Cyclosporine A kinetics in brain cell cultures and its potential of crossing the blood-brain barrier.

There is an increasing need to develop improved systems for predicting the safety of xenobiotics. However, to move beyond hazard identification the available concentration of the test compounds needs to be incorporated. In this study cyclosporine A (CsA) was used as a model compound to assess the kinetic profiles in two rodent brain cell cultures after single and repeated exposures. CsA induced-cyclophilin B (Cyp-B) secretion was also determined as CsA-specific pharmacodynamic endpoint. Since CsA is a potent p-glycoprotein substrate, the ability of this compound to cross the blood-brain barrier (BBB) was also investigated using an in vitro bovine model with repeated exposures up to 14days. Finally, CsA uptake mechanisms were studied using a parallel artificial membrane assay (PAMPA) in combination with a Caco-2 model. Kinetic results indicate a low intracellular CsA uptake, with no marked bioaccumulation or biotransformation. In addition, only low CsA amounts crossed the BBB. PAMPA and Caco-2 experiments revealed that CsA is mostly trapped to lipophilic compartments and exits the cell apically via active transport. Thus, although CsA is unlikely to enter the brain at cytotoxic concentrations, it may cause alterations in electrical activity and is likely to increase the CNS concentration of other compounds by occupying the BBBs extrusion capacity. Such an integrated testing system, incorporating BBB, brain culture models and kinetics could be applied for assessing neurotoxicity potential of compounds.

Medical nutrition in oncology : potential solution for managing malnutrition in cancer patients in Switzerland

The objective of this study is to: - Describe the cancer related complications, prevalence and economic burden of cancer; - Provide the review of the studies that have been done until now proving that specialized nutrition; can improve quality of life (QoL), shorten the length of hospital stay and reduce overall cost of patients care; - Describe different types of specialized nutritional support and tools/ guidelines used for nutritional screening; - Justify the use of specialized nutrition as an integral part of cancer treatment [Author, p. 6] [Contents] 3. General overview of cancer. 4. Specialized nutritional support and nutritional screening. 4.4 European guidelines for nutritional screening [Screening tools: Malnutrition Universal Screening Tool (MUST); Nutritional Risk Screening (NRS-2002); Mini Nutritional Assessment (MNA)]. 5. Implementation of nutritional support in Swiss hospitals as an integral part of oncology treatment. 5.1 Nutritional guidelines used in Switzerland. 5.2 Status of prevention of malnutrition in cancer patients in Swiss hospitals. 5.3 Malnutrition in Swiss hospitals: medical costs and potential economies. 5.4 Recommendations for implementation of nutritional guidelines and nutritional support in Swiss hospitals.