The enigmatic eosinophil: investigation of the biological role of eosinophils in parasitic helmint infection

In many helminth infected hosts the number of eosinophils increases dramatically, often without any concurrent increases in the number of other leukocytes, so that eosinophils become the dominant cell type. Many experimental investigations have shown that the eosinophilia is induced by interleukin-5 (IL-5) but its functional significance remains unclear. Mice genetically deficient in IL-5 (IL-5-/-) have been used to evaluate the functional consequences of the IL-5 dependent eosinophilia in helminth infected hosts. Host pathology and level of infection were determined in IL-5-/- and wild type mice infected with a range of species representative of each major group of helminths. The effects of IL-5 deficiency were very heterogeneous. Of the six species of helminth examined, IL-5 dependent immune responses had no detectable effect in infections with three species, namely the cestodes Mesocestoides corti and Hymenolepis diminuta and the trematode Fasciola hepatica. In contrast, IL-5 dependent immune responses were functionally important in mice infected with three species, notably all nematodes. Damage to the lungs caused by migrating larvae of Toxocara canis was reduced in IL-5-/- mice. Infections of the intestine by adult stages of either Strongyloides ratti or Heligmosomoides polygyrus were more severe in IL-5-/- mice. Adult intestinal nematodes were clearly deleteriously affected by IL-5 dependent processes since in its presence there were fewer worms which had reduced fecundity and longevity. The implications of these results for the viability of using inhibitors of IL-5 as a therapy for asthma are considered.

Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

Structural and functional interaction sites between Na,K-ATPase and FXYD proteins.

Several members of the FXYD protein family are tissue-specific regulators of Na,K-ATPase that produce distinct effects on its apparent K(+) and Na(+) affinity. Little is known about the interaction sites between the Na,K-ATPase alpha subunit and FXYD proteins that mediate the efficient association and/or the functional effects of FXYD proteins. In this study, we have analyzed the role of the transmembrane segment TM9 of the Na,K-ATPase alpha subunit in the structural and functional interaction with FXYD2, FXYD4, and FXYD7. Mutational analysis combined with expression in Xenopus oocytes reveals that Phe(956), Glu(960), Leu(964), and Phe(967) in TM9 of the Na,K-ATPase alpha subunit represent one face interacting with the three FXYD proteins. Leu(964) and Phe(967) contribute to the efficient association of FXYD proteins with the Na,K-ATPase alpha subunit, whereas Phe(956) and Glu(960) are essential for the transmission of the functional effect of FXYD proteins on the apparent K(+) affinity of Na,K-ATPase. The relative contribution of Phe(956) and Glu(960) to the K(+) effect differs for different FXYD proteins, probably reflecting the intrinsic differences of FXYD proteins on the apparent K(+) affinity of Na,K-ATPase. In contrast to the effect on the apparent K(+) affinity, Phe(956) and Glu(960) are not involved in the effect of FXYD2 and FXYD4 on the apparent Na(+) affinity of Na,K-ATPase. The mutational analysis is in good agreement with a docking model of the Na,K-ATPase/FXYD7 complex, which also predicts the importance of Phe(956), Glu(960), Leu(964), and Phe(967) in subunit interaction. In conclusion, by using mutational analysis and modeling, we show that TM9 of the Na,K-ATPase alpha subunit exposes one face of the helix that interacts with FXYD proteins and contributes to the stable interaction with FXYD proteins, as well as mediating the effect of FXYD proteins on the apparent K(+) affinity of Na,K-ATPase.

Thrombolyse de l'accident vasculaire cérébral ischémique aigu: rôles du praticien et de l'hôpital périphérique [Thrombolysis of acute ischemic cerebral vascular accident: roles of the physician and the peripheral hospital]

Thrombolysis administered intravenously within 3 hours (or within 6 hours intra-arterially) after symptoms onset improves the functional outcome of acute ischemic stroke patients. In Switzerland this treatment is only performed by specialized centers. At the level of a community hospital or a general practitioner, the management is based on the appropriate selection of patients in whom thrombolysis could be indicated, followed by their immediate transfer to a reference medical center. Because of the very short therapeutic window, specific criteria have to be used. We present the guidelines of Les Cadolles Hospital in Neuchâtel established in collaboration with the Department of Neurology of the University Hospital of Lausanne and a retrospective analysis of emergency admissions for suspected stroke at Les Cadolles between January 1st 2001 and December 31st 2002.

An Investigation on the Ecology of Triatoma vitticeps (Stal, 1859) and its Possible Role in the Transmission of Trypanosoma cruzi, in the Locality of Triunfo, Santa Maria Madalena Municipal District, State of Rio de Janeiro, Brazil

From January 1989 to April 1995, 465 specimens of Triatoma vitticeps were collected in the locality of Triunfo, 2nd District of Santa Maria Madalena municipal district, State of Rio de Janeiro. The bugs were found indoors by local residents with predominance of adults. The flight activity was high in hot months when the incidence in the domicile also increased. Two hundred and two bugs (111 alive and 91 dead) were examined for Trypanosoma cruzi infection. This was detected in 31 of the dead bugs (34%) and 88 (79%) of the live bugs examined. With a view to investigate the possible vertebrate hosts of the T. cruzi isolates, the blood of 122 mammals was examined through Giemsa-stained smears, hemocultures and xenodiagnosis. T. cruzi was detected in three specimens of Didelphis marsupialis and T. (M.) theileri was detected in one specimen of Bos taurus. The parasites were isolated from triatomine feces, xenoculture and hemoculture. No evidence of human infection was detected in 58 inhabitants examined, as evaluated by indirect imunofluorescence technique using T. cruzi epimastigotes as antigens. These results show that T. vitticeps is still a sylvatic species although nymphs have been found inside the domicile. Thus, an epidemiological vigilance is necessary to know the behaviour of this species following the continuous modifications promoted by the presence of man.

Sub-cortical and brainstem sites associated with chemo-stimulated increases in ventilation in humans.

We investigated the neural basis for spontaneous chemo-stimulated increases in ventilation in awake, healthy humans. Blood oxygen level dependent (BOLD) functional MRI was performed in nine healthy subjects using T2 weighted echo planar imaging. Brain volumes (52 transverse slices, cortex to high spinal cord) were acquired every 3.9 s. The 30 min paradigm consisted of six, 5-min cycles, each cycle comprising 45 s of hypoxic-isocapnia, 45 s of isooxic-hypercapnia and 45 s of hypoxic-hypercapnia, with 55 s of non-stimulatory hyperoxic-isocapnia (control) separating each stimulus period. Ventilation was significantly (p<0.001) increased during hypoxic-isocapnia, isooxic-hypercapnia and hypoxic-hypercapnia (17.0, 13.8, 24.9 L/min respectively) vs. control (8.4 L/min) and was associated with significant (p<0.05, corrected for multiple comparisons) signal increases within a bilateral network that included the basal ganglia, thalamus, red nucleus, cerebellum, parietal cortex, cingulate and superior mid pons. The neuroanatomical structures identified provide evidence for the spontaneous control of breathing to be mediated by higher brain centres, as well as respiratory nuclei in the brainstem.

A Preliminary Investigation on the Chemical Composition of the Cell Surface of Five Enteropathogenic Escherichia coli Serotypes

The cell surfaces of five enteropathogenic Escherichia coli serotypes (O111:H2; O111:H12; O125:H9; O119:H6; O26:H11) were assayed by chemical methods, lectin agglutination tests and spectroscopy associated to transmission electron microscopy. Results of lectin agglutination assays showed that all strains reacted with mannosebinding lectins. Strains belonging to serotype O125:H9 also agglutinated with lectins which recognize galactose and Nacetylgalactosamine residues. The bacterial cells were treated with 0.01M phosphate buffered saline (pH 7.0) at 100oC for 2 hr and the extracts were submitted to precipitation and fractionated by Cetavlon. Phosphate, total sugar and protein contents were determined. Gas liquid chomatography-mass spectrometry analysis of alditol acetates showed the presence of galactose, mannose, fucose, glucose and traces of ribose. Spectroscopic analysis of intact cells showed the presence of a capsule-like structure which was not totally preserved after extraction. Some cells were still surrounded by an amorphous capsular-like material after polysaccharide extraction.

Penetration Sites and Migratory Routes of Angiostrongylus costaricensis in the Experimental Intermediate Host (Sarasinula marginata)

The intermediate hosts of Angiostrongylus costaricensis are terrestrian molluscs, mostly of the family Veronicellidae. The present work aimed at clarifying more accurately the sites of penetration and the migratory routes of A. costaricensis in the tissue slugs and at verifying the pattern of the perilarval reaction at different times of infection. Slugs were individually infected with 5,000 L1, and killed from 30 min to 30 days after infection. From 30 min up to 2 hr after infection, L1 were found within the lumen of different segments of the digestive tube having their number diminished in more advanced times after exposition until complete disappearance. After 30 min of exposition, percutaneous infection occurred, simultaneously to oral infection. Perilarval reaction was observed from 2 hr of infection around larvae in fibromuscular layer, appearing later (after 6 hr) around larvae located in the viscera. A pre-granulomatous reaction was characterized by gradative concentration of amebocytes around larvae, evolving two well-organized granulomas. In this work we confirmed the simultaneous occurrence of oral and percutaneous infections. Perilarval reaction, when very well developed, defined typical granulomatous structure, including epithelioid cell transformation. The infection also caused a systemic mobilization of amebocytes and provoked amebocyte-endothelium interactions.

Evaluation of postmortem MDCT and MDCT-angiography for the investigation of sudden cardiac death related to atherosclerotic coronary artery disease.

The goal of this study was to evaluate the diagnostic value of postmortem multi-computed tomography (MDCT) and MDCT-angiography for sudden cardiac deaths related to ischemic heart disease. Twenty three cases were selected based on clinical history and the results of native MDCT, multiphase post-mortem CT-angiography and conventional autopsy were compared. Radiological examination showed calcification of coronary arteries in 78% of the cases, most of which were not detailed at autopsy. MDCT-angiography allowed better visualization of the coronary arteries than MDCT and permitted the evaluation of stenoses and occlusions. Of the 14 cases of coronary thrombosis detected at conventional autopsy, 11 were visible as stop of perfusion with CT-angiography and three were found to be partly perfused. One case had an old thrombosis with collateral circulation. One case had a coronary artery postmortem clot found with MDCT-angiography. Coronary artery calcifications are more easily detected and documented with radiological examination than with conventional autopsy. MDCT is of limited diagnostic value for ischemic heart disease. MDCT-angiography, when correctly interpreted, is a reasonable tool to view the morphology of coronary arteries, rule out significant coronary artery stenoses, identify occlusions and direct sampling for histological examination.

Déterminants de l'évolution de la mesure d'indépendance fonctionnelle (MIF) des patients avec accident vasculaire cérébral lors de la neuroréhabilitation multiprofessionnelle intensive

Introduction :¦Généralement, toute personne souffrant de déficits neurologiques suite à un accident vasculaire cérébral (AVC) devrait bénéficier d'un traitement multiprofessionnel intensif de neuroréhabilitation. Or, on constate que, malgré une même prise en charge, tous les patients n'évoluent pas de façon similaire. Si nous pouvions déterminer précocement le potentiel de récupération fonctionnelle de chaque patient, nous pourrions adapter le programme de réadaptation à ses besoins et à ses capacités.¦Objectifs :¦Identifier les facteurs prédictifs précoces du devenir fonctionnel des patients victimes d'AVC, sous traitement multiprofessionnel intensif de neuroréhabilitation.¦Matériel et méthode :¦Enquête prospective d'observation de suivi d'une cohorte de 176 patients victimes d'un premier AVC et admis dans le service de neuropsychologie et de neuroréhabilitation du CHUV, entre 2005 et 2010. L'état fonctionnel des patients a été évalué à l'aide de l'échelle de Mesure d'Indépendance Fonctionnelle (MIF), lors de leur entrée et de leur sortie du service de réadaptation.¦Résultats :¦Une analyse multivariée a mis en évidence que le fait d'être un homme, d'avoir moins de 55 ans, d'avoir un score de MIF supérieur à 100 lors de l'entrée en neuroréhabilitation, de bénéficier d'au minimum 70 jours de réhabilitation, de gagner chaque semaine au minimum 10% du gain de MIF possible et de ne pas souffrir ni d'aphasie, ni d'héminégligence, ni de spasticité, ni de complications durant le séjour de réadaptation étaient des facteurs prédictifs précoces d'une bonne évolution fonctionnelle sous traitement multiprofessionnel intensif de neuroréhabilitation.¦Conclusion :¦Tous les patients n'évoluent pas de façon identique sous traitement multiprofessionnel intensif de neuroréhabilitation ; une prise en charge adaptée, en particulier concernant l'intensité des traitements, devrait être proposée.

Final Report on the Review of the Home Accident Prevention Strategy Action Plan 2004-2009 (PDF 147KB)

Report on the Review of the Home Accident Prevention Strategy & Action Plan 2004-09