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Zagreb, Croatia

The University of Zagreb is the largest Croatian university and the oldest continuously operating university in the area covering Central Europe south of Vienna and all of Southeastern Europe. As of 2011, University of Zagreb is ranked among the 500 Best Universities of the world by the Shanghai Academic Ranking of World Universities. Wikipedia.

Jakovljevic M.,University of Zagreb
European Neuropsychopharmacology

Placebo and nocebo responses fascinate, confuse, mystify and challenge. They are genuine social, cultural and psychobiological phenomena which can significantly modify the overall treatment outcome. The placebo-nocebo phenomenon represents a very good model for our better understanding the role of treatment context and how the words, indices, symbols and icons act on our brains. Placebo response is associated with reward expectancy and relief of anticipatory anxiety, while nocebo response is related to lack of reward/positive expectancy and to increase of anticipatory anxiety. Placebo-nocebo responses are mediated through changes in various cortico-subcortical networks and psychophysiological systems. In spite of many existing complementary theories and still growing research on placebo and nocebo response, the implementation of our current knowledge to benefit basic research, clinical trials and routine clinical practice is still so scarce. © 2013 Elsevier B.V. and ECNP. Source

Orsolic N.,University of Zagreb
Cancer and Metastasis Reviews

Bee venom (BV) (api-toxin) has been widely used in the treatment of some immune-related diseases, as well as in recent times in treatment of tumors. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects. The conjugation of cell lytic peptide (melittin) with hormone receptors and gene therapy carrying melittin can be useful as a novel targeted therapy for some types of cancer, such as prostate and breast cancer. This review summarizes the current knowledge regarding potential of bee venom and its compounds such as melittin to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. The recent applications of melittin in various cancers and a molecular explanation for the antiproliferative properties of bee venom are discussed. © 2011 Springer Science+Business Media, LLC. Source

Reiner Z.,University of Zagreb
Nature Reviews Cardiology

Statins are widely used in the evidence-based lowering of cardiovascular disease (CVD) risk. The use of these drugs for secondary prevention of CVD is well founded, but their expanding use in primary prevention - in individuals without documented CVD - has raised some concerns. Firstly, evidence suggests that, in primary prevention, statins substantially decrease CVD morbidity, but only moderately reduce CVD mortality. Secondly, long-term statin use might cause adverse effects, such as incident diabetes mellitus. Thirdly, the cost-effectiveness of such a strategy is unclear, and has to be balanced against the risk of 'overmedicating' the general population. Data clearly support the use of statins for primary prevention in high-risk individuals, in whom the strategy is cost-effective and the benefits exceed the risks. Whether primary prevention is beneficial in individuals at low or moderate risk is not certain. Therefore, the prescription of statins for primary prevention should be individualized on the basis of clinical judgment, particularly for low-risk individuals. In appropriately selected individuals, statins should also be used for primary prevention of ischaemic stroke and transient ischaemic attack. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Reiner Z.,University of Zagreb
Nutrition, Metabolism and Cardiovascular Diseases

Background and aims: Many patients treated with statins are considered statin-resistant because they fail to achieve adequate reduction of low density lipoprotein cholesterol (LDL-C) levels. Some patients are statin-intolerant because they are unable to tolerate statin therapy at all or to tolerate a full therapeutic statin dose because of adverse effects, particularly myopathy and increased activity of liver enzymes. Results: The resistance to statins has been associated with polymorphisms in the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-R), P-glycoprotein (Pg-P/ABCB1), breast cancer resistance protein (BCRP/ABCG2), multidrug resistance-associated proteins (MRP1/ABCC1 and MRP2/ABCC2), organic anion transporting polypeptides (OATP), RHOA, Nieman-Pick C1-like1 protein (NPC1L1), farnesoid X receptor (FXR), cholesterol 7alpha-hydroxylase (CYP7A1), Apolipoprotein E (ApoE), proprotein convertase subtilisin/kexin type 9 (PCSK9), low density lipoprotein receptor (LDLR), lipoprotein (a) (LPA), cholesteryl ester transfer protein (CETP), and tumor necrosis factor α (TNF-α) genes. However, currently, there is still not enough evidence to advocate pharmacogenetic testing before initiating statin therapy. Patients with inflammatory states and HIV infection also have diminished LDL-C lowering as a response to statin treatment. Pseudo-resistance due to nonadherence or non-persistence in real-life circumstances is probably the main cause of insufficient LDL-C response to statin treatment. Conclusions: If a patient is really statin-resistant or statin-intolerant, several other treatment possibilities are nowadays available: ezetimibe alone or in combination with bile acid sequestrants, and possibly in the near future mipomersen, lomitapide, or monoclonal antibodies against PCSK9. © 2014 Elsevier B.V. Source

Reiner Z.,University of Zagreb
Current Atherosclerosis Reports

Owing to the progressive aging of the population, and the fact that cardiovascular disease (CVD) is the leading cause of death among the elderly, the prevention of CVD in the elderly is becoming increasingly important. Although there is no doubt that statin treatment should be used for reducing CVD risk in the elderly in secondary prevention in the same way as in younger individuals, the evidence that such treatment really prolongs life in elderly subjects in primary prevention is still not so clear. However, it seems that it does reduce CVD morbidity in elderly individuals. Because of limited evidence regarding the benefit of such therapy, particularly in very old subjects (older than 80-85 years), the decision whether to treat or not treat an elderly individual with statins in primary prevention should be based on good clinical judgment and considering the individual subject's situation regarding comorbidities, polypharmacy, and possible adverse effects. © Springer Science+Business Media 2014. Source

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