Comparison of the TaqMan and LightCycler systems in pharmacogenetic testing: evaluation of the CYP2C9*2/*3 polymorphisms.

Background: Pharmacogenetic testing for drugmetabolizing enzymes is not yet widely used in clinical practice. Methods: In an attempt to facilitate the application of this procedure, we have compared two real-time PCRbased methods, the TaqMan_ and the LightCycler_ for the pharmacogenetic evaluation of CYP2C9*2/*3 polymorphisms. Results and Conclusion: Both procedures are suitable for pharmacogenetic studies. The TaqMan procedure was less expensive in terms of cost per sample, but the TaqMan apparatus is more expensive than the LightCycler apparatus

CXCL16/CXCR6 axis drives microglia/macrophages phenotype in physiological conditions and plays a crucial role in glioma

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM). Considering that CXCL16 specific receptor CXCR6 is diffusely expressed in the brain including in microglia cells, we wanted to investigate the role of CXCL16 in the modulation of microglia cell activity and phenotype, and in the progression of glioma. Here we report that CXCL16 drives microglia polarization toward an anti-inflammatory phenotype, also restraining microglia polarization toward an inflammatory phenotype upon LPS and IFN? stimulation. In the context of glioma, we demonstrate that CXCL16 released by tumor cells is determinant in promoting glioma associated microglia/macrophages (GAMs) modulation toward an anti-inflammatory/pro-tumor phenotype, and that cxcr6ko mice, orthotopically implanted into the brain with GL261 glioma cells,survive longer compared to wild-type mice. We also describe that CXCL16/CXCR6 signaling acts directly on mouse glioma cells, as well as human primary GBM cells, promoting tumor cell growth, migration and invasion. All together these data suggest that CXCL16 signaling could represent a good target to modulate microglia phenotype in order to restrain inflammation or to limit glioma progression

Geological constraints for a conceptual evolutionary model of the slope deformations affecting Mt. Nuovo at Ischia (Italy)

ischia island was the scenario of several Holocene slope in- stability events occurred at different scales, from shallow mass movements, triggered by meteo-climatic forcing, up to massive rock slope failures such as large debris avalanches these last ones related to the volcano-tectonic dynamics of a resurgent caldera. the present study focuses on the gravitational deformation that in- volves Mt. nuovo, located in the western portion of Mt. epomeo resurgent block. a high-resolution engineering-geological model was reconstructed according to a multi-modelling approach sup- ported by field geo-structural evidences and constrained by pas- sive seismic investigations. it revealed a complex morpho-struc- tural setting and led to the identification of a multiple compound mechanism, involving a rock mass volume of about 190 million of cubic meters. the obtained geological model shows a partial structural control of the pre-existing tectonic pattern on slope deformation mechanisms, highlighting geometric and volumetric similarities between the Mt. nuovo ongoing deformation and an already oc- curred rock avalanche. the defined conceptual evolutionary mod- el allows to hypothesize the role of inner pressures constraining the shear zone initiation and propagation and making reliable a future scenario of generalized collapse. Starting from these new field and laboratory data, numerical models will be reconstructed in order to depict the evolution of the gravitational slope deformation, evaluate its sensitivity and constrain future evolutionary instability scenarios

HPV vaccine: knowledge and acceptance to ensure effectiveness

The new Vaccine technologies against transmissible and non-transmissible diseases, such as cancer, have had an impact on international public health. The human papillomavirus (HPV) vaccine is used on a large scale in immunization programs in more than 58 countries, with resultant efficacy and safety for precursor lesions of cervical cancer, in addition to anogenital lesions. After the introduction of quadrivalent HPV vaccine (6,11,16 and 18) in Brazil in 2014, monitoring the vaccination coverage and the development of HPV prevalence incidence of cervical abnormalities and precancerous lesions must be observed, as well as morbidity and mortality trends from in situ and invasive cancer. Encouraging information, counseling and continuing education is recommended as a strategy to broaden vaccine acceptance in order to sediment its implementation and ensure effectiveness in reducing new cases of cervical cancer in the future

KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment

Malignant gliomas are among the most frequent and aggressive cerebral tumors, characterized by high proliferative and invasive indexes. Standard therapy for patients, after surgery and radiotherapy, consists of temozolomide (TMZ), a methylating agent that blocks tumor cell proliferation. Currently, there are no therapies aimed at reducing tumor cell invasion. Ion channels are candidate molecular targets involved in glioma cell migration and infiltration into the brain parenchyma. In this paper we demonstrate that: i) blockade of the calcium-activated potassium channel KCa3.1 with TRAM-34 has co-adjuvant effects with TMZ, reducing GL261 glioma cell migration, invasion and colony forming activity, increasing apoptosis, and forcing cells to pass the G2/M cell cycle phase, likely through cdc2 de-phosphorylation; ii) KCa3.1 silencing potentiates the inhibitory effect of TMZ on glioma cell viability; iii) the combination of TMZ/TRAM-34 attenuates the toxic effects of glioma conditioned medium on neuronal cultures, through a microglia dependent mechanism since the effect is abolished by clodronate-induced microglia killing; iv) TMZ/TRAM-34 co-treatment increases the number of apoptotic tumor cells, and the mean survival time in a syngeneic mouse glioma model (C57BL6 mice implanted with GL261 cells); v) TMZ/TRAM-34 co-treatment reduces cell viability of GBM cells and cancer stem cells (CSC) freshly isolated from patients.Taken together, these data suggest a new therapeutic approach for malignant glioma, targeting both glioma cell proliferating and migration, and demonstrate that TMZ/TRAM-34 co-treatment affects both glioma cells and infiltrating microglia, resulting in an overall reduction of tumor cell progression

Emergency decompressive craniectomy after removal of convexity meningiomas

BACKGROUND: Convexity meningiomas are benign brain tumors that are amenable to complete surgical resection and are associated with a low complication rate. The aim of this study was to identify factors that result in acute postoperative neurological worsening after the removal of convexity meningiomas. METHODS: Clinical evaluation and neuroradiological analysis of patients who underwent removal of a supratentorial convexity meningioma were reviewed. Patients were selected when their postoperative course was complicated by acute neurological deterioration requiring decompressive craniectomy. RESULTS: Six patients (mean age: 43.3 years) underwent surgical removal of a supratentorial convexity meningioma. Brain shift (mean: 9.9 mm) was evident on preoperative imaging due to lesions of varying size and perilesional edema. At various times postoperatively, patient consciousness worsened (up to decerebrate posture) with contralateral paresis and pupillary anisocoria. Computed tomography revealed no postoperative hematoma, however, did indicate increased brain edema and ventricular shift (mean: 12 mm). Emergency decompressive craniectomy and brief ventilator assistance were performed in all patients. Ischemia of the ipsilateral posterior cerebral artery occurred in 3 patients and hydrocephalus occurred in 2 patients. Outcome was good in 2, fair in 2, 1 patient had severe disability, and 1 patient died after 8 months. CONCLUSIONS: Brain shift on preoperative imaging is a substantial risk factor for postoperative neurological worsening in young adult patients after the removal of convexity meningiomas. Emergency decompressive craniectomy must be considered because it is effective in most cases. Other than consciousness impairment, there is no reliable clinical landmark to guide the decision to perform decompressive craniectomy; however, brain ischemia may have already occurred

Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors

[Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and stable in physiological media that has been developed as a possible viable alternative to platinum-based drugs for anticancer therapy. HydroCuP potently inhibited the growth of human cancer cells derived from solid tumors by inducing endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis with a preferential efficacy against cancer rather than non-cancer cells. Aim of the present study was to assess the therapeutic potential of HydroCuP in vivo, in syngenic and xenograft murine models of solid tumors by triggering the Unfolded Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced a markedly higher reduction of tumor growth associated with minimal animal toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was extremely effective in both oxaliplatin-sensitive and resistant models. The favorable in vivo tolerability of HydroCuP was also correlated to an encouraging biodistribution profile. Additionally, no signs of drug-related neurotoxicity and nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP appears worth of further investigation to evaluate its therapeutic activity towards a broad spectrum of solid malignancies

Concepts and movements in health promotion to guide educational practices

Introduction: in health promotion, practices are necessary to trigger mechanisms aimed at the creation or recreation of a new mode of enhancing health, in order to overcome the still-oriented actions of the biological approach. Prevailing actions oh health care, although important to the sector, do not advance toward a positive concept. Objective: to analyse the historical process of health as a concept and care models in the search for a new model of health promotion. Methods: This is a refl ective review designed to understand and appraise the international and national literature from Medline/PubMed, Lilacs and the Scientifi c Electronic Library (Scielo). For the organization of data, articles were separated by themes, and the process of categorisation was conducted based on content analysis.Results: Despite having the knowledge that consistent actions with the assumptions of health promotion are of great importance to quality of life and equity in health, implementing them remains a challenge due to the predominance of curative practices and an individualistic approach. These practices, in turn, are revealed to be a refl ection of the concept of health that has passed from the absence of disease to a process related to social, political, economic and cultural factors. Conclusion: The concept of health has been transformed from historical ideas, refl ecting the emergence of new formulations about thinking and doing and, consequently, new proposals for changes in welfare models of health. Therefore, although the new model of healthcare has been structured from a health promotion perspective; there are still features of hegemonic models with the predominance of curative practices