Safety and performance of a system specifically designed for selective site pacing

Introduction: In the right ventricle, selective site pacing (SSP) has been shown to avoid detrimental hemodynamic effects induced by right ventricular apical pacing and, in the right atrium, to prevent the onset of atrial fibrillation and to slow down disease progression. The purpose of our multicenter observational study was to describe the use of a transvenous 4‐French catheter‐delivered lead for SSP in the clinical practice of a large number of centers. Methods: We enrolled 574 patients in whom an implantable device was indicated. In all patients, SSP was achieved by using the Select Secure System? (Medtronic Inc., Minneapolis, MN, USA). Results: In 570 patients, the lead was successfully implanted. In 125 patients, atrial SSP was performed: in 75 (60%) the lead was placed in the interatrial septum, in 31 (25%) in the coronary sinus ostium, and in 19 (15%) in the Bachman bundle. Ventricular SSP was undertaken in 138 patients: in 105 (76%) the high septal right ventricular outflow tract (RVOT) position was paced, in seven (5%) the high free‐wall RVOT, in 25 (18%) the low septal RVOT, and in one (1%) the low free‐wall RVOT. In the remaining 307 patients, the His zone was paced: in 87 (28%) patients, direct His‐bundle pacing and in 220 (72%) patients para‐hisian pacing was achieved. Adequate pacing parameters and a lead‐related complication rate of 2.6% were recorded during a follow‐up of 20 ± 10 months. Conclusions: Our results demonstrated that many sites, in the right atrium, in the right ventricle, and in His‐bundle region, can be paced using the Select Secure System?. (PACE 2011; 34:339–347)     

Innovative non-animal testing strategies for reproductive toxicology: the contribution of Italian partners within the EU project ReProTect

Reproductive toxicity, with its many targets and mechanisms, is a complex area of toxicology; thus, the screening and identification of reproductive toxicants is a main scientific challenge for the safety assessment of chemicals, including the European Regulation on Chemicals (REACH). Regulatory agencies recommend the implementation of the 3Rs principle (refinement, reduction, replacement) as well as of intelligent testing strategies, through the development of in vitro methods and the use of mechanistic information in the hazard identification and characterization steps of the risk assessment process. The EU Integrated Project ReProTect (6th Framework Programme) implemented an array of in vitro tests to study different building blocks of the mammalian reproductive cycle: methodological developments and results on male and female germ cells, prostate and placenta are presented.     

Cytokine components and mucosal immunity in the oviduct of Xenopus laevis (amphibia, pipidae)

Most studies on the mucosal immunity in female reproductive tissues have been performed in mammals. In all species, apart from their reproductive strategies, immunity in the genital mucosa is required to defend the host against luminal pathogens.In this study we investigated the role of the innate immunity of the oviductal mucosa of Xenopus laevis, an amphibian characterized by external fertilization. In particular we examined the expression and localization of Interleukin-1β (IL1B), Macrophage migration inhibitory factor (MIF) and Interleukin-1 receptor type 1 (IL1R1) in different oviductal portions including an upper glandular region, an intermediate and a lower aglandular region (the ovisac). Tissues were examined by immunohistochemistry and western blot using polyclonal antibodies against human molecules.IL1B, MIF and IL1R1 were all shown in the three oviductal regions examined, albeit with a general increase towards the external environment. A substantial difference among the cytokine components was also observed mainly in the epithelium of the glandular and intermediate regions. Specifically, all three molecules were expressed by the luminal ciliated cells while only IL1R1 was present in the unciliated cells at the bottom of the epithelial ingrowths. The expression of IL1R1 in these cells appeared as a continuous layer separating the epithelium from the underlying tissues.While supporting the role of the innate immune system for host’s defense against pathogens, the peculiar distribution of the cytokine components in the oviduct of X. laevis suggests novel immunologic strategies useful to assure gland secretion essential for egg formation and fertilization.     

With time on our side? Task-dependent compensatory processes in graceful aging

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.     

Response to Intracanal Medication in Immature Teeth with Pulp Necrosis: An Experimental Model in Rat Molars

Introduction

The present study aimed at developing an experimental model in rat molars for evaluating treatment strategies in necrotic immature teeth.

Methods

To define the periods to be adopted in the experimental procedures and to confirm induction of periapical lesions and interruption of root embryogenesis, the left lower first molars of 4-weeks-old Wistar rats underwent pulpectomy and were left open to the oral environment. Comparisons with the right lower first molars (vital teeth) were performed in animals with ages of 7, 10, 13, and 16 weeks. In another group of animals the teeth were left open for 3 weeks, and then interventions for disinfection including the use of an antibiotic paste were carried out. Root formation was then assessed after 3 and 6 weeks on the basis of radiographic and histologic evaluation.

Results

Vital teeth showed increase of root length and hard tissue thickness throughout the experimental periods. On the other hand, induction of necrosis arrested root formation. Teeth subjected to disinfection with sodium hypochlorite associated with the triple antibiotic paste showed significant reduction of periapical lesions, gain in root length, and increased wall thickness compared with the control (P < .05).

Conclusions

The root canal disinfection protocol used was able to reduce periapical lesion size and improve root development. The experimental model presented should contribute to studies that aim at improving therapeutic strategies for necrotic immature teeth by using a rat model.     

Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophils

Human polymorphonuclear neutrophils (PMN) chemotax to a foreign entity. When the chemoattractants' origins are reached, specific receptors bind to the invader's surface, initiating phagocytosis, phagosome formation, and fusion with granule membranes, generating the bactericidal oxidative burst, and releasing lytic enzymes, specific peptides, and proteins. We explored the initial signaling involved in these functions by observing na?ve, unprimed PMN in suspension using fluorescent indicators of cytoplasmic signals (Delta[Ca(2+)](i) and DeltapH(i)) and of bactericidal entities (oxidative species and elastase) exposed to N-formyl-methionyl-leucyl-phenylalanine (fMLP) and/or multivalent immune complexes (IC). fMLP and IC each initiate a rapid transient rise in [Ca(2+)](i), mostly from intracellular stores, simultaneously with a drop in pH(i); these are followed by a drop in [Ca(2+)](i) and a rise in pH(i), with the latter being due to a Na(+)/H(+) antiport. The impact of a second stimulation depends on the order in which stimuli are applied, on their dose, and on their nature. Provided that [Ca(2+)](i) is restored, 10(-7) M fMLP, previously shown to elicit maximal Delta[Ca(2+)](i) but no bactericidal functions, did not prevent the cells' responses with Delta[Ca(2+)](i) to a subsequent high dose of fMLP or IC; conversely, cells first exposed to 120 mug/ml IC, previously shown to elicit maximal Delta[Ca(2+)](i) and bactericidal functions, exhibited no subsequent Delta[Ca(2+)](i) or DeltapH(i) to either stimulus. While exposure to 10(-7) M fMLP, which saturates the PMN high-affinity receptor, did not elicit bactericidal release from these na?ve unprimed PMN in suspension, 10(-5) M fMLP did, presumably via the low-affinity receptor, using a different Ca(2+) source.     

DNA vaccination elicits protective immune responses against pandemic and classic swine influenza viruses in pigs

Swine influenza is a highly contagious viral infection in pigs that significantly impacts the pork industry due to weight loss and secondary infections. There is also the potential of a significant threat to public health, as was seen in 2009 when the pandemic H1N1 influenza virus strain emerged from reassortment events among avian, swine, and human influenza viruses within pigs. As classic and pandemic H1N1 strains now circulate in swine, an effective vaccine may be the best strategy to protect the pork industry and public health. Current inactivated-virus vaccines available for swine influenza protect only against viral strains closely related to the vaccine strain, and egg-based production of these vaccines is insufficient to respond to large outbreaks. DNA vaccines are a promising alternative since they can potentially induce broad-based protection with more efficient production methods. In this study we evaluated the potentials of monovalent and trivalent DNA vaccine constructs to (i) elicit both humoral and gamma interferon (IFN-γ) responses and (ii) protect pigs against viral shedding and lung disease after challenge with pandemic H1N1 or classic swine H1N1 influenza virus. We also compared the efficiency of a needle-free vaccine delivery method to that of a conventional needle/syringe injection. We report that DNA vaccination elicits robust serum antibody and cellular responses after three immunizations and confers significant protection against influenza virus challenge. Needle-free delivery elicited improved antibody responses with the same efficiency as conventional injection and should be considered for development as a practical alternative for vaccine administration.