ABSTRACT
BACKGROUND: In Poland, the prevalence of cardiovascular diseases is increasing. This might be associated with the constantly growing proportion of elderly people and inappropriate cardiovascular prevention. This study aimed to evaluate the frequency of use of oral antiplatelet (OAP) and oral anticoagulant (OAC) drugs among older people in Poland and to assess their association with cardiovascular risk factors. METHODS: The study was based on data collected during the implementation of a multicentre, publicly funded research project called PolSenior. RESULTS: The study group consisted of 4,979 people with the average age of 79.35 ± 8.69 years. Among them, 1,787 people (35.9%) used at least one drug in the prevention of cardiovascular diseases. OAPs were used regularly by 1,648 (33.1%) elderly people and OACs were used by 165 elderly people (3.3%). Acetylsalicylic acid was used by 32.2% of elderly people. Use of drugs significantly depended on age (p < 0.01), sex (p < 0.01), place of residence (p < 0.001), level of education (p < 0.0001) and personal income (p < 0.0001). Among all the respondents treated with OAPs, therapy was applied as secondary cardiovascular prevention in 717 respondents (43.5%), and as primary prevention in 705 respondents (42.8%). Among the respondents treated with OACs, 117 (71%) elderly people had a history of atrial fibrillation. Secondary cardiovascular prevention should be considered in a further 482 respondents (15.1% of untreated elderly people), and primary cardiovascular prevention in 1,447 respondents (45.3%). CONCLUSIONS: Our study is the first to determine the frequency of use of OAP and OAC drugs among elderly people in Poland in relation to cardiovascular risk factors. The most commonly used drug for cardiovascular prevention is acetylsalicylic acid, but it appears that it is used too rarely in high-risk patients. Educational programs should be developed among general practitioners concerning current recommendations for pharmacological cardiovascular prevention.
Subject(s)
Anticoagulants/therapeutic use , Cardiovascular Diseases/prevention & control , Platelet Aggregation Inhibitors/therapeutic use , Administration, Oral , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Female , Humans , Male , Poland , Risk FactorsABSTRACT
Thioredoxins (Trx) are ubiquitous multifunctional low-molecular weight proteins that together with thioredoxin reductases (TrxR) participate in the maintenance of protein thiol homeostasis in NADPH-dependent reactions. An increasing number of data reveal that the Trx-TrxR system is an attractive target for anticancer therapies. In this work, we have elaborated a new and simple synthetic approach employing Ugi reaction to synthesize several new inhibitors of this system. The influence of various electrophilic fragments of this new class of compounds on the inhibition of the Trx-TrxR system was evaluated. As a result, a new compound 19a (SK053), which inhibits the activity of the Trx-TrxR system and exhibits antitumor activity, was obtained. Biologic analyses revealed that 19a inhibits induction of NF-κB and AP-1 and decreases H(2)O(2) scavenging capacity in tumor cells. Altogether, we show that 19a is a novel potential antitumor peptidomimetic inhibitor that can be used as a starting compound for further optimization.
Subject(s)
Antineoplastic Agents/chemical synthesis , Dipeptides/chemical synthesis , Methacrylates/chemical synthesis , Peptidomimetics/chemical synthesis , Thioredoxin-Disulfide Reductase/antagonists & inhibitors , Thioredoxins/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cytotoxins/chemical synthesis , Cytotoxins/chemistry , Cytotoxins/pharmacology , Dipeptides/chemistry , Dipeptides/pharmacology , Drug Screening Assays, Antitumor , Free Radical Scavengers/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Methacrylates/chemistry , Methacrylates/pharmacology , Mice , Mice, Inbred BALB C , NF-kappa B/antagonists & inhibitors , NF-kappa B/biosynthesis , Neoplasm Transplantation , Peptidomimetics/chemistry , Peptidomimetics/pharmacology , Reactive Oxygen Species/metabolism , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/chemistry , Structure-Activity Relationship , Thioredoxin-Disulfide Reductase/chemistry , Thioredoxin-Disulfide Reductase/metabolism , Thioredoxins/chemistry , Thioredoxins/metabolism , Transcription Factor AP-1/antagonists & inhibitors , Transcription Factor AP-1/biosynthesis , Transplantation, HeterologousABSTRACT
Photodynamic therapy (PDT) is a clinically approved method of tumor treatment. Its unique mechanism of action results from minimal invasiveness and high selectivity towards transformed cells. However, visible light used to excite most photosensitizers has rather limited ability to penetrate tissues resulting in insufficient destruction of deeply seated malignant cells. Therefore, novel strategies for further potentiation of the anticancer effectiveness of PDT have been developed. These include combined treatments with surgery, chemo- and radiotherapy, strategies targeting cytoprotective mechanisms induced in PDT-treated cells, as well as attempts aimed at enhancement of PDT-mediated antitumor immune response. Moreover, new photosensitizers and novel light sources are being developed. Impressive progress in nanotechnology and understanding of tumor cell biology rise hopes for further improvements in this elegant and promising method of cancer treatment.
