Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells

Glioblastoma is the most common malignant brain tumor in adults. The currently available treatments offer only a palliative survival advantage and the need for effective treatments remains an urgent priority. Activation of the p53 growth suppression/apoptotic pathway is one of the promising strategies in targeting glioma cells. We show that the quinoline derivative chloroquine activates the p53 pathway and suppresses growth of glioma cells in vitro and in vivo in an orthotopic (U87MG) human glioblastoma mouse model. Induction of apoptosis is one of the mechanisms underlying the effects of chloroquine on suppressing glioma cell growth and viability. siRNA-mediated downregulation of p53 in wild-type but not mutant p53 glioblastoma cells substantially impaired chloroquine-induced apoptosis. In addition to its p53-activating effects, chloroquine may also inhibit glioma cell growth via p53-independent mechanisms. Our results clarify the mechanistic basis underlying the antineoplastic effect of chloroquine and reveal its therapeutic potential as an adjunct to glioma chemotherapy

The role of transplanted Schwann cells in promoting regeneration of rat optic nerve (abstracts)

Current concern for ensuring the air-worthiness of the aging commercial air fleet has prompted the establishment of broad-agency programs to develop NDT technologies that address specific aging-aircraft issues.[1, 2] One of the crucial technological needs that has been identified is the development of rapid, quantitative systems for depot-level inspection of bonded aluminum lap joints on aircraft.[1–3] Research results for characterization of disbond and corrosion based on normal-incidence pulse-echo measurement geometries are showing promise, but are limited by the single-site nature of the measurement which requires manual or mechanical scanning to inspect an area. [4–7] One approach to developing efficient systems may be to transfer specific aspects of current medical imaging technology to the NDT arena. Ultrasonic medical imaging systems offer many desirable attributes for large scale inspection. They are portable, provide real-time imaging, and have integrated video tape recorder and printer capabilities available for documentation and post-inspection review. Furthermore, these systems are available at a relatively low cost (approximately $50,000 to$200,000) and can be optimized for use with metals with straight-forward modifications. As an example, ultrasonic phased-array and linear array imaging technology, which was first developed for use in the medical industry, has been successfully implemented for some NDT applications by other investigators. [8–10

Clinical management of chronic inflammatory demyelinating polyneuropathy (CIDP) in Europe and India: An exploratory study

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder causing inflammatory demyelination of peripheral nerves and consecutive disability. Diagnostic criteria and treatments are well established, but it is unknown how clinical practice may differ in different geographical regions. In this multicentre study, clinical management of CIDP was compared in 44 patients from Germany, India and Norway regarding diagnostic and therapeutic procedures. All centres used EFNS/PNS diagnostic criteria for CIDP but diagnostic workup varied regarding screening for infectious diseases, genetic testing and nerve biopsy. Intravenous immunoglobulin and prednisolone were the most common therapies in all centres with differences in indication and dosage. Patients from the Indian cohort were the most severely affected with less diverse therapeutic approaches, whereas psychological strain did not differ significantly from the two other cohorts. Our exploratory study discloses an unaddressed issue in management of CIDP that should be further investigated to optimise standard of care for CIDP worldwide

Ventral striatal prediction error signaling is associated with dopamine synthesis capacity and fluid intelligence

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subsample of 17 subjects also with positron emission tomography using 6-[18F]fluoro-L-DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA Kmath image). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that individual differences in the capacity for flexible problem solving relate to ventral striatal activation during reward-related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity

Honeybee locomotion is impaired by Am-CaV3 low voltage-activated Ca(2+) channel antagonist.

Voltage-gated Ca(2+) channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca(2+) channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides. We have isolated the 3 genes coding for the 3 Ca(2+) channels expressed in Apis mellifera. This work provides the first detailed characterization of the honeybee T-type CaV3 Ca(2+) channel and demonstrates the low toxicity of inhibiting this channel. Comparing Ca(2+) currents recorded in bee neurons and myocytes with Ca(2+) currents recorded in Xenopus oocytes expressing the honeybee CaV3 gene suggests native expression in bee muscle cells only. High-voltage activated Ca(2+) channels could be recorded in the somata of different cultured bee neurons. These functional data were confirmed by in situ hybridization, immunolocalization and in vivo analysis of the effects of a CaV3 inhibitor. The biophysical and pharmacological characterization and the tissue distribution of CaV3 suggest a role in honeybee muscle function