Las falacias que se autorefutan y la consequentia mirabilis

Los argumentos autorefutatorios han sido estudiados desde la Antigüedad clásica y su análisis con los instrumentos que proporcionan la lógica y la teoría de la argumentación contemporáneas ha adquirido cierta intensidad en las últimas décadas. Este trabajo estará dedicado al estudio de la manera en la que algunas falacias -formales o informales- se pueden refutar a sí mismas mediante los llamados argumentos saccherianos. Un argumento de este tipo tiene premisas que formulan afirmaciones metalógicas verdaderas y una conclusión que afirma la invalidez de la forma argumental que ese argumento ejemplifica. Con la ayuda de la regla de la consequentia mirabilis es posible concluir que la forma argumental en cuestión es inválida. Si bien en un artículo reciente Michael Veber propone aplicar la técnica autorefutatoria saccheriana a falacias informales tales como la falacia ad hominem, manifiesta ciertas prevenciones respecto de la extensión del campo de aplicación de esa técnica a las falacias informales. Se argumentará en este trabajo que esas prevenciones no están injustificadas ya que la construcción de los argumentos saccherianos adecuados para mostrar la invalidez de las falacias informales puede resultar más trabajoso y, además, no está garantizada la existencia de tales argumentos en el caso de este tipo de falacias

Las falacias que se autorefutan y la consequentia mirabilis

Los argumentos autorefutatorios han sido estudiados desde la Antigüedad clásica y su análisis con los instrumentos que proporcionan la lógica y la teoría de la argumentación contemporáneas ha adquirido cierta intensidad en las últimas décadas. Este trabajo estará dedicado al estudio de la manera en la que algunas falacias -formales o informales- se pueden refutar a sí mismas mediante los llamados argumentos saccherianos. Un argumento de este tipo tiene premisas que formulan afirmaciones metalógicas verdaderas y una conclusión que afirma la invalidez de la forma argumental que ese argumento ejemplifica. Con la ayuda de la regla de la consequentia mirabilis es posible concluir que la forma argumental en cuestión es inválida. Si bien en un artículo reciente Michael Veber propone aplicar la técnica autorefutatoria saccheriana a falacias informales tales como la falacia ad hominem, manifiesta ciertas prevenciones respecto de la extensión del campo de aplicación de esa técnica a las falacias informales. Se argumentará en este trabajo que esas prevenciones no están injustificadas ya que la construcción de los argumentos saccherianos adecuados para mostrar la invalidez de las falacias informales puede resultar más trabajoso y, además, no está garantizada la existencia de tales argumentos en el caso de este tipo de falacias

Las falacias que se autorefutan y la consequentia mirabilis

Los argumentos autorefutatorios han sido estudiados desde la Antigüedad clásica y su análisis con los instrumentos que proporcionan la lógica y la teoría de la argumentación contemporáneas ha adquirido cierta intensidad en las últimas décadas. Este trabajo estará dedicado al estudio de la manera en la que algunas falacias -formales o informales- se pueden refutar a sí mismas mediante los llamados argumentos saccherianos. Un argumento de este tipo tiene premisas que formulan afirmaciones metalógicas verdaderas y una conclusión que afirma la invalidez de la forma argumental que ese argumento ejemplifica. Con la ayuda de la regla de la consequentia mirabilis es posible concluir que la forma argumental en cuestión es inválida. Si bien en un artículo reciente Michael Veber propone aplicar la técnica autorefutatoria saccheriana a falacias informales tales como la falacia ad hominem, manifiesta ciertas prevenciones respecto de la extensión del campo de aplicación de esa técnica a las falacias informales. Se argumentará en este trabajo que esas prevenciones no están injustificadas ya que la construcción de los argumentos saccherianos adecuados para mostrar la invalidez de las falacias informales puede resultar más trabajoso y, además, no está garantizada la existencia de tales argumentos en el caso de este tipo de falacias

Carotid Surgery : A posse ad esse non valet consequentia

According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.

New rotenoids from roots of Mirabilis jalapa

Four new rotenoids named mirabijalone A-D-1) (1-4), together with 9-O-methyl-4-hydroxyboeravinone B (5), boeravinone C (6) and F (7), and 1,2,3,4-tetrahydro-1-methylisoquinoline-7,8-diol (8), were isolated from the roots of Mirabilis jalapa. The structures of these compounds were determined on the basis of their HR-EI-MS, IR, UV, H-1- and C-13-NMR (DEPT). and 2D NMR (HMQC, HMBC, NOESY) data. Among them, 1,2,3,4-tetrahydro-1-methylisoquinoline-7,8-diol (8) showed a 48% inhibition against HIV-1 reverse transcriptase at 210 mug/ml.

The use of lytic bacteriophages in the prevention and eradication of biofilms of Proteus mirabilis and Escherichia coli.

Antibiotics have been the cornerstone of the clinical management of bacterial infections since their discovery in the early part of the last century. Eight decades later, their widespread, often indiscriminate use, has resulted in an overall reduction in their effectiveness, with reports of multidrug-resistant bacteria now commonplace. Increasing reliance on indwelling medical devices, which are inherently susceptible to biofilm-mediated infections, has contributed to unacceptably high rates of nosocomial infections, placing a strain on healthcare budgets. This study investigates the use of lytic bacteriophages in the treatment and prevention of biofilms of bacterial species commonly associated with infections of indwelling urological devices and catheter-associated urinary tract infections. The use of lytic bacteriophages against established biofilms of Proteus mirabilis and Escherichia coli is described, whereby biofilm populations have been reduced successfully by three to four log cycles (99.9-99.99% removal). The prevention of biofilm formation on Foley catheter biomaterials following impregnation of hydrogel-coated catheter sections with a lytic bacteriophage has also been investigated. This has revealed an approximate 90% reduction in both P. mirabilis and E. coli biofilm formation on bacteriophage-treated catheters when compared with untreated controls.

ZapA, a virulence factor in a rat model of Proteus mirabilis-induced acute and chronic prostatitis.

Our knowledge of pathogenesis has benefited from a better understanding of the roles of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in prostatitis, rats were infected with either wild-type (WT) P. mirabilis or its isogenic ZapA- mutant KW360. The WT produced both acute and chronic prostatitis showing the typical histological progressions that are the hallmarks of these diseases. Infection with the ZapA- mutant, however, resulted in reduced levels of acute prostatitis, as determined from lower levels of tissue damage, bacterial colonization, and inflammation. Further, the ZapA- mutant failed to establish a chronic infection, in that bacteria were cleared from the prostate, inflammation was resolved, and tissue was seen to be healing. Clearance from the prostate was not the result of a reduced capacity of the ZapA- mutant to form biofilms in vitro. These finding clearly define ZapA as an important virulence factor in both acute and chronic bacterial prostatitis.

Comprehensive Inhibitor Profiling Of The Proteus Mirabilis Metalloprotease Virulence Factor Zapa (Mirabilysin)

In this study we report for the first time the comprehensive inhibitor profiling of the Proteus mirabilis metalloprotease virulence factor, ZapA (mirabilysin) using a 160 compound focused library of N-alpha mercaptoamide dipeptides, in order to map the S1´ and S2´ binding site preferences of this important enzyme. This study has revealed a preference for the aromatic residues tyrosine and tryptophan in P1´ and aliphatic residues in P2´. From this library, six compounds were identified which exhibited sub- to low micromolar Ki values. The most potent inactivator, SH-CO2-Y-V-NH2 was capable of preventing ZapA-mediated hydrolysis of heat denatured IgA, indicating these inhibitors may be capable of protecting host proteins against ZapA during colonisation and infection.

Comparison of the binding specificity of two bacterial metalloproteases, LasB of Pseudomonas aeruginosa and ZapA of Proteus mirabilis, using N-alpha mercaptoamide template-based inhibitor analogues

The metalloproteases ZapA of Proteus mirabilis and LasB of Pseudomonas aeruginosa are known to be virulence factors their respective opportunistic bacterial pathogens, and are members of the structurally related serralysin and thermolysin families of bacterial metalloproteases respectively. Secreted at the site of infection, these proteases play a key role in the infection process, contributing to tissue destruction and processing of components of the host immune system. Inhibition of these virulence factors may therefore represent an antimicrobial strategy, attenuating the virulence of the infecting pathogen. Previously we have screened a library of N-alpha mercaptoamide dipeptide inhibitors against both ZapA and LasB, with the aim of mapping the S1' binding site of the enzymes, revealing both striking similarities and important differences in their binding preferences. Here we report the design, synthesis, and screening of several inhibitor analogues, based on two parent inhibitors from the original library. The results have allowed for further characterization of the ZapA and LasB active site binding pockets, and have highlighted the possibility for development of broad-spectrum bacterial protease inhibitors, effective against enzymes of the thermolysin and serralysin metalloprotease families.

Outer membrane protein profiles and multilocus enzyme electrophoresis analysis for differentiation of clinical isolates of Proteus mirabilis and Proteus vulgaris

Outer membrane protein (MP) profiles and multilocus enzyme electrophoresis (MEE) analysis were used as tools for differentiating clinical isolates of Proteus spp. Fourteen distinct MP profiles were established by sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis in 54 clinical isolates of Proteus spp. (44 strains identified as P. mirabilis and 10 strains identified as P. vulgaris). Forty-one isolates of P. mirabilis and eight isolates of P. vulgaris were grouped within six and three MP profiles, respectively. The remaining P. mirabilis and P. vulgaris isolates had unique profiles. MEE analysis was used to further discriminate among the strains belonging to the same MP groups. Thirty-five distinct electrophoretic types (ETs) were identified among P. mirabilis isolates. The isolates of P. mirabilis from the four most common MP groups were subgrouped into 30 ETs. All of the P. vulgaris strains had unique ETs. The results suggest that upon biochemical classification of Proteus isolates as P. mirabilis or P. vulgaris, further differentiation among strains of the same species can be obtained by the initial determination of MP profiles followed by MEE analysis of strains with identical MPs.