RESUMEN
Over the past 30 years, much has been learned regarding iron homeostatic regulation in budding yeast, S. cerevisiae, including the identity of many of the proteins and molecular-level regulatory mechanisms involved. Most advances have involved inferring such mechanisms based on the analysis of iron-dysregulation phenotypes arising in various genetic mutant strains. Still lacking is a cellular- or system-level understanding of iron homeostasis. These experimental advances are summarized in this review, and a method for developing cellular-level regulatory mechanisms in yeast is presented. The method employs the results of Mössbauer spectroscopy of whole cells and organelles, iron quantification of the same, and ordinary differential equation-based mathematical models. Current models are simplistic when compared to the complexity of iron homeostasis in real cells, yet they hold promise as a useful, perhaps even required, complement to the popular genetics-based approach. The fundamental problem in comprehending cellular regulatory mechanisms is that, given the complexities involved, different molecular-level mechanisms can often give rise to virtually indistinguishable cellular phenotypes. Mathematical models cannot eliminate this problem, but they can minimize it.
Asunto(s)
Homeostasis , Hierro , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Hierro/metabolismo , Simulación por Computador , Modelos Biológicos , Espectroscopía de Mossbauer/métodos , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
Various iron-containing medicaments, vitamins and dietary supplements are used or developed for treatment and prevention of the iron deficiency anemia which is very dangerous for human and may cause various disorders. From the other hand, blood losses, iron poor diet, microelements (co-factors) deficiency, metabolic failures, absorption problems, etc. can change the iron status and affect the health. These pharmaceuticals contain iron compounds in the ferrous and ferric states. It is known that ferrous salts are more suitable for the intestinal intake than ferric ones. On the other hand, pharmaceutically important ferritin analogues contain ferric hydrous oxides and appear to be effective for both injections and peroral administration. 57Fe Mössbauer spectroscopy is a unique physical technique which allows one to study various iron-containing materials including pharmaceuticals. Therefore, this technique was applied to study iron-containing pharmaceuticals for the analysis of the iron state, identification of ferric and ferrous compounds, revealing some structural peculiarities and for detection of aging processes in relation to the iron compounds. This review considers the main results of a long experience in the study of iron-containing pharmaceuticals by Mössbauer spectroscopy with critical analysis that may be useful for pharmacists, biochemists, biophysicists, and physicians.
Asunto(s)
Anemia Ferropénica , Espectroscopía de Mossbauer , Espectroscopía de Mossbauer/métodos , Humanos , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/prevención & control , Hierro/química , Compuestos Férricos/química , Compuestos Ferrosos/química , Preparaciones Farmacéuticas/química , AnimalesRESUMEN
Con el acrónimo SAPHO se ha conseguido agrupar un conjunto de patologías benignas, que combinan afectación osteoarticular y cutánea, cuyo diagnóstico es principalmente clínico apoyado en los hallazgos de imagen, donde la gammagrafía ósea adquiere un papel relevante por su sensibilidad y precocidad. Presentamos 8 pacientes con síndrome de SAPHO que inician el cuadro clínico con manifestaciones dermatológicas. Todos presentaron lesiones pustulosas palmo-plantares, de reciente comienzo o con evolución en brotes. Algunos asociaron dolores osteoarticulares en hombros, región esternal, lumbar o en miembros inferiores. La gammagrafía ósea realizada con 99mTc-difosfonatos demostró hallazgos patológicos en todos los pacientes, detectándose afectación en articulaciones esternoclaviculares, la localización más frecuente, en 7 de ellos, así como en otras localizaciones menos típicas(AU)
The SAPHO acronym corresponds to a group of benign conditions that combine osteoarticular and skin involvement whose diagnosis is mainly clinical and is supported by imaging findings. The bone scintigraphy has a relevant role due to its sensitivity and early detection ability. We present 8 patients with SAPHO syndrome whose clinical involvement began with skin manifestations. All of them had palmoplantar pustulosis, either of recent onset or outbreak evolution. Some had associated osteoarticular pain in shoulders, sternum, lumbar area or limbs. Bone scintigraphy with Tc-99m-diphosphonate showed pathological findings in all the patients, detecting sternoclavicular joint damage, this being the most frequent involvement in 7 of them, and also in other less usual localizations(AU)