The current therapies against cancer showed limited success. Nanotechnology is a promising strategy for cancer tracking, diagnosis, and therapy. The hybrid nanotechnology assembled several materials in a multimodal system to develop multifunctional approaches to cancer treatment. The quantum dot and polymer are some of these hybrid nanoparticle platforms. The quantum dot hybrid system possesses photonic and magnetic properties, allowing photothermal therapy and live multimodal imaging of cancer. These quantum dots were used to convey medicines to cancer cells. Hybrid polymer nanoparticles were utilized for the systemic delivery of small interfering RNA to malignant tumors and metastasis. They allowed non-invasive imaging to track in real-time the biodistribution of small interfering RNA in the whole body. They offer an opportunity to treat cancers by specifically silencing target genes. This review highlights the major nanotechnology approaches to effectively treat cancer and metastasis.

Paludisme "a word derived from Latin palus meaning swamp" or Malaria " a word derived from Italian mala'ria meaning bad air", designed by the bad air from swamps, is an infectious disease caused by a parasite of the genus Plasmodium transmitted by female mosquitoes of the genus Anopheles generating millions of deaths each year.Biological membranes have a major role in cells invasion by Malaria parasites.Phosphatidylserine and phosphatidylinositol are essential for the invasion of erythrocytes by Plasmodium.Plasmodium binds to the erythrocyte membrane via glycolipids.Cholesterol is responsible for the uptake of host proteins and maintenance of intracellular parasitophorous vacuolar membrane.Malaria parasites invade red blood cells by binding to multiple membrane receptors at the level of the spectrin, band 3, actin, glycophorin, band 4.1, band 4.2, aquaporin-1, band 7, and ankyrin.Parasitic proteins such as the reticulocyte-binding like family bind to the membrane erythrocytic proteins and play a major role in the mechanisms of invasion of red blood cells by Plasmodium.Susceptibility to Plasmodium invasion is linked to the terminal stages of the differentiation of red blood cells.This review highlights the complex interactions between biological membranes and malaria parasites.

A new method for the detection by flow cytometry of anti-double-stranded DNA antibodies and of circulating immune complexes (IC) containing endogenous DNA (IC-eDNA) is described. From each serum sample, two samples were taken, one was used to detect IC-eDNA. The other to detect anti-DNA antibodies was incubated with calf thymus DNA. ICs were isolated by polyethylene glycol precipitation or by cryoprecipitation, after which immunoglobulins were labeled with FITC-conjugated anti-human globulin. Serum samples from 63 systemic lupus erythematosus (SLE) patients, 32 incomplete lupus, and 87 control patients were tested. Detection of anti-dsDNA antibodies by flow cytometry had a diagnostic sensitivity and specificity almost comparable to routine tests, the fluorescent enzyme immunoassay EliA™-dsDNA test, and the ultrasensitive Crithidia luciliae indirect immunofluorescence test. In 21 (33%) out of 63 SLE serum samples, IC-eDNA was detected. In these samples, free anti-dsDNA antibodies were hardly detectable or undetectable by flow cytometry or by routine tests. When anti-DNA antibodies are neutralized by endogenous DNA and can no longer be detected by routine tests, the serologic diagnosis and the follow-up of relapses in patients with SLE is compromised. To overcome this obstacle, we propose an accessible solution: the detection of circulating IC-eDNA by flow cytometry.

Biomedical engineering handles the organization and functioning of medical devices in the hospital. This is a strategic function of the hospital for its balance, development, and growth. This is a major focus in internal and external reports of the hospital. It's based on piloting of medical devices needs and the procedures of biomedical teams’ intervention. Multi-year projects of capital and operating expenditure in medical devices are planned as coherently as possible with the hospital's financial budgets. An information system is an essential tool for monitoring medical devices engineering and relationship with medical services.

[This corrects the article DOI: 10.1371/journal.pone.0158235.].

Le bleu patenté (BP) est un colorant des voies lymphatiques utilisé pour le repérage du ganglion sentinelle, pouvant être responsable de réactions d’hypersensibilité immédiate. Nous avons mené une étude rétrospective en incluant tous les patients testés au BP dans le service de dermato-allergologie de l’hôpital Tenon. L’objectif de cette étude était d’étudier l’intérêt des tests cutanés. Seize femmes étaient adressées pour suspicion de réaction allergique au BT. Quatorze patientes avaient présenté des réactions d’allure allergique lors du repérage du ganglion sentinelle par le BP au cours d’une anesthésie générale. Deux des 16 patientes n’avaient jamais reçu de BP : une était testée en prévention avant une injection de BP pour repérage du ganglion sentinelle et une autre en raison d’une suspicion d’allergie au bleu indigo. Les manifestations cliniques étaient variées : choc anaphylactique dont deux arrêts cardiaques (n = 10), urticaire généralisée dont deux urticaires bleutées (n = 4). Le délai des réactions, précisé chez quatre des patients, était de moins de dix minutes après injection de BP. Quatorze patientes ont eu successivement des prick-tests et des tests intradermiques avec des concentrations progressivement croissantes au BP et aux produits anesthésiques. Le latex était aussi testé. Treize de ces 14 patientes avaient des tests positifs pour le BP, contre indiquant définitivement cette molécule. Une des patientes avait un test négatif au BP mais positif au suxaméthonium. Les 2 patientes n’ayant jamais eu d’injection de BP avaient des tests négatifs. Une patiente sur les 6 testées au bleu de méthylène avait également un test positif à ce colorant. Nos résultats soulignent l’intérêt des tests cutanés au BP dans l’exploration de réactions d’hypersensibilités immédiates. Les tests au BP ne semblent pas irritants aux concentrations utilisées car trois patientes dont une exposée au BP avaient des tests négatifs. Des cas de co-sensibilisation au BP et bleu de méthylène ont été rapportés dans la littérature comme chez une de nos patiente, incitant à la prudence vis-à-vis de ce colorant. Dans cette étude, les tests cutanés ont permis de confirmer une réaction allergique au BP.

Les héparines non fractionnées et de bas poids moléculaires sont connues pour être à l’origine de manifestations allergiques, en particulier d’éruptions eczématiformes localisées pouvant se généraliser. Les réactions croisées avec d’autres héparines et leurs dérivés étant fréquentes, l’identification d’alternatives thérapeutiques est indispensable. Cette étude rétrospective a porté sur les patients adressés dans le service de dermatologie et d’allergologie de l’hôpital Tenon entre 2000 et 2012 pour suspicion d’allergie aux héparines non fractionnées (HNF) ou de bas poids moléculaire (HBPM), et qui avaient eu des tests cutanés positifs pour au moins une héparine. Tous les patients ont été recontactés en 2012 pour savoir s’ils avaient repris une héparine depuis le bilan. Dix-neuf patients avaient au moins un test cutané positif pour une héparine, dont un patient avec choc anaphylactique et 18 avec des eczémas localisés (12) ou généralisés (6). L’héparine la plus fréquemment incriminée était l’énoxaparine sodique (13/19) ; une HBPM était majoritairement incriminée (18 patients pour une HBPM et 1 pour une HNF). Chez ces 18 patients, 16 avaient aussi des tests positifs pour une HNF, 9 pour un héparinoïde et un pour une hirudine. Les tests au fondaparinux (pentasaccharide synthétique) effectués chez 11 des 19 patients étaient toujours négatifs. Sept de ces 11 patients ont eu du fondaparinux depuis les tests cutanés : 5 sans manifestation et 2 avec une éruption localisée aux points d’injection. Nos résultats soulignent une plus grande fréquence des réactions d’hypersensibilité retardée par rapport aux réactions immédiates avec les héparines. Les tests cutanés peuvent aider à identifier des molécules de remplacement ; le fondaparinux serait une alternative, mais le diagnostic de certitude repose sur la réintroduction. Allergic hypersensitivity to unfractioned or low-molecular-weight heparins is uncommon but is known, and in particular the most common form is localized dermatitis, although such cases have seldom turned into maculopapular exanthema. Since cross-reactions with other heparins are frequent, identification of therapeutic alternatives is essential. This retrospective study included patients referred to the Department of Dermatology and Allergology at Tenon Hospital between 2000 and 2012 with suspicion of allergy to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and sensitized to at least one heparin (i.e. positive skin tests to at least one heparin). The heparins and hirudins used were tested in the forearm by means of intradermal skin tests. All patients were contacted in 2012 to establish whether they had used some form of heparin since the cutaneous allergy tests. Nineteen patients had at least one positive skin test for heparin; 1 patient had presented anaphylactic shock, while 18 others had presented localized eczema (12) or generalized dermatitis (6). The heparin most often responsible for these adverse reactions was enoxaparin (13/19). An LMWH was responsible in most cases (18 vs. 1 with UFH). Of these 18 patients, 16 also presented positive skin tests for UFH, 9 for synthetic heparinoid and 1 for hirudin. 11/19 patients were tested for fondaparinux (a synthetic pentasaccharid) and all had negative skin tests. 5/7 patients with negative skin tests had taken fondaparinux without any visible reaction, whereas 2 who also tested negative experienced localized eruption at the injection site. Our results underline the greater frequency of delayed hypersensitivity reactions compared with immediate reactions to heparins. Skin tests can help to identify substitution molecules. Fondaparinux might be an alternative but certain diagnosis relies on rechallenge.

BACKGROUND:Allergic hypersensitivity to unfractioned or low-molecular-weight heparins is uncommon but is known, and in particular the most common form is localized dermatitis, although such cases have seldom turned into maculopapular exanthema. Since cross-reactions with other heparins are frequent, identification of therapeutic alternatives is essential. PATIENTS AND METHODS:This retrospective study included patients referred to the Department of Dermatology and Allergology at Tenon Hospital between 2000 and 2012 with suspicion of allergy to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and sensitized to at least one heparin (i.e. positive skin tests to at least one heparin). The heparins and hirudins used were tested in the forearm by means of intradermal skin tests. All patients were contacted in 2012 to establish whether they had used some form of heparin since the cutaneous allergy tests. RESULTS:Nineteen patients had at least one positive skin test for heparin; 1 patient had presented anaphylactic shock, while 18 others had presented localized eczema (12) or generalized dermatitis (6). The heparin most often responsible for these adverse reactions was enoxaparin (13/19). An LMWH was responsible in most cases (18 vs. 1 with UFH). Of these 18 patients, 16 also presented positive skin tests for UFH, 9 for synthetic heparinoid and 1 for hirudin. 11/19 patients were tested for fondaparinux (a synthetic pentasaccharid) and all had negative skin tests. 5/7 patients with negative skin tests had taken fondaparinux without any visible reaction, whereas 2 who also tested negative experienced localized eruption at the injection site. DISCUSSION:Our results underline the greater frequency of delayed hypersensitivity reactions compared with immediate reactions to heparins. Skin tests can help to identify substitution molecules. Fondaparinux might be an alternative but certain diagnosis relies on rechallenge.

L’hépatite aiguë à VHE devient de plus en plus fréquente chez les patients immunodéprimés. Il n’existe pas à l’heure actuelle de recommandation pour la prise en charge de cette infection en cas de traitement immunosuppresseur.Nous rapportons un cas d’hépatite aiguë à VHE traitée efficacement par ribavirine chez une patiente suivie pour une polyarthrite rhumatoïde (PR) traitée par rituximab.Une femme de 51 ans suivie pour une PR traitée par rituximab a été hospitalisée pour ictère secondaire à une hépatite aiguë à VHE. Elle a été traitée par ribavirine 800 mg deux fois par jour pendant 2 mois avec une bonne efficacité et tolérance. Finalement trois mois après l’hépatite aiguë à VHE, l’activité de la PR a requis deux nouvelles perfusions de 1000 mg de rituximab. Le traitement a été bien toléré sans récidive d’hépatite aiguë à VHE. Après un suivi de 8 mois par PCR du VHE dans le sang, il n’a pas été mis en évidence de récurrence d’hépatite aiguë ni d’évolution vers une forme chronique d’hépatite E.Ce cas met en lumière l’efficacité et la sûreté de la réintroduction du rituximab après deux mois de traitement par ribavirine et PCR VHE négative.

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P < 0.001) or MAT 10/22 (46%, P < 0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls.

Nous rapportons le premier cas de méningite aiguë aseptique induite par la rifampicine chez une patiente jeune, suivie pour un lupus systémique. Les méningites aseptiques induites par les médicaments sont rares, mais volontiers trompeuses et difficiles à diagnostiquer. Elles sont nettement plus fréquentes chez les patients porteurs d’une maladie auto-immune, notamment le lupus systémique. Les médicaments les plus souvent responsables sont les anti-inflammatoires non stéroïdiens, les antibiotiques, les immunoglobulines intraveineuses et les biothérapies.

We report the first case of acute drug-induced aseptic meningitis (DIAM) due to rifampin in a young female with systemic lupus erythematosus (SLE). DIAM is uncommon and its diagnosis is often difficult. This type of drug hypersensitivity is more frequently observed in patients with a history of auto-immune disease, particularly SLE. The major categories of causative agents are: nonsteroidal anti-inflammatory drugs, antimicrobials, intravenous immunoglobulins and biotherapies.

BACKGROUND:To confirm allergy to beta-lactam (BL), a basophil activation test in flow cytometry based on CD63 up-regulation was described. CD203c is a more recent basophil activation marker and up to day there is no consensus about which marker is the more sensitive one. CD203c has not yet been evaluated in the diagnosis of BL allergy.OBJECTIVE:The aim of the study was to compare the reliability of CD203c to CD63 for the diagnosis of amoxicillin (AX) allergy, which is nowadays the most frequent BL allergy.METHODS:Twenty-seven patients with an immediate positive skin test (ST) to AX, 20 had had anaphylaxis with AX and 7 had urticaria and/or angioedema, were compared with 14 controls with no allergy to BL and to six patients with delayed positive ST to AX.RESULTS:In the anaphylaxis group, AX induced up-regulation of CD203c in the basophils of 12 patients out of 20 (60%) and of CD63 in four patients (20%) (P<0.02). Two patients out of seven with urticaria or angioedema had a positive result with CD203c and CD63. In patients who had anaphylaxis, ampicillin (AMP) induced CD203c up-regulation in eight out of 12 (67%) patients tested, and CD63 up-regulation in 4 out of 12 (33%) (all patients who had anaphylaxis could not be tested with AMP). False-positive results were observed with CD203c as well as CD63, and for 10 patients indeed this was confirmed by a negative drug provocation test. The origin of conflicting results between CD63 and CD203c might be at least the targeting of basophils based on anti-IgE labelling. Among IgE(+) gated cells, by means of CD33, a marker of monocytes, a contamination up to 50% by monocytes was detected. In contrast to CD63, CD203c is an activation marker specific of basophils with a basal low-level expression in resting basophils. Thus, IgE and CD203c double targeting of basophils avoids the contamination by monocytes.CONCLUSION:CD203c seems to be a more sensitive activation marker of basophils than CD63 for the diagnosis of amoxicillin allergy.

Background: Atopic dermatitis of the head and neck (HNAD) has been recognized as a separate entity. Malassezia furfur, a lipophilic yeast, is considered to be a pathogenic allergen in this form of atopic dermatitis. Objective: The purpose of this study was to determine the level of IgE anti-M.-furfur antibodies and their relation to the severity of the disease. Methods: IgE anti-M.-furfur antibodies were assayed in 106 patients with HNAD. Controls included 25 patients with non-HNAD, 20 with nonatopic dermatitis and 16 with seborrheic dermatitis (including 4 with AIDS). Results: There was a highly significant correlation between the level of anti-M.-furfur IgE and clinical severity. Furthermore, there was a significant but smaller correlation between total IgE and clinical severity. In patients with HNAD, total IgE was higher amongst men. Conclusion: IgE anti-M.-furfur antibodies are a good and specific marker for HNAD. IgE M. furfur levels are strongly correlated with the severity of the disease.

Pour l’exploration d’une allergie in vitro, la cytométrie de flux a rendu accessible des tests cellulaires pratiqués jusque-là par des laboratoires de recherche. L’analyse par cytométrie de l’activation in vitro des polynucléaires basophiles est devenue courante. Après incubation avec l’allergène, les basophiles sont fixés puis marqués avec des anticorps anti-IgE, leur activation est détectée avec les anticorps monoclonaux anti-CD63 ou anti-CD203c. Dans le diagnostic d’une allergie de type immédiat, les tests sur les basophiles sont un complément au dosage des IgE spécifiques. Avec certains allergènes, en particulier médicamenteux, la cytométrie de flux a une sensibilité supérieure au dosage des IgE spécifiques. L’interprétation des résultats peut être délicate, en particulier des concentrations élevées de certains médicaments peuvent se révéler toxiques in vitro. La cytométrie offre aussi l’opportunité d’explorer les allergies ayant pour mécanisme l’immunité cellulaire. La détection de la synthèse de cytokines dans les lymphocytes T ou les basophiles, après incubation avec l’allergène est techniquement au point. Il reste à démontrer l’intérêt diagnostique. L’exploration de l’allergie par la cytométrie de flux est appelée à se développer.

For the laboratory investigation of allergic diseases, flow cytometric methods to detect leukocytes that have been activated by allergen in vitro have recently been developed. Cellular tests for the detection of in vitro-activated blood basopbils are complementary to specific IgE determinations. After in vitro incubation with allergen, basophils are fixed and then labeled with anti-IgE antibodies, and activation is then identified with anti-CD63 or anti-CD203c monoclonal antibodies. Assays based on basophil activation complement the measurement of specific IgE. With some allergens, particularly in cases of drug-induced allergy, flow cytometry has greater sensitivity than specific IgE determination. However, high concentrations of drugs can induce cell toxicity, and this may be confused with basophil activation. Cytometry can also be used to explore allergies with a cell-mediated mechanism. The detection of cytokine synthesis in T cells and basophils incubated with allergen is now technically feasible, but the usefulness of this procedure in the diagnosis of allergy remains to be demonstrated. We believe that the application of flow cytometry to the investigation of allergy is likely to increase. (C) 2003 Elsevier SAS. Tous droits reserves.