Rosmarinic Acid and Its Methyl Ester as Antimicrobial Components of the Hydromethanolic Extract of Hyptis atrorubens

Primary biological examination of four extracts of the leaves and stems of Hyptis atrorubens Poit. (Lamiaceae), a plant species used as an antimicrobial agent in Guadeloupe, allowed us to select the hydromethanolic extract of the stems for further studies. It was tested against 46 microorganisms in vitro. It was active against 29 microorganisms. The best antibacterial activity was found against bacteria, mostly Gram-positive ones. Bioautography enabled the isolation and identification of four antibacterial compounds from this plant: rosmarinic acid, methyl rosmarinate, isoquercetin, and hyperoside. The MIC and MBC values of these compounds and their combinations were determined against eight pathogenic bacteria. The best inhibitory and bactericidal activity was found for methyl rosmarinate (0.3 mg/mL). Nevertheless, the bactericidal power of rosmarinic acid was much faster in the time kill study. Synergistic effects were found when combining the active compounds. Finally, the inhibitory effects of the compounds were evaluated on the bacterial growth phases at two different temperatures. Our study demonstrated for the first time antimicrobial activity of Hyptis atrorubens with identification of the active compounds. It supports its traditional use in French West Indies. Although its active compounds need to be further evaluated in vivo, this work emphasizes plants as potent sources of new antimicrobial agents when resistance to antibiotics increases dramatically

Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links

BACKGROUND: Evidence for an increased prevalence of candidaemia and for high associated mortality in the 1990s led to a number of different recommendations concerning the management of at risk patients as well as an increase in the availability and prescription of new antifungal agents. The aim of this study was to parallel in our hospital candidemia incidence with the nature of prescribed antifungal drugs between 1993 and 2003. METHODS: During this 10-year period we reviewed all cases of candidemia, and collected all the data about annual consumption of prescribed antifungal drugs RESULTS: Our centralised clinical mycology laboratory isolates and identifies all yeasts grown from blood cultures obtained from a 3300 bed teaching hospital. Between 1993 and 2003, 430 blood yeast isolates were identified. Examination of the trends in isolation revealed a clear decrease in number of yeast isolates recovered between 1995–2000, whereas the number of positive blood cultures in 2003 rose to 1993 levels. The relative prevalence of Candida albicans and C. glabrata was similar in 1993 and 2003 in contrast to the period 1995–2000 where an increased prevalence of C. glabrata was observed. When these quantitative and qualitative data were compared to the amount and type of antifungal agents prescribed during the same period (annual mean defined daily dose: 2662741; annual mean cost: 615629 €) a single correlation was found between the decrease in number of yeast isolates, the increased prevalence of C. glabrata and the high level of prescription of fluconazole at prophylactic doses between 1995–2000. CONCLUSION: Between 1993 and 2000, the number of cases of candidemia halved, with an increase of C. glabrata prevalence. These findings were probably linked to the use of Fluconazole prophylaxis. Although it is not possible to make any recommendations from this data the information is nevertheless interesting and may have considerable implications with the introduction of new antifungal drugs

Ploidy of Cell-Sorted Trophic and Cystic Forms of Pneumocystis carinii

Once regarded as an AIDS-defining illness, Pneumocystis pneumonia (PcP) is nowadays prevailing in immunocompromised HIV-negative individuals such as patients receiving immunosuppressive therapies or affected by primary immunodeficiency. Moreover, Pneumocystis clinical spectrum is broadening to non-severely-immunocompromised subjects who could be colonized by the fungus while remaining asymptomatic for PcP, thus being able to transmit the infection by airborne route to susceptible hosts. Although the taxonomical position of the Pneumocystis genus has been clarified, several aspects of its life cycle remain elusive such as its mode of proliferation within the alveolus or its ploidy level. As no long-term culture model exists to grow Pneumocystis organisms in vitro, an option was to use a model of immunosuppressed rat infected with Pneumocystis carinii and sort life cycle stage fractions using a high-through-put cytometer. Subsequently, ploidy levels of the P. carinii trophic and cystic form fractions were measured by flow cytometry. In the cystic form, eight contents of DNA were measured thus strengthening the fact that each mature cyst contains eight haploid spores. Following release, each spore evolves into a trophic form. The majority of the trophic form fraction was haploid in our study. Some less abundant trophic forms displayed two contents of DNA indicating that they could undergo (i) mating/fusion leading to a diploid status or (ii) asexual mitotic division or (iii) both. Even less abundant trophic forms with four contents of DNA were suggestive of mitotic divisions occurring following mating in diploid trophic forms. Of interest, was the presence of trophic forms with three contents of DNA, an unusual finding that could be related to asymmetrical mitotic divisions occurring in other fungal species to create genetic diversity at lower energetic expenses than mating. Overall, ploidy data of P. carinii life cycle stages shed new light on the complexity of its modes of proliferation

Candida albicans et maladie de Crohn

La maladie de Crohn (MC) est avec la rectocolite hémorragique (RCH) une des formes de Maladies Inflammatoires Chroniques de l'Intestin (MICI). L'étiologie de la MC reste encore inconnue. Cependant, il est établi que les mécanismes physiopathologiques de la MC reposent sur des facteurs de susceptibilité génétique, des facteurs environnementaux, associés à une dérégulation de la réponse immunitaire intestinale, notamment vis-à-vis de la flore endogène. Parallèlement au processus inflammatoire responsable des lésions, les patients développent une réponse humorale dirigée contre différents antigènes microbiens. Parmi eux, des anti-levures sont fréquemment rapportés chez les patients atteints de MC. Il s'agit des anticorps anti-Saccharomyces cerevisiae. Le laboratoire est à l'origine du test immuno-enzymatique de détection de ces anticorps, qui utilise le mannane d'une souche de S. cerevisiae (SU1) et qui ont été dénommés ASCA. Les premières études séro-épidemiologiques issues du laboratoire ont montré que les ASCA sont présents chez 60% des patients atteints de MC et 10% des patients atteints de RCH. Ils sont également présents chez 20 à 25% des parents sains du premier degré de patients atteints de MC, contre seulement 7% dans la population témoin. Les ASCA sont maintenant largement utilisés par les gastroentérologues pour le diagnostic et la stratification phénotypique des patients MC. Malgré de nombreuses publications sur les ASCA comme marqueur de la MC, l'immunogène et les mécanismes à l'origine de leur production sont toujours inconnus. La première étape a consisté à étudier l'influence de la génétique sur les ASCA, par l'étude de leur prévalence chez des jumeaux monozygotes et dizygotes atteints de MICI. Nos résultats suggèrent que les ASCA serait le marqueur d'une réponse à un antigène environnemental, dont le niveau de réponse serait génétiquement déterminé. L'étape suivante a concerné la recherche d'un immunogène pour les ASCA. Nous avons exploré si, contrairement à la levure exogène S. cerevisiae, Candida albicans, une levure commensale du tube digestif humain, mais aussi un pathogène fongique opportuniste majeur, pouvaient exprimer les épitopes majeurs reconnus par les ASCA. Un programme en plusieurs étapes, basé sur des observations cliniques et des études expérimentales sur les relations structure/immunogénicité des oligomannosides de levures dans la MC et dans les candidoses nous a permis de démonter que C. albicans peut être un immunogène à l'origine des ASCA. Ces conclusions nous ont conduits à étudier les relations entre la colonisation intestinale par C. albicans, les réponses sérologiques anti-levures, et le génotype des patients dans des familles affectées par la MC. Nous avons confirmé que la colonisation par C. albicans influence à la fois la production des anticorps anti-C. albicans et des ASCA chez les parents sains des patients MC. Chez les patients atteints, les ASCA étaient indépendants de la colonisation par C. albicans. Cependant nous avons pu observer une corrélation entre la colonisation par C. albicans et la seropositivité ASCA chez les patients MC positifs en anticorps anti-C. albicans. Ces résultats renforcent notre conclusion que C. albicans est un immunogène pour les ASCA chez l'homme. L'ensemble de ces travaux, qui correspondent à une première étape dans la description des mécanismes à l'origine de la synthèse des ASCA, nous a permis de faire progresser nos connaissances dans le domaine de la physiopathologie de la MC.LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Les pathologies du cheveu et du cuir chevelu (traitements et conseils à l'officine)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Effects of surgical facemasks on perceived exertion during submaximal exercise test in healthy children.

Only a few data associated to wearability of facemask during exercise are available in children. The aim of the study was to evaluate the effect of wearing a facemask on perceived exertion (primary aim), dyspnea, physical performance, and cardiorespiratory response during a submaximal exercise test in children aged between 8 and 12 years. This study was performed in 2021 in healthy volunteer children from 8 to 12 years. They performed prospectively two 1-min sit-to-stand tests (STST), with or without a surgical facemask. The perceived exertion (modified Borg scale), dyspnea (Dalhousie scale), heart rate, and pulsed oxygen saturation were recorded before and after STST. The STST measured the submaximal performance. Thirty-eight healthy children were recruited (8-9 years: n = 19 and 10-11 years: n = 19). After the STST, the perceived exertion increased with or without a facemask (8-9 years group: + 1 [0.6; 1.4] and + 1.6 [1.0; 2.1] - 10-11 years group: + 1.3 [0.7; 1.8] and + 1.9 [1.3; 2.6]) and it was higher with the facemask. The difference between the two conditions in perceived exertion was not clinically relevant in any group (mBorgf: 0.56 pts and 0.68 pts, respectively). The different domains of dyspnea assessed with Dalhousie scale were not influenced by the facemask. The submaximal performance measured by the STST was not changed by the mask whatever the age group. The cardio-respiratory demand was not clinically modified.Conclusion: The surgical facemask had no impact on dyspnea, cardiorespiratory parameters, and exercise performance during a short submaximal exercise in healthy children

Colonization of Mice by Candida albicans Is Promoted by Chemically Induced Colitis and Augments Inflammatory Responses through Galectin‐3

International audienc

Treatment with P28GST, a schistosome-derived enzyme, after acute colitis induction in mice: Decrease of intestinal inflammation associated with a down regulation of Th1/Th17 responses.

BackgroundP28GST, a 28Kd glutathione S-transferase enzymatic protein derived from a schistosome helminth prevents experimental colitis when administered subcutaneously in the presence of adjuvant by decreasing pro-inflammatory Th1/Th17 response. Given the antioxidant properties of P28GST, we evaluated its anti-inflammatory potential when administered locally after colitis induction in the absence of adjuvant.MethodsColitis was induced in BALB/c mice by rectal administration of TNBS, followed by two intraperitoneal injections of P28GST at day 1 and day 2. Mice were sacrificed 48h after TNBS administration and evaluated for macroscopic and histological scores, myeloperoxidase (MPO) quantification and cytokine messenger RNA expression in the colonic tissues.ResultsBoth clinical and histological scores significantly decreased in mice treated with P28GST at 5 or 50μg/kg when compared to vehicle- treated mice. A significant reduction of MPO was detected in colonic tissues from P28GST-treated mice, similarly to mice treated with methylprednisolone as the reference treatment. Pro-inflammatory cytokines TNF, IL-1β, and IL-6, mRNA as well as serum levels were down-regulated in mice colonic tissues treated with P28GST at 5 or 50μg/kg. In addition, a significant decrease of mRNA expression levels of T-bet, and ROR-γ, respective markers of Th1 and Th17 cells was observed. Whereas no significant effect was detected on Gata3 mRNA, a marker of Th2 cells, the Arg/iNOS mRNA levels significantly increased in P28GST-treated mice, suggesting the induction of M2 macrophages.ConclusionsThese findings provide evidence that P28GST injected locally after colitis induction induces a potent decrease of colitis inflammation in mice, associated to downregulation of Th1/Th17 response, and induction of anti-inflammatory alternatively activated macrophages

The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn's disease.

International audienceBACKGROUND: Crohn's disease (CD) is associated with elevated anti-glycans antibody response in 60% of CD patients, and 25% of healthy first-degree relatives (HFDRs), suggesting a genetic influence for this humoral response. In mice, anti-glucan antibody response depends on the NLRP3 inflammasome. Here, we explored the effect of mutated CARD8, a component of the inflammasome, on anti-glycans antibody response in human. METHODS: The association between p.C10X mutation (rs2043211) of the CARD8 gene and the levels of anti-glycans antibody response was examined in 39 CD families. The family-based QTDT association test was used to test for the genetic association between CARD8 p.C10X mutation and anti-glycan antibodies in the pedigrees. The difference in antibody responses determined by ELISA was tested in a subgroup of CD probands (one per family) and in a subgroup of HFDRs using the Wilcoxon Kruskal Wallis non-parametric test. RESULTS: The QTDT familial transmission tests showed that the p.C10X mutation of CARD8 was significantly associated with lower levels of antibody to mannans and glucans but not chitin (p=0.024, p=0.0028 and p=0.577, for ASCA, ALCA and ACCA, respectively). These associations were independent of NOD2 and NOD1 genetic backgrounds. The p.C10X mutation significantly associated or displayed a trend toward lower ASCA and ALCA levels (p=0.038 and p=0.08, respectively) only in the subgroup of CD probands. Such associations were not significant for ACCA levels in both subgroups of CD probands and of HFDRs. CONCLUSION: Our results show that ASCA and ALCA but not ACCA levels are under the influence of CARD8 genotype. Alteration of CARD8, a component of inflammasome, is associated with lower levels of antibodies directed to mannans and glucans at least in CD patients