RESUMEN
Iron-refractory iron deficiency anemia (IRIDA) is an inherited iron metabolism disorder caused by mutations in TMPRSS6 gene encoding matriptase-2, which results in increased hepcidin synthesis. The hallmarks of the disease are hypochromic microcytic anemia, low transferrin saturation, slightly low or normal ferritin levels in contrast to classic iron deficiency anemia (IDA), inadequate response to oral iron, and only a partial response to parenteral iron. We report here a 6-year-old Syrian boy with unexplained microcytic anemia since one year of age. Genetic analysis of the TMPRSS6 gene revealed a novel homozygous nonsense mutation in exon 3 (c.234C > G; p.Y78* or p.Tyr78*). In the presence of hypochromic microcytic anemia accompanied by atypical iron parameters not in accordance with classic IDA, and inadequate response to iron therapy, IRIDA should be remembered in the differential diagnosis.
Asunto(s)
Anemia Hipocrómica , Anemia Ferropénica , Anemia Ferropénica/genética , Niño , Codón sin Sentido , Humanos , Masculino , Proteínas de la Membrana/genética , Mutación , Serina Endopeptidasas/genética , HermanosRESUMEN
Aneugenic compounds are able to cause chromosome missegregation during mitosis which results in aneuploidy in cells that are able to survive. Aneuploidy is considered a key early condition in the progression from a normal cell into a cancerous cell. The possible toxicity of therapeutic lithium has raised concern because lithium salts are currently widely prescribed as an efficient treatment of manic-depressive disorders and numerous undesirable side effects of long-term treatment have been reported to date. We have observed a dose-dependent cytotoxic effect of both Li2CO3 and LiCl in AA8 CHO cells, while no genotoxic damage was detected. Mitotic abnormalities such as multipolar anaphases and lagging chromosomes leading to the presence of micronuclei in the next interphase were frequently observed after treatment with lithium salts. Thus, the effectiveness of both lithium salts to induce alterations in the normal segregation of chromosomes could be ascribed to interference with proteins involved in the organization and/or function of the mitotic apparatus.
Asunto(s)
Aneugénicos/toxicidad , Aneuploidia , Antimaníacos/toxicidad , Carbonato de Litio/toxicidad , Cloruro de Litio/toxicidad , Mitosis/efectos de los fármacos , Animales , Células CHO , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Daño del ADN , Relación Dosis-Respuesta a Droga , Micronúcleos con Defecto Cromosómico/inducido químicamenteRESUMEN
The potential mutagenicity of a zinc phosphate (Poscal), a polycarboxylate (Aqualox) and glass ionomer cements with (Argion) and without (Meron) silver reinforcement were characterized by employing the Ames Salmonella/microsome test. The materials were eluted in dimethyl sulphoxide or physiologic saline and the aliquots were used either immediately or after an incubation period of 24h at 37 degrees C. Mutagenic effects of the materials were tested on Salmonella typhimurium strains TA 98, TA 100, TA 102 and TA 1535 using the standard plate incorporation assay, and in the presence or absence of S9 fraction from rat liver. Poscal and Aqualox elicited mutagenic effects on S. typhimurium TA 98 and TA 1535, whereas Meron exhibited mutagenic effects on S. typhimurium TA 98. No mutagenic effects were detected for Argion. The type of solvent, dose of the material and incubation as well as the interactions between these factors exhibited varying degrees of influences on the mutagenic activities of the cements (P<0.05 and P<0.1). We conclude that zinc phosphate, polycarboxylate, and glass ionomer cements may have possible mutagenic activities.