10 ns PEFs induce a histological response linked to cell death and cytotoxic T-lymphocytes in an immunocompetent mouse model of peritoneal metastasis

Purpose The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. Methods In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin–eosin–safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. Results 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). Conclusions The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM (AU)

10 ns PEFs induce a histological response linked to cell death and cytotoxic T-lymphocytes in an immunocompetent mouse model of peritoneal metastasis.

PURPOSE: The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. METHODS: In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin-eosin-safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. RESULTS: 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). CONCLUSIONS: The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

Image effects in transport at metal-molecule interfaces.

We present a method for incorporating image-charge effects into the description of charge transport through molecular devices. A simple model allows us to calculate the adjustment of the transport levels, due to the polarization of the electrodes as charge is added to and removed from the molecule. For this, we use the charge distributions of the molecule between two metal electrodes in several charge states, rather than in gas phase, as obtained from a density-functional theory-based transport code. This enables us to efficiently model level shifts and gap renormalization caused by image-charge effects, which are essential for understanding molecular transport experiments. We apply the method to benzene di-amine molecules and compare our results with the standard approach based on gas phase charges. Finally, we give a detailed account of the application of our approach to porphyrin-derivative devices recently studied experimentally by Perrin et al. [Nat. Nanotechnol. 8, 282 (2013)], which demonstrates the importance of accounting for image-charge effects when modeling transport through molecular junctions.

Histopathologic evaluation of arterial wall response to 5 neurovascular mechanical thrombectomy devices in a swine model.

BACKGROUND AND PURPOSE: Five commercial devices are available for mechanical thrombectomy in acute ischemic stroke. This study evaluated and compared the resultant arterial damage from these devices. MATERIALS AND METHODS: Wall damage after 4 wall-contact devices (the Merci retriever, Catch thromboembolectomy system, and Solitaire FR revascularization devices of 4 and 6 mm) and 1 aspiration device (the Penumbra System) was evaluated in the superficial femoral arteries of 20 male swine. Each device was tested with and without intraluminal clot. Twenty control vessels were not subjected to any intervention. Acute histopathologic changes were evaluated. RESULTS: In the device samples, endothelial denudation (72.8 ± 29.4% versus 0.9 ± 1.9%, P < .0001), medial layer edema (52 ± 35.9% versus 18.1 ± 27.8%, P = .004), and mural thrombus (5.3 ± 14.2% versus 0%, P = .05) were found to a greater extent compared with the control samples. The aspiration device provoked more intimal layer (100 ± 79.1% versus 58.8 ± 48.9%, P = .27) and medial layer (75 ± 35.4% versus 46.3 ± 34.8%, P = .13) edema than the wall-contact devices. CONCLUSIONS: All devices caused vascular injuries extending into the medial layer. The aspiration device was associated with more intimal and medial layer edema, compared with the wall-contact devices except for the Catch thromboembolectomy system.

Measurement of particle and gaseous pollution of the atmosphere due to buses.

Measurements were carried out in a street reserved for diesel-engine bus traffic for concentrations of suspended dust, the distribution of aerosol particles according to size (0.01-25 microns) and the CO, HC and NOx concentrations. It was found that the bus traffic had an appreciable effect on the amounts of NOx, suspended dust, nucleus mode aerosol particles (0.03 micron) and large 1.5 microns, particles, and smaller effects on the considerable amounts of accumulation mode aerosol (0.2 micron) and large 3.5 microns particles.