Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males.

Background: The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis.

Objectives: The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture.

The human placental proteome is affected by maternal smoking.

Detrimental effects of maternal smoking on the term placental proteome and steroid-metabolizing activities, and maternal hormone levels, were studied by using seven non-smoker and seven smoker placentae. Smoking significantly affected 18% of protein spots. The functional networks affected were i) cell morphology, cellular assembly and organization, cellular compromise (15 hits) and ii) DNA replication, recombination, and repair, energy production, nucleic acid metabolism (6 hits).

The fetal ovary exhibits temporal sensitivity to a 'real-life' mixture of environmental chemicals.

The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence. Prolonged exposure to environmental chemicals (ECs) can perturb this process with detrimental consequences for offspring. Here we report on the exposure of pregnant ewes to an environmental mixture of ECs derived from pastures fertilized with sewage sludge (biosolids): a common global agricultural practice.

Exposure to chemical cocktails before or after conception--- the effect of timing on ovarian development.

Exposure of female fetuses to environmental chemicals (ECs) during pregnancy results in a disturbed ovarian adult phenotype. We investigated the influence of pre- and/or post-conception exposure to low-level mixtures of ECs on the structure and function of the fetal ovine ovary. We examined ovarian morphology, expression of oocyte and granulosa cell-specific genes and proteome.

Use of a computerized order set to increase prescription of calcium and vitamin D supplementation in patients receiving glucocorticoids.

Background: American College of Rheumatology guidelines recommend that patients taking glucocorticoids also take calcium and vitamin D supplements, regardless of the dose or intended duration of glucocorticoid use, to decrease their risk of glucocorticoid-induced osteopenia or osteoporosis (GIOP).

Objective: To increase the number of prescriptions made for calcium and vitamin D in patients who receive a prescription for glucocorticoids using an automated, computerized order set.

Design: Pre-post test design.

Peri-conceptional changes in maternal exposure to sewage sludge chemicals disturbs fetal thyroid gland development in sheep.

Ewes were exposed to sewage sludge-fertilized pastures in a study designed investigate pre-conceptual and/or gestational exposure to environmental chemicals. The in utero impact on fetal thyroid morphology and function at day 110 (of 145) of pregnancy was then determined. Pre-conceptual exposure increased the relative thyroid organ weights in male fetuses.

Impact of sublethal levels of environmental pollutants found in sewage sludge on a novel Caenorhabditis elegans model biosensor.

A transgenic strain of the model nematode Caenorhabditis elegans in which bioluminescence reports on relative, whole-organism ATP levels was used to test an environmentally-relevant mixture of pollutants extracted from processed sewage sludge. Changes in bioluminescence, following exposure to sewage sludge extract, were used to assess relative ATP levels and overall metabolic health. Reproductive function and longevity were also monitored.

Effects of exposure to environmental chemicals during pregnancy on the development of the male and female reproductive axes.

There is a large body of literature describing effects of environmental chemicals (ECs), many of them anthropogenic with endocrine-disrupting properties, on development in rodent laboratory species, some of which lead to impaired reproduction and adverse health. This literature joins extensive human epidemiological data and opportunistic wildlife findings on health effects of ECs. In contrast, the effect of endocrine disruption on foetal development and reproductive performance in domestic species is less extensively documented.

Foetal and post-natal exposure of sheep to sewage sludge chemicals disrupts sperm production in adulthood in a subset of animals.

Exposure to ubiquitous, environmental chemicals (ECs) has been hypothesized as a cause for declining male reproductive health. Understanding the long-term effects of EC exposure on reproductive health in humans requires animal models and exposure to 'real life', environmentally relevant, mixtures during development, a life stage of particular sensitivity to ECs. The aim of this study was to evaluate the effects of in utero and post-natal exposure to environmentally relevant levels of ECs, via sewage sludge application to pasture, on the adult male sheep testis.

Impact of endocrine-disrupting compounds (EDCs) on female reproductive health.

Evidence is accumulating that environmental chemicals (ECs) including endocrine-disrupting compounds (EDCs) can alter female reproductive development, fertility and onset of menopause. While not as clearly defined as in the male, this set of abnormalities may constitute an Ovarian Dysgenesis Syndrome with at least some origins of the syndrome arising during foetal development. ECs/EDCs have been shown to affect trophoblast and placental function, the female hypothalamo-pituitary-gonadal axis, onset of puberty and adult ovarian function.

Maternal and fetal tissue accumulation of selected endocrine disrupting compounds (EDCs) following exposure to sewage sludge-treated pastures before or after conception.

Liver concentrations of selected pollutant classes were determined in groups of sheep fetuses and their dams, at 55 (Experiment 1) and 110 (Experiment 2) days of gestation (term = 145 d) following exposure, throughout their breeding lives and after mating, to pasture treated with either inorganic fertiliser (control, CC) or with sewage sludge (treated, TT). In a unique study designed to separate the respective contributions of environmental sources and mobilised tissue to the available EDC burden, in additional groups of animals, pollutant burdens at 110 days gestation were assessed following exposure to the respective treatments, either throughout their breeding lives until mating, but not thereafter (TC), or only between mating and slaughter (CT) (Experiment 3). With very few exceptions, maternal and fetal liver concentrations of diethylhexyl phthalate (DEHP) and selected polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDE) and polycyclic aromatic hydrocarbons (PAHs) were not significantly affected by sludge exposure in any group.

Effects of environmental pollutants on the reproduction and welfare of ruminants.

Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone.

Foetal hypothalamic and pituitary expression of gonadotrophin-releasing hormone and galanin systems is disturbed by exposure to sewage sludge chemicals via maternal ingestion.

Animals and humans are chronically exposed to endocrine disrupting chemicals (EDCs) that are ubiquitous in the environment. There are strong circumstantial links between environmental EDC exposure and both declining human/wildlife reproductive health and the increasing incidence of reproductive system abnormalities. The verification of such links, however, is difficult and requires animal models exposed to 'real life', environmentally relevant concentrations/mixtures of environmental contaminants (ECs), particularly in utero, when sensitivity to EC exposure is high.

Exposure to a complex cocktail of environmental endocrine-disrupting compounds disturbs the kisspeptin/GPR54 system in ovine hypothalamus and pituitary gland.

Background: Ubiquitous environmental chemicals, including endocrine-disrupting chemicals (EDCs), are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to "real-life," environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal.

Objectives: We evaluated the effects of maternal exposure to a pollutant cocktail (sewage sludge) on the ovine fetal reproductive neuroendocrine axes, particularly the kisspeptin (KiSS-1)/GPR54 (G-protein-coupled receptor 54) system.

Absence of chlamydial deoxyribonucleic acid from testicular and epididymal samples from men with obstructive azoospermia.

Objective: To identify Chlamydia trachomatis DNA by polymerase chain reaction in the upper genital tract of men with obstructive azoospermia compared with men seeking vasectomy reversal.

Design: Case-control study.

Setting: Tertiary referral center, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.

In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep.

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using 'real life' in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture.

Molecular epidemiology of macrolide resistance in beta-haemolytic streptococci of Lancefield groups A, B, C and G and evidence for a new mef element in group G streptococci that carries allelic variants of mef and msr(D).

Objectives: To study the molecular mechanisms of erythromycin resistance in beta-haemolytic streptococci of Lancefield groups A, B, C and G.

Methods: Erythromycin-resistant clinical isolates from North East Scotland were collected over 2 years. Resistance phenotypes were determined by disc diffusion and MICs by Etest.

Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae isolates from blood and noninvasive sites.

Erythromycin-resistant isolates of Streptococcus pneumoniae from blood cultures and noninvasive sites were studied over a 3-year period. The prevalence of erythromycin resistance was 11.9% (19 of 160) in blood culture isolates but 4.

Osmoprotection of Escherichia coli by peptone is mediated by the uptake and accumulation of free proline but not of proline-containing peptides.

The effect of meat peptone type I (Sigma) on the growth of Escherichia coli cells under hyperosmotic stress has been investigated. Peptone is a complex mixture of peptides with a small content of free amino acids, which resembles nutrients found in natural environments. Our data showed that peptone enhances the growth of E.

The role of peptide metabolism in the growth of Listeria monocytogenes ATCC 23074 at high osmolarity.

The growth of Listeria monocytogenes ATCC 23074 in defined medium is sensitive to high osmolarity when compared with its growth in complex media, such as brain heart infusion (BHI). The two major contributors to this difference in growth rate are the availability in BHI of the osmoprotectant glycine betaine and peptides. Peptone plays two major roles: firstly as a nutritional supplement for protein synthesis, and secondly as a source of amino acids and peptides that serve as a mechanism of maintaining turgor.

A di- and tripeptide transport system can supply Listeria monocytogenes Scott A with amino acids essential for growth.

Listeria monocytogenes takes up di- and tripeptides via a proton motive force-dependent carrier protein. This peptide transport system resembles the recently cloned and sequenced secondary di- and tripeptide transport system of Lactococcus lactis (A. Hagting, E.

Evidence for the involvement of distinct signal transduction pathways in the regulation of constitutive and interferon gamma-dependent gene expression of NADPH oxidase components (gp91-phox, p47-phox, and p22-phox) and high-affinity receptor for IgG (Fc gamma R-I) in human polymorphonuclear leukocytes.

We recently showed that mRNA levels coding the high-affinity Fc gamma receptor for IgG (Fc gamma R-I, CD64) and two of the components of the phagocytic superoxide anion-generating system--the heavy-chain subunit of cytochrome b558 (gp91-phox) and the 47-Kd cytosolic factor (p47-phox)--are modulated by interferon gamma (IFN-gamma). In this study, we examined whether dexamethasone (DEX) affects gp91-phox and p47-phox mRNA expression of human polymorphonuclear leukocytes (PMN), treated or not with IFN-gamma. We also investigated whether staurosporine, a general inhibitor of protein kinases, influences gp91-phox, p47-phox, and Fc gamma R-I gene expression in PMN treated with or without IFN-gamma.

Amiloride does not influence the capability of interferon gamma to potentiate superoxide anion and hydrogen peroxide release by human mononuclear phagocytes.

Since the molecular mechanisms of macrophage activation in response to interferon gamma (IFN-gamma) are still not well defined we have investigated whether amiloride, a specific inhibitor of the Na+/H+ antiporter, had any effect on the IFN-gamma-mediated potentiation of human monocyte and monocyte-derived macrophage capability to produce O2- (respiratory burst). Here, we demonstrate that amiloride neither inhibits the capability of IFN-gamma to activate the mononuclear phagocyte respiratory burst nor influences IFN-gamma induction of steady-state mRNA levels for 2 components of the superoxide anion-generating enzyme system. On the contrary, we show that IFN-gamma-enhanced expression of the HLA-DR alpha gene is significantly inhibited by amiloride These data indicate that Na+/H+ antiporter stimulation by IFN-gamma is not involved in the mechanism of activation of macrophage oxidative metabolism.