103 research outputs found

    Procedures and Frequencies of Embalming and Heart Extractions in Modern Period in Brittany. Contribution to the Evolution of Ritual Funerary in Europe.

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    The evolution of funeral practices from the Middle Ages through the Modern era in Europe is generally seen as a process of secularization. The study, through imaging and autopsy, of two mummies, five lead urns containing hearts, and more than six hundred skeletons of nobles and clergymen from a Renaissance convent in Brittany has led us to reject this view. In addition to exceptional embalming, we observed instances in which hearts alone had been extracted, a phenomenon that had never before been described, and brains alone as well, and instances in which each spouse's heart had been placed on the other's coffin. In some identified cases we were able to establish links between the religious attitudes of given individuals and either ancient Medieval practices or more modern ones generated by the Council of Trent. All of these practices, which were a function of social status, were rooted in religion. They offer no evidence of secularization whatsoever

    The cystic fibrosis transmembrane recruiter the alter ego of CFTR as a multi-kinase anchor

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    This review focuses on a newly discovered interaction between protein kinases involved in cellular energetics, a process that may be disturbed in cystic fibrosis for unknown reasons. I propose a new model where kinase-mediated cellular transmission of energy provides mechanistic insight to a latent role of the cystic fibrosis transmembrane conductance regulator (CFTR). I suggest that CFTR acts as a multi-kinase recruiter to the apical epithelial membrane. My group finds that, in the cytosol, two protein kinases involved in cell energy homeostasis, nucleoside diphosphate kinase (NDPK) and AMP-activated kinase (AMPK), bind one another. Preliminary data suggest that both can also bind CFTR (function unclear). The disrupted role of this CFTR-kinase complex as ‘membrane transmitter to the cell’ is proposed as an alternative paradigm to the conventional ion transport mediated and CFTR/chloride-centric view of cystic fibrosis pathogenesis. Chloride remains important, but instead, chloride-induced control of the phosphohistidine content of one kinase component (NDPK, via a multi-kinase complex that also includes a third kinase, CK2; formerly casein kinase 2). I suggest that this complex provides the necessary near-equilibrium conditions needed for efficient transmission of phosphate energy to proteins controlling cellular energetics. Crucially, a new role for CFTR as a kinase controller is proposed with ionic concentration acting as a signal. The model posits a regulatory control relay for energy sensing involving a cascade of protein kinases bound to CFTR

    β-Lactam Effects on Mixed Cultures of Common Respiratory Isolates as an Approach to Treatment Effects on Nasopharyngeal Bacterial Population Dynamics

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    BACKGROUND: Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: A computerized two-compartment pharmacodynamic model was used to explore beta-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX) 875 mg tid, amoxicillin/clavulanic acid (AMC) 875/125 mg tid and cefditoren (CDN) 400 mg bid regimens over 24 h. Strains and MICs (microg/ml) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), S. pneumoniae (2, 2 and 0.25), a beta-lactamase positive H. influenzae (BL(+); >16, 2 and 0.06) and a beta-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06). Mixture of identical 1:1:1:1 volumes of each bacterial suspension were prepared yielding an inocula of approximately 4 x 10(6) cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. beta-lactamase production decreased AMX concentrations and fT(>MIC) against S. pneumoniae (from 43.2% to 17.7%) or S. pyogenes (from 99.9% to 24.9%), and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL(+) and S. pneumoniae) was eradicated. Resistance of CDN to TEM beta-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT(>MIC) >58%), and reduced in 94% S. pneumoniae counts (fT(>MIC) approximately 25%). CONCLUSIONS/SIGNIFICANCE: Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for beta-lactamase resistant cephalosporins with high activity against streptococci

    Non-capsulated and capsulated Haemophilus influenzae in children with acute otitis media in Venezuela: a prospective epidemiological study

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    <p>Abstract</p> <p>Background</p> <p>Non-typeable <it>Haemophilus influenzae </it>(NTHi) and <it>Streptococcus pneumoniae </it>are major causes of bacterial acute otitis media (AOM). Data regarding AOM are limited in Latin America. This is the first active surveillance in a private setting in Venezuela to characterize the bacterial etiology of AOM in children < 5 years of age.</p> <p>Methods</p> <p>Between December 2008 and December 2009, 91 AOM episodes (including sporadic, recurrent and treatment failures) were studied in 87 children enrolled into a medical center in Caracas, Venezuela. Middle ear fluid samples were collected either by tympanocentesis or spontaneous otorrhea swab sampling method. Standard laboratory and microbiological techniques were used to identify bacteria and test for antimicrobial resistance. The results were interpreted according to Clinical Laboratory Standards Institute (CLSI) 2009 for non-meningitis isolates. All statistical analyses were performed using SAS 9.1 and Microsoft Excel (for graphical purposes).</p> <p>Results</p> <p>Overall, bacteria were cultured from 69.2% (63 of the 91 episodes); at least one pathogen (<it>S. pneumoniae, H. influenzae, S. pyogenes </it>or <it>M. catarrhalis</it>) was cultured from 65.9% (60/91) of episodes. <it>H. influenzae </it>(55.5%; 35/63 episodes) and <it>S. pneumoniae </it>(34.9%; 22/63 episodes) were the most frequently reported bacteria. Among <it>H. influenzae </it>isolates, 62.9% (22/35 episodes) were non-capsulated (NTHi) and 31.4% (11/35 episodes) were capsulated including types d, a, c and f, across all age groups. Low antibiotic resistance for <it>H. influenzae </it>was observed to amoxicillin/ampicillin (5.7%; 2/35 samples). NTHi was isolated in four of the six <it>H. influenzae </it>positive samples (66.7%) from recurrent episodes.</p> <p>Conclusions</p> <p>We found <it>H. influenzae </it>and <it>S. pneumoniae </it>to be the main pathogens causing AOM in Venezuela. Pneumococcal conjugate vaccines with efficacy against these bacterial pathogens may have the potential to maximize protection against AOM.</p

    Gene Therapy of Pancreatic Cancer

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