Malignant Glioma Therapy by Vaccination with Irradiated C6 Cell-Derived Microvesicles Promotes an Antitumoral Immune Response.

Glioblastoma is the most common and malignant tumor of the CNS, with a mean survival of 14 months after diagnosis. Its unfavorable prognosis reveals the need for novel therapies. It is known that radiation can induce a systemic antitumor effect. Tumor cells produce and release microvesicles in response to cell damage such as radiation. Microvesicles contain a plethora of bioactive molecules, including antigens involved in modulation of the immune response. In this study, we characterized and evaluated irradiated C6 cell-derived microvesicles as a therapeutic vaccination in C6 malignant glioma. Cultured C6 glioma cells were irradiated with a single dose of 50 Gy to obtain the microvesicles. Subcutaneous implantation of C6 cells was performed when the tumor reached 2 cm in diameter, and non-irradiated and irradiated C6 cell-derived microvesicles were administered subcutaneously. Tumor growth, apoptosis, and immunophenotypes were determined. Reduction of tumor volume (more than 50%) was observed in the group treated with irradiated C6 cell-derived microvesicles compared with the control (p = 0.03). The percentages of infiltrative helper, cytotoxic, and regulatory T lymphocytes as well as apoptotic cells were increased in tumors from immunized rats compared with controls. These findings make microvesicle-based vaccination a promising immunotherapeutic approach against glioblastoma.

The shift in GH3 cell shape and cell motility is dependent on MLCK and ROCK.

Cytoskeletal organization, actin-myosin contractility and the cell membrane together regulate cell morphology in response to the cell environment, wherein the extracellular matrix (ECM) is an indispensable component. Plasticity in cell shape enables cells to adapt their migration mode to their surroundings. GH3 endocrine cells respond to different ECM proteins, acquiring different morphologies: a rounded on collagen I-III (C I-III) and an elongated on collagen IV (C IV). However, the identities of the molecules that participate in these responses remain unknown. Considering that actin-myosin contractility is crucial to maintaining cell shape, we analyzed the participation of MLCK and ROCK in the acquisition of cell shape, the generation of cellular tension and the cell motility mode. We found that a rounded shape with high cortical tension depends on MLCK and ROCK, whereas in cells with an elongated shape, MLCK is the primary protein responsible for cell spreading. Further, in cells with a slow and directionally persistent motility, MLCK predominates, while rapid and erratic movement is ROCK-dependent. This behavior also correlates with GTPase activation. Cells on C I-III exhibited higher Rho-GTPase activity than cells on C IV and vice versa with Rac-GTPase activity, showing a plastic response of GH3 cells to their environment, leading to the generation of different cytoskeleton and membrane organizations and resulting in two movement strategies, rounded and fibroblastoid-like.

Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

Retinoic acid reduces solvent-induced neuropathy and promotes neural regeneration in mice.

In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid.

[Clinical practice guideline for the diagnosis and treatment of hyperprolactinemia]. / Guía de práctica clínica para el diagnóstico y tratamiento de la hiperprolactinemia.

BACKGROUND: Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment. OBJECTIVE: Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia. METHOD: It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia. RESULTS: During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here. CONCLUSIONS: It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.

Immunohistochemical Expression of Ki-67, Dopamine D1 and Dopamine D2 Receptors in Meningiomas in a Tertiary Institution in Mexico.

Objectives Meningiomas (MNGs) are the most common intracranial tumors found in the adult population. While most intracranial MNGs may be surgically removed, a subset of patients remains ineligible for conventional treatment. This is either because of a lack of surgical access or due to atypical, anaplastic or invasive characteristics of the tumors. These patients may benefit from targeted therapies that focus on cell receptor expression. The aim of this study was to assess dopamine receptor (DR) and Ki-67 expression in the MGNs of patients treated with surgery in the Instituto Nacional de Neurología y Neurocirugía, Mexico. Materials and methods This study analyzed 23 patients with confirmed MNG diagnoses (10 female and 13 male (mean age: 44.5 years)) who had undergone surgical resection between 2010 and 2014 at our institution. In the collected samples, we performed analyses for Ki-67, Dopamine 1 and Dopamine 2 receptors' expression. Results For the markers Ki-67, DR-D1 and DR-D2, the mean percentual expressions were 18.9%, 23.02% and 8.33%. No significant correlation was found between the expressions of these receptors and the studied MNG characteristics. The expression index of Ki-67 showed a significant relation with mean age (p = 0.03) and prolactin levels (p = 0.02). Conclusions Samples showed varied expressions of the studied receptors. Despite the difference in expressions between the markers, more studies are needed to confirm the findings. In contrast to previous studies, we could not find any relationship between D2-R and tumor characteristics.

Pituitary Teratoma: A Case Series of Three Cases.

Mature cystic teratoma (MCT) is a benign germ cell tumor, histologically comprising components derived from mesoderm, ectoderm, and endoderm layer tissue. MCT usually has foci of intestinal components and colonic epithelia. Pituitary teratomas containing complete colon features are very rare. Here, we present three cases of sellar teratoma in two men aged 50 and 65 years and a woman aged 30 years. All patients presented with asthenia, adynamia, and loss of strength. A pituitary mass was incidentally observed on magnetic resonance imaging. Histological features showed a mature teratoma formed by gut and colonic epithelium, extended lymphoid tissue with the formation of Peyer's patches, and muscular layer vestiges with a fibrous capsule. The immunohistochemical panel showed reactivity to cytokeratin (CK)7, CKAE6/AE7, carcinoembryonic antigen, octamer-binding transcription factor 4, cluster of differentiation (CD)20, CD3, vimentin, muscle actin, and pituitary tumor-transforming gene 1 in isolated cells. However, alpha-fetoprotein, beta-human chorionic gonadotropin, human placental lactogen, CK20, tumor suppressor protein 53, and Kirsten rat sarcoma were negative. This article describes the clinical and histological features of rare sellar masses as well as survival after therapy.

Macro Pituitary Adenoma and Frontal Calcified Cavernous Malformation: A Coincidence or a True Partnership?

Collision tumors are rare neoplasms composed of two different types of histological tissues in the same organ. The most frequent association with cerebral cavernous malformations (CCMs) are meningiomas, gliomas, and gangliogliomas, while the most frequent sellar collision is between pituitary adenoma (PA) and craniopharyngiomas, and still very few cases have been reported. We present the case of a 43-year-old woman who started two months ago with a fall from her height followed by severe headache and bilateral hemianopsia. An isointense, enhancing sellar tumor, and a right frontal lesion compatible with CCM were observed on MRI. Surgery was performed through anterior interhemispheric and endoscopic transnasal approaches for the cavernoma and the sellar tumor, respectively, removing both lesions and sending them to pathology. The sellar tumor corresponded to a PA showing positive immunohistochemistry for prolactin and follicle-stimulating hormone (FSH). In the post-op period, the patient developed a seizure and diabetes insipidus, for which she received appropriate treatment. Our findings were conclusive with a collision tumor, since both lesions presented two different histological tissues. Different densities were observed in both lesions using imaging studies, which were later confirmed with histopathology and immunohistochemistry.

Lactate-Loaded Nanoparticles Induce Glioma Cytotoxicity and Increase the Survival of Rats Bearing Malignant Glioma Brain Tumor.

A glioblastoma is an aggressive form of a malignant glial-derived tumor with a poor prognosis despite multimodal therapy approaches. Lactate has a preponderant role in the tumor microenvironment, playing an immunoregulatory role as well as being a carbon source for tumor growth. Lactate homeostasis depends on the proper functioning of intracellular lactate regulation systems, such as transporters and enzymes involved in its synthesis and degradation, with evidence that an intracellular lactate overload generates metabolic stress on tumor cells and tumor cell death. We propose that the delivery of a lactate overload carried in nanoparticles, allowing the intracellular release of lactate, would compromise the survival of tumor cells. We synthesized and characterized silica and titania nanoparticles loaded with lactate to evaluate the cellular uptake, metabolic activity, pH modification, and cytotoxicity on C6 cells under normoxia and chemical hypoxia, and, finally, determined the survival of an orthotopic malignant glioma model after in situ administration. A dose-dependent reduction in metabolic activity of treated cells under normoxia was found, but not under hypoxia, independent of glucose concentration. Lactated-loaded silica nanoparticles were highly cytotoxic (58.1% of dead cells) and generated significant supernatant acidification. In vivo, lactate-loaded silica nanoparticles significantly increased the median survival time of malignant glioma-bearing rats (p = 0.005) when administered in situ. These findings indicate that lactate-loaded silica nanoparticles are cytotoxic on glioma cells in vitro and in vivo.

Teratoma With Malignant Ectomesenchymoma in the Pineal Region: A Case Report.

Tumors involving the pineal gland include germinomas, non-germinomatous, and parenchymal tumors. Sometimes these tumors can be differentiated into rhabdomyosarcoma, which is an aggressive and rapidly recurring sarcoma but is a rare event. We present the case of a 23-year-old male, with an eight-year-long history of a non-treated brain tumor compatible with a teratoma. Chemotherapy and radiotherapy were offered, and two years later, malignant transformation to astrocytoma, rhabdomyosarcoma, neural cell carcinoma, ganglioglioma, and low-grade chondrosarcoma was noted. Immunohistochemistry was valuable in differentiating these entities that confirmed the diagnosis. Malignant transformations may be secondary to the normal transformation of multipotent embryonic cells into more developed tissues after radiotherapy of teratoma and malignant ectomesenchymoma transformation.

Aged garlic extract attenuates cerebral damage and cyclooxygenase-2 induction after ischemia and reperfusion in rats.

Different garlic products reduce the cerebral ischemic damage due to their antioxidant properties. In this work, we investigated the effect of aged garlic extract (AGE) on cyclooxygenase-2 (COX-2) protein levels and activity, and its role as a possible mechanism of neuroprotection in a cerebral ischemia model. Animals were subjected to 1 h of ischemia plus 24 h of reperfusion. AGE (1.2 ml/kg weight, i.p.) was administered at onset of reperfusion. To evaluate the damage induced by cerebral ischemia, the neurological deficit, the infarct area, and the histological alterations were measured. As an oxidative stress marker to deoxyribonucleic acid, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined. Finally, as inflammatory markers, TNFα levels and COX-2 protein levels and activity were measured. AGE treatment diminished the neurological alterations (61.6%), the infarct area (54.8%) and the histological damage (37.7%) induced by cerebral ischemia. AGE administration attenuated the increase in 8-OHdG levels (77.8%), in TNFα levels (76.6%), and in COX-2 protein levels (73.6%) and activity (30.7%) induced after 1 h of ischemia plus 24 h of reperfusion. These data suggest that the neuroprotective effect of AGE is associated not only to its antioxidant properties, but also with its capacity to diminish the increase in TNFα levels and COX-2 protein expression and activity. AGE may have the potential to attenuate the cerebral ischemia-induced inflammation.

Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas.

Pituitary adenomas (PAs) can be unpredictable and aggressive tumors. No reliable markers of their biological behavior have been found. Here, a proteomic analysis was applied to identify proteins in the expression profile between invasive and non-invasive PAs to search for possible biomarkers. A histopathological and immunohistochemical (adenohypophyseal hormones, Ki-67, p53, CD34, VEGF, Flk1 antibodies) analysis was done; a proteomic map was evaluated in 64 out of 128 tumors. There were 107 (84%) invasive and 21 (16%) non-invasive PAs; 80.5% belonged to III and IV grades of the Hardy-Vezina classification. Invasive PAs (n = 56) showed 105 ± 43 spots; 86 ± 32 spots in non-invasive PAs (n = 8) were observed. The 13 most prominent spots were selected and 11 proteins related to neoplastic process in different types of tumors were identified. Hint1 (Histidine triad nucleotide-binding protein 1) high expression in invasive PA was found (11.8 ± 1.4, p = 0.005), especially at high index (>10; p = 0.0002). High Hint1 expression was found in invasive VEGF positive PA (13.8 ± 2.3, p = 0.005) and in Flk1 positive PA (14.04 ± 2.28, p = 0.006). Hint1 is related to human tumorigenesis by its interaction with signaling pathways and transcription factors. It could be related to invasive behavior in PAs. This is the first report on Hint expression in PAs. More analysis is needed to find out the possible role of Hint in these tumors.

Neuroprotective effect of DAHK peptide in an occlusive model of permanent focal ischemia in rats.

This study examined the neuroprotective ability of tetrapeptide L-Asp-Ala-His-Lys (DAHK) in permanent middle cerebral artery occlusion in rats. One DAHK dose (16 mg/kg) or saline solution were i.v. administered 30 min after occlusion and neurological deficit was evaluated at 2, 24, 48, 72 and 96 h using Longa scoring scale. The striatum infarction area was evaluated until 96 h after occlusion in both groups after staining with hematoxylin-eosin. DAHK-treated group showed a significant (P < 0.05) protection of 70% of neurological deficit at 96 h after occlusion, in comparison with the control-group that showed permanent neurological deficit. The DAHK-treated group showed a significant (P < 0.05) reduction of 52% infarction area in the striatum, as compared to control values. Results presented here support the possible therapeutic application of DAHK as a neuroprotective agent in human patients with stroke, as the peptide is part of human serum albumin, already being tested in clinical trials.

Epithelial cell adhesion molecule expression in pituitary adenomas: an immunohistochemical study.

An important amount of data correlating the expression of epithelial cell adhesion molecule (Ep-CAM) with cellular proliferation and de-differentiation could directly contribute to carcinogenesis. The aim of this study is to evaluate prognosis relevance of Ep-CAM expression in a group of pituitary adenomas. Epithelial cell adhesion molecule, proliferating cell nuclear antigen, and microvascular density labeling indices in pituitary adenomas were determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. We evaluated 45 adenomas. Sixty-two percent were nonsecretor adenomas and 37.8% were secretor tumors. Immunohistochemistry was scored for immunoexpression of Ep-CAM (cytoplasmic, membrane, and mixed pattern). Proliferating cell nuclear antigen and vascular density (CD34) labeling indices were assessed. Statistical significance was observed between Ep-CAM cytoplasmic immunoreactions (P = .000) and higher proliferating cell nuclear antigen (P = .001) in secretor adenomas compared with nonsecretor tumors. Vascular density labeling indices did not show statistical significance. Therefore, Ep-CAM could be evaluated to distinguish secretor and nonsecretor pituitary adenomas. These suggest that the markers could predict the growth potential of individual pituitary adenomas.

Resveratrol reduces cerebral edema through inhibition of de novo SUR1 expression induced after focal ischemia.

Cerebral edema is a clinical problem that frequently follows ischemic infarcts. Sulfonylurea receptor 1 (SUR1) is an inducible protein that can form a heteromultimeric complex with aquaporin 4 (AQP4) that mediate the ion/water transport involved in brain tissue swelling. Transcription of the Abcc8 gene coding for SUR1 depends on the activity of transcriptional factor SP1, which is modulated by the cellular redox environment. Since oxidative stress is implicated in the induced neuronal damage in ischemia and edema formation, the present study aimed to evaluate if the antioxidant resveratrol (RSV) prevents the damage by reducing the de novo expression of SUR1 in the ischemic brain. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion followed by different times of reperfusion. RSV (1.9 mg/kg; i.v.) was administered at the onset of reperfusion. Brain damage and edema formation were recognized by neurological evaluation, time of survival, TTC (2,3,5-Triphenyltetrazolium chloride) staining, Evans blue extravasation, and water content. RSV mechanism of action was studied by SP1 binding activity measured through the Electrophoretic Mobility Shift Assay, and Abcc8 and Aqp4 gene expression evaluated by qPCR, immunofluorescence, and Western blot. We found that RSV reduced the infarct area and cerebral edema, prevented blood-brain barrier damage, improved neurological performance, and increased survival. Additionally, our findings suggest that the antioxidant activity of RSV targeted SP transcription factors and inhibited SUR1 and AQP4 expression. Thus, RSV by decreasing SUR1 expression could contribute to reducing edema formation, constituting a therapeutic alternative for edema reduction in stroke.

Resveratrol Activates Neuronal Autophagy Through AMPK in the Ischemic Brain.

During cerebral ischemia, oxygen and glucose levels decrease, producing many consequences such as the generation of reactive oxygen species, tissue injury, and the general metabolism collapse. Resveratrol triggers signaling dependent on the protein kinase activated by adenosine monophosphate (AMPK), the sensor of cellular energy metabolism that regulates autophagy, eliminates damaged mitochondria, and increases energy sources. In the present study, we investigated the participation of AMPK activation in the protective effect of resveratrol on cerebral ischemia and excitotoxicity. We found that resveratrol increased the levels of phosphorylated AMPK in the cerebral cortex of rats subjected to middle cerebral artery occlusion (MCAO) and in primary cultured neurons exposed to glutamate-induced excitotoxicity. Resveratrol (1.8 mg/Kg; i. v.; administered at the beginning of reperfusion) decreased the infarct area and increased survival of rats subjected to MCAO. In neuronal cultures, resveratrol treatment (40 µM, after excitotoxicity) reduced the production of superoxide anion, prevented the overload of intracellular Ca+2 associated to mitochondrial failure, reduced the release of the lactate dehydrogenase enzyme, and reduced death. It also promoted mitophagy (increased Beclin 1 level, favored the recruitment of LC3-II, reduced LAMP1, and reduced mitochondrial matrix protein HSP60 levels). In both models, inhibition of AMPK activation with Compound C obstructed the effect of resveratrol, showing that its protective effect depends, partially, on the activation of the AMPK/autophagy pathway.

Resveratrol Prevents GLUT3 Up-Regulation Induced by Middle Cerebral Artery Occlusion.

Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to oxidative stress and inflammation modulate GLUT3 expression, the purpose of this work was to assess the effect of resveratrol on GLUT3 expression levels after ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by different times of reperfusion. Resveratrol (1.9 mg/kg; i. p.) was administered at the onset of the restoration of the blood flow. Quantitative-PCR and Western blot showed that MCAO provoked a substantial increase in GLUT3 expression in the ipsilateral side to the lesion of the cerebral cortex. Immunofluorescence assays indicated that GLUT3 levels were upregulated in astrocytes. Additionally, an important increase in GLUT3 occurred in other cellular types (e.g., damaged neurons, microglia, or infiltrated macrophages). Immunodetection of the microtubule-associated protein 2 (MAP2) showed that MCAO induced severe damage to the neuronal population. However, the administration of resveratrol at the time of reperfusion resulted in injury reduction. Resveratrol also prevented the MCAO-induced increase of GLUT3 expression. In conclusion, resveratrol protects neurons from damage induced by ischemia and prevents GLUT3 upregulation in the damaged brain that might depend on AMPK activation.

Antioxidant Properties and Protective Effects of Some Species of the Annonaceae, Lamiaceae, and Geraniaceae Families against Neuronal Damage Induced by Excitotoxicity and Cerebral Ischemia.

This study aimed to compare the antioxidant activities of extracts obtained from three plant families and evaluate their therapeutic effect on strokes. Ethanol extracts were obtained from either the leaf or the aerial parts of plants of the families Annonaceae (Annona cherimola, A. diversifolia, A. muricata, A. purpurea, and A. reticulata), Lamiaceae (Salvia amaríssima and S. polystachya), and Geraniaceae (Geranium niveum and G. mexicanum). Extracts were analyzed in terms of hydroxyl radical (OH•), peroxyl radical (ROO•), and superoxide anion (O2•-). The efficiency of the extracts to prevent neuronal death induced by excitotoxicity was tested with the tetrazolium assay, the O2•- scavenging capacity was evaluated with the dihydroethidium dye, and the protective effect of the extracts with the highest antioxidant activity was tested on a stroke experimental model. The extracts' IC50 values (µg/mL) of scavenging varied from 98.9 to 155.04, 4.5 to 102.4, and 20.2 to 118.97 for OH•, ROO•, and O2•-, respectively. In the excitotoxicity model, Annonaceae extracts were highly cytotoxic while Lamiaceae and Geraniaceae reduced intracellular O2•- production and protect neurons against oxidative stress. Salvia polystachya reduced cerebral damage, as well as improved survival and behavior after ischemia. Our results encouraged the use of plant extracts as natural antioxidants to minimize neuronal injury following stroke.

Expression of epithelial cell adhesion molecule and pituitary tumor transforming gene in adamantinomatous craniopharyngioma and its correlation with recurrence of the tumor.

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine disorders and often locally aggressive. The reliable criteria for predicting the tumor behavior are still lacking. It has been suggested that proliferative potential of the tumor cells is necessary for recurrence. The aim of this study was to evaluate the activity and correlation of epithelial cell adhesion molecule (Ep-CAM) and pituitary tumor transforming gene (PTTG-1) immunoexpression that is possibly related to relapse in 40 patients with adamantinomatous craniopharyngioma. The study involved clinical and pathologic analysis. Of the subjects, 49% were females and 51% were males. The mean age of the patients was 37 years. Relapsing rate at 5 years was 46% and for death was 22.5%. Histologically, whorl-like arrays and dense or hypercellular stellate reticulum cells were correlated with recurrence. Epithelial CAM and PTTG-1 were also higher in stellate reticulum cells and in whorl-like arrays. Both were higher in recurrence/regrowth tumors than in primary one. The PTGG-1 expression in craniopharyngioma may suggest hypophyseal metaplasia. The Ep-CAM and PTTG-1 expression in craniopharyngioma could be used as prediction markers of relapsing tumor. It has been suggested that proliferative potential of the tumor cells is necessary for recurrence.

Diallyl Trisulfide Protects Rat Brain Tissue against the Damage Induced by Ischemia-Reperfusion through the Nrf2 Pathway.

Stroke is a public health problem due to its high mortality and disability rates; despite these, the pharmacological treatments are limited. Oxidative stress plays an important role in cerebral damage in stroke and the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) confers protection against oxidative stress. Different compounds, such as diallyl trisulfide (DATS), have the ability to activate Nrf2. DATS protects against the damage induced in oxygen-glucose deprivation in neuronal cells; however, in in vivo models of cerebral ischemia, DATS has not been evaluated. Male Wistar rats were subjected to 1 h of ischemia and seven days of reperfusion and the protective effect of DATS was evaluated. DATS administration (IR + DATS) decreased the infarct area and brain damage in the striatum and cortex; improved neurological function; decreased malondialdehyde and metalloproteinase-9 levels; increased Nrf2 activation in the cortex and the expression of superoxide dismutase 1 (SOD1) in the nucleus, SOD2 and glutathione S-transferase (GST) in the striatum and cortex; and increased the activity of catalase (CAT) in the striatum and glutathione peroxidase (GPx) in the cortex. Our results demonstrate the protective effect of DATS in an in vivo model of cerebral ischemia that involves Nrf2 activation.