The effect of humic acid substances on the thyroid function and structure in lead poisoning

Lead (Pb) is a heavy metal, which adversely affects thyroid gland function and structure. Due to its high molecular weight and abundant functional groups, humic acid substances (HAS) can form chelates with heavy metals. The experiment was conducted to evaluate the prophylactic effect of HAS on thyroid hormone levels and histopathological lesions of laying hens exposed to lead (Pb) poisoning. After a week of adaptation, 192 Lohmann White laying hens (25 weeks of age) were fed one of four diets: a basal diet (BD) or the BD with HAS (0.15%), with Pb (0.3 g/kg), or with both. Experimental groups were replicated in 12 cages, with four hens each. Pb poisoning did not alter triiodothyronine (FT3; 3.22 ± 0.20 ng/dL) or thyroxine (FT4; 0.71 ± 0.08 ng/dL) concentrations, but caused a 167% increase in thyroid stimulating hormone (TSH) concentration. HAS supplementation returned the high TSH levels of hens exposed to Pb poisoning to normal values. Degenerative changes in the epithelial cells of the thyroid gland of the hens exposed to Pb poisoning were evidenced. Connective tissue cells in the interfollicular area and total amount of colloids with partially atrophic follicles were observed. These histopathological findings were less severe when HAS was added to the diet. In conclusion, HAS alleviates the effects of Pb poisoning on thyroid gland function and structure, possibly preventing its internalization by the tissue by forming chelates and exerting anti-inflammatory effects

Milk Lipid and Protein Profiles of Abkhazian and Kackar Goats

Fat and protein profiles of milk of Abkhazian and Kackar goats, Caucasian breeds, were compared in this study. The milk samples (n= 60) from 60 Abkhazian and Kackar goats were subjected to assessments of lipid profile using the high performance thin layer chromatography and protein profile using the sodium dodecyl sulphate polyacrylamide gel electrophoresis. The milk lipid and protein contents as well as their fractions were compared using student t-test. Total lipid content was 4.23±0.022 g/dl and 3.44±0.026 g/dl for Abkhazian and Kackar goat milk (P<0.0001). Milk triacylglycerol, free fatty acid and diacylglycerol fractions were different (P<0.05), but the cholesterol fraction was similar. Total protein content was 3.94 g/dl and 3.75 g/dl for Abkhazian and Kackar goat milk (P<0.007). The milk fat globule membrane protein mucine1 and xhantine oxidase, α-lactalbumin, α-casein, and κ-casein fractions were different (P<0.05). In conclusion, milk lipid and protein profile differs between Abkhazian and Kackar goats despite living in the same ecosystem. Differences in milk lipid and protein profile could be pertinent to human nutrition and health

Impact of pro-domain stability of matrix metalloproteinase-8 on the outcome of sepsis

Citation: Berx, B., M. Dickey-Collas, M.D. Skogen, Y.-H. De Roeck, H. Klein, R. Barciela, R.M. Forster, E. Dombrowsky, M. Huret, M. Payne, Y. Sagarminaga, and C. Schrum. 2011. Does operational oceanography address the needs of fisheries and applied environmental scientists? Oceanography 24(1):166–171, doi:10.5670/oceanog.2011.14.Although many oceanographic data products are now considered operational, continued dialogue between data producers and their user communities is still needed. The fisheries and environmental science communities have often been criticized for their lack of multidisciplinarity, and it is not clear whether recent developments in operational oceanographic products are addressing these needs. The International Council for the Exploration of the Sea (ICES) Working Group on Operational Oceanographic products for Fisheries and Environment (WGOOFE) identified a potential mismatch between user requirements and the perception of requirements by the providers. Through a questionnaire (98 respondents), WGOOFE identified some of these issues. Although products of physical variables were in higher demand, several biological parameters scored in the top 10 rankings. Users placed specific focus on historic time series products with monthly or annual resolution and updating on similar time scales. A significant percentage requested access to numerical data rather than graphical output. While the outcomes of this survey challenge our views of operational oceanography, several initiatives are already attempting to close the gap between user requirements and products available

The Role of the Receptor for Advanced Glycation End-Products in a Murine Model of Silicosis

Background: The role of the receptor for advanced glycation end-products (RAGE) has been shown to differ in two different mouse models of asbestos and bleomycin induced pulmonary fibrosis. RAGE knockout (KO) mice get worse fibrosis when challenged with asbestos, whereas in the bleomycin model they are largely protected against fibrosis. In the current study the role of RAGE in a mouse model of silica induced pulmonary fibrosis was investigated. Methodology/Principal Findings: Wild type (WT) and RAGE KO mice received a single intratracheal (i.t.) instillation of silica in saline or saline alone as vehicle control. Fourteen days after treatment mice were subjected to a lung mechanistic study and the lungs were lavaged and inflammatory cells, protein and TGF-β levels in lavage fluid determined. Lungs were subsequently either fixed for histology or excised for biochemical assessment of fibrosis and determination of RAGE proteinand mRNA levels. There was no difference in the inflammatory response or degree of fibrosis (hydroxyproline levels) in the lungs between WT and RAGE KO mice after silica injury. However, histologically the fibrotic lesions in the RAGE KO mice had a more diffuse alveolar septal fibrosis compared to the nodular fibrosis in WT mice. Furthermore, RAGE KO mice had a significantly higher histologic score, a measure of affected areas of the lung, compared to WT silica treated mice. A lung mechanistic study revealed a significant decrease in lung function after silica compared to control, but no difference between WT and RAGE KO. While a dose response study showed similar degrees of fibrosis after silica treatment in the two strains, the RAGE KO mice had some differences in the inflammatory response compared to WT mice. Conclusions/Significance: Aside from the difference in the fibrotic pattern, these studies showed no indicators of RAGE having an effect on the severity of pulmonary fibrosis following silica injury. © 2010 Ramsgaard et al

Farsighted Risk Mitigation of Lateral Movement Using Dynamic Cognitive Honeypots

Lateral movement of advanced persistent threats has posed a severe security challenge. Due to the stealthy and persistent nature of the lateral movement, defenders need to consider time and spatial locations holistically to discover latent attack paths across a large time-scale and achieve long-term security for the target assets. In this work, we propose a time-expanded random network to model the stochastic service links in the user-host enterprise network and the adversarial lateral movement. We design cognitive honeypots at idle production nodes and disguise honey links as service links to detect and deter the adversarial lateral movement. The location of the honeypot changes randomly at different times and increases the honeypots' stealthiness. Since the defender does not know whether, when, and where the initial intrusion and the lateral movement occur, the honeypot policy aims to reduce the target assets' Long-Term Vulnerability (LTV) for proactive and persistent protection. We further characterize three tradeoffs, i.e., the probability of interference, the stealthiness level, and the roaming cost. To counter the curse of multiple attack paths, we propose an iterative algorithm and approximate the LTV with the union bound for computationally efficient deployment of cognitive honeypots. The results of the vulnerability analysis illustrate the bounds, trends, and a residue of LTV when the adversarial lateral movement has infinite duration. Besides honeypot policies, we obtain a critical threshold of compromisability to guide the design and modification of the current system parameters for a higher level of long-term security. We show that the target node can achieve zero vulnerability under infinite stages of lateral movement if the probability of movement deterrence is not less than the threshold

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 mu g/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5-4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6-3.8, p <0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2-3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5-6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6-9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.Peer reviewe

Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study

Introduction: Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole blood taken from patients with sepsis.Methods: We performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal blood purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function. Results: Hemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cellmediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function. Conclusions: Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better blood purification therapies. © 2013 Rimmelé et al.; licensee BioMed Central Ltd

Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model

Introduction: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues.Methods: In total, 76 male adult Sprague-Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann-Whitney U test.Results: Apheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals.Conclusions: Our results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung. © 2014 Peng et al