The antigenotoxic potential of dietary flavonoids

Human exposure to genotoxic agents has dramatically increased. Both endogenous (reactive species generated during physiological and pathological processes) and exogenous (UV light, ionizing radiation, alkylating agents, antimetabolites and topoisomerase inhibitors, air, water and food pollutants) factors can impair genomic stability. The cumulative DNA damage causes mutations involved in the development of cancer and other disorders (neuromuscular and neurodegenerative diseases, immune deficiencies, infertility, cardiovascular diseases, metabolic syndrome and aging). Dietary flavonoids have protective effects against DNA damage induced by different genotoxic agents such as mycotoxins, food processing-derived contaminants (polycyclic aromatic hydrocarbons, N-nitrosamines), cytostatic agents, other medications (estrogenic and androgenic hormones), nicotine, metal ions (Cd²⁺, Cr⁶⁺), radiopharmaceuticals and ionizing radiation. Dietary flavonoids exert their genoprotection by reducing oxidative stress and modulation of enzymes responsible for bioactivation of genotoxic agents and detoxification of their reactive metabolites. Data on structure–activity relationship is sometimes contradictory. Free hydroxyl groups on the B ring (catechol moiety) and C-3 position of the C ring are important structural features for the antigenotoxic activity. As dietary flavonoids are extensively metabolized, more in vivo studies are needed for a better characterization of their antigenotoxic potential.     

Erythropoietin stimulates the coronary collateral development in patients with coronary chronic total occlusion

Objective

Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion.

Methods

A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3).

Results

There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = ?0.210, p = 0.006).

Conclusions

Serum EPO is a useful biomarker for coronary collateral development in patients with CTO.

     

Natural products from marine invertebrates against <Emphasis Type="Italic">Leishmania</Emphasis> parasites: a comprehensive review

Parasitic infections by Leishmania parasites remains a severe public health problem, especially in developing countries where it is highly endemic. Chemotherapy still remains a first option for the treatment of those diseases, despite the fact that available drugs exhibit a variety of shortcomings. Thus, innovative, less toxic more affordable and effective antileishmanial agents are urgently needed. The marine environment holds an immeasurable bio- and chemical diversity, being a valuable source of natural products with therapeutic potential. As invertebrates comprise about 60 % of all marine organisms, bioprospecting this class of organisms for antileishmanial properties may unravel unique and selective hit molecules. In this context, this review covers results on the literature of marine invertebrate extracts and pure compounds evaluated against Leishmania parasites mainly by in vitro methods. It comprises results obtained from the phyla Porifera, Cnidaria, Bryozoa (Ectoprota), Mollusca, Echinodermata, Annelida, Cetnophora, Platyhelminthes, sub phyla Crustacea (phylum Arthropoda) and Tunicata (phylum Chordata). Moreover, structure–activity relationships and possible mechanisms of action are mentioned, whenever available information is provided. About 70 species of marine invertebrates belonging to seven different phyla are included in this work. Besides a variety of crude extracts, a total of 140 pure compounds was tested against different Leishmania species. Although the research on the antileishmanial potential of marine invertebrates is in its early beginnings, promising results have been achieved that encourage further research. As more extracts and compounds are being screened, the possibility of finding active and selective antileishmanial molecules increases, rising new hope in the search for new treatments against leishmaniases.     

Elm defence against herbivores and pathogens: morphological,chemical and molecular regulation aspects

Elms (Ulmus spp.) have long been appreciated for their environmental tolerance, landscape and ornamental value, and the quality of their wood. Although elm trees are extremely hardy against abiotic stresses such as wind and pollution, they are susceptible to attacks of biotic stressors. Over 100 phytopathogens and invertebrate pests are associated with elms: fungi, bacteria and insects like beetles and moths, and to a lesser extent aphids, mites, viruses and nematodes. While the biology of the pathogen and insect vector of the Dutch elm disease has been intensively studied, less attention has been paid so far to the defence mechanisms of elms to other biotic stressors. This review highlights knowledge of direct and indirect elm defences against biotic stressors focusing on morphological, chemical and gene regulation aspects. First, we report how morphological defence mechanisms via barrier formation and vessel occlusion prevent colonisation and spread of wood- and bark-inhabiting fungi and bacteria. Second, we outline how secondary metabolites such as terpenoids (volatile terpenoids, mansonones and triterpenoids) and phenolics (lignans, coumarins, flavonoids) in leaves and bark are involved in constitutive and induced chemical defence mechanisms of elms. Third, we address knowledge on how the molecular regulation of elm defence is orchestrated through the interaction of a huge variety of stress- and defence-related genes. We conclude by pointing to the gaps of knowledge on the chemical and molecular mechanisms of elm defence against pest insects and diseases. An in-depth understanding of defence mechanisms of elms will support the development of sustainable integrated management of pests and diseases attacking elms.     

Mechanism of Zinc absorption in plants: uptake,transport, translocation and accumulation

Zinc (Zn) is an essential micronutrient for plants and animals. Unfortunately, deficiency of Zn in humans has increased on a global scale. The main reason of this micronutrient deficiency is dietary intakes of food with low Zn levels. Adoption of biofortification approaches would result in Zn enrichment of target tissue to a considerable extent. However, there is a basic need to understand Zn absorption mechanisms in plants prior to exploitation of such practical approaches. Zn absorption is a complex physiological trait which is mainly governed by Zn transporters and metal chelators of plant system. Plant growth stage, edaphic factors, season etc. also influence Zn efficiency of particular species. Molecular studies in Zn hyperaccumulators have already demonstrated the participation of specific Zn transporters, vacuolar sequestration and detoxification mechanisms in maintenance of Zn homeostasis. These have been described in detail in present review and provide opportunities for utilization in biofortification programmes. However, issues such as lesser bioavailability of Zn in target organ, uptake of toxic divalent cations (Cd, Ni, Pb, As etc.) along with Zn, sink activity and dilution in Zn concentration in response to sink number etc. in biofortified crops need further investigation. In order to design novel strategy in biofortification programmes, future researches should focus on physiological performance and yield penalties in concerned crop, metabolic load in term of organic acid production and crosstalk of Zn with other mineral nutrients under low and high Zn conditions.     

High-value products from macroalgae: the potential uses of the invasive brown seaweed<Emphasis Type="Italic">, Sargassum muticum</Emphasis>

Marine seaweeds represent an abundant source of natural products and may harbour valuable chemicals. The brown seaweed Sargassum muticum is an invasive species to the coasts of the British Isles, mainland Europe and North America. Attempts at its eradication and control have generally not been successful, although time-consuming and costly. Commercial exploration of this biomass for food, fuel and pharmaceutical products could encourage its harvesting and control. Though S. muticum might be unsuitable as a source of biofuel due to high ash and water content, this rapidly growing macroalga has a naturally high content of antioxidants, carotenoids and phenols, including the well-known anti-cancer compound fucoxanthin, making this species a potential source of a range of pharmaceutically relevant materials.     

Patients with heart failure with preserved ejection fraction and low levels of natriuretic peptides

Aims

Heart failure with preserved ejection fraction (HFpEF) is common and its management remains difficult. B-type natriuretic peptide (BNP) levels are used to diagnose heart failure, and as an entry criterion for inclusion into trials. We investigated a population of HFpEF patients who had been randomised into a study based on clinical parameters, and compared those with low BNP levels to those with elevated BNP levels.

Methods

We examined patients who had been enrolled in the Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure (COACH), with preserved left ventricular ejection fraction (LVEF ≥ 40 %), and compared those with low BNP (< 100 pg/ml; n = 30) to those with elevated BNP (≥ 100 pg/ml; n = 127). Baseline characteristics, comorbidities, biomarkers, quality of life, and outcome parameters (hospitalisations and death) were compared between the groups. To validate our findings, we repeated all analyses for NT-proBNP (< 300 pg/ml and ≥ 300 pg/ml).

Results

Patients were similar with regard to most clinical characteristics (including age, sex, and LVEF), biomarkers, and comorbidities. In contrast, patients with a low BNP had higher body mass index levels (31 kg/m² vs. 27 kg/m²; p < 0.01) and lower cardiac troponin I (9 pg/ml vs. 15 pg/ml; p = 0.02). In addition, these patients were less frequently prescribed diuretics and beta-blockers. No differences in quality of life, heart failure related symptoms and the primary and secondary outcomes were observed between these groups. These observations were confirmed for NT-proBNP.

Conclusion

Among the patients with clinically diagnosed HFpEF, those with low BNP are strikingly similar to those with elevated BNP levels, except for BMI, which was significantly higher in these patients.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-016-0816-8) contains supplementary material, which is available to authorized users.     

Treatment of pulmonary arterial hypertension in congenital heart disease in Singapore versus the Netherlands: age exceeds ethnicity in influencing clinical outcome

Background

Advanced treatment of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is increasingly applied worldwide following the—mainly Western world based—international PAH-CHD guidelines. However, studies comparing clinical presentation and outcome after the initiation of PAH-specific treatment are lacking. We aimed to analyse this in a Singaporean and Dutch cohort of PAH-CHD patients.

Methods

Adult CHD patients starting PAH-specific therapy, enrolled in two nationwide registries, were analysed. Patients received phosphodiesterase-type-5 inhibitors, endothelin receptor antagonists, or a combination. Change in six-minute walk test (6MWT) during follow-up was analysed using linear mixed model analysis. Determinants for mortality were assessed using Cox proportional hazard analyses.

Results

A total of 74 patients, 45 Dutch (mean age 47?±?14 years) and 29 Singaporean (mean age 41?±?14 years) were analysed. Despite a lower 6MWT (312 versus 395 metres, p?=?0.01) and peak VO₂ (35 versus 49?% of predicted, p?=?0.01) at baseline in Singaporean patients, the treatment effect was similar in the two populations. Age at initiation of therapy (per 5 year lower age, β?=?+?4.5, p?=?0.017) was the strongest predictor of improvement in exercise capacity, corrected for ethnicity, baseline 6MWT, sex and CHD defect.

Conclusions

Patients from Singapore had a worse clinical performance at baseline compared with the PAH-CHD patients from the Netherlands. No relation between ethnicity and improvement in 6MWT after PAH-specific therapy was found. Age at initiation of PAH-specific therapy was the strongest predictor of treatment efficacy and mortality, emphasising the need for early initiation of treatment in these patients.

     

Out-of-hospital cardiac arrest: the prospect of E-CPR in the Maastricht region

Aim

The current outcome of out-of-hospital cardiac arrest (OHCA) patients in the Maastricht region was analysed with the prospect of implementing extracorporeal cardiopulmonary resuscitation (E-CPR).

Methods

A retrospective analysis of adult patients who were resuscitated for OHCA during a 24-month period was performed.

Results

195 patients (age 66 [57–75] years, 82 % male) were resuscitated for OHCA by the emergency medical services and survived to admission at the emergency department. Survival to hospital discharge was 46.2 %. Notable differences between non-survivors and survivors were observed and included: age (70 [58–79] years) vs. (63 [55–72] years, p = 0.01), chronic heart failure (18 vs. 7 %, p = 0.02), shockable rhythm (67 vs. 99 %, p < 0.01), and return of spontaneous circulation (ROSC) at departure from the site of the arrest (46 vs. 99 %, p < 0.01) and on arrival to the emergency department (43 vs. 98 %, p < 0.01), respectively. Acute coronary syndrome was diagnosed in 32 % of non-survivors vs. 59 % among survivors, p < 0.01. Therapeutic hypothermia was provided in non-survivors (20 %) vs. survivors (43 %), p < 0.01. Percutaneous coronary intervention (PCI) was performed in 14 % of non-survivors while 52 % of survivors received PCI (p < 0.01). No statistical significance was observed in terms of gender, witnessed arrest, bystander CPR, or automated external defibrillator deployed among the cohort. At hospital discharge, moderately severe neurological disability was present in six survivors.

Conclusion

These observations are compatible with the notion that a shockable rhythm, ROSC, and post-arrest care improve survival outcome. Potentially, initiating E-CPR in the resuscitation phase in patients with a shockable rhythm and no ROSC might serve as a bridge to definite treatment and improve survival outcome.