Evaluation of mutagenic activity in an extract of pepper tree stem bark (Schinus terebinthifolius Raddi)

An extract (decoction) from pepper tree stem bark (Schinus terebinthifolius Raddi) is widely used in Brazil as a topical antiinflammatory agent and to cicatrize wounds. The extract contains catechin, tannins, terpenes, flavonoids, and saponins; of these components, both mutagenic potential and antioxidant properties have been ascribed to flavonoids. The mutagenicity of some flavonoids is believed to be associated with the formation of reactive oxygen species and seems to depend on the number and position of hydroxyl groups. In the present study, we evaluated an extract of S. terebinthifolius in a series of cell-free and bacterial assays in order to determine its genotoxic potential. The extract was negative in a cell-free plasmid DNA test, indicating that it did not directly break DNA. Positive results, however, were obtained in the SOS chromotest, in a forward mutagenesis assay employing CC104 and CC104mutMmutY strains of Escherichia coli, and in the Salmonella reversion assay, using strains TA97, TA98, TA100, and TA102. All the bacterial tests were performed without exogenous metabolic activation due to the topical use of this preparation. The results indicate that pepper tree stem bark extract produces DNA damage and mutation in bacteria, and that oxidative damage may be responsible for the genotoxicity.     

Association between tDCS computational modeling and clinical outcomes in depression: data from the ELECT-TDCS trial

European Archives of Psychiatry and Clinical Neuroscience - Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention investigated for the treatment of...     

MC3T3‐E1 Cells Behavior on Surfaces Bombarded by Argon Ions in Planar Cathode Discharge

To evaluate the effect of topography in nanoscale, titanium surfaces were bombarded by argon ions (a chemically inert gas), in an atmosphere of plasma. The effects of surface parameters on morphology, adhesion, proliferation, and MC3T3‐E1 preosteoblasts differentiation were analyzed. Nontreated (smooth) surfaces were used as a control. The levels of average roughness (Ra) observed in bombarded and smooth titanium surfaces were of 95 and 14 nm, respectively. The wettability increased on treated surfaces. The number of attached cells (30 and 60 min) was significantly higher on the bombarded surface. The cell proliferation after 3 and 7 days was also significantly higher on the ion‐bombarded surface. In addition, the ALP activity and expression of osteocalcin were higher in cells grown on the treated surface. The results showed that bombardment with argon ions increased the roughness and the wettability of the Ti surface, promoting a significant increase in the adhesion, proliferation, and differentiation of preosteoblasts.     

Genotoxicity induced by saponified coconut oil surfactant in prokaryote systems

Surfactants are amphiphilic substances with special properties and chemical structures that allow a reduction in interfacial tension, which permits an increase in molecule solubilization. The critical micelle concentration (CMC) is an important characteristic of surfactants that determines their aggregate state, which is generally related to its functional mechanism. In this work the genotoxic potential of saponified coconut oil (SCO), a surfactant obtained from Cocos nucifera, was analyzed using prokaryote systems. DNA strand breaks were not observed after treatment of a plasmid with SCO. Negative results were also obtained in the SOS Chromotest using Escherichia coli strains PQ35 and PQ37. A moderate toxicity of SCO was observed after treatment of strain CC104 with a concentration above its CMC, in which micelles were found. Nevertheless, this treatment was not cytotoxic to a CC104mutMmutY strain. Furthermore, in this DNA repair-deficient strain treatment with a SCO dose below its CMC, in which only monomers were found, demonstrated the possibility of an antioxidant effect, since a reduction in spontaneous mutagenesis frequency was observed. Finally, in an Ames test without metabolic activation mutagenicity induction was observed in strains TA100 and TA104 with treatment doses below the CMC. The cytotoxic, antioxidant and mutagenic effects of SCO can be influenced by the aggregational state.     

BC nanofibres: In vitro study of genotoxicity and cell proliferation

Nanomaterials have unusual properties not found in the bulk materials, which can be exploited in numerous applications such as biosensing, electronics, scaffolds for tissue engineering, diagnostics and drug delivery. However, research in the past few years has turned up a range of potential health hazards, which has given birth to the new discipline of nanotoxicology. Bacterial cellulose (BC) is a promising material for biomedical applications, namely due its biocompatibility. Although BC has been shown not to be cytotoxic or genotoxic, the properties of isolated BC nanofibres (NFs) on cells and tissues has never been analysed. Considering the toxicity associated to other fibre-shaped nanoparticles, it seems crucial to evaluate the toxicity associated to the BC-NFs.     

Effect of titanium surface modified by plasma energy source on genotoxic response in vitro

Titanium (Ti) is currently the most widely used material for the manufacture of orthopedic and dental implants. Changes in the surface of commercial pure Ti (cp Ti) can determine the functional response of cells, and is therefore a critical factor for the success of the implant. However, the genotoxicity of titanium surfaces has been poorly studied. Thus, the purpose of this study was to evaluate the genotoxic potential of a new titanium surface developed by plasma treatment using argon-ion bombardment and compare it with an untreated titanium surface. Accordingly, comet assay, analysis of chromosomal aberrations (CAs), and Cytokinesis Block Micronucleus (CBMN) assay were carried out, using CHO-K1 (Chinese hamster ovary) cells grown on both titanium surfaces. Our results show that the untreated titanium surface caused a significant increase in % tail moment, in the number of cells with CAs, tetraploidy, micronucleus frequency, and other nuclear alterations when compared with the negative control and with the plasma-treated titanium surface. This difference may be attributed to increased surface roughness and changes in titanium oxide layer thickness.     

Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive–compulsive disorder

Nearly one-third of patients with obsessive–compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale–Brown Obsessive–Compulsive Scale (Y–BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.     

Gray matter volumes in obsessive-compulsive disorder before and after fluoxetine or cognitive-behavior therapy: a randomized clinical trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n=38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n=36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n=26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n=13), whereas no significant GM volume changes were observed in CBT-treated patients (n=13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action.     

Caudate volume differences among treatment responders,non-responders and controls in children with obsessive–compulsive disorder

Treatment response in obsessive–compulsive disorder (OCD) is heterogeneous and the neurobiological underpinnings of such variability are unknown. To investigate this issue, we looked for differences in brain structures possibly associated with treatment response in children with OCD. 29 children with OCD (7–17 years) and 28 age-matched controls underwent structural magnetic resonance imaging. Patients then received treatment with fluoxetine or group cognitive-behavioral therapy during 14 weeks, and were classified as treatment responders or non-responders. The caudate nucleus, thalamus and orbitofrontal cortex were selected a priori, according to previous evidence of their association with OCD and its treatment. Gray matter (GM) volume comparisons between responders, non-responders and controls were performed, controlling for total GM volume. 17 patients were classified as responders. Differences among responders, non-responders and controls were found in both caudate nuclei (both p-values = 0.041), but after Bonferroni correction for multiple comparisons, these findings were non-significant. However, after excluding the effect of an outlier, findings were significant for the right caudate (p = 0.004). Pairwise comparisons showed larger caudate GM volume in responders versus non-responders and controls, bilaterally. The right caudate accounted for 20.2% of the variance in Y-BOCS changes after treatment in a linear regression model, with a positive correlation (p = 0.016). We present a possible neural substrate for treatment response in pediatric OCD, which is in line with previous evidence regarding the caudate nucleus. Considering the limitations, further research is needed to replicate this finding and elucidate the heterogeneity of treatment response in children with OCD (National Clinical Trials Registration Number: NCT01148316).