Relationship between oxidative stress and cognitive impairment in the elderly of rural vs. urban communities

Psychological stress and environmental pollution are frequently associated to urban environment and oxidative stress (OxS). Likewise, OxS is a risk factor for cognitive impairment (CI) in the elderly. Therefore, we hypothesized that the prevalence of CI in subjects of the urban area could be higher than in those of the rural area, and linked to higher OxS. The aim of the study was to determine the relationship between OxS and CI in elderly individuals from rural and urban settings in Mexico. Plasmatic TBARS, plasma total antioxidant status, and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in 104 urban and 85 rural elderly individuals. Cognitive functions were evaluated through the Mini Mental State Examination. We found a greater proportion of subjects with OxS and CI in urban than in rural areas (25% vs. 9%), with an odds ratio of 5.67 (CI95% 1.14-38.02, p < 0.05). Our findings suggest that the elderly in urban areas have more OxS and a higher risk of developing CI compared with elderly individuals in a rural environment.     

Interleukin-1 beta (IL-1beta) induces tumor necrosis factor alpha (TNF-alpha) expression on mouse myeloid multipotent cell line 32D cl3 and inhibits their proliferation

Interleukin-1 alpha (IL-1alpha) and beta (IL-1beta) are well known factors that stimulate hematopoiesis, nevertheless there are reports that show that they can also inhibit this activity. While both IL-1alpha and IL-1beta induce the expression of hematopoietic cytokines, such as growth factors and their receptors on myeloid cells, helping thus to regulate hematopoiesis, it is not known if their inhibitory activity is also mediated through the induction of other specific cytokines. In this work we show that recombinant human IL-1beta (rhIL-1beta) inhibits the proliferation of a mouse IL-3-dependent myeloid multipotent cell line (32D cl3), without inducing its differentiation. We show that rhIL-1beta induces in 32D cl3 cells the expression of the tumor necrosis factor alpha (TNF-alpha) gene, a well known growth inhibitor, and that the rhIL-1beta growth inhibition property on 32D cl3 cells is partially due to this secreted TNF-alpha, hinting thus that the inhibition of hematopoiesis by IL-1 is mediated through other induced cytokines.     

The productive conformation of prostaglandin G2 at the peroxidase site of prostaglandin endoperoxide H synthase: docking, molecular dynamics, and site-directed mutagenesis studies

We present a plausible productive conformation obtained by docking calculations for the binding of prostaglandin G2 (PGG2) to the peroxidase site of prostaglandin endoperoxide H synthase-1 (PGHS-1, COX-1). The enzyme-substrate complex stability was verified by molecular dynamics. Structural analysis reveals the requirements for enzyme-substrate recognition and binding: the PGG2 15-hydroperoxide group is in the proximity of the heme iron and participates in a hydrogen bond network with the conserved His207 and Gln203 and a water molecule, whereas the carboxylate group forms salt bridges with the remote Lys215 and Lys222. Site-directed mutagenesis showed that a single mutation of Lys215 or Lys222 does not affect enzyme activity, whereas dual mutation of these residues, to either alanine or glutamate, significantly decreases turnover. This indicates that the conserved cationic pocket is involved in enzyme-substrate binding.     

Circulating Endothelial Cells and Procoagulant Microparticles in Patients with Glioblastoma: Prognostic Value

Aim

Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter.

Methods

Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification.

Results

Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001). After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99^th percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004).

Conclusion

Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma.     

Value of repeated fine needle aspiration cytology in patients with nodular goiter

OBJECTIVE: To assess the value of reaspiration cytology in benign nodular thyroid disease. DESIGN: We prospectively studied 400 patients (365 women, 35 men) aged 46 years (18-89) with nodular thyroid disease and initial benign fine needle aspiration cytology (FNAC). Reaspiration of the same nodule was performed in a median follow-up time of 14 months (6-18). RESULTS: Repeat FNAC was benign in 346 patients (86.5%), insufficient for diagnosis in 42 (10.5%), suspicious in 16 (2.5%) and malignant in 2 (0.5%). All diagnostic changes to suspicious malignant cytology took place in patients with solitary nodules. Surgery confirmed thyroid cancer in the 2 patients with malignant cytology, in 5 of 10 patients with suspicious cytology and in none of 39 patients with benign cytology who underwent surgery for other reasons. Clinical changes (size increase or local symptoms) were not related to changes in cytologic diagnosis after a second aspiration, nor with the results of the biopsy. CONCLUSION: Repeat aspiration cytology of thyroid nodules may correct initial false negative results because of cytologic misdiagnosis, occurring in 1.75% of patients, whereas clinical changes did not contribute to diagnosis change. Repeat aspiration cytology is recommended in all patients with nodular goiter.     

Circulating Endothelial Cells and Microparticles as Prognostic Markers in Advanced Non-Small Cell Lung Cancer

Background

Circulating endothelial cells and microparticles have prognostic value in cancer, and might be predictors of response to chemotherapy and antiangiogenic treatments. We have investigated the prognostic value of circulating endothelial cells and microparticles in patients treated for advanced non-small cell lung cancer.

Methodology/Principal Findings

Peripheral blood samples were obtained from 60 patients before first line, platinum-based chemotherapy +/− bevacizumab, and after the third cycle of treatment. Blood samples from 60 healthy volunteers were also obtained as controls. Circulating endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Phosphatidylserine-positive microparticles were evaluated by flow cytometry. Microparticle-mediated procoagulant activity was measured by the endogen thrombin generation assay. Results: pre- and posttreatment levels of markers were higher in patients than in controls (p<0.0001). Elevated levels of microparticles were associated with longer survival. Elevated pretreatment levels of circulating endothelial cells were associated with shorter survival.

Conclusions/Significance

Circulating levels of microparticles and circulating endothelial cells correlate with prognosis, and could be useful as prognostic markers in patients with advanced non-small cell lung cancer.