Imaging mass spectrometry (IMS) of cortical lipids from preclinical to severe stages of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples. The present study uses the matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), permitting the direct anatomical analysis of lipids in postmortem brain sections from AD patients, which are compared with the intensity of the lipid signal in samples from matched subjects with no neurological diseases. The frontal cortex samples from AD patients were classified in three groups based on Braak's histochemical criteria, ranging from non-cognitively impaired patients to those severely affected. The main results indicate a depletion of different sulfatide lipid species from the earliest stages of the disease in both white and gray matter areas of the frontal cortex. Therefore, the decrease in sulfatides in cortical areas could be considered as a marker of the disease, but may also indicate neurochemical modifications related to the pathogenesis of the disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Lipid mapping of the rat brain for models of disease.

Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K+ and PC (32: 0)+K+ distributed primarily in gray matter, and PC (36: 1)+K+ and PC (38: 1)+Na+ distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K+ in white matter, and PA (38: 5)+K+ in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H+ in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H+ in white matter. Phosphatidylserines (PS): PS (34: 1)-H+ in gray matter, and PS (38: 1)-H+ in white matter. Sphingomyelin (SM) SM (d18: 1/16: 0)-H+ in ventricles and SM (d18: 1/18: 0)-H+ in gray matter. Sulfatides (ST): ST (d18: 1/24: 1)-H+ in white matter. The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer's disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

[Measuring Kt by ionic dialysance is a useful tool for assessing dialysis dose in critical patients]. / La determinación del Kt por dialisancia iónica es una herramienta útil para la evaluación de la dosis de diálisis en pacientes críticos.

AIM: To evaluate the Kt assessed through ionic dializance (KtOCM) in UCI patients undergoing renal replacement therapy for acute kidney injury, comparing the results with those obtained through the urea removal rate method determined by dialyzate collection (Kturea). MATERIAL AND METHODS: 18 adult UCI staying individuals suffering from renal replacement therapy requiring oliguric acute kidney injury were included in this study. RRT consisted in intermittent or extended hemodialysis performed through a Fresenius 4008E dialysis machine equipped with an on-line clearance monitor (OCM Fresenius). The KtOCM results were provided automatically. The Spearman correlation test was used to assess the relationship between the two exploratory methods and the Student s t test to compare the results obtained by the KtOCM and the Kturea. RESULTS: 35 treatments were analyzed. There were not statistically significant differences between the results form the KtOCM and the Kturea (34.9 +/- 10.69 vs 32.78 +/- 11.31, p = NS). A remarkable association was find between both methods (r = 0.87; 95CI, 0.76-0.94; p < 0.001). CONCLUSIONS: The assessment of Kt through ionic dialyzance is a simple method to estimate the dose of dialysis in critically ill patients and is and useful tool to monitor and adjust the RRT in real time according to a target dose.

Mortality risk factors in elderly patients in intensive care without limitation of therapeutic effort. / Factores de riesgo de mortalidad de los pacientes ancianos en cuidados intensivos sin limitación del esfuerzo de tratamiento.

OUTCOME: To determine mortality prognostic factors in elderly patients who are admitted to intensive care units (ICUs) due to acute critical illness. DESIGN: A prospective cohort study was carried out. SETTING: A polyvalent Intensive Care Unit at a University Hospital in Argentina. PATIENTS OR PARTICIPANTS: We included 249 patients over 65years of age who were consecutively admitted to the ICU and required mechanical ventilation for more than 48hours, between January 2011 and December 2012. Patients with degenerative neurological disease, limitation of therapeutic effort or on chronic mechanical ventilation were excluded. PRINCIPAL VARIABLES OF INTEREST: In-hospital mortality, comorbidity (Charlson index), APACHEII score, and pre-acute illness status were recorded: nutritional status (subjective global assessment), functionality (activities of daily living [ADL] and Barthel index), cognitive abilities (Short Reporting Questionnaire on Cognitive Decline in the Elderly [S_IQCODE]) and quality of life (EQ-5D). RESULTS: The in-hospital mortality rate was 52%. Logistic regression analysis, after adjusting for APACHEII score and age, identified the following independent variables associated to mortality: male gender (OR: 2.46, 95%CI: 1.37-4.42), moderate malnutrition (OR: 2.07, 95%CI: 1.09-3.94), severe malnutrition (OR: 2.20, 95%CI: 1.06-4.59), and ADL<6 (OR: 2.35, 95%CI: 1.16-4.75). CONCLUSIONS: In our study, chronological age was not associated to in-hospital mortality. However, loss of functional independence (assessed by ADL) and malnourishment were shown to be strong prognostic factors; knowing these baseline characteristics from ICU admission would be useful when making decisions regarding the intensity of treatment.

Prevalence of antibody to the variant repeat of the circumsporozoite protein of Plasmodium vivax in Peru.

Individuals living in a malaria-endemic area in northern Peru were found to have antibodies to the variant repeat sequence of the circumsporozoite (CS) protein of Plasmodium vivax. The presence of IgG antibody to the predominant repeat sequence GDRAA/DGPA represented by the recombinant protein NS1(81) V20 (V20), and the variant repeat sequence ANGAGNQPG contained in the synthetic peptide Pvk247, was determined by enzyme-linked immunosorbent assay. IgG antibodies to the repeats were present in 78 (26%) of 298 serum samples; 56% of the positive serum samples had antibodies to V20 and 60% had antibodies to Pvk247. These findings stress the importance of considering the variant epitope in designing a vaccine based on the repeat region of the vivax CS protein. In a malaria-endemic area such as the one in this study, in which exposure to the variant repeat epitope may be as frequent as exposure to the predominant repeat, a vaccine based solely on the predominant repeat epitope may be ineffective against the variant form.

Carboxylated zinc-phthalocyanines--II. Dimerization and singlet molecular oxygen sensitization in hexadecyltrimethylammonium bromide micelles.

The dimerization of the diamide of zinc-tetracarboxyphthalocyanine was studied spectroscopically in hexadecyltrimethylammonium bromide (CTAB) micelles at surfactant concentrations from 0.026 to 0.1 M and dye concentrations between 0.1 and 10 microM. The apparent dimerization constant in CTAB 0.1 M is 8.6 x 10(5) M-1, while the intramicellar dimerization constant is 1.8 x 10(3). The dimer absorption spectrum was also obtained. Singlet molecular oxygen sensitization was studied by steady state photolysis using 1,3-diphenylisobenzofurane as scavenger in 0.1 M CTAB. The usual sensitization mechanism is extended to include dimer reactions. Singlet molecular oxygen sensitization yields for monomer and dimer in the micelles are 0.7 and 0.1, respectively. With the reported values it is possible to calculate the average yield of singlet molecular oxygen production at any surfactant and dye concentrations.

Meso-substituted cationic porphyrins of biological interest. Photophysical and physicochemical properties in solution and bound to liposomes.

A series of cationic porphyrins with 1-4 positive charges are studied: mono(N-methyl-4-pyridyl)triphenylporphine chloride [Mono], cis(N-methyl-4-pyridyl)diphenylporphine chloride [Cis], tri(N-methyl-4-pyridyl)monophenylporphine chloride [Tri] and tetra(N-methyl-4-pyridyl)porphine chloride [Tetra]. Their photophysical properties are measured in small unilamellar vesicles and compared with those in homogeneous solution. Liposomes of L-alpha-dimyristoyl-phosphatidylcholine (100 nm diameter) and L-alpha-dipalmitoyl-phosphatidylcholine (50 nm diameter) in phosphate-buffered saline (pH = 7.4) or D2O 0.15 M NaCl were used. The effect of the medium microheterogeinity is discussed. The triplet quantum yields in liposomes for all the porphyrins are about 0.7, similar to the value obtained for Tetra in aqueous media. The singlet molecular oxygen quantum yields for the hydrophilic compounds Tri and Tetra are greater than those of the hydrophobic ones, Mono and Cis. Also, association constants (KL) of the dyes to liposomes and their localization within the membranes are determined from fluorescence and fluorescence polarization measurements, respectively. KL values are in the range of 10(4)-10(5) M-1 for all the compounds, indicating that hydrophobic and coulombic interactions between porphyrins and liposomes are responsible for the dye association. Fluorescence polarization experiments indicate that Mono and Cis can penetrate into the lipidic phase, and that Tri and Tetra are located near the polar heads of the lipidic molecules.

Plasmodium vivax VK247 and VK210 circumsporozoite proteins in Anopheles mosquitoes from Andoas, Peru.

Anopheles mosquitoes captured in Andoas, Peru, a Plasmodium vivax-endemic area in the Peruvian Amazon region, contained both VK210 and VK247 P. vivax circumsporozoite (CS) proteins. Approximately 0.9% of the 4,403 mosquitoes tested by enzyme-linked immunosorbent assay were positive; 28% and 72% of the positive mosquitoes contained VK210 and VK247 CS proteins, respectively. These findings correlate strongly with a recent report of the presence of antibodies in residents of this area that recognize the VK210 and VK247 repeats, clearly indicating that both P. vivax CS protein polymorphs are common in the region.

[Evaluation of hemodynamic and respiratory variables in patients with acute respiratory distress syndrome in two ventilatory modes]. / Evaluación de variables hemodinámicas y respiratorias en pacientes con síndrome de distress respiratorio agudo bajo dos modos ventilatorios.

The aim of the present study was to evaluate the hemodynamic and respiratory variations in patients with acute respiratory distress syndrome (ARDS) under two conditions: volume controlled ventilation (VCV) and pressure controlled inverse ratio ventilation (PCIRV). Seventeen patients with ARDS and the following criteria were included: lung injury score > 2.5 and peak inspiratory pressure > or = 40 cm H2O under VCV, constant flow and I/E ratio of 1/2. Measurements were obtained in VCV and after one hour in PCIRV with I/E ratio 2/1 using a similar PEEP value than VCV. PCIRV was accompanied by a significant lower tidal volume (736.10 +/- 119.20 vs 540.35 +/- 84.66 p < 0.001), peak inspiratory pressure (43.60 +/- 5.50 vs 26.26 +/- 3.47 p < 0.0001) and plateau pressure (37.64 +/- 3.70 vs 25.30 +/- 3.50 p < 0.001) and a significant higher: respiratory frequency (17.70 +/- 2.10 vs 20.94 +/- 3.38 p < 0.002), mean airway pressure (16.20 +/- 3.00 vs 19.41 +/- 2.80 p < 0.003) and static compliance (25.84 +/- 5.42 vs 35.18 +/- 9.39 p < 0.002). Similar values in the hemodynamic and oxygenation variables were observed between both groups. Our results show that PCIRV allow to ventilate patients with lower peak inspiratory and plateau pressures without significant changes in hemodynamic and oxygenation parameters. The conventional tidal volumes are excessive for lungs with SDRA, which is shown with the improvement in the static compliance and the airway pressures in PCIRV. PCIRV mode at the same PEEPt level as VCV, with normal I/E ratio does not improve the oxygenation, despite the higher level of the mean airway pressure.

[Somatostatin in the emergency treatment of upper digestive hemorrhage in patients with portal hypertension]. / Somatostatina en el tratamiento de emergencia de la hemorragia digestiva alta en hipertensos portales.

During a 2-yr period 15 patients (17 episodes) with variceal bleeding (VB) and 7 with cirrhosis and acute gastroduodenal haemorrhage (GDH) received intravenous somatostatin (250 mcg per hr after a bolus of 250 mcg). Initial control of bleeding was achieved in 13 (76%) with VB and in all with GDH. Three of the 4 patients with VB and 2 with GDH who rebled during treatment were controlled increasing the infusion to 500 mcg/hr. Patients with VB received somatostatin for 24 hrs, time selected for initiating injection sclerotherapy, and those with GDH for 48-72 hrs. At 24 hrs 71% of patients with VB and all with GDH were free of bleeding. Combining different therapies VB was controlled in 16 of the 17 episodes (94%) with only one death. No complications were observed in any of the 22 patients treated.

[Renal failure in patients with liver transplant: incidence and predisposing factors]. / Insuficiencia renal en pacientes con trasplante hepático: incidencia y factores predisponentes.

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

[Incidence rate trends for colorectal cancer in Navarre (North of Spain) in the 1990-2005 period]. / Tendencias en las tasas de incidencia de cáncer colorrectal en Navarra en el periodo 1990-2005.

BACKGROUND: In Spain, an increase in the incidence of colorectal cancer (CRC) has been observed in both sexes in recent years, probably due to an improved diagnostic, the westernization of dietary habits, and worse obesity levels, among others factors. In this work, the CRC incidence rate trends in different health areas in Navarre (northern Spain) are studied during the 1990-2005 period. METHODS: An estimated incidence trend curve for each health area and the corresponding confidence bands were obtained for each gender using P-spline models. RESULTS: These results show an increasing trend of CRC in most of the areas in both sexes, being less pronounced in women than in men. In the central area of Pamplona (the capital) a decreasing trend has been observed for men during the period studied. CONCLUSIONS: Primary prevention is the best strategy to change the increasing trend observed in most areas of the province of Navarre. However, a healthy lifestyle has long-term results, so it is important to have an early detection program that would serve as a short-term prevention strategy.

Lanzamiento de un programa de ECMO en un hospital universitario de la Argentina / Launching a program of ECMO in a hospital University of Argentina

El objetivo de este trabajo es describir el proceso para implementar un programa de ECMO en un hospital universitario de Buenos Aires, y transmitir los resultados a los tres años. Se realizó un análisis retrospectivo de 27 pacientes con ECMO desde enero de 2011: once pacientes con síndrome de dificultad respiratoria aguda y 16 postrasplante de pulmón con hipoxemia. La mediana de la edad era de 43 años (rango intercuartil 23-53); la mediana del puntaje APACHE II fue de 19 (rango intercuartil 14-21), la mediana de la PaFi, 100 (rango intercuartil 78-121) y la tasa de mortalidad, del 29%. Estos programas son factibles en la región con el entrenamiento adecuado.(AU)

The aim of this paper is to describe the process to implement an ECMO program at a university hospital in Buenos Aires, and to transmit the results after three years. A retrospective analysis of 27 patients with ECMO from January 2011 was performed, this includes patients with acute respiratory distress syndrome (n=11) and lung transplantation with hypoxemia (n=16). Patients had a median age of 43 years (IQR: 23-53), with a median APACHE II score of 19 (IQR: 14-21), a median PAFI of 100 (IQR: 78-121) and the mortality rate was 29%. These programs are feasible in the region with the right training.(AU)

Hipotermia en el tratamiento del traumatismo de cráneo grave. Caso clínico y revisión de la literatura / Hypothermia in the treatment of skull trauma serious. Clinical case and review of literature

El tratamiento de la hipotermia comenzó hace más de cuatro décadas, pero en los últimos años, su uso cobró más relevancia, por lo que se realizaron múltiples estudios. Lamentablemente, los resultados son controvertidos en el tratamiento de la hipertensión intracraneal secundaria al trauma. Presentamos a un paciente con traumatismo de cráneo grave e hipertensión intracraneal resistente, en el que se utilizó la hipotermia controlada, con buena respuesta.(AU)

Treatment of hypothermia started more than four decades ago. But in recent years its use became more relevant, and multiple studies were performed. Results are controversial in the treatment of intracranial hypertension in trauma. We present a patient with severe cranial trauma and refractory intracranial hypertension, treated with controlled hypothermia, with a good response.(AU)

Balance hídrico y uso de drogas vasoactivas como predictores de mortalidad en pacientes con lesión pulmonar aguda y síndrome de distress respiratorio agudo: Estudio multicéntrico / Water balance and drug use vasoactive as predictors of mortality in patients with acute lung injury and respiratory distress syndrome acute: Multicentric study

Introducción. Desde la década de 1990, la mortalidad por el síndrome de distress respiratorio agudo ha disminuido. Sin embargo, no hay datos concluyentes acerca de que una nueva estrategia sea responsable de esta evolución (p. ej., el manejo de los fluidos). Aún no se ha dilucidado cuál es la cantidad óptima de fluidos para tratar a estos pacientes. Clásicamente la discusión se basa en estrategias liberales o conservadoras. Objetivo. El objetivo principal fue conocer cómo impacta el balance de fluidos asociado con el uso de noradrenalina en la evolución. Materiales y métodos. Se llevó a cabo un estudio observacional en 87 pacientes con síndrome de distress respiratorio agudo entre agosto y diciembre de 2007, en tres hospitales universitarios. Se utilizó el protocolo de tratamiento estándar de las Unidades de Cuidados Intensivos permitiendo la expansión en forma liberal cuando se sospechaba hipovolemia no resuelta. Resultados. Se detectaron tres situaciones de mayor riesgo y mala evolución: a) la asociación de noradrenalina y balance positivo de fluidos <2500 ml en las primeras 24 h (OR: 5,4; IC95%: 2,1-13,9; p = 0,0004), b) la asociación de noradrenalina y balance acumulativo >5500 ml en las primeras 72 h (OR: 2,7; IC95%: 1,1-6,5; p = 0,032) y c) pacientes con puntaje APACHE II >21, noradrenalina y balance positivo <2500 ml en las primeras 24 h (OR: 8,4; IC95%: 1,8-39; p = 0,008). Conclusión. La utilización de noradrenalina y escaso fluido en estrategias de reanimación que intentan "proteger" al pulmón con lesión parece no ser adecuada, según este estudio observacional(AU)

Introduction. Recent studies have shown an important decline in mortality due to acute respiratory distress syndrome since 1990. However, to date, there is no definitive evidence to demonstrate that any mode of specific therapeutic approach (i.e., fluid management) make a difference in survival or other outcome measures. The optimal fluid management of acute lung injury is not established. Classically there are two arguments: the wet or dry strategy. Objective. The main goal was to know the impact on outcome of fluid balance and the use of noradrenaline as a vasoactive drug. Materials and methods. In this observational study, 87 ventilated patients with acute respiratory distress syndrome were included from August to December 2007 in three University Critical Care Units. A standard protocol of resuscitation was used, fluid intake was liberal only in hypovolemic patients. Results. Three categories of risk and poor outcome were detected: a) noradrenaline plus positive fluid balance <2500 mL in first day (OR: 5.4; IC95%: 2.1-13.9; p = 0.0004), b) noradrenaline plus a cumulative positive balance >550 mL in first 72 hours (OR: 2.7; IC95%: 1.1-6.5; p = 0.032), c) APACHE II >21 and noradrenaline plus positive fluid balance <2500 mL in the first day (OR: 8.4; IC95%: 1.8-39; p = 0.008). Conclusion. The use of noradrenaline and conservative resuscitation with fluid in critically ill patients with acute respiratory distress syndrome in order to minimize the risk of excessive fluid therapy was associated with poor outcome and higher mortality(AU)

Antibody response of humans to the circumsporozoite protein of Plasmodium vivax.

We studied the interaction of sera from residents of an area in northern Peru where vivax malaria is endemic with four recombinant DNA-derived circumsporozoite (CS) proteins of Plasmodium vivax. The antigens used in the enzyme-linked immunosorbent assay included one Escherichia coli-produced and three Saccharomyces cerevisiae-produced recombinant proteins. Three of the proteins (NS1(81)V20, Vivax-1, and Vivax-2) contain the entire central repeat region of the P. vivax CS protein, and one protein (Vivax-3) contains only two repeat sequences. Vivax-1, Vivax-2, and Vivax-3 contain different lengths of sequences flanking the repeats. A higher percentage of the sera had antibodies to Vivax-2 and Vivax-3, the two proteins containing the longest nonrepeat sequences, than to NS1(81)V20 or Vivax-1. Children less than 5 years of age did not have immunoglobulin G antibodies to NS1(81)V20; however, they had antibodies to Vivax-1, Vivax-2, and Vivax-3. The finding that individuals living in a malaria-endemic area produce antibodies to peptides containing nonrepeat regions of the CS protein emphasizes the need to characterize the immune response to these regions in naturally exposed and experimentally immunized humans.