Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte–neuron interaction

Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN‐mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N‐methyl‐D‐aspartate (50 µM DL‐AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra‐ and extracellular Ca²⁺ chelators (10 µM BAPTA‐AM and 1 mM EGTA, respectively) and Ca²⁺ influx through L‐type voltage‐dependent Ca²⁺ channel (10 µM verapamil) are implicated in QUIN‐mediated effects. Cells immunostained for the neuronal markers βIII‐tubulin and microtubule‐associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN‐treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron–astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.     

Identification of specific antibodies against the Ag85C-MPT51-HspX fusion protein (CMX) for serological screening of tuberculosis in endemic area

Objectives: Development of new tools for rapid and accurate diagnosis of tuberculosis (TB) is considered a strategy for controlling the disease. The recombinant CMX fusion protein is composed of immunodominant epitopes of the Ag85C (Rv0129c), MPT51 (Rv3803c) and the entire HspX (Rv2031c) proteins from Mycobacterium tuberculosis H37Rv (Mtb). The aim of this study was to evaluate the applicability of a test using the CMX protein in individuals suspected of TB.

Methods: Indirect ELISA was used to measure serum anti-CMX IgM and IgG in individuals with pulmonary TB.

Results: Patients with pulmonary TB had higher titers of IgM (OD = 0.502 ± 0.281) than healthy controls (OD = 0.200 ± 0.125). The cutoff for IgM-ELISA was determined using ROC curve analyzes (AUC = 0.868) with a sensitivity of 80.1% and a specificity of 78.2%. Patients with pulmonary TB also had higher titers of IgG (OD = 0.525 ± 0.391) than healthy controls (OD = 0.215 ± 0.077). The cutoff for IgG-ELISA was determined using ROC curve analyzes (AUC = 0.864) with a sensitivity of 81.7% and a specificity of 74.7%.

Conclusion: The results suggest that the recombinant protein CMX can be used in a serological test to complement the screening of individuals suspected of having active pulmonary TB.     

Mobility therapy and central or peripheral catheter-related adverse events in an ICU in Brazil

OBJECTIVE:

To determine whether mobility therapy is associated with central or peripheral catheter-related adverse events in critically ill patients in an ICU in Brazil.

METHODS:

A retrospective analysis of the daily medical records of patients admitted to the Clinical Emergency ICU of the University of São Paulo School of Medicine Hospital das Clínicas Central Institute between December of 2009 and April of 2011. In addition to the demographic and clinical characteristics of the patients, we collected data related to central venous catheters (CVCs), hemodialysis (HD) catheters and indwelling arterial catheters (IACs): insertion site; number of catheter days; and types of adverse events. We also characterized the mobility therapy provided.

RESULTS:

Among the 275 patients evaluated, CVCs were used in 49%, HD catheters were used in 26%, and IACs were used in 29%. A total of 1,268 mobility therapy sessions were provided to patients while they had a catheter in place. Catheter-related adverse events occurred in 20 patients (a total of 22 adverse events): 32%, infection; 32%, obstruction; and 32%, accidental dislodgement. We found that mobility therapy was not significantly associated with any catheter-related adverse event, regardless of the type of catheter employed: CVC-OR = 0.8; 95% CI: 0.7-1.0; p = 0.14; HD catheter-OR = 1.04; 95% CI: 0.89-1.21; p = 0.56; or IAC-OR = 1.74; 95% CI: 0.94-3.23; p = 0.07.

CONCLUSIONS:

In critically ill patients, mobility therapy is not associated with the incidence of adverse events involving CVCs, HD catheters, or IACs.