In vivo response of KHT sarcomas to combination chemotherapy with radiosensitizers and BCNU.

Female C3H/HeJ mice bearing intramuscularly transplanted KHT sarcomas were treated with a single dose of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, 30 mg/kg, i.p.) alone or in combination with a single dose of misonidazole (MISO, 1.0 mg/g, i.p.) or its desmethylated metabolite Ro-05-9963 (2.0 mg/g, i.p.). The effectiveness of drug therapy was assessed by a tumour growth-delay assay (i.e. measuring the median time required for tumours to grow to treatment size x 4). The relative efficacy of administering the nitroimidazoles in various schedules ranging from 12 h before to 12 h after BCNU administration also was evaluated. Untreated control KHT tumours grew to the initial size x 4 in a median time of 4 days. No significant growth delay was seen in mice treated with either nitroimidazole alone, whilst treatment with BCNU alone produced a median growth delay of 7 days. Combination chemotherapy with 9963 administration 3 h after BCNU significantly increased the median tumour growth delay to 9 days. However, no significant growth delay was produced in any of the other combinations of these agents. The median growth delay was significantly reduced to 5 days when MISO was administered 3 h before BCNU, whereas MISO administered simultaneously 3,6, or 12 h after BCNU significantly enhanced delays ( 9 days). These results indicate that both MISO and 0063 may be combined with conventional therapeutic agents, in this particular case a nitrosourea, to produce an enhanced tumour response. The production of such a response appears to be nitroimidazole as well as schedule dependent

Nitrosourea-misonidazole combination chemotherapy: effect on KHT sarcomas, marrow stem cells and gut.

C3H/HeJ mice bearing i.m. transplanted KHT sarcomas were treated with varying doses of either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin; CHLZ) as single agents or in combination with 1 mg/g of the chemical radiosensitizer, misonidazole (MISO). Using an in vivo-in vitro tumour-excision assay, the administration of MISO simultaneously with or 3 h after low doses of BCNU (less than 20 mg/kg) was found to give a dose-modification factor (DMF) of approximately 1.65 relative to BCNU alone. At higher doses of BCNU, there was less enhancement of cell kill. The DMF for tumour growth delay was likewise dependent on BCNU dose, continuously decreasing with increasing BCNU dose. In contrast, the anti-tumour activity of CHLZ, assessed by both clonogenic cell survival and tumour-growth delay, was not significantly enhanced by the addition of MISO. The enhancement of gastrointestinal toxicity and haematotoxicity by BCNU-MISO combinations was assessed by LD50/7 and CFU-S assays, respectively. MISO enhanced BCNU marrow toxicity by a factor of 1.2-1.3, whilst gut toxicity was enhanced by a factor of approximately 1.2

Vertical visual features have a strong influence on cuttlefish camouflage

Author Posting. © Marine Biological Laboratory, 2013. This article is posted here by permission of Marine Biological Laboratory for personal use, not for redistribution. The definitive version was published in Biological Bulletin 224 (2013): 110-118.Cuttlefish and other cephalopods use visual cues from their surroundings to adaptively change their body pattern for camouflage. Numerous previous experiments have demonstrated the influence of two-dimensional (2D) substrates (e.g., sand and gravel habitats) on camouflage, yet many marine habitats have varied three-dimensional (3D) structures among which cuttlefish camouflage from predators, including benthic predators that view cuttlefish horizontally against such 3D backgrounds. We conducted laboratory experiments, using Sepia officinalis, to test the relative influence of horizontal versus vertical visual cues on cuttlefish camouflage: 2D patterns on benthic substrates were tested versus 2D wall patterns and 3D objects with patterns. Specifically, we investigated the influence of (i) quantity and (ii) placement of high-contrast elements on a 3D object or a 2D wall, as well as (iii) the diameter and (iv) number of 3D objects with high-contrast elements on cuttlefish body pattern expression. Additionally, we tested the influence of high-contrast visual stimuli covering the entire 2D benthic substrate versus the entire 2D wall. In all experiments, visual cues presented in the vertical plane evoked the strongest body pattern response in cuttlefish. These experiments support field observations that, in some marine habitats, cuttlefish will respond to vertically oriented background features even when the preponderance of visual information in their field of view seems to be from the 2D surrounding substrate. Such choices highlight the selective decision-making that occurs in cephalopods with their adaptive camouflage capability.This work was funded by the United States Department of Defense (grant number W911- NF-07-D-0001)

Multimodal alterations of directed connectivity profiles in patients with attention-deficit/hyperactivity disorders

Functional and effective connectivity measures for tracking brain region interactions that have been investigated using both electroencephalography (EEG) and magnetoencephalography (MEG) bringing up new insights into clinical research. However, the differences between these connectivity methods, especially at the source level, have not yet been systematically studied. The dynamic characterization of coherent sources and temporal partial directed coherence, as measures of functional and effective connectivity, were applied to multimodal resting EEG and MEG data obtained from 11 young patients (mean age 13.2 ± 1.5 years) with attention-deficit/hyperactivity disorder (ADHD) and age-matched healthy subjects. Additionally, machine-learning algorithms were applied to the extracted connectivity features to identify biomarkers differentiating the two groups. An altered thalamo-cortical connectivity profile was attested in patients with ADHD who showed solely information outflow from cortical regions in comparison to healthy controls who exhibited bidirectional interregional connectivity in alpha, beta, and gamma frequency bands. We achieved an accuracy of 98% by combining features from all five studied frequency bands. Our findings suggest that both types of connectivity as extracted from EEG or MEG are sensitive methods to investigate neuronal network features in neuropsychiatric disorders. The connectivity features investigated here can be further tested as biomarkers of ADHD