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The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic has become a major public health issue worldwide. Developing and evaluating rapid and easy‐to‐perform diagnostic tests is a high priority. The current study was designed to assess the diagnostic performance of an antigen‐based rapid detection test (COVID‐VIRO®) in a real‐life setting. Two nasopharyngeal specimens of symptomatic or asymptomatic adult patients hospitalized in the Infectious Diseases Department or voluntarily accessing the COVID‐19 Screening Department of the Regional Hospital of Orléans, France, were concurrently collected. The diagnostic specificity and sensitivity of COVID VIRO® results were compared to those of real‐time reverse‐transcriptase quantitative polymerase chain reaction (RT‐qPCR) results. A subset of patients underwent an additional oropharyngeal and/or saliva swab for rapid testing. A total of 121 patients confirmed to be infected and 127 patients having no evidence of recent or ongoing infection were enrolled for a total of 248 nasopharyngeal swab specimens. Overall, the COVID‐VIRO® sensitivity was 96.7% (CI, 93.5%–99.9%). In asymptomatic patients, symptomatic patients having symptoms for more than 4 days and those with an RT‐qPCR cycle threshold value ≥ 32, the sensitivities were 100%, 95.8%, and 91.9%, respectively. The concordance between RT‐qPCR and COVID VIRO® rapid test results was 100% for the 127 patients with no SARS‐CoV‐2 infection. The COVID‐VIRO® test had 100% specificity and sensitivity greater than 95%, which are better than the recommendations set forth by the WHO (specificity ≥ 97%–100%, sensitivity ≥ 80%). These rapid tests may be particularly useful for large‐scale screening in emergency departments, low‐resource settings, and airports.

IntroductionThe SARS-CoV-2 pandemic has become a major public health issue worldwide. Developing and evaluating rapid and easy-to-perform diagnostic tests is an absolute priority. The current study was designed to assess diagnostic performances of an antigen-based rapid detection test (COVID-VIRO®) in a real-life setting.MethodsTwo nasopharyngeal specimens of symptomatic or asymptomatic adult patients hospitalized in the Infectious Diseases Department or voluntarily accessing the COVID-19 Screening Department of the Regional Hospital of Orléans, France, were concurrently collected. COVID VIRO® diagnostic specificity and sensitivity were assessed in comparison to real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) results. A subset of patients underwent an additional oropharyngeal and/or a saliva swab for rapid testing.Results121 patients already having a confirmed infection and 127 patients having no evidence of recent or ongoing infection were enrolled, for a total of 248 couple of nasopharyngeal swab specimens. Overall COVID-VIRO® sensitivity was 96.7% (IC: 93.5%-99.9%). In asymptomatic patients, symptomatic patients having symptoms for more than 4 days and those having a RT-qPCR Cycle threshold value ≥32, sensitivity was of 100%, 95.8% and 91.9% respectively. The concordance between RT-qPCR and COVID VIRO® rapid test was 100% for the 127 patients with no SARS-CoV-2 infection.ConclusionCOVID-VIRO® test had 100% specificity and above 95% sensitivity, better than WHO recommendations (specificity ≥97-100%, sensitivity ≥80%). These rapid tests are particularly interesting for large-scale screening in Emergency Department, low resource settings and airports.

International audience; The temporomandibular joint (TMJ) is one of the most utilized joints of the human body, not even resting during sleep (for instance people suffering of bruxism). The TMJ disc, a fibrocartilage, allows smooth joint movement and serves as a stress/force distributor between the temporal bone and the condyle. Being a crucial part of the joint, its biomechanical behaviour has to be studied, however tests on complete discs are rare. Among mechanical characterisation procedures, spherical compression does not require specific sample preparation hence discs can keep their integrity (Lee et al. 2016). Furthermore, different disc regions can be tested, and the compression tool radius can be adapted to the disc’s biconcavity. Experimentally the spherical compression tool displacement d is measured, which generally is different from the penetration depth δ. Therefore, the disadvantage of such a test lies in obtaining stress-strain curves since the contact radius a related to the penetration depth δ is required to evaluate the representative stress and strain σ* and ε*. Actually, the Hertz model based on contact of a sphere with a linear elastic half-space is used as a first approximation (Tappert et al. 2017).

Bien que les cocci a Gram positifs soient impliques dans la moitie des causes de sepsis documentes, les chocs toxiques lies a ces bacteries sont rares. Par definition, le choc toxique, qu’il soit d’origine staphylococcique (CTstaph) ou streptococcique (CTstrep), implique la production, seule ou en association avec d’autres facteurs de virulence, d’exotoxines superantigeniques, qui induisent une production excessive de cytokines pro-inflammatoires. Le CTstaph est soit menstruel (colonisation d’un tampon absorbant ou d’un sterilet, production de TSST-1 (toxic shock syndrome toxin-1), hemocultures negatives, mortalite faible), soit non menstruel (le plus souvent postoperatoire, colonisation ou infection locale, production de TSST-1 ou d’enterotoxine, hemocultures positives dans 50 % des cas, mortalite dans 20–25 % des cas). Le CTstrep est le plus souvent associe a un tableau de fasciites necrosantes (hemocultures positives dans 60 % des cas, mortalite allant jusqu’a 80 % lorsqu’il existe une myosite associee). La prise en charge des defaillances d’organe est similaire a celle du choc septique. L’eradication mecanique de la source de production de toxine est indispensable (retrait du tampon ou du sterilet dans les CTstaph menstruels, reprise chirurgicale meme en l’absence de signes inflammatoires locaux dans les CTstaph non menstruels postoperatoires et chirurgie agressive dans les CTstrep avec fasciite necrosante). L’antibiotherapie doit etre bactericide (β-lactamine a fortes doses), et il est propose d’adjoindre des therapeutiques antitoxiniques comme la clindamycine (la grande majorite des souches de Staphylococcus aureus et Streptococcus pyogenes responsables de choc toxique en France est sensible a la clindamycine) ou les immunoglobulines polyvalentes, notamment en cas de choc refractaire.

Background Aortic oesophageal Doppler (ODM) allows continuous non-invasive haemodynamic monitoring. We tested to confirm if residents and nurses were able to reposition oesophageal probe (OP), obtain aortic blood flow of good quality and so perform reliable static and dynamic haemodynamic assessments. Methods Prospective observational study assessing ODM measurements were obtained by six residents and three nurses after they have participated in training. Measured (aortic diameter) and calculated haemodynamic data [indexed stroke volume (SVI), cardiac index] were directly obtained from ODM, after residents and nurses repositioned the OP. In a second group of patients, we tested the ability of residents and nurses to detect rapid haemodynamic changes after a passive leg raising. SVI comparison was the primary end point. Statistical analysis was performed using the method of Bland and Altman. Results Sixty-six haemodynamic measurements were performed on 42 patients. Mean bias for SVI between the skilled physician and residents, and between the skilled physician and nurses were −0.9 ± 5.2 ml/m2 (P = 0.15), with a percentage error of 31%, and 0.9 ± 5.1 ml/m2 (P = 0.14), with a percentage error of 33%, respectively. There was an excellent correlation for SVI between the physician and residents (r = 0.9; P

Resume Introduction Le granulome elastolytique annulaire a cellules geantes est une dermatose granulomateuse rare. Elle est caracterisee histologiquement par la phagocytose des fibres elastiques par des cellules multinucleees. Nous rapportons l’evolution favorable d’un cas apres PUVAtherapie et traitement par antipaludeens de synthese. Observation Un homme de 67 ans, ancien viticulteur, avait des lesions annulaires a bordures surelevees des epaules et du tronc, tres prurigineuses, evoluant depuis plusieurs mois. L’examen histologique d’une biopsie de la bordure erythemateuse etait caracteristique d’un granulome elastolytique annulaire a cellules geantes. Differents traitements topiques s’etaient averes inefficaces et une corticotherapie generale avait attenue le prurit mais sans effet sur les lesions cutanees. Une PUVAtherapie entrainait une regression des lesions du tronc, mais l’eruption s’etendait sur les bras et se couvrait de microkystes epidermiques. La PUVAtherapie etait arretee et un traitement par antipaludeens de synthese (hydroxychloroquine 400 mg/j) etait entrepris, suivi d’une regression complete des lesions. Discussion Le granulome annulaire elastolytique a cellules geantes a ete isole en 1979 par Hanke et al. a propos de cinq cas feminins. Il s’agit d’une dermatose rare dont une trentaine de cas ont ete rapportes dans la litterature anglo-saxonne. L’aspect clinique est assez evocateur, avec des lesions erythemato-papuleuses isolees ou groupees en anneaux a bordures surelevees et a centre plus clair d’evolution atrophique. Les lesions predominent souvent sur les zones photoexposees. L’aspect histologique est caracteristique, avec une image de granulome elastophagique a cellules geantes qui donne son nom a cette affection. Cet aspect permet de le differencier d’autres maladies granulomateuses. L’etiologie est inconnue et le traitement empirique. L’evolution spontanee vers la guerison est possible et aucun traitement n’a obtenu des resultats constants. Dans notre cas, la PUVAtherapie a obtenu un resultat partiel et les antipaludeens de synthese une regression complete des lesions residuelles.

Resume Introduction Le psoriasis blaschko-lineaire est une entite rare n’ayant fait l’objet que des publications de cas isoles. Cette forme de psoriasis pose des problemes de diagnostic differentiel avec les autres dermatoses inflammatoires blaschko-lineaires. Nous rapportons un cas original, dont le caractere lineaire a ete revele a la suite d’un traitement par infliximab. Observation Un homme de 29 ans avait un psoriasis chronique evoluant depuis 17 ans et resistant a differents traitements systemiques. Le traitement par infliximab a la dose de 5 mg/kg, institue a j1, j15 puis tous les deux mois, permettait a partir de la quatrieme perfusion la disparition de la quasitotalite des lesions cutanees. Il persistait uniquement des lesions psoriasiques erythemato-squameuses, non pustuleuses, a disposition blaschko-lineaire, strictement unilaterales sur le bras gauche et le membre inferieur gauche. Ces lesions persistaient apres dix cures d’infliximab, alors qu’aucune autre lesion ne reapparaissait. Discussion Cette observation est originale par la revelation de lesions blaschko-lineaires lors du traitement par infliximab, alors que les plaques diffuses de psoriasis avaient totalement disparu. Cela suggere qu’il existait, chez ce malade, deux populations cellulaires ayant une reponse therapeutique differente de la biotherapie.

Resume Introduction Les lymphomes T de l’hypoderme sont rares et leur diagnostic est souvent difficile. Nous rapportons deux observations de lymphome T sous-cutane, simulant une panniculite, traites initialement par une corticotherapie generale. Observations Cas n o 1. Une femme de 75 ans avait un placard erythemateux et plusieurs nodules des membres inferieurs evoluant depuis quatre mois, sans alteration de l’etat general. L’examen histologique d’un nodule associe aux immunomarquages etait evocateur d’un lymphome T sous-cutane de phenotype CD4− CD8+ CD56−. L’evolution etait favorable sous corticotherapie, puis radiotherapie. Cas n o 2. Une femme de 53 ans avait des plaques infiltrees d’evolution fluctuante depuis une dizaine d’annees. Une panniculite lupique avait ete evoquee mais non confirmee. A l’occasion d’une nouvelle poussee de panniculite, l’examen histologique trouvait un infiltrat lymphoide de l’hypoderme. Les immunomarquages et le genotypage des lymphocytes permettaient de diagnostiquer un lymphome T sous-cutane de phenotype CD4− CD8+ CD56−. Le genotypage des lymphocytes cutanes montrait une monoclonalite T (de type alpha beta). L’evolution etait favorable avec une corticotherapie generale maintenue quelques mois. Par la suite, des nodules reapparaissaient ponctuellement. Une abstention therapeutique etait decidee. Discussion On distingue actuellement deux types de lymphomes touchant preferentiellement l’hypoderme ; leur pronostic et leurs implications therapeutiques divergent. Dans ces deux observations, il s’agissait d’un lymphome T sous-cutane CD8+, d’evolution indolente. Cette faible evolutivite peut poser le probleme du diagnostic differentiel avec une panniculite lupique. Dans ce type de lymphome de faible malignite, le traitement de premiere intention pourrait etre limite a une corticotherapie generale.

Thoracic aortic mural thrombus is a rare entity and potential source of serious systemic emboli. The progress of computed tomography (CT) angiography and the current use of transesophageal echocardiography (TEE) after any embolic event have considerably increased the frequency of diagnostic and there is a growing interest about the etiopathogenesis, which is still widely misunderstood. Therapeutic management remains controversial. We present a case of floating thrombus in the thoracic aorta detected by contrast-enhanced CT scan. This thrombus was responsible for two close major embolic events and was therefore managed surgically. Finally, outcome was favorable.

In this work, the interaction of memantine with human serum albumin (HSA) immobilized on porous silica particles was studied using a biochromatographic approach. The determination of the enthalpy change at different pH values suggested that the protonated group in the memantine–HSA complex exhibits a heat protonation with a magnitude around 65 kJ mol−1. This value agrees with the protonation of a guanidinium group, and confirmed that an arginine group may become protonated in the memantine–HSA complex formation. The thermodynamic data showed that memantine–HSA binding, for low temperature (

Resume Introduction Nous avons, par une enquete, evalue la prevalence et les pratiques de prise en charge des plaies chroniques dans 14 etablissements de soins de suite et de readaptation (SSR) et soins de longue duree (SLD) du Haut-Rhin et apprecie l’interet des medecins et du personnel infirmier quant a la creation d’une « Equipe Mobile Plaies et Cicatrisation » (EMPC). Methodes Notre enquete, anonyme et de type transversal, s’appuyait sur les resultats de deux questionnaires, l’un concernant le malade, l’autre le personnel medical et infirmier. Resultats Quatre-vingt-seize malades sur les 1 163 hospitalises au moment de notre enquete repondaient aux criteres d’inclusion. La prevalence globale des plaies etait de 8,3 p. 100, celle des escarres 6,4 p. 100 et celle des ulceres de jambe 1,6 p. 100. Aucun cas de plaie sur pied diabetique n’a ete recense. La population etudiee se caracterisait par un sex-ratio H/F de 0,37, une moyenne d’âge de 86 ans pour les femmes et 76 ans pour les hommes. La duree d’evolution moyenne des escarres etait de 6 mois et de 14 mois pour les ulceres de jambe avec une recidive dans 36 p. 100 des cas d’escarres et 52,6 p. 100 des cas d’ulceres de jambe. L’etiologie des ulceres n’etait pas definie dans pres de la moitie des cas. Des prelevements bacteriologiques avaient ete effectues dans sept cas. Le nettoyage des plaies se faisait le plus souvent avec du savon et du serum physiologique. Une detersion mecanique avait ete pratiquee dans quatre cas. Les hydrocolloides etaient les pansements les plus prescrits dans la prise en charge des escarres, alors que les interfaces etaient les plus utilisees pour les ulceres de jambe. Aucune prescription d’antibiotique topique n’a ete relevee. Une echelle d’evaluation de la douleur n’avait ete utilisee que dans 18 cas, et une anesthesie de surface dans un cas, avant la detersion d’un ulcere de jambe. Une echelle d’evaluation du risque d’escarre avait ete remplie pour 27 des 75 malades atteints d’escarres et deux tiers d’entre eux etaient alites sur des matelas de type preventif. Douze des 19 malades atteints d’ulceres de jambe portaient des bandes de compression quotidiennement. La majorite des medecins jugeait bonnes ses connaissances dans le domaine des plaies chroniques, contrairement aux infirmiers qui dans 72 p. 100 des cas les estimaient moyennes voire insuffisantes. Tout le personnel infirmier et 11 des 13 medecins etaient interesses par la venue d’une equipe specialisee pour les cas difficiles. Discussion Les principales pratiques en adequation avec les recommandations etaient l’emploi de pansements modernes, bien que leur renouvellement semble trop frequent, l’utilisation anecdotique de solutions antiseptiques, l’abandon des antibiotiques topiques, la realisation d’un bilan nutritionnel. Deux tiers des malades atteints d’ulcere de jambe portaient des bandes de compression. En revanche, l’application d’anesthesiant de surface, la detersion manuelle, l’utilisation de grilles d’evaluation de la douleur et du risque d’escarre, la realisation du bilan etiologique des ulceres de jambes restent a optimiser. Conclusion Cette enquete, menee prealablement a la creation d’une « Equipe Mobile Plaies et Cicatrisations » basee aux Hopitaux Civils de Colmar, a pu mettre en evidence la forte motivation des medecins et du personnel infirmier pour beneficier d’une formation specifique ainsi que de conseils pratiques pour la prise en charge des plaies chroniques. Elle a permis de mieux cibler les besoins educatifs des etablissements de SSR et SLD dans le domaine de la prise en charge des plaies chroniques.

Otitis externa in dogs and cats is always caused by a combination of yeasts and bacteria, among which the most important are Malassezia pachydermatis, Staphylococcus intermedius and Pseudomonas species. These organisms often develop resistance to classical antimicrobial agents. Therefore, the aim of this study was to investigate the antimicrobial activities of an ethyl acetate leaf extract of Harungana madagascariensis against the organisms cited, to carry out the phytochemical investigation of this extract and to determine its bioactive chemical class using dilution techniques, the bioautography method and the standard phytochemical method described by Harborne (1973). Phytochemical analysis revealed the presence of saponins, tannins, flavonoids, alkaloids and anthracenic derivatives. The bioassay showed that the antimicrobial properties may be attributed to astilbin, a flavanone derivative identified on the basis of its spectroscopic data. The results suggest that the extract could be used in an antimicrobial preparation effective against the whole range of organisms incriminated in otitis externa in dogs and cats, with a minimal inhibitory concentration (MIC) of 250 μg/ml.

Novel features of DNA structure, recognition and discrimination have been recently elucidated through the solution structural characterization of DNA aptamers that bind cofactors, amino acids and peptides with high affinity and specificity. Multidimensional nuclear magnetic resonance methodologies have been successfully applied to solve the solution structures. In this work, it was demonstrated that capillary electrophoresis was a powerful tool allowing the fundamental study of the binding mechanism between a DNA aptamer and three ligands, adenosine and adenylate compounds, i.e., adenosine diphosphate (ADP) and adenosine triphosphate (ATP). In order to gain further insight into this binding, thermodynamic measurements under different values of parameters (such as salt nature and its concentration (x) in the run buffer) were carried out. The results showed that dehydration at the binding interface, van der Waals interactions, H-bonding and adjustment of the aptamer recognition surface were implied in the aptamer-ligand association. As well, it was demonstrated that the addition in the medium of the sodium monovalent cation Na(+) or the nickel divalent cation Ni(2+) decreased the complex formation. Separation efficiency and peak shape can also be improved by Mg(2+) divalent cation, which increased the mass transfer kinetics during the ligand-aptamer binding process. A significant separation for the worst separated pair of peaks on the electropherogram ((ADP, ATP) peak pair) was thus achieved.

The role of the Mg2+ cation on huperzine molecule binding (drugs used for Alzheimer disease) on human serum albumin (HSA) was studied by affinity chromatography. The thermodynamic data corresponding to this binding were determined for a wide range of Mg2+ concentrations (x). For each solute, the huperzine binding on HSA was divided into two Mg2+ concentration regions. For a low x value, below x c (1.2 mM), the binding decrease with x. For x above x c the hydrophobic effect and van der Waals interactions between the huperzine molecule and the HSA implied a decrease in its binding. These results showed that for patients with Alzheimer disease, an Mg2+ supplementation during treatment with these huperzine molecules can increase the active pharmacological molecule concentration.

In a previous manuscript [C. Andre, A. Berthelot, J.F. Robert, M. Thomassin, Y.C. Guillaume, J. Pharm. Bio. Med., in press], the Mg 2+ effect on the testosterone displacement equilibrium from its human serum albumin (HSA) binding site by DHEA was investigated using a thermodynamic approach. In this paper, a novel concept based on the competitive Langmuir distribution isotherms was proposed to calculate the association constant of the HSA–hormone binding and to confirm the Mg 2+ role on the testosterone displacement equilibrium from its HSA binding site by DHEA. Thus, both the HSA–hormone binding and the displacement equilibrium processes were reanalysed. The results obtained confirmed that: – DHEA and testosterone bound on the same HSA site; – DHEA displaced well testosterone to its HSA binding site; – Mg 2+ cation led a change on both the HSA–hormone binding and the displacement equilibrium at a critical Mg 2+ concentration x c around 1 mM.

In this paper, the effect of sucrose concentration ( x ) on the dehydroepiandrosterone (DHEA)–human serum albumin (HSA) binding was investigated by a biochromatographic approach. A mathematical development based on fractal geometry is proposed to provide a more realistic picture of the DHEA–HSA binding. The fractal dimension D of the cavity surface and the thermodynamic data of the binding mechanism were calculated at different sucrose concentrations in the bulk solvent. Results showed that under a critical sucrose concentration value x c (domain I), the enhancement of the DHEA–HSA binding intensity was principally due to the increase of hydrophobic interaction between DHEA and HSA cavity. Above x c (domain II), the salting-out agent levelled the HSA cavity surface irregularity and, consequently, the DHEA affinity for the HSA decreased. Moreover, for the domain II, the HSA–DHEA binding and the thermodynamic data are discussed using fractal concept of surface fluctuations.

Trimethylpsoralen (TMP) is often used to treat skin diseases (i.e., psoriasis, vitiligo, etc.). This drug permeates moderately the skin barrier. In the present study, we investigated the effect of formulation on the improvement of TMP skin bioavailability. Three formulations were performed. Each form (liposomes, nanospheres, and EtOH solution) contained 0.05% of TMP. For each preparation, the quantity deposited on the skin surface was 250 µg (Q0). The TMP percutaneous penetration through ex-vivo human skin was processed by Franz® cells (n=4) using a human albumin solution (1.4% w/v) as receiver medium. The percentages of the extracted TMP that permeated through the skin and that were retained in the skin over 24 h, were calculated with respect to Q0. The values obtained were reported, respectively, as follows: EtOH solution (1.33 vs. 0.08%), liposomes (0.93 vs. 0.93%), and PLG-nanospheres (0.79 vs. 3.01%). So, considering the correlation between the cumulated amounts of TMP permeated through the skin and the TMP stocked in the skin, the nanosphere form showed the higher quantity of TMP accumulated in the skin structures. On the other hand, the maximum value of the flux (ng/cm2/h) in the steady state of TMP incorporated in each formulation was at 6 h for all formulations: 173.5±1.06 (EtOH solution) > 120.4±1.06 (liposomes) > 93.82±0.88 (PLG-nanospheres). These results indicate that the controlled release of TMP by incorporation in PLG-nanospheres may increase drug content in the skin, while maintaining a minimal percutaneous absorption. Finally, this work shows that the PLG-nanospheres could constitute a promising approach for controlling TMP release in order to maintain its topical activity. Drug Dev. Res. 61:86–94, 2004. © 2004 Wiley-Liss, Inc.

The Ca 2+ cation effect on the antihypertensive molecule binding on human serum albumin (HSA) was studied by biochromatography. The thermodynamic parameters corresponding to this binding were determined for a wide range of Ca 2+ concentration ( x ). For the two antihypertensive molecules under study, their binding to HSA can be divided into two Ca 2+ cation concentration regions due to a HSA phase transition. This result was confirmed by an enthalpy-entropy investigation. For a low x value (below x c =1.6 mmol l −1 ), the HSA cavity was in an ordered solid-like state leading to an increase in the interactions between the antihypertensive drugs and the HSA cavity and consequently, a solute–HSA affinity increase. For x above x c , the HSA cavity was in a disordered solid-like state, implying a decrease in the antihypertensive drug–HSA binding.

The chiral recgonition mechanism for a series of phenoxypropionic acid herbicides was investigated in reversed phase liquid chromatography (RPLC) on a teicoplanin stationary phase over a wide range of column temperatures. Thermodynamic constants, of the transfer of an enantiomer from the mobile to the teicoplanin stationary phases were determined. The van't Hoff plots for all solutes had a break at a critical temperature T* showing a variation in the enantiomer retention mechanism due to a change in the conformational state of the teicoplanin, structure. Additionally, enthalpy-entropy compensation confirmed both the change in enantiomer interaction mechanism observed for regions T T* and the independence of this mechanism from (i) herbicide molecular structure,s i.e. the position of the chloro group on the phenol ring and (ii) the carbon absolute configuration. Moreover, the increasing enantioselectivity with increasing methanol fraction in the mobile phase was attributed to restriction of the solute association in the teicoplain, stationary phase, leading to favorable stereoselective interactions. This behavior was used to optimize chromatographic conditions for separation of herbicide enantiomers on teicoplanin.

Most of the cardioprotective effects of long-chain omega 3 fatty acids, namely docosahexaenoic (DHA; 22:6n-3) and eicosapentaenoic (EPA; 20:5n-3), are due to their hypotriglyceridemic and anti-inflammatory effects, which lower the risk for cardiovascular disease and myocardial infarction. Little is known on the direct preventive activities of DHA and EPA on heart function. In isolated hearts, we studied (1) whether infused DHA is able to protect the heart from ischemia/reperfusion damage and (2) the role played by Notch-mediated signal transduction pathways in myocardial infarction. Perfusion with DHA before and before/after induction of ischemia reperfusion significantly diminished cardiac damage and afforded antioxidant protection. Mechanistically, infusion of DHA before and before/after the induction of ischemia differentially modulated the expression of Notch2 and 3 target genes. In particular, DHA increased the expression of Hey1 when infused pre- and pre/post-ischemia; Jagged 1 and the Notch2 receptors increased with DHA pre-ischemia, but not pre/post; Notch2 and 3 receptors as well as Delta increased following DHA administration pre- and (especially) pre/post-ischemia. In conclusion, while the precise nature of the Notch-mediated protection from ischemia/reperfusion afforded by DHA is as yet to be fully elucidated, our data add to the growing body of literature that indicates how systemic administration of DHA provides cardiovascular protection.

Chromatographic temperature studies and differential scanning calorimetry have been used to elucidate the mechanism of retention of dansyl amino acids by human serum albumin (HSA) as stationary phase in reversed-phase liquid chromatography (RPLC) (Guillaume et al.,Anal. Chem. 1997,69, 4979). A novel mathematical development is proposed for description of HSA-dansyl amino acid association when HSA is used as mobile-phase modifier and C18 as stationary phase. The solute retention factor depends on the concentration of HSA in the bulk mobile phase and on the binding constant for the guest-HSA complex. The degree of complexationn c (the amount, %, of guest complexed) was determined. Enthalpy-entropy compensation was also analyzed in relation to this mathematical model to confirm the complexation behavior of the solute with HSA. Variation of the binding constant with the concentration of sodium phosphate, i.e. with the electrostatic force controlling HSA-solute association, is described. This theoretical model enabled estimation of the surface charge density (σ/F) and the accessible solvent surface area of the site II binding cavity; these were found to be approximately 8.7×10−7 mol m−2 and 2 nm2.

BACKGROUND Ethnicity, when it is used to mean shared genetic inheritance within a group, has become one of the most important factors in determining prostate carcinoma risk. Genetic polymorphisms were hypothesized to be the probable explanation for differences in risk among ethnic groups. The authors evaluated the association between polymorphisms in genes involved in the androgen biosynthesis and metabolism pathway and the risk of prostate carcinoma. METHODS Two hundred twenty-six patients with the pathologic diagnosis of sporadic prostate tumor and 156 healthy matched (age, ethnic group) male controls from a large epidemiologic cohort were genotyped for previously described polymorphisms in the androgen receptor (AR), 5α-reductase type II (SRD5A2), p450c17 (CYP17), and aromatase (CYP19) genes. The different polymorphisms in prostate carcinoma patients also were analyzed according to age of onset, preoperative prostate-specific antigen level, tumor stage, and tumor grade. RESULTS The distribution of the tetranucleotide simple tandem repeat polymorphism (STRP) in intron 4 of CYP19 was significantly different in control and cancer patients (P = 0.012). The 171 allele and the 187 allele were associated with prostate carcinoma risk (P = 0.05 and P = 0.045, respectively). Conversely, no association was observed between prostate carcinoma risk and the other polymorphisms studied as follow: the CAG repeat in exon 1 of AR, the (TA)n dinucleotide repeat polymorphism in the 3′ untranslated region, and the A49T or V89L substitutions in SDR5A2, the single base pair (bp) (a T to C transition) polymorphism that creates an additional Sp1-type (CCACC box) promoter site in CYP17. In prostate carcinoma patients, CAG repeats of AR, and TA repeats of SDR5A2 are associated with age of onset (P = 0.05 and P < 0.001, respectively). CONCLUSIONS The association between the 171-bp allele of CYP19 and prostate carcinoma risk suggests that aromatase could be used as a new indicator for prostate carcinoma prevention in men of White French ethnogeographic origin. Conversely, it is possible that an individual carries both a high- and a low-risk marker (e.g., CYP17 A2 allele and V89L in SRD5A2) resulting in no overall difference in risk observed across the population. For these reasons, the development of a polygenic model, incorporating multiple loci from the individual genes may maximize the chance of identifying individuals with high-risk genotypes. Cancer 2001;92:1130–7. © 2001 American Cancer Society.

A chemometric method was applied to investigate the binding mechanism of Ca2+ and Mg2+ to human serum albumin (HSA) using a bio-chromatographic approach. The effects of the bulk solvent pH, its ionic strength and column temperature on the transfer of Ca2+ and Mg2+ from the bulk solvent to immobilized human serum albumin as a stationary phase were studied. Thermodynamic parameters corresponding to this transfer were determined from linear van’t Hoff plots. Enthalpy-entropy compensation revealed that the ion binding mechanism to HSA was independent of ionic strength and pH, and the same for the two cations. The results corroborated the fact that HSA can be assimilated by a weak cation-exchanger and the Ca-HSA (or Mg-HSA) binding is controlled by electrostatic attraction for different “non specific” areas of serum albumin.

The effect of perchlorate anion as mobile phase modifier on the separation factor, α, forN-(dansyl)-dl-norvaline andN-(dansyl)-dl-tryptophan on a human serum albumin (HSA) column was studied by varying the concentration,c, of the chaotropic agent and the column temperatureT. Gibbs-Helmholtz parameters Δ(ΔH) and Δ(ΔS) between thed andl enantiomers were determined from linear van't Hoff plots of lnα against 1/T. Thermodynamic results indicated that the enhancement of the separation factor observed asc was increased was enthalpically controlled owing to stereoselective H-bonding interactions. Such behavior was used to optimize the chromatographic conditions for separation ofN-(dansyl)-amino acids on HSA.

Bacteremic pasteurellosis is an uncommon form of Pasteurella multocida infection, usually involved in local infections. This systemic infection often occurs in immuno-compromised patient such as cirrhotic or alcoholic patients, with a high mortality rate (up to 60%). Septic shock may occur and neurological disorders or coma are frequent. We report such a case. Treatment associated local care, antibiotics (beta-lactam antibiotics plus fluoroquinolone) during 14 days and resuscitation of septic shock. Owing these therapies, septic shock was successfully treated without complications.

Sarcoidosis or granulomatous reactions have rarely been reported in association with malignant melanoma (MM). We describe seven patients who presented with both granulomatous disease and MM, and discuss the physiopathological and prognostic significance of this association. In three patients, the granulomatosis was diagnosed as true sarcoidosis and in one patient, as tumour-associated granuloma. In three cases, designated here as atypical tumour-associated granulomatoses, the presence of clear-cut pulmonary granulomatous nodules was typical neither for sarcoidosis nor for tumour-associated granuloma and was highly suggestive of melanoma metastases. Mediastinal lymphadenopathy was present in every patient. In all seven patients, the question of mediastinal or pulmonary involvement or relapse of the MM was raised, but could be confirmed in only one patient. MM can be associated with granulomatous disease. Knowledge of this association has implications in the management of patients with MM.

Resume Introduction Les dermites de contact purpuriques sont rares et mal connues. Observation Un malade de 27 ans, ayant des antecedents personnels de dermatite atopique dans l’enfance, a consulte pour une eruption papulo-purpurique chronique evoluant depuis 7 ans. Le prurit etait modere. Les lesions touchaient de maniere profuse les paumes, les plantes, les membres superieurs et inferieurs, epargnant le tronc. Il s’agissait de papules purpuriques, parfois crouteuses, confluant en larges plaques. Le tableau evoquait en premier lieu une vasculite, mais l’examen histologique et les examens paracliniques eliminaient ce diagnostic. Les tests epicutanes etaient en faveur d’une dermite de contact au chrome. L’interrogatoire oriente retrospectif confirmait la pertinence du test en revelant le port regulier de vetements en cuir. Une guerison durable etait observee apres eviction de l’allergene. Discussion Les dermatoses purpuriques de contact sont rares. Elles ont essentiellement ete decrites pour des allergenes constituants du caoutchouc ou des colorants vestimentaires. Notre observation est remarquable par l’intensite des lesions, simulant une vasculite et par l’originalite de l’allergene incrimine, le chrome, present dans des vetements en cuir. Elle souligne l’interet des tests cutanes systematiques devant une dermatose chronique non etiquetee. Il s’agit, a notre connaissance, du premier cas decrit de dermite de contact purpurique au chrome.

Resume Introduction La fluindione est un anticoagulant de la famille des antivitamines K largement prescrit en France. Si ses effets secondaires hemorragiques sont classiques, les reactions de toxicite immunoallergique sont en revanche moins bien connues. Nous rapportons un cas de syndrome d’hypersensibilite a la fluindione. Observation Une femme de 75 ans etait hospitalisee pour une eruption erythemato-papuleuse diffuse associee a un œdeme intense du visage. Les symptomes etaient apparus 3 semaines apres l’introduction d’un traitement par fluindione, allopurinol et perindopril. Les examens biologiques objectivaient une hyperleucocytose avec eosinophilie, une hepatite mixte et une insuffisance renale moderee. L’ensemble etait tres evocateur d’un syndrome d’hypersensibilite medicamenteuse. Alors que l’allopurinol et le perindopril etaient arretes, la fluindione etait transitoirement interrompue en raison d’un surdosage. Sa reintroduction entrainait une recidive rapide et plus intense de la symptomatologie clinique et biologique. L’arret du traitement permettait une regression complete des symptomes. Les tests epicutanes realises a distance etaient positifs avec la fluindione, negatifs avec le perindopril et l’allopurinol. Discussion Cette observation est caracteristique d’un syndrome d’hypersensibilite medicamenteuse a la fluindione avec un test de reintroduction et des tests epicutanes positifs. Peu de syndromes d’hypersensibilite a la fluindione ont ete rapportes dans la litterature, alors que cette molecule est largement prescrite en France. L’atteinte cutanee peut etre absente. Les manifestations immunoallergiques comme la fievre, les hepatites, les nephropathies tubulo-interstitielles rapportees au cours de traitements par la fluindione pourraient etre rattachees a ce syndrome. Les tests epicutanes, de realisation simple, peuvent constituer une aide precieuse pour etablir la responsabilite du medicament.

The interaction of a series of steroid hormones (DHEA, progesterone, testosterone, estradiol) with serum albumin immobilized on porous silica particles and the effect of reactive oxygen species and nitric oxide on this interaction were studied using a biochromatographic approach. The determination of enthalpy and entropy changes of this binding indicated that van der Waals interactions and hydrogen bonds predominated the hormone association with albumin. Reactive oxygen species (H 2 O 2 and OH ) increased the hormone binding affinity to albumin. On the other hand, this binding was decreased with the presence of NO . This variation was due to conformational changes in the binding region explained by the oxidation of some residues such as free thiol and arginine. The thermodynamic analysis showed that free radical affects the van der Waals forces and/or a hydrogen bond of the hormone binding with albumin. These results explained the role of reactive oxygen species and nitric oxide in the hormone free fraction level in the blood.

Objective: Cast nephropathy, due to free light chain (FLC) toxicity, is the main cause of acute kidney injury in multiple myeloma, with about 10% of patients requiring dialysis. In these patients, in addition to chemotherapy that prevents FLC production, daily hemodialysis using high cutoff or adsorptive membranes, showed promising results by decreasing quickly toxic serum FLC concentrations. Case history: We report here the case of 2 patients presenting with acute kidney injury and high FLC serum concentration and M-components one with IgG Kappa and the other with IgD lambda. Both were treated with bortezomib and dexamethasone and received a 24-h continuous hemodialysis using a high and sharp cutoff (around 35,000 Daltons) polysulfone membrane (ultraflux ® HD 1000, Fresenius Medical Care GmbH, Bad Homburg, Germany) with citrate regional anticoagulation using a safe and dedicated device (multi filtrate Ci-Ca ® ). Conclusion: Despite similar range of depuration, serum plasma FLC decreased importantly in the patient with the kappa type who recovered but was unchanged in the lambda type patient who remained under maintenance dialysis. Further studies are needed to confirm this new approach therapy.

The acetylcholinesterase enzyme (AChE) was immobilized on a chromatographic support to study the effect of magnesium on the binding mechanism of five AChE inhibitors (donepezil, tacrine, galanthamine, physostigmine and huperzine). The determination of the enthalpy and entropy changes of this binding at different magnesium concentration values suggested that van der Waals interactions and hydrogen bonds predominated the donepezil and tacrine association to AChE. As well, hydrophobic and electrostatic forces seemed to be the major interactions controlling the huperzine, galanthamine and physostigmine association with AChE. In addition, it appeared that magnesium cation increased the binding affinity of galanthamine and physostigmine to the active site gorge of AChE. A comparison of the inhibitors hydrophobicity to their relative bound percentage with AChE showed an affinity enhanced with the increase in the molecule hydrophobicity and confirmed that the hydrophobic forces played an important role in the AChEI-AChE binding process. This novel biochromatographic column could be useful to find a specific inhibitor for this enzyme and so open new perspectives to be investigated.

A biochromatographic approach is developed to measure for the first time thermodynamic data and magnesium (Mg(2+)) effect for the binding of testosterone (TT) to sex hormone-binding globulin (SHBG) in a wide temperature range. For this, the SHBG was immobilized on a chromatographic support. It was established that this novel SHBG column was stable during an extended period of time. The affinity of TT to SHBG is high and changes slightly with the Mg(2+) concentration because the number of Mg(2+) linked to binding is low. The determination of the testosterone retention with the steroid hormone at different Mg(2+) concentrations and temperatures demonstrated that the Mg(2+) binding heat effect associated with this Mg(2+) release or uptake during this binding was in magnitude around 17kJ/mol corresponding to the model describing the electrostatic attraction that occurs between the negatively charged non specific areas of SHBG and the positively charged of magnesium. At all the magnesium concentrations studied, the DeltaH values were negative due to van der Waals interactions and hydrogen bonding which are engaged at the complex interface confirming strong TT-SHBG hydrogen bond networks. As well, the DeltaS values were all positive due to hydrophobic forces in the testosterone-SHBG complex formation. In addition our results suggest that adaptive conformational transitions contribute to the specific testosterone-SHBG complex formation. As well, in the biological Mg(2+) concentration domain, it was clearly demonstrated that there was an uncompetitive inhibition of Mg(2+) on TT-SHBG binding which led an enhancement of bioavailable TT. Our work indicated that our biochromatographic approach could soon become very attractive for study other SHBG-steroid (or phytoestrogen) binding.

A double blind, placebo-controlled trial was performed to test the efficacy of prevention of nosocomial infections by selective digestive decontamination. Placebo or tobramycin (80 mg) and colistin (100 mg) was given four times daily via the gastric tube. Amphotericin B (500 mg/6 h) was administered to all patients. As our ICU is divided into two separate subunits, intestinal decontamination or placebo was administered alternatively to patients of the two subunits during two 3-month periods, separated by a 2-month period without prevention. The decontamination (n = 97) and placebo groups (n = 84) were similar with respect to age, sex, severity score and diagnostic categories on admission. Intestinal decontamination alone failed to significantly reduce the number of infected patients (26% vs 34.5%, p = 0.20), but was effective on ICU-acquired infections (0.33 vs 0.60, p = 0.02) especially gram-negative infection rates (0.17 vs 0.43, p = 0.01). The onset of the first ICU-acquired infection was delayed (9 vs 13 days, p less than 0.001) and incidence of pneumonia (2 vs 13 cases, p less than 0.01) including bacterial pneumonia (0 vs 8 cases, p less than 0.01) was significantly decreased. However, mean ICU stay and mortality were not significantly modified by intestinal decontamination.

In this work, the interaction of a series of acetylcholinesterase inhibitors (AChEIs; donepezil, galanthamine, huperzine and neostigmine) with human serum albumin (HSA) immobilized on porous silica particles was studied using a biochromatographic approach. For all the tested AChEI molecules, linear retention plots were observed at all temperatures. An analysis of the thermodynamics (i.e. enthalpy (DeltaH degrees ), entropy ((S degrees *)) of the interaction of the AChEI molecules with the immobilized human serum albumin was also carried out. The (H degrees and (S degrees * values for donepezil, galanthamine and neostigmine, were negative due to van der Waals interactions and hydrogen bonding which govern this association with albumin. Whereas the positive values of (H degrees and (S degrees * of huperzine binding on HSA indicated a predominance of hydrophobic interactions. The association of AChEIs with HSA was increased linearly with pH. A comparative thermodynamic study with benzodiazepine molecules was also done to determine the potential binding site of these drugs on HSA.

In this paper, we present an automatic, robust and reliable process to quantify liver steatosis. The degree of steatosis is a useful marker of steatohepatitis. This degree is routinely assessed visually by an expert and then lacks of accuracy and robustness. The process that we have developed is divided in two steps. A fuzzy classification first merges into classes pixels according to their intensity. We use a generalized objective function that allows to detect micro and blurredness vacuoles of steatosis. Then, regions with inhomogeneous texture and irregular shape were eliminated with compactness and standard deviation parameters. The obtained results are good correlated with expert graduation (in five levels). A better correlation is obtained with a more precise grading.

International audience; The retention of 8-methoxypsoralen (8-MOP) on an immobilised hydroxypropyl-beta-cyclodextrin (HP-beta-CD) column was analysed in HPLC by the determination of its Langmuir distribution isotherm. A such method was used to confirm the potential drug complexing role of this cyclodextrin. The 8-MOP/HP-beta-CD association constant (K) was equal to 29.5 and 18.7 M-1, respectively, at a temperature equal to 5 and 25 degrees C, respectively. These association constant values were used to determine the cytotoxicity profile of human keratinocyte cell line (HaCaT) in relation to the complex concentration. It was showed through these data that HP-beta-CD had a cytoprotective since a reverse effect of HP-beta-CD on 8-MOP cytotoxicity was observed.

The mechanisms of (i) the binding of two sex-hormones (i.e. progesterone and beta-estradiol) to human serum albumin (HSA) and (ii) the progesterone displacement of its HSA binding cavity by beta-estradiol were studied by biochromatography using three different methods. In the first time, zonal elution method was used to prove the direct competition effect between the two sex-hormone. In the second time, the competition effect between beta-estradiol and progesterone to bound on the same HSA site was analysed by the competitive bi-Langmuir approach. Finally, the thermodynamic data of these two binding processes were studied. The Gibbs free energy value (Delta(approximately)G degrees) of the displacement equilibrium was negative demonstrating that beta-estradiol displaced progesterone of its HSA binding cavity. Moreover, the effect of two chloride modifiers (i.e. Na(+), Mg(2+)) on these two binding processes were analysed. Results showed that in the salt biological concentration ranges, the Mg(2+) cation enhanced strongly the bioavailable progesterone, whereas the Na(+) cation interacted slowly on the progesterone displacement of its HSA binding site by beta-estradiol. This study showed that it must be useful to carry out more in vivo test on the magnesium supplementation effect for women who suffer from estrogen dominance syndrome.

In this paper, a new and efficient method for synthesis of phloroglucinol with an overall yield of 60% was described. As well, the phloroglucinol association on an immobilized human serum albumin (HSA) column was analyzed in biochromatography by the determination of its Langmuir distribution isotherms. The role of the magnesium cation Mg2+ on the phloroglucinol-HSA binding process was as well analyzed. The results showed that in the Mg2+ concentration range (0.7-2 mM) (including its biological concentration range, i.e. 0.75-0.90 mM), increasing the Mg2+ concentration increased the fraction of free phloroglucinol (not linked with HSA) and thus its biological effect.

Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.

In previous studies the degree of embolization detected by transoesophageal echocardiography (TEE) during cemented total hip arthroplasty (THA) did not correlate with changes in haemodynamic variables nor did it result in persistent ventilation-perfusion mismatching. The aim of this study was to record evidence of embolism and to relate the findings to demographic data and the subsequent clinical course of the patients during THA.Forty-eight patients scheduled to undergo elective cemented THA during general anaesthesia were monitored. A TEE probe was inserted with special attention to the right atrium (RA), the right ventricle (RV) Haemodynamic (heart rate, arterial blood pressure, central venous pressure) and blood-gas variables were measured repeatedly during the operative procedure (after induction, placement of the acetabular component, placement of the femoral component, relocation of the hip joint). Grading of venous embolism at these times was based on the size of particles detected by TEE (three-minutes video segments of each periods) and correlated with demographic, haemodynamic and blood-gas data.The TEE monitoring revealed showers of echogenic material traversing the RA and RV in all but one patients during reaming and cementing of the acetabular and femoral components, and during relocation of the hip joint. No correlation was observed between frequency or size of embolic particles and demographic or blood-gas and haemodynamic variables studied at the same times.This study failed to show any clinical impact of TEE detected emboli during cemented THA.