Arsenic toxicity,mutagenesis, and carcinogenesis – a health risk assessment and management approach

A comprehensive analysis of published data indicates that arsenic exposure induces cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and various types of cancer. Although exposure may occur via the dermal, and parenteral routes, the main pathways of exposure include ingestion, and inhalation. The severity of adverse health effects is related to the chemical form of arsenic, and is also time- and dose-dependent. Recent reports have pointed out that arsenic poisoning appears to be one of the major public health problems of pandemic nature. Acute and chronic exposure to arsenic has been reported in several countries of the world where a large proportion of drinking water (groundwater) is contaminated with high concentrations of arsenic. Research has also pointed significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. There is therefore a great need for developing a comprehensive health risk assessment (RA) concept that should be used by public health officials and environmental managers for an effective management of the health effects associated with arsenic exposure. With a special emphasis on arsenic toxicity, mutagenesis, and carcinogenesis, this paper is aimed at using the National Academy of Science's RA framework as a guide, for developing a RA paradigm for arsenic based on a comprehensive analysis of the currently available scientific information on its physical and chemical properties, production and use, fate and transport, toxicokinetics, systemic and carcinogenic health effects, regulatory and health guidelines, analytical guidelines and treatment technologies.     

Milk derived bioactive peptides and their impact on human health – A review

Milk-derived bioactive peptides have been identified as potential ingredients of health-promoting functional foods. These bioactive peptides are targeted at diet-related chronic diseases especially the non-communicable diseases viz., obesity, cardiovascular diseases and diabetes. Peptides derived from the milk of cow, goat, sheep, buffalo and camel exert multifunctional properties, including anti-microbial, immune modulatory, anti-oxidant, inhibitory effect on enzymes, anti-thrombotic, and antagonistic activities against various toxic agents. Majority of those regulate immunological, gastrointestinal, hormonal and neurological responses, thereby playing a vital role in the prevention of cancer, osteoporosis, hypertension and other disorders as discussed in this review. For the commercial production of such novel bioactive peptides large scale technologies based on membrane separation and ion exchange chromatography methods have been developed. Separation and identification of those peptides and their pharmacodynamic parameters are necessary to transfer their potent functional properties into food applications. The present review summarizes the preliminary classes of bioactive milk-derived peptides along with their physiological functions, general characteristics and potential applications in health-care.     

Targeting improved resilience in Merino sheep – Correlations between immune competence and health and fitness traits

Resilience can be defined as the ability of an animal to remain productive in the face of diverse environmental challenges. Several factors contribute to an animal’s resilience including its ability to resist disease, cope with climatic extremes and respond to stressors. Immune competence, a proxy trait for general disease resistance, is expected to contribute to an animal’s resilience. This research aimed to develop a practical method to assess immune competence in Merino sheep which would not restrict the future sale of tested animals, and to estimate genetic parameters associated with the novel trait. We also aimed to explore associations between immune competence and other industry-relevant disease resistance and fitness-related traits and to assess the ability of immune competence phenotypes to predict health outcomes. Here, the ability of Merino wethers (n = 1 339) to mount both an antibody-mediated and cell-mediated immune response was used to define their immune competence phenotype. For that purpose, antigens in a commercial vaccine were administered at the commencement of weaning and their responses were assessed. Univariate sire models were used to estimate variance components and heritabilities for immune competence and its component traits. Bivariate sire models were used to estimate genetic correlations between immune competence and a range of disease resistance and fitness-related traits. The heritability of immune competence and its component traits, antibody-mediated immune response and cell-mediated immune response were estimated at 0.49 ± 0.14, 0.52 ± 0.14 and 0.36 ± 0.11, respectively. Immune competence was favourably genetically correlated with breech flystrike incidence (?0.44 ± 0.39), worm egg count (?0.19 ± 0.23), dag score (?0.26 ± 0.31) and fitness compromise (?0.35 ± 0.24) but not fleece rot (0.17 ± 0.23). Results suggest that selection for immune competence has the potential to improve the resilience of Merino sheep; however, due to the large standard errors associated with correlation estimates reported here, further studies will be required in larger populations to validate associations between immune competence and disease resistance and fitness traits in Australian Merino sheep.     

Cadmium and health in the 21st Century – historical remarks and trends for the future

The first health effect of cadmium (Cd) was lung damage, reported in workers already in the 1930's, while bone effects and proteinuria were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from cadmium pollution were issued in the 1970's. WHO, 1992, identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's population groups in China exposed to Cd via rice were studied and new information on skeletal, renal and reproductive toxicity of Cd was obtained in the ChinaCad project. There was a decrease in Bone Mineral Density (BMD), an increased prevalence of fractures and an increased urinary content of marker proteins of renal dysfunction among persons with long term exposure to Cd. The development of such biomarkers can be seen as a result of applied 'proteomics' research. Variation in metallothionein gene expression was related to development of renal dysfunction, supporting the usefulness of this 'genomic' approach. The ongoing rapid development of 'genomics' and 'proteomics' technologies will improve possibilities for molecular epidemiology studies in the future, providing an even better basis for preventive action. In many countries, Cd exposures are now under better control than in the past. The target for the 21st century is to achieve a totally acceptable exposure situation without adverse health effects from Cd.     

Controlling the risks to health and environment from biotechnology — what is the European Community doing?

The EEC is an economic community which must endeavour to unify the regulation of trade and environment among its member states. The establishment of international regulatory standards in biotechnology will be relatively less hindered by entrenched national legislation and practices than in other industrial sectors. Rapid progress towards a common biotechnology market will benefit both manufacturers and research in Europe, and provide common standards of health and environmental protection.     

Marine biodiversity and ecosystem functioning: what's known and what's next?

Marine ecosystems are experiencing rapid and pervasive changes in biodiversity and species composition. Understanding the ecosystem consequences of these changes is critical to effectively managing these systems. Over the last several years, numerous experimental manipulations of species richness have been performed, yet existing quantitative syntheses have focused on a just a subset of processes measured in experiments and, as such, have not summarized the full data available from marine systems. Here, we present the results of a meta‐analysis of 110 marine experiments from 42 studies that manipulated the species richness of organisms across a range of taxa and trophic levels and analysed the consequences for various ecosystem processes (categorised as production, consumption or biogeochemical fluxes). Our results show that, generally, mixtures of species tend to enhance levels of ecosystem function relative to the average component species in monoculture, but have no effect or a negative effect on functioning relative to the ‘highest‐ performing’ species. These results are largely consistent with those from other syntheses, and extend conclusions to ecological functions that are commonly measured in the marine realm (e.g. nutrient release from sediment bioturbation). For experiments that manipulated three or more levels of richness, we attempted to discern the functional form of the biodiversity–ecosystem functioning relationship. We found that, for response variables related to consumption, a power‐function best described the relationship, which is also consistent with previous findings. However, we identified a linear relationship between richness and production. Combined, our results suggest that changes in the number of species will, on average, tend to alter the functioning of marine ecosystems. We outline several research frontiers that will allow us to more fully understand how, why, and when diversity may drive the functioning of marine ecosystems. Synthesis The oceans host an incredible number and variety of species. However, human activities are driving rapid changes in the marine environment. It is imperative we understand ecosystem consequences of any associated loss of species. We summarized data from 110 experiments that manipulated species diversity and evaluated resulting changes to a range of ecosystem responses. We show that losing species, on average, decreases productivity, growth, and a myriad of other processes related to how marine organisms capture and utilize resources. Finally, we suggest that the loss of species may have stronger consequences for some processes than others.     

Do physicians assess lifestyle health risks during general medical examinations? A survey of general practitioners and obstetrician-gynecologists in Quebec

BACKGROUND: In Canada several guidelines have been published for the screening of lifestyle health risks during general medical examinations. The authors sought to examine the extent to which such screening practices have been integrated into medical practice, to measure physicians'' perceived level of difficulty in assessing these risks and to document physicians'' evaluation of their formal medical training in lifestyle risk assessment. METHODS: An anonymous mail survey was conducted in 1995 in Quebec with a stratified random sample of 1086 general practitioners (GPs) and with all 241 obstetrician-gynecologists (Ob-Gyns). The authors evaluated the proportion of physicians who reported routine assessment (with 90% or more of their patients) of substance use, family violence and sexual history during general medical examinations of adult and adolescent patients; the proportion of those who find inquiring about these issues difficult; and the proportion of those who evaluated their medical training in lifestyle risk assessment as adequate or excellent. RESULTS: The overall response rate was 72.6%. Among adult patients, 82.2% of the GPs reported routinely assessing tobacco use, 67.2% alcohol consumption, 34.2% illicit drug use and 3.2% family violence; the corresponding proportions for assessment among adolescent patients were 77.1%, 61.8%, 52.9% and 5.6%. Comparatively fewer Ob-Gyns reported routinely assessing these issues (56.1%, 28.6%, 20.4% and 1.3% respectively among adults and 62.7%, 35.2%, 26.8% and 2.8% respectively among adolescents). In the area of sexual history, condom use was routinely assessed by more Ob-Gyns than GPs (47.0% v. 28.2%); however, the proportion of Ob-Gyns and GPs was equally low for assessing number of partners (24.8% and 23.1%), sexual orientation (18.8% and 16.9%) and STD risk (26.2% and 21.2%). The vast majority of GPs and Ob-Gyns reported finding it difficult to assess family violence (86.5% and 93.0%) and sexual abuse (92.7% and 92.4% respectively). Over 80% of the physicians felt that they had had adequate or excellent medical training in assessing risk behaviours for heart disease and STD risk. The proportion who felt this way about their training in screening for illicit drug use, family violence and sexual abuse ranged between 12.7% and 31.6%. INTERPRETATION: Although morbidity and mortality associated with smoking, alcohol consumption, illicit drug use, unsafe sexual practices, family violence and sexual abuse have been well documented, routine screening for these risk factors during general medical examinations has yet to be integrated into medical practice.     

Actin-associated proteins and cardiomyopathy—the ‘unknown’ beyond troponin and tropomyosin

It has been known for several decades that mutations in genes that encode for proteins involved in the control of actomyosin interactions such as the troponin complex, tropomyosin and MYBP-C and thus regulate contraction can lead to hereditary hypertrophic cardiomyopathy. In recent years, it has become apparent that actin-binding proteins not directly involved in the regulation of contraction also can exhibit changed expression levels, show altered subcellular localisation or bear mutations that might lead to hereditary cardiomyopathies. The aim of this review is to look beyond the troponin/tropomyosin mechanism and to give an overview of the different types of actin-associated proteins and their potential roles in cardiomyocytes. It will then discuss recent findings relevant to their involvement in heart disease.     

An RGA – like marker detects all known Lr21 leaf rust resistance gene family members in Aegilops tauschii and wheat

Leaf rust is one of the most important diseases of wheat worldwide, particularly in the Great Plains region of the USA. One long-term strategy for the control of this disease may be through durable genetic resistance by gene pyramiding. An important step in this strategy is identifying molecular markers linked to different leaf rust-resistance genes. Here we report the molecular tagging of a leaf rust-resistance gene that may have the potential for durable resistance through further genetic manipulation and gene pyramiding. Lr39 was previously designated for a leaf rust-resistance gene introgressed from Aegilops tauschii accession TA1675 into the common wheat germplasm WGRC2. Lr40 was designated for a gene derived from Ae. tauschii accession TA1649 and is present in germplasm WGRC7. These genes are now believed to be allelic to Lr21, which was transferred to wheat from a different accession of Ae. tauschii. Molecular mapping of Lr39 and Lr40 indicates that both genes come from TA1649. WGRC2 and WRGC7 also have a similar infection type against rust culture PRTUS6. We suggest the designation of the gene in WGRC2 should be changed to Lr40. RFLP marker KSUD14 (locus Xksud14) was found 0.2-cM proximal to Lr40 in a WGRC2/Wichita F₂ population (218 individuals), and co-segregated with the gene in a WGRC7/ Wichita F₂ population (165 individuals). A PCR-based molecular marker developed from the sequence-tagged-site (STS) of Xksud14 was mapped to the same locus as the RFLP marker KSUD14 in both populations. KSUD14 has the structure of a resistance gene analog (RGA) including kinase2a and kinase3 domains similar to the Cre3 gene of wheat and the rust resistance gene Rp1-D of maize. When the PCR products amplified from KSU14 STS were cleaved with restriction enzyme MspI, an 885-bp fragment was found in WGRC2, WGRC7, the Lr21 near-isogenic line, and eight accessions of Ae. tauschii shown to have resistance gene alleles at the Lr21 locus. The KSUD14 PCR-based assay provides an excellent marker for Lr40 and Lr21 in diverse wheat breeding and wild Ae. tauschii populations. Received: 22 December 2000 / Accepted: 12 February 2001     

INFLAM – INFLAMmation in Brain and Vessels with Iron Nanoparticles and Cell Trafficking: A Multiscale Approach of Tissue Microenvironment,Iron Nanostructure and Iron Biotransformation

Background

Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke.

Marine chemical ecology: what''s known and what''s next?

In this review, I summarize recent developments in marine chemical ecology and suggest additional studies that should be especially productive. Direct tests in both the field and laboratory show that secondary metabolites commonly function as defenses against consumers. However, some metabolites also diminish fouling, inhibit competitors or microbial pathogens, and serve as gamete attractants; these alternative functions are less thoroughly investigated. We know little about how consumers perceive secondary metabolites or how ecologically realistic doses of defensive metabolites affect consumer physiology or fitness, as opposed to feeding behavior. Secondary metabolites have direct consequences, but they do not act in isolation from other prey characteristics or from the physical and biological environment in which organisms interact with their natural enemies. This mandates that marine chemical ecology be better integrated into a broader and more complex framework that includes aspects of physiological, population, community, and even ecosystem ecology. Recent advances in this area involve assessing how chemically mediated interactions are affected by physical factors such as flow, desiccation, UV radiation, and nutrient availability, or by biological forces such as the palatability or defenses of neighbors, fouling organisms, or microbial symbionts. Chemical defenses can vary dramatically among geographic regions, habitats, individuals within a local habitat, and within different portions of the same individual. Factors affecting this variance are poorly known, but include physical stresses and induction due to previous attack. Studies are needed to assess which consumers induce prey defenses, how responses vary in environments with differing physical characteristics, and whether the ‘induced’ responses are a direct response to consumer attack or are a defense against microbial pathogens invading via feeding wounds. Although relatively unstudied, ontogenetic shifts in concentrations and types of defenses occur in marine species, and patterns of larval chemical defenses appear to provide insights into the evolution of complex life cycles and of differing modes of development among marine invertebrates. The chemical ecology of marine microbes is vastly underappreciated even though microbes produce metabolites that can have devastating indirect effects on non-target organisms (e.g., red tide related fish kills) and significantly affect entire ecosystems. The natural functions of these metabolites are poorly understood, but they appear to deter both consumers and other microbes. Additionally, marine macro-organisms use metabolites from microbial symbionts to deter consumers, subdue prey, and defend their embryos from pathogens. Microbial chemical ecology offers unlimited possibilities for investigators that develop rigorous and more ecologically relevant approaches.     

Editorial – Clonal plants and environmental heterogeneity – space, time and scale

The fifth Clonal Plant Workshop entitled 'Clonal plants and environmental heterogeneity – space, time and scale' was held at the University of Wales, Bangor, from the 9th to the 14th September 1997. The workshops began in 1988, when a small group of plant scientists with different backgrounds met in the Netherlands to discuss plant clonality. This meeting was followed by workshops in 1990, 1992 and 1995 in Sweden, the Czech Republic and Hungary, respectively. The purpose of the Bangor meeting was to continue to integrate knowledge from a wide range of biological disciplines to attempt a better understanding of clonal plants in the context of the heterogeneous environments in which they occur. This special issue is a collection of a number of the presentations at the Bangor workshop. The effects of spatial and temporal environmental heterogeneity on individuals, populations and communities are, of course, diverse, and this collection of papers is not intended to provide a synthesis of the ecological consequences of environmental heterogeneity. Rather, this special issue more accurately reflects progress in various areas of clonal plant research including population dynamics of ramets and genets, mathematical modelling and molecular techniques. We wish to thank all participants of the workshop for their contribution and trust that they found the meeting as stimulating and enjoyable as we did. We are indebted to the authors and the many referees for their friendly cooperation and to Plant Ecology for publishing the proceedings. We also gratefully acknowledge the financial support of the following that made the workshop possible: The British Ecological Society, The Tansley Fund of the New Phytologist Trust, The Countryside Council for Wales, The Institute of Terrestrial Ecology (Bangor) and Skye Instruments Ltd, Wales.     

Preparation and Characterization of SDF-1α-Chitosan-Dextran Sulfate Nanoparticles

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under appropriate conditions. The glycan nanoparticles are useful carriers for protein factors, which facilitate the in vivo delivery of the proteins and sustain their retention in the targeted tissue. The glycan polyelectrolyte complexes are also ideal for protein delivery, as the incorporation is carried out in aqueous solution, which reduces the likelihood of inactivation of the proteins. Proteins with a heparin-binding site adhere to dextran sulfate readily, and are, in turn, stabilized by the binding. These particles are also less inflammatory and toxic when delivered in vivo. In the protocol described below, SDF-1α (Stromal cell-derived factor-1α), a stem cell homing factor, is first mixed and incubated with dextran sulfate. Chitosan is added to the mixture to form polyelectrolyte complexes, followed by zinc sulfate to stabilize the complexes with zinc bridges. The resultant SDF-1α-DS-CS particles are measured for size (diameter) and surface charge (zeta potential). The amount of the incorporated SDF-1α is determined, followed by measurements of its in vitro release rate and its chemotactic activity in a particle-bound form.     

Magnetic–Plasmonic FePt@Ag Core–Shell Nanoparticles and Their Magnetic and SERS Properties

Magnetic–plasmonic FePt@Ag core–shell nanoparticles (NPs) with different Ag shell thicknesses were successfully synthesized using a seed-mediated method. They presented not only localized surface plasmon resonance in the visible region, but also superparamagnetic behavior at room temperature. When normalized by the weight of FePt, the saturation magnetization of the FePt@Ag NPs was found to be higher than that of FePt NPs, suggesting that the Ag shell effectively passivated the FePt NP surfaces, avoiding the direct interaction between the FePt core and surface capping ligands that typically forms a magnetically dead layer in FePt NPs. Despite the high colloidal stability and the small size of the FePt@Ag NPs, the NPs were easily separated using a permanent magnet. The surface enhanced Raman scattering (SERS) activity of the FePt@Ag NPs was then examined using thiophenol as a Raman reporter molecule and was found to be equivalent to that of Ag NPs. Moreover, the SERS activity of the FePt@Ag NPs was enhanced when a magnetic field was applied during the preparation of the SERS substrate (FePt@Ag NP film). These FePt@Ag NPs hold promise as dual-functional sensing probes for environmental and diagnostic applications.     

Wonder or evil?: Multifaceted health hazards and health benefits of Cannabis sativa and its phytochemicals

Cannabis sativa, widely known as ‘Marijuana’ poses a dilemma for being a blend of both good and bad medicinal effects. The historical use of Cannabis for both medicinal and recreational purposes suggests it to be a friendly plant. However, whether the misuse of Cannabis and the cannabinoids derived from it can hamper normal body physiology is a focus of ongoing research. On the one hand, there is enough evidence to suggest that misuse of marijuana can cause deleterious effects on various organs like the lungs, immune system, cardiovascular system, etc. and also influence fertility and cause teratogenic effects. However, on the other hand, marijuana has been found to offer a magical cure for anorexia, chronic pain, muscle spasticity, nausea, and disturbed sleep. Indeed, most recently, the United Nations has given its verdict in favour of Cannabis declaring it as a non-dangerous narcotic. This review provides insights into the various health effects of Cannabis and its specialized metabolites and indicates how wise steps can be taken to promote good use and prevent misuse of the metabolites derived from this plant.     

Lipoxygenases – Structure and reaction mechanism

Lipid oxidation is a common metabolic reaction in all biological systems, appearing in developmentally regulated processes and as response to abiotic and biotic stresses. Products derived from lipid oxidation processes are collectively named oxylipins. Initial lipid oxidation may either occur by chemical reactions or is derived from the action of enzymes. In plants this reaction is mainly catalyzed by lipoxygenase (LOXs) enzymes and during recent years analysis of different plant LOXs revealed insights into their enzyme mechanism. This review aims at giving an overview of concepts explaining the catalytic mechanism of LOXs as well as the different regio- and stereo-specificities of these enzymes.     

Aspergillus-specific antibodies – Targets and applications

Aspergillus is a fungal genus comprising several hundred species, many of which can damage the health of plants, animals and humans by direct infection and/or due to the production of toxic secondary metabolites known as mycotoxins. Aspergillus-specific antibodies have been generated against polypeptides, polysaccharides and secondary metabolites found in the cell wall or secretions, and these can be used to detect and monitor infections or to quantify mycotoxin contamination in food and feed. However, most Aspergillus-specific antibodies are generated against heterogeneous antigen preparations and the specific target remains unknown. Target identification is important because this can help to characterize fungal morphology, confirm host penetration by opportunistic pathogens, detect specific disease-related biomarkers, identify new candidate targets for antifungal drug design, and qualify antibodies for diagnostic and therapeutic applications. In this review, we discuss how antibodies are raised against heterogeneous Aspergillus antigen preparations and how they can be characterized, focusing on strategies to identify their specific antigens and epitopes. We also discuss the therapeutic, diagnostic and biotechnological applications of Aspergillus-specific antibodies.