, are warranted.

Termocoagulación gasseriana por radiofrecuencia en 825 pacientes con neuralgia trigeminal / Radiofrequency retrogasserian termocoagulation in 825 patients with trigeminal neuralgia

Se presentan 825 pacientes con el diagnóstico de neuralgia trigeminal a los que se les realizó la técnica de termo-coagulación percutánea selectiva del ganglio de gasser atendiendo de forma específica a la rama causante del dolor, en el servicio de neurocirugía del Hospital Clínico Quirúrgico Hermanos Ameijeiras" en el período de 1988 al 2003. Nuestro propósito principal fue lograr el alivio del dolor evaluando las siguientes variables: resultados quirúrgicos inmediatos y a largo plaza tomando como límite mínimo un año de postoperatorio, clasificación topográfica de la rama afectada, evolución, complicaciones y beneficios de la técnica. En todos los casos la evolución postquirúrgica superó el año como mínimo y se obtuvieron buenos resultados en el 90.2 % (AU)

We present 825 patients suffering of trigeminal neuralgia, who had a selective percoutaneous technique of Gaesser Ganglio termocoagulation; each neural branch that caused pain was treated. The experience was carried out at the Department of Neurosurgery of the University Hospital Hermanos Ameijeiras, La Habana Cuba, from 1988 to 2003. We aimed to obtain pain relief and record these variables: immediate surgical results and long-term evolution (one year postoperative at last); topographic classification of the affected branch; evolution, complications and benefits derived from the first year. A good outcome was obtained in 90.2% the cases (AU)

Termocoagulación facetaria lumbar. Experiencia en 252 pacientes / Thermocoagulation of lumbar facet joints. Experience in 252 patients

Se presentan 252 pacientes con el diagnóstico de dolorlumbar facetario a los que se le realizó la técnica quirúrgicade termocoagulación percutánea de la faceta articular.Nuestro propósito principal fue aliviar el dolor en estos pacientes,evaluamos la eficacia de la técnica con un 74,7%de resultados quirúrgicos satisfactorios, así como la descripciónde diferentes aspectos como: edad, sexo, causas yla topografía segmentaria del dolor

Two hundred fifty two patients with diagnosis of lumbarfacet joint pain underwent the surgical technique ofpercutaneous thermocoagulation of the facet joint. Ourmajor aim was to relief pain in those patients. We assessthe effectiveness of the technique, with 74.7% ofsurgical success, and we also describe different aspectssuch as: age, sex, causes and segmentary pain topography

Estudio comparativo entre la termocoagulación retrogasseriana y la microcompresión con balón catéter en la neuralgia trigeminal / Gasserian thermocoagulation and microcompression with balloon catheter in trigeminal neuralgia

Se presentan 180 pacientes con el diagnóstico de neuralgiatrigeminal, a 90 se les realizó termocoagulación percutáneadel ganglio de Gasser por radiofrecuencia y a los otros 90 microcompresión percutánea retrogasseriana conbalón catéter de Fogarty. Nuestro propósito principal fuealiviar el dolor facial en pacientes portadores de neuralgiatrigeminal, evaluamos los resultados de ambas técnicas, asícomo la descripción de diferentes aspectos que comprendieron:clasificación clínico-topográfica de las ramas afectadas,evolución, resultados quirúrgicos inmediatos y a largoplazo (tomando como límite mínimo el año de operado),además de las complicaciones y ventajas de ambos procederesquirúrgicos. En ambos procederes los buenos resultadosquirúrgicos sobrepasaron el 90%

We present 180 patients diagnosed of trigeminal neuralgia,90 of which underwent percutaneous thermocoagulationof the Gasser’s ganglion with radiofrequency and theother 90 underwent retrogasserian percutaneous microcompressionwith Fogarty balloon catheter. Our main purposewas to relief facial pain in patients with trigeminalneuralgia. We review the results of both techniques anddescribe different aspects such as clinicotopographic classificationof the branches involved, evolution, short-term andlong-term surgical results (taking as lower limit one year afterthe surgery), as well as complications and benefits ofthe two surgical procedures. In both cases, good surgicalresults were obtained in excess of 90%

[Stereotaxic biopsy and 192Ir implant in intracranial tumors. A review of 7 years of experience]. / Biopsia estereotáxica e implante de Ir-192 en tumores intracraneales. Revisión de 7 años de experiencia.

INTRODUCTION: The combination of stereotaxic techniques, advances in neuroimaging and the creation of continually improving software has permitted stereotaxic biopsy of cerebral lesions at the most varied sites. Improvement in the method of permanent interstitial radiation (brachytherapy) improves the precision with which the radioactive sources may be inserted, releasing a maximum dose of radiation to the tumour with minimum radiation to the surrounding tissue. PATIENTS AND METHODS: We treated 237 patients (aged 1 to 78 years) with intracranial lesions, all included in the protocol of our centre. Stereotaxic systems of Leksell, Riechert-Mundinger, Micromar and Estereoflex were used. The procedure was in three stages: acquisition of the image, surgical planning and surgical operation. The imaging guide was the computerized axial tomography (CAT). RESULTS: Stereotaxic biopsy guided by CAT images was done in 153 patients. These were divided into three groups, taking the biopsy findings as the reference: group A (primary tumors, 128), group B (metastatic tumors, 15) and group C (non-malignant lesions, 10). Ninety six permanent implants of 192Ir were inserted, with a low dose of 4-7 cGy/h and a total dose of 80-120 Gy. CONCLUSIONS: Stereotaxic biopsy is a very effective procedure with a significantly low range of complications. The permanent implant with a low dose rate, well situated and using a source of 192Ir is a safe, simple, effective method for the treatment of primary and recurrent glial tumours, and non-glial tumours which fulfil criteria for this type of brachytherapy.

Biopsia estereotáxica e implante de 192Ir en tumores intracraneales.Revisión de siete años de experiencia / Stereotaxic biopsy and implantation of 192Ir in intracranial tumors. A review of seven years experience

Introducción. La combinación de técnicas estereotáxicas, los avances en las neuroimágenes y la creación de programas informáticos cada vez más óptimos ha permitido la realización de biopsias estereotáxicas a lesiones cerebrales en las más variadas localizaciones. El perfeccionamiento del método de radiación intersticial permanente (braquiterapia) mejora la exactitud en la colocación de las fuentes radiactivas, liberando una dosis de radiación máxima al tumor con mínima irradiación del tejido normal que lo rodea. Pacientes y métodos. Fueron tratados 237 pacientes (de 1 a 78 años) con lesiones intracraneales, todos ellos incluidos en el protocolo de nuestra institución; se utilizaron los sistemas estereotáxicos de Leksell, Riechert-Mundinger, Micromar y Estereoflex. El procedimiento constó de tres etapas: adquisición de la imagen, planificación quirúrgica e intervención quirúrgica. La guía por imagen fue la tomografía axial computadorizada (TAC). Resultados. Se realizó biopsia estereotáxica guiada por imágenes de TAC a 153 pacientes, los cuales se dividieron en tres grupos tomando como referencia el hallazgo de la biopsia: grupo A (tumores primarios, 128); grupo B (tumores metastásicos, 15), y grupo C (lesiones no malignas, 10). Se realizaron 96 implantes permanentes de 192Ir con una tasa de dosis baja de 4-7 cGy/h con dosis total de 80 a 120 Gy. Conclusiones. La biopsia estereotáxica es un procedimiento muy eficaz con un margen de complicaciones significativamente bajo. El implante permanente de tasa de dosis baja, bien localizado y utilizando una fuente de 192Ir es un método simple, seguro y eficaz en el tratamiento de tumores gliales primarios y recurrentes, así como en otros no gliales que reúnan los criterios para dicha modalidad de braquiterapia (AU)

Biopsia estereotáxica e implante de 192Ir en tumores intracraneales: revisión de siete años de experiencia / Stereotaxic biopsy and implantation of 193Ir in intracranial tumors: a review of seven years experience

Introducción. La combinación de técnicas estereotáxicas, los avances en las neuroimágenes y la creación de programas informáticos cada vez más óptimos ha permitido la realización de biopsias estereotáxicas a lesiones cerebrales en las más variadas localizaciones. El perfeccionamiento del método de radiación intersticial permanente (braquiterapia) mejora la exactitud en la colocación de las fuentes radiactivas, liberando una dosis de radiciación máxima al tumor con mínima irradiación del tejido normal que lo rodea. Pacientes y métodos. Fueron tratados 237 pacientes (de 1 a 78 años) con lesiones intracraneales, todos ellos incluidos en el protocolo de nuestra institución; se utilizaron los sitemas estereotáxicos de Leksell, Riechert-Mundinger, Micromar y Estereoflex. El procedimiento constó de tres etapas: adquisición de la imagen, planificación quirúrgica e intervención quirúrgica. La guía por imagen fue la tomografía axial computarizada (TAC). Resultados. Se realizó biopsia estereotáxica guiada por imágenes de TAC a 153 pacientes, los cuales se dividieron en tres grupos tomando como referencia el hallazgo de la biopsia: grupo A (tumores primarios, 128); grupo B (tumores metastásicos, 15), y grupo C (lesiones no malignas, 10). Se realizaron 96 implantes permanentes de 192Ir con una tasa de dosis baja de 4-7 cGy/h con dosis total de 80 a 120 Gy. Conclusiones. La biopsia estereotáxica es un procedimiento muy eficaz con un margen de complicaciones significativamente bajo. El implante permanente de tasa de dosis baja, bien localizado y utilizando una fuente de 192Ir es un método simple, seguro y eficaz en el tratamiento de tumores gliales primarios y recurrentes, así como en otros no gliales que reunan los criterios para dicha modalidad de braquiterapia(AU)

Chemical modification of nodulisporic acid A: preliminary structure-activity relationships.

Medicinal chemistry efforts were initiated to identify the key constituents of the nodulisporic acid A (1) pharmacophore that are integral to its potent insecticidal activity. New semisynthetic derivatives delineated 1 into 'permissive' and 'nonpermissive' regions and led to the discovery of new nodulisporamides with significantly improved flea efficacy.

SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin.

Thrombin-mediated changes in endothelial cell adherens junctions modulate vascular permeability. We demonstrate that the nonreceptor protein-tyrosine phosphatase SHP2 co-precipitates with VE-cadherin complexes in confluent, quiescent human umbilical vein endothelial cells. Ligand-binding blots using a SHP2-glutathione S-transferase fusion peptide established that SHP2 associates selectively with beta-catenin in VE-cadherin complexes. Thrombin treatment of human umbilical vein endothelial cells promotes SHP2 tyrosine phosphorylation and dissociation from VE-cadherin complexes. The loss of SHP2 from the cadherin complexes correlates with a dramatic increase in the tyrosine phosphorylation of beta-catenin, gamma-catenin, and p120-catenin complexed with VE-cadherin. We propose that thrombin regulates the tyrosine phosphorylation of VE-cadherin-associated beta-catenin, gamma-catenin, and p120-catenin by modulating the quantity of SHP2 associated with VE-cadherin complexes. Such changes in adherens junction complex composition likely underlie thrombin-elicited alterations in endothelial monolayer permeability.

Surfactant-induced alteration of arachidonic acid metabolism of mammalian cells in culture.

Primary irritancy in human and animal skin is characterized by an inflammatory reaction mediated, in part, by membrane-derived arachidonate metabolites. One of the mechanisms of this reaction was investigated in cultured mammalian cells using three surfactants: linear alkyl benzene sulfonate (LAS), alkyl ethoxylate sulfate (AEOS), and TWEEN 20. These compounds listed in order in vivo irritancy are LAS greater than AEOS greater than TWEEN 20. Each of these compounds was studied in C3H-10T1/2 cells and human keratinocytes which had been prelabeled with 3H-labeled arachidonic acid (AA). After labeling, media were removed, cells were washed, and fresh media with or without surfactant were added. Cells were then incubated for 2 hr, media were removed and centrifuged, and an aliquot was assayed by liquid scintillation for release of label. In C3H-10T1/2 cells LAS and AEOS in 5-50 microM concentration stimulated 2 to 10 times the release of [3H]AA as compared to controls. In contrast, concentrations of 50-100 microM of TWEEN were required to release [3H]AA. With keratinocytes the same rank order of surfactant concentrations necessary for release was obtained as found with C3H-10T1/2 cells. High-performance liquid chromatography of media extracts of both cell systems revealed surfactant stimulation of the production of cyclooxygenase AA metabolites. These results confirm the induction of release by primary irritants of fatty acid groups from membrane phospholipids. Subsequent metabolism of these fatty acid groups are an integral part of the primary irritant response. Data presented with three known irritants in this in vitro model show a direct correlation with in vivo studies.