Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo

Photodynamic therapy (PDT) exerts direct cytotoxic effects on tumor cells, destroys tumor blood and lymphatic vessels and induces local inflammation. Although PDT triggers the release of immunogenic antigens from tumor cells, the degree of immune stimulation is regimen-dependent. The highest immunogenicity is achieved at sub-lethal doses, which at the same time trigger cytoprotective responses, that include increased expression of glucose-regulated protein 78 (GRP78). To mitigate the cytoprotective effects of GRP78 and preserve the immunoregulatory activity of PDT, we investigated the in vivo efficacy of PDT in combination with EGF-SubA cytotoxin that was shown to potentiate in vitro PDT cytotoxicity by inactivating GRP78. Treatment of immunocompetent BALB/c mice with EGF-SubA improved the efficacy of PDT but only when mice were treated with a dose of EGF-SubA that exerted less pronounced effects on the number of T and B lymphocytes as well as dendritic cells in mouse spleens. The observed antitumor effects were critically dependent on CD8(+) T cells and were completely abrogated in immunodeficient SCID mice. All these results suggest that GRP78 targeting improves in vivo PDT efficacy provided intact T-cell immune system

An evaluation of family physicians' educational needs and experiences in health promotion and disease prevention in Poland and Lithuania - a qualitative study

Reikšminiai žodžiai: Ligų prevencija; Sveikatos stiprinimas; Šeimos gydytojai; Šeimos gydytojų rengimas; Šeimos gydytojų švietimo poreikiai; Disease prevention; Family physicians; Family physicians educational needs; Health promotion; Training of family physician

Central and territorial governmental institutions involved in health promotion for older people in European Union countries

Defining, planning and achieving health goals including health promotion and health promotion for older people (HP4OP) are always the responsibility of the public authority. In European countries the public health and health promotion strategic framework, including HP4OP is provided by the ministry of health or others national public health organisations, which are responsible for defining of legal regulations on the different aspects of health promotion. The goal of this article is the analysis of the central and territorial government (CTG) sector’s involvement in the issue of HP4OP, their functions, activities and responsibilities in this area. The analysis is focused on the main differences and similarities between CTG’s institutions. The authors triangulated data collected using varied methods: literature review, questionnaire research (conducted in European Pro-Health 65+ project’s countries) and in-depth interviews with national experts from selected countries. In the majority of analysed countries, the central government and municipalities are the main stakeholders responsible for providing funding for these programs. The operational level for the implementation of majority HP4OP is the local level. Research countries have been identified as strongly varying in institutional, legal and political specificity. The analysis shows the increasing position of HP4OP in public health policy.  Many of the identified problems come from the implementation of a fragmented approach, the duplication of efforts undertaken by different stakeholders and the lack of a co-ordinated strategy and dedicated legal regulations at both the national and regional/local levels

MEDICAL SERVICE STAFF: PROBLEMS AND PROPOSED ACTIONS

Efektywność systemu ochrony zdrowia i jakość realizowanych świadczeń medycznych uzależnione są w głównej mierze od wiedzy, umiejętności i motywacji pracowników. Stąd krytyczna rola i znaczenie personelu medycznego dla prawidłowego działania jednostek ochrony zdrowia i całego systemu. Powszechnie uważa się, że czynnikiem warunkującym prawidłowe funkcjonowanie systemu opieki zdrowotnej w kraju jest wielkość i jakość kadry medycznej. Dobrze wykształcony i zmotywowany personel medyczny stanowi fundament pomyślnego osiągania celów zdrowotnych, jakie stoją przed systemem zdrowotnym każdego kraju.The effectiveness of the healthcare system and the quality of medical services depends largely on the knowledge, skills, and motivation of employees, hence the critical role and importance of medical personnel in the proper functioning of healthcare units and the system in its entirety. It is commonly believed that the size and quality of medical staff influences the proper functioning of a country's healthcare system. What is more, well-trained and motivated medical staff is the cornerstone of the successful achievement of the healthcare objectives faced by each country's health care system

Inhibition of thioredoxin-dependent H2O2 removal sensitizes malignant B-cells to pharmacological ascorbate

L-ascorbate (L-ASC) is a widely-known dietary nutrient which holds promising potential in cancer therapy when given parenterally at high doses. The anticancer effects of L-ASC involve its autoxidation and generation of H2O2, which is selectively toxic to malignant cells. Here we present that thioredoxin antioxidant system plays a key role in the scavenging of extracellularly-generated H2O2 in malignant B-cells. We show that inhibition of peroxiredoxin 1, the enzyme that removes H2O2 in a thioredoxin system-dependent manner, increases the sensitivity of malignant B-cells to L-ASC. Moreover, we demonstrate that auranofin (AUR), the inhibitor of the thioredoxin system that is used as an antirheumatic drug, diminishes the H2O2-scavenging capacity of malignant B-cells and potentiates pharmacological ascorbate anticancer activity in vitro and in vivo. The addition of AUR to L-ASC-treated cells triggers the accumulation of H2O2 in the cells, which results in iron-dependent cytotoxicity. Importantly, the synergistic effects are observed at as low as 200 µM L-ASC concentrations. In conclusion, we observed strong, synergistic, cancer-selective interaction between L-ASC and auranofin. Since both of these agents are available in clinical practice, our findings support further investigations of the efficacy of pharmacological ascorbate in combination with auranofin in preclinical and clinical settings