Distinct Effects of Delta 9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

Context: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. Objective: To investigate the effects of 2 main psycho-active constituents of Cannabis sativa (Delta 9-tetrahydrocannabinol [Delta 9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. Design: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta 9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. Participants: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. Main Outcome Measures: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. Results: Delta 9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta 9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta 9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Conclusions: Delta 9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta 9-THC may be related to effects in other brain regions.

Glutamate and the neural basis of the subjective effects of ketamine

Context: Ketamine evokes psychosislike symptoms, and its primary action is to impair N-methyl-D-aspartate glutamate receptor neurotransmission, but it also induces secondary increases in glutamate release. Objectives: To identify the sites of action of ketamine in inducing symptoms and to determine the role of increased glutamate release using the glutamate release inhibitor lamotrigine. Design: Two experiments with different participants were performed using a double-blind, placebo-controlled, randomized, crossover, counterbalanced-order design. In the first experiment, the effect of intravenous ketamine hydrochloride on regional blood oxygenation level dependent (BOLD) signal and correlated symptoms was compared with intravenous saline placebo. In the second experiment, pretreatment with lamotrigine was compared with placebo to identify which effects of ketamine are mediated by increased glutamate release. Setting: Wellcome Trust Clinical Research Facility, Manchester, England. Participants: Thirty-three healthy, right-handed men were recruited by advertisements. Interventions: In experiment 1, participants were given intravenous ketamine (1-minute bolus of 0.26 mg/ kg, followed by a maintenance infusion of 0.25 mg/ kg/ h for the remainder of the session) or placebo (0.9% saline solution). In experiment 2, participants were pretreated with 300 mg of lamotrigine or placebo and then were given the same doses of ketamine as in experiment 1. Main Outcome Measures: Regional BOLD signal changes during ketamine or placebo infusion and Brief Psychiatric Rating Scale and Clinician- Administered Dissociative States Scale scores. Results: Ketamine induced a rapid, focal, and unexpected decrease in ventromedial frontal cortex, including orbitofrontal cortex and subgenual cingulate, which strongly predicted its dissociative effects and increased activity in mid- posterior cingulate, thalamus, and temporal cortical regions (r= 0.90). Activations correlated with Brief Psychiatric Rating Scale psychosis scores. Lamotrigine pretreatment prevented many of the BOLD signal changes and the symptoms. Conclusions: These 2 changes may underpin 2 fundamental processes of psychosis: abnormal perceptual experiences and impaired cognitive- emotional evaluation of their significance. The results are compatible with the theory that the neural and subjective effects of ketamine involve increased glutamate release.

Modulation of Auditory and Visual Processing by Delta-9-Tetrahydrocannabinol and Cannabidiol: an fMRI Study

Although the effects of cannabis on perception are well documented, little is known about their neural basis or how these may contribute to the formation of psychotic symptoms. We used functional magnetic resonance imaging (fMRI) to assess the effects of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during visual and auditory processing in healthy volunteers. In total, 14 healthy volunteers were scanned on three occasions. Identical 10mg THC, 600mg CBD, and placebo capsules were allocated in a balanced double-blinded pseudo-randomized crossover design. Plasma levels of each substance, physiological parameters, and measures of psychopathology were taken at baseline and at regular intervals following ingestion of substances. Volunteers listened passively to words read and viewed a radial visual checkerboard in alternating blocks during fMRI scanning. Administration of THC was associated with increases in anxiety, intoxication, and positive psychotic symptoms, whereas CBD had no significant symptomatic effects. THC decreased activation relative to placebo in bilateral temporal cortices during auditory processing, and increased and decreased activation in different visual areas during visual processing. CBD was associated with activation in right temporal cortex during auditory processing, and when contrasted, THC and CBD had opposite effects in the right posterior superior temporal gyrus, the right-sided homolog to Wernicke`s area. Moreover, the attenuation of activation in this area (maximum 61, -15, -2) by THC during auditory processing was correlated with its acute effect on psychotic symptoms. Single doses of THC and CBD differently modulate brain function in areas that process auditory and visual stimuli and relate to induced psychotic symptoms. Neuropsychopharmacology (2011) 36, 1340-1348; doi:10.1038/npp.2011.17; published online 16 March 2011

Changes in facial morphology after adenotonsillectomy in mouth-breathing children

Background. Morphological and dentofacial alterations have been attributed to impaired respiratory function. Objective. To examine the influence of mouth breathing (MB) on children facial morphology before and after adenoidectomy or adenotonsillectomy. Methods. Thirty-three MB children who restored nasal breathing (NB) after surgery and 22 NB children were evaluated. Both groups were submitted to lateral cephalometry, at time 1 (T1) before and at time 2 (T2) 28 months on average postoperatively. Results. Comparison between the MB and NB groups at T1 showed that mouth breathers had higher inclination of the mandibular plane; more obtuse gonial angle; dolichofacial morphology; and a decrease in the total and inferior posterior facial heights. Twenty-eight months after the MB surgical intervention, they still presented a dolichofacial morphologic pattern. During this period, MB altered the face growth direction and decreased their mandible plane inclination, with reduction in the SN.GoGn, PP.MP, SNGn, and ArGo.GoMe parameters as well as an increase in BaN.PtGn. Conclusion. After the MB rehabilitation, children between 3 and 6 years old presented significant normalization in the mandibular growth direction, a decrease in the mandible inclination, and an increase in the posterior facial height. Instead, they still persisted with a dolichofacial pattern when compared with nasal breathers.

Cephalometric evaluation of facial pattern and hyoid bone position in children with obstructive sleep apnea syndrome

Objectives: To assess the development of face and hyoid bone in children with obstructive sleep apnea syndrome (OSAS) through lateral cephalometries. Materials and methods: Children aged 7-10 years with mixed dentition and with no previous otorhinolaryngologic, orthodontic or speech therapy treatments were studied. Twenty nasal breathers were compared to 20 mouth breathing children diagnosed as OSAS patients. All children underwent otorhinolaryngologic evaluation and cephalometries; children with OSAS also underwent nocturnal polysomnography in a sleep laboratory. Results: Children with OSAS presented increase in total and lower anterior heights of the face when compared to nasal breathers. In addition, children with OSAS presented a significantly more anterior and inferior position of the hyoid bone than nasal breathers. No significant differences in upper, anterior or posterior heights of the face were observed between groups. Conclusion: The results suggest that there are evident and early changes in facial growth and development among children with OSAS, characterized by increased total and inferior anterior heights of the face, as well as more anterior and inferior position of the hyoid bone. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Does rapid maxillary expansion increase nasopharyngeal space and improve nasal airway resistance?

Objective: To evaluate the effect of rapid maxillary expansion (RME) on the dimension of the nasopharyngeal space and its relation to nasal airway resistance. Methods: Twenty-five school-age children (from 7 to 10 year-old) with mouth and/or mixed breathing, with mixed dentition and uni- or bilateral posterior crossbite involving the deciduous canines and the first permanent molars, were evaluated. RME was placed and remained during 90 days. Rhinomanometry and orthodontic documentation were performed at four different times, i.e., before (T(1)), immediately after (T(2)), 90 days (T(3)) and 30 months (T(4)) after RME. Results: Differences in nasopharyngeal area and in nasal airway resistance were observed only 30 months after RME, and could be explained by facial growth, and not because of the orthodontic procedure. Conclusion: RME does not influence on nasopharyngeal area or nasal airway resistance in long-term evaluation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Long-term effects of rapid maxillary expansion on nasal area and nasal airway resistance

Background: Rapid maxillary expansion (RME) may improve the nasal respiratory pattern This study was performed to evaluate the effect of RME on the nasal cavity by acoustic rhinometry and computed rhinomanometry and to determine nasal and maxillary width by posteroanterior cephalometric radiography, up to 30 months after the orthodontic procedure Methods: Twenty-seven children with oral breathing, ranging in age from 7 to 70 years, and with mixed dentition were selected The children had unior bilateral posterior crossbite involving deciduous canines and the first permanent molars All subjects were submitted to nasofibroscopy, acoustic rhinometry, and computed rhinomanometry and posteroanterior cephalometric radiography at four different tunes, i e, before expansion, immediately, 90 days and 30 months after expansion Results: The mean linear left-to-right nasal cavity lateral prominence and left-to-right jugal ponds cephalometric measures increased considerably after expansion and this increase was maintained throughout the period of evaluation There was an immediate significant decrease in nasal resistance, up to 90 days after RME, but the nasal resistance increased 30 months after the procedure The acoustic rhinometry results did not show any difference in values throughout time Conclusion: RME significantly increased nasal and maxillary width as measured by frontal cephalometry, but the nasal mucosal effects were more subtle Also, the influence of RME on nasal resistance was not stable, and nasal resistance values returned to close to the initial ones after 30 months (Am J Rhinol Allergy 24, 161-165, 2010, doi 10.2500/ajra.2010.24.3440)

OCT findings in macular hole formation in eyes with complete vitreofoveal separation

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.

Orbital Involvement in Craniofacial Brown Tumors

Purpose: To describe the clinical and radiologic features of orbital involvement in craniofacial brown tumors and to compare the rate of brown tumors in primary and secondary hyperparathyroidism. Methods: A retrospective hospital-based study of 115 patients with chronic kidney disease and secondary hyperparathyroidism and 34 with primary hyperparathyroidism was conducted. Laboratory results such as serum levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone were recorded. Demographic data (age, sex, duration of disease) and image findings (bone scan scintigraphy, skull and long bone x-rays, CT) were also obtained. The main outcome measures were analysis of clinical, biochemical, and radiologic findings of all patients. Results: Of the 115 patients with chronic kidney disease, 10 (8.7%) had brown tumors in different bones of the skeleton. Five patients had lesions in the craniofacial bones. The maxilla, mandible, maxillary sinus, and nasal cavity were the most affected sites. The orbit was involved in 2 patients with lesions arising in the maxillary and ethmoid sinuses. One patient had facial leontiasis. All patients with brown tumors had extremely high levels of parathyroid hormone (>1,000 pg/ml, normal values 10-69 pg/ml) and alkaline phosphatase (>400 U/l, normal values 65-300 U/l). The mean serum levels of phosphorus and calcium were not abnormal among the patients with brown tumors. Age and time of renal failure were similar for patients with and without brown tumors. Among the patients with primary hyperparathyroidism, only 2 (5.8%) had brown tumors, and in just 1, the lesion was localized in the craniofacial skeleton. A 2-tailed Z test applied to compare the proportion of occurrence of brown tumors in the 2 groups revealed that the difference at the 90% of confidence level was not significant. Conclusions: Brown tumors are equally found in secondary and primary hyperparathyroidism. Craniofacial brown tumors involve the orbit, usually because of the osteodystrophy process that involves the maxilla and paranasal sinuses. The lesions do not necessarily need to be excised and may regress spontaneously after the control of hyperparathyroidism.

Can eccentric arterial plaques alone cause flow stagnation points and favour thrombus incorporation?

We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas.

Ossifying fibroma: A rare cause of orbital inflammation

Purpose: To describe the clinical and radiologic features of 4 cases of ossifying fibroma affecting the orbit and to review the literature on orbital involvement by the tumor. Methods: Small case series. Results: Four patients (3 children and 1 adult) with ossifying fibromas invading the orbit were examined. Two of the 3 children were examined for ossifying fibromas on the orbital roof. One had the psammomatoid form of the disease and the other the trabecular variant. Despite striking differences in the histologic pattern and in the radiologic appearance of the lesions, both children displayed a significant degree of orbital inflammation mimicking orbital cellulitis. The third child and the adult patient had the orbit involved by trabecular ossifying fibromas invading the orbital floor. The tumor of the adult clearly originated in the maxilla, filled the maxillary sinus, and eroded the orbital floor. The tumor of the third child occupied the maxillary, ethmoid, and sphenoid sinuses. In both cases, the clinical presentation was painless eye dystopia and proptosis. Conclusions: Regardless of the histologic pattern (trabecular or psammomatoid), ossifying fibromas can induce a substantial degree of orbital inflammation in children and must be included in the differential diagnosis of acute orbital inflammation during childhood.

Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle

PURPOSE. Surgical recession of an extraocular muscle (EOM) posterior to its original insertion is a common form of strabismus surgery, weakening the rotational force exerted by the muscle on the globe and improving eye alignment. The purpose of this study was to assess myosin heavy chain (MyHC) isoform expression and satellite cell activity as defined by Pax7 expression in recessed EOMs of adult rabbits compared with that in muscles tenotomized but not recessed and with that in normal control muscles. METHODS. The scleral insertion of the superior rectus muscle was detached and sutured either 7 mm posterior to its original insertion site (recession surgery) or at the same site (tenotomy). One day before euthanatization, the rabbits received bromodeoxyuridine (BrdU) injections. After 7 and 14 days, selected EOMs from both orbits were examined for changes in fast, slow, neonatal, and developmental MyHC isoform expression, Pax7 expression, and BrdU incorporation. RESULTS. Recession and tenotomy surgery resulted in similar changes in the surgical EOMs. These included a decreased proportion of fast MyHC myofibers, an increased proportion of slow MyHC myofibers, and increased BrdU-positive satellite cells. Similar changes were seen in the non-operated contralateral superior rectus muscles. The ipsilateral inferior rectus showed reciprocal changes to the surgical superior rectus muscles. CONCLUSIONS. The EOMs are extremely adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression. These adaptive responses could be manipulated to improve surgical success rates. (Invest Ophthalmol Vis Sci. 2010;51:5646-5656) DOI:10.1167/iovs.10-5523

Mechanical behavior of prosthesis in Toucan beak (Ramphastos toco)

The purpose of this study is to characterize the structure of the beak of Toco Toucan (Ramphastos toco) and to investigate means for arresting fractures in the rhinotheca using acrylic resin. The structure of the rhamphastid bill has been described as a sandwich structured composite having a thin exterior comprised of keratin and a thick foam core constructed of mineralized collagenous rods (trabeculae). The keratinous rhamphotheca consists of superposed polygonal scales (approximately 50 pm in diameter and 1 mu m in thickness). In order to simulate the orientation of loading to which the beak is subjected during exertion of bite force, for example, we conducted flexure tests on the dorso-ventral axis of the maxilla. The initially intact (without induced fracture) beak fractured in the central portion when subjected to a force of 270 N, at a displacement of 23 mm. The location of this fracture served as a reference for the fractures induced in other beaks tested. The second beak was fractured and repaired by applying resin on both lateral surfaces. The repaired maxilla sustained a force of 70 N with 6.5 mm deflection. The third maxilla was repaired similarly except that it was conditioned in acid for 60s prior to fixation with resin. It resisted a force of up to 63 N at 6 mm of deflection. The experimental results were compared with finite element calculations for unfractured beak in bending configuration. The repaired specimens were found to have strength equal to only one third of the intact beak. Finite element simulations allow visualization of how the beak system (sandwich shell and cellular core) sustains high flexural strength. (C) 2010 Elsevier B.V. All rights reserved.

Shared and differential traits in the accessory olfactory bulb of caviomorph rodents with particular reference to the semiaquatic capybara

The vomeronasal system is crucial for social and sexual communication in mammals. Two populations of vomeronasal sensory neurons, each expressing G alpha i2 or G alpha o proteins, send projections to glomeruli of the rostral or caudal accessory olfactory bulb, rAOB and cAOB, respectively. In rodents, the G alpha i2- and G alpha o-expressing vomeronasal pathways have shown differential responses to small/volatile vs. large/non-volatile semiochemicals, respectively. Moreover, early gene expression suggests predominant activation of rAOB and cAOB neurons in sexual vs. aggressive contexts, respectively. We recently described the AOB of Octodon degus, a semiarid-inhabiting diurnal caviomorph. Their AOB has a cell indentation between subdomains and the rAOB is twice the size of the cAOB. Moreover, their AOB receives innervation from the lateral aspect, contrasting with the medial innervation of all other mammals examined to date. Aiming to relate AOB anatomy with lifestyle, we performed a morphometric study on the AOB of the capybara, a semiaquatic caviomorph whose lifestyle differs remarkably from that of O. degus. Capybaras mate in water and scent-mark their surroundings with oily deposits, mostly for male-male communication. We found that, similar to O. degus, the AOB of capybaras shows a lateral innervation of the vomeronasal nerve, a cell indentation between subdomains and heterogeneous subdomains, but in contrast to O. degus the caudal portion is larger than the rostral one. We also observed that four other caviomorph species present a lateral AOB innervation and a cell indentation between AOB subdomains, suggesting that those traits could represent apomorphies of the group. We propose that although some AOB traits may be phylogenetically conserved in caviomorphs, ecological specializations may play an important role in shaping the AOB.

Esthetic restorative materials and opposing enamel wear

This in vitro study compared the effects of a gold alloy (Degulor M), four dental ceramics (IPS Empress, IPS Empress 2, Duceram Plus, Duceram. LFC) and a laboratory-processed composite (Targis) on the wear of human enamel. The amount of wear of the enamel (dental cusps) and restorative materials (disks) were tested in water at 37 degrees C under standard load (20 N), with a chewing rate of 1.3 Hz and was determined after 150,000 and 300,000 cycles. Before the test, the average surface roughness of the restorative materials was analyzed using the Ra parameter. The results of this study indicate that Targis caused enamel wear similar to Degulor M and resulted in significantly less wear than all the ceramics tested. IPS Empress provoked the greatest amount of enamel wear and Degulor M caused less vertical dimension loss. Targis could be an appropriate alternative material to ceramic, because it is esthetic and produces opposing enamel wear comparable to gold alloy.