Cortical Representation of Tympanic Membrane Movements due to Pressure Variation: An fMRI Study

Middle ear sensory information has never been localized in the homunculus of the somatosensory cortex (S1). We investigated the somatosensory representation of the middle ear in 15 normal hearing subjects. We applied small air pressure variations to the tympanic membrane while performing a 3T-fMRI study. Unilateral stimulations of the right ear triggered bilateral activations in the caudal part of the postcentral gyrus in Brodmann area 43 (BA 43) and in the auditory associative areas 42 (BA 42) and 22 (BA 22). BA 43 has been found to be involved in activities accompanying oral intake and could be more largely involved in pressure activities in the oropharynx area. The tympanic membrane is indirectly related to the pharynx area through the action of tensor tympani, which is a Eustachian tube muscle. The Eustachian tube muscles have a role in pressure equalization in the middle ear and also have a role in the pharyngeal phase of swallowing. Activation of BA 42 and BA 22 could reflect activations associated with the bilateral acoustic reflex triggered prior to self-vocalization to adjust air pressure in the oropharynx during speech. We propose that BA 43, 42, and 22 are the cortical areas associated with middle ear function. We did not find representation of tympanic membrane movements due to pressure in S1, but its representation in the postcentral gyrus in BA 43 seems to suggest that at least part of this area conveys pure somatosensory information

Biosynthesis and Toxicological Effects of Patulin

Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects

Tests cognitifs utilisables par le médecin généraliste pour le diagnostic précoce de la maladie d'Alzheimer (revue de la littérature dans la base de données Medline de 1995 à septembre 2005)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Intérêt des anticorps recombinants dans la protection médicale contre les agents du bioterrorisme : l'exemple de la maladie du charbon

Les anticorps recombinants forment une classe thérapeutique en plein essor ; ils sont particulièrement bien adaptés à la prise en charge du risque biologique agressif grâce à leur action immédiate et fréquemment synergique avec les autres molécules thérapeutiques existantes, leur longue demi-vie et leur bonne tolérance. Le charbon est une maladie de première importance concernant ce risque, et sa pathogénie dépend de toxines qui peuvent être neutralisées par les anticorps. Ces toxines sont formées par l'association de trois types de sous-unités (PA, LF, EF). Plusieurs anticorps recombinants anti-PA ont été développés, y compris par notre équipe, en utilisant une approche originale. Nous avons également développé un anti-LF, conformément aux recommandations des experts. Notre anticorps anti-PA, et dans une moindre mesure notre anti-LF, seront présentés

Cortical Representation of Tympanic Membrane Movements due to Pressure Variation: An fMRI Study

Middle ear sensory information has never been localized in the homunculus of the somatosensory cortex (S1). We investigated the somatosensory representation of the middle ear in 15 normal hearing subjects. We applied small air pressure variations to the tympanic membrane while performing a 3T-fMRI study. Unilateral stimulations of the right ear triggered bilateral activations in the caudal part of the postcentral gyrus in Brodmann area 43 (BA 43) and in the auditory associative areas 42 (BA 42) and 22 (BA 22). BA 43 has been found to be involved in activities accompanying oral intake and could be more largely involved in pressure activities in the oropharynx area. The tympanic membrane is indirectly related to the pharynx area through the action of tensor tympani, which is a Eustachian tube muscle. The Eustachian tube muscles have a role in pressure equalization in the middle ear and also have a role in the pharyngeal phase of swallowing. Activation of BA 42 and BA 22 could reflect activations associated with the bilateral acoustic reflex triggered prior to self-vocalization to adjust air pressure in the oropharynx during speech. We propose that BA 43, 42, and 22 are the cortical areas associated with middle ear function. We did not find representation of tympanic membrane movements due to pressure in S1, but its representation in the postcentral gyrus in BA 43 seems to suggest that at least part of this area conveys pure somatosensory information

Antibodies against Anthrax Toxins: A Long Way from Benchlab to the Bedside

Anthrax is an acute disease caused by the bacterium Bacillus anthracis, and is a potential biowarfare/bioterrorist agent. Its pulmonary form, caused by inhalation of the spores, is highly lethal and is mainly related to injury caused by the toxins secretion. Antibodies neutralizing the toxins of B. anthracis are regarded as promising therapeutic drugs, and two are already approved by the Federal Drug Administration. We developed a recombinant human-like humanized antibody, 35PA83 6.20, that binds the protective antigen and that neutralized anthrax toxins in-vivo in White New Zealand rabbits infected with the lethal 9602 strain by intranasal route. Considering these promising results, the preclinical and clinical phase one development was funded and a program was started. Unfortunately, after 5 years, the preclinical development was cancelled due to industrial and scientific issues. This shutdown underlined the difficulty particularly, but not only, for an academic laboratory to proceed to clinical development, despite the drug candidate being promising. Here, we review our strategy and some preliminary results, and we discuss the issues that led to the no-go decision of the pre-clinical development of 35PA83 6.20 mAb. Our review provides general information to the laboratories planning a (pre-)clinical development

Efficacy of a Vaccine Based on Protective Antigen and Killed Spores against Experimental Inhalational Anthrax▿ ‡

Protective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA-FIS and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to recombinant anthrax PA from Bacillus anthracis (rPA)-FIS administered by various immunization protocols and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain of B. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal immunoglobulin G response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and antispore antibody were also significantly higher: nine and eight times higher, respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulent B. anthracis strain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 50% lethal doses (LD50) and against an aerosol with 75 LD50 of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax