Orthogonal subspace signal processing algorithms (OSPA) have been developed to extract the optical thickness of a porous silicon layer to within one part in 105 from its reflectivity spectrum. This is equivalent to a limit of detection (LOD) of ∼40 pm change in optical thickness for a 3 µm thick layer, or an LOD of 1/2000 of a monolayer coverage with antibodies, of molecular weight 160 k Daltons, within a layer with pores of 100 nm diameter. A large molecule {horseradish peroxidase (HRP), MWt 40 kDa} has been detected at a concentration of 1 µg/ml by measuring its direct binding to anti‐HRP antibodies immobilised within a porous silicon layer. A competitive assay has been demonstrated for the detection of a small molecule {2, 4, 6 trinitrotoluene (TNT), MWt 227 Da} at 10 µg/ml. The projected LODs for HRP and TNT by these assays are 50 ng/ml and 1 µg/ml respectively. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Rates of neurodevelopmental handicap are high among extremely low birthweight survivors, and the first 48 postnatal hours probably give the greatest opportunity for preventing damage. However, at this time, families are in turmoil and may have difficulty in coming to terms with a small baby in intensive care. We recently had to abandon an observational, non-invasive study because of practical difficulties arising from the new Research Governance Framework,1 and we would like to share this experience, and its implications, with the research community. We needed parental consent for …

The sensitivity of the optical reflectivity of porous silicon structures to the refractive index of liquid within the pores is studied for a single layer, a Bragg mirror and a microcavity. Sucrose solutions of concentration in the range 0.05 to 1.0% by weight are introduced into the pores within a flow cell in order to change the refractive index of the liquid in the pores from 1.3330 to 1.3344. Optimum wavelengths for detection via reflectivity changes are determined based on a signal to noise analysis. The optical thickness of the single layer is also monitored by measuring the fringe spacing via a Fourier transform technique. It is just possible to detect the effect of a change in refractive index of liquid in the pores of 0.00007 for both the reflectivity and optical thickness approaches.

To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently large to allow easy ingress of reagents and the layer must also display Fabry-Perot optical cavity modes. Here the detection antibody is rabbit IgG and the analyte is a-rabbit Ige conjugated to horseradish peroxidase (HRP). For. this model system, the pores should be >50 nm in diameter. Such diameters have been obtained in 0.05 Omega cm n-type silicon using anodisation followed by chemical etching in ethanolic KOH and also, by anodising 0.005 Omega cm p-type material. The latter also displays optical cavity modes. Tnt: silicon surface is oxidised in ozone, silanised using aminopropyl-methoxysilanes with one, two or three methoxy groups, and cross linked to Ige using glutaraldehyde. High specific binding is found fur mono-, di- and tri-methoxy silanes, but the lowest nonspecific binding is found fur silanisation with the tri-methoxy silane.

The ability of selected food colours to interact with isolated guinea-pig ileum was investigated using a gut bath system. Studies revealed that guinea-pig ileum was specifically sensitive to tartrazine. Intestinal contraction occurred dose-dependently down to a minimum effective dose of 10 μM. All other colours examined proved negative. Studies investigating the biological activity of structural analogues of tartrazine revealed the ability to initiate intestinal contraction was associated with the presence of the carboxylic acid residue at the R l position of the pyrazole ring. Blocking studies showed that tartrazine contraction was inhibited by atropine alone but not by any other blocking agent tested, implying that tartrazine acts either directly or indirectly upon the muscarinic acetylcholine receptor associated with parasympathetic innervation.

Confronted with the decision to initiate dialysis, patients and caregivers often seek information about how expected survival chances evolve, both initially and afterward, providing the patient survives beyond arbitrary periods of time. Large registry data, used to examine these issues, may be subject to early ascertainment bias, such as those accruing from nonregistration of with end-stage kidney disease who die shortly after dialysis initiation and inclusion of patients with acute kidney injury with slower than typical recovery rates. Despite these caveats, available studies have suggested that mortality hazards are much higher in the first 3 months of renal replacement therapy. Prominent modifiable associations of early mortality include late referral to nephrology services, initial dialysis with vascular catheters, and, most problematically, higher glomerular filtration rates at initiation of renal replacement therapy. Despite their imperfections, currently available information is relatively user-unfriendly and could be better leveraged to help patients and treatment teams make better decisions.

Part 1 The basis of the immune system - cells of the immune system regulation of the immune system by pharmacological and biological mediators homeostatic mechanisms in the immune response. Part 2 Immunotoxicology (current concepts): toxic consequences of chemical interactions with the immune system adverse immunological effect of drugs and other chemicals and methods to detect them contact sensitivity the lung as a target organ intolerance and allergic reactions to food components and additives the effect of nutrition on the immune system psychoneuroimmunology interaction between the immune system, endocrine system and nervous system. Part 3 Specific examples relating to the immunotoxic/health effects of chemicals: mineral dusts - asbestos, silica and others occupational asthma and allergic reactions to inhaled chemicals PCB intoxication TCDD intoxication, toxic oil and others. Part 4 Methods of assessing immunotoxic events in experimental systems: hypersensitivity - adverse drug reaction histopathological approaches specific immuno function assays integrating in vitro systems with animal models in mechanistic studies of immunotoxic agents molecular immunotoxicology concluding remarks.

In order to verify the effect of social behavior and geographical isolation on the genetic structure of the Himalayan marmot (Marmota himalayana) population, we examined the genetic diversity of Himalayan marmots alongside the Qinghai–Tibet Railway using microsatellite markers. Eight microsatellite loci were used to examine 120 animals of 4 populations: Ulan (U), Delhi (D), Tuotuohe (T) and Ando (A). The results show that: (1) Himalayan marmots alongside the Qinghai–Tibet Railway are highly genetically diversified. The allele number (Na), effective allele number (Ne), observed heterozygosity (Ho), Nei’s expected heterozygosity (He) and polymorphism information content (PIC) of the total Himalayan marmot population were 4.75, 3.0332, 0.6990, 0.6672, 0.6102, respectively. (2) Himalayan marmots may be able to avoid inbreeding by a mechanism that will prevent the genetic diversity reduction caused by their social lifestyle. Heterozygote excess was observed at most loci. The inbreeding coefficients within the subpopulation (FIS), in the total population (FIT), the differentiation index of population (FST), and the gene flow (Nm) were −0.2265, −0.0477, 0.1458, and 1.4646, respectively. (3) The genetic differentiation of the Himalayan marmot population was in accordance with Wright’s “isolation by distance” theory. The Mantel test indicates that the correlation between genetic distance and geographic distance was significant (P < 0.05, r = 0.698). (4) Each of the four geographical populations had moderate differentiation. Both geographic distance and isolation could affect the population genetic structure of the Himalayan marmot. The maximum gene flow (3.5915), the smallest genetic differentiation index (0.0651), the lowest genetic distance (0.0700) and the highest genetic identity (0.9526) were all between the Ulan population and Delhi populations. (5) The cluster analysis, based on Nei’s standard genetic distance, showed that the populations of Delhi and Ulan were first merged in a cluster, and then Tuotuohe population was merged in the clustering. The Ando population was the last element in the clustering.

Carrageenans are a group of high molecular weight sulphated polygalactans which find extensive use in the food industry as thickening, gelling and protein-suspending agents. Although there is no evidence to suggest that the persorption of small amounts of carrageenans across the intestinal barrier poses an acute toxic hazard, they are known to be biologically active in a number of physiological systems and extended oral administration in laboratory animals has been shown to modify both in vivo and in vitro immune competence. Whereas this effect could be attributed to carrageenan having a selective toxic effect on antigen-processing macrophages, additional studies suggest that macrophages can also influence immune responses by the timed release of immunoregulatory mediators. Evidence in support of this comes from in vitro studies which demonstrate that carrageenan-treated macrophages can, depending on conditions and time of administration, release either stimulatory or inhibitory factors. The former is known to be the immunostimulatory agent interleukin 1 (IL-1). The inhibitory factor, which is produced at an early stage following exposure to non-toxic doses of carrageenans, has yet to be formally identified but it is believed to be a prostaglandin because of its specific mode of action and short biological half-life. At present it is impossible to relate these studies to the human situation. Although it is established that carrageenans can cross the intestinal barrier of experimental animals, there is no evidence to suggest that the limited uptake that may occur in man in any way interferes with normal immune competence. Nevertheless, increased exposure may occur in the neonate during weaning, and adults and children following allergic reactions and episodes of gastrointestinal disease. Further studies under such conditions now seem warranted in order to elucidate the possible immunological consequences which may be associated with enhanced uptake of carrageenans in vulnerable groups.

Organotins are currently one of the most studied groups of organometallic compounds; their novel and often unique chemical properties have intrigued chemists for over 100 years and, today, many of these compounds find extensive use in agriculture and industry. Over the years, however, a number of the organotins have been demonstrated to be toxic and there is now increasing concern that their widespread use may cause adverse effects within environmental and biological systems. This article reviews and updates the current literature concerning organotin toxicology. It identifies the various target organs and systems, discusses mechanisms and species susceptibility, and directs the reader to additional sources of more specialized information as appropriate.

Iota-carrageenan can both enhance agglutinating antibody responses and trigger reaginic antibody production against a protein associated antigen in rats. The present study investigates the strain specificity of this phenomenon and compares the adjuvanticity of high and low molecular weight iota-carrageenan with a series of structurally distinct polysaccharides (pectin, pectic acid, dextran and dextran sulphate). Using ovalbumin as the test antigen, high molecular weight iota-carrageenan induced a potent ovalbumin specific reaginic antibody response in PVG and Hooded Lister strain rats, an intermediate response in Sprague Dawley rats and a weak response in DA, AO and F344 strain rats. Further studies in PVG rats revealed that the nature and magnitude of the antibody response induced was influenced by the type of polysaccharide carrier used. Thus, whereas, high molecular weight carrageenan enhanced the agglutinating antibody (agglutinin) response and simultaneously elicited de novo reaginic antibody production to co-administered ovalbumin, low molecular weight carrageenan facilitated reaginic antibody production but had no effect on the agglutinin response. Pectin and dextran had no effect on the agglutinin response and failed to elicit reaginic antibody production. Conversely, pectic acid and dextran sulphate enhanced the agglutinin response and elicited a transient reaginic anti-ovalbumin response.

Experimental studies using rats have shown that small quantitites of orally administered carrageenan accumulate in the Peyer’s patches and caecal lymph node prior to transport to the mesenteric lymph node and peripheral tissues. Whilst there is no evidence to suggest that the persorption of small amounts of carrageenan across the intestinal barrier in any way poses an acute toxic hazard, carrageenan is a biologically active molecule (Di Rosa, 1972) and its extended oral administration was shown to modify systemic immune competence (see Nicklin and Miller, 1984 plus Nicklin, Baker & Miller in this volume). Whereas this effect could be attributed to carrageenan having a selective toxic effect on antigen processing macrophages, additional studies suggest that macrophages may also influence immune responses by the release of immunoregulatory mediators. In view of the continuing wide application of carrageenan in the food and drug industry an investigation into the effects of this material on the immunoregulatory role of macrophages was considered particularly relevant. The present study described a series of experiments designed to determine whether macrophages treated with toxic/subtoxic doses of carrageenan are capable of affecting lymphocyte activity in vitro.

Carrageenan is the generic name given to high-molecular-weight( 100,000 daltons) sulphated polygalactans derived from certain species of red algae. Three basic types can be isolated: k, i, and 1. These have differing colloidal properties and are characterised by the type of intergalactan bonding and the degree of sulphation (Rees, 1972).Carrageenans are used extensively in the food industry as thickening, gelling and protein-suspending agents. Initially, all grades of carrageenan were considered safe by the Food and Drug Administration(FDA, 1959) and were permitted for use as regulated food additives (FDA, 1969). However, subsequent reports implicated degraded forms of carrageenan (mol wt 30,000) in the induction of ulcers and metaplastic changes in the intestinal tract of a number of species of experimental animals (Fabian, et al., 1973; Sharratt, et al., 1970; Watt & Marcus, 1970). Although some of these findings were contested by other studies (Maillet, et al., 1970; Sharratt, et al., 1971) the FDA ruled that food-grade carrageenans should have an average molecular weight exceeding 100,000 (FDA, 1972). It is known however that carrageenans may undergo some degree of hydrolysis at gastric pH (Stoloff, 1959; Glicksman, 1969) and a small proportion of the lower molecular weight polygalactan units produced can apparently gain access to the body tissues by persorption (Pittman, et al., 1976).

Virus-associated mass mortalities among several marine mammal populations inhabiting industrialized coastal areas have generated an interest in wildlife immunotoxicology. Despite the isolation of previously uncharacterized viruses from victims, a contribution of immunotoxic contaminants to the severity of the outbreaks could not be ruled out. Fish-eating marine mammals, including seals, occupy high trophic levels in the aquatic food chain, and accumulate high levels of contaminants including polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychorinated dibenzofurans (PCDFs). Such chemicals have been found to be immunotoxic at low doses in studies of laboratory animals. While associations have been established between environmental contaminants and various adverse biological effects in certain free-ranging seal populations, evidence for immunotoxicity has, until recently, been lacking. To this end, we carried out an immunotoxicological study, in which captive harbor seals were fed herring from either relatively uncontaminated sites of the Atlantic Ocean, or from the highly contaminated Baltic Sea. In this review, we summarize the contaminant-related immunosuppression observed in the captive group of seals fed herring from the Baltic Sea, and discuss these results in the context of what is currently known about outbreaks of virus infection, comparative immunology, and environmental contaminants. We also describe two parallel studies, in which laboratory rats exposed as adults or perinatally to the contaminants in the Baltic Sea herring, exhibited immunotoxicity. On the basis of these and other studies, we conclude that complex mixtures of environmental contaminants may represent a real immunotoxic risk to free-ranging marine mammals in many areas of Europe and North America.