Childhood radiation‐associated atypical meningioma with novel complex rearrangements involving chromosomes 1 and 12

Meningiomas are recognized as the most common late complication following radiotherapy. However, cytogenetic studies in childhood atypical radiation‐induced meningioma are sporadic, mainly because this condition generally occurs after a long latent period. In the present study we show the results of conventional and molecular cytogenetics in a 14‐year‐old boy with a secondary atypical meningioma. Apart from numerical changes, we found complex aberrations with the participation of chromosomes 1, 6 and 12. The invariable presence of loss of 1p was demonstrated by fluorescent in situ hybridization (FISH) analysis with probes directed to telomeric regions and by comparative genome hybridization (CGH). Previous cytogenetic studies on adult spontaneous and radiation‐associated meningiomas showed loss of chromosome 22 as the most frequent change, followed by loss of the short arm of chromosome 1. To the best of our knowledge this is the first report of highly complex chromosome aberrations in the pediatric setting of meningioma.     

The longitudinal course of cognition in older adults with bipolar disorder

Objectives:  Epidemiological studies suggest that elders with bipolar disorder (BD) may be at increased risk for dementia compared to the general population. We sought to investigate whether older adults with BD would present with more cognitive dysfunction than expected for their age and education, and whether they would experience a more rapid cognitive decline over three-year prospective follow-up.
Methods:  Thirty-three subjects age ≥ 50, mean (SD) age 69.7 (7.9) years, with BD I (n = 28) and II (n = 5) had neuropsychological examination at baseline and longitudinally over three years. All subjects were administered the Dementia Rating Scale (DRS) when euthymic. Thirty-six mentally healthy comparators ('controls'), equated on age and education, were selected from ongoing studies in our research center examining the longitudinal relationship between late-life mood disorders and cognitive function.
Results:  Compared to mentally healthy comparators, subjects with BD performed significantly worse on the DRS at baseline [mean (SD) 135.2 (4.7); n = 33 versus 139.5 (3.3); n = 36], and over follow-up [131.9 (7.7); n = 14 versus 139.1 (3.4); n = 22]. There was a group-by-time interaction between the subjects with BD and the controls [group × time: F (1,64) = 5.07, p = 0.028].
Conclusions:  In our study, older adults with BD had more cognitive dysfunction and more rapid cognitive decline than expected given their age and education. Cognitive dysfunction and accelerated cognitive decline may lead to decreased independence, with increased reliance on family and community supports, and potential placement in assisted-living facilities.     

In vivo and in vitro antimalarial activity of 4-nerolidylcatechol

4‐Nerolidylcatechol (4‐NC) isolated from Piper peltatum L. (Piperaceae) was evaluated for in vitro antiplasmodial activity against Plasmodium falciparum (cultures of both standard CQR (K1) and CQS (3D7) strains and two Amazonian field isolates) and for in vivo antimalarial activity using the Plasmodium berghei‐murine model. 4‐NC exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4‐NC administered orally and subcutaneously at doses of 200, 400 and 600 mg/kg/day suppressed the growth of P. berghei by up to 63% after four daily treatments (days 1–4). Also, 4‐NC exhibited important in vitro antiplasmodial activity against both standard and field P. falciparum strains in which 50% inhibition of parasite growth (IC₅₀) was produced at concentrations of 0.05–2.11 μg/mL and depended upon the parasite strain. Interestingly, healthy (non‐infected) mice that received 4‐NC orally presented (denatured) blood plasma which exhibited significant in vitro activity against P. falciparum. This is evidence that mouse metabolism allows 4‐NC or active metabolites to enter the blood. Further chemical and pharmacological studies are necessary to confirm the potential of 4‐NC as a new antimalarial prototype. Copyright © 2011 John Wiley & Sons, Ltd.     

Pentoxifylline sensitizes human cervical tumor cells to cisplatin-induced apoptosis by suppressing NF-kappa B and decreased cell senescence

Background

Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated.

Methods

We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis.

Results

Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of specific inflammatory cytokines in FS-fed mice.

Conclusions

Dietary FS given post-XRT mitigates radiation effects by decreasing pulmonary fibrosis, inflammation, cytokine secretion and lung damage while enhancing mouse survival. Dietary supplementation of FS may be a useful adjuvant treatment mitigating adverse effects of radiation in individuals exposed to inhaled radioisotopes or incidental radiation.