SALUD PÚBLICA: un campo de confrontación del paradigma disciplinar y transdisciplinar / PUBLIC HEALTH: A confrontation field of the disciplinary and transdisciplinary paradigm

Objetivo. Revisar y evaluar conclusiones contradictorias sobre el abordaje del objeto de la salud pública desde el paradigma disciplinar y transdisciplinar, según sus implicaciones prácticas y pertinencia en el ámbito educativo. Materiales y métodos. Revisión sistemática de artículos científicos de revistas indexadas, sobre el objeto de estudio y práctica de la salud pública, ontología y epistemología de los paradigmas disciplinar- transdisciplinar y la incidencia de dichas teorías en el campo de la educación. Resultados. Hay artículos que describen los fundamentos teóricos de los paradigmas disciplinar y transdisciplinar, y las relaciones de multi e interdisciplinariedad. Se obtuvieron conceptos del objeto de la salud pública que dieron reflejo de su polisemia y complejidad, confrontándolo desde cada uno de los paradigmas y limitaciones disciplinares. Otros artículos refieren una sinergia existente entre ambos paradigmas y la necesidad de actualizar las propuestas educativas para hacerlas pertinentes a las necesidades actuales. Conclusiones. La complejidad de la salud pública del siglo XXI demanda una actualización conceptual. El objeto de estudio de la salud pública puede ser mejor estudiado desde la transdisciplinariedad, debido a las limitaciones metodológicas de las disciplinas. Puede existir sinergismo entre los modelos disciplinar y transdisciplinar en la producción de conocimiento. En la práctica se dificulta aplicar las teorías transdisciplinares, por tanto, las universidades tienen el reto de liderar el proceso de transformación, introduciendo cambios en los procesos formativos que permitan a los futuros profesionales en salud pública, encontrar en la transdisciplinariedad, una herramienta para fortalecer la investigación y el diálogo de saberes

Objective. To review and evaluate contradictory conclusions about an approach to the focus of public health from the disciplinary and transdisciplinary paradigm, according to its practical implications and relevance in the educational field. Materials and methods. A systematic review of scientific articles of indexed journals, on the object of study and practice of public health, ontology, and epistemology of disciplinary-transdisciplinary paradigms and the incidence of theories in the field of education. Results. Some articles describe the theoretical foundations of disciplinary and transdisciplinary paradigms, and multi and interdisciplinary relations. The concepts of the object of public health that reflected its polysemy and complexity were obtained, confronting each of the models and disciplinary tendencies. Other articles refer to an existing offer between both standards and the need to update educational ideas to do the things pertinent to current needs. Conclusions. The complexity of public health in the 21st century demands a conceptual update. Researchers can address the focus of a study of public health from transdisciplinarity, due to the methodological limitations of the disciplines. There can be synergism between disciplinary and transdisciplinary models in the production of knowledge. In practice, transdisciplinary theories are difficult; universities have the challenge of leading the transformation process and the introduction of training processes that allow future professionals in public health to find in transdisciplinarity, a tool to strengthen research and knowledge dialogue.

Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series.

OBJECTIVES: To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. DESIGN: Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. SETTING: University and hospital clinics. POPULATION: Pregnant women with HIV. METHODS: Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. MAIN OUTCOME MEASURES: Rate of invasive testing, intrauterine death, HIV transmission. RESULTS: Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011-2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. CONCLUSIONS: The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. TWEETABLE ABSTRACT: No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens.

Fucoxanthin in association with vitamin C acts as modulators of human neutrophil function.

INTRODUCTION: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing and digesting bacteria and fungi. During this process, neutrophils produce reactive oxygen species (ROS), which in excess, can damage the cells themselves and surrounding tissues. The carotenoid fucoxanthin (Fc) has been studied concerning its antioxidant and anti-inflammatory actions. Vitamin c (Vc) also demonstrates potent antioxidant action. This study aimed to evaluate the effect of Fc (2 µM) in association with Vc (100 µM) on functional parameters of human neutrophils in vitro. MATERIALS AND METHODS: We evaluated the migration and phagocytic capacity, intracellular calcium mobilization, ROS production (O2(·)⁻, H2O2, HOCl), myeloperoxidase activity, profile of antioxidant enzymes, phosphorylation of p38 MAPK and p65 NFκB subunit, GSH/GSSG ratio and release of pro-inflammatory cytokines (TNF-α and IL-6) in neutrophils under different stimuli. RESULTS: We verified an increase in phagocytic capacity for all treatments, together with an increase in intracellular calcium only in cells treated with Fc and Fc + Vc. ROS production was reduced by all treatments, although Vc was a better antioxidant than Fc. Phosphorylation of the p-65 subunit of NFκB was reduced in cells treated with Fc + Vc and release of TNF-α and IL-6 was reduced by all treatments. These findings indicate that the regulation of inflammatory cytokines by neutrophils is not exclusively under the control of the NFκB pathway. Fc reduced the activity of some antioxidant enzymes, whereas Vc increased GR activity and the GSH/GSSG ratio. CONCLUSION: In conclusion, the results presented in this study clearly show an immunomodulatory effect of the carotenoid fc alone or in combination with Vc on the function of human neutrophils.

Análisis genético molecular en atrofia muscular espinal / Molecular evaluation in infantile spinal muscular atrophy

Introducción: La atrofia muscular espinal de la infancia (AMEi) es una enfermedad neurodegenerativa, causada principalmente por deleciones del gen SMN 1 en su locus 5q11.1-13.3. La severidad va desde el tipo I, que compromete la vida en edades tempranas, hasta el tipo IV. Objetivos: Se describen hallazgos moleculares en pacientes con AME, nacionalmente remitidos al Instituto de Neurología y Neurocirugía así como se reporta la frecuencia por 100.000 habitantes en cada una de las provincias de la isla. Pacientes y Métodos: 105 pacientes fueron estudiados, remitidos entre 1997 y 2011. Para la detección de las deleciones se utilizó la técnica de reacción en cadena de la polimerasa (PCR) con cebadores correspondientes a los exones 7 y 8 del gen SMN 1, y digestión con enzimas DraI y DdeI respectivamente y analizados en gel de agarosa al 2 por ciento. Resultados y Discusión: Se encontró un 59 por ciento diagnosticados como AME I, 28,6 por ciento AME II, 12,4 por ciento AME III. Del total de casos 36,2 por ciento resultaron tener deleción de los exones 7 y 8, 35,2 por ciento deleción del exón 7 solamente y 28,2 por ciento no presentaron deleción de los exones correspondientes. Se discuten dichos resultados de acuerdo a la literatura internacional. Se presentan los resultados de frecuencias por 100.000 habitantes en cada provincia del país y discuten dichas frecuencias de acuerdo a la diversidad ancestral de la población cubana. Se concluye lo novedoso del estudio que constituye el primer reporte en una población caribeña.

Introduction: Infantile Spinal Muscular Atrophy (infantile SMA) is a neurodegenerative disease caused primarily by the deletion of the SMN1 gene at 5q11.1 - 13.3. Its severity ranges from type I, in early childhood, to type IV. Objectives: To describe molecular findings in patients with SMA, who were nationally referred to the Institute of Neurology and Neurosurgery and to describe the frequency per 100,000 people in each province of the island. Patients and Methods: 105 patients, referred between 1997 and 2011, were studied. The polymerase chain reaction (PCR) technique was used to detect the deletions of exons 7 and 8 of the SMN1 gene, and DraI and DdeI enzymes, in 2 percent agarose gel, were used for digestion. Results: 59 percent of the patients were diagnosed with SMA I, 28.6 percent with SMA II and 12.4 percent with SMA III. 36.2 percent of total patients presented deletions of exons 7, 8, 35.2 percent only deletion of exon 7 and 28.2 percentdid not present deletion of exons. Conclusion: These results are discussed according to the international literature. The frequency per 100,000 inhabitants in each province is presented and discussed according to ancestral diversity of the Cuban population. Also, the originality of the study is mentioned as it is the first report of this type in a Caribbean population.

Isoinertial and isokinetic sprints: muscle signalling.

To determine if the muscle signalling response to a 30 s all-out sprint exercise is modulated by the exercise mode and the endocrine response, 27 healthy volunteers were divided in 2 groups that performed isokinetic (10 men and 5 women) and isoinertial (7 men and 5 women) Wingate tests. Blood samples and vastus lateralis muscle biopsies were taken before, immediately after, 30 and 120 min after the sprints. Groups were comparable in age, height, body weight, percentage of body fat, peak power per kg of lower extremities lean mass (Pmax) and muscle fibre types. However, the isoinertial group achieved a 25% greater mean power (Pmean). Sprint exercise elicited marked increases in the musculus vastus lateralis AMPKα, ACCß, STAT3, STAT5 and ERK1/2 phosphorylation (all P<0.05). The AMPKα, STAT3, and ERK1/2 phosphorylation responses were more marked after the isoinertial than isokinetic test (interaction: P<0.01). The differences in muscle signalling could not be accounted for by differences in Pmax, although Pmean could explain part of the difference in AMPKα phosphorylation. The leptin, insulin, glucose, GH, IL-6, and lactate response were similar in both groups. In conclusion, the muscle signalling response to sprint exercise differs between isoinertial and isokinetic sprints.

Carbonyl stress and a combination of astaxanthin/vitamin C induce biochemical changes in human neutrophils.

The purpose of the present study was to find out whether co-treatment of human neutrophils with high glucose and methylglyoxal (MGO) can alter the biochemical parameters of human neutrophils. We also examined if astaxanthin associated with vitamin C can improve those biochemical parameters. Neutrophils from healthy subjects were treated with 20mM of glucose and 30 µM MGO followed or not by the addition of the antioxidants astaxanthin (2 µM) and vitamin C (100 µM). MGO/high glucose treatment reduced the phagocytic capacity and the G6PDH, total/SOD and GR activities. Additionally, there was an increase in the activity of myeloperoxidase (MPO) with consequent increase in the hypochlorous acid production, CAT activity and in the release of IL-6 cytokine without changes in intracellular calcium mobilization. Our study also shows that the association of astaxanthin with vitamin C greatly improved neutrophil phagocytic capacity, decreasing all reactive oxygen species measured, pro-inflammatory IL-1ß and TNF-α release, MPO activity and HClO production. The combination of astaxanthin with vitamin C alone has more antioxidant and anti-inflammatory effects than when they were in the presence of MGO/high glucose. Injury to the function of neutrophils due to high glucose and methylglyoxal appears not to involve oxidative stress or calcium release. The association of antioxidants astaxanthin and vitamin C promoted a significant improvement in the function of neutrophils and in the redox status.

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans.

AIM/HYPOTHESIS: The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss. METHODS: Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O(2) flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry. RESULTS: During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C. CONCLUSIONS: In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.

Estudio serológico de leptospirosis en caninos de un albergue en el estado Aragua / Serological Study of Leptospirosis in Canines from a Shelter in the State of Aragua

Se realizó un estudio epidemiológico transversal, en un albergue para caninos callejeros, con el objetivo de conocer la seroprevalencia de Leptospira spp. La muestra estuvo constituida por 30 caninos, seleccionados de una población total de 53 animales. Para la selección de los animales, no se consideraron las variables edad y sexo; igualmente, se excluyeron del estudio, los individuos con pobre condición corporal. El diagnóstico se realizó mediante la prueba de aglutinación microscópica (MAT, Micro Agglutination Test), empleando una batería de ocho serovares: icterohaemorrhagiae, canicola, ballum, pomona, grippotyphosa, hardjo, hebdomadis y wolfii, para confrontar los sueros. Todas las muestras analizadas resultaron positivas a la microaglutinación, lo que representa una seroprevalencia de 100%. Todos los sueros reaccionaron a más de un serovar, siendo la coaglutinación mas frecuente a los serovares icterohaemorrhagiae, canicola y hardjo. El título más alto encontrado fue de 1:400, correspondiente a los serovares hardjo y canicola.

To determine the seroprevalence of Leptospira spp., an epidemiological transversal study in stray dogs from a shelter was conducted. Thirty dogs were sampled from a population of 53 animals, disregarding both age and sex. Animals with poor body condition were excluded from the study. The diagnose was made by the Micro Agglutination Test (MAT) using a battery of eight serovars (icterohaemorrhagiae, canicola, ballum, pomona, grippotyphosa, hardjo, hebdomadis, and wolfii) to challenge sera. The results of the study show that all samples analyzed were positive to microagglutination, which represents a 100% seroprevalence. All sera reacted to more than one serovar, being coagglutination more frequent to icterohaemorrhagiae, canicola and hardjo. The highest titer (1:400) corresponded to the hardjo and canicola serovar.

Regulation of DNA-dependent protein kinase by protein kinase CK2 in human glioblastoma cells.

The DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the nonhomologous end-joining pathway of DNA double-strand breaks repair. Although DNA-PK has been biochemically characterized in vitro, relatively little is known about its functions in the context of DNA repair and how its kinase activity is precisely regulated in vivo. Here, we report that cellular depletion of the individual catalytic subunits of protein kinase CK2 by RNA interference leads to significant cell death in M059K human glioblastoma cells expressing DNA-PKcs, but not in their isogenic counterpart, that is M059J cells, devoid of DNA-PKcs. The lack of CK2 results in enhanced DNA-PKcs activity and strongly inhibits DNA damage-induced autophosphorylation of DNA-PKcs at S2056 as well as repair of DNA double-strand breaks. By the application of the in situ proximity ligation assay, we show that CK2 interacts with DNA-PKcs in normal growing cells and that the association increases upon DNA damage. These results indicate that CK2 has an important role in the modulation of DNA-PKcs activity and its phosphorylation status providing important insights into the mechanisms by which DNA-PKcs is regulated in vivo.

Naturally acquired inhibitory antibodies to Plasmodium vivax Duffy binding protein are short-lived and allele-specific following a single malaria infection.

The Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five cross-sectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBP(II)), we performed in vitro assays with mammalian cells expressing DBP(II) sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBP(II) are short-lived and biased towards a specific allele.

The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis.

Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory beta-subunit of protein kinase CK2 by RNA interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found that CK2beta participates in PLK1-Wee1 complex formation whereas its cellular depletion leads to disruption of PLK1-Wee1 interaction and reduced Wee1 phosphorylation at Ser53 and 121. The data reported here reinforce the notion that CK2beta has functions that are independent of its role as the CK2 regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.

Epidemiology of neonatal infections.

The World Health Organization estimates that more than 4 million neonates die each year and 98% of these deaths occur in developing countries. Infections are among the main causes of neonatal mortality. The neonatal health is intrinsically linked to the mother's health and the care she receives before, during and immediately after delivery. If in resource-rich countries improvements in perinatal conditions, prevention and management of fetal-neonatal infections have reduced the burden of neonatal morbidity and mortality, in resource-limited areas they have only just improved and many barriers remain still to be overcome. Prematurity is often due to fetal infections and represents a significant risk factor for nosocomial infections.

Linfangioma cervical cavernoso en un gemelo: analísis crítico del diagnóstico y manejo perinatal / Cervical lymphangioma in a twin: prenatal diagnosis and perinatal management

Los tumores fetales son hallazgos infrecuentes y muchas veces no diagnosticados prenatalmente. El objetivo de este trabajo es presentar y discutir en forma critica el diagnostico y manejo prenatal de un gemelo portador en un linfangioma cervical cavernoso, incluyendo el procedimiento EXIT.

Fetal cervical tumors are uncommon, and not always prenataly diagnosticated. We describe the prenatal findings and prenatal management in a case of cervical cavernous lymphangioma in one twin, including EXIT procedure.

Evaluación del esfínter anal mediante ecografía tridimensional en mujeres en edad reproductiva / Evaluation of anal sphincter by three-dimensional ultrasonography in women of reproductive age

Abstract. Our purpose was to compare the use of convex transvaginal probe and volumetric transvaginal probe to evaluate the anal sphincter anatomy in women. We studied asymptomatic women divided in two groups. Group 1: fifteen women were scanned using a 5-8 MHz convex transvaginal probe, as was previously described. Group 2: thirty seven women were scanned using a 5-9 MHz volumetric transvaginal probes. The probe was placed in the fourchette in a transverse fashion, the volumes were acquired and saved for later analysis using 3D extended imaging and its modality tools. In group 3 we considered 3 patients with pathology of the anal sphincter. We were able to visualize the start-shaped mucosal folds, the hypoechoic internal and hyperechoic external anal sphincters and the levator ani in a transverse and sagittal fashion in all the patients. Using three dimensional volume data, we were able to display a sequence of frames and to select the best slice to do measurements or to review anatomic details. Using oblique modality, a sagittal view and a coronal view were easily obtained, which may be rotated in 360º. Post processing tools were used to obtain a better contrast and to improve the view of anatomic details. In Group 3, we were able to demonstrate the presence of damage of the external sphincter in all cases, and in one a recto-vaginal fistula was easily seen. We obtain clear images of the anal sphincter anatomy in all women studied, either using a convex or a volumetric transvaginal probes, as was previously reported. This was an easily applicable method, with the advantage that the volume data allows to do later analysis, to improve contrast, and to visualize the anatomy from any spatial position, to get a free coronal view not possible to obtain by convex probes.

Resumen. Nuestro propósito fue comparar el uso de los transductores transvaginales convexo y volumétricos en la evaluación del esfínter anal en 55 mujeres en edad reproductiva, las que fueron divididas en tres grupos. Grupo 1: quince mujeres fueron estudiadas usando un conductor convexo transvaginal (5-8 MHz), el cual se situó perpendicular a la horquilla vulvar obteniéndose imágenes transversales y sagitales del esfínter anal. Grupo 2: treinta y siete mujeres fueron estudiadas con transductores transvaginales volumétricos (5-9 MHz). En ellas, una vez obtenida una imagen transversal de la región del esfínter anal se adquirió 2-3 volúmenes por pacientes, que se almacenaron y se estudiaron en forma diferida. En el Grupo 3 se incluyó a tres mujeres con patología del esfínter anal. En los Grupos 1 y 2 observamos los siguientes detalles anatómicos: 1)Mucosa anal; zonas hiperecoicas e irregulares centrales. 2) Esfínter anal interno; un anillo hipoecoico que rodea a la mucosa. 3) Esfínter anal externo; anillo hiperecoico que rodea externamente al anterior, y 4) Músculo elevador del ano; estructura hiperecoica que rodea en forma de hamaca al esfínter externo. El uso de los transductores volumétricos nos permitió visualizar además la anatomía del esfínter anal desde cualquier posición espacial, efectuar análisis diferidos con personas de mayor experiencia, y mejorar el manejo de la información con las herramientas disponibles en el postproceso. En el grupo 3 las lesiones del esfínter anal fueron fácilmente evidenciadas. Concluimos que el uso de los transductores transvaginales convexos y/o volumétricos en la evaluación del esfínter anal es una técnica fácil, lográndose con ambos imágenes del complejo esfinteriano de muy buena calidad. Además con el uso de transductores volumétricos se agregan todas las ventajas de la ecografía tridimensional.

Validation of protein kinase CK2 as oncological target.

Protein kinase CK2 is a highly conserved enzyme composed of two catalytic subunits alpha and/or alpha' and two regulatory subunits beta whose activity is elevated in diverse tumour types as well as in highly proliferating tissues. Several results suggest that the overexpression of either CK2 catalytic subunits or the CK2 holoenzyme contributes to cellular transformation. In a similar vein, experiments performed compromising the intracellular expression of CK2 has led to somehow contradictory results with respect to the ability of this enzyme to control survival and apoptosis. To better elucidate the role of CK2 in programmed cell death, we have depleted cells of CK2 catalytic subunits by the application of antisense oligodeoxynucleotides and siRNAs techniques, respectively. Our results indicate that protein kinase CK2 is characterized by an extremely high stability that might be due to its association with other intracellular proteins, enhanced half-life or lower vulnerability towards proteolytic degradation. In addition, we show that despite the effectiveness of the methods applied in lowering CK2 kinase activity in all cells investigated, CK2 might not by itself be sufficient to trigger enhanced drug-induced apoptosis in cells.

Estradiol prevents amyloid-beta peptide-induced cell death in a cholinergic cell line via modulation of a classical estrogen receptor.

The pathology of Alzheimer's disease includes amyloid-beta peptide aggregation that contributes to degeneration of cholinergic neurons. Even though the underlying molecular mechanisms remain unclear, recent in vitro evidence supports a protective role for estrogens against several neurotoxic agents. Here we report that, in a murine cholinergic cell line (SN56), the massive cell death induced by 1-40 fragment of amyloid-beta peptide was prevented by 17beta-estradiol through a mechanism that may involve estrogen receptor activation. The protective effect of estradiol was observed in a dose-dependent manner, and was completely blocked by the pure antiestrogen ICI 182,780. In contrast, the inactive isomer 17alpha-estradiol consistently showed weaker neuroprotection than the native hormone that was unaffected by ICI 182,780 treatment. In addition, equivalent concentrations of 17beta-estradiol enhanced luciferase activity in cells transfected with a luciferase reporter gene driven by tandem estrogen response elements. Estrogen-induced luciferase activity was blocked by ICI 182,780, indicating estrogen receptor-dependent transcriptional activity. We also observed by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry that increasing concentrations of 17beta-estradiol enhanced the expression of estrogen receptor alpha mRNA and protein during amyloid-beta-induced toxicity. Under these conditions, it was found by confocal microscopy that the localization of estrogen receptor alpha in the absence of hormone was mainly extranuclear. However, the receptor was consistently observed also at the nuclear region after estrogen exposure. Overall, these data suggest that estrogen may exert neuroprotective effects against amyloid-beta-induced toxicity by activation of estrogen receptor-mediated pathways. In addition, intracellular estrogen receptors are up-regulated by their cognate hormone even during exposure to neurotoxic agents.

An ICI 182,780-sensitive, membrane-related estrogen receptor contributes to estrogenic neuroprotective actions against amyloid-beta toxicity.

Although estrogen (E2)-related neuroprotection has been repeatedly demonstrated in different models, the involvement of non-classical estrogen receptors (ERs) in this activity remains unclear. Using SN56 murine cholinergic cell line from the basal forebrain, we present evidence indicating that an ER associated with the plasma membrane participates in estrogen-dependent reduction of neuronal death induced by amyloid-beta peptide (Abeta) toxicity. Exposure to either E2 or estradiol-horseradish peroxidase (E-HRP) for 15 min significantly reduced Abeta-induced cell death. This effect was decreased by the ER antagonist ICI 182,780 as well as by MC-20 antibody directed to a region neighboring the ligand-binding domain of ERa. Using MC-20 antibody in unpermeabilized SN56 cells, we detected a protein at the plasma membrane region. The binding of impermeant forms of E2, E-HRP, and E-BSA-FITC to specific sites of SN56 plasma membrane was blocked by pre-incubation with E2, ICI 182,780, and MC-20 antibody in a concentration-dependent manner. Thus, a membrane-related ER that shares some structural homologies with ERalpha may participate in estrogen-mediated neuroprotection.

[Pseudomonas aeruginosa bacteremia: clinical and epidemiological patterns and treatment]. / Bacteriemias por Pseudomonas aeruginosa: epidemiología, clínica y tratamiento. Estudio prospectivo de siete años.

Pseudomonas aeruginosa bacteremia has the highest mortality among Gram-negative infections. We studied its clinical and epidemiological patterns in order to achieve an early and accurate diagnosis and treatment. We prospectively studied 211 cases of P. aeruginosa bacteremia admitted to our hospital from 1991 to 1998. All patients had at least one positive blood culture for P. aeruginosa and clinical symptoms of bacteremia. The prognosis of the underlying disease, past illnesses, foci location, initial clinical status, type of bacteremia, complications, and the type of antibiotic treatment were analyzed. Clinical and microbiological controls were carried out at baseline, at the end of the treatment period, and 1 month later. Of the 211 cases, 73% were men with a mean age of 56.5 years. Overall, 45.5% were hospitalized in the ICU, 28% in the surgical ward, and 26% in the medical service, with a mean length of stay of 40.4 days. As risk factors we identified a length of stay more than 14 days (76.7%), previous manipulations (87.6%), and surgery (44.5%). A total of 43.1% had had an infection in the last 6 weeks, and 46.4% were treated with antibiotics, usually broad-spectrum antibiotics without activity against P. aeruginosa. The most frequent underlying diseases were neoplasia (25.5%), postsurgical cardiopathy (24.1%), nephrosis (22.7%), chronic obstructive pulmonary disease (17.5%) and diabetes (13.2%). The most frequent foci were pulmonary (29.3%), urinary (21.8%), and undetermined (38.3%). The mortality rate was 27.9% and was considered related to P. aeruginosa bacteremia in 76.2% of the cases. The antibiotic treatment was considered adequate in 89% of the cases. It was concluded that knowledge of the clinical and epidemiological factors of patients with P. aeruginosa bacteremia may help to optimize its management and to reduce its morbidity and mortality.

Siameses o gemelos unidos toracoonfalópagos y revisión de bibliografía nacional e internacional / Siamese or conjoined thoracoonphalopagus twins and review of national and international literature

Presentamos el caso clínico de gemela unida o siamés toracoonfalópago. Se destaca el diagnóstico prenatal, el manejo clínico y la resolución planificada del parto por operación cesárea, contando con un apoyo neonatológico de cuidado intensivo. Se da a conocer una revisión bibliográfica nacional e internacional.

A case of female thoraco omphalopagus conjoined twins is described. Antenatal diagnosis procedures, obstetric management and rational planning by cesarean section with neonatal intesive care facilities are discussed. A review reports national and international is presented.

FAS-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction.

We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging agents. Interestingly this effect is only seen in cell lines with an embryonic origin and not when cells have entered a differentiated state. It is further shown that the CK2 specific phosphorylation sites in the FAF1 molecule, i.e. serines 289 and 291 influence this complex formation. Mutation of the CK2 phosphorylation sites in the FAF1 molecule to alanine leads to a 1.5 to 2.0-fold higher association between CK2 and FAF1. Since the CK2 activity did not increase concomitantly with the complex formation we conclude that the FAF1 becomes to the CK2 enzyme so that a normal enzyme catalysis does not take place anymore. Subcellular localization experiments involving CK2 subunits and FAF1 show a co-localization of both CK2 subunits and FAF1 in the peri-nuclear cytoplasm. The majority of CK2 subunits is found in the nucleus. FAF1 is also found in the nucleoli. The results obtained further support the view that protein kinase CK2 plays an important role in certain steps of apoptosis.