Metabolic features of neutrophilic differentiation of HL-60 cells in hyperglycemic environments.

INTRODUCTION: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study. RESEARCH DESIGN AND METHODS: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations. RESULTS: Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation. CONCLUSIONS: HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

Neutrophils, an emerging new therapeutic platform.

Neutrophils possess unique characteristics that render them indispensable to health, and patients with irregular neutrophil counts or functions suffer from increased morbidity and mortality. As neutrophils are short-lived postmitotic cells, genetic aberrations cannot be corrected directly in neutrophils and must be targeted in their progenitors. Neutrophils are increasingly being contemplated for a range of therapeutic applications, including restoration or modulation of immune function and targeting of solid tumors. This review addresses the state-of-the-art in neutrophil transfusions and their possible applications for infectious disease prevention and treatment. It offers a landscape of the most recent gene therapy approaches to address neutrophil-related genetic diseases. We also discuss how ongoing research could broaden the applicability of neutrophil-based therapies to solid cancer treatments and beyond.

Differential characteristics of acute heart failure in very elderly patients: the prospective RICA study.

INTRODUCTION: Acute heart failure (AHF) is a frequent epidemic in geriatrics. The main aim of this study was to evaluate the clinical and prognostic differences of very elderly patients with AHF compared to the rest, and evaluate the factors associated with 90-day mortality. METHODS: We analyzed 3828 patients hospitalized for AHF with an age of ≥ 70 years. The population was divided into three groups: 70-79, 80-89 and ≥ 90 years old (nonagenarians). The baseline characteristics of patients nonagenarians were compared with the rest. In the group of nonagenarians, their clinical characteristics were analyzed according to the left ventricular ejection fraction (LVEF) and the factors associated with mortality at 90 days of follow-up. RESULTS: Nonagenarians showed higher comorbidity and cognitive deterioration, worse basal functional status, and preserved LVEF. Alternatively, they presented a lower rate of diabetes mellitus, lower incidence of de novo AHF, and lower prescription of angiotensin-converting-enzyme inhibitors, aldosterone blockers, anticoagulants, and statins at hospital discharge. Of the total, 334 patients (9.3%) had died by 90 days. The 90-day mortality rate was highest in nonagenarians (7.1% vs 9.8% vs 17%; p = 0.001). Multivariate analysis showed that renal failure, New York Heart Association (NYHA) functional classifications of III-IV, and a more advanced functional deterioration at baseline are predictors of mortality within 90 days. CONCLUSIONS: The AHF in patients nonagenarians has a different clinical profile compared to younger patients and a higher mortality. In this subgroup of patients having a worse baseline functional status, higher NYHA classification (III-IV), and renal failure are predictors of 90-day mortality.

Alteraciones pulmonares en pacients con sindrome de inmunodeficiencia adquirida / Pulmonary manifestations in patients with adcquired immunodeficiency syndrome

Las alteraciones pulmonares en pacientes con SIDA son muy frecuentes y comunmente se deben a infecciones por gérmenes oportunistas. En las series estadounidenses predominan las infecciones por Pneumocystis carinii y citomegalovirus; en otras poblaciones, las infecciones por microbacterias son frecuentes. En el Hospital General de México predominaron las neumonías agudas e infecciones por citomegalovirus, Mycobacterium tuberculosis, Pneumocystis carinii y las neumonías intersticiales. El diagnóstico precoz y tratamiento adecuado de estas complicaciones son esenciales en el cuidado de los pacientes con SIDA

Metodología del estudio de los pacientes infectados por virus de la inmunodeficiencia humana y criterios actuales para el diagnóstico de SIDA / Methodology for the study of patients infected with the human immunedeficiency virus and current criteria for the diagnosis of AIDS

Este artículo resume los métodos y criterios diagnósticos que se utilizan en la actualidad para la clasificación clínica de los pacientes infectados por virus de la inmunodeficiencia humana. Se señalan los métodos de laboratorio más empleaddos y su interpretación. También se proporciona la última revisión de los criterios diagnósticos elaborada por el Centro para el Control de Enfermedades de Atlanta, Georgia, para el diagnóstico de síndrome de inmunodeficiencia adquirida .