Effect of treadmill exercise on lumbar vertebrae in ovariectomized rats: anthropometrical and mechanical analyses

The purpose of this study was to examine the preventive effect of exercise on lumbar vertebrae in ovariectomized rats. Three-month-old female Wistar rats were divided into 3 groups: control group (A, n = 10); non-exercised ovariectomized group (B, n = 7) and exercised ovariectomized group (C, n = 7). The rats from group C were subjected to treadmill exercise (15 m/minute in the initial six weeks and 19 m/minute in the next six weeks, 1 hour/day, 4 days/week) for 12 weeks. At death, the fourth lumbar vertebrae were removed and an anthropometrical analysis by a paquimeter and a mechanical compression test by a universal test machine were performed. After 12 weeks, the ovariectomy decreased the superior-inferior vertebral height and the maximal braking load in group B compared to group A, while the exercise increased the vertebral mass in group C compared to both groups A and B (p < 0.01) and the stiffness compared to group B. We concluded the physical activity has an important role to prevent the osteopenia in lumbar vertebrae.

Error in body weight estimation leads to inadequate parenteral anticoagulation

Parenteral anticoagulation is a cornerstone in the management of venous and arterial thrombosis. Unfractionated heparin has a wide dose/response relationship, requiring frequent and troublesome laboratorial follow-up. Because of all these factors, low-molecular-weight heparin use has been increasing. Inadequate dosage has been pointed out as a potential problem because the use of subjectively estimated weight instead of real measured weight is common practice in the emergency department (ED). To evaluate the impact of inadequate weight estimation on enoxaparin dosage, we investigated the adequacy of anticoagulation of patients in a tertiary ED where subjective weight estimation is common practice. We obtained the estimated, informed, and measured weight of 28 patients in need of parenteral anticoagulation. Basal and steady-state (after the second subcutaneous shot of enoxaparin) anti-Xa activity was obtained as a measure of adequate anticoagulation. The patients were divided into 2 groups according the anticoagulation adequacy. From the 28 patients enrolled, 75% (group 1, n = 21) received at least 0.9 mg/kg per dose BID and 25% (group 2, n = 7) received less than 0.9 mg/kg per dose BID of enoxaparin. Only 4 (14.3%) of all patients had anti-Xa activity less than the inferior limit of the therapeutic range (<0.5 UI/mL), all of them from group 2. In conclusion, when weight estimation was used to determine the enoxaparin dosage, 25% of the patients were inadequately anticoagulated (anti-Xa activity <0.5 UI/mL) during the initial crucial phase of treatment. (C) 2011 Elsevier Inc. All rights reserved.

Serotonergic neurotransmission in the dorsal raphe nucleus recruits in situ 5-HT2A/2C receptors to modulate the post-ictal antinociception

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and humans. The aim of this study was to assess the involvement of the dorsal raphe nucleus (DRN) in the post-ictal antinociception. The second aim was to study the role of serotonergic intrinsic mechanisms of the DRN in this hypo-algesic phenomenon. Pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl- influx antagonist, was peripherally used to induce tonic-clonic seizures in Wistar rats. The nociceptive threshold was measured by the tail-flick test. Neurochemical lesions of the DRN, performed with microinjection of ibotenic acid (1.0 mu g/0.2 mu L), caused a significant decrease of tonic-clonic seizure-induced antinociception, suggesting the involvement of this nucleus in this antinociceptive Process. Microinjections of methysergide (1.0 and 5.0 mu g/0.2 mu L), a non-selective serotonergic receptor antagonist, into DRN caused a significant decrease in the post-ictal antinociception in seizing animals, compared to controls, in all post-ictal periods Presently studied. These findings were corroborated by microinjections of ketanserin (at 1.0 and 5.0 mu g/0.2 mu L) into DRN. Ketanserin is an antagonist with large affinity for 5-HT2A/2C serotonergic receptors, which, in this Case, Caused a significant decrease in the tail-flick latencies in seizing animals, compared to controls after the first 20 min following tonic-clonic convulsive reactions. These results indicate that serotonergic neurotransmission of the DRN neuronal clusters is involved in the organization of the post-ictal hypo-algesia. The 5-HT2A/2C receptors of DRN neurons seem to be critically involved in the increase of nociceptive thresholds following tonic-clonic seizures. (c) 2008 Elsevier Inc, All rights reserved.

GABA(A) receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception

Dysfunction in the hypothalamic GABAergic system has been implicated in panic syndrome in humans. Furthermore, several studies have implicated the hypothalamus in the elaboration of pain modulation. Panic-prone states are able to be experimentally induced in laboratory animals to study this phenomenon. The aim of the present work was to investigate the involvement of medial hypothalamic nuclei in the organization of panic-like behaviour and the innate fear-induced oscillations of nociceptive thresholds. The blockade of GABA(A) receptors in the neuronal substrates of the ventromedial. or dorsomedial hypothalamus was followed by elaborated defensive panic-like reactions. Moreover, innate fear-induced antinociception was consistently elicited after the escape behaviour. The escape responses organized by the dorsomedial and ventromedial hypothalamic nuclei were characteristically more elaborated, and a remarkable exploratory behaviour was recorded during GABA(A) receptor blockade in the medial hypothalamus. The motor characteristic of the elaborated defensive escape behaviour and the patterns of defensive alertness and defensive immobility induced by microinjection of the bicuculline either into the dorsomedial. or into the ventromedial hypothalamus were very similar. This was followed by the same pattern of innate fear-induced antinociceptive response that lasted approximately 40 min after the elaborated defensive escape reaction in both cases. These findings suggest that dysfunction of the GABA-mediated neuronal system in the medial hypothalamus causes panic-like responses in laboratory animals, and that the elaborated escape behaviour organized in both dorsomedial and ventromedial hypothalamic nuclei are followed by significant innate-fear-induced antinociception. Our findings indicate that the GABA(A) receptor of dorsomedial and ventromedial hypothalamic nuclei are critically involved in the modulation of panic-like behaviour. (C) 2009 Elsevier B.V. All rights reserved.

Glomerular Nucleus of the Weakly Electric Fish, Gymnotus sp.: Cytoarchitecture, Histochemistry, and Fiber Connections-Insights from Neuroanatomy to Evolution and Behavior

The present study provides a detailed description of morphological and hodological aspects of the glomerular nucleus in the weakly electric fish Gymnotus sp., and explores the evolutionary and functional implications flowing from this analysis. The glomerular nucleus of Gymnotus shows numerous morphological similarities with the glomerular nucleus of percomorph fish, although cytoarchitectonically simpler. In addition, congruence of the histochemical acetylcholinesterase (AChE) distribution with cytoarchitectonic data suggests that the glomerular nucleus, together with the ventromedial cell group of the medial subdivision of the preglomerular complex (PGm-vmc) rostrally, and the subglomerular nucleus (as identified by Maler et al. [1991] J Chem Neuroanat 4:1-38) caudally, may form a distinct longitudinally organized glomerular complex. Our results show that an important source of sensory afferents to the glomerular nucleus originates in the pretectal and electrosensorius nuclei. The glomerular nucleus in turn projects to the hypothalamus (inferior lobe and anterior hypothalamus), to the anterior tuberal nucleus, and to the medial region of the preglomerular nucleus (PGm). These data suggest that visual and electrosensory information reach the glomerular nucleus and are relayed to the hypothalamus and, via PGm, to the pallium. Such connections are similar to those of the glomerular nucleus in percomorphs and the posterior pretectal nucleus in osteoglossomorph, esocids, and salmonids, where they comprise one component of a visual processing pathway. In Gymnotiform fish, however, the pretectal region that projects to the glomerular nucleus is dominated by electrosensory input (visual input is minor), which is consistent with the dominant role of electroreception in these fish. J. Comp. Neurol. 519:1658-1676, 2011. (c) 2011 Wiley-Liss, Inc.

Role of the superior colliculus in the expression of acute and kindled audiogenic seizures in Wistar audiogenic rats

P>Purpose: The role of the superior colliculus (SC) in seizure expression is controversial and appears to be dependent upon the epilepsy model. This study shows the effect of disconnection between SC deep layers and adjacent tissues in the expression of acute and kindling seizures. Methods: Subcollicular transections, ablation of SC superficial and deep layers, and ablation of only the cerebral cortex were evaluated in the Wistar audiogenic rat (WAR) strain during acute and kindled audiogenic seizures. The audiogenic seizure kindling protocol started 4 days after surgeries, with two acoustic stimuli per day for 10 days. Acute audiogenic seizures were evaluated by a categorized seizure severity midbrain index (cSI) and kindled seizures by a severity limbic index (LI). Results: All subcollicular transections reaching the deep layers of the SC abolished audiogenic seizures or significantly decreased cSI. In the unlesioned kindled group, a reciprocal relationship between limbic and brainstem pattern of seizures was seen. The increased number of stimuli provoked an audiogenic kindling phenomenon. Ablation of the entire SC (ablation group) or of the cerebral cortex only (ctx-operated group) hampered the acquisition of limbic behaviors. There was no difference in cSI and LI between the ctx-operated and ablation groups, but there was a difference between ctx-operated and the unlesioned kindled group. There was also no difference in cSI between SC deep layer transection and ablation groups. Results of histologic analyses were similar for acute and kindled audiogenic seizure groups. Conclusions: SC deep layers are involved in the expression of acute and kindled audiogenic seizure, and the cerebral cortex is essential for audiogenic kindling development.

Puzzling challenges in contemporary neuroscience: Insights from complexity and emergence in epileptogenic circuits

The brain is a complex system that, in the normal condition, has emergent properties like those associated with activity-dependent plasticity in learning and memory, and in pathological situations, manifests abnormal long-term phenomena like the epilepsies. Data from our laboratory and from the literature were classified qualitatively as sources of complexity and emergent properties from behavior to electrophysiological, cellular, molecular, and computational levels. We used such models as brainstem-dependent acute audiogenic seizures and forebrain-dependent kindled audiogenic seizures. Additionally we used chemical OF electrical experimental models of temporal lobe epilepsy that induce status epilepticus with behavioral, anatomical, and molecular sequelae such as spontaneous recurrent seizures and long-term plastic changes. Current Computational neuroscience tools will help the interpretation. storage, and sharing of the exponential growth of information derived from those studies. These strategies are considered solutions to deal with the complexity of brain pathologies such as the epilepsies. (C) 2008 Elsevier Inc. All rights reserved.

Inhibitory network interactions shape the auditory processing of natural communication signals in the songbird auditory forebrain

The role of GABA in the central processing of complex auditory signals is not fully understood. We have studied the involvement of GABA(A)-mediated inhibition in the processing of birdsong, a learned vocal communication signal requiring intact hearing for its development and maintenance. We focused on caudomedial nidopallium (NCM), an area analogous to parts of the mammalian auditory cortex with selective responses to birdsong. We present evidence that GABA(A)-mediated inhibition plays a pronounced role in NCM`s auditory processing of birdsong. Using immunocytochemistry, we show that approximately half of NCM`s neurons are GABAergic. Whole cell patch-clamp recordings in a slice preparation demonstrate that, at rest, spontaneously active GABAergic synapses inhibit excitatory inputs onto NCM neurons via GABA(A) receptors. Multi-electrode electrophysiological recordings in awake birds show that local blockade of GABA(A)-mediated inhibition in NCM markedly affects the temporal pattern of song-evoked responses in NCM without modifications in frequency tuning. Surprisingly, this blockade increases the phasic and largely suppresses the tonic response component, reflecting dynamic relationships of inhibitory networks that could include disinhibition. Thus processing of learned natural communication sounds in songbirds, and possibly other vocal learners, may depend on complex interactions of inhibitory networks.

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFq. Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyms. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD. (C) 2011 Elsevier B.V. All rights reserved.

Is the Full Version of the AUDIT Really Necessary? Study of the Validity and Internal Construct of Its Abbreviated Versions

Background: This study was aimed at assessing the psychometric qualities of the abbreviated versions of the Alcohol Use Disorders Identification Test (AUDIT-3, AUDIT-4, AUDIT-C, AUDIT-PC, AUDIT-QF, FAST, and Five-Shot) and at comparing them to the 10-item AUDIT and the CAGE in 2 samples of Brazilian adults. Methods: The validity and internal consistency of the scales were assessed in a sample of 530 subjects attended at an emergency department and at a Psychosocial Care Center for Alcohol and Drugs. The Structured Clinical Interview for DSM-IV was used as the diagnostic comparative measure for the predictive validity assessment. The concurrent validity between the scales was analyzed by means of Pearson`s correlation coefficient. Results: The assessment of the predictive validity of the abbreviated versions showed high sensitivity (of 0.78 to 0.96) and specificity (of 0.74 to 0.94) indices, with areas under the curve as elevated as those of the AUDIT (0.89 and 0.92 to screen for abuse and 0.93 and 0.95 in the screening of dependence). The CAGE presented lower indices: 0.81 for abuse and 0.87 for dependence. The analysis of the internal consistency of the AUDIT and its versions exhibited Cronbach`s alpha coefficients between 0.83 and 0.94, while the coefficient for the CAGE was 0.78. Significant correlations were found between the 10-item AUDIT and its versions, ranging from 0.91 to 0.99. Again, the results for the CAGE were satisfactory (0.77), although inferior to the other instruments. Conclusions: The results obtained in this study confirm the validity of the abbreviated versions of the AUDIT for the screening of alcohol use disorders and show that their psychometric properties are as satisfactory as those of the 10-item AUDIT and the CAGE.

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.

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.

Expression of transcription factors NF-kappa B and AP-1 in nasal polyposis

Background The treatment and prognosis of nasal polyposis (NP) may be influenced by transcription factors, but their expression is poorly understood. Objective To determine the expression of transcription factors [(nuclear factor-kappa B) NF-kappa B and (activator protein) AP-1], cytokines [IL-1 beta, TNF-alpha and (granulocytes and macrophage colony-stimulating factor) GM-CSF], growth factor (b-FGF), chemokine (eotaxin-2) and adhesion molecule (ICAM-1) in NP in comparison with nasal mucosa controls. Methods Cross-sectional study. Twenty biopsies of nasal polyps were compared with eight middle turbinate biopsies. p65, c-Fos, IL-1 beta, TNF-alpha, ICAM-1, b-FGF, eotaxin-2 and GM-CSF were analysed through RQ-PCR, and p65 and c-Fos were also analysed through Western blotting. Results NF-kappa B expression was increased in patients with NP when compared with control mucosa (P < 0.05), whereas AP-1 expression did not differ significantly between groups. Expressions of IL-1 beta, eotaxin-2 and b-FGF were also increased in patients with NP compared with controls (P < 0.05). Conclusions The transcription factor NF-kappa B is more expressed in NP than in control mucosa. This is important in NP because NF-kappa B can induce the transcription of cytokines, chemokines and adhesion molecules, which play an important role in the inflammatory process. Moreover, transcription factors influence the response to corticosteroids, which are the basis of NP treatment. Transcription factor AP-1 does not seem to have a significant role in the pathological process.

Predicting Hospital Mortality in Critically Ill Cancer Patients according to Acute Kidney Injury Severity

Background: Acute kidney injury (AKI) is a frequent complication in hospitalized patients, especially in those in intensive care units (ICU). The RIFLE classification might be a valid prognostic factor for critically ill cancer patients. The present study aims to evaluate the discriminatory capacity of RIFLE versus other general prognostic scores in predicting hospital mortality in critically ill cancer patients. Methods: This is a single-center study conducted in a cancer-specialized ICU in Brazil. All of the 288 patients hospitalized from May 2006 to June 2008 were included. RIFLE classification, APACHE II, SOFA, and SAPS II scores were calculated and the area under receiver operating characteristic (AROC) curves and logistic multiple regression were performed using hospital mortality as the outcome. Results: AKI, defined by RIFLE criteria, was observed in 156 (54.2%) patients. The distribution of patients with any degree of AKI was: risk, n = 96 (33.3%); injury, n = 30 (10.4%), and failure, n = 30 (10.4%). Mortality was 13.6% for non-AKI patients, 49% for RIFLE `R` patients, 62.3% for RIFLE `I` patients, and 86.8% for RIFLE `F` patients (p = 0.0006). Logistic regression analysis showed that RIFLE criteria, APACHE II, SOFA, and SAPS II were independent factors for mortality in this population. The discrimination of RIFLE was good (AROC 0.801, 95% CI 0.748-0.854) but inferior compared to those of APACHE II (AROC 0.940, 95% CI 0.915-0.966), SOFA (AROC 0.910, 95% CI 0.876-0.943), and SAPS II (AROC 0.869, 95% CI 0.827-0.912). Conclusion: AKI is a frequent complication in ICU patients with cancer. RIFLE was inferior to commonly used prognostic scores for predicting mortality in this cohort of patients. Copyright (C) 2011 S. Karger AG, Basel