RESUMEN
Meningococcal disease was first clinically characterised by Gaspard Vieusseux in 1805, and its causative agent was identified by Anton Weichselbaum in 1887, who named it Diplococcus intracellularis menigitidis. From the beginning, the disease was dreaded because of its epidemic nature, predilection for previously healthy children and adolescents, and high mortality. In the last decade of the 19th century, the concept of serum therapy for toxin-related bacterial diseases was identified. This concept was applied to meningococcal disease therapy, in an independent way, by Wilhelm Kolle, August von Wasserman, and Georg Jochmann in Germany, and Simon Flexner in the USA, resulting in the first successful approach for the treatment of meningococcal disease. During the first three decades of the 20th century, serum therapy was the standard treatment for meningococcal disease. With the advent of sulphamides first and then antibiotics, serum therapy was abandoned. The great challenges that infectious diseases medicine is facing and the awaiting menaces in the future in terms of increasing antibiotic resistance, emergence of new pathogens, and re-emergence of old ones without effective therapy, make passive immunotherapy a promising tool. Acknowledging the achievements of our predecessors might teach us some lessons to bring light to our future.
Asunto(s)
Epidemias/historia , Infectología/historia , Infecciones Meningocócicas/tratamiento farmacológico , Infecciones Meningocócicas/historia , Adolescente , Niño , Alemania , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Inmunización Pasiva , Infecciones Meningocócicas/líquido cefalorraquídeo , Infecciones Meningocócicas/mortalidad , Vacunas Meningococicas , Neisseria meningitidis/aislamiento & purificación , p-Aminoazobenceno/análogos & derivados , p-Aminoazobenceno/uso terapéuticoRESUMEN
INTRODUCTION: The origin of syphilis is a matter of debate and two "historical" hypotheses explain its emergence. AIM: We present here a review about syphilis history. METHODS: A review of literature about syphilis history using the following keywords: "syphilis," "history," and "treponema." RESULTS: The Columbian opinion is that syphilis came from the New World (America) with the crews of Christopher Columbus's fleet. As Naples fell before the invading army of Charles the VIII in 1495, a plague broke out among the French leader's troops. When the army disbanded shortly after the campaign, the troops, composed largely of mercenaries, returned to their homes and disseminated the disease across Europe. Indeed, there were reports that indigenous peoples of the New World suffered from a similar condition. CONCLUSION: Regardless of the Columbian and the Pre-Columbian theories, syphilis remains an international disease, growing nowadays with HIV infection. Despite history, politics, paleopathology and molecular approaches, the origin of the disease remains an enigma.
Asunto(s)
Sífilis/historia , Europa (Continente)/epidemiología , Infecciones por VIH/epidemiología , Historia Medieval , Humanos , Personal Militar/historia , Poesía como Asunto/historia , Sífilis/tratamiento farmacológico , Sífilis/epidemiología , Treponema pallidum/aislamiento & purificación , p-Aminoazobenceno/análogos & derivados , p-Aminoazobenceno/historia , p-Aminoazobenceno/uso terapéuticoRESUMEN
Hematopoietic stem cells (HSCs) are enriched for aldehyde dehydrogenase (ALDH) activity and ALDH is a selectable marker for human HSCs. However, the function of ALDH in HSC biology is not well understood. We sought to determine the function of ALDH in regulating HSC fate. Pharmacologic inhibition of ALDH with diethylaminobenzaldehyde (DEAB) impeded the differentiation of murine CD34(-)c-kit(+)Sca-1(+)lineage(-) (34(-)KSL) HSCs in culture and facilitated a ninefold expansion of cells capable of radioprotecting lethally irradiated mice compared to input 34(-)KSL cells. Treatment of bone marrow (BM) 34(-)KSL cells with DEAB caused a fourfold increase in 4-week competitive repopulating units, verifying the amplification of short-term HSCs (ST-HSCs) in response to ALDH inhibition. Targeted siRNA of ALDH1a1 in BM HSCs caused a comparable expansion of radioprotective progenitor cells in culture compared to DEAB treatment, confirming that ALDH1a1 was the target of DEAB inhibition. The addition of all trans retinoic acid blocked DEAB-mediated expansion of ST-HSCs in culture, suggesting that ALDH1a1 regulates HSC differentiation via augmentation of retinoid signaling. Pharmacologic inhibition of ALDH has therapeutic potential as a means to amplify ST-HSCs for transplantation purposes.
Asunto(s)
Aldehído Deshidrogenasa/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Citoprotección/fisiología , Inhibidores Enzimáticos/farmacología , Células Madre Hematopoyéticas/enzimología , Trasplante de Células Madre/métodos , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Animales , Antineoplásicos/farmacología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , División Celular/efectos de los fármacos , División Celular/fisiología , Células Cultivadas , Citoprotección/efectos de los fármacos , Inhibidores Enzimáticos/uso terapéutico , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de la radiación , Humanos , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , ARN Interferente Pequeño/genética , Radiación Ionizante , Retinal-Deshidrogenasa , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Tretinoina/metabolismo , Tretinoina/farmacología , p-Aminoazobenceno/análogos & derivados , p-Aminoazobenceno/farmacología , p-Aminoazobenceno/uso terapéuticoRESUMEN
The important chemotherapeutic agents, Prontosil and pentenylpenicillin (penicillin F), were investigated initially by two men, Domagk and Fleming, who had been influenced by the horrendous wound infections of World War I. The very different pathways leading to their development and to that of the successor antibacterials (sulfa drugs, further penicillins, semi-synthetic penicillins), including the role played by patents, are discussed.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Descubrimiento de Drogas/historia , Penicilinas/uso terapéutico , p-Aminoazobenceno/análogos & derivados , Antibacterianos/síntesis química , Infecciones Bacterianas/historia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Masculino , Patentes como Asunto , Penicilinas/síntesis química , p-Aminoazobenceno/síntesis química , p-Aminoazobenceno/uso terapéuticoAsunto(s)
Infección Puerperal/historia , Infecciones Estreptocócicas/historia , Animales , Bacteriología/historia , Femenino , Historia del Siglo XX , Humanos , Ratones , Infección Puerperal/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Sulfonamidas/historia , Sulfonamidas/uso terapéutico , Reino Unido , p-Aminoazobenceno/análogos & derivados , p-Aminoazobenceno/historia , p-Aminoazobenceno/uso terapéuticoAsunto(s)
Penicilinas/historia , Antibacterianos/historia , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/historia , Salud Global , Historia del Siglo XX , Humanos , Penicilinas/aislamiento & purificación , Penicilinas/uso terapéutico , Terminología como Asunto , p-Aminoazobenceno/análogos & derivados , p-Aminoazobenceno/historia , p-Aminoazobenceno/uso terapéuticoRESUMEN
1. As an extension of our previous study of quinacrine and its derivatives, chelating chemicals were screened to obtain more effective, better brain-permeable antiprion compounds using either prion-infected neuroblastoma cells or brain capillary endothelial cells.2. Eleven chemicals were found to have antiprion activity. Most of them shared a common structure consisting of benzene or naphthalene at either end of an azo bond. Structure-activity data suggest that chelating activity is not necessary but might contribute to the antiprion action.3. Chrysoidine, a representative compound found here, was about 27 times more effective in the antiprion activity and five times more efficiently permeable through the brain capillary endothelial cells than quinacrine was.4. These chemicals might be useful as compounds for development of therapeutics for prion diseases.
Asunto(s)
Encéfalo/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Quelantes/farmacología , Células Endoteliales/efectos de los fármacos , Priones/antagonistas & inhibidores , Quinacrina/farmacología , p-Aminoazobenceno/análogos & derivados , Animales , Encéfalo/metabolismo , Evaluación Preclínica de Medicamentos , Células Endoteliales/metabolismo , Ratones , Modelos Biológicos , Proteínas PrPSc/metabolismo , Enfermedades por Prión/prevención & control , Priones/efectos de los fármacos , Priones/metabolismo , Unión Proteica , Quinacrina/uso terapéutico , Proteínas Recombinantes/metabolismo , Células Tumorales Cultivadas , p-Aminoazobenceno/farmacología , p-Aminoazobenceno/uso terapéuticoAsunto(s)
Sulfonamidas/historia , p-Aminoazobenceno/análogos & derivados , Animales , Infecciones Bacterianas/tratamiento farmacológico , Inglaterra , Alemania , Historia del Siglo XX , Humanos , Sulfonamidas/uso terapéutico , Estados Unidos , p-Aminoazobenceno/historia , p-Aminoazobenceno/uso terapéuticoRESUMEN
The significance of the discovery of prontosil in 1932 as the initiating step in the development of the modern era of antimicrobial chemotherapy is reviewed. The history of the discovery and the development of chemotherapeutic agents, from penicillin in 1929 to present-day antibiotics, are summarized. The various mechanisms by which bacteria are able to overcome the protective effects of these therapeutic agents (from the sulphonamides to the new fluoroquinolones) and develop resistance to them are discussed in detail. Attempts to elucidate the mechanisms by which resistance to chemotherapeutic agents develops are vital to the future of antimicrobial chemotherapy.