Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2005/56447-7, 2009/53447-7, 2008/52657-5]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Níveis diferentes de MT-I/II entre pacientes com MTLE com ou sem crise generalizada: os níveis hipocampais de MT-I/II afetam o alastramento das crises, ou o alastramento das crises promove expressão diferencial de MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns

Toxoplasmose do sistema nervoso central em paciente sem evidência de imunossupressão: relato de caso

O quadro clínico da toxoplasmose adquirida em pacientes imunocompetentes habitualmente não inclui manifestações neurológicas focais, o que é freqüente em pacientes imunodeprimidos, como aqueles com síndrome da imunodeficiência adquirida. Este trabalho tem como objetivo relatar o caso de uma paciente adulta que apresentou abscessos cerebrais por Toxoplasma gondii, sem evidência de qualquer fator causador de imunossupressão

Cytogenetic findings in pediatric radiation-induced atypical meningioma after treatment of medulloblastoma: case report and review of the literature

Ionizing radiation is the most recognized risk factor for meningioma in pediatric long-term cancer survivors. Information in this rare setting is exceptional. We report the clinical and cytogenetic findings in a radiation-induced atypical meningioma following treatment for desmoplastic medulloblastoma in a child. This is the second study to describe the cytogenetic aspects on radiation-induced meningiomas in children. Chromosome banding analysis revealed a 46, XX, t(1;3)(p22;q12), del(1)(p?)[8]/46, XX[12]. Loss of chromosome 1p as a consequence of irradiation has been proposed to be more important in the development of secondary meningiomas in adults. Deletions in the short arm of chromosome 1 also appear to be a shared feature in both pediatric cases so far analyzed.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2010/15,717-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Correction: Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy.

[This corrects the article DOI: 10.1371/journal.pone.0044709.]

Components of the Canonical and Non-Canonical Wnt Pathways Are Not Mis-Expressed in Pituitary Tumors

<div><p>Introduction</p><p>Canonical and non-canonical Wnt pathways are involved in the genesis of multiple tumors; however, their role in pituitary tumorigenesis is mostly unknown.</p> <p>Objective</p><p>This study evaluated gene and protein expression of Wnt pathways in pituitary tumors and whether these expression correlate to clinical outcome.</p> <p>Materials and Methods</p><p>Genes of the Wnt canonical pathway: activating ligands (<i>WNT11, WNT4, WNT5A</i>), binding inhibitors (<i>DKK3, sFRP1</i>), β-catenin (<i>CTNNB1</i>), β-catenin degradation complex (<i>APC, AXIN1, GSK3β</i>), inhibitor of β-catenin degradation complex (<i>AKT1</i>), sequester of β-catenin (<i>CDH1</i>), pathway effectors (<i>TCF7, MAPK8, NFAT5</i>), pathway mediators (<i>DVL-1, DVL-2, DVL-3, PRICKLE, VANGL1</i>), target genes (<i>MYB, MYC, WISP2, SPRY1, TP53, CCND1</i>); calcium dependent pathway (<i>PLCB1, CAMK2A, PRKCA, CHP</i>); and planar cell polarity pathway (<i>PTK7, DAAM1, RHOA</i>) were evaluated by QPCR, in 19 GH-, 18 ACTH-secreting, 21 non-secreting (NS) pituitary tumors, and 5 normal pituitaries. Also, the main effectors of canonical (β-catenin), planar cell polarity (JNK), and calcium dependent (NFAT5) Wnt pathways were evaluated by immunohistochemistry.</p> <p>Results</p><p>There are no differences in gene expression of canonical and non-canonical Wnt pathways between all studied subtypes of pituitary tumors and normal pituitaries, except for <i>WISP2,</i> which was over-expressed in ACTH-secreting tumors compared to normal pituitaries (4.8x; p = 0.02), NS pituitary tumors (7.7x; p = 0.004) and GH-secreting tumors (5.0x; p = 0.05). β-catenin, NFAT5 and JNK proteins showed no expression in normal pituitaries and in any of the pituitary tumor subtypes. Furthermore, no association of the studied gene or protein expression was observed with tumor size, recurrence, and progressive disease. The hierarchical clustering showed a regular pattern of genes of the canonical and non-canonical Wnt pathways randomly distributed throughout the dendrogram.</p> <p>Conclusions</p><p>Our data reinforce previous reports suggesting no activation of canonical Wnt pathway in pituitary tumorigenesis. Moreover, we describe, for the first time, evidence that non-canonical Wnt pathways are also not mis-expressed in the pituitary tumors.</p> </div

Immunocytochemistry for β-catenin, JNK, and NFAT5 in normal pituitaries, ACTH-secreting pituitary tumor, GH-secreting pituitary tumor, and non-secreting pituitary tumor (x40).

<p>ACTH and GH immune positivity are shown in the region of the tumor sample immunostained for β-catenin, JNK and NFAT. Craniopharyngioma tissue and two positive samples from GH-secreting pituitary tumors were used as positive controls for β-catenin, NFAT5, and JNK antibodies, respectively.</p

Wnt Pathway gene expression in Pituitary Tumors.

<p>Wnt Pathway gene expression in Pituitary Tumors.</p

Hierarchical clustering for canonical and non-canonical Wnt pathway genes in normal pituitary and in different subtypes of the pituitary tumors.

<p>HN: normal pituitary; ACTH: ACTH-secreting pituitary tumor; GH: GH-secreting pituitary tumor; NS: non-secreting pituitary tumor.</p