Anti-aversive effects of the atypical antipsychotic, aripiprazole, in animal models of anxiety

Aripiprazole is a unique antipsychotic that seems to act as a partial agonist at dopamine D2-receptors, contrasting with other drugs in this class, which are silent antagonists. Aripiprazole may also bind to serotonin receptors. Both neurotransmitters may play major roles in aversion-, anxiety-and panic-related behaviours. Thus, the present work tested the hypothesis that this antipsychotic could also have anti-aversive properties. Male Wistar rats received injections of aripiprazole (0.1-10 mg/kg) and were tested in the open field, in the elevated plus and T mazes (EPM and ETM, respectively) and in a contextual fear conditioning paradigm. Aripiprazole (1mg/kg) increased the percentage of entries onto the open arms of the EPM and attenuated escape responses in the ETM. In the latter model, the dose of 0.1 mg/kg also decreased the latency to leave the enclosed arm, suggesting anxiolytic- and panicolytic-like properties. This dose also decreased the time spent in freezing in a contextual fear conditioning. No significant motor effects were observed at these doses. The present data support the hypothesis that aripiprazole could inhibit anxiety-related responses. Acting as a partial agonist at dopamine receptors, this drug could effectively treat schizophrenia and, in contrast with most antipsychotic drugs, alleviate aversive states.

Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors

Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10 min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10 min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors. (C) 2010 Elsevier B.V. All rights reserved.

Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT(1A) receptors

Background and purpose: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF). Experimental approach: Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg.kg(-1)), imipramine (30 mg.kg(-1)) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg.kg(-1), i.p.), a 5-HT(1A) receptor antagonist, before CBD (30 mg.kg(-1)) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg.kg(-1)) and submitted to the forced swimming test. Key results: CBD (30 mg.kg(-1)) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg.kg(-1)) treatment did not change hippocampal BDNF levels. Conclusion and implications: CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT(1A) receptors. British Journal of Pharmacology (2010) 159, 122-128; doi:10.1111/j.1476-5381.2009.00521.x; published online 4 December 2009

Masticatory muscle activity in children with a skeletal or dentoalveolar open bite

Forty-five children (31 boys and 14 girls), aged 6-11 years, were included in the study, 15 with a skeletal anterior open bite (SAOB), 15 with a dentoalveolar anterior open bite (DAOB), and 15 with a normal occlusion (CG), defined by clinical evaluation and lateral cephalograms. EMG recordings of the temporal and masseter muscles were performed under maximal voluntary clenching and during chewing. Analysis of variance was used for inter-group analysis, followed by the Tukey post hoc test. A Student`s t-test for paired data was used for intra-group analysis. There were statistically significant differences among the three groups (P < 0.05), with the mean EMG being highest in the CG and lowest in children with a SAOB. The percentage EMG activity during chewing in relation to that during maximal voluntary clenching was more than 100 per cent in the SAOB group. The CG and DAOB groups presented higher EMG activity during clenching compared with chewing (P < 0.001), as well as a greater difference between tasks. In the SAOB group, the neuromuscular system appeared to have a lower capacity to produce EMG activity according to the task, while that in the DAOB group suggests that their functional capacity during growth should also be carefully observed.

Cloning, expression and purification of a glycosylated form of the DNA-binding protein Dps from Salmonella enterica Typhimurium

Dps, found in many eubacterial and archaebacterial species, appears to protect cells from oxidative stress and/or nutrient-limited environment. Dps has been shown to accumulate during the stationary phase, to bind to DNA non-specifically, and to form a crystalline structure that compacts and protects the chromosome. Our previous results have indicated that Dps is glycosylated at least for a certain period of the bacterial cell physiology and this glycosylation is thought to be orchestrated by some factors not yet understood, explaining our difficulties in standardizing the Dps purification process. In the present work, the open reading frame of the dps gene, together with all the upstream regulatory elements, were cloned into a PCR cloning vector. As a result, the expression of dps was also controlled by the plasmid system introduced in the bacterial cell. The gene was then over-expressed regardless of the growth phase of the culture and a glycosylated fraction was purified to homogeneity by lectin-immobilized chromatography assay. Unlike the high level expression of Dps in Salmonella cells, less than 1% of the recombinant protein was purified by affinity chromatography using jacalin column. Sequencing and mass spectrometry data confirmed the identity of the dps gene and the protein, respectively. In spite of the low level of purification of the jacalin-binding Dps, this work shall aid further investigations into the mechanism of Dps glycosylation. (C) 2008 Elsevier Inc. All rights reserved.

Historia Nova do Brasil: revisiting a polemical work

This article discusses the texts and purposes of the Historia Nova do Brasil series, a joint production of the Ministerio da Educacao e Cultura and the Instituto Superior de Estudos Brasileiros (Iseb) launched in 1964 and soon aborted by the military dictatorship. The intent is to reconstitute its context to present the many influences on this project and to examine its impact and the debates and disputes that resulted, to try to recover the details of this important effort at renewing the teaching of history in Brazil.

Esthetic and functional restoration for an anterior open occlusal relationship with multiple diastemata: A multidisciplinary approach

An anterior open occlusal relationship and diastemata may negatively interfere with the harmony of the smile, often requiring a multidisciplinary intervention. This clinical report presents an integrated orthodontic, periodontal, and restorative solution for an anterior open occlusal relationship associated with multiple diastemata and discusses the most relevant aspects related to Its etiology and treatment planning.

Stability of anterior open-bite treatment with occlusal adjustment

Introduction: In this study, we aimed to evaluate the long-term stability of anterior open-bite treatment with occlusal adjustment and the dentinal sensitivity caused by this procedure in the long term. Methods: The sample comprised 17 open-bite patients who experienced relapse of the negative vertical overbite after orthodontic treatment and were retreated with occlusal adjustment. The cephalometric changes were evaluated on lateral cephalograms obtained before and after the occlusal adjustment and in the long term (mean, 3.4 years after occlusal adjustment). Dentinal sensitivity was also evaluated before the occlusal adjustment, and 1.35 months, 4.61 months, and 3.4 years later. The cephalometric statuses between the 3 evaluations were compared with analysis of variance (ANOVA) and Tukey tests. The percentages of clinically significant relapse were calculated. To compare dentinal sensitivity at the several stages, nonparametric Friedman and Wilcoxon tests were performed. Results: Statistically significant relapse of anterior open bite occurred in 33.3% of the patients. Those who had the procedure before 21 years of age were most likely to experience relapse. Dentinal sensitivity remained within the normal range in the long term. Conclusions: Despite the statistically significant relapse of anterior open bite, clinically significant stability was found in 66.7% of the patients. (Am J Orthod Dentofacial Orthop 2010; 138:14.e1-14.e7)

Open-bite orthodontic-surgical treatment in the Klippel-Trenaunay-Weber syndrome: a case report

We describe the orthodontic treatment of a patient with Klippel-Trenaunay-Weber syndrome (KTWS) who received orthodontic treatment that included rapid palatal expansion and orthognathic surgery. There is no report in the literature with this orthodontic treatment protocol, that was considered successful. The pros and cons of this approach as well as the risks involved are discussed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: e17-e25)

Lateral open bite: Treatment and stability

Because of their multifactorial etiologies, dental and skeletal open bites are among the most difficult malocclusions to treat to a successful and stable result. Etiologic factors include vertical maxillary excess, skeletal pattern, abnormalities in dental eruption, and tongue-thrust problems. The purpose of this article was to report the treatment of an adult patient with a lateral open bite and a unilateral posterior crossbite. The treatment involved nonextraction therapy, including intermaxillary elastics, to obtain dentoalveolar extrusion in the region of the lateral open bite. The treatment results were successful and remained stable 2 years later. (Am J Orthod Dentofacial Orthop 2010;137:701-11)

Evaluation of anterior open-bite treatment with occlusal adjustment

Introduction: The purpose of this study was to evaluate the cephalometric and occlusal changes, the functional occlusion, and the dentinal sensitivity of anterior open-bite treatment with occlusal adjustment. Methods: The sample comprised 20 patients who experienced relapse of the anterior open bite (mean, -1.06 mm). Occlusal adjustment was performed until a positive overbite was established. Cephalometric changes were evaluated on lateral cephalograms taken before and after the occlusal adjustment. The functional occlusion analysis consisted of evaluating immediate anterior and canine guidance and the number of teeth in contact before and after the procedure. Dentinal sensitivity was evaluated before, shortly after, and 4.61 months after the occlusal adjustment. Pretreatment and posttreatment cephalometric changes and the number of teeth in contact were compared with dependent t tests. Percentages of anterior and canine guidance before and after the adjustment procedure were compared with the McNemar test. To compare dentinal sensitivity at several stages, the nonparametric Friedman test was used, followed by the Wilcoxon test. Results: Significant increases in overbite and mandibular protrusion were seen, as were significant decreases in apical base discrepancy, facial convexity, and growth pattern angles. The percentages of immediate anterior and canine guidance increased significantly, as did the number of teeth with occlusal contacts. Dentinal sensitivity increased immediately after the adjustment but decreased to normal levels after 4.61 months. Conclusions: Occlusal adjustment is a viable treatment alternative for some open-bite patients; it establishes positive vertical overbite and improves the functional occlusion with only transient dentinal sensitivity.

Long-term stability of surgical-orthodontic open-bite correction

Introduction: The objective of this study was to evaluate the long-term stability of open-bite surgical-orthodontic correction. Methods: Thirty-nine patients at an initial mean age of 20.83 years were evaluated cephalometrically at pretreatment (T1), immediately after treatment (T2), and at the last recall (T3), with a mean follow-up time of 8.22 years. The surgical protocol included single-jaw or double-jaw surgery. Because the patients had different anteroposterior malocclusions, the sample was divided into a Class I and Class II (I-II) subgroup (3 Class I, 20 Class II malocclusion patients) and a Class III subgroup (16 patients). The dentoskeletal characteristics of the total sample and the subgroups were compared at T1, T2, and T3 with dependent analysis of variance (ANOVA). Results: Overbite relapse in the posttreatment period was statistically significant in the whole sample and the Class I-II subgroup. Fourteen patients of the whole sample (35.9%) had clinically significant open-bite relapse (negative overbite). Conclusions: There was a statistically significant open-bite relapse in the overall sample and in the Class I-II subgroup. The clinically significant values of long-term open-bite correction stability were 64.11%, 47.82%, and 87.50% in the overall sample, the Class I-II subgroup, and the Class III subgroup, respectively. (Am J Orthod Dentofacial Orthop 2010;138:254.e1-254.e10)