Gap-junctional communication between neurons and astrocytes dissociated from rat brain was identified in culture by using dye-transfer assays and electrophysiological measurements. Cell types were identified by using antibodies against ␤-tubulin III, glial fibrillary acidic protein, and 2,3-cyclic-nucleotide phosphohydrolase, which are antigenic determinants of neurons, astroglia, and oligodendrocytes, respectively. Dye coupling was examined as a function of time after dissociated embryonic brain cells were plated onto confluent monolayers of postnatal astrocytes by intracellularly injecting the fluorochrome Lucifer yellow. Coupling of neurons to the astrocytic monolayer was most frequent between 48 h and 72 h in culture and declined over the next 4 days. This gradual uncoupling was accompanied by progressive neuronal maturation, as indicated by morphological measurements in camera lucida drawings. Dye spread was abolished reversibly by octanol, an agent that blocks gap junction channels in other systems. Double whole-cell voltage-clamp measurements confirmed the presence of heterocellular electrical coupling in these cocultures. Coupling was also seen between neurons and astrocytes in cocultures of cells dissociated from embryonic cerebral hemispheres but was rarely detectable in cocultures of postnatal brain cells. These data strongly suggest that junctional communication may provide metabolic and electrotonic interconnections between neuronal and astrocytic networks at early stages of neural development and that such interactions are weakened as differentiation progresses.The nervous system has great complexity in terms of the diversity of cellular contacts and the broad range of information processing performed by neural cells. Thoroughly debated and overwhelmingly accepted nearly a century ago, the neuron doctrine (1) not only established cellular individuality in the brain parenchyma but also designated neurons as the functional elements in signaling in the central nervous system (CNS). As a consequence, research has focused on elucidating the cellular and molecular details of neuronal pathways, whereas glial cells have been regarded as elements of structural and trophic support, with no direct influence in information processing. However, in the past few years, evidence has accumulated indicating that glial networks may provide functional support to neuronal activity and may constitute dynamic pathways for electrical and chemical signaling in the CNS. Studies showing synchronous metabolic and electrical responses in astrocytes mediated by neuronal-glial interactions demonstrate that, in culture, both slow and rapid calcium waves propagate through the functional syncytium provided by the astrocytic network in response to iontophoretic application of glutamate to astrocytes (2) and to firing of glutamatergic neurons (3, 4). Conversely, the propagation of astrocytic calcium waves to neurons has been more recently reported (5-7). Calcium signaling from astrocytes to neurons in culture was proposed to ...

Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines. We evaluated the cell death, cell cycle arrest and cell proliferation, mainly through PKC expression, by flow cytometry and western blot analysis and, ultimately, cell migration capability and F-actin filament disorganization by fluorescence microscopy. We demonstrated that the constitutive activation of p-PKC seems to be one of the main metabolic implicated on GBM malignancy. Despite of its higher resistance, possibly due to the overexpression of P-glycoprotein and stem-like cell markers, GBM11 cells presented a subtle different chemotherapeutic response compared to U87 and U118 cells. The GBM11, U87, U118 cell lines show subtle molecular differences, which clearly indicate the characterization of GBM heterogeneity, one of the main reasons for tumor resistance. The adding of cellular heterogeneity in molecular behaviour constitutes a step closer in the understanding of resistant molecular mechanisms in GBM, and can circumvents the eventual impaired therapy.

BackgroundGlioblastoma (GBM) is the most common primary brain tumor and the most aggressive glial tumor. This tumor is highly heterogeneous, angiogenic, and insensitive to radio- and chemotherapy. Here we have investigated the progression of GBM produced by the injection of human GBM cells into the brain parenchyma of immunocompetent mice.MethodsXenotransplanted animals were submitted to magnetic resonance imaging (MRI) and histopathological analyses.ResultsOur data show that two weeks after injection, the produced tumor presents histopathological characteristics recommended by World Health Organization for the diagnosis of GBM in humans. The tumor was able to produce reactive gliosis in the adjacent parenchyma, angiogenesis, an intense recruitment of macrophage and microglial cells, and presence of necrosis regions. Besides, MRI showed that tumor mass had enhanced contrast, suggesting a blood–brain barrier disruption.ConclusionsThis study demonstrated that the xenografted tumor in mouse brain parenchyma develops in a very similar manner to those found in patients affected by GBM and can be used to better understand the biology of GBM as well as testing potential therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-923) contains supplementary material, which is available to authorized users.

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4. Fraser HS, Wilson WA, Rose E, Thomas EJ, Sissons GP. Dengue fever in Jamaica with shock and hypocomplementaemia, haemorrhagic, visceral and neurological complications. West Indian Med J 1978;27:106 -116. 5. Yamamoto Y, Takasaki T, Yamada K, et al. Acute disseminated encephalomyelitis following dengue fever. J Infect Chemother 2002;8:175-177. 6. Janssen HL, Bienfait HP, Jansen CL, et al. Fatal cerebral oedema associated with primary dengue infection. J Infect 1998;36:344 -346. 7. Nogueira RMR, Filippis AMB, Coelho JMO, et al. Dengue virus infection of the central nervous system (CNS): a case report from Brazil. Southeast AsianAcquired hepatocerebral degeneration (AHCD) is usually described in patients with chronic liver diseases with portalsystemic shunting and previous episodes of acute hepatic encephalopathy. We describe an atypical case with no overt evidence of hepatic disease in which the characteristic neuroradiologic findings first called attention to the diagnosis. Case report. A 45-year-old man had progressive quadriparesis, dysphagia, and dysphonia for 18 months. He then developed back pain, urinary retention, and weight loss. There was no history of alcoholism or electrolyte disturbances. The general physical examination was unremarkable. The neurologic examination disclosed mental slowing, asymmetric spastic quadriparesis predominating in the lower limbs, mild arm ataxia, dysarthria, and left palate paresis. EMG, CSF, and slitlamp examination were normal. Cranial CT showed moderate corticosubcortical atrophy; MRI revealed symmetric focal lesions in the cerebellar peduncles and white matter (figure, A through D). The patient developed recurrent fever from Staphylococcus aureus infection of undetermined origin. Liver enzymes were normal (alanine aminotransferase, 38 U/L; aspartate aminotransferase, 41 U/L), and ammonia level was not measured. IV administration of oxacillin for 14 days was associated with fluctuating cholestatic jaundice, with no evidence of biliary dilation or other visceral lesions on ultrasound studies. Abdominal Doppler and CT studies disclosed a complete portal vein thrombosis with marked collateral retroperitoneal circulation. Rectal biopsy was negative for Schistosoma mansoni ova. One week after the antibiotic was withheld, the patient developed marked jaundice, followed by disorientation, oliguria, metabolic acidosis, and finally respiratory failure. Once again, S. aureus was isolated in blood cultures, and the patient was admitted to the intensive care unit, where he died on day 55 after admission.

Heparin is a centennial anticoagulant drug broadly employed for treatment and prophylaxis of thromboembolic conditions. Although unfractionated heparin (UFH) has already been shown to have remarkable pharmacological potential for treating a variety of diseases unrelated with thromboembolism, including cancer, atherosclerosis, inflammation, and virus infections, its high anticoagulant potency makes the doses necessary to exert non-hemostatic effects unsafe due to an elevated bleeding risk. Our group recently developed a new low-anticoagulant bovine heparin (LABH) bearing the same disaccharide building blocks of the UFH gold standard sourced from porcine mucosa (HPI) but with anticoagulant potency approximately 85% lower (approximately 25 and 180 Heparin International Units [IU]/mg). In the present work, we investigated the pharmacokinetics profile, bleeding potential, and anticancer properties of LABH administered subcutaneous into mice. LABH showed pharmacokinetics profile similar to HPI but different from the low-molecular weight heparin (LMWH) enoxaparin and diminished bleeding potential, even at high doses. Subcutaneous treatment with LABH delays the early progression of Lewis lung carcinoma, improves survival, and brings beneficial health outcomes to the mice, without the advent of adverse effects (hemorrhage/mortality) seen in the animals treated with HPI. These results demonstrate that LABH is a promising candidate for prospecting new therapeutic uses for UFH.

Background: Breast leiomyosarcoma is a rare subtype of breast sarcoma, constituting 5–10% of the cases. Less than one-third of reported cases are located in the nipple papillary region, making it an extraordinarily rare malignancy, responsible for less than 0.1% of all malignant breast tumors. As no radiological criteria allow definitive diagnosis of papillary leiomyosarcoma, histopathological and immunohistochemical examination of suspicious lesions is required. The prognosis is generally optimistic compared with those for other breast sarcomas.Case presentation: A 54-year-old previously healthy woman reported the appearance of a nodule in her right nipple in the preceding 9 months, associated with pruritus. Physical examination revealed that the lesion had a cystic consistency and measured approximately 3.0 cm. Imaging examinations showed no involvement of the adjacent breast parenchyma or axillary region and the lesion was classified as Breast Imaging-Reporting and Data System (BI-RADS) category IV. The lesion was excised, and the histopathological diagnosis was well-differentiated leiomyosarcoma of the mammary papilla, with immunohistochemical examination showing positivity for smooth-muscle tissue antigens. A staging CT examination was performed, showing no evidence of distant metastasis. After 2 years of follow-up, the patient shows no sign of tumor recurrence.Conclusion: Although rare, leiomyosarcoma must be included in differential diagnosis of breast masses, especially those involving the periareolar region. Due to its good prognosis, reporting on this type of tumor is important to guide therapeutic planning, and to identify and track possible complications of its underdiagnosis.

Granulomas hialinizantes são lesões fibrosantes benignas que em geral se apresentam radiologicamente sob a forma de nódulos múltiplos, freqüentemente escavados e/ou calcificados. Neste trabalho é relatado o caso de uma paciente de 28 anos de idade que apresentou a doença provavelmente secundária a infecção tuberculosa prévia. Ressalta-se a necessidade da inclusão deste diagnóstico diferencial frente ao quadro radiológico de múltiplas lesões nodulares.