Células cebadas en pulmón y nervio periférico en la intoxicación crónica con karwinskia humboldtiana en rata wistar: estudios histológico e histoquímico / Lung and peripheral nerve mast cells in chronic intoxication with karwinskia humboldtiana in wistar rat: histological and histochemical studies

Karwinskia humboldtiana (Kh) es un arbusto venenoso responsable de numerosos casos de intoxicación accidental en humanos. En estudios previos en nuestro laboratorio reportamos un incremento de células cebadas en nervio periférico (NP) durante la intoxicación con Kh, este hallazgo no ha sido reportado previamente en otros órganos durante esta intoxicación por lo que en el presente estudio buscamos la presencia de estas células en otros órganos, además de distinguir subpoblaciones de células cebadas mediante reacciones histoquímicas para la identificación de los gránulos de secreción. El objetivo de este estudio fue evaluar la presencia de células cebadas en órganos distintos al NP y diferenciar histoquímicamente la composición de sus gránulos. Se utilizaron 32 ratas Wistar, se dividieron en cuatro grupos (n= 8) en donde 5 ratas de cada grupo fueron intoxicadas y 3 fueron control no intoxicadas. A las ratas intoxicadas se les administraron por vía oral 3,5 g/kg del fruto seco y molido de Kh fraccionados en 5 dosis de 1,5; 0,5, 0,5; 0,5 y 0,5 g/kg los días 0, 3, 7, 10 y 14 respectivamente. Las ratas control solo recibieron agua. Cada grupo fue sacrificado a diferentes tiempos según la evolución de la parálisis. Se obtuvieron muestras de Hígado, Riñón, Pulmón y SNP, se procesaron hasta obtener bloques de parafina, se obtuvieron cortes y se tiñeron con azul de toluidina, PAS, Azul alciano/PAS y Azul alciano/Safranina. Se identificó la presencia de células cebadas en NP y pulmón con la tinción de azul de toluidina y se realizo un estudio morfométrico observando un incremento progresivo del número de células cebadas por grupo así como variaciones histoquímicas en sus gránulos en cada etapa y órgano analizado, lo que sugiere la participación de las células cebadas y sus secreciones en cada una de las etapas de la intoxicación crónica con el fruto maduro de Kh.

Karwinskia humboldtiana (Kh) is a poisonous shrub causing a number of accidental intoxications in humans. In previous studies in our laboratory, we reported an increased number of mast cells present in peripheral nerve of Kh intoxicated rats. This finding has not been reported in other organs of intoxicated animals. For this reason, in the present study we searched for mast cells in several organs, identifying mast cell subpopulations on the basis of different histochemical reactivity of their secretory granules. Thus the objective of the present study was to evaluate the presence of mast cells in organs other than peripheral nerve and, to distinguish mast cells by their granule content, applying histochemical reactions. 32 Wistar rats were divided into 4 groups (n=8). For each group, 5 rats were intoxicated with Kh and 3 received water only as a control.Intoxicated rats received 3.5 g/ Kg body weight of dry powder of Kh fruits, fractionated in 5 doses as follows 1.5, 0.5, 0.5, 0.5, 05 on days 0, 3,7,10,14 respectively. Control rats received water only. Each group was killed at different times during paralysis evolution. Samples of liver, kidney, lung and brain, were obtained and processed by routine technique until paraffin embedding. Sections were obtained and stained with toluidine blue, PAS, alcian blue/PAS and alcian blue/safranin. Mast cells infiltrates were observed in peripheral nerve and lung. Mast cells were counted. An increasing number of mast cells were recorded as well as variations in the histochemical pattern of their granules for each organ. These findings suggest a role for mast cells and their secretions in the intoxication with mature fruit of Kh.

Enhancing global capacity in the surveillance, prevention, and control of chronic diseases: seven themes to consider and build upon.

BACKGROUND: Chronic diseases are now a major health problem in developing countries as well as in the developed world. Although chronic diseases cannot be communicated from person to person, their risk factors (for example, smoking, inactivity, dietary habits) are readily transferred around the world. With increasing human progress and technological advance, the pandemic of chronic diseases will become an even bigger threat to global health. METHODS: Based on our experiences and publications as well as review of the literature, we contribute ideas and working examples that might help enhance global capacity in the surveillance of chronic diseases and their prevention and control. Innovative ideas and solutions were actively sought. RESULTS: Ideas and working examples to help enhance global capacity were grouped under seven themes, concisely summarised by the acronym "SCIENCE": Strategy, Collaboration, Information, Education, Novelty, Communication and Evaluation. CONCLUSION: Building a basis for action using the seven themes articulated, especially by incorporating innovative ideas, we presented here, can help enhance global capacity in chronic disease surveillance, prevention and control. Informed initiatives can help achieve the new World Health Organization global goal of reducing chronic disease death rates by 2% annually, generate new ideas for effective interventions and ultimately bring global chronic diseases under greater control.

Based on HLA-DR beta1* allele binding specificities, striking differences in distance and TCR Contacting Residue Orientation can be observed in modified protection-inducing malarial synthetic peptides.

An anti-malarial vaccine is urgently needed, especially against P. falciparum which causes 2 to 3 million deaths each year, mostly in Sub-Saharan African children. This vaccine should contain molecules from the parasite's different developmental stages due to the parasite's remarkable complexity and genetic variability. The first approach using synthetic peptides from different parasite stage molecules (the SPf66 malaria vaccine) conferred limited protective efficacy in Aotus monkeys and in large field-trials carried out in different parts of the world SPf66 contains red blood cell (RBC) binding merozoite peptides for which immune responses against them are genetically controlled by HLA-DR region. Therefore, a systematic search of conserved high activity binding peptides (HABP) was undertaken aimed at using them as immunogens. However, these peptides were poorly immunogenic and had poor protection-inducing capacity against experimental challenge with a P. falciparum strain highly infective for Aotus monkeys an experimental model with an immune system quite similar to humans. Modifications were thus made to key residues to render them immunogenic and protection-inducing. These native and modified HABPs' three-dimensional structure was determined by (1)H-NMR studies and their ability in forming stable Major Histocompatibility Class II - peptide (MHCII-peptide) complexes was correlated with their ability to bind in vitro to purified HLA-DR beta1* molecules. Our experimental data suggests a correlation between modified HABPs' three-dimensional structure, HLA-DR beta1* binding preferences and their protection-inducing capacity in monkeys. Furthermore, the data presented here indicates that a synthetic peptide vaccine's three-dimensional structural features dictate both HLA-DR beta1* allele binding preference (imposing genetic restriction on the immune response) and on these vaccines' protection-inducing value. Basic knowledge of a parasite's functionally active peptides, their 3D structure and their interaction for forming the MHC II- peptide-TCR complex will thus contribute towards designing fully effective multi-component, multi-stage subunit-based malarial vaccines.

Serine repeat antigen peptides which bind specifically to red blood cells.

It has been reported that serine repeat antigen (SERA) binds directly to human erythrocyte membranes, inside-out vesicles and intact mouse erythrocytes. Similarly, mAbs specific against SERA are effective in blocking red blood cell (RBC) invasion by P. falciparum merozoites. Furthermore, the N-terminal recombinant SERA fragment inhibits the merozoite invasion of erythrocyte. In this study of 49 non-overlapping 20-residue-long peptides encompassing the whole SERA protein FCR3 strain, seven peptides having high RBC binding activity were found. Six of these peptides (three from the SERA N-terminal domain) are located in conserved regions and show affinity constants between 150 and 1100 nM, Hill coefficients between 1.5 and 3.0 and 30000-120000 binding sites per cell. Some of these peptides inhibited in vitro merozoite invasion of erythrocyte and intra-erythrocytic development. Residues which are critical in the binding to erythrocytes (in bold face), i.e. 6725 (YLKETNNAISFESNSGSLEKK), 6733 (YALGSDIPEKCDTLASNCFLS), 6737 (YDNILVKMFKTNENNDKSELI), 6746 (DQGNCDTSWIFASKYHLETI), 6754 (YKKVQNLCGDDTADHAVNIVG) and 6762 (NEVSERVHVYHILKHIKDGK), were determined by means of competition assays with high-binding peptide glycine analogues. The identification of peptides which bind to erythrocyte membrane is important in understanding the process of RBC invasion by P. falciparum merozoites.

Tratamiento antitrombótico en la fibrilación auricular no reumática. ¿Cumplimos las recomendaciones de los ensayos clínicos? / Antithrombotic treatment in nonrheumatic atrial fibrilation: do we follow clinical trial recomendations?

Objetivos: Distintos ensayos clínicos han demostrado que el tratamiento antitrombótico puede ser eficaz en la prevención del ictus en pacientes con fibrilación auricular (FA) no reumática. El objetivo del presente estudio fue conocer si se cumplen las recomendaciones de los grandes ensayos clínicos en la práctica clínica y, valorar los factores que pueden influir en la decisión del distinto tratamiento antitrombótico empleado. Métodos: Analizamos la historia clínica de 225 pacientes diagnosticados de FA no reumática en Cáceres durante los meses de Febrero y Marzo de 1998. Se excluyeron 20 pacientes por contraindicación para mantener tratamiento antitrombótico o, sin evidencia de FA crónica, por lo que finalmente 205 enfermos formaron parte del estudio. Se compararon los pacientes que seguían tratamiento antitrombótico (anticoagulante o antiagregante) y sin tratamiento, con distintas características demográficas y factores de riesgo embolígeno. Resultados: De los 205 enfermos que formaron parte del estudio, 149 (72,6%) tenían un riesgo embolígeno elevado. Sesenta y dos pacientes (30,2%) del total seguían tratamiento con anticoagulantes, 94 (45,8%) antiagregantes, 5 (2,4%) doble tratamiento y 49 (24%) no realizaban ningún tipo de tratamiento. No hubo diferencias entre el grupo de pacientes con tratamiento anticoagulante, antiagregante o sin tratamiento respecto a la edad, sexo, presencia de cardiopatía isquémica, hipertensión arterial e insuficiencia cardiaca en los últimos 3 meses, mientras que, el antecedente de accidente cerebrovascular y otras variables ecocardiográficas (valvulopatía, calcificación valvular, disfunción ventricular) fueron mas frecuentes en los pacientes anticoagulados y antiagregados, que en aquellos sin tratamiento. Conclusiones: Un alto porcentaje de pacientes con FA no reumática sigue algún tipo de tratamiento preventivo antitrombótico, aunque posiblemente todavía un gran número de enfermos con FA podría beneficiarse del tratamiento anticoagulante. En nuestro medio, la valoración terapéutica de los enfermos con FA crónica debería tener en cuenta, además de hallazgos ecocardiográficos, otras características clínicas, como hipertensión arterial, cardiopatía isquémica e insuficiencia cardiaca (AU)

[Antithrombotic treatment in non-rheumatic atrial fibrillation. Do we follow the recommendations of clinical trials?]. / Tratamiento antitrombótico en la fibrilación auricular no reumática. Cumplimos las recomendaciones de los ensayos clínicos?

OBJECTIVES: Several clinical trials have demonstrated that antithrombotic treatment may be effective in prevention of stroke in nonrheumatic atrial fibrillation (AF). The aim of this study was to assess if we follow clinical trial recommendations in community practice. METHODS: We analyzed 225 medical records of patients diagnosed of nonrheumatic AF in Cáceres, during February and March 1998. Patients who were contraindicated to follow antiagreggation or anti-coagulation treatment were excluded. We compared patients with and without antithrombotic treatment with different demographic characteristics and embolic risk factors. RESULTS: 205 patients were included in the study, 149 (72.6%) had high embolic risk. 62 (30.2%) followed anticoagulation, 94 (45.8%) antiaggregation treatment, 5 (2.4%) both treatment and 49 (24%) were not receiving therapy. We didn't findings differences between age, sex, presence of ischemic heart disease, hypertension and congestive heart failure in last three months compared with the patients in respect to the group of patients with anticoagulation and antiaggregation therapy or without it. We determinate as well that previous stroke and echocardiographical finds (valve disease, valve calcification, ventricular dysfunction) were more frequent in the anticoagulation and antiaggregate patients than in those without therapy. CONCLUSION: A high range of nonrheumatic AF patients take any kind of antithrombotic preventive therapy, though a great number of patients with high embolic risk could still get benefits from anticoagulation therapy. We should considerate in the therapy assessment some other clinical characteristics as hypertension, isquemic heart disease and heart failure apart from echocardiographical findings.

Reduced amide pseudopeptide analogues of a malaria peptide possess secondary structural elements responsible for induction of functional antibodies which react with native proteins expressed in Plasmodium falciparum erythrocyte stages.

A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high-binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines.

Hipertiroxinemia en la enfermedad trofoblastica. / Hyperthyroxinemia in trophoblastic disease

Con el fin de analizar las variaciones de las hormonas tiroideas cen el embarazo molar se estudiaron 13 casos. Las hormonas tiroideas en la sangre se cuantificaron periodicamente hasta 12 semanas despues del vaciamiento molar. La captacion de T3 se mantuvo baja durante todo el estudio, debido a la elevacion en la globulina transportadora de hormonas tiroideas por el efecto del embarazo y despues por los anticonceptivos hormonales. Se demostro hipertiroxinemia con T4 total de 18.25% + ou - 1.47 ng/dl e indice de tiroxina libre de 6.0 + ou - 0.61, cifras que alcanzaron valores normales hasta la segunda y primera semanas postevacuacion respectivamente.No obstante lo anterior, ninguna de las pacientes tuvo datos clinicos de hipertiroidismo

[Health and the development of a rural health service system]. / La salud y el desarrollo en un sistema rural de servicios de salud.

The first part of this article reviews the interesting experience of the Center for Multidisciplinary Research in Rural Development (CIMDER) of Cali, Colombia, in the application of a model for the integrated development of health services. The strategies used in the model were: services available to all individuals and families in the community, use of accessible technology, community participation, and cooperation between the health sector and other development sectors. The second part briefly reviews the role of the nurse in health and development and takes issue with the traditional narrow view of the sphere of action of nursing as a profession. It is asserted that, in order to bring about the extension of health services and community development, it is necessary that the nurse serve in a position of leadership on a multidisciplinary team as either coordinator of services, supervisor of personnel, or education, and as liaison for the formal health care system with the community to enlist its active participation.

La salud y el desarrollo en un sistema rural de servicios de salud / Health and the development of a rural health service system

The first part of this article reviews the interesting experience of the Center for Multidisciplinary Research in Rural Development (CIMDER) of Cali, Colombia, in the application of a model for the integrated development of health services. The strategies used in the model were: services available to all individuals and families in the community, use of accessible technology, community participation, and cooperation between the health sector and other development sectors. The second part briefly reviews the role of the nurse in health and development and takes issue with the traditional narrow view of the sphere of action of nursing as a profession. It is asserted that, in order to bring about the extension of health services and community development, it is necessary that the nurse serve in a position of leadership on a multidisciplinary team as either coordinator of services, supervisor of personnel, or education, and as liaison for the formal health care system with the community to enlist its active participation (Au)