Bacterial DNA activates human neutrophils by a CpG-independent pathway

Bacterial DNA stimulates macrophages, monocytes, B lymphocytes, NK cells, and dendritic cells in a CpG-dependent manner. In this work we demonstrate that bacterial DNA, but not mammalian DNA, induces human neutrophil activation as assessed by L-selectin shedding, CD11b upregulation, and stimulation of cellular shape change, IL-8 secretion, and cell migration. Induction of these responses is not dependent on the presence of unmethylated CpG motifs, as neutrophil stimulatory properties were neither modified by CpG-methylation of bacterial DNA nor reproduced by oligonucleotides bearing CpG motifs. We found that human neutrophils express Toll-like receptor (TLR) 9 mRNA. However, as expected for a CpG-independent mechanism, activation does not involve a TLR9-dependent signaling pathway; neutrophil stimulation was not prevented by immobilization of bacterial DNA or by wortmannin or chloroquine, two agents that inhibit TLR9 signaling. Of note, both single-stranded and double-stranded DNA were able to induce activation, suggesting that neutrophils might be activated by bacterial DNA at inflammatory foci even in the absence of conditions required to induce DNA denaturation. Our findings provide the first evidence that neutrophils might be alerted to the presence of invading bacteria through recognition of its DNA via a novel mechanism not involving CpG motifs.     

A simple prognostic score for risk assessment in patients with acute pancreatitis

BackgroundAcute pancreatitis (AP) is a common disease that poses potential serious problems. Its clinical course is often unpredictable. Identification of high risk patients enables early appropriate treatment.MethodsWe conducted a prospective study to develop a new prognostic method that can objectively and easily grade the severity of AP within the first 72 h of admission. The prediction rule was based on clinical and analytical parameters in 308 patients admitted in a community-based hospital. We validated the score in 193 additional patients in the same hospital.ResultsIndependent prognostic factors related to poor prognosis were age > 65 years, leucocytes > 13,000/mm³, albumin < 2.5 mg/dL, calcium < 8.5 mg/dL and reactive C protein > 150 mg/dL. We assigned points to each of the independent factors for complicated AP in proportion to the regression coefficients. We defined three different risk groups according to the points obtained in the prediction rule. Low risk, 0 points (18% patients, 0% risk), moderate, 1–3 points (56% patients, 19% risk) and high, 4–6 points (26% patients, 73% risk). The sensitivity of this formula was 90% with specificity of 63%. The positive and negative predictive values were 50% and 94% respectively.ConclusionsOur simple prediction rule is an additional tool that may help physicians stratifying the severity of AP. Patients with high risk for complicated AP should be kept under close surveillance whereas low risk patients would not need special monitoring.     

A Decreased Response to Resistin in Mononuclear Leukocytes Contributes to Oxidative Stress in Nonalcoholic Fatty Liver Disease

Digestive Diseases and Sciences - Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of...     

Rentabilidad del estudio genético mediante técnicas de next-generation sequencing masiva de pacientes con miocardiopatía arritmogénica de alto riesgo

Introduction and objectives

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC.

Hypovitaminosis D: a widespread epidemic

Vitamin D insufficiency is widespread, regardless of geographical location. It is particularly prevalent in the elderly and has far-ranging health consequences including: osteoporosis, falls, increased risk of cancer, and altered glucose and lipid metabolism. Increasing evidence strongly supports the benefits of vitamin D supplementation and also reveals that present recommendations are inadequate, especially for older individuals. Although additional studies are still needed to further optimize diagnostic and therapeutic approaches, physicians should consider prescribing cholecalciferol--at least 2000 international units (IU) per day--to all elderly patients. Oral cholecalciferol supplementation at that level is inexpensive, safe, and effective, and has great potential to improve the quality of life of the elderly.