Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces

Several neuropsychiatry disorders have shown a sexual dimorphism in their incidence, symptom profile and therapeutic response. A better understanding of the impact of sex hormones in emotional processing sexual dimorphism could bring tight to this important clinical finding. Some studies have provided evidence of sex differences in the identification of emotional faces, however, results are inconsistent and such inconsistency could be related to the lack of experimental control of the sex hormone status of participants. More recently, a few studies evaluated the modulation of facial emotion recognition by the phase of the menstrual cycle and sex hormones, however, none of them directly compared these results with a group of men. We evaluated the accuracy of facial emotion recognition in 40 healthy volunteers. Eleven women were assigned to early follicular group, nine women to the ovulatory group and 10 women to luteal group, depending on the phase of menstrual cycle, and a group of 10 men were also evaluated. Estrogen, progesterone and testosterone levels were assessed. The performance of the groups in the identification of emotional faces varied depending on the emotion. Early follicular group were more accurate to perceive angry faces than all other groups. Sadness was more accurately recognized by early follicular group than by luteal group and regarding the recognition of fearful faces a trend to a better performance and a significantly higher accuracy was observed, respectively, in the early follicular group and in the ovulatory group, in comparison to men. In women, estrogen negatively correlated to the accuracy in perception of angry mate faces. Our results indicate sex hormones to be implicated in a sexual dimorphism in facial emotion recognition, and highlight the importance of estrogen specifically in the recognition of negative emotions such as sadness, anger and fear. (C) 2009 Elsevier Ltd. All rights reserved.

Leigh-like syndrome with the T8993G mutation in the mitochondrial ATPase 6 gene: long-term follow-up discloses a slowly progressive course

We describe the long-term clinical outcome of a patient with Leigh-like syndrome presenting as an early onset encephalopathy and peripheral neuropathy caused by the T8993G mutation in the mitochondrial DNA (mtDNA). Clinical follow-up for 20 years revealed a peculiar pattern of slow disease progression, characterized by the addition of new minor deficits, while worsening of previous symptoms was mild. Brain MRI revealed cerebellar atrophy, diffuse demyelination of corona radiata and parietal white matter, and bilateral and symmetrical putaminal lesions. The proportion of mutant mtDNAs in blood was 72% (+/- 0.02%) and in skeletal muscle was 81% (+/- 0.4%). Leigh-like syndrome caused by the T8993G mtDNA mutation is a progressive disease, although not necessarily associated with an aggressive clinical course. (C) 2009 Elsevier B.V. All rights reserved.

Neural Basis of Delta-9-Tetrahydrocannabinol and Cannabidiol: Effects During Response Inhibition

Background: This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task. Methods: Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design. Results: Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms. Conclusions: These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.

Neurobiology of panic disorder: From animal models to brain neuroimaging

Evidence from animal models of anxiety has led to the hypothesis that serotonin enhances inhibitory avoidance (related to anxiety) in the forebrain, but inhibits one-way escape (panic) in the midbrain periaqueductal gray (PAG). Stressing the difference between these emotions, neuroendocrinological results indicate that the hypothalamic-pituitary-adrenal axis is activated by anticipatory anxiety, but not by panic attack nor by electrical stimulation of the rat PAG. Functional neuroimaging has shown activation of the insula and upper brain stem (including PAG), as well as deactivation of the anterior cingulated cortex (ACC) during experimental panic attacks. Voxel-based morphometric analysis of brain magnetic resonance images has shown a grey matter volume increase in the insula and upper brain stem, and a decrease in the ACC of panic patients at rest, as compared to healthy controls. The insula and the ACC detect interoceptive stimuli, which are overestimated by panic patients. It is suggested that these brain areas and the PAG are involved in the pathophysiology of panic disorder. (C) 2008 Elsevier Ltd. All rights reserved.

Neurophysiological findings of the late-onset, dominant, proximal spinal muscular atrophies with dysautonomia because of the VAPB PR056SER mutation

The vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) Pro56Ser Mutation has been identified in Brazilian families showing various motor neuron syndromes. However, the neurophysiological characteristics of these patients have not been detailed, and some questions Still need to be solved, such as the possible presence of myotonia and the origin of the abdominal protrusion seen in most patients. The eventual finding of suggestive electrophysiological characteristics would be helpful not only for clinical diagnosis but also to selection of the appropriate DNA test. To clarify these questions we carried out sensory and motor conduction Studies, including symphatetic skin response, and needle examination in six genetically proven affected members. The electromyographic findings were those of a slowly progressive motor neuron disorder. Topographically, the abdominal muscles were severely affected, but the facial and laryngeal muscles were preserved or very mildly involved. Sensory conduction studies and sympathetic Skin responses were normal. No myotonic discharge was recorded. These findings are indistinguishable from those of other motor neuron disorders, although the predominant involvement of the proximal limbs and of the abdominal muscles may be of some help in the appropriate clinical setting.

Involvement of the central nervous system in the chronic form of Chagas` disease

Background and purpose: Apart from the central nervous system parasitic invasion in chagasic immunodeficient patients and strokes due to heart lesions provoked by the disease, the typical neurological syndromes of the chronic phase of Chagas` disease (CD) have not yet been characterized, although involvement of the peripheral nervous system has been well documented. This study aims at investigating whether specific signs of central nervous system impairment might be associated with the disease. Methods: Twenty-seven patients suffering from the chronic form of Chagas` disease (CCD) and an equal number of controls matched for sex, age, educational and socio-cultural background, and coming from the same geographical regions, were studied using neurological examinations, magnetic resonance images, and electroencephalographic frequency analysis. Results: Nineteen patients were at the stage A of the cardiac form of the disease (without documented structural lesions or heart failure). Dizziness, brisk reflexes, and ankle and knee areflexia were significantly more prevalent in the patients than in the controls. The significant findings in quantitative electroencephalogram were an increase in the theta relative power and a decrease in the theta dominant frequency at temporal-occipital derivations. Subcortical, white matter demyelination was associated with diffuse theta bursts and theta-delta slowing in two patients. Conclusions: Our findings suggest a discrete and unspecific functional cortical disorder and possible white matter lesions in CD. The focal nervous system abnormalities in CD documented here did not seem to cause significant functional damage or severely alter the patient`s quality of life. (C) 2008 Elsevier B.V. All rights reserved.

Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2

Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot Marie Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de nova mutation was found in exon 4 (c.310C > T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes. (C) 2011 Elsevier B.V. All rights reserved.

Anxiolytic and panicolytic effects of escitalopram in the elevated T-maze

Escitalopram is a highly selective inhibitor of serotonin re-uptake that is used to treat anxiety disorders. In the present study, we investigated the effects of acute, sub-chronic ( 14 days) and chronic ( 21 days) administration of escitalopram ( 2, 4 and 8 mg/kg, P0) on the performance of rats in the elevated T-maze. For comparison, imipramine ( 15 mg/ kg, P0) was also studied. The apparatus is made of three elevated arms of equal dimension, one enclosed transversal to the two open arms. Inhibitory avoidance of the open arms, trained in the enclosed arm, has been related to generalised anxiety disorder, while one-way escape from one open arm, to panic disorder. After acute administration, the three doses of escitalopram impaired avoidance ( anxiolytic effect), while imipramine was ineffective. Escape was unaffected by either drug. With sub-chronic administration, both drugs were ineffective on either avoidance or escape. After chronic treatment, avoidance was impaired by imipramine and by the two highest doses of escitalopram. In addition, escape was impaired (panicolytic effect) by imipramine and by the highest dose of escitalopram. Locomotion measured in a square arena was increased by the three doses of escitalopram, given chronically. Therefore, both imipramine and escitalopram had anxiolytic and panicolytic-like effects after chronic administration, but acutely only escitalopram decreased anxiety. Since no such effect was observed following subchronic administration, it is likely that the mechanisms of the early and late anxiolytic actions of escitalopram are different.

Dorsal cutaneous branch of the ulnar nerve: a light and electron microscopy histometric study

This study describes the normal morphology and morphometry of the dorsal cutaneous branch of the ulnar nerve (DCBU) in humans. Fourteen nerves of eight donors were prepared by conventional techniques for paraffin and epoxy resin embedding. Semiautomatic morphometric analysis was performed by means of specific computer software. Histograms of the myelinated and unmyelinated fiber population and the G-ratio distribution of fibers were plotted. Myelinated fiber density per nerve varied from 5,910 to 10,166 fibers/mm(2), with an average of 8,170 +/- 393 fibers/mm(2). The distribution was bimodal with peaks at 4.0 and 9.5 mu m. Unmyelinated fiber density per nerve varied from 50,985 to 127,108, with an average of 78,474 +/- 6, 610 fibers/mm(2), with a unimodal distribution displaying a peak at 0.8 mu m. This study thus adds information about the fascicles and myelinated and unmyelinated fibers of DCBU nerves in normal people, which may be useful in further studies concerning ulnar nerve neuropathies, mainly leprosy neuropathy.

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

A new DTL-electrode holder for recording of electroretinograms in animals

Purpose: Contact lens electrodes (CLEs) are frequently used to register electroretinograms (ERGs) in small animals such as mice or rats. CLEs are expensive to buy or difficult to be produced individually. In addition, CLE`s have been noticed to elicit inconstant results and they carry potential to injure the cornea. Therefore, a new electrode holder was constructed based on the clinically used DTL-electrode and compared to CLEs. Material and methods: ERGs were recorded with both electrode types in nine healthy Brown-Norway rats under scotopic conditions. For low intensity responses a Naka-Rushton function was fitted and the parameters V(max), k and n were analyzed. The a-wave, b-wave and oscillatory potentials were analyzed for brighter flash intensities (1-60 scot cd s/m(2)). Repeatability was assessed for both electrode types in consecutive measurements. Results: The new electrode holder was faster in setting up than the CLE and showed lower standard deviations. No corneal alterations were observed. Slightly higher amplitudes were recorded in most of the measurements with the new electrode holder (except amplitudes induced by 60 cd s/m(2)). A Bland-Altman test showed good agreement between the DTL holder and the CLE (mean difference 35.2 mu V (Holder-CLE)). Pearson`s correlation coefficient for test-retest-reliability was r = 0.783. Conclusions: The DTL holder was superior in handling and caused far less corneal problems than the CLE and produced comparable or better electrophysiological results. The minimal production costs and the possibility of adapting the DTL holder to bigger eyes, such as for dogs or rabbits, offers with broader application prospects. (C) 2010 Elsevier B.V. All rights reserved.

Modeling upper eyelid kinematics during spontaneous and reflex blinks

To test a mathematical model for measuring blinking kinematics. Spontaneous and reflex blinks of 23 healthy subjects were recorded with two different temporal resolutions. A magnetic search coil was used to record 77 blinks sampled at 200 Hz and 2 kHz in 13 subjects. A video system with low temporal resolution (30 Hz) was employed to register 60 blinks of 10 other subjects. The experimental data points were fitted with a model that assumes that the upper eyelid movement can be divided into two parts: an impulsive accelerated motion followed by a damped harmonic oscillation. All spontaneous and reflex blinks, including those recorded with low resolution, were well fitted by the model with a median coefficient of determination of 0.990. No significant difference was observed when the parameters of the blinks were estimated with the under-damped or critically damped solutions of the harmonic oscillator. On the other hand, the over-damped solution was not applicable to fit any movement. There was good agreement between the model and numerical estimation of the amplitude but not of maximum velocity. Spontaneous and reflex blinks can be mathematically described as consisting of two different phases. The down-phase is mainly an accelerated movement followed by a short time that represents the initial part of the damped harmonic oscillation. The latter is entirely responsible for the up-phase of the movement. Depending on the instantaneous characteristics of each movement, the under-damped or critically damped oscillation is better suited to describe the second phase of the blink. (C) 2010 Elsevier B.V. All rights reserved.

Surface electromyographic assessment of patients with long lasting temporomandibular joint disorder pain

The normalized electromyographic characteristics of masticatory muscles in patients with temporomandibular joint disorders (TMD) and healthy controls were compared. Thirty TMD patients (15 men, 15 women, mean age 23 years) with long lasting pain (more than 6 months), and 20 control subjects matched for sex and age were examined. All patients had arthrogenous TMD according to the Research Diagnostic Criteria for TMD (RDC/TMD). Surface electromyography of masseter and temporal muscles was performed during maximum teeth clenching either on cotton rolls or in intercuspal position. Standardized EMG indices and the median power frequency were obtained, and compared between the two groups and sexes using ANOVAs. During clenching, the TMD patients had larger asymmetry in their temporalis muscles, larger temporalis activity relative to masseter, and reduced mean power frequencies than the control subjects (p < 0.05, ANOVA). In both groups, the mean power frequencies of the temporalis muscles were larger than those of the masseter muscles (p < 0.001). No sex related differences, and no sex x group interactions were found. In conclusion, young adult patients with long lasting TMD have an increased and more asymmetric standardized activity of their temporalis anterior muscle, and reduced mean power frequencies, relative to healthy controls. (C) 2011 Elsevier Ltd. All rights reserved.

Epidemiology of meningococcal disease in Latin America: current situation and opportunities for prevention

Objective: Meningococcal disease continues to be a serious public health concern, being associated with high morbidity and mortality rates in many countries from Latin America. In addition to discussing recent changes in the epidemiology of meningococcal disease in the region, we also analyse the development and potential impact of new vaccines on the prevention of meningococcal disease. Methods: MEDLINE, SciELO, LILACS and websites of the national Ministries of Health databases were searched using the terms meningococcal disease, meningococcal epidemiology, Neisseria meningitidis, meningococcal vaccines and the name of Latin America countries, from 1998 to 2008, with emphasis on review articles, clinical trials and epidemiological studies. Results: Epidemiology of meningococcal disease in Latin America is characterized by marked differences from country to country. The overall incidence of meningococcal disease per year varied from less than 0.1 cases per 100,000 inhabitants in countries like Mexico to two cases per 100,000 inhabitants in Brazil. The highest age-specific incidence of meningococcal disease occurred in infants less than 1 year of age. Serogroups B and C were responsible for the majority of cases reported, but the emergence of serogroups W135 and Y was reported in some countries. Serogroup A disease is now rare in Latin America. Discussion: Although a few countries have established meningitis surveillance programs, the information is not uniform, and the quality of the reported data is poor in the majority of the region. The availability of new effective meningococcal conjugate vaccines and promising protein-based vaccine candidates against meningococcus B highlights the importance of a better understanding of the true burden of meningococcal disease in Latin America and also the need for cost-effectiveness studies before incorporating the new meningococcal vaccines to national immunization programs.

Tolerance to the cataleptic effect that follows repeated nitric oxide synthase inhibition may be related to functional enzymatic recovery

Systemic or intra-striatal acute administration of nitric oxide synthase (NOS) inhibitors causes catalepsy in rodents. This effect disappears after sub-chronic treatment. The aim of the present study was to investigate if this tolerance is related to changes in the expression of NOS or dopamine-2 (D(2)) receptor or to a recovery of NOS activity. Male albino Swiss mice (25-30 g) received single or sub-chronic (once a day for 4 days) i.p. injections of saline or L-nitro-arginine (L-NOARG, 40 mg/kg), a non-selective inhibitor of neuronal nitric oxide synthase (nNOS). Twenty-four hours after the last injection, the animals were killed and their brains were removed for immunohistochemistry assay to detect the presence of nNOS or for `in-situ` hybridisation study using (35)S-labeled oligonucleotide probe complementary to D(2) receptor mRNA. The results were analysed by computerised densitometry. Independent groups of animals received the same treatment, but were submitted to the catalepsy test and had their brain removed to measure nitrite and nitrate (NOx) concentrations in the striatum. Acute administration of L-NOARG caused catalepsy that disappeared after sub-chronic treatment. The levels of NOx were significantly reduced after acute L-NOARG treatment. The decrease in NOx after drug injection suffered a partial tolerance after sub-chronic treatment. The catalepsy time after acute or sub-chronic treatment with L-NOARG was negatively (r = -0.717) correlated with NOx levels. Animals that received repeated L-NOARG injections also showed an increase in the number of nNOS-positive neurons in the striatum. No change in D(2) receptor mRNA expression was found in the dorsal striatum, nucleus accumbens and substantia nigra. Together, these results suggest that tolerance to L-NOARG cataleptic effects do not depend on changes in D(2) receptors. They may depend, however, on plastic changes in nNOS neurons resulting in partial recovery of NO formation in the striatum.