Lipoamino acid-based adjuvant carrier system: Enhanced immunogenicity of group a streptococcal peptide epitopes

Lipoamino acid-based synthetic peptides (lipid core peptides, LCP) derived from the type-specific and conserved region determinants of group A streptococci (GAS) were evaluated as potential candidate sequences in a vaccine to prevent GAS-associated diseases, including rheumatic heart, disease and poststreptococcal acute glomerulonephritis. The LCP peptides had significantly enhanced immunogenicity as compared with the monomeric peptide epitopes. Furthermore, the peptides incorporated into the LCP system generated epitope-specific antibodies without the use of any conventional adjuvant.

The blood volumes of the primary and secondary circulatory system in the Atlantic cod Gadus morhua L., using plasma bound Evans Blue and compartmental analysis

The volume of the primary (PCS) and secondary (SCS) circulatory system in the Atlantic cod Gadus morhua was determined using a modified dye dilution technique. Cod (N=10) were chronically cannulated in the second afferent branchial artery with PE-50 tubing. Evans Blue dye was bound to harvested fish plasma at a concentration of 1 mg dye ml(-1) plasma, and injected at a concentration of 1 mg kg(-1) body mass. Serial sampling from the cannula produced a dye dilution curve, which could be described by a double exponential decay equation. Curve analysis enabled the calculation of the primary circulatory and total distribution volume. The difference between these volumes is assumed to be the volume of the SCS. From the dilution curve, it was also possible to calculate flow rates between and within the systems. The results of these experiments suggest a plasma volume in the PCS of 3.42+/-0.89 ml 100 g(-1) body mass, and in the SCS of 1.68+/-0.35 ml 100 g(-1) body mass (mean +/- S.D.) or approximately 50% that of the PCS. Flow rates to the SCS were calculated as 2.7% of the resting cardiac output. There was an allometric relationship between body mass and blood volumes. Increasing condition factor showed a tendency towards smaller blood volumes of the PCS, expressed as percentage body mass, but this was not evident for the volume of the SCS.

Mechatronic system for ABO human blood typing

In medical emergency situations, when a patient needs a blood transfusion, the universal blood type O− is administered. This procedure may lead to the depletion of stock reserves of O− blood. Nowadays, there is no commercial equipment capable of determining the patient's blood type in situ, in a fast and reliable process. Human blood typing is usually performed through the manual test, which involves a macroscopic observation and interpretation of the results by an analyst. This test, despite of having a fast response time, may lead to human errors, which sometimes can be fatal to the patient. This paper presents the development of an automatic mechatronic prototype for determining human blood typing (ABO and Rh systems) through image processing techniques. The prototype design takes into account the characteristics of reliability of analysis, portability, and response time allowing the system to be used in emergency situations. The developed prototype performs blood and reagents mixture acquires the resultant image and processes the data (based on image processing techniques) to determine the sample blood type. It was tested in a laboratory, using cataloged samples of blood types, provided by the Portuguese Institute of Blood and Transplantation. Hereafter, it is expected to test and validate the prototype in clinical environments.

VirtualECare: group decision supported by idea generation and argumentation

In the last years there has been a considerable increase in the number of people in need of intensive care, especially among the elderly, a phenomenon that is related to population ageing (Brown 2003). However, this is not exclusive of the elderly, as diseases as obesity, diabetes, and blood pressure have been increasing among young adults (Ford and Capewell 2007). As a new fact, it has to be dealt with by the healthcare sector, and particularly by the public one. Thus, the importance of finding new and cost effective ways for healthcare delivery are of particular importance, especially when the patients are not to be detached from their environments (WHO 2004). Following this line of thinking, a VirtualECare Multiagent System is presented in section 2, being our efforts centered on its Group Decision modules (Costa, Neves et al. 2007) (Camarinha-Matos and Afsarmanesh 2001).On the other hand, there has been a growing interest in combining the technological advances in the information society - computing, telecommunications and knowledge – in order to create new methodologies for problem solving, namely those that convey on Group Decision Support Systems (GDSS), based on agent perception. Indeed, the new economy, along with increased competition in today’s complex business environments, takes the companies to seek complementarities, in order to increase competitiveness and reduce risks. Under these scenarios, planning takes a major role in a company life cycle. However, effective planning depends on the generation and analysis of ideas (innovative or not) and, as a result, the idea generation and management processes are crucial. Our objective is to apply the GDSS referred to above to a new area. We believe that the use of GDSS in the healthcare arena will allow professionals to achieve better results in the analysis of one’s Electronically Clinical Profile (ECP). This attainment is vital, regarding the incoming to the market of new drugs and medical practices, which compete in the use of limited resources.

ABS4GD: a multi-agent system that simulates group decision processes considering emotional and argumentative aspects

Emotion although being an important factor in our every day life it is many times forgotten in the development of systems to be used by persons. In this work we present an architecture for a ubiquitous group decision support system able to support persons in group decision processes. The system considers the emotional factors of the intervenient participants, as well as the argumentation between them. Particular attention will be taken to one of components of this system: the multi-agent simulator, modeling the human participants, considering emotional characteristics, and allowing the exchanges of hypothetic arguments among the participants.

VirtualECare: group support in collaborative networks organizations for digital homecare

Collaborative Work plays an important role in today’s organizations, especially in areas where decisions must be made. However, any decision that involves a collective or group of decision makers is, by itself complex, but is becoming recurrent in recent years. In this work we present the VirtualECare project, an intelligent multi-agent system able to monitor, interact and serve its customers, which are, normally, in need of care services. In last year’s there has been a substantially increase on the number of people needed of intensive care, especially among the elderly, a phenomenon that is related to population ageing. However, this is becoming not exclusive of the elderly, as diseases like obesity, diabetes and blood pressure have been increasing among young adults. This is a new reality that needs to be dealt by the health sector, particularly by the public one. Given this scenarios, the importance of finding new and cost effective ways for health care delivery are of particular importance, especially when we believe they should not to be removed from their natural “habitat”. Following this line of thinking, the VirtualECare project will be presented, like similar ones that preceded it. Recently we have also assisted to a growing interest in combining the advances in information society - computing, telecommunications and presentation – in order to create Group Decision Support Systems (GDSS). Indeed, the new economy, along with increased competition in today’s complex business environments, takes the companies to seek complementarities in order to increase competitiveness and reduce risks. Under these scenarios, planning takes a major role in a company life. However, effective planning depends on the generation and analysis of ideas (innovative or not) and, as a result, the idea generation and management processes are crucial. Our objective is to apply the above presented GDSS to a new area. We believe that the use of GDSS in the healthcare arena will allow professionals to achieve better results in the analysis of one’s Electronically Clinical Profile (ECP). This achievement is vital, regarding the explosion of knowledge and skills, together with the need to use limited resources and get better results.

The influence of the blood pressure on the venous cerebral flow measured by magnetic susceptibility (SWI) technique

Susceptibility Weighted Image (SWI) is a Magnetic Resonance Imaging (MRI) technique that combines high spatial resolution and sensitivity to provide magnetic susceptibility differences between tissues. It is extremely sensitive to venous blood due to its iron content of deoxyhemoglobin. The aim of this study was to evaluate, through the SWI technique, the differences in cerebral venous vasculature according to the variation of blood pressure values. 20 subjects divided in two groups (10 hypertensive and 10 normotensive patients) underwent a MRI system with a Siemens® scanner model Avanto of 1.5T using a synergy head coil (4 channels). The obtained sequences were T1w, T2w-FLAIR, T2* and SWI. The value of Contrast-to-Noise Ratio (CNR) was assessed in MinIP (Minimum Intensity Projection) and Magnitude images, through drawing free hand ROIs in venous structures: Superior Sagittal Sinus (SSS) Internal Cerebral Vein (ICV) and Sinus Confluence (SC). The obtained values were presented in descriptive statistics-quartiles and extremes diagrams. The results were compared between groups. CNR shown higher values for normotensive group in MinIP (108.89 ± 6.907) to ICV; (238.73 ± 18.556) to SC and (239.384 ± 52.303) to SSS. These values are bigger than images from Hypertensive group about 46 a.u. in average. Comparing the results of Magnitude and MinIP images, there were obtained lower CNR values for the hypertensive group. There were differences in the CNR values between both groups, being these values more expressive in the large vessels-SSS and SC. The SWI is a potential technique to evaluate and characterize the blood pressure variation in the studied vessels adding a physiological perspective to MRI and giving a new approach to the radiological vascular studies.

Group decision making for selection of an information system in a business context

The main objective of this work is to report on the development of a multi-criteria methodology to support the assessment and selection of an Information System (IS) framework in a business context. The objective is to select a technological partner that provides the engine to be the basis for the development of a customized application for shrinkage reduction on the supply chains management. Furthermore, the proposed methodology di ers from most of the ones previously proposed in the sense that 1) it provides the decision makers with a set of pre-defined criteria along with their description and suggestions on how to measure them and 2)it uses a continuous scale with two reference levels and thus no normalization of the valuations is required. The methodology here proposed is has been designed to be easy to understand and use, without a specific support of a decision making analyst.

ABO System: molecular mimicry of Ascaris lumbricoides

A. lumbricoides has been associated to the ABO System by various authors. The objective was to detect ABO System epitopes in A. lumbricoides of groups O, A, B and AB patients. 28 adult parasites were obtained from children to be used as assay material. The patients ABO blood groups were determined. Extracts of A. lumbricoides [AE] were prepared by surgical remotion of the cuticle and refrigerated mechanical rupture. Agglutination Inhibition (AI) and Hemoagglutination Kinetics (HK) tests were used with the [AE]. Of the 28 [AE], eight belonged to O group patients, 15 to A group, three to B group and the remaining two to AB children. The AI Test showed A epitopes in two [AE] of group A patients and B epitopes in two [AE] of group B patients. The HK Test showed B antigenic determiners in two [AE] of group B patients and in two [AE] of group AB patients as well as A antigenic determiners in one [AE] of A group patient. Of the 28 [AE] studied in both tests B epitopes were detected in all [AE] from B and AB patients and A epitopes in three of the 15 [AE] of group A patients. The experiments carried out suggest that A. lumbricoides might absorb A and B antigens from the host, and/or modify the cuticular carbohydrates expression as a kind of antigenic mimicry.

Intravenous Busulfan for Autologous Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia: a Survey of 952 Patients on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.

Investigación de defectos genéticos en el sistema de la fosforilasa hepática en pacientes argentinos. Definición nosológica mediante una estrategia de análisis molecular. Investigation of genetic defects in the hepatic phosphorylase system in Argentinean patients. Nosological definition by molecular analysis strategy.

Las Enfermedades de Atesoramiento de Glucógeno (EAGs) también llamadas Glucogenosis comprenden un grupo de entidades causadas por una deficiencia enzimática específica relacionada con la vía de síntesis o degradación de esta macromolécula. La heterogeneidad fenotípica de los pacientes afectados dificulta la identificación de las diferentes variantes de EAG y por ende la correcta definición nosológica. En el Centro de Estudio de las Metabolopatías Congénitas, CEMECO, se fueron definiendo los diferentes tipos de Glucogenosis a través de una estrategia multidisciplinaria que integra distintos niveles de investigación clínica y complementaria, laboratorio metabólico especializado, enzimático, histomorfológico y de análisis molecular. Sin embargo, en algunos enfermos, entre los que se encuentran aquellos con defectos en el sistema de la fosforilasa hepática (EAG-VI y EAG-IX), la exacta definición nosológica aún no está resulta. La EAG-VI se refiere a un defecto en la fosforilasa hepática, enzima codificada por el gen PYGL, mientras que la EAG-IX es causada por un defecto genético en una de las subunidades de la fosforilasa b quinasa hepática codicadas por los genes PHKA2, PHKB y PHKG2, respectivamente. El objetivo del presente trabajo es propender a la definición nosológica de pacientes con defectos en el sistema de la fosforilasa mediante una estrategia de análisis molecular investigando los genes PYGL, PHKA2, PHKB y PHKG2. Los pacientes incluidos en este estudio deberán ser compatibles de padecer una EAG-VI o EAG-IX sobre la base de síntomas clínicos y hallazgos bioquímicos. La metodología incluirá la determinación de la enzima fosforilasa b quinasa en glóbulos rojos y dentro del análisis molecular la extracción de DNA genómico a partir de sangre entera para la amplificación por PCR de los exones más las uniones exon/intron de los genes PHKG2 y PYGL y la extracción de RNA total y obtención de cDNA para posterior amplificación de los cDNA PHKA2 y PHKB. Todos los fragmentos amplificados serán sometidos a análisis de secuencia de nucleótidos. Resultados esperados. Este trabajo, primero en Argentina, permitirá establecer las bases moleculares de los defectos del sistema de la fosforilasa hepática (EAG-VI y EAG-IX). El poder lograr este nivel de investigación traerá aparejado, una oferta integrativa en el vasto capítulo de las glucogenosis hepáticas, con extraordinaria significación en la práctica asistencial para el manejo, pronóstico y correspondiente asesoramiento genético. Hepatic glycogen storage diseases (GSDs) are a group of disorders produced by a deficiency in a specific protein involved in the metabolism of glycogen causing different types of GSDs. Phenotypic heterogeneity of affected patients difficult to identify the different GSD variants and therefore the correct definition of the disease. In the “Centro de Estudio de las Metabolopatías Congénitas”, CEMECO, were defined the different GSD types by a protocol which included complex gradual levels of clinical, biochemical, enzymatic and morphological investigation. However, in some patients, like those one with defects in the hepatic phosphorylase system (GSD-VI and GSD-IX) the exact definition of the disease has not yet been resolved. The GSD-VI is produced by a defect in the PYGL gen that encode the liver phosphorylase, while the GSD-IX is caused by a genetic defect in one of the Phosphorylase b kinase subunits, encoded by the PHKA2, PHKB and PHKG2 genes, respectively. The aim of the present study is to define the phosphorylase system defects in argentinian patients through a molecular strategy that involve the investigation of PYGL, PHKA2, PHKB and PHKG2 genes. Patients included in the present study must be compatible with a GSD-VI or GSD-IX on the bases of clinical symptoms and biochemical findings. The phosphorylase b kinase activity will be assay on in blood red cells. The molecular study will include genomic DNA extraction for the amplification of PHKG2 and PYGL genes and the total RNA extraction for amplification of the PHKA2 and PHKB cDNA by PCR. All PCR-amplified fragments will be subjected to direct nucleotide sequencing. This work, first in Argentina, will make possible to establish the molecular basis of the defects on the hepatic phosphorylase system (GSD-VI and GSD IX). To achieve this level of research will entail advance in the study of the hepatic glycogen storage disease, with extraordinary significance in the treatment, prognosis and the genetic counselling.

Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

Abstract Background: Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness. Objective: To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness. Methods: Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively). Results: The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586). Conclusion: Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Association of CYP3A5 genotypes with blood pressure and renal function in African families.

OBJECTIVE: Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families. METHODS: Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations. RESULTS: CYP3A5*1 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A5*1 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A5*1 carriers (P for interaction = 0.02). CONCLUSIONS: These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium- related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling.

National Blood Strategy Implementation Group Report

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