Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

Electrochemotherapy has a direct cytotoxic effect on tumour cells, and presumably, a vascular disrupting effect. In this study, on the basis of the prediction of the mathematical model, histological evaluation and physiological measurements of the tumours were carried out to confirm that electroporation and electrochemotherapy of tumours have a vascular disrupting action. In the study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM) given intravenously (1 mg kg−1), application of electric pulses (8 pulses, 1040 V, 100 μs, 1 Hz) or a combination of both – electrochemotherapy. The vascular effect was determined by laser Doppler flowmetry, power Doppler ultrasonographic imaging and Patent blue staining. The extent of tumour hypoxia was determined immunohistochemically by hypoxia marker pimonidazole and partial pressure of oxygen (pO2) in tumours by electron paramagnetic resonance oximetry. Electrochemotherapy with BLM induced good antitumour effect with 22 days, tumour growth delay and 38% tumour cures. The application of electric pulses to the tumours induced instant but transient tumour blood flow reduction (for 70%) that was recovered in 24 h. During this tumour blood flow reduction, we determined an increase in hypoxic tumour area for up to 30%, which was also reflected in reduced tumour oxygenation (for 70%). According to the described mathematical model, endothelial cells lining in tumour blood vessels are exposed to a ∼40% higher electric field than the surrounding tumour cells, and therefore easily electroporated, allowing access of high BLM concentration to the cytosol. Consequently, electrochemotherapy has, besides the immediate vascular disrupting action, also a delayed one (after 24 h), as a consequence of endothelial cell swelling and apoptosis demonstrated by extensive tumour necrosis, tumour hypoxia, prolonged reduction of tumour blood flow and significant tumour growth delay, and tumour cures. Our results demonstrate that in addition to the well-established direct cytotoxic effect on tumour cells, electrochemotherapy also has an indirect vascular disrupting action resulting altogether in extensive tumour cell necrosis leading to complete regression of tumours

Accounting for International War: The State of the Discipline

In studies of war it is important to observe that the processes leading to so frequent an event as conflict are not necessarily those that lead to so infrequent an event as war. Also, many models fail to recognize that a phenomenon irregularly distributed in time and space, such as war, cannot be explained on the basis of relatively invariant phenomena. Much research on periodicity in the occurrence of war has yielded little result, suggesting that the direction should now be to focus on such variables as diffusion and contagion. Structural variables, such as bipolarity, show contradictory results with some clear inter-century differences. Bipolarity, some results suggest, might have different effects on different social entities. A considerable number of studies analysing dyadic variables show a clear connection between equal capabilities among contending nations and escalation of conflict into war. Finally, research into national attributes often points to strength and geographical location as important variables. In general, the article concludes, there is room for modest optimism, as research into the question of war is no longer moving in non-cumulative circles. Systematic research is producing results and there is even a discernible tendency of convergence, in spite of a great diversity in theoretical orientations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69148/2/10.1177_002234338101800101.pd

Natural Hazard Assessment for Land-use Planning in Serbia. International journal of environmental research

ABSTRACT: The territory of Serbia is vulnerable to various types of natural hazards and the risk is not equal across the entire territory; it varies depending on the type of hazard and the expected potential for damage. The first aim of this research was to determine the geographical distributions of the major types of natural hazards. Seismic hazards, landslides, rock falls, floods, torrential floods, excessive erosion, droughts and forest fires are the most significant natural hazards within the territory of Serbia. Areas vulnerable to some of these natural hazards were singled out using analytical maps; their area relative to the total area of Serbia was defined, along with the total surface area that is vulnerable to each type of natural hazard. Upper intensity values for single natural hazards were measured; these values represent the limiting factor for land-use planning at the given level. Based on these analyses, an integral map of the natural hazards of the territory was created using multi-hazard assessment. Hence, a recent state of the natural hazard vulnerabilities of the territory of Serbia was created and then an integral map was made. The integral map showed spatial distribution of the different types of hazards that are considered to be limiting factors for the highest level of land-use planning. The results presented in this article are the first multi-hazard assessment and the first version of the integral map of natural hazards distribution in Serbia for land-use planning, which is important both nationally and regionally

From A Study of War to peace research: some criteria and strategies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67729/2/10.1177_002200277001400416.pd