Compartmentalized Cerebral Metabolism of [1,6-(13)C]Glucose Determined by in vivo (13)C NMR Spectroscopy at 14.1 T.

Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by (13)C nuclear magnetic resonance (NMR) spectroscopy upon infusion of (13)C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-(13)C]glucose and (13)C enrichment in the brain metabolites was measured by (13)C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining (13)C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (V(TCA)) and neurotransmission rate (V(NT)) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial V(TCA) was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (V(PC)) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.

Risk factors for positive tuberculin skin tests among migrant and resident children in Lausanne, Switzerland.

SETTING: Ambulatory paediatric clinic in Lausanne, Switzerland, a country with a significant proportion of tuberculosis (TB) among immigrants. AIM: To assess the factors associated with positive tuberculin skin tests (TST) among children examined during a health check-up or during TB contact tracing, notably the influence of BCG vaccination (Bacille Calmette Guérin) and history of TB contact. METHOD: A descriptive study of children who had a TST (2 Units RT23) between November 2002 and April 2004. Age, sex, history of TB contact, BCG vaccination status, country of origin and birth outside Switzerland were recorded. RESULTS: Of 234 children, 176 (75%) had a reaction equal to zero and 31 (13%) tested positive (>10 mm). In a linear regression model, the size of the TST varied significantly according to the history of TB contact, age, TB incidence in the country of origin and BCG vaccination status but not according to sex or birth in or outside Switzerland. In a logistic regression model including all the recorded variables, age (Odds Ratio = 1.21, 95% CI 1.08; 1.35), a history of TB contact (OR = 7.31, 95% CI 2.23; 24) and the incidence of TB in the country of origin (OR = 1.01, 95% CI 1.00; 1.02) were significantly associated with a positive TST but sex (OR = 1.18, 95% CI 0.50; 2.78) and BCG vaccination status (OR = 2.97, 95% CI 0.91; 9.72) were not associated. CONCLUSIONS: TB incidence in the country of origin, BCG vaccination and age influence the TSTreaction (size or proportion of TST > or = 10 mm). However the most obvious risk factor for a positive TST is a history of contact with TB.

Immune monitoring design within the developmental pipeline for an immunotherapeutic or preventive vaccine

Immunotherapy is defined as the treatment of disease by inducing, enhancing, or suppressing an immune response, whereas preventive vaccination is intended to prevent the development of diseases in healthy subjects. Most successful prophylactic vaccines rely on the induction of high titers of neutralizing antibodies. It is generally thought that therapeutic vaccination requires induction of robust T-cell mediated immunity. The diverse array of potential or already in use immunotherapeutic and preventive agents all share the commonality of stimulating the immune system. Hence, measuring those vaccination-induced immune responses gives the earliest indication of vaccine take and its immune modulating effects.

Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.

A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.

Estructura, distribución y abundancia de peces demersales: Crucero: Tareq II, 7605 (13 de mayo - 3 de junio 1976)

Presenta los resultados obtenidos a bordo del BI-TAREQ-II en el otoño de 1976, cuyo objetivo fue realizar un diagnóstico del estado de los stocks de peces para consumo humano, con la finalidad de ayudar a definir estrategias especificas para mejorar los niveles de explotación.

Informe estadístico y económico de la pesca exploratoria de recursos pelágicos realizada por las PEEAS (pequeñas empresas de extracción de anchoveta) en el periodo del 13 de febrero al 20 de junio de 1982

Presenta un ensayo para abarcar las etapas de la extracción y desembarque, la transformación de los productos industriales de reducción y el culminar estimando el valor económico de dichos productos, permitiendo así una aproximación al conocimiento de un tipo de pesquería notable por su accionar y su incidencia en las especies en las que se sustenta y sobre el cual el IMARPE despliega parte importante de su esfuerzo.

Biomasa, distribución y concentración de los principales recursos pelágicos. Crucero 9502-04 BIC NSP-1 9502 (13 febrero - 05 abril, 1995)

Presenta los estimados de biomasa, distribución delos principales recursos pelágicos: anchoveta, sardina, jurel y caballa existentes en el Perú y se determina así mismo el grado de mezcla de estos recursos a partir de los lances de comprobación y la interrelación recurso/ambiente.

Aspectos biológicos - pesqueros de los recursos pelágicos. Crucero de evaluación de recursos pelágicos 9502-04 BIC SNP-1 (13 febrero - 05 abril, 1995)

Describe los niveles de abundancia , distribución, concentración y características biológicas de las poblaciones de la anchoveta y sardina a principios de 1995, así como conocer las características del ambiente y su influencia sobre el reclutamiento. La información proviene de las capturas y muestreos biológicos de 129 lances de comprobación ejecutados durante el crucero. La composición por especies estuvo conformada principalmente por anchoveta (Engraulis ringens), sardina (Sardinops sagax sagax), jurel (Trachurus picturatus murphyi) y caballa (Scomber japonicus peruanus). Otras especies fueron el bagre con faja (Galeichthys peruvianus), falso volador (Prionotus stephanophrys), múnida (Pleuroncodes monodon), etc.

Condiciones oceanográficas del mar peruano durante el crucero de evaluación de recursos pelágicos 9502-04 BIC/SNP-1 (13 febrero - 05 abril, 1995)

Presenta los resultados de las condiciones físicas y químicas (contenido de oxígeno disuelto y clorofila "a") observadas en superficie y capas subsuperficiales del mar y se dan perspectivas del comportamiento de ambiente para los próximos meses. Las características del ambiente indicaron un calentamiento de magnitud moderada al sur del Callao y condiciones cuasi-normales al norte del Callao que confirmaron la continuación del proceso de normalización del mar peruano iniciado en febrero de 1995.

Aspectos hidroquímicos del mar peruano. Crucero de evaluación de recursos pelágicos 9502- 04 BIC /NSP-1 (13 febrero - 05 abril, 1995)

Da a conocer la distribución superficial y de profundidad hasta 200 m. de las sales nutritivas, que conjuntamente al oxigeno disuelto y clorofila "a" tiene enorme importancia desde el punto de vista biológico, por ser elementos fundamentales en la síntesis orgánica del agua de mar.

Características del zooplancton e ictioplancton durante el periodo de verano 1995 frente a la costa peruana (13 febrero - 05 abril, 1995)

Presenta características del zooplancton e ictiopancton frente a la costa peruana, encontradas durante el crucero de Evaluación de los recursos pelágicos abordo del BIC SNP-1 llevado a cabo del 13 de febrero al 05 de abril, así como la distribución y concentración de huevos y larvas de los recursos anchoveta y sardina.

Fitoplancton durante el crucero de evaluación de recursos pelágicos (13 febrero - 05 abril, 1995) BIC SNP-1

Describe las muestras de fitoplancton en 127 estaciones de Tacna a Tumbes. Paralelamente en los perfiles hidrográficos se colectaron muestras de agua con botellas Niskin. Se determinó un total de 143 especies de fitoplancton: 86 diatomeas, 44 dinoflagelados, 7 cocolitofóridos, 6 fitoflagelados y 2 silicoflagelados. Las concentraciones máximas de fitoplancton, mayores de 10.000 cel/50 mL, a 10 m de profundidad se encontraron en la franja costera, predominando diatomeas de alta tasa de reproducción, las cuales corresponden a una comunidad en la primera fase de la sucesión fitoplanctónica.

Operación Eureka XXVIII (12-13 Nov.1973) y la pesca de comprobación (14-17 Nov.1973), Diagnóstico del estado del stock de anchoveta en Noviembre de 1973

Expone la situación general del recurso anchoveta, su condición biológica, distribución, procesos de reagrupación de cardúmenes, accesibilidad para la pesca, su ambiente abiótico y un diagnóstico del estado del stock de la anchoveta.

Prevalence rate and reasons for refusals of influenza vaccine in elderly.

More knowledge on the reasons for refusal of the influenza vaccine in elderly patients is essential to target groups for additional information, and hence improve coverage rate. The objective of the present study was to describe precisely the true motives for refusal. All patients aged over 64 who attended the Medical Outpatient Clinic, University of Lausanne, or their private practitioner's office during the 1999 and 2000 vaccination periods were included. Each patient was informed on influenza and its complications, as well as on the need for vaccination, its efficacy and adverse events. The vaccination was then proposed. In case of refusal, the reasons were investigated with an open question. Out of 1398 patients, 148 (12%) refused the vaccination. The main reasons for refusal were the perception of being in good health (16%), of not being susceptible to influenza (15%), of not having had the influenza vaccine in the past (15%), of having had a bad experience either personally or a relative (15%), and the uselessness of the vaccine (10%). Seventeen percent gave miscellaneous reasons and 12% no reason at all for refusal. Little epidemiological knowledge and resistance to change appear to be the major obstacles for wide acceptance of the vaccine by the elderly.

New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site.

Although increasing evidence suggests that CTL are important to fight the development of some cancers, the frequency of detectable tumor-specific T cells is low in cancer patients, and these cells have generally poor functional capacities, compared with virus-specific CD8(+) T cells. The generation with a vaccine of potent CTL responses against tumor Ags therefore remains a major challenge. In the present study, ex vivo analyses of Melan-A-specific CD8(+) T cells following vaccination with Melan-A peptide and CpG oligodeoxynucleotides revealed the successful induction in the circulation of effective melanoma-specific T cells, i.e., with phenotypic and functional characteristics similar to those of CTL specific for immunodominant viral Ags. Nonetheless, the eventual impact on tumor development in vaccinated melanoma donors remained limited. The comprehensive study of vaccinated patient metastasis shows that vaccine-driven tumor-infiltrating lymphocytes, although activated, still differed in functional capacities compared with blood counterparts. This coincided with a significant increase of FoxP3(+) regulatory T cell activity within the tumor. The consistent induction of effective tumor-specific CD8(+) T cells in the circulation with a vaccine represents a major achievement; however, clinical benefit may not be achieved unless the tumor environment can be altered to enable CD8(+) T cell efficacy.