Helicobacter pylori‐derived neutrophil‐activating protein increases the lifespan of monocytes and neutrophils

An invariable feature of Helicobacter pylori‐infected gastric mucosa is the persistent infiltration of inflammatory cells. The neutrophil‐activating protein (HP‐NAP) has a pivotal role in triggering and orchestrating the phlogistic process associated with H. pylori infection. Aim of this study was to address whether HP‐NAP might further contribute to the inflammation by increasing the lifespan of inflammatory cells. We report that HP‐NAP is able to prolong the lifespan of monocytes, in parallel with the induction of the anti‐apoptotic proteins A1, Mcl‐1, Bcl‐2 and Bcl‐X_L. This effect does not result from a direct action on the apoptotic machinery, but rather it requires the release of endogenous pro‐survival factors, such as interleukin‐1β, which probably acts in synergy with other unidentified mediators. We also report that HP‐NAP promotes the survival of Ficoll‐purified neutrophils in a monocyte‐dependent fashion: indeed, mononuclear cell depletion of Ficoll‐purified neutrophils completely abolished the pro‐survival effect by HP‐NAP. In conclusion, our data reinforce the notion that HP‐NAP has a pivotal role in sustaining a prolonged activation of myeloid cells.     

Periodontal therapy increases neutrophil extracellular trap degradation

In periodontitis, polymorphonuclear leucocytes (PMNs) are activated. They entrap and eliminate pathogens by releasing neutrophil extracellular traps (NETs). Abnormal NET degradation is part of a pro-inflammatory status, affecting co-morbidities such as cardiovascular disease. We aimed to investigate the ex vivo NET degradation capacity of plasma from periodontitis patients compared to controls (part 1) and to quantify NET degradation before and after periodontal therapy (part 2). Fresh NETs were obtained by stimulating blood-derived PMNs with phorbol 12-myristate 13-acetate. Plasma samples from untreated periodontitis patients and controls were incubated for 3 h onto freshly generated NETs (part 1). Similarly, for part 2, NET degradation was studied for 91 patients before and 3, 6 and 12 mo after non-surgical periodontal therapy with and without adjunctive systemic antibiotics. Finally, NET degradation was fluorospectrometrically quantified. NET degradation levels did not differ between periodontitis patients and controls, irrespective of subject-related background characteristics. NET degradation significantly increased from 65.6 ± 1.7% before periodontal treatment to 75.7 ± 1.2% at 3 mo post periodontal therapy, and this improvement was maintained at 6 and 12 mo, irrespective of systemic usage of antibiotics. Improved NET degradation after periodontitis treatment is another systemic biomarker reflecting a decreased pro-inflammatory status, which also contributes to an improved cardiovascular condition.     

Fatal pulmonary acariasis in an aged indoor rhesus macaque (Macaca mulatta)

Pulmonary acariasis is a sporadic, incidental finding in colony‐raised rhesus macaques (Macaca mulatta). Prophylactic treatment in indoor‐raised and indoor‐housed macaques is not routine due to low prevalence, lack of clinical significance, and potential risk of toxicosis. This case is an unusually severe infestation of Pneumonyssus simicola in an indoor‐housed rhesus macaque, which ultimately resulted in this animal's death.     

The neutrophil-activating protein of Helicobacter pylori (HP-NAP) as an immune modulating agent

During evolution microorganisms have developed several immune modulating strategies. The Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor that attracts and activates neutrophils, and promotes their endothelial adhesion and the production of oxygen radicals and chemokines, including CXCL8, CCL3 and CCL4. HP-NAP, a TLR2 agonist, is an immune modulator able to induce the expression of interleukin-12 (IL-12) and IL-23 by human neutrophils and monocytes. In fact, HP-NAP has the potential to shift antigen-specific T-cell responses from a predominant Th2 to a polarized Th1 cytotoxic phenotype, characterized by high levels of interferon-gamma and tumor necrosis factor-alpha production. Thus, HP-NAP is a key factor driving Th1 inflammation in H. pylori infection and may be a new tool for future therapeutic strategies aimed at redirecting Th2 into Th1 responses, for example in atopy, vaccinology and cancer immunotherapy.     

Chromatin structure and evolution in the human genome

Background  

Evolutionary rates are not constant across the human genome but genes in close proximity have been shown to experience similar levels of divergence and selection. The higher-order organisation of chromosomes has often been invoked to explain such phenomena but previously there has been insufficient data on chromosome structure to investigate this rigorously. Using the results of a recent genome-wide analysis of open and closed human chromatin structures we have investigated the global association between divergence, selection and chromatin structure for the first time.     

Toxicity study in juvenile rats with the α4β2 nicotinic acetylcholine receptor partial agonist CP-601,927

BACKGROUND: CP‐601927 is a selective α₄β₂ nicotinic acetylcholine receptor (nAChR) partial agonist. The objective of this study was to assess the potential effects persisting into adulthood when CP‐601,927 was administered to neonatal/juvenile rats. Since the juvenile toxicity study was being performed early in the development program and this study would represent the longest dosing period yet evaluated, the study design incorporated standard endpoints typically evaluated in a general toxicity screening study. METHODS: CP‐601,927 was administered to Sprague‐Dawley rats from postnatal day (PND) 7–70 by oral gavage at doses of 0.3, 1, or 3 mg/kg. During treatment animals were evaluated for growth, development, and sexual maturation. At the end of the treatment period general toxicity screening endpoints were collected (e.g., organ weights, histology, clinical chemistry). Following a 2‐week latency period, animals were evaluated for CNS function in a comprehensive behavioral training battery consisting of a functional observational battery, motor activity, acoustic startle response, and learning and memory evaluations. Reproductive competency was evaluated by mating treated rats and allowing pregnant dams to deliver and rear their litters until PND 10. RESULTS AND CONCLUSIONS: Treatment‐related findings included the death of 2 males receiving 3 mg/kg CP‐601,927, and transient reductions in body weight for both males and females during the third week of dosing which quickly recovered to control levels. The only treatment‐related alteration in behavior was decreased motor activity, which occurred only in females at the highest dose tested. CP‐601,927 had no effect on acoustic startle response, learning and memory, sexual maturation, reproductive capacity, or general toxicity endpoints. Birth Defects Res (Part B) 92:323–332, 2011. © 2011 Wiley‐Liss, Inc.