Bovine milk is a nutritious food commodity extensively produced and consumed in Punjab, Pakistan. This study assesses the concentration profile of organochlorine pesticides (OCP; 18 compounds) in ...buffaloes and cow’s milk in eight major districts of Punjab, Pakistan and the potential impacts of such exposure. The total OCPs in buffaloes and cow’s milk samples ranged from 3.93 to 27.63 ng mL−1 and 14.64–77.93 ng mL−1 respectively. The overall pattern of mean OCPs concentration in buffaloes and cows milk showed that Hexachlorocyclohexanes (HCHs) are predominant followed by Heptachlors and Dichlorodiphenyltrichloroethane (DDTs). So far, the concentration profile depicted that ∑HCHs, ∑DDTs and ∑Heptachlors did not exceed the maximum residual limits set for buffaloes and cow’s milk. The spatial trends in terms of cluster analysis depicted significant variation (p > 0.05) among the districts in one cluster probably owing to local conditions. Furthermore, recently used DDTs were also identified at some of the selected districts. The risk assessment suggests that the estimated daily intake for each OCP was in accordance with the acceptable daily intake, thus single compound exposure does not pose a significant carcinogenic risk. However, the hazard ratios indicated that the values for ∑DDTs posed risk in adults consuming cow’s milk whereas children may face carcinogenic risk on the consumption of both buffalo and cow’s milk. The risk may be altered where mixture is considered, furthermore, regarding carcinogenic risks a continuous monitoring based ecological analysis is recommended in the future.
•Hexachlorocyclohexanes were predominant in bovine milk.•Significant variation of selected organochlorines among different districts.•Fresh inputs of Dichlorodiphenyltrichloroethane were identified at some locations.•Carcinogenic risk were reported for children.
Much about the neuroendocrine control of reproduction is inferred from changes in the episodic release of luteinizing hormone (LH), as measured in samples of peripheral blood. This, however, assumes ...that LH precisely mirrors gonadotropin‐releasing hormone (GnRH) release from the hypothalamus. Because GnRH is not measurable in peripheral blood, characterization of the relationship between these two hormones required the simultaneous measurement of GnRH and LH in pituitary portal and peripheral blood, respectively. Here, we review the history of why and how portal blood collection was developed, the aspects of the true output of the central component of the hypothalamic–pituitary–gonadal axis that this methodology helped clarify, and conditions under which the pituitary fails to serve as an adequate bioassay for the release pattern of GnRH.
The history of pituitary portal blood collection for the assessment of releasing factors is reviewed.
Anthropogenic chemicals are ubiquitous throughout the environment. Consequentially, humans are exposed to hundreds of anthropogenic chemicals daily. Current chemical risk assessments are primarily ...based on testing individual chemicals in rodents at doses that are orders of magnitude higher than that of human exposure. The potential risk from exposure to mixtures of chemicals is calculated using mathematical models of mixture toxicity based on these analyses. These calculations, however, do not account for synergistic or antagonistic interactions between co-exposed chemicals. While proven examples of chemical synergy in mixtures at low doses are rare, there is increasing evidence that, through non-conformance to current mixture toxicity models, suggests synergy. This review examined the published studies that have investigated exposure to mixtures of chemicals at low doses in mammalian in vivo systems. Only seven identified studies were sufficient in design to directly examine the appropriateness of current mixture toxicity models, of which three showed responses significantly greater than additivity model predictions. While the remaining identified studies were unable to provide evidence of synergistic toxicity, it became apparent that many results of such studies were not always explicable by current mixture toxicity models. Additionally, two data gaps were identified. Firstly, there is a lack of studies where individual chemical components of a complex mixture (>10 components) are tested in parallel to the chemical mixture. Secondly, there is a lack of dose-response data for mixtures of chemicals at low doses. Such data is essential to address the appropriateness and validity of future chemical mixture toxicity models.
Background
Thromboembolic disease is a major cause of mortality in dogs with immune‐mediated hemolytic anemia (IMHA). At present, no reliable biomarkers of individual patient thrombotic risk are ...available. In human medicine, increased urinary thromboxane concentrations have utility as markers of prothrombotic tendency in various situations.
Hypothesis/Objectives
First, to determine if urinary 11‐dehydrothromboxane B2 (u11‐dTXB) concentrations are increased in dogs with primary IMHA compared to normal dogs; second, to assess whether u11‐dTXB concentration is associated with survival, known prognostic indicators, or frequency of thrombosis in dogs with IMHA.
Animals
Twenty client‐owned dogs diagnosed with primary IMHA and 17 healthy dogs volunteered by hospital staff.
Methods
Prospective case‐control study. A previously validated ELISA was used to measure urine 11‐dTXB concentrations, which were normalized to urine creatinine concentration (u11‐dTXB:Cr). Samples were obtained at presentation from patients with primary IMHA. Standard clincopathological data at baseline and survival data were collected. Urinary 11‐dTXB:Cr was compared between outcome subgroups, and correlated with known markers of disease severity.
Results
Baseline u11‐dTXB:Cr was significantly higher in dogs with IMHA than in healthy dogs (median, 3.75; range, 0.83‐25.36 vs 0.65; 0.24‐2.57; P = .003) but did not differ between dogs with IMHA that survived and did not survive to 30 days after presentation, nor between dogs with and without clinical suspicion of thrombotic disease.
Conclusions and Clinical Importance
Urinary 11‐dTXB:Cr is increased in dogs with IMHA compared to healthy controls, consistent with a prothrombotic state. However, in this IMHA population u11‐dTXB:Cr was not associated with survival or suspected thrombosis.
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. The effects of ECs/EDCs are complex, not least because it is emerging that low-level, ‘real-life’ mixtures of ECs/EDCs may carry significant biological potency. In addition, there is evidence that ECs/EDCs can alter the epigenome in a sexually dimorphic manner, which may lead to changes in the germ line and perhaps even to transgenerational effects. This review summarises the evidence for EC, including EDC, involvement in female reproductive dysfunction, it highlights potential mechanisms of EC action in the female and emphasises the need for further research into EC effects on female development and reproductive function.
There is growing international interest in how environmental conditions experienced during development can shape adult phenotypes and the extent to which such induced changes are adaptive. One ...physiological system that links an individual to changes in environmental circumstances during development is the hypothalamic-pituitary-adrenal axis. Mammalian studies have linked early postnatal stress to later changes in the hypothalamic-pituitary-adrenal axis; however, the physiological link lactational corticosterone (CORT) transfer between mother and offspring during postnatal development constrains the ability to determine the direct effects of such stressors on subsequent physiology and behavior. Here we present a novel model using an avian species, the zebra finch (Taeniopygia guttata), in which maternal hormonal transfer during postnatal development is likely to be absent. Postnatal exposure of chicks to the stress hormone CORT was manipulated for a 16-d period up until nutritional independence (28 d), and the long-term effects on the physiological response to stress determined. CORT doses were scaled to mimic the physiological response of juvenile birds to a capture-handling-restraint protocol. CORT-fed birds showed exaggerated and prolonged responses to acute stress at 60 d of age. Our results clearly demonstrate that postnatal stress has significant long-term effects on the physiological stress response in birds and provides a potential mechanism underlying long-term behavioural responses to developmental conditions. This study represents the first direct evidence for postnatal glucocorticoid programming of the stress response using this novel model for postnatal stress. This model therefore provides an important tool with which to investigate the role of glucocorticoids in shaping adult phenotypes.
Post-natal exposure to glucocorticoids has long-term effects on the physiological response to stress in birds.
Abstract Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential ...to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens ( Gallus gallus domesticus ). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research.
Two-component, self-assembling nanoparticles represent a versatile platform for multivalent presentation of viral antigens. Computational design of protein nanoparticles with differing sizes and ...geometries enables combination with antigens of choice to test novel multimerization concepts in immunization strategies where the goal is to improve the induction and maturation of neutralizing antibody lineages. Here, we describe detailed antigenic, structural, and functional characterization of computationally designed tetrahedral, octahedral, and icosahedral nanoparticle immunogens displaying trimeric HIV envelope glycoprotein (Env) ectodomains. Env trimers, based on subtype A (BG505) or consensus group M (ConM) sequences and engineered with SOSIP stabilizing mutations, were fused to an underlying trimeric building block of each nanoparticle. Initial screening yielded one icosahedral and two tetrahedral nanoparticle candidates, capable of presenting twenty or four copies of the Env trimer. A number of analyses, including detailed structural characterization by cryo-EM, demonstrated that the nanoparticle immunogens possessed the intended structural and antigenic properties. When the immunogenicity of ConM-SOSIP trimers presented on a two-component tetrahedral nanoparticle or as soluble proteins were compared in rabbits, the two immunogens elicited similar serum antibody binding titers against the trimer component. Neutralizing antibody titers were slightly elevated in the animals given the nanoparticle immunogen and were initially more focused to the trimer apex. Altogether, our findings indicate that tetrahedral nanoparticles can be successfully applied for presentation of HIV Env trimer immunogens; however, the optimal implementation to different immunization strategies remains to be determined.
Two related actinomycetes, Glycomyces sp. strain NRRL B-16210 and Stackebrandtia nassauensis NRRL B-16338, were identified as potential phosphonic acid producers by screening for the gene encoding ...phosphoenolpyruvate (PEP) mutase, which is required for the biosynthesis of most phosphonates. Using a variety of analytical techniques, both strains were subsequently shown to produce phosphonate-containing exopolysaccharides (EPS), also known as phosphonoglycans. The phosphonoglycans were purified by sequential organic solvent extractions, methanol precipitation, and ultrafiltration. The EPS from the Glycomyces strain has a mass of 40 to 50 kDa and is composed of galactose, xylose, and five distinct partially O-methylated galactose residues. Per-deutero-methylation analysis indicated that galactosyl residues in the polysaccharide backbone are 3,4-linked Gal, 2,4-linked 3-MeGal, 2,3-linked Gal, 3,6-linked 2-MeGal, and 4,6-linked 2,3-diMeGal. The EPS from the Stackebrandtia strain is comprised of glucose, galactose, xylose, and four partially O-methylated galactose residues. Isotopic labeling indicated that the O-methyl groups in the Stackebrandtia phosphonoglycan arise from S-adenosylmethionine. The phosphonate moiety in both phosphonoglycans was shown to be 2-hydroxyethylphosphonate (2-HEP) by 31P nuclear magnetic resonance (NMR) and mass spectrometry following strong acid hydrolysis of the purified molecules. Partial acid hydrolysis of the purified EPS from Glycomyces yielded 2-HEP in ester linkage to the O-5 or O-6 position of a hexose and a 2-HEP mono(2,3-dihydroxypropyl)ester. Partial acid hydrolysis of Stackebrandtia EPS also revealed the presence of 2-HEP mono(2,3-dihydroxypropyl)ester. Examination of the genome sequences of the two strains revealed similar pepM-containing gene clusters that are likely to be required for phosphonoglycan synthesis.
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.
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.
Four groups of sheep (n = 10–12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography/tandem mass spectroscopy.
Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzoaanthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma-secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure.
Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.
•Chronic exposure to environmental chemicals affects liver physiology.•Proteomic measurements showed widespread dysregulation in the exposed livers.•Exposure dysregulated important plasma proteins such as albumin and transferrin•Reduction in total lipids in the exposed female livers•Increase in cancer markers in the exposed male livers
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