A morphometric study on the longitudinal and lateral symmetry of the sural nerve in mature and aging female rats

Aging affects peripheral nerve function and regeneration in experimental models but few literature reports deal with animals aged more than one year. We investigated morphological and morphometric aspects of the sural nerve in aging rats. Female Wistar rats 360, 640 and 720 days old were killed, proximal and distal segments of the right and left sural nerves were prepared for light microscopy and computerized morphometry. No morphometric differences between proximal and distal segments or between right and left sides at the same levels were found in all experimental groups. No increase in fiber and axon sizes was observed from 360 to 720 days. Likewise, no difference in total myelinated fiber number was observed between groups. Myelinated fiber population distribution was bimodal, being the 720-days old animals` distribution shifted to the left, indicating a reduction of the fiber diameters. The 9 ratio distribution of the 720-days old animals` myelinated fiber was also shifted to the left, which suggests axonal atrophy. Morphological alterations due to aging were observed, mainly related to the myelin sheath, which suggests demyelination. Large fibers were more affected than the smaller ones. Axon abnormalities were not as common or as obvious as the myelin changes and Wallerian degeneration was rarely found. These alterations were observed in all experimental groups but were much less pronounced in rats 360 days old and their severity increased with aging. in conclusion, the present study indicates that the aging neuropathy present in the sural nerve of female rats is both axonal and demyelinating. (C) 2008 Elsevier B.V. All rights reserved.

Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection

Severe dengue infection in humans causes a disease characterized by thrombocytopenia, increased levels of cytokines, increased vascular permeability, hemorrhage, and shock. Treatment is supportive. Activation of platelet-activating factor (PAF) receptor (PAFR) on endothelial cells and leukocytes induces increase in vascular permeability, hypotension, and production of cytokines. We hypothesized that activation of PAFR could account for the major systemic manifestations of dengue infection. Inoculation of adult mice with an adapted strain of Dengue virus caused a systemic disease, with several features of the infection in humans. In PAFR(-/-) mice, there was decreased thrombocytopenia, hemoconcentration, decreased systemic levels of cytokines, and delay of lethality, when compared with WT infected mice. Treatment with UK-74,505, an orally active PAFR antagonist, prevented the above-mentioned manifestations, as well as hypotension and increased vascular permeability, and decreased lethality, even when started 5 days after virus inoculation. Similar results were obtained with a distinct PAFR antagonist, PCA-4246. Despite decreased disease manifestation, viral loads were similar (PAFR(-/-)) or lower (PAFR antagonist) than in WT mice. Thus, activation of PAFR plays a major role in the pathogenesis of experimental dengue infection, and its blockade prevents more severe disease manifestation after infection with no increase in systemic viral titers, suggesting that there is no interference in the ability of the murine host to deal with the infection. PAFR antagonists are disease-modifying agents in experimental dengue infection.

Puzzling challenges in contemporary neuroscience: Insights from complexity and emergence in epileptogenic circuits

The brain is a complex system that, in the normal condition, has emergent properties like those associated with activity-dependent plasticity in learning and memory, and in pathological situations, manifests abnormal long-term phenomena like the epilepsies. Data from our laboratory and from the literature were classified qualitatively as sources of complexity and emergent properties from behavior to electrophysiological, cellular, molecular, and computational levels. We used such models as brainstem-dependent acute audiogenic seizures and forebrain-dependent kindled audiogenic seizures. Additionally we used chemical OF electrical experimental models of temporal lobe epilepsy that induce status epilepticus with behavioral, anatomical, and molecular sequelae such as spontaneous recurrent seizures and long-term plastic changes. Current Computational neuroscience tools will help the interpretation. storage, and sharing of the exponential growth of information derived from those studies. These strategies are considered solutions to deal with the complexity of brain pathologies such as the epilepsies. (C) 2008 Elsevier Inc. All rights reserved.

Tuberculosis among health care workers in a Brazilian tertiary hospital emergency unit

The Brazilian emergency system is being reorganized as a hierarchy in the region of Ribeirao Preto, state of Sao Paulo. We found increased occupational risk for tuberculosis in this region tertiary reference center-a nurse technician (Incidence rate [IR] 526.3/100000 inhabitants) had a risk of tuberculosis 12.6 (95% confidence interval [CI], 2.57-37.23) greater than the city population (41.8/100000 inhabitants). The system reorganization will have to make the centers adequate to deal with this problem. (C) 2008 Elsevier Inc. All rights reserved.

In vitro evidence for immune evasion activity by human plasmin associated to pathogenic Leptospira interrogans

Leptospirosis is a widespread re-emerging zoonosis of human and veterinary concern. It has been shown that virulent leptospires protect themselves against the host`s innate immune system, a strategy that allows the bacteria to reach immunologically safe environments. Although extensive studies on host pathogen interactions have been performed, little is known on how leptospires deal with host immune attack. In a previous work, we demonstrated the ability of leptospires to bind human plasminogen (PLC), that after treatment with activators, conferred plasmin (PLA) activity on the bacteria surface. In this study, we show that the PLA activity associated to the outer surface of Leptospira could interfere with the host immune attack by conferring some evasion advantage during infection. We demonstrate that PLA-coated leptospires interfere with complement Ob and IgG depositions on the bacterial surface, probably through the degradation of these components, thus diminishing opsonization process. Similar decrease on the deposition was observed when normal and immune sera from patients diagnosed with leptospirosis were employed as a source of IgG. We believe that decreasing opsonization by PLA generation might be an important aspect of the leptospiral immune escape strategy and survival. To our knowledge, this is the first proteolytic activity of plasmin associated-Leptospira related to anti-opsonic properties reported to date. (C) 2011 Elsevier Ltd. All rights reserved.

Behavior: A Relevant Tool for Brain-immune System Interaction Studies

Neuroimmunomodulation describes the field focused on understanding the mechanisms by which the central nervous system interacts with the immune system, potentially leading to changes in animal behavior. Nonetheless, not many articles dealing with neuroimmunomodulation employ behavior as an analytical endpoint. Even fewer papers deal with social status as a possible modifier of neuroimmune phenomena. In the described sets of experiments, we tackle both, using a paradigm of social dominance and subordination. We first review data on the effects of different ranks within a stable hierarchical relationship. Submissive mice in this condition display more anxiety-like behaviors, have decreased innate immunity, and show a decreased resistance to implantation and development of melanoma metastases in their lungs. This suggests that even in a stable, social, hierarchical rank, submissive animals may be subjected to higher levels of stress, with putative biological relevance to host susceptibility to disease. Second, we review data on how dominant and submissive mice respond differentially to lipopolysaccharide (LPS), employing a motivational perspective to sickness behavior. Dominant animals display decreased number and frequency in several aspects of behavior, particularly agonistic social interaction, that is, directed toward the submissive cage mate. This was not observed in submissive mice that maintained the required behavior expected by its dominant mate. Expression of sickness behavior relies on motivational reorganization of priorities, which are different along different social ranks, leading to diverse outcomes. We suggest that in vitro assessment of neuroimmune phenomena can only be understood based on the behavioral context in which they occur.