Moderate exercise improves gait stability in disabled elders

Background: Decreased muscle strength impedes elders' functional performance in daily activities such as gait. The mechanisms whereby increased strength improves gait are unknown.Methods: A prospective, blinded, randomized trial of moderate intensity strength exercise was conducted and its impact was measured on functional mobility during gait in 132 functionally limited elders. Lower extremity strength was measured, including hip abductor, hip extensor, and knee extensor strength. Of the 132 subjects, 120 subjects (mean age, 75.lyrs) completed 6 months of elastic band resistance training at least 3 times a week or served as no-exercise controls.Results: Subjects increased their lower extremity strength in the exercise and control groups, by 17.6% and 7.3% (p < .01), respectively. Gait stability improved significantly more in the exercise group than in the control group (p < .05). Increases in forward gait velocity were not significantly different between groups. Peak mediolateral velocity and base of support improved in the exercise group, but not in the control group. Change in lower extremity strength correlated significantly but weakly with many of the gait variables.Conclusions: Gait stability, especially mediolateral steadiness, improved in the exercise group but not in the control group. These results show that even moderate strength gains benefit gait performance in elders and thus provide a sound basis for encouraging low-intensity strength training for elders with functional limitations.     

Allergic challenge-elicited lipid bodies compartmentalize in vivo leukotriene C4 synthesis within eosinophils

Eosinophils are an important source of leukotriene (LT)C(4), which can be synthesized within lipid bodies-cytoplasmic organelles where eicosanoid formation may take place. Allergy-driven lipid body formation and function have never been investigated. Here, we studied the in vivo induction and role of lipid bodies within eosinophils recruited to sites of allergic inflammation. Using two murine models of allergic inflammation (asthma and pleurisy), we verified that parallel to the eosinophil influx, allergic challenge also induced lipid body formation within recruited eosinophils. Neutralizing antibodies to eotaxin/CCL11, RANTES/CCL5, or CCR3 partially inhibited lipid body formation within recruited eosinophils in the allergic pleurisy model. Likewise, intrapleural administration of RANTES or eotaxin also induced significant influx of eosinophils loaded with lipid bodies. By immunolabeling, we detected the presence of a key enzyme involved in the leukotriene metabolism-5-lipoxygenase-within eosinophil lipid bodies formed in vivo after allergen challenge. Furthermore, specific immunolocalization of newly formed LTC(4) demonstrated that lipid bodies were the sites of formation of this eicosanoid within infiltrating eosinophils. Therefore, allergic inflammation triggers in vivo formation of new lipid bodies within infiltrating eosinophils, a phenomenon largely mediated by eotaxin/RANTES acting via CCR3 receptors. Such in vivo allergen-driven lipid bodies function as intracellular compartments of LTC(4) synthesis.     

Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration

The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response.     

The cellular biology of eosinophil eicosanoid formation and function

Eosinophils are capable of generating eicosanoid derivatives of arachidonic acid by means of cyclooxygenase and the 5- and 15-lipoxygenase (LO) pathways. Moreover, eosinophils, because of their expression of leukotriene (LT) C(4) synthase, are a major source of 5-LO-derived cysteinyl LTs, which are potent paracrine mediators of bronchial obstruction and inflammation pertinent to asthma. The regulation of eicosanoid formation within eosinophils involves activation of key enzymes at specific intracellular sites. Calcium ionophore-elicited translocation of 5-LO to the membranes of the nuclear envelope is associated with LTC(4) formation. In addition, lipid bodies, the formation of which is initiated by specific receptor-mediated signaling pathways, are sites of cyclooxygenase- and LO-pathway eicosanoid formation. Newly formed LTC(4) can be immunolocalized at perinuclear membranes in ionophore-activated eosinophils and at lipid bodies in CCR3 agonist (eg, eotaxin) chemokine-stimulated eosinophils. The local generation of eicosanoids at distinct sites within eosinophils may be important for the roles of these eicosanoids, both as paracrine mediators pertinent to inflammation and as intracrine signal-transducing mediators that help regulate cellular responses of eosinophils.     

Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia

Interferon (IFN)-gamma, the main cytokine responsible for immunological defense against Toxoplasma gondii, is essential in all infected tissues, including the central nervous system. However, IFN-gamma-activated microglia may cause tissue injury through production of toxic metabolites such as nitric oxide (NO), a potent inducer of central nervous system pathologies related to inflammatory neuronal disturbances. Despite potential NO toxicity, neurodegeneration is not commonly found during chronic T. gondii infection. In this study, we describe decreased NO production by IFN-gamma-activated microglial cells infected by T. gondii. This effect involved strong inhibition of iNOS expression in IFN-gamma-activated, infected microglia but not in uninfected neighboring cells. The inhibition of NO production and iNOS expression were parallel with recovery of neurite outgrowth when neurons were co-cultured with T. gondii-infected, IFN-gamma-activated microglia. In the presence of transforming growth factor (TGF)-beta1-neutralizing antibodies, the beneficial effect of the parasite on neurons was abrogated, and NO production reverted to levels similar to IFN-gamma-activated uninfected co-cultures. In addition, we observed Smad-2 nuclear translocation, a hallmark of TGF-beta1 downstream signaling, in infected microglial cultures, emphasizing an autocrine effect restricted to infected cells. Together, these data may explain a neuropreservation pattern observed during immunocompetent host infection that is dependent on T. gondii-triggered TGF-beta1 secretion by infected microglia.     

Chest computed tomography findings in severe influenza pneumonia occurring in neutropenic cancer patients

OBJECTIVE:

To describe the chest computed tomography findings for severe influenza H1N1 infection in a series of hospitalized neutropenic cancer patients.

METHODS:

We performed a retrospective systematic analysis of chest computed tomography scans for eight hospitalized patients with fever, neutropenia, and confirmed diagnoses of influenza H1N1. The clinical data had been prospectively collected.

RESULTS:

Six of eight patients (75%) developed respiratory failure and required intensive care. Prolonged H1N1 shedding was observed in the three mechanically ventilated patients, and overall hospital mortality in our series was 25%. The most frequent computed tomography findings were ground-glass opacity (all patients), consolidation (7/8 cases), and airspace nodules (6/8 cases) that were frequently moderate or severe. Other parenchymal findings were not common. Five patients had features of pneumonia, two had computed tomography findings compatible with bronchitis and/or bronchiolitis, and one had tomographic signs of chronicity.

CONCLUSION:

In this series of neutropenic patients with severe influenza H1N1 infection, chest computed tomography demonstrated mainly moderate or severe parenchymatous disease, but bronchiolitis was not a common feature. These findings associated with febrile neutropenia should elicit a diagnosis of severe viral infection.     

Intellectual functioning of childhood leukemia survivors - relation to Tau protein - a marker of white matter injury

PurposeChemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can influence on brain functioning in the future. In a prospective study we analysed the cognitive functions of ALL survivors in relation to Tau protein as a marker of white matter injury.Material and methodsThirty-one survivors of childhood ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated with chemotherapy alone, rested in first remission; underwent Intelligence tests- Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the treatment.ResultsThe analysis showed that all survivors attained the average scores in intelligence tests. A negative correlation was found between methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had higher values of Performance Intelligence Quotient (PIQ) than males. A negative correlation was noted of Tau protein levels obtained from the last CSF with: Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and FFD but not with Verbal Comprehension Index.ConclusionOur results suggest the possibility of white matter injury during the treatment for ALL with chemotherapy alone. Elevated Tau protein level in CSF at the end of treatment might indicate future difficulties in neurocognitive functioning.     

Polyclonal antibodies against properly folded Dengue virus NS1 protein expressed in E. coli enable sensitive and early dengue diagnosis

The non-structural 1 (NS1) protein plays an important role in dengue diagnosis because it has been detected as a soluble serum antigen in both primary and secondary infections. The NS1 protein was expressed in Escherichia coli cells, and the efficiency of four different refolding protocols was tested. All of the protocols generated dimeric NS1 in a conformation similar to that of the protein expressed by eukaryotic cells. A polyclonal antibody produced from the properly folded E. coli recombinant NS1 (rNS1) protein proved to be a useful tool for the diagnosis of Dengue virus because it detected 100% of the Dengue virus 2 (DENV2) in infected patients’ sera and 60% of the DENV IgM-positive sera not detected by commercial NS1-based diagnostic kits. These data suggest a high-efficiency method for correctly folding rNS1 that maintains its structural and immunogenic properties. In addition, a detection method using the polyclonal antibody against correctly folded rNS1 seemed to be more sensitive and efficient for NS1 detection in serum, highlighting its usefulness for developing a high-sensitivity diagnostic kit.