Acute administration of methionine and/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex

Metabolic Brain Disease - High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia...     

Surgical anatomy of the maxillary nerve in the zygomatic region

Anatomic knowledge on the zygomatic fossa is of primary importance to improve the regional anesthetic technique of the maxillary nerve. Few reports in the literature have addressed the trajectory of the maxillary nerve and its branches in this region; thus, this study aimed at presenting information about the trajectory of these nerves. Thirty human half-heads of both genders were fixed in 10% formalin and demineralized in 5% nitric acid, and the maxillary nerve was dissected since its origin on the pterygopalatine fossa until penetration into the inferior orbital fissure. It was observed that the maxillary nerve sends one to three posterior superior alveolar branches and tuberal descendent branches, which supply the soft tissue structures of the region. The posterior superior alveolar nerves are inferiorly oriented near the maxillary tuberosity, where they penetrate the alveolar canals with the posterior superior alveolar artery and send small nerve branches that continue in an extraosseous trajectory. This study found that nearly 2/3 of the trajectory of the maxillary nerve is located in the zygomatic region, with a short segment (1/3) in the pterygopalatine fossa.     

Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model

Multimodal combinations of target agents with radiation and chemotherapy may enhance cancer treatment efficacy; however, despite these treatments, gliomas recur early due to their highly proliferative, infiltrative and invasive behaviors. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intensive interest in recent years since they may provide a sustained, controlled and targeted delivery. In the present study, we investigated the effect of indomethacin-loaded nanocapsules in an experimental glioma model. The rats treated with indomethacin-loaded nanocapsules demonstrated a significant reduction in tumor size and half of these animals presented just cells with characteristics of a residual tumor, as shown by immunostaining for nestin. Pathological analyses showed that the treated gliomas presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. An important finding of the present study is that indomethacin carried by polymeric nanocapsules achieved higher intracerebral drug concentrations than those of indomethacin in solution. Furthermore, indomethacin achieved a greater concentration in the hemisphere where the glioma was implanted, compared with the contralateral healthy hemisphere. Indomethacin-loaded nanocapsule treatment did not cause characteristics of toxicity and increased the survival of animals. Thus, our results show that polymeric nanocapsules are able to increase the intratumoral bioavailability of indomethacin and reduce the growth of implanted gliomas. Data suggest that indomethacin-loaded nanocapsules could offer new and potentially highly effective strategies for the treatment of malignant gliomas.     

Neuroinflammatory responses following zinc or branched-chain amino acids supplementation in obese rats

Metabolic Brain Disease - The excessive production of pro-inflammatory mediators, characteristic of obesity, leads to neuroinflammation. Zinc (Zn) and the branched-chain amino acids (BCAA) are...     

NFκB inhibitors induce cell death in glioblastomas

Identification of novel target pathways in glioblastoma (GBM) remains critical due to poor prognosis, inefficient therapies and recurrence associated with these tumors. In this work, we evaluated the role of nuclear-factor-kappa-B (NFκB) in the growth of GBM cells, and the potential of NFκB inhibitors as antiglioma agents. NFκB pathway was found overstimulated in GBM cell lines and in tumor specimens compared to normal astrocytes and healthy brain tissues, respectively. Treatment of a panel of established GBM cell lines (U138MG, U87, U373 and C6) with pharmacological NFκB inhibitors (BAY117082, parthenolide, MG132, curcumin and arsenic trioxide) and NFκB-p65 siRNA markedly decreased the viability of GBMs as compared to inhibitors of other signaling pathways such as MAPKs (ERK, JNK and p38), PKC, EGFR and PI3K/Akt. In addition, NFκB inhibitors presented a low toxicity to normal astrocytes, indicating selectivity to cancerous cells. In GBMs, mitochondrial dysfunction (membrane depolarization, bcl-xL downregulation and cytochrome c release) and arrest in the G2/M phase were observed at the early steps of NFκB inhibitors treatment. These events preceded sub-G1 detection, apoptotic body formation and caspase-3 activation. Also, NFκB was found overstimulated in cisplatin-resistant C6 cells, and treatment of GBMs with NFκB inhibitors overcame cisplatin resistance besides potentiating the effects of the chemotherapeutics, cisplatin and doxorubicin. These findings support NFκB as a potential target to cell death induction in GBMs, and that the NFκB inhibitors may be considered for in vivo testing on animal models and possibly on GBM therapy.     

Selective NTPDase2 expression modulates in vivo rat glioma growth

The ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are a family of ectoenzymes that hydrolyze extracellular nucleotides, thereby modulating purinergic signaling. Gliomas have low expression of all E-NTPDases, particularly NTPDase2, when compared to astrocytes in culture. Nucleotides induce glioma proliferation and ATP, although potentially neurotoxic, does not evoke cytotoxic action on the majority of glioma cultures. We have previously shown that the co-injection of apyrase with gliomas decreases glioma progression. Here, we tested whether selective re-establishment of NTPDase2 expression would affect glioma growth. NTPDase2 overexpression in C6 glioma cells had no effect on in vitro proliferation but dramatically increased tumor growth and malignant characteristics in vivo . Additionally, a sizable platelet sequestration in the tumor area and an increase in CD31 or platelet/endothelial cell adhesion molecule-1 (PECAM-1), vascular endothelial growth factor and OX-42 immunostaining were observed in C6-Enhanced Yellow Fluorescent Protein (EYFP)/NTPDase2-derived gliomas when compared to controls. Treatment with clopidogrel, a P2Y₁₂ antagonist with anti-platelet properties, decreased these parameters to control levels. These data suggest that the ADP derived from NTPDase2 activity stimulates platelet migration to the tumor area and that NTPDase2, by regulating angiogenesis and inflammation, seems to play an important role in tumor progression. In conclusion, our results point to the involvement of purinergic signaling in glioma progression. ( Cancer Sci 2009)     

Antiproliferative effect of quercetin in the human U138MG glioma cell line

Recent epidemiological and dietary intervention studies in animals and humans have suggested that diet-derived flavonoids, in particular quercetin, may play a beneficial role by preventing or inhibiting tumorigenesis. The aim of this study was to evaluate whether quercetin may act differently on cancer and normal neuronal tissue. In order to investigate this, the U138MG human glioma cell line and hippocampal organotypic cultures were used. The study showed that quercetin induced in glioma cell cultures results in (a) a decrease in cell proliferation and viability, (b) necrotic and apoptotic cell death, (c) arrest in the G2 checkpoint of the cell cycle, and (d) a decrease of the mitotic index. Furthermore, we demonstrated that while quercetin promotes cancer regression it was able to protect the hippocampal organotypic cultures from ischemic damage. To sum up, our results suggest that quercetin induced growth inhibition and cell death in the U138MG human glioma cell line, while exerting a cytoprotective effect in normal cell cultures.     

Tendencies of studies addressing the eldest individuals of aged population in the community: a (inter)national systematic review

The purpose of this study was to identify and analyze the tendencies and types of studies published in Brazil and abroad, involving elders aged>80 years, living in the community. A systematic review of national literature was performed using the LILACS and SciELO databases, and PUBMED and EMBASE for international literature, covering publications of the last two decades. Twelve national and 162 international references were selected. Biological sciences were the prevalent area both at the national (50%) and international (74.1%) levels. All national studies were observational, 91.7% of which were cross-sectional. Of the international studies, 93.3% were observational, 48.1% of which were cross-sectional and 37.6% were cohort studies. The United States were the country responsible for 41.4% of all international publications. Brazil and China were the only developing countries with international publications. Despite the significant number of international scientific publications as of 2005, this fact has not been observed at the national level.