Ivaldo Silva

Estrogen, progestogen and tamoxifen increase synaptic density of the hippocampus of ovariectomized rats

The effects of gonadal steroids or tamoxifen over the synaptic density of the CA1 region of the hippocampus was investigated in ovariectomized (OVX) rats. Chronic oral administration of conjugated equine estrogen, conjugated equine medroxyprogesterone, a combination of both or tamoxifen was performed in ovariectomized (OVX) rats over a period of 60 days. Synaptic density of the stratum radiatum of the CA1 region was evaluated by means of electron microscopy. Significant increases in the range of 34-49% were found for treated animals as compared to OVX controls not subject to hormonal replacement. Our results confirm previously reported effects of estradiol over synaptic density in this region and reports for the first time an effect of medroxyprogesterone (alone or in combination with estrogen) and tamoxifen. Our findings support the notion that hormonal replacement therapy and tamoxifen might have beneficial effects for cognitive function.

Brain abnormalities in Williams syndrome: A review of structural and functional magnetic resonance imaging findings

Williams syndrome (WS) is rare genetic form of mental retardation caused by a microdeletion on chromosome 7q11.23 that causes cognitive impairment and a variety of physical abnormalities. MRI studies of WS have demonstrated a series of brain abnormalities, including decreased brain size, with a relatively greater decrease in the volume of the cerebral white matter volume as compared to the cerebral gray matter. Moreover there is evidence that the posterior cerebrum is more affected in that persons with WS have a greater ratio of frontal to posterior regional volume. These findings are further supported by automated analyses that have shown reduced gray matter density in the superior parietal lobe areas. Functional MRI studies have demonstrated hypofunction immediately adjacent to, and anterior to, the intraparietal sulcus, a region in which structural brain differences had been identified. These anatomical and functional differences are consistent with the neuropsychological profile of WS - in particular, with evidence of dorsal stream visual processing deficits. To date, however, studies have always been performed in comparison to intellectually average controls. It is not clear, therefore, if findings are specific to the WS population or whether they represent a morphological disturbance characteristic of mental retardation, irrespective of genetic etiology. In this article, we reviewed recent advances underlying the structural and functional neural substrate of WS in Medical Literature Analysis and Retrieval System Online (MEDLINE; 1997-2007).

Onset of estrogen replacement has a critical effect on synaptic density of CA1 hippocampus in ovariectomized adult rats.

ObjectivesThe aim of this study was to evaluate differences between estrogen replacement therapy initiated either 4 or 12 days after ovariectomy on the synaptic density of the hippocampal CA1 field in rats. DesignFemale, adult, Wistar rats were ovariectomized bilaterally under ether anesthesia and divided among the following groups: 1) estrogen (conjugated equine estrogen 50 &mgr;g in 0.5 mL of propylene glycol, daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 5); 2) propylene glycol (0.5 mL daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 4); 3) estrogen (conjugated equine estrogen 50 &mgr;g in 0.5 mL of propylene glycol, daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3); 4) propylene glycol (0.5 mL daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3). At the end of the treatment, the rats were processed for electron microscopy and light analysis. ResultsSynaptic density in all of the CA1 strata subjected to evaluation was significantly higher in animals in which estrogen replacement was initiated 4 days after ovariectomy as compared with controls. In contrast, initiation of treatment after a 12-day interval did not result in recovery of synaptic density in any of the CA1 strata and was significantly lower than that of the animals subjected to hormone replacement after a 4-day delay (P < 0.01). ConclusionThe delay for hormone replacement therapy might have critical implications for modulating synaptic density.

Personality traits in juvenile myoclonic epilepsy: Evidence of cortical abnormalities from a surface morphometry study

Cluster B personality disorders (PD), characterized as emotional instability, immaturity, lack of discipline, and rapid mood changes, have been observed among patients with juvenile myoclonic epilepsy (JME) and have been associated with a worse seizure outcome. Proper understanding of the neurobiology of PD associated with JME could contribute to understanding the basis for earlier and more effective interventions. In the present study, volumetric and geometric features of cortical structure were assessed through an automated cortical surface reconstruction method aiming to verify possible structural cortical alterations among patients with JME. Twenty-two patients with JME with cluster B PD, 44 patients with JME without psychiatric disorders, and 23 healthy controls were submitted to a psychiatric evaluation through SCID I and SCID II and to an MRI scan. Significant cortical alterations in mesiofrontal and frontobasal regions, as well as in other limbic and paralimbic regions, were observed mainly in patients with JME with PD. The present study adds evidence to the hypothesis of frontal and limbic involvement in the pathophysiology of cluster B PD in JME, regions linked to mood and affective regulation, as well as to impulsivity and social behavior. Moreover, a multidimensional pattern of frontal, limbic, and paralimbic changes was observed through a method of structural analysis which offers different and simultaneous geometric features, allowing the elaboration of important pathophysiologic insights about cluster B PD in JME.

Nanotechnology in Phytotherapy: Antiinflammatory Effect of a Nanostructured Thymol Gel from Lippia sidoides in Acute Periodontitis in Rats

Lippia sidoides Cham (Verbenaceae) is largely distributed in the northeastern region of Brazil. It is popularly known as ‘Alecrim‐pimenta’. Recent studies have shown that some species of Lippia have interesting pharmacological activities. This study aimed to evaluate the effect of a nanostructured thymol gel (TG) 1.2 mg/g on acute phase of ligature‐induced periodontitis model [acute periodontal disease (APD)] in rats. APD was induced in 24 Wistar rats subjected to ligature placement on left molars in maxillae. Animals were treated with TG, immediately after APD induction. Saline‐based gel was utilized as negative control and diethylammonium diclofenac gel 10 mg/g was used as positive control. Animals were randomly assigned into the groups. The periodontium and the surrounding gingiva were examined at histopathology, as well as the neutrophil influx into the gingiva was assayed using myeloperoxidase activity levels by ELISA method. TG treatment reduced tissue lesion at histopathology coupled to decreased myeloperoxidase activity production in gingival tissue when compared with the saline gel control group (p < 0.05). The TG gel was able to provide a significant myeloperoxidase decreasing in gingiva tissue confirming to be effective in reducing gingival inflammation in this model. Copyright

Morphometric hemispheric asymmetry of orbitofrontal cortex in women with borderline personality disorder: a multi-parameter approach.

Functional imaging studies have implicated the orbitofrontal cortex (OFC) in the pathophysiology of borderline personality disorder (BPD). To date, however, volume-based magnetic resonance imaging (MRI) studies have yielded mixed results. We used a surface-based processing approach that allowed us to measure five morphometric cortical features of the OFC, including volumetric (cortical thickness and surface area) and geometric (mean curvature, depth of sulcus, and metric distortion - three indicators of cortical folding) parameters. Participants comprised 25 female BPD patients with no other current psychiatric comorbidity and 25 age- and gender-matched healthy controls who received structural MRI scans. Images were processed using the Freesurfer package. All BPD patients had a history of comorbid psychiatric disorder(s) and were currently on medications. Compared with controls, the BPD group showed reduced cortical thickness, surface area, mean curvature, depth of sulcus, and metric distortion in the right medial OFC. In the left medial OFC, the BPD group had reduced cortical thickness and mean curvature, but increased metric distortion. This study confirmed the utility of surface-based analysis in the study of BPD cortical structures. In addition, we observed extensive structural abnormalities in the medial OFC of female subjects with BPD, findings that were most pronounced in the right OFC, with preliminary data suggesting hemispheric asymmetry.

Brain health and cognitive and mood disorders in ageing women

Improved medical, economic and socio-cultural conditions have increased life expectancy, especially for women. The incidence of hypertension, diabetes mellitus, psychiatric and degenerative brain diseases, especially stroke and dementia, are more frequently seen in older people. Each of these conditions can separately, or in combination, result in similar signs and symptoms of cognition, memory, mood and motor function disorders. Therefore, it is important to understand the effects of normal ovarian ageing and the menopause on the nervous system, as well as the hallmarks of disease entities; many of these are described here. Also, the complexity of these issues is increased by the similarity of their effects to those of the polypharmacy and metabolic imbalances that are common in this population. These are complex issues, and it may be difficult and time-consuming to discern between normal brain functional changes and specific pathology in practice. Early evaluation of correctable possibilities, including imaging studies, may be key to management. Referral to specialists for diagnosis before starting clinical treatment is useful to address these issues.

The integrity of corpus callosum and cluster B personality disorders: a quantitative MRI study in juvenile myoclonic epilepsy.

Evidence suggests increased prevalence of cluster B personality disorders (PD) among patients with juvenile myoclonic epilepsy (JME), which has been associated with worse seizure control and more psychosocial dysfunctions. A preliminary voxel-based morphometry study demonstrated corpus callosum (CC) volume reduction in patients with JME and cluster B PD, particularly in the posterior midbody and isthmus. In this study we aimed to follow up these results with region of interest analysis. Sixteen JME patients with cluster B PD, 38 JME patients without any psychiatric disorder, and 30 demographically matched healthy controls submitted to a psychiatric evaluation and a magnetic resonance imaging scan. The total and regional callosal areas were obtained from the midsagittal slice using a semi-automated program. Psychiatric evaluation was performed through SCID-I and -II. Significant reductions in the posterior region of the CC were observed in the JME with PD group relative to the other groups. These data support previous findings of callosal reductions in cluster B PD, as well as a possible involvement of CC in patients with JME and such personality characteristics.

Absence of gender effect on amygdala volume in temporal lobe epilepsy

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres.

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats

PURPOSE To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0+/-2.9 mmHg and 111.0+/-6.7 mmHg, respectively) within 60 minutes. TNF-alpha levels in BAL do not differ significantly in the HCl+P group (516.0+/-5.9 pg/mL), and the HCl+S (513.0+/-10.6 pg/mL). CONCLUSION The use of prone position improved oxygenation, but did not reduce TNF-alpha in BAL upon lung dysfunction induced by HCl.