Abstract:The use of nanotechnology in medicine and more specifi cally drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifi cally for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus infl uencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also infl uence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential benefi cial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specifi c testing would be needed.

To clarify inconsistencies in the literature we performed a systematic review to identify the incidence, risk factors and outcome of early hepatic artery thrombosis (eHAT) after liver transplantation. We searched studies identified from databases (MEDLINE, EMBASE, Science Citation Index) and references of identified studies. Seventy-one studies out of 999 screened abstracts were eligible for this systematic review. The incidence of eHAT was 4.4% (843/21, 822); in children 8.3% and 2.9% in adults (p < 0.001). Doppler ultrasound screening (DUS) protocols varied from 'no routine' to 'three times a day.' The median time to detection was at day seven. The overall retransplantation rate was 53.1% and was higher in children (61.9%) than in adults (50%, p < 0.03). The overall mortality rate of patients with eHAT was 33.3% (range: 0-80%). Mortality in adults (34.3%) was higher than in children (25%, p < 0.03). The reported risk factors for eHAT were, cytomegalovirus mismatch (seropositive donor liver in seronegative recipient), retransplantation, arterial conduits, prolonged operation time, low recipient weight, variant arterial anatomy, and low volume transplantation centers. eHAT is associated with significant graft loss and mortality. Uniform definitions of eHAT and uniform treatment modalities are obligatory to confirm these results and to obtain a better understanding of this disastrous complication.

SUMMARY BackgroundIt is controversial whether proton pump inhibitor use leads to fundic gland polyp development.

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