RESUMEN
Idebenone, a synthetic analogue of coenzyme Q10, has been shown to improve cardiac function in patients with Friedreich ataxia and a deficiency of respiratory chain complexes I-III. We describe a woman with severe combined right and left heart failure due to a mitochondrial cardiomyopathy. The patient underwent an endomyocardial biopsy as part of an evaluation for cardiac transplantation. It showed severely decreased respiratory complex activities dependent on CoQ, pointing to CoQ depletion. Following idebenone treatment there was a dramatic improvement in her clinical status with resolution of the heart failure.
Asunto(s)
Benzoquinonas/uso terapéutico , Cardiomiopatías/tratamiento farmacológico , Miopatías Mitocondriales/complicaciones , Adulto , Antioxidantes/uso terapéutico , Biopsia , Cardiomiopatías/enzimología , Cardiomiopatías/etiología , Cardiomiopatías/patología , Complejo I de Transporte de Electrón , Complejo II de Transporte de Electrones , Complejo III de Transporte de Electrones/deficiencia , Femenino , Humanos , Miopatías Mitocondriales/tratamiento farmacológico , Miopatías Mitocondriales/enzimología , Complejos Multienzimáticos/deficiencia , NADH NADPH Oxidorreductasas/deficiencia , Oxidorreductasas/deficiencia , Succinato Deshidrogenasa/deficiencia , Ubiquinona/análogos & derivadosRESUMEN
Endotoxin-associated protein (EAP), a gram-negative bacterial cell wall component, was evaluated for its effects on hematopoietic colony formation in vitro. Colony-stimulating activity, induced by EAP on circulating and bone marrow progenitor cells, was found to be partially mediated by T cells and augmented by interleukin-3. The addition of anti-human interleukin-1 (IL-1) antibodies reduced EAP activity, suggesting that EAP may induce IL-1 production. However, EAP was shown to promote the growth of mature progenitor cells independently, unlike the effects of IL-1 on the hematopoietic system. These studies demonstrate that bacterial components other than lipopolysaccharide, such as EAP, may have hematopoietic activity.
Asunto(s)
Proteínas Bacterianas/farmacología , Endotoxinas/farmacología , Hematopoyesis/efectos de los fármacos , Lípido A/farmacología , Células Cultivadas , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Interleucina-1/fisiología , Interleucina-3/farmacología , Linfocitos T/fisiologíaRESUMEN
Hematopoiesis was evaluated in 15 B-CLL patients using the mixed colony formation assay. The mean growth of all types of colonies in B-CLL peripheral blood was significantly lower than that of 10 normal controls (p less than 0.05). To investigate whether TNF is the cytokine involved in the reduced growth of hematopoietic progenitors in B-CLL, neutralizing anti-TNF antibodies (anti-TNF Abs) were added to the cultures. Anti-TNF Abs optimized in vitro hematopoiesis in 11 out of 15 B-CLL patients and a significant growth increase in all types of colonies was noted as compared to baseline cultures (p less than 0.05). In patients with stage IV disease, the increase in both mixed and erythroid colonies was more prominent than in patients with earlier disease stages. This optimization of growth was also observed in normal control cultures containing accessory cells. However, high TNF levels were measured in conditioned media from CLL patients and suppressed normal bone marrow hematopoietic progenitors growth. In contrast no TNF was detected in normal conditioned media. It is concluded that TNF and other cytokines, among them IL-3, play a role in the regulation of hematopoietic function in some B-CLL cases. These findings may have clinical applicability.