Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy <it>in vitro</it>.</p> <p>Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells.</p> <p>PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested <it>in vivo </it>and <it>in vitro</it>.</p> <p>Results</p> <p>High HO-1 expression in PaCa cell lines was associated with increased chemoresistance <it>in vitro</it>. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects <it>in vivo </it>significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects.</p> <p>Conclusion</p> <p>In summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy <it>in vivo</it>. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.</p

Quality and Safety Aspects of Infant Nutrition

Quality and safety aspects of infant nutrition are of key importance for child health, but oftentimes they do not get much attention by health care professionals whose interest tends to focus on functional benefits of early nutrition. Unbalanced diets and harmful food components induce particularly high risks for untoward effects in infants because of their rapid growth, high nutrient needs, and their typical dependence on only one or few foods during the first months of life. The concepts, standards and practices that relate to infant food quality and safety were discussed at a scientific workshop organized by the Child Health Foundation and the Early Nutrition Academy jointly with the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, and a summary is provided here. The participants reviewed past and current issues on quality and safety, the role of different stakeholders, and recommendations to avert future issues. It was concluded that a high level of quality and safety is currently achieved, but this is no reason for complacency. The food industry carries the primary responsibility for the safety and suitability of their products, including the quality of composition, raw materials and production processes. Introduction of new or modified products should be preceded by a thorough science based review of suitability and safety by an independent authority. Food safety events should be managed on an international basis. Global collaboration of food producers, food-safety authorities, paediatricians and scientists is needed to efficiently exchange information and to best protect public health. Copyright (C) 2012 S. Karger AG, Base

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Indicators Of Sustainable Economic Growth And Their Management

The article discusses fundamentals of formation of sustainable economic growth indicators, criteria and factors of their qualitative and quantitative measurement, which contribute to objective orientation of development of parameters pertaining to sustainable economy. The variety of economic relations inevitably results a broad choice of parameters describing economic development. However, parameters of sustainable economic development do not serve only as a means of expression of economic processes. Additional requirements are imposed on parameters of sustainable development, which do not only allow to evaluate the becoming of economic processes but also to ensure their integrity with indicators of subsystems of sustainable development in other countries and the possibility of assessment of systemic impact of investment decisions and other kinds of solutions. Assessment of parameters of sustainable economic growth in this article will be carried out employing comparative analysis of scientific literature and methodological recommendations of international organisations. Also, the measurement indicators of environmental sustainability will be developed and analysed

Organization of the Housing Construction Business by Assessing the Legal Background

Straipsnyje nagrinėjami busto statybos versle susiklostantys teisiniai santykiai tarp būsto įgijėjo ir rangovo arba investuotojo. Analizuojama būsto statybos verslo teisinė aplinka akcentuojant atskirų verslo organizavimo būdų teisinio reglamentavimo ypatumus bei privalumus ir trūkumus. Straipsnyje aptariami tiek verslo bendruomenei plačiai žinomi verslo organizavimo būdai, tokie kaip statybos ranga ar pirkimas-pardavimas, tiek mažiau žinomi, tačiau šiandienėje rinkos situacijoje galintys būti naudingi ilgalaikės nuomos ar namų statybos bendrijos steigimo atvejai. Daug dėmesio skiriama būsto įgijėjo fizinio asmens, kaip vartotojo, teisių apsaugos mechanizmui, įtvirtintam įstatymuose ir skirtinguose verslo organizavimo būduose taikomam skirtinga apimtimi. Straipsnyje atkreipiamas dėmesys į Lietuvos teismų praktiką analizuojamais klausimais.Article deals with legal relationship established in the housing construction business between the housing acquirer and the contractor or the investor. The legal environment of business is analyzed by highlighting the peculiarities, advantages and drawbacks of legal regulation of particular business organization methods. The article discusses both, business organization principles widely known to society such as construction outsourcing or sale-purchase, and less known, however capable of being useful in the current market situation cases of long-term lease or the establishment of housing association. A lot of attention is devoted to the rights protection mechanism of the natural person/housing acquirer as a consumer established in the laws and different business organization principles applicable to a different extent. The article pays special attention to the Lithuanian court practice on the issues analyzed

Supplementary Material for: Development of the Visual System in a Burrow-Nesting Seabird: Leach's Storm Petrel

<p>Little is known about the development of vision in wild birds. It is unknown, for example, whether the ability to see can be predicted by the level of prenatal growth or whether the eyes are open at hatching in a particular species. In this study, we investigated the growth of eyes, the formation of retinal ganglion cell topography, and the appearance of simple, visually guided behaviours in chicks of a small procellariiform seabird, Leach's storm petrel (<i>Oceanodroma leucorhoa</i>). This semi-precocial species, which has a well-developed sense of smell, nests in underground burrows where adults provision chicks for 6-8 weeks in the dark before fledging. Retinal ganglion cell topographic maps revealed that fine-tuning of cell distribution does not happen early in development, but rather that the ganglion cell layer continues to mature throughout provisioning and probably even after fledging. While the olfactory bulbs reached adult size around 7 weeks after hatching, the eyes and telencephalon continued to grow. Optokinetic head response and artificial burrow finding experiments indicated that chicks in the 2nd week after hatching lack even the most basic visually guided behaviours and are probably blind. Thus, vision in Leach's storm petrel chicks starts to function sometime around the 3rd week after hatching, well after the eyes have opened and the olfactory system is functional.</p

Application Of Constructs In Commercial Dispute Resolution

Conflicts in the business sector, in particular causes of conflicts and conflict management, have been analysed in detail and described by a number of scholars. However, the stage of conflict evolving into a dispute and the involvement of the parties to the conflict into litigation as a form of dispute resolution has been analysed considerably less often, although the greatest damage to business is caused namely at this stage. This article discusses how constructs can be effectively applied in the litigation process to achieve successful dispute resolution. It analyses the reasons for choosing this method, as well as the participants and their influence on the course of dispute and its outcomes. The identified peculiarities of the litigation process are described and analysed in detail by invoking Lithuanian case law. Based on these peculiarities, the authors developed the methodology that, with the use of legal constructs, can help to model effective conduct of the parties for having their dispute resolved in court