Inducible nitric oxide synthase in pityriasis lichenoides lesions

Pityriasis lichenoides (PL) is an inflammatory skin disease of unknown etiology. Nitric oxide (NO) has emerged as an important mediator of many physiological functions. The importance of NO-mediated signaling in skin diseases has been reported by several studies. A review of clinical records and histopathological slides of 34 patients diagnosed with PL was performed. Three different groups of skin biopsies including PL chronica (24 patients), PL et varioliformis acuta (10 patients) and 15 normal skin samples were subjected to the immunohistochemistry technique for inducible nitric oxide synthase (iNOS) detection. Normal skin group exhibited a few number of iNOS-positive cells in the dermis and rare positive cells in the upper epidermis, unlike abundant epidermal and dermal iNOS expression observed in both PL groups. According to our results, we hypothesize that NO produced by iNOS could participate in PL pathogenesis. Abnormal and persistent responses to unknown antigens, probably a pathogen, associated with NO immunoregulatory functions could contribute to the relapsing course observed in PL. NO anti-apoptotic effect on T-cell lymphocytes could play a role on maintenance of reactive T cells, leading to a T-cell lymphoid dyscrasia. Di Giunta G, Goncalves da Silva AM, Sotto MN. Inducible nitric oxide synthase in pityriasis lichenoides lesions.J Cutan Pathol 2009; 36: 325-330. (C) Blackwell Munksgaard 2008.

Influence of ankle functional instability on the ankle electromyography during landing after volleyball blocking

The purpose of this study was to describe, interpret and compare the EMG activation patterns of ankle muscles - tibialis anterior (TA), peroneus longus (PL) and gastrocnemius lateralis (GL) - in volleyball players with and without ankle functional instability (FI) during landing after the blocking movement. Twenty-one players with FI (IG) and 19 controls (CG) were studied. The cycle of movement analyzed was the time period between 200 ms before and 200 ms after the time of impact determined by ground reaction forces. The variables were analyzed for two different phases: pre-landing (200 ms before impact) and post-landing (200 ms after impact). The RMS values and the timing of onset activity were calculated for the three studied muscles, in both periods and for both groups. The co-activation index for TA and PL, TA and GL were also calculated. Individuals with FI presented a lower RMS value pre-landing for PL (CG = 43.0 perpendicular to 22.0; IG = 26.2 perpendicular to 8.4, p < 0.05) and higher RMS value post-landing (CG = 47.5 perpendicular to 13.3; IG = 55.8 perpendicular to 21.6, p < 0.10). Besides that, in control group PL and GL activated first and simultaneously, and TA presented a later activation, while in subjects with FI all the three muscles activated simultaneously. There were no significant differences between groups for co-activation index. Thus, the rate of contraction between agonist and antagonist muscles is similar for subjects with and without FI but the activation individually was different. Volleyball players with functional instability of the ankle showed altered patterns of the muscles that play an important role in the stabilization of the foot-ankle complex during the performance of the blocking movement, to the detriment of the ligament complex, and this fact could explain the usual complaints in these subjects. (C) 2007 Elsevier Ltd. All rights reserved.

Neurodynamics of an election

Variables influencing decision-making in real settings, as in the case of voting decisions, are uncontrollable and in many times even unknown to the experimenter. In this case, the experimenter has to study the intention to decide (vote) as close as possible in time to the moment of the real decision (election day). Here, we investigated the brain activity associated with the voting intention declared 1 week before the election day of the Brazilian Firearms Control Referendum about prohibiting the commerce of firearms. Two alliances arose in the Congress to run the campaigns for YES (for the prohibition of firearm commerce) and NO (against the prohibition of firearm commerce) voting. Time constraints imposed by the necessity of studying a reasonable number (here, 32) of voters during a very short time (5 days) made the EEG the tool of choice for recording the brain activity associated with voting decision. Recent fMRI and EEG studies have shown decision-making as a process due to the enrollment of defined neuronal networks. In this work, a special EEG technique is applied to study the topology of the voting decision-making networks and is compared to the results of standard ERP procedures. The results show that voting decision-making enrolled networks in charge of calculating the benefits and risks of the decision of prohibiting or allowing firearm commerce and that the topology of such networks was vote-(i.e., YES/NO-) sensitive. (C) 2010 Elsevier B.V. All rights reserved.

A Graphical Representation Model for Telemedicine and Telehealth Center Sustainability

This study shows the creation of a graphical representation after the application of a questionnaire to evaluate the indicative factors of a sustainable telemedicine and telehealth center in Sao Paulo, Brazil. We categorized the factors into seven domain areas: institutional, functional, economic-financial, renewal, academic-scientific, partnerships, and social welfare, which were plotted into a graphical representation. The developed graph was shown to be useful when used in the same institution over a long period and complemented with secondary information from publications, archives, and administrative documents to support the numerical indicators. Its use may contribute toward monitoring the factors that define telemedicine and telehealth center sustainability. When systematically applied, it may also be useful for identifying the specific characteristics of the telemedicine and telehealth center, to support its organizational development.

Family Environment and Pediatric Major Depressive Disorder

Background: The risks for depression broadly include biological and environmental factors. Furthermore, having a family member suffering from major depression is also likely to have consequences for the family environment. Further research aimed at understanding the effects of having a child with major depression on family interaction patterns is warranted. Methods: We studied 31 families with an 8- to 17-year-old child (mean age +/- SD = 12.9 +/- 2.7 years) who met the DSM-IV criteria for major depressive disorder (MDD) and 34 families with no mentally ill children (mean age 8 SD = 12.6 +/- 2.9 years) or parents. Children and their parents were assessed with the K-SADS-PL (Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version) interview. Parents completed the Moos Family Environment Scale (FES) to assess their perceptions of current family functioning. Data were analyzed using the nonparametric Wilcoxon-Mann-Whitney test. Results: Families of MDD children showed significantly different patterns of family functioning on FES subscales representing relationships and personal growth dimensions. The families with MDD children showed higher levels of conflict (p < 0.001) and lower levels of cohesion (p < 0.001), expressiveness (p = 0.003) and active-recreational orientation (p = 0.02) compared to the families without mentally ill children. Conclusion: Families with MDD children show a lower degree of commitment, provide less support to one another, provide less encouragement to express feelings and have more conflicts compared to families with no mentally ill children or parents. Interventions aimed at improving family dynamics may be beneficial to MDD children and their families. Copyright (C) 2010 S. Karger AG, Basel

Adipose tissue mesenchymal stem cell expansion in animal serum-free medium supplemented with autologous human platelet lysate

BACKGROUND: Mesenchymal stem cells (MSCs) have been considered for human regenerative therapy applications, and safe culture and expansion protocols are needed especially in the context of interspecies contamination. Human platelet lysate (PL) has been proposed as animal serum substitute during in vitro MSC expansion. In this work, a simplified and efficient method to obtain autologous PL to replace animal serum in cell culture applications is described. STUDY DESIGN AND METHODS: PL obtained by freezing and centrifugation procedures was tested as medium supplement for human adipose mesenchymal stem cell (hASC) culture. Differential proliferation, immunophenotypic changes, and differentiation under PL or fetal bovine serum (FBS) were assessed. RESULTS: In contrast to 10% FBS supplementation, cell population doubling time was significantly lower when hASCs were cultured with the same concentration of PL ( PL 22.9 +/- 1.5 hr vs. FBS 106.7 +/- 6.5 hr, t test, p < 0.05). Furthermore, hASCs maintained with 2.5% PL supplementation also showed satisfactory results. Immunophenotypic analysis revealed no differences between hASCs cultivated with PL or FBS supplementation and both cultures retained the potential to differentiate into adipose cells. These results demonstrate that autologous PL obtained from the same donor can be used as animal serum substitute in hASC culture. CONCLUSIONS: Taken together, evidence is provided that platelets provided by a single donor are sufficient to obtain PL for hASC propagation for clinical-scale applications mitigating the potential untoward side effects associated with the use of animal-derived reagents.

The effects of bromazepam over the temporo-parietal areas during the performance of a visuomotor task: A qEEG study

This study investigated the effects of bromazepam on qEEG when 14 healthy subjects were asked to perform a visuomotor task (i.e., motor vehicle driving task). The subjects were exposed to two experimental conditions: the placebo (PL) and 6 mg of bromazepam (Br 6 mg), following a randomized, double-blind design on different days. Specifically, we observe absolute power extracted from qEEG data for theta band. We expected to see a decrease in absolute theta power in the temporal and parietal areas due to the influence of bromazepam for the experimental group when compared with the placebo group. We found a main effect for the condition factor for electrodes T3, T4, P3 and P4. We also observed a main effect for the period factor for electrodes P3 and P4. We observed that the ingestion of 6 mg of bromazepam induces different patterns in theta power at the temporal and parietal sites. We concluded that 6 mg of bromazepam was an important factor in the fluctuation of the activities in the temporal and parietal areas. We then hypothesize about the specific role of this drug during the execution of a visuomotor task and within the sensorimotor integration process. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam

The aim of this study was to investigate the influence of bromazepam on EEG and the motor learning process when healthy subjects were submitted to a typewriting task. We investigated bromazepam due to its abuse by various populations and its prevalent clinical use among older individuals which are more sensitive to the negative effects of long half-life benzodiazepines. A randomized double-blind design was used with subjects divided into three groups: placebo (n = 13), bromazepam 3 mg (n = 13) and bromazepam 6 mg (n = 13). EEG data comprising theta, alpha and beta bands was recorded before, during and after the motor task. Our results showed a lower relative power value in the theta band in the Br 6 mg group when compared with PL. We also observed a reduction in relative power in the beta band in the Br 3 mg and Br 6 mg when compared with PL group. These findings suggest that Br can contribute to a reduced working memory load in areas related to attention processes. On the other hand, it produces a higher cortical activation in areas associated with sensory integration. Such areas are responsible for accomplishing the motor learning task. The results are an example of the usefulness of integrating electrophysiological data, sensorimotor activity and a pharmacological approach to aid in our understanding of cerebral changes produced by external agents. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Family environment patterns in families with bipolar children

Background: We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). Methods: We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Results: Parents of bipolar children reported lower levels of family cohesion (p<0.001), expressiveness (p=0.005), active-recreational orientation (p<0.001), intellectual-cultural orientation (p=0.04) and higher levels of conflict (p<0.001) compared to parents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.03 1) and cohesion (p=0.014) in families where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Limitations: Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Conclusion: Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder. (C) 2007 Elsevier B.V. All rights reserved.

Lectin extracted from Canavalia grandiflora seeds presents potential anti-inflammatory and analgesic effects

Neutrophil migration is responsible for tissue damage observed in inflammatory diseases and is also implicated in inflammatory nociception. The use of lectins has been demonstrated to be effective in different activities including anti-inflammatory, antimicrobial, and in cancer therapy. In this study, we addressed the potential use of a lectin from Canavalia grandiflora seeds (ConGF) to control neutrophil migration and inflammatory hypernociception. Pretreatment of the animals intravenously (15 min before) with ConGF inhibited neutrophil migration to the peritoneal cavity in a dose-dependent fashion confirmed by an inhibition of rolling and adhesion of leukocytes by intravital microscopy. Another set of experiments showed that pretreatment of the animals with ConGF inhibited the mechanical hypernociception in mice induced by the i.pl. injection of carrageenan or formalin. This anti-nociceptive effect correlated with an effective blockade of neutrophil influx, as assessed by the hind paw tissue myeloperoxidase levels. Furthermore, ConGF had important inhibitory effects on the mouse carrageenan-induced paw edema. In addition, animals treated with ConGF showed inhibition of cytokines release. In conclusion, we demonstrated that the lectin ConGF inhibits neutrophil migration and mechanical inflammatory hypernociception.

The role of PKA and PKC epsilon pathways in prostaglandin E(2)-mediated hypernociception

Background and purpose: Protein kinase (PK) A and the epsilon isoform of PKC (PKC epsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKC epsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception. Experimental approach: Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKC epsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws. Key results: Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKC epsilon (PKC epsilon I) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKC epsilon, while the hypernociception induced by paw injection of PKC epsilon agonist was not affected by an inhibitor of PKA (AKAPI). Conclusions and implications: Taken together, these findings are consistent with the suggestion that PKA activates PKC epsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception.

Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron

Previous work from our group showed that intrathecal (i.t.) administration of substances such as glutamate, NMDA, or PGE(2) induced sensitization of the primary nociceptive neuron (PNN hypernociception) that was inhibited by a distal intraplantar (i.pl.) injection of either morphine or dipyrone. This pharmacodynamic phenomenon is referred to in the present work as ""teleantagonism``. We previously observed that the antinociceptive effect of i.t. morphine could be blocked by injecting inhibitors of the NO signaling pathway in the paw (i.pl.), and this effect was used to explain the mechanism of opioid-induced peripheral analgesia by i.t. administration. The objective of the present investigation was to determine whether this teleantagonism phenomenon was specific to this biochemical pathway (NO) or was a general property of the PNNs. Teleantagonism was investigated by administering test substances to the two ends of the PNN (i.e., to distal and proximal terminals; i.pl. plus i.t. or i.t. plus i.pl. injections). We found teleantagonism when: (i) inhibitors of the NO signaling pathway were injected distally during the antinociception induced by opioid agonists; (ii) a nonselective COX inhibitor was tested against PNN sensitization by IL-1 beta; (iii) selective opioid-receptor antagonists tested against antinociception induced by corresponding selective agonists. Although the dorsal root ganglion seems to be an important site for drug interactions, the teleantagonism phenomenon suggests that, in PNNs, a local sensitization spreads to the entire cell and constitutes an intriguing and not yet completely understood pharmacodynamic property of this group of neurons.

Prelimbic but not infralimbic cortex is involved in the pressor response to chemoreflex activation in awake rats

The ventral portion of the medial prefrontal cortex comprises the prelimbic cortex (PL) and the infralimbic cortex (IL). Several studies have indicated that both the PL and the IL play an important role in cardiovascular control. Chemoreflex activation by systemic administration of potassium cyanide (KCN) evokes pressor and bradycardiac responses in conscious rats, in addition to an increase in respiratory frequency. We report here a comparison between the effects of pharmacological inhibition of PL and IL neurotransmission on blood pressure and heart rate responses evoked by chemoreflex activation using KCN (i.v.) in conscious rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl(2) (1 mm) into the PL evoked a significant attenuation of the pressor response, without affecting the chemoreflex-induced heart rate decrease. However, IL local synapse inhibition evoked no changes in cardiovascular responses induced by chemoreflex activation. Thus, our results suggest that the pressor but not the bradycardiac response to chemoreflex activation is, at least in part, mediated by local neurotransmission present in the PL cortex, without influence of the IL cortex.

Acute reversible inactivation of the ventral medial prefrontal cortex induces antidepressant-like effects in rats

The ventral medial prefrontal cortex (vMPFC) has direct connections to subcortical, diencephalic and brainstem structures that have been closely related to depression. However, studies aimed at investigating the role of the vMPFC in the neurobiology of depression have produced contradictory results. Moreover, the precise involvement of vMPFC anatomic subdivisions, the prelimbic(PL) and the infralimbic (IL) cortices, in regulating depressive-like behavior have been poorly investigated. The forced swimming test (FST) is a widely employed animal model aimed at detecting antidepressant-like effects. Therefore, to further investigate a possible involvement of the vMFPC in depressive-like behavior, rats bilaterally implanted with cannulae aimed at the PL or IL prefrontal cortices were submitted to 15 min of forced swimming (pre-test) followed, 24 h later, by a 5-min swimming session (test), where immobility time was registered. Synaptic transmission in these regions was temporarily inhibited using local microinjection of cobalt chloride at different periods of the experimental procedure (before or after the pre-test or before the test). PL inactivation decreased immobility time independently of the time of the injection. In the IL inactivation induced a significant antidepressant-like effect when performed immediately before the pre-test or before the test, but not after the pre-test. These results suggest that activation of the vMPFC is important for the behavioral changes observed in rats submitted to the FST. They further indicate that, although both the PL and IL cortices are involved in these effects, they may play different roles. (C) 2010 Elsevier B.V. All rights reserved.

Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats

Rationale: Systemic administration of cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is able to attenuate cardiovascular and behavioral (freezing) changes induced by re-exposure to a context that had been previously paired with footshocks. The brain sites mediating this effect, however, remain unknown. The medial prefrontal cortex (mPFC) has been related to contextual fear conditioning. Objectives: (1) To verify, using c-Fos immunocytochemistry, if the mPFC is involved in the attenuation of contextual fear induced by systemic administration of CBD; (2) to investigate if direct microinjections of CBD into mPFC regions would also attenuate contextual fear. Results: Confirming previous results systemic administration of CBD (10 mg/kg) decreased contextual fear and associated c-Fos expression in the prefrontal cortex (prelimbic and infralimbic regions). The drug also attenuated c-Fos expression in the bed nucleus of the stria terminalis (BNST). Direct CBD (30 nmol) microinjection into the PL prefrontal cortex reduced freezing induced by re-exposure to the aversively conditioned context. In the infralimbic (IL) prefrontal cortex, however, CBD (30 nmol) produced an opposite result, increasing the expression of contextual fear conditioning. This result was confirmed by an additional experiment where the conditioning session was performed under a less aversive protocol. Conclusion: These results suggest that the PL prefrontal cortex may be involved in the attenuation of contextual fear induced by systemic injection of CBD. They also support the proposition that the IL and PL play opposite roles in fear conditioning. A possible involvement of the BNST in CBD effects needs to be further investigated. (C) 2009 Elsevier B.V. All rights reserved.