Maurício Scopel Hoffmann

Na+,K+-ATPase activity impairment after experimental traumatic brain injury: relationship to spatial learning deficits and oxidative stress.

Traumatic brain injury (TBI) is a devastating disease that commonly causes persistent mental disturbances and cognitive deficits. Although studies indicate that oxidative stress and functional deficits occurring after TBI are interrelated events, the knowledge of the mechanisms underlying the development of such cognitive deficits has been limited. Thus, in the present study, we investigated the effect of fluid percussion brain injury (FPI) on a spatial learning task and levels of oxidative stress markers, namely, protein carbonylation and thiobarbituric acid-reactive substances (TBARS) and Na+,K+-ATPase activity 1 or 3 months after FPI in rats. Statistical analysis revealed that FPI increased the scape latency and mean number of error in Barnes maze test 1 and 3 months after FPI. We also found that protein carbonylation and TBARS content increased in the parietal cortex 1 and 3 months after FPI. In addition, 3 months after FPI, protein carbonylation levels increased both in ipsilateral and contralateral cortices of FPI animals. Indeed, statistical analysis revealed a decrease in Na+,K+-ATPase activity in the cerebral cortex of 1 month FPI animals. Furthermore, the decrease in enzyme activity found 3 months was larger, when compared with 1 month after FPI. These results suggest that cognitive impairment following TBI may result, at least in part, from increase of two oxidative stress markers, protein carbonylation and TBARS that occurs concomitantly to a decrease in Na+,K+-ATPase activity.

Adaptation to oxidative challenge induced by chronic physical exercise prevents Na+,K+-ATPase activity inhibition after traumatic brain injury

Physical exercise is likely to alter brain function and to afford neuroprotection in several neurological diseases. Although the favorable effects of physical exercise on traumatic brain injury (TBI) patients is well known, little information is available regarding the role of free radicals in the improvement induced by physical exercise in an experimental model of TBI induced by fluid percussion injury (FPI). Thus, we investigated whether 6 weeks of swimming training protects against oxidative damage (measured by protein carbonylation and thiobarbituric acid-reactive substances-TBARS) and neurochemical alterations represented by immunodetection of alpha subunit and activity of Na(+),K(+)-ATPase after FPI in cerebral cortex of rats. Statistical analysis revealed that physical training protected against FPI-induced TBARS and protein carbonylation increase. In addition, physical training was effective against Na(+),K(+)-ATPase enzyme activity inhibition and alpha(1) subunit level decrease after FPI. Pearsons correlation analysis revealed that the decrease in levels of catalytic alpha(1) subunit of Na(+),K(+)-ATPase induced FPI correlated with TBARS and protein carbonylation content increase. Furthermore, the effective protection exerted by physical training against FPI-induced free radical correlated with the immunocontent of the catalytic alpha(1) subunit maintenance. These data suggest that TBI-induced reactive oxygen species (ROS) generation decreases Na(+),K(+)-ATPase activity by decreasing the total number of enzyme molecules, and that physical exercise protects against this effect. Therefore, the effective protection of selected targets, such as Na(+),K(+)-ATPase induced by physical training, supports the idea that physical training may exert prophylactic effects on neuronal cell dysfunction and damage associated with TBI.

The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury.

Although the importance of brain trauma as risk factor for the development of epilepsy is well established, the mechanisms of epileptogenesis are not well understood. In the present study, we revealed that the injection of a subthreshold dose of PTZ (30 mg/Kg, i.p.) after 5 weeks of injury induced by Fluid Percussion Brain Injury (FPI) decreased latency for first clonic seizures, increased the time of spent generalized tonic-clonic seizures and electrocorticographic (EEG) wave amplitude. In addition, statistical analysis revealed that N-acetylcysteine (NAC) (100mg/kg) supplementation during 5 weeks after neuronal injury protected against behavioral and electrographical seizure activity elicited by subthreshold dose of PTZ. The supplementation of this antioxidant compound also protected against the Na(+),K(+)-ATPase activity inhibition and concomitant increase in the levels of oxidative stress markers (protein carbonylation and thiobarbituric acid-reactive substances-TBARS) in site and peri-contusional cortical tissue. In summary, the current experiments clearly showed that FPI model induces early posttraumatic seizures and suggest that an alteration in the lipid/protein oxidation, membrane fluidity, and Na(+),K(+)-ATPase activity may be correlated with neuronal excitability, a significant component of the secondary injury cascade that accompanies TBI.

A general psychopathology factor (P factor) in children: Structural model analysis and external validation through familial risk and child global executive function.

High rates of comorbidities and poor validity of disorder diagnostic criteria for mental disorders hamper advances in mental health research. Recent work has suggested the utility of continuous cross-cutting dimensions, including general psychopathology and specific factors of externalizing and internalizing (e.g., distress and fear) syndromes. The current study evaluated the reliability of competing structural models of psychopathology and examined external validity of the best fitting model on the basis of family risk and child global executive function (EF). A community sample of 8,012 families from Brazil with children ages 6–12 years completed structured interviews about the child and parental psychiatric syndromes, and a subsample of 2,395 children completed tasks assessing EF (i.e., working memory, inhibitory control, and time processing). Confirmatory factor analyses tested a series of structural models of psychopathology in both parents and children. The model with a general psychopathology factor (“P factor”) with 3 specific factors (fear, distress, and externalizing) exhibited the best fit. The general P factor accounted for most of the variance in all models, with little residual variance explained by each of the 3 specific factors. In addition, associations between child and parental factors were mainly significant for the P factors and nonsignificant for the specific factors from the respective models. Likewise, the child P factor—but not the specific factors—was significantly associated with global child EF. Overall, our results provide support for a latent overarching P factor characterizing child psychopathology, supported by familial associations and child EF.

Treadmill Exercise Protects Against Pentylenetetrazol-Induced Seizures and Oxidative Stress after Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and significant resources are required to develop a better understanding of the pathologic mechanism as targets for potential therapies. Thus, we decided to investigate whether physical exercise after fluid percussion injury (FPI) protects from oxidative and neurochemical alterations as well as from behavioral electroencephalographic (EEG) seizures induced by subeffective convulsive doses of pentylenetetrazol (PTZ; 35 mg/kg). Behavioral and EEG recordings revealed that treadmill physical training increased latency to first clonic and tonic-clonic seizures, attenuated the duration of generalized seizures, and protected against the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. EEG recordings also revealed that physical exercise prevented PTZ-induced amplitude increase in TBI animals. Neurochemical analysis showed that exercise training increased glutathione/oxidized glutathione ratio and glutathione levels per se. Exercise training was also effective against alterations in the redox status, herein characterized by lipid peroxidation (thiobarbituric acid reactive substances), protein carbonyl increase, as well as the inhibition of superoxide dismutase and Na⁺,K⁺-ATPase activities after FPI. On the other hand, histologic analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal damage in cerebral cortex 4 weeks after injury and that physical exercise did not protect against neuronal injury. These data suggest that the ability of physical exercise to reduce FPI-induced seizures is not related to its protection against neuronal damage; however, the effective protection of selected targets, such as Na⁺/K⁺-ATPase elicited by physical exercise, may represent a new line of treatment for post-traumatic seizure susceptibility.

Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury

Achievements made over the last years have highlighted the important role of creatine in health and disease. However, its effects on hyperexcitable circuit and oxidative damage induced by traumatic brain injury (TBI) are not well understood. In the present study we revealed that severe TBI elicited by fluid percussion brain injury induced oxidative damage characterized by protein carbonylation, thiobarbituric acid reactive species (TBARS) increase and Na(+),K(+)-ATPase activity inhibition 4 and 8 days after neuronal injury. Statistical analysis showed that after TBI creatine supplementation (300 mg/kg, p.o.) decreased the levels of protein carbonyl and TBARS but did not protect against TBI-induced Na(+),K(+)-ATPase activity inhibition. Electroencephalography (EEG) analysis revealed that the injection of a subconvulsant dose of PTZ (35 mg/kg, i.p.), 4 but not 8 days after neuronal injury, decreased latency for the first clonic seizures and increased the time of spent generalized tonic-clonic seizures compared with the sham group. In addition, creatine supplementation had no effect on convulsive parameters induced by a subconvulsant dose of PTZ. Current experiments provide evidence that lipid and protein oxidation represents a separate pathway in the early post-traumatic seizures susceptibility. Furthermore, the lack of consistent anticonvulsant effect exerted by creatine in this early phase suggests that its apparent antioxidant effect does not protect against excitatory input generation induced by TBI.

Positive Attributes Buffer the Negative Associations Between Low Intelligence and High Psychopathology With Educational Outcomes

Objective This study examines the extent to which children’s positive attributes are distinct from psychopathology. We also investigate whether positive attributes change or “buffer” the impact of low intelligence and high psychopathology on negative educational outcomes. Method In a community sample of 2,240 children (6–14 years of age), we investigated associations among positive attributes, psychopathology, intelligence, and negative educational outcomes. Negative educational outcomes were operationalized as learning problems and poor academic performance. We tested the discriminant validity of psychopathology versus positive attributes using confirmatory factor analysis (CFA) and propensity score matching analysis (PSM), and used generalized estimating equations (GEE) models to test main effects and interactions among predictors of educational outcomes. Results According to both CFA and PSM, positive attributes and psychiatric symptoms were distinct constructs. Positive attributes were associated with lower levels of negative educational outcomes, independent of intelligence and psychopathology. Positive attributes buffer the negative effects of lower intelligence on learning problems, and higher psychopathology on poor academic performance. Conclusion Children’s positive attributes are associated with lower levels of negative school outcomes. Positive attributes act both independently and by modifying the negative effects of low intelligence and high psychiatric symptoms on educational outcomes. Subsequent research should test interventions designed to foster the development of positive attributes in children at high risk for educational problems.

Resultados de dois esquemas de tratamento da pielonefrite durante a gravidez e correlação com o desfecho da gestação

PURPOSE To determine the epidemiological profile of women admitted for urinary tract infection as well as to verify the most prevalent agents and response to antibiotic therapy. METHODS A retrospective study of 106 pregnant women admitted to a university hospital for urinary tract infection treatment during the period between January 2007 to December 2010. The evaluation was based on analysis of the medical records of these pregnant women, with the observation of hospitalization and pregnancy data, as well as its outcome. Statistical analysis was performed using Statistical Package for the Social Science, version 15.0. The bilateral Fisher exact test and Students t test were used for data analysis, as well as descriptive statistical methods. RESULTS Positive urine cultures were observed in 60.5% of pregnant women admitted due to urinary tract infection. The most frequent infectious agent was Escherichia coli and no difference in resistance, recurrence or complications was observed between the most frequent etiologic agents. Pregnant women with previous UTI had a higher recurrence risk (OR=10.8; p<0.05). The antibiotics most commonly used during hospitalization were ampicillin and cefazolin. Change of therapeutic agent due to bacterial resistance occurred in 11.9% of patients who took cefazolin and in 20% of patients who took ampicillin (OR=5.5; p<0.05). The rate of gestational complications was the same for both treatments. There was no difference in mean number of days of hospitalization between the treatments. CONCLUSION In the studied population ampicillin showed a higher rate of bacterial resistance than cefazolin, requiring a larger number of treatment regimen exchanges, without resulting in differences in clinical outcome or time of hospitalization.PURPOSE: To determine the epidemiological profile of women admitted for urinary tract infection as well as to verify the most prevalent agents and response to antibiotic therapy. METHODS: A retrospective study of 106 pregnant women admitted to a university hospital for urinary tract infection treatment during the period between January 2007 to December 2010. The evaluation was based on analysis of the medical records of these pregnant women, with the observation of hospitalization and pregnancy data, as well as its outcome. Statistical analysis was performed using Statistical Package for the Social Science, version 15.0. The bilateral Fisher exact test and Students t test were used for data analysis, as well as descriptive statistical methods. RESULTS: Positive urine cultures were observed in 60.5% of pregnant women admitted due to urinary tract infection. The most frequent infectious agent was Escherichia coli and no difference in resistance, recurrence or complications was observed between the most frequent etiologic agents. Pregnant women with previous UTI had a higher recurrence risk (OR=10.8; p<0.05). The antibiotics most commonly used during hospitalization were ampicillin and cefazolin. Change of therapeutic agent due to bacterial resistance occurred in 11.9% of patients who took cefazolin and in 20% of patients who took ampicillin (OR=5.5; p<0.05). The rate of gestational complications was the same for both treatments. There was no difference in mean number of days of hospitalization between the treatments. CONCLUSION: In the studied population ampicillin showed a higher rate of bacterial resistance than cefazolin, requiring a larger number of treatment regimen exchanges, without resulting in differences in clinical outcome or time of hospitalization.

Cross-Sectional and Longitudinal Associations of Temperament and Mental Disorders in Youth

Here we evaluate the cross-sectional and longitudinal associations between temperament and mental disorders in adolescents. Temperament was assessed in a cohort of 1540 youths by the revised self-report Early Adolescence Temperament Questionnaire (EATQ-R) at baseline and confirmatory factor analyses were used to test the best empirical model. Mental disorders were assessed by parental interview using the Development and Well-Being Behavior Assessment at baseline and at 3-year follow-up. Participants were grouped into Typically Developing Comparisons, Phobias, Distress, Attention-Deficit/Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders (DBD). Logistic regression models tested the effects of temperament on incidence and remission of mental disorders. The bifactor model of EATQ-R presented the best fit. Distress, ADHD and DBD have lower levels of effortful control in baseline. Adjusted longitudinal analysis showed that effortful control predicted lower incidence of Phobias (OR 0.74; p = 0.018), distress (OR 0.74; p = 0.014) and DBD (OR 0.68; p = 0.037). Temperament factors did not predicted remission rates.

Specific and social fears in children and adolescents: separating normative fears from problem indicators and phobias

Objective: To distinguish normative fears from problematic fears and phobias. Methods: We investigated 2,512 children and adolescents from a large community school-based study, the High Risk Study for Psychiatric Disorders. Parent reports of 18 fears and psychiatric diagnosis were investigated. We used two analytical approaches: confirmatory factor analysis (CFA)/item response theory (IRT) and nonparametric receiver operating characteristic (ROC) curve. Results: According to IRT and ROC analyses, social fears are more likely to indicate problems and phobias than specific fears. Most specific fears were normative when mild; all specific fears indicate problems when pervasive. In addition, the situational fear of toilets and people who look unusual were highly indicative of specific phobia. Among social fears, those not restricted to performance and fear of writing in front of others indicate problems when mild. All social fears indicate problems and are highly indicative of social phobia when pervasive. Conclusion: These preliminary findings provide guidance for clinicians and researchers to determine the boundaries that separate normative fears from problem indicators in children and adolescents, and indicate a differential severity threshold for specific and social fears.