Fighting corruption with pyramids: A Law and Economics approach to combating corruption in post-socialist countries

Corruption is, in the last two decades, considered as one of the biggest problems within the international community, which harms not only a particular state or society but the whole world. The discussion on corruption in law and economics approach is mainly run under the veil of Public choice theory and principal-agent model. Based on this approach the strong international initiatives taken by the UN, the OECD and the Council of Europe, provided various measures and tools in order to support and guide countries in their combat against corruption. These anti-corruption policies created a repression -prevention-transparency model for corruption combat. Applying this model, countries around the world adopted anti-corruption strategies as part of their legal rules. Nevertheless, the recent researches on the effects of this move show non impressive results. Critics argue that “one size does not fit all” because the institutional setting of countries around the world varies. Among the countries which experience problems of corruption, even though they follow the dominant anti-corruption trends, are transitional, post-socialist countries. To this group belong the countries which are emerging from centrally planned to an open market economy. The socialist past left traces on institutional setting, mentality of the individuals and their interrelation, particularly in the domain of public administration. If the idiosyncrasy of these countries is taken into account the suggestion in this thesis is that in public administration in post-socialist countries, instead of dominant anti-corruption scheme repression-prevention-transparency, corruption combat should be improved through the implementation of a new one, structure-conduct-performance. The implementation of this model is based on three regulatory pyramids: anti-corruption, disciplinary anti-corruption and criminal anti-corruption pyramid. This approach asks public administration itself to engage in corruption combat, leaving criminal justice system as the ultimate weapon, used only for the very harmful misdeeds.

Use of VEGFR-2 targeted microbubbles (BR55, Bracco imaging) for the early ultrasound evaluation of response to antiangiogenic treatment in a xenograft model of hepatocarcinoma

Aim: To evaluate the early response to treatment to an antiangiogenetic drug (sorafenib) in a heterotopic murine model of hepatocellular carcinoma (HCC) using ultrasonographic molecular imaging. Material and Methods: the xenographt model was established injecting a suspension of HuH7 cells subcutaneously in 19 nude mice. When tumors reached a mean diameter of 5-10 mm, they were divided in two groups (treatment and vehicle). The treatment group received sorafenib (62 mg/kg) by daily oral gavage for 14 days. Molecular imaging was performed using contrast enhanced ultrasound (CEUS), by injecting into the mouse venous circulation a suspension of VEGFR-2 targeted microbubbles (BR55, kind gift of Bracco Swiss, Geneve, Switzerland). Video clips were acquired for 6 minutes, then microbubbles (MBs) were destroyed by a high mechanical index (MI) impulse, and another minute was recorded to evaluate residual circulating MBs. The US protocol was repeated at day 0,+2,+4,+7, and +14 from the beginning of treatment administration. Video clips were analyzed using a dedicated software (Sonotumor, Bracco Swiss) to quantify the signal of the contrast agent. Time/intensity curves were obtained and the difference of the mean MBs signal before and after high MI impulse (Differential Targeted Enhancement-dTE) was calculated. dTE represents a numeric value in arbitrary units proportional to the amount of bound MBs. At day +14 mice were euthanized and the tumors analyzed for VEGFR-2, pERK, and CD31 tissue levels using western blot analysis. Results: dTE values decreased from day 0 to day +14 both in treatment and vehicle groups, and they were statistically higher in vehicle group than in treatment group at day +2, at day +7, and at day +14. With respect to the degree of tumor volume increase, measured as growth percentage delta (GPD), treatment group was divided in two sub-groups, non-responders (GPD>350%), and responders (GPD<200%). In the same way vehicle group was divided in slow growth group (GPD<400%), and fast growth group (GPD>900%). dTE values at day 0 (immediately before treatment start) were higher in non-responders than in responders group, with statistical difference at day 2. While dTE values were higher in the fast growth group than in the slow growth group only at day 0. A significant positive correlation was found between VEGFR-2 tissue levels and dTE values, confirming that level of BR55 tissue enhancement reflects the amount of tissue VEGF receptor. Conclusions: the present findings show that, at least in murine experimental models, CEUS with BR55 is feasable and appears to be a useful tool in the prediction of tumor growth and response to sorafenib treatment in xenograft HCC.