RESUMEN
The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR-mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signalling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 deficiency syndrome.
RESUMEN
The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018), and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity.
Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Doxorrubicina/toxicidad , Cardiopatías/inducido químicamente , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antioxidantes/metabolismo , Roturas del ADN , Doxorrubicina/administración & dosificación , Esquema de Medicación , Cardiopatías/metabolismo , Cardiopatías/patología , Inyecciones Intraperitoneales , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Necrosis , Ratas Wistar , Factores de TiempoRESUMEN
The differential diagnosis and work-up of a patient with chest pain during pregnancy is presented in this article. This is followed by discussions of cardiac emergencies including hypertensive crisis, pulmonary edema, arrhythmias, cardiopulmonary resuscitation, myocardial infarction, and aortic dissection.
Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/terapia , Dolor en el Pecho/etiología , Complicaciones del Embarazo/etiología , Disección Aórtica/complicaciones , Disección Aórtica/terapia , Aneurisma de la Aorta/complicaciones , Aneurisma de la Aorta/terapia , Arritmias Cardíacas/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/complicaciones , Infarto del Miocardio/etiología , Infarto del Miocardio/terapia , Embarazo , Complicaciones Cardiovasculares del Embarazo/etiología , Complicaciones Cardiovasculares del Embarazo/terapia , Edema Pulmonar/complicaciones , Edema Pulmonar/tratamiento farmacológico , Edema Pulmonar/etiologíaRESUMEN
Os autores descrevem um caso de associacao de leishmaniose visceral, SIDA e provavel tuberculose disseminada. Discutem a possibilidade de associacao desta protozoonose e infeccao pelo virus da Imunodeficiencia Adquirida (VIH) principalmente pelo aumento de prevalencia de infeccao pelo VIH em areas endemicas para o calazar. A presenca de imunodepressao pelo VIH possibilita manifestacoes de agentes oportunistas muitas vezes associados e relacionados com as endemias prevalentes nestas regioes de subdesenvolvimento.
Asunto(s)
Humanos , Adulto , Leishmaniasis Visceral/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Tuberculosis/diagnóstico , Diagnóstico Diferencial , Leishmaniasis Visceral/patología , Infecciones OportunistasRESUMEN
This is a case report that describe an association of AIDS, visceral leishmaniasis and probable disseminated tuberculosis. Due to the spread of AIDS in developing areas worldwide this association would be more frequently, seen on subjects from endemic areas where this protozoonosis is prevalent. More than one opportunistic infection related with the endemic diseases of the developing regions can be associated with those immunocompromised patients.