RESUMEN
Our study aimed to assess the severity of severe acute respiratory syndrome coronavirus 2 infection in hospitalized infants under 40 days old, across 21 Belgian hospitals between 2020 and 2022. Of the 365 infants studied, 14.2% needed respiratory support. The median hospital stay was 3 days (interquartile range, 2-4), and there were no deaths. Infection severity was similar during the Omicron and Alpha/Delta periods.
Asunto(s)
COVID-19 , Hospitalización , Tiempo de Internación , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Bélgica/epidemiología , Lactante , Hospitalización/estadística & datos numéricos , Recién Nacido , Masculino , Femenino , Tiempo de Internación/estadística & datos numéricos , Índice de Severidad de la EnfermedadRESUMEN
Stress can promote palatable food intake, and consumption of palatable foods may dampen psychological and physiological responses to stress. Here we develop a rat model of daily limited sweetened drink intake to further examine the linkage between consumption of preferred foods and hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Adult male rats with free access to water were given additional twice-daily access to 4 ml sucrose (30%), saccharin (0.1%; a noncaloric sweetener), or water. After 14 d of training, rats readily learned to drink sucrose and saccharin solutions. Half the rats were then given chronic variable stress (CVS) for 14 d immediately after each drink exposure; the remaining rats (nonhandled controls) consumed their appropriate drinking solution at the same time. On the morning after CVS, responses to a novel restraint stress were assessed in all rats. Multiple indices of chronic stress adaptation were effectively altered by CVS. Sucrose consumption decreased the plasma corticosterone response to restraint stress in CVS rats and nonhandled controls; these reductions were less pronounced in rats drinking saccharin. Sucrose or saccharin consumption decreased CRH mRNA expression in the paraventricular nucleus of the hypothalamus. Moreover, sucrose attenuated restraint-induced c-fos mRNA expression in the basolateral amygdala, infralimbic cortex, and claustrum. These data suggest that limited consumption of sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses, and calories contribute but are not necessary for this effect. Collectively the results support the hypothesis that the intake of palatable substances represents an endogenous mechanism to dampen physiological stress responses.
Asunto(s)
Ingestión de Líquidos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Estrés Psicológico/fisiopatología , Sacarosa/farmacología , Adaptación Psicológica , Hormona Adrenocorticotrópica/sangre , Animales , Ritmo Circadiano , Ingestión de Alimentos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Long-Evans , Estrés Psicológico/metabolismoRESUMEN
Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have implicated hypothalamic peptides and receptors of the corticotropin releasing factor (CRF) family as putative mediators of burn-induced hypermetabolism. Increased neuronal activity at the CRF type 2 receptor (CRF R-2) appeared particularly involved in the expression of elevated resting energy expenditure (REE) following major burn trauma. In the present study we continued these investigations of CRF R-2 mediation of burn-induced hypermetabolism, demonstrating that 3rd ventricle injection of CRF R-2 antisense oligodeoxynucleotide (ODN) normalized REE in burned rats. Similar treatments with CRF or CRF R-1 antisense ODNs had no significant effect in burned rats. In addition, 3rd ventricle injection of the selective CRF R-2 antagonist, antisauvagine-30, also reduced REE significantly in burned rats, while similar treatment with the selective CRF R-1 antagonist, antalarmin, was without effect. To determine which endogenous peptide was altered following burn we measured hypothalamic levels of urocortin (UCN) and CRF 15 days after burn injury, finding UCN was significantly elevated by nearly 3-fold, while CRF level tended to be decreased. We also assessed hypothalamic mRNA peptide and receptor expression by real-time PCR 7, 14, and 21 days post-burn, observing decreased CRF expression 7 and 21 days post-burn, decreased UCN-2 expression 7 days post-burn, and no significant alteration in UCN-1 at any time point. However, CRF R-2 mRNA was elevated at each post-burn time point. These results continue to suggest that increased neuronal activity is integrally involved in the mediation of burn-induced hypermetabolism, and that one of the UCN peptides may be the endogenous ligand affecting this receptor.
Asunto(s)
Quemaduras/metabolismo , Metabolismo Energético/fisiología , Hipotálamo/metabolismo , Enfermedades Metabólicas/metabolismo , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Animales , Anorexia/metabolismo , Quemaduras/complicaciones , Quemaduras/tratamiento farmacológico , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Expresión Génica , Hipotálamo/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/etiología , Oligonucleótidos Antisentido/farmacología , Fragmentos de Péptidos/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Receptores de Hormona Liberadora de Corticotropina/genética , UrocortinasRESUMEN
Total parenteral nutrition (TPN) of rats has been demonstrated to produce hypoplasia of gut mucosa, and to be associated with reduced immune response and elevated translocation of bacteria from gut to mesenteric lymph nodes, spleen and liver. Treatment of rats being maintained on TPN with the proglucagon fragment, glucagon-like peptide-2 (GLP-2), has been shown to totally prevent small intestine mucosal hypoplasia. In the present study, we found that depletion of polyamines with alpha-difluromethylornithine (DFMO) significantly reduced the efficacy of GLP-2 in preserving gut mucosa in rats maintained on TPN for 8 days. Co-infusion of GLP-2 with TPN prevented loss of protein and mucosa in duodenum, jejunum and ileum, but not in colon. Addition of DFMO to the infusate prevented the protective effects of GLP-2 in the duodenum and jejunum. In the jejunum, putrescine and spermidine were reduced in DFMO-treated rats, while the ileum exhibited reductions of these polyamines in rats infused with TPN or TPN plus GLP-2. DFMO infusion further reduced these polyamines in the ileum, while levels of spermine were increased. Concentrations of ornithine decarboxylase were elevated in jejunum of rats infused with TPN or TPN plus GLP-2, but were reduced significantly in DFMO-treated rats. These results suggest that normal levels of polyamines are necessary for the expression of GLP-2-induced hyperplasia. Differential effects of GLP-2 and DFMO across gut segments may relate to regional differences in proliferative and anti-apoptotic effects of the treatments.
Asunto(s)
Péptidos Similares al Glucagón/farmacología , Intestino Grueso/anomalías , Intestino Grueso/efectos de los fármacos , Intestino Delgado/anomalías , Intestino Delgado/efectos de los fármacos , Nutrición Parenteral Total/efectos adversos , Poliaminas/farmacología , Alimentación Animal , Animales , Péptido 2 Similar al Glucagón , Péptidos Similares al Glucagón/administración & dosificación , Intestino Grueso/anatomía & histología , Intestino Delgado/anatomía & histología , Masculino , Tamaño de los Órganos , Poliaminas/administración & dosificación , Ratas , Ratas Endogámicas F344RESUMEN
Immature myeloid cells have been implicated as a source of postburn inflammation, and the appearance of these cells correlates with enhanced upregulation of hematopoiesis. The role of proliferative cells in postburn immune changes has not been directly tested. Gemcitabine, a ribonucleotide reductase inhibitor, has been shown to deplete proliferative immature myeloid cells in tumor models while sparing mature cells, leading to restored lymphocyte function and tumor regression. We treated burn mice at postburn day 6 (PBD6) with 120 mg/kg gemcitabine. On PBD8, splenocytes were taken and stimulated with LPS, peptidoglycan, or concanavalin A. The blood and spleen cell populations were enumerated by flow cytometry or automated cell counter. In addition, mice treated with gemcitabine were given LPS or infected with Pseudomonas aeruginosa at PBD8, and mortality was monitored. Gemcitabine depleted burn-induced polymorphonuclear leukocytes and inflammatory monocytes without affecting mature F4/80 macrophages. This was accompanied by reduced TNFα, IL-6, and IL-10 production by burn splenocytes. Burn splenocytes stimulated with mitogens exhibited increased nitric oxide production relative to sham mice. In vivo treatment of burn mice with gemcitabine blocked these burn-induced changes without damaging lymphocyte function. Treatment of burn mice with gemcitabine ameliorated burn-induced susceptibility to LPS and infiltration of polymorphonuclear leukocytes into the liver and lung. Finally, gemcitabine treatment blocked the protective effect of burn injury upon P. aeruginosa infection. Our report shows that proliferative cells are major drivers of postburn immune changes and provides evidence that implicates immature myeloid cells in these processes.
Asunto(s)
Quemaduras/inmunología , Desoxicitidina/análogos & derivados , Células Mieloides/efectos de los fármacos , Ribonucleótido Reductasas/antagonistas & inhibidores , Animales , Quemaduras/tratamiento farmacológico , Concanavalina A/farmacología , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Evaluación Preclínica de Medicamentos , Interleucina-10/biosíntesis , Interleucina-6/biosíntesis , Recuento de Leucocitos , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Monocitos/fisiología , Células Mieloides/inmunología , Células Mieloides/metabolismo , Óxido Nítrico/biosíntesis , Peptidoglicano/farmacología , Infecciones por Pseudomonas/complicaciones , Bazo/inmunología , Bazo/patología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , GemcitabinaRESUMEN
The development of anorexia continues to be a serious treatment issue for cancer patients. Because the orexigenic peptide, ghrelin, is active through systemic routes and activates hypothalamic neuropeptide systems known to be refractory in anorectic tumor-bearing (TB) rats, we investigated whether it would prevent the development of cancer anorexia when infused continuously intravenously. The 24-h food intake was increased in nontumor-bearing (NTB) rats at a dose of 288 microg/day ghrelin. However, no tested dose of ghrelin, up to 576 microg/day, elicited increased feeding in TB rats prior to or subsequent to the development of anorexia. In hypothalamus, ghrelin-infused TB rats exhibited significantly increased concentration of neuropeptide Y (NPY) as compared to saline-infused TB rats. Hypothalamic expression of NPY and agouti-related protein (AgRP) messenger RNA were elevated in ghrelin-infused TB rats as compared to NTB rats, but saline-infused TB rats also exhibited increased expression of AgRP. Proopiomelanocortin message was reduced in ghrelin-infused and saline-infused TB rats as compared to noninfused TB control rats. Although ghrelin infusion did not preserve muscle protein, a significant saving in body fat was observed in TB rats. Thus, the adiposity effects of ghrelin did not require an orexigenic response to the peptide. These results suggest that continuous ghrelin infusion may not be an effective treatment for cancer anorexia.