Dapsone is not a Pharmacodynamic Lead Compound for its Aryl Derivatives.

BACKGROUND: The relatedness between the linear equations of thermodynamics and QSAR was studied thanks to the recently elucidated crystal structure complexes between sulfonamide pterin conjugates and dihydropteroate synthase (DHPS) together with a published set of thirty- six synthetic dapsone derivatives with their reported entropy-driven activity data. Only a few congeners were slightly better than dapsone. OBJECTIVE: Our study aimed at demonstrating the applicability of thermodynamic QSAR and to shed light on the mechanistic aspects of sulfone binding to DHPS. METHODS: To this end ligand docking to DHPS, quantum mechanical properties, 2D- and 3D-QSAR as well as Principle Component Analysis (PCA) were carried out. RESULTS: The short aryl substituents of the docked pterin-sulfa conjugates were outward oriented into the solvent space without interacting with target residues which explains why binding enthalpy (ΔH) did not correlate with potency. PCA revealed how chemically informative descriptors are evenly loaded on the first three PCs (interpreted as ΔG, ΔH and ΔS), while chemically cryptic ones reflected higher dimensional (complex) loadings. CONCLUSION: It is safe to utter that synthesis efforts to introduce short side chains for aryl derivatization of the dapsone scaffold have failed in the past. On theoretical grounds we provide computed evidence why dapsone is not a pharmacodynamic lead for drug profiling because enthalpic terms do not change significantly at the moment of ligand binding to target.

Gentamicin and tetracyclines for the treatment of human plague: review of 75 cases in new Mexico, 1985-1999.

Streptomycin, an antimicrobial with limited availability, is the treatment of choice for plague, a fulminating and potentially epidemic disease that poses a bioterrorism concern. We evaluated the efficacy of gentamicin and tetracyclines for treating human plague. A medical record review was conducted on all 75 patients with plague who were reported in New Mexico during 1985-1999. Fifty patients were included in an analysis that compared streptomycin-treated patients (n=14) with those treated with gentamicin and/or a tetracycline (n=36). The mean numbers of fever days, hospital days, and complications and the number of deaths did not differ between patients treated with streptomycin and those treated with gentamicin. One patient who received tetracycline alone experienced a serious complication. Gentamicin alone or in combination with a tetracycline was as efficacious as streptomycin for treating human plague. The efficacy of a tetracycline alone could not be determined from the study.

Triaga Brasilica: renewed interest in a seventeenth-century panacea.

Theriacs (electuaries prepared by mixing extracts of many plants) were known from antiquity until the eighteenth century as remedies for all kinds of envenomation, above all those due to the bites and stings of venomous animals, especially snakes. In colonial Brazil, the 'Brazilian theriac' was developed by Jesuit priests by gradually substituting native plants for components of their European model. Most of these ingredients, mentioned in an old manuscript, can be identified by their common names, which have survived the centuries.

Peste: guías de capacitación para profesionales y técnicos / Plague: training guides for professionals and technicians

Tiene como finalidad brindar pautas operativas que permitan unificar criterios en las Regiones y Subregiones de salud para la capacitación de los profesionales y técnicos que intervengan en el control y vigilancia de la peste. Consta de 6 guías que brindan información sobre las actividades de control que se deben realizar en el campo donde la participación de la comunidad representa un eje de acción

Inmunoprofilaxia de la peste / Immunoprophylaxis of the pest

La peste es una enfermedad infecciosa de tipo zoonótico que ha representado uno de los más serios problemas de salud pública en todo el mundo y debido a sus características pandémicas, mas que epidémicas, fue uno de los azotes de la antigüedad. Su agente etiológico es Yersinia pestis y la forma clínica más frecuente es una linfadentitis febril aguda o peste bubónica, aunque también se presentan formas septicémicas, neumónicas y meníngeas. En ausencia de tratamiento es sumamente mortal, pero esta se reduce notablemente si se instala una antibióticoterapia oportuna. La primera vacuna contra la peste fue elaborada por Haffkine en 1897 utilizando bacterias muertas; durante la Segunda Guerra Mundial y años después, en el ejército de los Estados Unidos se usó otro tipo de vacuna muerta con formalina y mediante sucesivas mejoras en los métodos de su producción se obtuvo, a partir de la cepa muy virulenta India 195/P de Y. pestis, la denominada vacuna contra la peste USP, medio E, ahora en uso; que se aplica en una primera serie de tres dosis intramusculares, la primera de 1 mL, seguida cuatro semanas más tarde de otra de 0.2 mL y 15 meses después de otros 0.2 mL. La efectividad de una serie primaria de vacunación nunca se ha medido en forma precisa; la experiencia en el campo indica que reduce la incidencia y severidad de la enfermedad posterior al piquete de pulgas infectadas. Se desconoce la protección que confiere contra la peste neumónica. Ya que la vacuna sólo aminora la sintomatología, se recomienda la administración profiláctica de antibióticos en todos los individuos que hayan estado expuestos al contagio, tengan o no antecedentes vacunales

Septicemic plague in New Mexico.

Eighteen of the 71 cases of plague reported in New Mexico from 1980 to 1984 were septicemic. We reviewed these cases to better describe the clinical presentation of this disorder and to identify risk factors for developing septicemic plague. The symptoms (fever, chills, malaise, headache, and gastrointestinal symptoms) and signs (tachycardia, tachypnea, and hypotension) of septicemic plague are similar to those of other forms of gram-negative septicemia. Abdominal pain was reported in nearly half of the cases, and differential white blood cell counts revealed a marked shift to the left. The risk of developing septicemic plague was higher for persons greater than 40 years of age. Because of empirical antibiotic treatment of older persons, deaths from septicemic plague occurred primarily among persons less than 30 years old. Deaths from septicemic plague could be reduced by aggressive antibiotic therapy for patients with a clinical presentation suggesting gram-negative septicemia, especially patients less than 30 years old.