Early-life stress affects behavioral and neurochemical parameters differently in male and female juvenile Wistar rats.

Neonatal handling is an early life stressor that leads to behavioral and neurochemical changes in adult rats in a sex-specific manner and possibly affects earlier stages of development. Here, we investigated the effects of neonatal handling (days 1-10 after birth) on juvenile rats focusing on biochemical parameters and olfactory memory after weaning. Male neonatal handled rats performed more crossings on the hole-board task, increased Na+ /K+ -ATPase activity in the olfactory bulb, and decreased acetylcholinesterase activity in the hippocampus versus non-handled males. Female neonatal handled animals increased the number of rearing and nose-pokes on the hole-board task, decreased glutathione peroxidase activity, and total thiol content in the hippocampus versus non-handled females. This study reinforces that early life stress affects behavioral and neurochemical parameters in a sex-specific manner even before the puberty onset.

Association between mode of delivery and neonatal deaths and complications in term pregnancy: a cohort study in Brazil.

AIM: Aim of the study was analyzing the association between mode of delivery and neonatal mortality/ morbidity in term pregnancy. METHODS: Cohort study with births of liveborn normally formed fetuses from single term pregnancies in a public teaching hospital in São Paulo, Brazil, from January 2003 to March 2004 (total of 1471 births). Data were collected from medical records. We defined 'elective caesareans' as those performed before labor. Four analyses were made: caesarean vs. vaginal, elective vs. non elective caesarean, elective caesarean vs. trial of labor, elective caesarean vs. women in labor. Outcomes studied were: neonatal deaths, jaundice, low Apgar score at 5 minutes, prolonged mechanical ventilation, convulsions, meconium aspiration syndrome, obstetrical trauma and late discharge. Adjustments were made for possible confounders. The chi square test was used along with logistic regression for the analyses. A significance level of 5% was assumed. RESULTS: A significant negative association between elective caesareans and neonatal death was found, neonatal complications taken as a whole and neonatal complications plus deaths. For example, elective caesarean versus women in labor for the outcome any neonatal complication, adjusted odds ratio 0.59; confidence interval 0.31-0.89. CONCLUSION: The study highlights a significant negative association of elective caesarean and neonatal mortality and morbidity in term pregnancy.

Isolation stress exposure and consumption of palatable diet during the prepubertal period leads to cellular changes in the hippocampus.

Social isolation is one of the most potent stressors in the prepubertal period and may influence disease susceptibility or resilience in adulthood. The glucocorticoid response and, consequently, the adaptive response to stress involve important changes in mitochondrial functions and apoptotic signaling. Previous studies have shown that consumption of a palatable diet reduces some stress effects. Therefore, the aim of the present study was to investigate whether isolation stress in early life can lead to cellular alterations in the hippocampus. For this, we evaluated oxidative stress parameters, DNA breakage index, mitochondrial mass and potential, respiratory chain enzyme activities, apoptosis, and necrosis in the hippocampus of juvenile male rats submitted or not to isolation stress during the pre-puberty period. We also verified whether consumption of a palatable diet during this period can modify stress effects. Results show that stress led to an oxidative imbalance, DNA breaks, increased the mitochondrial potential and early apoptosis, and decreased the number of live and necrotic cells. In addition, the palatable diet increased glutathione peroxidase activity, high mitochondrial potential and complex I-III activity in the hippocampus of juvenile rats. The administration of a palatable diet during the isolation period prevented the stress effects that caused the reduction in live cells and increased apoptosis. In conclusion, the stress experienced during the pre-pubertal period induced a hippocampal oxidative imbalance, DNA damage, mitochondrial dysfunction, and increased apoptosis, while consumption of a palatable diet attenuated some of these effects of exposure, such as the reduction in live cells and increased apoptosis, besides favoring an increase in antioxidant enzymes activities.

Into the island: a new technique of non-invasive cortical stimulation of the insula.

STUDY AIM: We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. INTRODUCTION: Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. METHODS: The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. RESULTS: Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. CONCLUSIONS: The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients.

Isolation stress during the prepubertal period in rats induces long-lasting neurochemical changes in the prefrontal cortex.

Social isolation during postnatal development leads to behavioral and neurochemical changes, and a particular susceptibility of the prefrontal cortex to interventions during this period has been suggested. In addition, some studies showed that consumption of a palatable diet reduces some of the stress effects. Therefore, our aim is to investigate the effect of isolation stress in early life on some parameters of oxidative stress and energy metabolism (Na(+),K(+)-ATPase activity, respiratory chain enzymes activities and mitochondrial mass and potential) in prefrontal cortex of juvenile and adult male rats. We also verified if the consumption of a palatable diet during the prepubertal period would reduce stress effects. The results showed that, in juvenile animals, isolation stress increased superoxide dismutase and Complex IV activities and these effects were still observed in the adulthood. An interaction between stress and diet was observed in catalase activity in juveniles, while only the stress effect was detected in adults, reducing catalase activity. Access to a palatable diet increased Na(+),K(+)-ATPase activity in juveniles, an effect that was reversed after removing this diet. On the other hand, isolation stress induced a decreased activity of this enzyme in adulthood. No effects were observed on glutathione peroxidase, total thiols and free radicals production, as well as on mitochondrial mass and potential. In conclusion, isolation stress in the prepubertal period leads to long-lasting changes on antioxidant enzymes and energetic metabolism in the prefrontal cortex of male rats, and a palatable diet was not able to reverse these stress-induced effects.

Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study.

BACKGROUND AND PURPOSE: Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing. METHODS: Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS. RESULTS: After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS. CONCLUSION: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation.

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation (P = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.

Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD.

BACKGROUND: Although depression is highly prevalent in Parkinson disease (PD), little is known about the neural correlates associated with depression and antidepressant treatment in PD. OBJECTIVE: To examine the effects of fluoxetine and repetitive transcranial magnetic stimulation (rTMS) on regional cerebral blood flow (rCBF) using SPECT in patients with PD and depression. METHODS: Twenty-six patients were enrolled into two groups: One received active rTMS and placebo medication and the other sham rTMS and fluoxetine 20 mg/day. Brain SPECT was performed at baseline and after 2 and 8 weeks. Changes in rCBF were compared across timepoints and correlated with clinical scores. In addition, baseline rCBF of these patients was compared with that of 29 healthy, age-matched subjects. RESULTS: At baseline, patients with PD and depression showed significantly lower rCBF in the left prefrontal cortex, posterior cingulate gyrus, left insula, and right parietal cortex when compared with healthy controls. Both treatments induced significant clinical improvement and increases in rCBF in the posterior cingulate gyrus and decreases in rCBF in the right medial frontal gyrus. These changes were significantly correlated to the clinical outcome. Furthermore, the comparison between these two treatments revealed that whereas rTMS treatment was associated with an increased perfusion in the right and left prefrontal cortex, fluoxetine treatment was associated with a relative rCBF increase in the occipital lobe. CONCLUSION: Depression in patients with Parkinson disease is correlated with a dysfunction of the frontal-limbic network that can be modulated by two different antidepressant therapies.

Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson's disease.

OBJECTIVE: To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on vocal function in Parkinson's disease (PD). MATERIAL AND METHODS: Two different sets of rTMS parameters were investigated on 30 patients with PD: active or sham 15 Hz rTMS of the left dorsolateral prefrontal cortex (LDLPFC) (110% of motor threshold (MT), 3000 pulses per session) and active 5 Hz rTMS of the primary motor cortex (M1)-mouth area (90% MT, 2250 pulses per session). A blind rater evaluated speech characteristics (acoustic and perceptual analysis of voice) and voice-related quality of life (V-RQOL). RESULTS: rTMS of LDLPFC resulted in mood amelioration and subjective improvement of the V-RQOL only (71.9% improvement, P < 0.001), but not in objective measures such as fundamental frequency (P = 0.86) and voice intensity (P = 0.99). On the other hand, rTMS of M1-mouth induced a significant improvement of the fundamental frequency (12.9% for men and 7.6% for women, P < 0.0001) and voice intensity (20.6%, P < 0.0001). CONCLUSIONS: Our findings provide initial evidence that rTMS of the primary motor cortex might yield a beneficial effect on vocal function in PD.

A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients.

The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke. Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected hand after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS.

Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson's disease.

OBJECTIVE: To study the efficacy of 15 Hz repetitive transcranial magnetic stimulation (rTMS) in treating depression in patients with Parkinson's disease. METHODS: 42 patients were enrolled into two groups: group 1, active rTMS (15 Hz rTMS for 10 days) and placebo drug treatment; group 2, sham rTMS and fluoxetine 20 mg/day. A specially designed sham coil was used for sham stimulation. The unified Parkinson's disease rating scale (UPDRS), activities of daily living (ADL), Hamilton rating scale for depression (HRSD), Beck depression inventory (BDI), and mini-mental state examination (MMSE) were assessed by a rater blinded to treatment arm. RESULTS: HRSD and BDI were improved to the same extent in both groups after two weeks of treatment (38% and 32% for group 1, 41% and 33% for group 2, respectively). At week 8 there was a tendency for worse motor UPDRS scores in group 2 (NS). ADL showed improvement at week 8 only in group 1. MMSE improved in both groups after treatment, but faster in group 1 than in group 2. There were fewer adverse effects in group 1 than in group 2. CONCLUSIONS: rTMS has the same antidepressant efficacy as fluoxetine and may have the additional advantage of some motor improvement and earlier cognitive improvement, with fewer adverse effects.

[Subcortical hyperintensities on magnetic resonance imaging: a comparison of normal and depressed elderly subjects]. / Hipersinais subcorticais no exame de ressonância magnética: comparação entre idosos deprimidos e idosos normais.

Previous studies reported that depressed subjects had more signal hyperintensities on magnetic resonance imaging scans than control subjects, but the subjects had cerebrovascular disease risk factors. This study used subjects with a history of major depression and matched comparison subjects, screened to exclude cerebrovascular risk factors, to determine whether depressed subjects had more white matter hyperintensities and other lesions. We evaluated the prevalence and severity of MRI signal hyperintensities in 30 elderly depressed patients and 20 controls matched for age. Deep matter hyperintensities, periventricular hyperintensities and subcortical gray hyperintensities were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. No significant differences were found between groups for the presence of subcortical gray matter, deep white matter and periventricular hyperintensities. These findings suggest that cerebrovascular disease risk factors most likely mediated the relationship between depression and hyperintensities in previous studies.

O impacto do uso de risperidona na qualidade de vida de pacientes esquizofrenicos / The impact of the treatment with risperidone in the schizophrenic patients quality of life

OBJETIVO: Este trabalho teve o objetivo de avaliar o impacto do uso da risperidona na qualidade de vida de pacientes esquizofrenicos. MATERIAIS E METODOS: 80 pacientes portadores de esquizofrenia(56 por cento subtipo paranoide) foram tratados com risperidona em um estudo prospectivo, longitudinal e aberto por seis meses para avaliar a eficacia terapeutica da medicaçäo, seus efeitos colaterais e seu impacto na qualidade de vida dos pacientes. Para avaliar a reposta terapeutica da risperidona foram utilizadas as escalas de avaliaçäo psiquiatrica breve (BPRS) e impressäo clínica global (CGI). A qualidade de vida foi avaliada pela escala de qualidade de vida (QLS) de HEINRICHS et al.,1984, além da escala de avaliaçäo da funçäo global (GAF). Os efeitos colaterais foram avaliados por relato espontaneo dos pacientes e os extra-piramidais pela escala UKU. RESULTADOS: Os pacientes apresentaram melhora significante em todas as escalas clínicas, em avaliaçöes após um, três e seis meses de tratamento com risperidona (p<0,001). Houve melhora significante no escore global da QLS e tambem no das suas subunidades (p<0,001). A mediçäo foi bem tolerada, sem aumento significante de efeitos colaterais extrapiramidais. DISCUSSAO E CONCLUSAO: Este estudo demonstra a importancia do antipsicotico atípico risperidona no tratamento da esquizofrenia, com importante impacto na qualidade de vida dos pacientes. Poeem, maiores estudos controlados duplo-cego precisam ser feitos comparando o impacto na qualidade de vida de risperidona com outros antipsicoticos, típicos ou atípicos

In vitro activity of teicoplanin against gram-positive cocci.

The glycopeptide susceptibility of 443 clinical isolates of gram-positive cocci collected from nine general hospitals in 1996 was determined according to the recommendations of the CA-SFM (the Antibiogram Committee of the French Society for Microbiology). In total, 234 isolates of Staphylococcus aureus, 84 isolates of coagulase-negative staphylococci (CNS), 98 enterococci and 27 streptococci were collected. The mecA gene confirming resistance to methicillin was found in 42.7% of S. aureus isolates and 51.2% of CNS isolates. No resistance to teicoplanin and vancomycin was found in S. aureus but four isolates of CNS had an MIC of teicoplanin > or = 8 mg/L. All isolates of Enterococcus faecalis tested were susceptible to both glycopeptides. This study confirms that teicoplanin has a very good in vitro activity against gram-positive cocci, isolated in France from nosocomial infections.

Clozapina, uma alternativa no tratamento dos transtornos afetivos bipolares resistentes e esquizoafetivos / Clozapine, on option in the therapy in bipolar refractory affective disorders and schizoaffectives

A clozapina é um psicofármico antigo que ainda hoje tem revolucionado o tratamento dos transtornos peiquiátricos. Essa droga foi desenvolvida na década de 60 e aprovada pelo FDA(Food and Drug Administration) em 1984 para o tratamento da esquizofrenia refratária. Dados recentes demonstram que ela também pode ser útil no controle dos quadros afetivos bipolares resistentes nos subtipos de ciclagem rápida, quadros mistos e nos transtornos esquizoafetivos

Estimulaçäo magnética transcraniana - uma propedêutica neurológica e uma terapêutica psiquiatriátrica / Transcranial magnetic stimulation - A neurologic propedeutic and a psychiatric therapy

A estimulaçäo magnética transcraniana é um método neurofisiológico que surgiu como uma alternativa técnica para a estimulaçäo elétrica cerebral na propedêutica neurológica de investigaçäo das lesöes dos tratos motores. A grande vantagem desta técnica é a estimulaçäo direta do córtex e talvez de regiöes subcorticais com ausência de contato de eletrodod, e por ser um procedimento näo invasivo é indolor. Recentemente também tem sido usada como método terapêutico em psiquiatria, principalmente nos quadros de transtornos afetivos, com uso potencial para outros quadros

Platelet monoamine oxidase in schizophrenia: a meta-analysis.

We did a meta-analysis on all publications (English and other languages) concerned with platelet monoamine oxidase (MAO) in schizophrenia. Essentially, when patients were medicated with a neuroleptic, most studies found that schizophrenics had lower platelet MAO levels than controls. Administration of neuroleptic lowers MAO levels. MAO levels in drug-free schizophrenics were similar to controls. Only a minority of studies found drug-free schizophrenics had decreased platelet MAO levels.

The prognosis of schizophrenia across cultures.

Taken as a whole, the reported cross-cultural studies of schizophrenia suggest that both the frequency of occurrence of the disease and the outcome for individual patients vary across cultures. Some of the observed variation in incidence rates is most likely secondary to differences in the use of diagnostic criteria, and this source of error is difficult to quantify. On the other hand, good evidence suggests that much of the variability in prognosis may be related to the sociocultural context of the patient's family. Personal dynamics within the family may therefore be an important mediator of the observed cross-cultural differences in the outcome of schizophrenia. The purpose of this paper is to review three areas of research in schizophrenia; namely, the importance in variation of the "first rank symptoms" and expressed emotion in families from different societies, and the findings of the World Health Organization International Pilot Study of Schizophrenia to demonstrate that patients with this disorder in developing countries have a more positive prognosis than do comparable patients in western industrialized societies.

[Acute lymphoblastic leukemia with major eosinophilia. Inaugural cardiac insufficiency, endocarditis grafting and valve replacement]. / Leucémie aiguë lymphoblastique avec grande éosinophilie. Insuffisance cardiaque inaugurale, greffe endocarditique et remplacement valvulaire.

Acute lymphoblastic leukemia (cytologically typical) was diagnosed in an 18-year-old man presenting with major eosinophilia. Prednisone therapy was initiated but sudden congestive heart failure occurred (left ventricular insufficiency with pulmonary edema). Concomitantly, blood counts became normal. Remission of the leukemic process was obtained while severe mitral regurgitation developed, due to bacterial endocarditis. Successful mitral valvuloplasty was achieved. Remission is still persisting one year after diagnosis.