Determination of protective properties of Bardejovske Kuple spa curative waters by rotational viscometry and ABTS assay

Mineral waters from Bardejovske Kupele spa are natural, strongly mineralized, with healing effects. They are classified as hydrocarbonic - containing chloride and sodium - carbonic, cold, hypotonic, with a relatively high boric acid content. Potential anti-oxidative effects of curative waters from Bardejovske Kupele were investigated against the hyaluronan (HA) degradation. High-molar-mass HA was exposed to the action of ascorbate and cupric ions, which initiate free-radical chain degradation. Time-dependent changes of dynamic viscosity (h) of the HA solutions were monitored by rotational viscometry. The radical scavenging capacity of curative waters was determined by the ABTS assay. Despite a significantly high content of transition metal ions, especially iron, remarkable protective effects of the two curative spa waters were found, namely Alzbeta and Klara. Even though “Alzbeta´s“ iron content was 3.5-fold higher than “Klara´s“, “Alzbeta“ was shown to have better protective properties against the HA degradation compared to “Klara“. Bolus addition of ferric ions to the reaction system instead of the natural iron-containing curative water caused a significant HA degradation. The ABTS decolorization assay revealed that the curative spa waters were proven as poorly effective scavengers of the ABTS·+ cation radical

Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats

Background: Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.Methods: Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.Results: There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.Conclusions: The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT- rats

Variation in the prices of oncology medicines across Europe and the implications for the future

Introduction/ Objectives: There are increasing concerns among health authorities regarding the sustainability of healthcare systems with growing expenditure on medicines including new high-priced oncology medicines. Medicine prices among European countries may be adversely affected by their population size and economic power to negotiate. There are also concerns that prices of patented medicines do not change once the prices of medicines used for negotiations substantially change. This needs to be investigated as part of the implications of low-cost generic oncology medicines. Methodology: Analysing principally reimbursed prices of patented oral oncology medicines (imatinib, erlotinib and fludarabine) between 2013 and 2017 across Europe and exploring correlations between GDP, population size, and prices. Comparing the findings with previous research regarding prices of oral generic oncology medicines. Results: The prices of imatinib, erlotinib and fludarabine did vary among European countries but showed limited price erosion over time in the absence of generics. There appeared to be no correlation between population size and prices. However, higher prices were seen among countries with higher GDP per capita which is a concern for lower income countries referencing these. Discussion and Conclusion: It is likely that the limited price erosion for patented oncology medicines will change across Europe with increased scrutiny over their prices and value as more medicines used for pricing decisions lose their patents combined with growing pressures on the oncology drug budget. In addition, discussions will continue regarding fair pricing for new oncology medicines and other approaches given ever rising prices with research showing substantial price reductions for oral oncology medicines (up to -97.8% for imatinib) once generics become available. We are also seeing appreciable price reductions for biosimilars further increasing the likelihood of these developments

Life-cycle phases of a zinc- and cadmium-resistant ecotype of Silene vulgaris in risk assessment of polymetallic mine soils.

Short-term exposure of plants to heavy metals is often used for risk assessment of metal-enriched soils (OECD guideline 208) without considering the reliability of the assessment for long-term exposure, i.e. for the completion of a plant's life-cycle. In the present study with 15 orogenic soils three phases of the life-cycle of a Zn-Cd-resistant ecotype of Silene vulgaris were studied to improve risk assessment of metal-enriched soils. The first phase, i.e. emergence of seedlings was not related to the water-soluble or total metal concentration of the soils. Seedling mortality was low as long as the water-soluble metal concentration did not surpass 0.15 μmol Zn and 0.04 μmol Cu