Evaluation of the effects of quercetin on brain lesions secondary to experimental hydrocephalus in rats.

INTRODUCTION: Hydrocephaly is a disease that affects not only the dynamics of the cerebrospinal fluid, but also other structures of the central nervous system. Although shunt is effective in reducing ventriculomegaly, many neurological damages are not reversed with surgery. Several studies demonstrate that oxidative stress is involved in the genesis of hydrocephalus lesions. OBJECTIVE: Evaluate the neuroprotective response of quercetin in hydrocephalus. MATERIALS AND METHODS: Male newborns rats were used, which received the 15% kaolin injection in the cisterna magna for induction of hydrocephalus. They were divided into control group (C), untreated hydrocephalic (HN), shunted hydrocephalic (HD), hydrocephalic treated with distilled water (HA), hydrocephalic treated with distilled water and shunt (HDA), hydrocephalic treated with quercetin peritoneal (HQp), hydrocephalic treated with quercetin peritoneal and shunt (HDQp), hydrocephalic treated with quercetin by gavage (HQg), and hydrocephalus treated with quercetin by gavage and shunt (HDQg). RESULTS: Quercetin significantly improved the immunohistochemical markers, mainly caspase and GFAP. There were no significant changes in clinical/behavioral assessment. The use of isolated quercetin does not alter the volume and ventricular size, and the realization of ventriculo-subcutaneous shunt in newborn rats with hydrocephalus presents a high morbi-mortality. CONCLUSION: The use of quercetin shows laboratory improvement of the effects of glial lesion and corpus callosum fibers and is therefore not justified by the use of the routine substance as neuroprotective.

P27/CDKN1B Translational Regulators in Pituitary Tumorigenesis.

In pituitary tumors, P27(CDKN1B) is underexpressed. We aimed to clarify whether translational regulation underlies this phenomenon. This study evaluated the expression of P27/CDKN1B, its targets (CCNE1, CDK2) and translational regulators (DKC1, RPS13, miR221, miR222) and screened for DKC1 variants in sporadic pituitary adenomas. Samples were obtained during transsphenoidal surgery from 48 patients with pituitary adenomas: 10 ACTH-, 17 GH-secreting, and 21 nonfunctioning (NFPA). The control group comprised 7 normal pituitaries (NP) obtained during autopsies. Gene expression was assessed by RT-PCR and protein expression by immunohistochemistry. The 15 exons of DKC1 were sequenced. P27 protein underexpression was observed in all adenomas subtypes (p=0.001). CCNE1 mRNA (p=0.01) overexpression, but not protein, was observed in NFPA. No differential gene expression among groups was observed in CDKN1B regulators RPS13 (p=0.23) and DKC1 (p=0.34). The expression of miR221 and miR222 was similar among tumors and NP. Frequent DKC1 variants (SNPs) were found in exon 14 and in the 3'-UTR in similar frequency to NCBI-dsSNP databases. We also observed rare DKC1 variants in 11% of the studied tumor samples, indicating a high prevalence in pituitary adenomas, however, in silico studies failed to indicate deleterious effects. The high frequency of DKC1 variants may influence, in some extent, pituitary tumors development, without clear role in its tumorigenesis. Our data reinforce the P27 underexpression in pituitary adenomas and provide further evidence of the post-translational machinery involvement, although this phenomenon cannot be explained either by mis-expression of P27 translational regulators - DKC1, RPS13, miR221, miR222 - or directly by DKC1 mutations.

Curative embolization of pediatric intracranial arteriovenous malformations using Onyx: the role of new embolization techniques on patient outcomes.

INTRODUCTION: Intracranial arteriovenous malformations (AVMs) are the most frequent cause of hemorrhagic strokes in the pediatric population. The study aim was to retrospectively assess the safety and efficacy of Onyx embolization with the intention to cure AVMs in a pediatric population. METHODS: A retrospective analysis of all patients (<18 years) who underwent endovascular embolization using Onyx at our institution was conducted. The primary endpoint was the composite complete angiographic occlusion of AVM immediately after the last embolization session that had no procedure-related complication requiring emergency surgery. Secondary endpoints were angiographic occlusion rates, procedure-related complications, and clinical outcomes after treatment and at the 6-month follow-up RESULTS: Twenty-three patients (mean age, 11.7 years) underwent a total of 45 embolization sessions. The median Spetzler-Martin grade was 3 (range 1 to 4). The primary endpoint was achieved in 19 patients (82.6 %). Complete angiographic occlusion of the AVM was obtained in 21 patients (91.3 %) immediately after embolization and at the 6-month follow-up. Embolization-related complications were observed in three patients (13 %). None of the complications resulted in permanent functional disability or death. In two patients (8.7 %), the AVM could not be completely occluded by embolization alone and the patients were referred to radiosurgery and microsurgery, respectively. CONCLUSION: Onyx embolization of AVM in pediatric patients with the intention to cure resulted in high occlusion rates without increasing neurological disability or death. The development of new embolization techniques and devices seems to improve the safety of Onyx embolization.

Telomere length and telomerase expression in pituitary tumors.

PURPOSE: Telomere dysfunction and telomerase activation underlie cancer transformation. This study aims to investigate the contribution of telomere biology to pituitary tumor behavior. SUBJECTS AND METHODS: Samples from 50 patients with pituitary tumors (11 ACTH-secreting, 18 GH-secreting, and 21 non-secreting tumors) and 7 subjects without pituitary lesions were collected. The expressions of telomerase essential components TERT and TERC and tumor telomere content were measured by quantitative PCR techniques. RESULTS: Telomerase (TERT) expression was detected in 36% of tumors. No correlation was observed between TERT and TERC expression level and tumor size in any tumor type. There was no association between gene expression and clinical findings. Telomere content (T/S ratio) was similar between pituitary adenomas (0.39 ± 0.16) and normal pituitaries (0.47 ± 0.12; p = 0.24) and also was between the different adenoma types: ACTH-secreting (0.43 ± 0.08), GH-secreting (0.31 ± 0.12), and non-secreting (0.42 ± 0.20; p = 0.10) tumors. CONCLUSIONS: The telomere content and expression of telomerase components are comparable between normal pituitary glands and tumor tissues, suggesting that telomere biology does not play an important role in pituitary tumor development.

Sonic Hedgehog pathway is upregulated in adamantinomatous craniopharyngiomas.

OBJECTIVES: Pituitary stem cells play a role in the oncogenesis of human adamantinomatous craniopharyngiomas (aCPs). We hypothesized that crosstalk between the Wnt/ß-catenin and Sonic Hedgehog (SHH) pathways, both of which are important in normal pituitary development, would contribute to the pathogenesis of aCPs. DESIGN: To explore the mRNA and protein expression of components of the SHH signaling pathway in aCPs and their relationship with the identification of CTNNB1/ß-catenin mutations and patients outcomes. PATIENTS AND METHODS: In 18 aCP samples, CTNNB1 was sequenced, and the mRNA expression levels of SHH pathway members (SHH, PTCH1, SMO, GLI1, GLI2, GLI3, and SUFU) and SMO, GLI1, GLI3, SUFU, ß-catenin, and Ki67 proteins were evaluated by quantitative real-time PCR and immunohistochemistry respectively. Anterior normal pituitaries were used as controls. Associations between molecular findings and clinical data were analyzed. RESULTS: The aCPs presented higher mRNA expression of SHH (+400-fold change (FC); P<0.01), GLI1 (+102-FC; P<0.001), and GLI3 (+5.1-FC; P<0.01) than normal anterior pituitaries. Longer disease-free survival was associated with low SMO and SUFU mRNA expression (P<0.01 and P=0.02 respectively). CTNNB1/ß-catenin mutations were found in 47% of the samples. aCPs with identified mutations presented with higher mRNA expression of SMO and GLI1 (+4.3-FC; P=0.02 and +10.2-FC; P=0.03 respectively). SMO, GLI1, GLI3, and SUFU staining was found in 85, 67, 93, and 64% of the samples respectively. Strong GLI1 and GLI3 staining was detected in palisade cells, which also labeled Ki67, a marker of cell proliferation. CONCLUSIONS: The upregulation of SHH signaling occurs in aCPs. Thus, activation of Wnt/ß-catenin and SHH pathways, both of which are important in pituitary embryogenesis, appears to contribute to the pathogenesis of aCP.

Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma.

Glioblastoma (GBM) is one of the most aggressive central nervous system tumors with a patient's median survival of <1 year. Polo-like kinases (PLKs) are a family of serine/threonine kinases that have key roles in cell cycle control and DNA-damage response. We evaluated PLK1, 2, 3 and 4 gene expression in 8 GBM cell lines and 17 tumor samples, and analyzed the effect of the PLK1 inhibition on SF188 and T98G GBM cell lines and 13 primary cultures. Our data showed PLK1 overexpression and a variable altered expression of PLK2, 3 and 4 genes in GBM tumor samples and cell lines. Treatments with nanomolar concentrations of BI 2536, BI 6727, GW843682X or GSK461364 caused a significant decrease in GBM cells proliferation. Colony formation was also found to be inhibited (P<0.05), whereas apoptosis rate and mitotic index were significantly increased (P<0.05) after PLK1 inhibition in both GBM cell lines. Cell cycle analysis showed an arrest at G2 (P<0.05) and cell invasion was also decreased after PLK1 inhibition. Furthermore, simultaneous combinations of BI 2536 and temozolomide produced synergistic effects for both the cell lines after 48 h of treatment. Our findings suggest that PLK1 might be a promising target for the treatment of GBMs.

Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age.

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

Impacto de la cirugía de la epilepsia infantil en el rendimiento intelectual / Impact of pediatric epilepsy surgery on intellectual efficiency

Introducción. La cirugía de la epilepsia podría ser una opción terapéutica muy prometedora para el control de las crisis en pacientes con crisis refractarias que no responden a la medicación. Otro factor importante a favor de la opción quirúrgica son los resultados cognitivos. Objetivo. Investigar la correlación entre los resultados tanto de las crisis como cognitivos tras la cirugía para tratar la epilepsiaen una población pediátrica.Pacientes y métodos. Se evaluó de manera retrospectiva a un total de 59 pacientes pediátricos antes y al menos seis meses después de la cirugía mediante la tercera edición de la escala de inteligencia para niños de Wechsler (escala global, escala verbal y escala manipulativa). Se dividió a los pacientes en dos grupos en función de la presencia o ausencia de la mejoría del control de las crisis tras la cirugía. Los datos que se recogían de cada niño incluían: tipo de epilepsia, etiología, edad de comienzo de la epilepsia, duración de la epilepsia y frecuencia de las crisis.Resultados. Al comparar los datos mediante un análisis multivariado de la varianza se observaron diferencias significativas en las escalas global, verbal y manipulativa preoperatorias (p = 0,01) con unos resultados mejores en el grupo con reducción de las crisis que en el grupo sin reducción de las crisis. El grupo con mejoría de las crisis consiguió una mejoría significativa en la escala manipulativa (p = 0,01) y el grupo sin mejoría de las crisis obtuvo un empeoramiento significativoen la escala verbal (p = 0,01).Conclusiones. Nuestros resultados sugieren que el éxito de la cirugía para el tratamiento de la epilepsia en la infancia cuando se logra un control de las crisis podría conllevar también una mejoría en la escala manipulativa, mientras que lapersistencia de las crisis podría empeorar la escala verbal (AU)

Introduction. Epilepsy surgery may be a promising alternative therapy for seizure control in patients with refractory seizures, resistant to medication. Cognitive outcome is another important factor in favor of the surgical decision. Aim. To investigate the correlation between seizure outcome and cognitive outcome after epilepsy surgery in a pediatric population. Patients and methods. A total of 59 pediatric patients were retrospectively assessed with the WISC-III (Full Scale, Verbal Scale and Performance Scale) before and, at least, 6 months after surgery. Patients were divided into two groups according whether or not improvement of seizure control after surgery. Data collected for each child included: epileptic syndrome, etiology, age at epilepsy onset, duration of epilepsy and seizure frequency. Results. Comparison using a MANOVA test revealed significant differences across pre-operative Full Scale, Verbal Scale and Performance Scale (p = 0.01) with seizure reduction group performing better than no seizure reduction group. Seizureimprovement group achieved significant Performance Scale improvement (p = 0.01) and no seizure improvement groupshowed significant Verbal Scale worsened after surgery (p = 0.01).Conclusions. Our results suggest that the success of the epilepsy surgery in childhood when the seizure control is achieved may also provide an improvement in the Performance Scale whereas the seizure maintenance may worsen the Verbal Scale (AU)

When your child with epilepsy die suddenly: febrile seizures are part of the process? / Quando seu filho com epilepsia morre subitamente: crises febris fazem parte do processo?

Febrile seizures (FS) affect almost 2-5 percent of children and factors related to an increase susceptibility of children to FS may involve an imbalance of inflammatory cytokines and genetic factors. FS had low morbidity, but may be associated with the occurrence of late chronic epilepsy. Here we describe factors related to FS and its possible correlation with SUDEP.

Crises febris (CF) afetam aproximadamente 2-5 por cento das crianças e os fatores envolvidos com essa maior susceptibilidade das crianças às CF podem estar relacionados com uma ação inadequada de citocinas inflamatórias, além de fatores genéticos. As CF têm baixa morbidade, mas podem estar associadas à ocorrência de epilepsia crônica. Nós discutiremos os fatores relacionados com CF, considerando-se sua possível associação com SUDEP.

Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks.

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks / Consumo de peixe, contaminantes e morte súbita em epilepsia: mais benefícios do que riscos

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

Pessoas com epilepsia têm um risco aumentado de morrer de forma prematura e a causa mais comum de morte relacionada à epilepsia encontra-se na categoria de morte súbita inesperada em epilepsia (SUDEP). SUDEP é um problema significativo para pacientes com epilepsia crônica não controlada. O principal objetivo nas pesquisas em SUDEP é o desenvolvimento de métodos capazes de levar à sua prevenção e ações outras que não medicamentosas e cirúrgicas que podem ser úteis. Os aspectos nutricionais, como por exemplo, a deficiência do ácido graxo ômega-3 pode ter um papel interessante neste cenário. Alguns estudos animais e clínicos têm sugerido que os ácidos graxos ômega-3 podem ser úteis na prevenção e no tratamento da epilepsia e, consequentemente, na SUDEP. Os únicos alimentos que contêm grandes proporções de ômega-3 são os frutos do mar (peixes e mariscos). No entanto, alguns peixes podem estar contaminados com metilmercúrio, o que pode levar a um efeito contrário ao benefício trazido pelos ácidos graxos ômega-3. Aqui, resumimos o conhecimento do papel do consumo de peixe nas pesquisas em epilepsia.

Discordant nadir GH after oral glucose and IGF-I levels on treated acromegaly: refining the biochemical markers of mild disease activity.

Biochemical markers for remission on acromegaly activity are controversial. We studied a subset of treated acromegalic patients with discordant nadir GH levels after oral glucose tolerance test (oGTT) and IGF-I values to refine the current consensus on acromegaly remission. We also compared GH results by two GH immunoassays. From a cohort of 75 treated acromegalic patients, we studied 13 patients who presented an elevated IGF-I despite post-oGTT nadir GH of < or =1 microg/l. The 12-h daytime GH profile (GH-12 h), nadir GH after oGTT, and basal IGF-I levels were studied in patients and controls. Bland-Altman method showed high concordance between GH assays. Acromegalic patients showed higher mean GH-12 h values (0.71+/-0.36 vs. 0.31+/-0.28 microg/l; p<0.05) and nadir GH after oGTT (0.48+/-0.32 vs. 0.097+/-0.002 microg/l; p<0.05) as compared to controls. Nadir GH correlated with mean GH-12 h (r=0.92, p<0.05). The mean GH-12 h value from upper 95% CI of controls (0.54 microg/l) would correspond to a theoretical normal nadir GH of < or =0.27 microg/l. Patients with GH nadir < or =0.3 microg/l had IGF-I between 100-130% ULNR (percentage of upper limit of normal range) and mean GH-12 h of 0.35+/-0.15, and patients with GH nadir >0.3 and < or =1 microg/l had IGF-I >130% ULNR and mean GH-12 h of 0.93+/-0.24 microg/l. Our data integrate daytime GH secretion, nadir GH after oGTT, and plasma IGF-I concentrations showing a continuum of mild residual activity in a subgroup of treated acromegaly with nadir GH values < or =1 microg/l. The degree of increased IGF-I levels and nadir GH after oGTT are correlated with the subtle abnormalities of daytime GH secretion.

Effect of multiple cranial burr hole surgery on prevention of recurrent ischemic attacks in children with moyamoya disease.

Moyamoya disease (MMD) is an uncommon cerebrovascular disorder characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. Direct and indirect bypass techniques have been devised with the aim of promoting neoangiogenesis. The current study aimed to investigate the role of multiple cranial burr hole (MCBH) operations in the prevention of cerebral ischemic attacks in children with MMD. Seven children suffering from progressive MMD were submitted to the MCBH and arachnoid opening technique. Ten to 20 burr holes were drilled in the fronto-temporo-parieto-occipital area of each hemisphere in each patient, depending on the site and extent of the disease. All patients were evaluated pre- and postoperatively by means of Barthel index (BI), CT, MR, angio-MR, and angiography. Patients had no recurrence of ischemic attacks postoperatively. Neoangiogenesis was observed in both hemispheres. One patient developed a persistent subdural collection after surgery, thus requiring placement of a subdural-peritoneal shunt. Postoperative BI was statistically significantly improved (P=0.02). This report suggests that MCBH for revascularization in MMD is a simple procedure with a relatively low risk of complications and effective for preventing cerebral ischemic attacks in children. In addition, MCBH may be placed as an adjunct to other treatments for MMD.

Differential expression of E-cadherin gene in human neuroepithelial tumors.

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Pregnancy outcome in ethanol-treated mice with folic acid supplementation in saccharose.

INTRODUCTION: Maternal folic acid deficiency is the most important metabolic factor in the etiology of neural tube defects (NTD) and is reduced by ethanol, which is extensively consumed by young women. OBJECTIVE: The objective of the study was to determine whether folic acid supplementation in dietary saccharose is efficient in the prevention NTD induced by ethanol in fetuses of Swiss mice. MATERIALS AND METHODS: Pregnant mice were divided into four groups of six animals each: control (C), ethanol (E), deficient-supplemented (DS), and deficient-supplemented + ethanol (DSE). Groups C and E received commercial mouse chow (containing 3 mg/kg folic acid) throughout the experiment, while groups DS and DSE received a folic acid-free diet with the addition of saccharose supplemented with folic acid (2 mg/kg folic acid) in water. Group E and DSE animals received ethanol (4 g/kg) administered intraperitoneally from the seventh to the ninth gestational day (gd) and were euthanized on the 18th gd, while groups C and DS received saline. RESULTS: Congenital anomalies were observed in groups E and DSE. The fetal weight and length of the animals in group E were lower than in groups C and DS and, in group DSE, were lower than in groups C and DS. The placental diameter of group E was smaller than that of group C, and the placental weight of group C animals was lower than that of groups E, DSE, and DS. CONCLUSION: The study demonstrated that dietary supplementation with folate in saccharose is an accessible means of consumption that could be further diffused but in an increased dose than recommended to reduce the teratogenic effects of ethanol.

Differential expression of E-cadherin gene in human neuroepithelial tumors

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Drug-resistance in central nervous system tumors: from the traditional cell-resistance model to the genetically driven approaches on therapy.

The advances in the cure rates observed in the oncology field in the past decades were not fully assembled by primary brain tumors. In this heterogeneous group of diseases, resistance to either chemotherapy or radiotherapy still is a major problem to be addressed. Several genetic and epigenetic events may directly influence the response to treatment in these tumors. Throughout recent discoveries, drug resistance in brain tumors was better understood as a final product of different and complexes pathways that interact and modulate cell performance to treatment. The last years experienced a new paradigm in the way brain tumor drug-resistance genes are elected out of the vast human genomic universe. In the former era, models of cell resistance that were documented on solid tumors other than brain were investigated at the central nervous system's counterpart. Nowadays, genomic-based hypothesis generation, supported by modern genetic technique tolls, seem effective in revealing new candidate-genes that might confer the resistance phenotype. Nevertheless, new treatment approaches and novel drugs based on the pharmacogenomic resistance profile, particularly for brain tumors, are just starting to become a reality for clinical purposes.

Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79 percent). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25 percent (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6 percent), which declined to 11 of 31 (35.5 percent) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.

Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy.

We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.