RESUMEN
Homeostasis of the biogenic polyamines spermine (Spm) and spermidine (Spd), present in µM-mM concentrations in all eukaryotic cells, is precisely regulated by coordinated activities of the enzymes of polyamine synthesis, degradation, and transport, in order to sustain normal cell growth and viability. Spermine oxidase (SMOX) is the key and most recently discovered enzyme of polyamine metabolism that plays an essential role in regulating polyamine homeostasis by catalyzing the back-conversion of Spm to Spd. The development of many types of epithelial cancer is associated with inflammation, and disease-related inflammatory stimuli induce SMOX. MDL72527 is widely used in vitro and in vivo as an irreversible inhibitor of SMOX, but it is also potent towards N1-acetylpolyamine oxidase. Although SMOX has high substrate specificity, Spm analogues have not been systematically studied as enzyme inhibitors. Here we demonstrate that 1,12-diamino-2,11-bis(methylidene)-4,9-diazadodecane (2,11-Met2-Spm) has, under standard assay conditions, an IC50 value of 169 µM towards SMOX and is an interesting instrument and lead compound for studying polyamine catabolism.
Asunto(s)
Anemia Hipocrómica/diagnóstico , Anciano , Anemia Hipocrómica/sangre , Niño , Índices de Eritrocitos , Femenino , Humanos , Hierro/sangreRESUMEN
A plea is made for the rationalization of medical education, with the aim of producing, at the end of 7 years, a doctor capable of at least one function, namely primary care, without further training. The course should contain enough to stimulate those motivated to specialize, although it should be brought home to them that they are losing certain privileges associated with patient relationships when they specialize. A thorough look at the degree of specialization should be taken to ensure that over-specialization does not fragment both the profession and the patient. Finally, we must be sure that when we delegate our respnsibilities we know what we are doing.
Asunto(s)
Educación Médica/normas , Medicina , Médicos de Familia , EspecializaciónRESUMEN
The control of extracellular acid-base balance is difficult to grasp unless it is realized that the pH of the blood depends upon the ratio H2CO3/NaHCO3 and that, without alteration of pulmonary ventilation, the H2CO3 neither rises nor falls. It must also be understood that the H+ ions, excreted by the kidneys, are byproducts of NaHCO3 reclamation and neogenesis and are not derived from metabolic acids.